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Satisfies NEW NJ
CME requirements as
mandated in 45:9-7.7 of
the New Jersey Statutes

Satisfies NJ CME requirements in End of Life Care.

ALL CME APPROVED FOR STATE LICENSE RENEWAL.
Course valid for credit through 10/31/2015.
InforMed is accredited by the Accreditation Council for Continuing Medical Education (ACCME)
to provide continuing medical education for physicians.

for the 2013 - 2015 licensure cycle

All licensed Physicians

2 credits of educational programs or topics related

to end-of-life care

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2014-2015 New Jersey Update for Physicians

ER/LA Opioid REMS Education* (3 Credits)..................................................... 1
Pain Management at the End of Life* (2 Credits).........................................31
Self-Directed Learning (free 1 Credit)..............................................................51
Self-Assessment (required to receive credit)................................................59
*Both of these courses satisfy the requirement shown above

FREE to all participants

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Course:REMS13Credits

OriginalReleaseDate11/2012 LastUpdate09/2013

ExpirationDate:10/31/2015

ER/LA Opioid REMS Education

This course is designed in accordance with the FDAs Blueprint for Prescriber Education for Extended-Release and Long-Acting
(ER/LA) Opioid Analgesics.
Audience
This course is designed for all physicians (MD/DO), physician
assistants and nurse practitioners.
Course Objective
The purpose of this course is to educate prescribers with regards
to Risk Evaluation and Mitigation Strategies (REMS) in
accordance with the FDA Blueprint for Prescriber Education.
Learning Objectives
Completion of this course will better enable the course participant to:

1.

Describe the two major competing responsibilities of

clinicians related to the prescription of opioid pain
medications
2. Describe 6 pain-related components of an initial patient
evaluation
3. Explain the term universal precautions as it applies to the
evaluation of patients for risk of opioid dependence or abuse
4. Describe 2 tools for patient risk assessment
5. Describe 3 advantages of creating written patient/provider
opioid agreements
6. Explain the value of function-based treatment goals as
opposed to pain-relief goals
7. Describe the 4 key steps to take prior to initiating treatment
with an opioid pain medication
8. Explain why special care must be taken with extendedrelease/long-acting (ER/LA) opioid formulations
9. Explain why methadone must be prescribed with particular
caution
10. Describe 2 ways to potentially address unpleasant or
intolerable opioid side effects
11. Explain the potential value of using PDMPs

1.
2.
3.

How to Receive Credit

Read the course materials
Complete the self-assessment questions at the end. A score
of 70% is required.
Return your customer information/answer sheet, evaluation,
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Accreditation Statement
Informed is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide continuing
medical education for physicians.
Designation of Credit
Informed designates this enduring material for a maximum of 3
AMA PRA Category 1 Credits. Physicians should claim only
the credit commensurate with the extent of their participation in
the activity.
This activity developed without Commercial Support

Faculty
Sorin J. Brull, MD, FCARCSI (Hon)
Professor of Anesthesiology, Mayo Clinic, College of Medicine
Consultant, Department of Anesthesiology, Mayo Clinic
Lynn R. Webster, MD, FACPM, FASAM
Medical Director and Founder, Lifetree Clinical Research &
Pain Clinic
Director-At-Large for the American Academy of Pain Medicine
Stewart B. Leavitt, MA, PhD
Executive Director, Pain Treatment Topics
Stephen Braun
Medical Writer
Braun Medical Media
Activity Director
Sarina J. Grosswald, EdD
Director of CME, Informed
SJ Grosswald & Associates
Disclosure
Resolution of Conflicts of Interest
In accordance with the ACCME Standards for Commercial
Support of CME, the Informed implemented mechanisms, prior to
the planning and implementation of this CME activity, to identify
and resolve conflicts of interest for all individuals in a position to
control content of this CME activity.
Staff and Content Validation Reviewer Disclosure
Informed staff involved with this activity and any content
validation reviewers of this activity have reported no relevant
financial relationships with commercial interests.
Planning Committee/Faculty Disclosure
The following faculty and/or planning committee members have
indicated they have no relationship(s) with industry to disclose
relative to the content of this CME activity:
Sarina J. Grosswald, EdD
Stephen Braun
The following faculty and/or planning committee members have
indicated that they have relationship(s) with industry to disclose:
Lynn R. Webster, MD, FACPM, FASAM has received
honoraria related to formal advisory activities and as a
consultant from American Academy of Pain Management,
American Board of Pain Medicine, Covidien Mallinckrodt,
Iroko Pharmaceuticals, LLC, Medtronic, Inc., Nektar
Therapeutics, Pfizer Inc., and Salix Pharmaceuticals, Inc.
Stewart B. Leavitt, MA, PhD has received unrestricted
Medical Education Grants from Purdue Pharmaceuticals,
Endo Pharmaceuticals, and Millenium Laboratories.
Sorin J. Brull, MD, FCARCSI (Hon) has received
honoraria from Merck, Inc as a member of their Global
Advisory Board.
2013. All rights reserved. These materials, except those in the public domain, may not
be reproduced without permission from InforMed. This publication is designed to
provide general information prepared by professionals in regard to the subject matter
covered. It is provided with the understanding that InforMed, Inc. is not engaged in
rendering legal, medical or other professional services. Although prepared by
professionals, this publication should not be utilized as a substitute for professional
services in specific situations. If legal advice, medical advice or other expert assistance
is required, the service of a professional should be sought.

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Best Practices for Opioid Prescribing in Chronic Non-Cancer Pain

Introduction
Opioid analgesics are widely accepted for
the treatment of severe acute pain and chronic pain
related to active cancer or at the end of life.1 The
widespread use of opioids for other types of
moderate-to-severe chronic pain, however, has been
evolving in the past 2 decades and continues to
generate controversy. Prior to the 1990s, clinicians
often viewed opioid pain medications with
skepticism and avoided prescribing them, even when
risks were thought to be low.2 This perspective gave
way to the recognition that many patients were being
under-treated for their pain, leading to increased
interest in the clinical value of opioids and a
dramatic rise in rates of opioid prescribing for
analgesia. Prescriptions for opioids escalated from
around 40 million in 1991 to roughly 257 million in
2009.3 In 2011, hydrocodone/acetaminophen was the
single most-prescribed drug in the U.S., with a little
over 4 million prescriptions dispensed.4
Unfortunately, escalating opioid prescribing
rates have been mirrored by similar escalations in
drug diversion and nonmedical uses of opioids. The
opioid medications associated with these problems
include immediate- and extended- release products,
as well as methadone. Many people directly affected
by the crisis have been previously healthy and have
had no history of substance misuse.5 The scope of
the problem can be seen in the following statistics:

In 2009, the latest year for which data are

available, an estimated 7 million
Americans were abusing prescription
drugsmore than the number abusing
cocaine, heroin, hallucinogens, and
inhalants, combined.6
Emergency-room visits related to nonmedical use of opioids rose 111% between
2004 and 2008.7
Between1998 and 2008, the rate of opioid
misuse increased 400%.8
Drug overdose is now the second-leading
cause of accidental death in America,
exceeded only by car crashes.9

This rising tide of abuse, addiction,

overdose, and death has led to calls for tighter

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regulation of opioid pain medications and for greater

prudence in prescribing on the part of clinicians. In
July 2012, the U.S. Food and Drug Administration
(FDA) released its final Risk Evaluation and
Mitigation Strategies (REMS) content guidelines for
prescriber education related to extended-release
(ER) and long-acting (LA) opioid analgesics.10 The
previous year, the White House Office of National
Drug Control Policy, in collaboration with other
branches of the federal government, introduced the
Action Plan To Address National Prescription Drug
Abuse Epidemic.11 These initiatives, echoing
statements in recent clinical guidelines, seek to
balance a crack-down on non-medical use of opioids
while simultaneously protecting the delivery of
effective pain management to legitimate patients.1
This CME monograph on best practices for
prescribing opioids for chronic noncancer pain is in
step with these important efforts, covering the
educational themes emphasized by the FDA and the
new federal plan to combat prescription drug misuse.
This program offers clinicians a solid foundation for
responsible and vigilant opioid prescribing.
Definitions
The International Association for the Study
of Pain defines chronic pain as pain that persists
beyond normal tissue healing time, which is
assumed to be three months.12 Numerous diseases
and syndromes can result in chronic pain. For the
purposes of this monograph, all chronic pain
disorders outside of cancer pain or pain at end of life
are collectively labeled chronic noncancer pain
(CNCP).
Many treatment modalities exist for
CNCPopioid pain medications are only one of
many tools in the pain management armamentarium.
Not all patients are appropriate candidates for opioid
medications, either because of the nature of their
condition, the existence of relevant comorbid
conditions, or their assessed risk for opioid abuse.
Opioid therapy may be a useful component of a pain
management plan, but in selecting patients for an
opioid trial, clinicians must weigh the potential
benefits of opioids against the risk of significant
harms, including a wide range of adverse effects as

well as adverse outcomes associated with abuse

potential.

based on promising interventions and expert

opinion, not rigorous evidence-based research:9

The Challenge of Pharmacovigilance

In their daily practice, clinicians who treat
patients with chronic non-cancer pain face must
balance pain relief with the risks associated with
opioid analgesics. The term pharmacovigilance
refers to the range of procedures and processes used
to achieve this balance. As will become clear
throughout this monograph, such procedures need
not be burdensome and are not unlike the kinds of
balancing acts required in the prescription of a great
many other therapeutic agents. What makes opioids
of particular concern is the fact that not only are they
potentially dangerous for patients, they are also
highly sought-after by recreational drug users and
criminal elements in society.
In their efforts to find the appropriate,
effective middle ground between relieving pain and
preventing diversion and misuse of prescription
opioids, clinicians must bear in mind the fact that the
problem of unrelieved pain remains as urgent as
ever. Chronic pain was estimated in a 2011 study to
affect approximately 100 million Americans and to
cost roughly $635 billion annually in treatment and
lost productivity.13 In fact, the incidence of chronic
pain in the U.S. is greater than that of diabetes, heart
disease, and cancer combined.14,15
At the same time, opioids are subject to
abuse, as previously mentioned, and also have a
wide range of potential adverse effects that can
predispose a patient to serious morbidity and even
mortality. Risk is increased among older adults;
those with impaired renal or hepatic function;
individuals with obesity, cardiopulmonary disorders,
sleep apnea, or mental illness; and in patients who
combine opioids with other respiratory depressants
such as alcohol, sedative-hypnotics,
benzodiazepines, or barbiturates.
The Centers for Disease Control and
Prevention (CDC) in 2010 issued recommendations
aimed at helping clinicians find a balance between
responsible opioid prescribing and minimizing the
risks of abuse, addiction, and drug diversion, though
the recommendations were acknowledged to be

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Use opioid medications for acute or chronic

pain only after determining that alternative
therapies do not deliver adequate pain relief.
The lowest effective dose of opioids should
be used.
In addition to behavioral screening and use
of patient contracts, consider random,
periodic, urine testing for opioids and other
drugs for any patient less than 65 years old
with non-cancer pain who is being treated
with opioids for more than six weeks.
Do not prescribe ER/LA opioids for acute
pain.
If your state has a prescription drug
monitoring program (PDMP) periodically
request a report on the history of opioid
prescriptions to your patients by other
providers.

The rest of this monograph details how to

implement these general guidelines in ways that are
consistent with the time and budgetary constraints
often found in modern practice settings.

Case Study: Initial Presentation

Matt Davidson, age 69, is a retired high school
physical education teacher. He presents to his
primary care physician for his annual physical
examination. He has a history of hypertension,
osteoarthritis, and prostate cancer, for which he was
treated 2 years ago with a combination of external
beam radiation and chemotherapy and now shows
no signs of disease, although he continues to be
troubled by mild urinary incontinence and erectile
dysfunction. On this visit, Mr. Davidson complains
of joint pain, as well as a burning, tingling pain in
his hands and feet and asks if anything can be done
for it. He says he has been taking between 800 and
1200 mg ibuprofen by mouth daily for the pain,
which he rates as 7-8 on a 10-point scale, but has
also been having heartburn as a result.
A full evaluation of the patients pain leads to a dual
diagnosis of osteoarthritis and peripheral
neuropathy secondary to chemotherapy. As part of
the evaluation, the patient is asked how his pain is

affecting his life and whether it is preventing him

from engaging in any activities. He reports
disturbed sleep, which he says makes him more
irritable during the day. He also says he no longer
plays tennis, walking has begun to hurt, and it is
becoming difficult to use the computer keyboard.

diagnostic studies or tests. As when assessing any

patient, clinicians should take the time to look
beyond the specific complaint or body part/system
and evaluate holistically the broader mental, cultural,
and socioeconomic contexts within which the chief
complaint is embedded.17

This information is used to create a treatment plan

with the functional goals of reducing nighttime
awakenings to no more than 1 per night; walking
daily at least 1 mile without pain; using the
computer without pain. A return to playing tennis is
left as a possible future goal if less strenuous goals
are achieved first. An extended-release oxycodone
product is prescribed, as well as a prophylactic
laxative. The patient is given printed information
about the safe use, storage, and disposal of opioid
medications.

History and Physical Exam

Assessing Patients for Opioid Therapy

It is important for clinicians to avoid the mistake of

assuming that if an organic pathology cannot be
found, the patients pain is all in their head. As
Goodwin and Bajwa (2004) note, Pain is what the
patient says it is.19 Psychological factors may be
important in a patients experience of pain, and the
importance of such factors should be taken seriously
and incorporated into the overall treatment plan.19

Physical exams conducted as part of an

assessment of pain should include an evaluation of
the patients nervous system, with focus on sensory
function. Clinicians should assess for allodynia (pain
from stimulation that would not normally evoke
pain, such as light touch), hyperalgesia (amplified
pain response to stimulation that would normally
evoke only mild pain), or pain insensitivity. A
sensory examination could include response to light
touch, light pressure, pinprick, cold or vibration.18

Determining if an opioid medication is

appropriate for a patient with chronic non-cancer
pain involves assessing both the condition itself and
the patients potential for misuse or abuse of the
medications. The FDA has recommended that
providers contemplating prescribing an opioid pain
medication complete a comprehensive history and
physical examination, including assessment of
psychosocial factors and family history of substance
misuse, as well as special considerations for the
elderly, women, children, and cultural/ethnic
groups.16 Regulators expect to see at least a basic
physical examination as part of the evaluation that
leads to treatment with controlled substances.17 The
exact components of the examination, however, are
left to the medical judgment of the clinician, who is
expected to have performed an examination
proportionate to the diagnosis that justifies a
treatment.

A comprehensive evaluation of a patient in

pain usually requires moving beyond the typical list
of questions asked during a general history. It may
be possible to gather this information before an inperson visit by using paper or online questionnaires.
In most cases where pain is the chief complaint, it is
appropriate to begin a conversation by asking about
the pain, but then it is usually best to review the
broader context and impact of that pain.17 Here are
some points that may be useful to cover in an initial
evaluation:17,18

Any basic pain assessment includes the

familiar elements of: chief complaint; history of
present illness; past medical, surgical, and
psychosocial history; family history; physical
examination; and examination of imaging and other

Location of pain
Character of pain (i.e., shooting or stinging,
continuous or intermittent, worse at night or
in the morning)
Lowest and highest pain on 0 to 10 scale in a
typical day

Figure 1: Numeric Pain Scale

0

No Pain

5
Moderate pain

10

Worst pain possible

Source: Goodwin J, Bajwa ZH. Evaluating the patient with chronic pain. In: Principles and Practice of Pain Medicine 2nd Ed. Warfield CA, and Bajwa
ZH., Eds. 2004. New York, NY, McGraw-Hill Companies, Inc. Page 65, column 1, paragraph 3.

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Usual pain on 0 to 10 scale on a typical day

(augmented by verbal descriptors)
How and when pain started
Exacerbating and relieving factors (i.e.,
stress, alcohol, other medical concerns)
Effect of pain on sleep
Effect of pain on mood
Effect of pain on functioning at work
Effect of pain on quality of personal life,
such as relationships, sex, or recreation
Is the patient involved in a legal or
protracted insurance process connected to
his or her chronic pain, such as a motor
vehicle accident or a disability case?
What activities could the patient do before
pain impacted his or her life that he or she
cant do now?
What does the patient expect from
medications or other treatments in terms of
analgesia or recovered function?
Review of past experience/exposure to
opioids
Review of past medical/surgical history
Review of family medical history
Assessment of patient history of drug,
alcohol, and tobacco use
Psychosocial evaluation (including history
of mental illness)

Table 1: Characteristics of Chronic-Pain

Patients v. Addicted Patients
Chronic-Pain Patient
Addicted Patient
Medication use is not
Medication use is out of
out of control
control
Medication use
Medication use impairs
improves quality of life
quality of life
Wants to decrease
Medication use
medication if adverse
continues or increases
effects develop
despite adverse effects
Is concerned about the
Unaware of or in denial
physical problem being
about any problems that
treated with the drug
develop as a result of
drug treatment
Follows the practitioner- Does not follow opioid
patient agreement for
agreement
use of the opioid
May have left over
Does not have leftover
medication
medication
Loses prescriptions
Always has a story about
why more drug is needed

During an initial evaluation, clinicians

should be alert for signs that a patient is minimizing
his or her pain. This may result from a variety of
psychological or emotional factors. For example,
some patients may worry that they will be labeled as
a complainer if they mention pain, or that their
health care provider will suspect they are addicted if
they ask about opioid pain medications. Other
patients may under-report pain because they fear that
pain medications will dull their cognitive abilities,
lead to addiction, or produce undesirable side
effects. Clinicians should be empathic, supportive
and honest, neither promising too much nor
removing all hope, when evaluating a patient in
chronic pain.18
Psychosocial Evaluation
Pain affects every aspect of a patients life.
It is vital, therefore, to evaluate the ways pain may
be impacting, or may be affected by, psychosocial
elements of a patients life.1 Clinicians must be alert
for signs of depression or anxiety, which are very
common. Be particularly alert for suicidal thoughts
since the risk of suicide is roughly double for
patients with chronic pain.20 Some freely-accessible
instruments for gathering a psychiatric history are
available [see, for example, the Depression Anxiety
& Positive Outlook Scale (ww.dapos.org) or the
Patient Health Questionnaire (PHQ Screeners
(www.phqscreeners.com)]. Referral to a mentalhealth professional is warranted if the clinicians
judgment suggests the patient has active
psychological issues beyond his or her expertise.
Clinicians should also probe for ways in
which pain may be affecting the patients family
system, work, or social activities. Pain can seriously
erode these spheres of life and evaluating these
challenges and addressing them during treatment
(for instance by referral to a vocational counselor or
social worker) is just as important as treating the
more immediate medical issues that may be
contributing to chronic pain.
Evaluating Patients for Risk of Opioid Dependence
or Abuse
Whenever a clinician considers treating pain
with a controlled substance, such as an opioid, risk

Adapted from: Webster LR, Dove B. Avoiding Opioid Abuse While

Managing Pain. Sunrise River Press, North Branch, MN. 2007.

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Table 2: Tools for Patient Risk Assessment

Tool
Current Opioid Misuse
Measure (COMM)

Diagnosis, Intractability,
Risk, Efficacy (DIRE)
Opioid Risk Tool (ORT)
Screener and Opioid
Assessment for Patients with
Pain, Version 1 and Revised
(SOAPP, and SOAPP-R)

Use
Monitor for misuse
by patients
currently on longterm opioid therapy
Screen for risk of
opioid
addiction
Screen for risk of
opioid addiction
Screen for risk of
opioid
addiction

Who
Administers?
Patient self-report

17 items

www.inflexxion.com/COMM/

Clinician

7 items

Belgrade MJ, et al. J Pain.

2006;7:671681.

Clinician or
patient self-report
Patient self-report

5 yes/no
questions
24 items

www.opioidrisk.com/node/887

of misuse or diversion is always a possibility, no

matter how remote, and must be assessed. Exactly
whom to suspect and when to be proactive in
investigating risk factors is an area of great debate.
To date, no convincing data exist to support the
strategy of focusing on any one specific population
or settingwhich means that prescribers must be
vigilant with all patients.17 The concept of universal
precautions has been applied to this approach,
which means that any patient in pain could have a
drug misuse problemjust as any patient requiring a
blood draw for a simple lab test could have HIV.21
Treating everyone with the same screens, diagnostic
tests, and administrative procedures can help remove
bias and level the playing field so everyone is treated
equally and screened thoroughly.
Nonetheless, it is also true that some patient
characteristics are predictive of a potential for drug
abuse, misuse, or other aberrant behaviors. The
factor that appears to be most strongly predictive in
this regard is a personal or family history of alcohol
or drug abuse.1 Some studies have also shown that
younger age and the presence of psychiatric
conditions are also associated with aberrant drugrelated behaviors.1
In evaluating patients with chronic pain for
risk of addiction or signs that they may be abusing a
controlled substance, it may be helpful to consider
the sets of characteristics listed in Table 1.
Many tools have been developed for the
formal assessment of a patients risk of having a
substance misuse problem, some of which are
appropriate for routine clinical use because they are
relatively brief and easily implemented. Table 2 lists
the tools that appear to have good content, and face
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Length

Access

www.inflexxion.com/SOAPP/

and construct validity for assessing patient risks

related to chronic opioid therapy, although to date,
no single tool has been widely endorsed or
thoroughly validated.1
Written Agreements
Written documentation of all aspects of a
patients care, including assessments, informed
consent, treatment plans, and provider/patient
agreements, are a vital part of opioid prescription
best practices. Such documentation provides a
transparent and enduring record of a clinicians
rationale for a particular treatment and provides a
basis for ongoing monitoring and, if needed,
modifications of a treatment plan.17
Many computerized systems are now
available for the acquisition, storage, integration,
and presentation of medical information. Most offer
advantages that will benefit both patients and
prescribers, such as maintaining up-to-date records,
and providing instant availability of information
relevant to prescribing or treatment. Although
automation can help, clear documentation is not
dependent on electronic record-keeping; it merely
requires a commitment to creating clear and
enduring communication in a systematic fashion.
Good documentation can be achieved with the most
elaborate electronic medical record systems, with
paper and pen, or with dictated notes. Clinicians
must decide for themselves how thoroughly, and
how frequently, their documentation of a patients
treatment should be.
Informed Consent
Informed consent is a fundamental part of

planning for any treatment, but it is critically

important in long-term opioid therapy, given the
potential risks of such therapy. At its best, consent
also fortifies the clinician/patient relationship.
Prescribers must be able to answer with
confidence four key questions when obtaining
informed consent in the context of treatment with
opioids:22
1. Does the patient understand the various
options for treatment?
2. Has the patient been reasonably informed
of the potential benefits and risks associated
with each of those options?
3. Is the patient free to choose among those
options, free from coercion by the healthcare
professional, the patients family, or others?
4. Does the patient have the capacity to
communicate his or her preferences
verbally or in other ways (e.g., if the patient
is deaf or mute)?

Department of Defense chartered an expert panel to

undertake a systematic review of existing medical
literature on this subject. In the clinical practice
guidelines resulting from that work, the panel
concluded that opioid treatment agreements are a
standard of care when prescribing long-term opioid
therapy.23 [Samples of several commonly-used
agreements, including a low-literacy version, are
available at: http://opioids911.org/media/doc/
Op911-OpioidRxAgreements.doc]
Provider/patient agreements have many
potential advantages, including:17

Documentation related to these key areas

can be accomplished by creating a separate paper or
electronic informed consent form or by
incorporating informed consent language into a
larger treatment plan or patient/provider agreement.

Patient-Provider Agreements
A written agreement between a clinician and
a patient about the specifics of their pain treatment
with opioids can help clarify the plan with the
patient, the patients family, and other clinicians
who may become involved in the patients care.1
Such agreements can also reinforce expectations
about the appropriate and safe use of opioids.1
Caution must be exercised, however, to ensure that
patient/provider agreements are not used in a
coercive way to unethically place patients in the
position of having to agree to its terms or else lose
an important component of their treatment (or even
lose all treatment).22
Although evidence is lacking about the most
effective methods to convey the information
included in most patient-provider agreements, such
agreements have been widely used and are
recommended by regulators and many experts on
treatment guidelines for long-term opioid therapy.1
Recently, the Veterans Administration and U.S.

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Allowing treatment to start on a note

of mutual respect and partnership
Enhancing transparency
Engaging patients in a collaborative
education and decision-making
process
Helping to set functional goals and
clarifying the clinicians and
patients roles and responsibilities in
attaining these goals
Documenting acceptance of
treatment risks and benefits
Documenting informed consent
Helping avoid misunderstandings
that may occur over long treatment
time periods
Providing a foundation for
subsequent decisions about changes
in medications or termination of
treatment

Clinicians should strive to craft agreements

that serve their patients best interests and avoid
coercive or punitive language. Thus, agreements
should avoid:17

Putting all burden on the patient rather

than sharing it between patient and
clinician
Framing the agreement in terms of
punishments for possible future crimes or
difficulties
Using language that is stigmatizing,
dominating, or pejorative
Using coercion in any way
Imposing limitations for the clinicians
convenience without clear and substantial
benefit for the patient.

Insisting on behaviors unrelated to actual

use of medications
Using the term fired to describe
termination of treatment.
Threatening abandonment or suggesting
that patients will not have continued
access to non-opioid pain relieving
treatments if opioids are terminated

To be effective, written agreements must be

clearly understood by the patient. This may require
the provision of agreements in multiple languages.
All agreements should be written at the sixth- to
seventh-grade level or even lower.24,25 Translators
may need to be provided for speakers of other
languages to ensure patient understanding and
effective informed consent. A patient who does not
fully understand the potential risks and benefits of a
treatment cannot be truly informed as required by
the legal and ethical guidelines for medical practice.
Time must be allowed for patients to ask questions,
and for prescribers to ensure patients understand
what they are being told. Some, or all, of these tasks
may be handled by trained personnel (or staff
members) rather than clinicians.
Although the term agreement is generally
perceived as being more patient-friendly than the
word contract, clinicians should understand that,
from a legal standpoint, any written or oral
agreement between a prescriber and a patient may be
considered a binding contract.26 Clinicians should
ensure that the terms in any agreement are
understood by the patient, and are acceptable,
attainable, and consistent with high-quality
practice.26
Creating Function-based Opioid Treatment Plans
Once a patient has been assessed and
accepted as a candidate for treatment with an opioid
pain medication, and after informed consent has
been obtained for such treatment, a written plan for
implementing the treatment should be drafted. Such
plans typically include a statement of the goals of
therapy. These goals should be written carefully in
light of the inherent subjectivity of pain. Since pain
itself cannot be measured objectively, framing
treatment goals solely in terms of pain relief means
that such goals cannot be objectively confirmed.

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Although a patients subjective pain and

suffering are obviously important factors, only the
functional impact of the pain can be measured and
used to create objective treatment goals. This impact
takes many forms, but typically chronic pain erodes
foundations of daily life, such as physical activity,
concentration, emotional stability, interpersonal
relationships, and sleep. This can, in turn, degrade
functioning at work or in the home, which can lead
to depression, anxiety, insomnia, and even suicide.
Clinicians should know that even relatively modest
reductions in pain can translate into significant
functional improvements as pain rating declines.27 A
20% reduction in a pain score (i.e., roughly two
points on the standard 0-10 pain scale) may be
acceptable if it produces significant functional
benefits for a patient.
Framing treatment goals in terms of
improved patient functioning, rather than merely
pain relief, offers two primary advantages to
clinicians:
Prescribing decisions (or decisions to

terminate treatment) are based on outcomes

that can be objectively demonstrated to both
clinician and patient (and, possibly, to the
patients family)
Individual differences in pain tolerance
become secondary to the setting and
monitoring of treatment goals, since
subjectively perceived levels of pain are not
the primary focus in determining
functionality.
Basing treatment plans on functional goals is
especially valuable in the context of prescribing
opioid pain medications, because such goals may
help differentiate a patient who is truly opioid
addicted from one who merely seems to be addicted.
This differentiation is possible because addiction
often leads to decreased functioning, while effective
pain relief typically improves functioning.
Functional decline itself may result from a
range of problems, including inadequate pain relief,
non-adherence to a regimen, function-limiting side
effects, or untreated affective disorders. Sometimes
impaired functioning is the result of addiction or
misuse, and these objective results may shed
valuable light on an otherwise confusing
presentation of a patients pain symptoms.

Functional treatment goals should be

realistic. Progress in restoring function is usually
slow and gains are typically incremental. Chronic
non-cancer pain is often marked by long-standing
physical and psychological deconditioning, and
recovery may require reconditioning that may take
weeks, months, or years. It is much better to set
goals that are slightly too low than slightly too high.
Raising goals after a patient has succeeded in
achieving them is far more motivational and
encouraging than lowering goals after a patient has
failed.
Table 3: Evidence for Functional Goals
Functional Goal
Begin physical therapy
Sleeping in bed as opposed
to lounge chair
Participation in pain support
group
Increased activities of daily
living
Walk around the block
Increased social activities
Resumed sexual relations
Returned to work

Daily exercise

Evidence
Letter from physical
therapist
Report by family member
or friend (either in-person
or in writing)*
Letter from group leader
Report by family member
or friend
Pedometer recordings or
written log of activity
Report by family member
or friend
Report by partner
Pay stubs from employer
or letter confirming the
patient is off of disability
leave
Gym attendance records or
report from family
member or friend

* Involving other persons requires explicit permission from the patient,

and this permission should be documented, preferably in writing.
Source: Fishman SM. Responsible Opioid Prescribing: A Clinicians
Guide, 2nd Ed. Waterford Life Sciences. 2012 (in press).

Table 3 illustrates some simple functional

goals and ways they might be verified.
The responsibility for obtaining evidence of
success in meeting a functional goal lies with the
patient and should be made explicit in the
prescribing agreement. If a patient is unable to
document or achieve the progress outlined in a
treatment plan, this may suggest a need for goal
readjustment.

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Components of an Effective Treatment Plan

The creation of an effective function-based
treatment plan must be a collaboration between
patient and clinician. A patients pain score will be
just one of many variables to be considered in
framing goals. These goals should be realistic,
meaningful to the patient, and verifiable. The details
of a function-based treatment plan are necessarily
specific to the patient, but one way to initiate the
process is to begin with the question: What do you
hope to do as a result of treatment that you cant do
now?
The treatment plan can include a discussion
of, and the setting of expectations about, periodic reassessment of goals. Patients may stabilize at a
certain level of function, and the clinician and
patient together must decide if this is acceptable or
whether changes are needed.
As is the case in drafting other types of
patient/provider documents, patients should be
reminded of the benefits and risks of a chosen
therapy. With opioids, these include the realities of
tolerance and physical dependence and the potential
need to taper the medication slowly to avoid
withdrawal. Patients must also be educated about the
possibility that opioids may be either ineffective or
have intolerable adverse effects, and that there is
also the possibility of psychological dependence,
which could lead to misuse or, less commonly,
addiction.
Another critical component of any treatment
plan is a description of how treatment with an opioid
medication might be terminated. Stopping opioid
therapy in cases of chronic non-cancer pain is often
more difficult than starting it. Being clear about the
conditions under which opioid therapy will end is
important because opioids are not curative, have no
standard duration of treatment, and may be
associated with substantial risks.17
Termination may be required for many
reasons, including:

Healing or resolution of a specific

pathology underlying the pain
The experience of intolerable side
effects
Lack of adequate response to a
medication in terms of either pain relief
or functional improvement

Evidence of non-medical or
inappropriate use of the medication(s)

If inappropriate use of a prescription

medication is discovered, treatment must usually be
suspended, although provisions should be in place
for continuation of some kind of pain treatment
and/or referral to other professionals or members of
a pain management team. Some clinicians may be
willing and able to continue a regimen of opioid
therapy even after the discovery of aberrant behavior
if done with intensified monitoring, patient
counseling, and careful documentation of all
directives. This level of vigilance and risk
management, however, may exceed the abilities and
resources of the average prescriber. In such cases,
referral to a provider with specialized skill or
experience in dealing with high-risk patients may be
prudent.
Case Study: Treatment Hits a Roadblock
Mr. Davidson returns for a follow-up after 2 weeks.
He reports that his arthritis pain has gotten only
slightly better, but that he is still experiencing the
burning/tingling pain in his hands and feet. He has
not achieved any of his functional goals. Upon
questioning, he reveals that he has not been taking
the opioid medication as frequently as prescribed
because he doesnt want to become an addict.
This common patient fear is allayed with careful,
compassionate education that explains the
differences between addiction and tolerance and
that communicates the key principle that proper use
of an opioid may improve functioning and quality of
life. The prescription for the ER-LA opioid is
continued, and a prescription for 10 mg extendedrelease gabapentin is added.
Initiating Treatment With Opioids
Prior to an initial prescription of an opioid
pain medication, clinicians should be certain that (1)
all other potentially effective treatments that offer a
more optimal benefit-to-risk profile have been
considered or tried; (2) a complete evaluation has
been performed and fully documented; (3) the
patients level of opioid tolerance has been
determined; and (4) informed consent and agreement

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to treat have been obtained.17 At the outset, both the

clinician and the patient should view a new opioid
prescription as a short-term trial of therapy.1 The
goal of the trial is to provide data to guide decisions
on the continued appropriateness of opioid
medications and on the specific dose and
formulation of medication used. Such a trial might
be as brief as a few days or as long as several
months.
Opioid selection, initial dosing, and titration
must be individualized to the patients health status,
previous exposure to opioids, and treatment plan.1
Although still not widely used, it is also becoming
increasingly possible to use commercially-available
genetic screening tools to assess for genetic
variations in drug metabolism that could affect the
way a patient responds to opioids.28 Caution should
be exercised when using opioids in patients with
conditions that may be complicated by adverse
effects from opioids, including chronic obstructive
pulmonary disease (COPD), congestive heart failure,
sleep apnea, current or past alcohol or substance
misuse, mental illness, advanced age, or patients
with a history of renal or hepatic dysfunction.29 In
addition, opioids should not be combined with other
respiratory depressants, such as sedative-hypnotics
(benzodiazepines or barbiturates) unless there is a
specific medical and/or psychiatric indication for
such a combination.30 In such cases, much more
intensive monitoring is required.
A decision to continue opioid therapy after
an appropriate trial should be based on careful
review of the trial outcomes. Outcomes to consider
include:17

Progress toward meeting therapeutic goals

Changes in functional status
Presence and nature of opioid-related
adverse effects
Changes in the underlying pain condition
Changes in medical or psychiatric
comorbidities
Degree of opioid tolerance in the patient
Identification of altered or aberrant
behaviors, misuse, or diversion

Dose Titration
Patients who are opioid-nave or have
modest previous opioid exposure should be started at
a low dose of a short-acting opioid and titrated

10

slowly upward to decrease the risk of opioid-related

adverse effects.1 If it is unclear whether a patient has
recently been using opioids (either prescribed or
non-prescribed), the clinician should assume that the
patient is opioid-nave (i.e., not tolerant) and proceed
as just described.
Opioid tolerance should be established
before prescribing an ER/LA opioid.30 The selection
of a starting dose and manner of titration are clinical
decisions that must be made on a case-by-case basis
because of the many variables involved. Some
patients, such as frail older persons or those with
comorbidities, may require an even more cautious
therapy initiation.1 Short-acting opioids are usually
safer for initial therapy since they have a shorter
half-life and may be associated with a lower risk of
overdose from drug accumulation.1
Further studies are needed to confirm more
consistent control of pain and improved adherence to
prescribed therapy with use of ER/LA opioids.1
Although low-dose, short-acting opioids may offer
the greatest safety for initiating opioid therapy,
clinicians must recognize that short-acting opioids
are not intrinsically safer than other formulations,
and stress to their patients the importance of strict
adherence to prescribed doses/administration.1
Considerations in Opioid Selection
Opioids, as a class, comprise many specific
agents available in a wide range of formulations. A
given patient might be appropriate for ER/LA
therapy only, short-acting only, or a combination of
an ER/LA opioid with a short-acting opioid for
breakthrough pain.
Short-acting, orally-administered opioids
typically have rapid onset of action (10-60 min.) and
relatively short duration of action (2-4 hours).31
They are used for acute or intermittent pain, or
breakthrough pain that occurs against a background
of a persistent level of pain.31 [Transmucosal
immediate-release fentanyl is a special class of
short-acting opioid that is only approved for
breakthrough pain in cancer, and there is a separate
FDA REMS devoted to this topic.]32
Combination products join an opioid with a
non-opioid analgesic, usually for use in patients with
moderate pain. Using a combination product when
dose escalation is required risks increasing adverse

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effects from the non-opioid co-analgesic, even if an

increase of the opioid dose is appropriate.17 In such
cases, using a pure opioid may be preferable.
Unfortunately, at this time, no pharmaceutically manufactured single-agent option for
hydrocodone is available, although clinical trials are
underway as part of an effort to secure FDA
approval for such an agent. Single-agent formulations are available for other types of opioids, such
as codeine, morphine, oxycodone, oxymorphone,
and hydromorphone. In 2011, the FDA announced
new rules that will limit to 325 mg the amount of
acetaminophen allowed in opioid combination
products in an attempt to limit liver damage and
other ill effects from the use of these products with
over-the-counter analgesics.33
ER/LA opioids usually have a relatively
slow onset of action (typically between 30 and 90
min.) and a relatively long duration of action (4 to
72 hrs).31 Such agents are typically used for patients
with constant background pain.31 These agents
achieve their extended activity in various ways.
Methadone and levorphanol have intrinsic
pharmacokinetic properties that make their effects
more enduring than many short-acting opioids.34
ER/LA agents such as controlled-release morphine,
oxycodone, or transdermal fentanyl achieve their
prolonged time course via a delivery system that is
modified to slow absorption or to slow the release of
the active ingredient.31 Clinicians should warn
patients that unless specifically instructed otherwise,
oral ER/LA opioids should not be broken, chewed,
or crushed, and patches should not be cut or torn
prior to use, since this may lead to rapid release of
the opioid and could cause overdose or death.
Prescribers should educate themselves about
the general characteristics, toxicities, and drug
interactions for ER/LA opioid products. [For
detailed information on current ER/LA opioid
analgesics, see the FDA Blueprint for Prescriber
Education, available at: http://www.er-laopioidrems.com]. Respiratory depression is the most
serious adverse effect of opioids as it can be
immediately life-threatening. Constipation is the
most common long-term side-effect but can often be
managed. Drug-drug interaction profiles vary among
the products. Knowledge of particular opioid-drug
interactions, and the underlying pharmacokinetic and
pharmacodynamic mechanisms, allows for the safer

11

administration of opioid analgesics.

Central nervous system depressants
(sedatives, hypnotics, tranquilizers, tricyclic
antidepressants and alcohol) can have a potentiating
effect on the sedation and respiratory depression due
to opioids.30 Alcohol consumption should be
avoided entirely with some oral products (e.g.
morphine, hydromorphone, oxymorphone) because
ethanol increases the plasma concentration of the
opioid.30
Opioids may enhance the neuromuscular
blocking action of skeletal relaxants and produce an
increased degree of respiratory depression. Using
opioids with monoamine oxidase inhibitors
(MAOIs) may result in possible increase in
confusion, anxiety, and respiratory depression.30
Opioids can reduce the efficacy of some
diuretics by inducing the release of antidiuretic
hormone (ADH).30 In addition, some opioids interact
with various cytochrome P450 enzyme inhibitors
and inducers and thus may result in higher or lower
than expected blood levels of the drug.
Methadone can be an effective opioid, but it
must be prescribed carefully and with full
knowledge of its highly variable pharmacokinetics
and pharmacodynamics. (See page 83 for a more
detailed discussion of methadone.)
Abuse-Deterrent Formulations
As concern has risen about opioid misuse
and abuse, efforts have been made to create abusedeterrent and tamper-resistant opioid formulations.
One class of deterrent formulation incorporates an
opioid antagonist into a separate compartment deep
within a single capsule; crushing the capsule releases
the antagonist and neutralizes the opioid effect.31
The central opioid antagonist compartment is
eliminated from the body unchanged if the capsule is
consumed normally without tampering. Another
strategy is to modify the physical structure of tablets
or incorporate compounds that make it difficult or
impossible to liquefy, concentrate, or otherwise
transform the tablets.31
Transdermal opioid formulations have been
perceived in the past as less vulnerable to misuse,
but such formulations can be abused. For example, a
transdermal, 7-day duration formulation of

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buprenorphine has been reported to be an

increasingly abused opioid, particularly in prison
populations.35 As a partial opioid agonist,
buprenorphine was thought to be a lower-risk agent
than full agonist opioids, however it is clear that this
medication can be as susceptible to abuse as fullopioid agonists.
Abuse-deterrent opioid formulations, of
course, do not prevent users from simply consuming
too much of a medication. These formulations may
help reduce the public health burden of prescription
opioid abuse, but the evidence to date is inadequate
to project whether this potential will actually be
achieved.31
Case Study: Progress
At follow-up visit 2 weeks later, Mr. Davidson
reports reduced pain and improved functioning. He
says his pain is now 3-4 on a 10-point scale. He can
now walk his dog twice daily, and is using the
computer keyboard without pain. He says his sleep
has improved as well. Mr. Davidson asks for a
higher dose of the opioid to see if I can get the pain
down to zero. Although seemingly reasonable, it is
explained to Mr. Davidson that, in fact, zero pain
is an unrealistic goal for anyone, and that
increasing the dose to achieve that goal would likely
incur a range of side effects that would erode his
overall quality of life. Although initially
disappointed, Mr. Davidson acknowledged the
explanation and did not press the issue.
Periodic Review and Monitoring
If a trial of an opioid medication is deemed
successful and opioid therapy is continued, periodic
review and monitoring should be performed for the
duration of treatment. The tests performed, questions
asked, and evaluations made should be tailored to
the patient as guided by the physicians clinical
judgment. For example, a physical examination may
or may not be required at each follow-up visit.
Clinicians must evaluate progress against agreedupon treatment goals and assess for a wide range of
potential adverse effects, ranging from physical side
effects such as constipation or sedation, to
behavioral side effects such as mood changes, signs
of drug craving or seeking, or impaired function in
various domains of daily living.17 As part of routine

12

practice, clinicians who prescribe opioids should

perform medication reconciliation at each patient
visit.36 The American Medical Association defines
medication reconciliation as making sense of a
patients medications and resolving conflicts
between different sources of information to
minimize harm and maximize therapeutic effects.36
The intensity and frequency of monitoring is
dependent on an assessment of the patients risk for
abuse, diversion, or addiction. Tools and techniques
similar or identical to those used during an initial
assessment of a patients risk can be used to reassess or monitor risk on an on-going basis.2
States vary in their requirements for
intervals at which follow-up visits are required when
controlled substances such as opioid medications are
prescribed. Although federal law allows for a 90-day
supply of prescriptions for patients receiving
schedule II drugs (who are otherwise deemed safe to
have this amount), state law can vary from 30 days
to 6 months.2 In cases where state and federal law
conflict, the most restrictive rule prevails.2
Relatively infrequent monitoring may be
appropriate for low-risk patients on a stable dose of
opioids. More frequent or intense monitoring is
appropriate for patients during the initiation of
therapy or if the dose, formulation, or opioid
medication is changed. Patients who may need more
frequent or intense monitoring include:17

Those with a prior history of an

addictive disorder, past abuse, or
other aberrant use
Those in an occupations demanding
mental acuity
Older adults
Patients with an unstable or
dysfunctional social environment
Those with comorbid psychiatric or
medical conditions

Daily or weekly monitoring may be

necessary for patients at very high risk for adverse
outcomes.
Reviewing Functional Goals
A key part of periodic monitoring is a
careful review of previously-agreed-upon functional
goals. Patients should come to appointments ready
to provide the evidence upon which an evaluation of
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progress can be made. This evidence should span as

many domains of a persons life as possible:
personal and social relationships, employment,
physical activities, health, hobbies, and spiritual
activities. Functional goals that are not attained
require investigation, possible adjustment, and
encouragement that future progress is possible. If the
goals have been attained, clinicians should be
supportive and positive, while setting new goals to
motivate further progress.
Functional goals related to physical activity
are sometimes not achieved by patients because they
report that the agreed-upon activity hurts too much.17
Such cases should be carefully evaluated before a
decision is made to increase the dose of an opioid
medication. All patientseven those with end-stage
diseasecan engage in some kind of physical
activity at least some time during the day. The
motions or activity may be extremely modest, yet
they may nonetheless serve as effective functional
goals. Patients with chronic pain often require such
micro-level goals and controlled, graduallyincreasing motion or activity over sustained periods
of time.
Managing Breakthrough Pain
Patients with chronic pain receiving a steady
dose of an opioid medication may experience
episodes of pain that break through the analgesic
effects of the steady-state drug (regardless of the
route of administration).1 Close monitoring of
breakthrough episodes is key to helping patients
reduce pain and facilitate functioning. Providing
patients either paper or electronic pain diaries can
help them track breakthrough episodes and spot
correlations between the episodes and variables in
the patients life. If specific triggers are identified,
this may provide opportunities for changes that will
reduce the prevalence of breakthrough episodes
without recourse to increased reliance on
medication.17
Non-opioid methods of dealing with
breakthrough pain (i.e., cold or warmth, massage,
yoga, acupuncture, meditation, electrical
stimulation) might be considered prior to any
increases in opioid medication; although research
evidence regarding many CAM (complementary and
alternative medicine) approaches is inconclusive. If
a short-acting opioid preparation is prescribed for

13

breakthrough pain, clinicians should remind patients

about the potentials problems of diversion and
misuse of these agents.

urine could indicate adulteration. If possible, urine

temperature and pH should be measured
immediately after collection.2

As with the management of the underlying

chronic pain condition, clinicians should use an
agreed-upon set of functional goals as a way to
monitor, and if necessary, adjust, the use of asneeded opioid medications for breakthrough pain.

One way to reduce the risk of urine test false

positives or false negatives is to develop a
relationship with a single laboratory, become
familiar with its testing tools and threshold values,
and use the same screening and confirmatory tests
regularly to build familiarity with the range of
normal results.17

Monitoring Adherence
Trust is a necessary part of any
patient/clinician relationship, but studies suggest that
in the context of controlled substances, it is unwise
to rely on a patients word that medications are
being consumed as prescribed.2 Although the use of
more objective ways to monitor adherence to
medication regimens is an imperfect science, such
methods remain an essential component of periodic
review. Multiple objective methods to assess
adherence exist, but there is no single best
approach and all such methods have both advantages
and potential drawbacks.
Drug testing should be approached in a
consensual manner as part of an agreed-upon
treatment plan and with the idea that such testing
benefits both the patient and the provider.2 The
potential benefits of clinical drug testing include:2

Serving as a deterrent to inappropriate

use
Providing objective evidence of
abstinence from drugs of abuse
Monitoring response to treatment
Assisting with a diagnosis
Helping patients allay concerns by
family members, employers, or lawenforcement
Demonstrating to regulatory authorities
a clinicians dedication to monitoring
best practices

In the context of family practice settings,

unobserved urine collection is usually an acceptable
procedure for drug testing. Prescribers, however,
should be aware of the many ways in which urine
specimens can be adulterated. Specimens should be
shaken to determine if soap products have been
added, for example. The urine color should be noted
on any documentation that accompanies the
specimen for evaluation, since unusually colored

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Prescribers should be familiar with the

metabolites associated with each opioid that may be
detected in urine, since the appearance of a
metabolite can be misleading.2 A patient prescribed
codeine, for example, may test positive for morphine
because morphine is a metabolite of codeine. Similar
misunderstandings may occur for patients prescribed
hydrocodone who appear positive for
hydromorphone or oxycodone and oxymorphone
(see Table 4).
Table 4: Urinary Analytes of Common Opioid
Pain Medications
Drug
Urinary Analytes
Morphine
Morphine
Hydromorphone
Codeine
Codeine
Codeine
Morphine
Hydrocodone
Hydrocodone
Hydrocodone
Hydromorphone
6-Hydrocodol
Oxycodone
Oxycodone
Oxymorphone
Hydrocodone
Source: Webster LR, and Dove B. Avoiding Opioid Abuse While
Managing Pain. Lifesource. 2007.

Case Study: A Caution Light

After 3 weeks, the physician is given a message that
a young woman has called requesting an early refill
of Mr. Davidsons opioid because hes suffering.
This raises the physicians suspicions. He accesses
his state Prescription Drug Monitoring Program to
see if Mr. Davidson might be getting prescriptions
from another provider. He is not, and nothing
appears unusual. The physician calls Mr. Davidson
directly and Mr. Davidson confirms that he did ask

14

his granddaughter to call for the prescription

because he was having increased pain after playing
tennis for an hour. Mr. Davidson is advised to
temporarily use an OTC NSAID (not more than 600
mg) and is asked to return for an in-person visit
within a week. At that visit, a range of nonpharmacological strategies are reviewed, with the
aim of providing additional pain relief and improved
function (i.e., post-exercise cold/warm treatments;
exercises to improve flexibility; massage; and the
use of an elbow brace to be used for tennis).
Using Prescription Drug Monitoring Programs
(PDMPs)
PDMPs can serve an important clinical
monitoring role. PDMPs use secure Internet sites to
offer point-of-care access to records of controlled
substances from other prescribers and dispensing
pharmacies. From these, clinicians can quickly glean
patterns of prescription drug use that can be helpful
in confirming or refuting suspicions of aberrant
behaviors. Information from a PDMP may also be
clinically relevant in that it may reveal that a patient
is being prescribed medications whose combinations
are contraindicated.
There is currently little uniformity,
information-sharing, or cooperation among state
PDMPs, but efforts are under way to improve this
situation. An advisory committee of the Council of
State Governments has endorsed the formation of an
interstate PDMP compact, and legislation to
accomplish this goal is currently being drafted.37 By
checking PDMP data (particularly for high-risk
patients), clinicians can get a sense of the controlled
substances that the patient has been receiving from
other prescribers and other pharmacies.38 Individuals
may have perfectly acceptable reasons for multiple
prescribing episodes, but the existence of such a
pattern should always trigger inquiry.
Common Issues Related to Opioid Pain
Medications
Preventing and Managing Opioid-Related Side
Effects
Many patients treated with an opioid will
experience side effects, the most common of which
is constipation. Other possible effects include:31

Respiratory depression

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Sedation
Urinary hesitancy or retention
Dry mouth
Nausea/vomiting
Itching
Sweating
Hypogonadism
Myoclonus

Some side effects, such as sedation, may

lessen over time after treatment initiation. Others,
such as constipation, rarely become less problematic.
Constipation is so common, in fact, that when
patients use opioids and do not have constipation,
clinicians should consider possible reasons ranging
from rapid bowel transit time to diversion.
Constipation requires proactive treatment, with
stimulating laxatives prescribed at the time of
initiating opioids, and frequent re-evaluation. With
the exception of constipation, uncomfortable or
unpleasant side effects may potentially be reduced
by switching to another opioid or route of
administration (such side effects may also be
alleviated with adjunctive medications).
Opioids and Pregnancy
Some data suggest an association between
the use of long-term opioid therapy during
pregnancy and adverse outcomes in newborns,
including low birth weight and premature birth,
though co-related maternal factors may play a role in
these associations and causality is not certain.1
Higher doses of antenatal methadone in tolerant
mothers do not seem to increase complication rates.1
Importantly, opioid withdrawal can be expected in
up to half of newborns of opioid-dependent
mothers.1 If a mother is receiving long-term opioid
therapy at or near the time of delivery, a professional
experienced in the management of neonatal
withdrawal should be available.1
Nonetheless, given the potential risks of
opioids during pregnancy, current American Pain
Society-American Academy of Pain Medicine (APSAAPM) guidelines suggest that clinicians should
encourage minimal or no use of opioids during
pregnancy unless the potential benefits outweigh
risks.1 If opioid medications are prescribed,
clinicians should thoroughly counsel pregnant
women about the potential risks and benefits, and

15

clinicians should be prepared to anticipate and

manage risks to the patient and newborn.
Driving and Work Safety
Driving while using opioid medications
remains a controversial issue. Particularly at the
initiation of therapy, opioid medications may cause
sleepiness, clouded thinking, decreased
concentration, slower reflexes, or incoordination, all
of which may pose a danger to the patient and others
when driving or operating machinery.1 On the other
hand, a number of epidemiologic studies failed to
show an association between long-term opioid use
and motor vehicle accidents, fatalities, or citations
for impaired driving.1 Since at least some of the
cognitive and motor-impairing effects of opioids
resolve with steady use and a consistent dose, some
activities or driving may be allowable at the
discretion of the clinicians medical judgment and in
the absence of signs of impairment.
Current APS-AAPM guidelines recommend
that all patients who are initially prescribed opioid
medications, or those who have their dose increased,
be advised not to drive or engage in potentially
dangerous work or other activities.1 There is no
consensus on exactly how long they should abstain
from driving. Patients should be educated about the
increased risk of impairment when starting opioid
therapy, when increasing doses, and when taking
other drugs or substances (such as, alcohol,
benzodiazepines, or even some cold remedies) that
may exacerbate cognitive and motor impairment.
Clinicians should be aware that certain professions
(i.e., school bus drivers and pilots) may be subject to
restrictions in the use of opioid medications.1
Clinicians should check with their state medical
society or the Federation of State Medical Boards to
obtain up-to-date information in this regard.
Screening for Endocrine Function
Both male and female patients on long-term
opioid therapy are at risk for hypogonadism, thus the
endocrine function of all patients should be assessed
at the start of long-term opioid therapy and at least
annually thereafter. The symptoms of hypogonadism
in both genders may include fatigue, mood changes,
decreased libido, loss of muscle mass, and
osteoporosis. Although there are insufficient data to

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recommend routine endocrine screening of

asymptomatic patients, current guidelines do
recommend such testing for patients exhibiting any
of the aforementioned signs and symptoms.1
Opioid Rotation
Opioid rotation means switching from one
opioid to another in order to better balance analgesia
and side effects. Rotation may be needed because of
a lack of efficacy (often related to tolerance),
bothersome or unacceptable side effects, increased
dosing that exceeds the recommended limits of the
current opioid (e.g., dose limitations of cocompounded acetaminophen), or inability to absorb
the medication in its present form (i.e., if there is a
change in the patients ability to swallow, switch to
a formulation that can be absorbed by a different
route such as transdermal.)31
Because of the large number of variables
involved in how any given opioid will affect any
given patient, opioid rotation must be approached
cautiously, particularly when converting from an
immediate-release formulation to an ER/LA
product.31 An equianalgesic chart should be used
when changing from one opioid to another or from
one route of administration to another. Such charts
must be used carefully, however. A high degree of
variation has been found across the various charts
and online calculator tools, and may account for
some overdoses and fatalities.39 The optimal dose for
a specific patient must be determined by careful
titration and appropriate monitoring, and clinicians
must be mindful that patients may exhibit
incomplete cross-tolerance to different types of
opioids because of differences in the receptors or
receptor sub-types to which different opioids bind.31
In some cases, because of the risk of
potential harm during the time of rotating from one
chronic opioid regimen to another, it may be wise to
initially use lower doses of an ER/LA opioid than
might be suggested by equianalgesic charts, while
temporarily liberalizing, as needed, the use of a
short-acting opioid. This would then be followed by
gradual titration of the LA opioid to the point where
the as-needed short-acting opioid is incrementally
reduced, until no longer necessary.

16

Managing Non-Adherent Patients

Case Study: Stable Improvement

Patients who begin to exhibit aberrant drugrelated behaviors or non-adherence to a prescription

should be monitored more strictly than compliant
patients. Suspicion that a patient is non-adherent
should prompt a thorough investigation of the
situation, including an honest evaluation of the
patient/provider relationship. The way clinicians
interact with patients can affect the relationship (for
better or worse) and influence treatment outcomes.17
A clinicians negative reactions to non-adherence
might include anger at the patient, disappointment
and sadness at the apparent betrayal of trust, or fear
that the patients behavior could expose the provider
to legal jeopardy.17

After a slight dose adjustment of the gabapentin, Mr.

Davidson reports continued functional progress and
acceptable levels of pain. He has increased his level
of physical activity and reports that his mood and
general health are better as a result. He states he
would like to try to taper his use of the opioid, and
he is given clear and specific instructions for how to
do that.

Before accusing a patient of not adhering to

a prescribed regimen, clinicians should assess the
situation fully. Possible reasons for non-adherence
include:

Inadequate pain relief

Misunderstanding of the specifics of
the prescription
Misunderstandings related to lack of
fluency with English
Attempts to stretch a medication
in order to save money
Cultural or familial pressure not to
take a medication
Stigma about taking a pain
medication
Overmedication and fears about
addiction
Misunderstanding of a prescription
by a caregiver who has taken
responsibility for daily apportioning
of medications
Confusion between two medications
that look very similar to each other

The use of patientprovider agreements

and/or informed consent documents can help
clinicians navigate the uncertainties that can arise in
cases of real or apparent non-adherence, and may
help make the process less confrontational.
Consultation with an addiction medicine specialist
or psychiatrist may be necessary if addiction is
suspected or if a patients behavior becomes so
problematic that it jeopardizes the clinician/patient
relationship.

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Treatment Termination
Reasons for discontinuation of an opioid
analgesic can include the healing of or recovery
from an injury, medical procedure, or condition;
intolerable side effects; lack of response; or
discovery of misuse of medications. Regardless of
the reason, termination should be accomplished so as
to minimize unpleasant or dangerous withdrawal
symptoms by tapering the opioid medication slowly,
or by carefully changing to a new formulation.
Approaches to weaning range from a slow 10%
reduction per week to a more aggressive 25 to 50%
reduction every few days.1 In general, a slower taper
will produce fewer unpleasant symptoms of
withdrawal.
In general, opioid therapy must be
discontinued or re-evaluated whenever the risk of
therapy is deemed to outweigh the benefits being
provided. A clinician may choose to continue opioid
treatment with intensified monitoring, counseling,
and careful documentation if it is deemed in the best
interest of the patient. This requires, however,
careful consideration and a well-documented risk
management plan that addresses the greater
resources necessary for opioid continuation
following evidence of misuse.
If termination of the provider/patient
relationship is deemed necessary, clinicians must
ensure that the patient is transferred to the care of
another provider and ensure that the patient has
adequate medications to avoid unnecessary risk,
such as from uncontrolled or potentially dangerous
withdrawal.17 Practitioners can be held accountable
for patient abandonment if medical care is
discontinued without justification or adequate
provision for subsequent care.

17

Methadone
Methadone has recently received growing
attention and concern because it is frequently
involved in unintentional overdose deaths.40 These
deaths have escalated as methadone has increasingly
been used as an analgesic drug for chronic pain.41 At
one time, methadone had been used almost
exclusively in opioid maintenance therapy programs
to treat addiction. Its relatively long plasma
elimination half-life compared to its relatively short
analgesic half-life makes it optimal for maintenance,
allowing for once-daily dosing. But methadone only
exerts potent analgesic effects in the early phase of
its elimination half-life, and this, along with the fact
that it is among the least expensive opioids, has led
to a dramatic increase in its use for alleviating
chronic non-cancer pain.1
Methadone has unique pharmacokinetic and
pharmacodynamic characteristics that add
substantial risk to its use. Although its chemical
structure is different from classic opioids such as
morphine, methadone acts on the same set of opioid
receptors, though with different affinities for the
various opioid receptor subtypes.34 In addition,
methadone possess non-opioid receptor effects that
may explain some of its potential special efficacy.
These varied effects across opioid receptors, along
with its non-opioid properties, have garnered
methadone the reputation of being a broad
spectrum opioid.34 For a number of reasons,
however, methadone must be titrated very carefully
in order to avoid overdose. These reasons include:34

An analgesic half-life much shorter than

its elimination half-life (leading to
accumulation)
Metabolism by a group of liver enzymes
that differ from those associated with
most other opioids, hence leading to
unexpected drug-drug interactions
Significant genetic variations in the liver
enzymes that metabolize methadone,
which contribute to the unpredictability
of methadones effects and side effects
Metabolism may be affected by cigarette
smoking (which accelerates elimination)
and alcohol consumption (which can
augment methadone toxicity acutely and
accelerate metabolism with chronic use)

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The APS/AAPM guidelines recommend a

starting dose in most opioid-naive patients of 2.5 mg
every 8 hours, with dose increases occurring no
more frequently than weekly.1 The lowest possible
dose titration should be followed even in opioidtolerant patients because methadone appears to be
more potent in patients who have been using higher
doses of the pre-switch opioid. The total daily dose
of methadone on the first day of treatment should
not ordinarily exceed 30-40 mg/d regardless of prior
exposure.42 In older patients or those with renal or
hepatic comorbidities, lower starting doses, less
frequent dosing, and more cautious dose titration are
recommended. Because of its long half-life and
variable pharmacokinetics, methadone is not
recommended to treat breakthrough pain or as an asneeded medication.
When rotating from another opioid to
methadone, extreme caution must be used when
referring to equianalgesic conversion tables. The
consensus recommendations from an expert panel
suggest a 75 to 90% decrement in the equianalgesic
dose from conventional conversion tables when a
switch is made from another opioid to methadone.43
Because the risk of overdose is particularly
acute with methadone, patients should be educated
about these risks and counseled to use methadone
exactly as prescribed. They should also be warned
about the dangers of mixing unauthorized substances
with their medication. Benzodiazepines, in
particular, pose a threat. Death investigations often
find that benzodiazepines have been used in
combination with methadone and other opioids.40
Other respiratory depressants, including alcohol,
pose similar risks. Dosing should, therefore, be
conservative and cautious until patients demonstrate
the ability to tolerate and use the drug safely.
In 2006, the FDA issued a public health
advisory warning that methadone can cause serious
cardiac conduction disturbances, including QT
interval prolongation and Torsades de Pointes, a
potentially fatal ventricular arrhythmia.44 It appears
that methadone-related corrected QT (QTc) interval
prolongation and cardiac arrhythmias can occur at
any dose but are more likely at higher doses or with
concomitant use of drugs that interact with
methadone or that themselves prolong QTc.
Although uncommon, the cardiac arrhythmias that
can be induced by methadone can be lethal if not

18

detected. The cardiac health of patients who are

candidates for methadone should be assessed, with
particular attention paid to any history of heart
disease or arrhythmias.45 An initial ECG may be
advisable prior to starting methadone, particularly if
a patient has a specific cardiac disease or cardiac
risk factors or is taking agents that may interact with
methadone.45
Required Patient Education
Thorough patient education about the safe
use, storage, and disposal of opioid medications is
an essential part of best practices opioid
prescribing. This education can be partially
integrated into standard patient/provider agreements
or informed consent documents. As with other
patient-directed materials, education must be
provided in a language and at a reading level
(typically 6th-7th grade) appropriate for a clinicians
patient population. Examples of effective patient
education can be found at websites, such as
Opioids911-Safety (www.opioids911.org).
Safe use of opioid medications means that
patients carefully follow clinician instructions,
including special directions about timing of doses
and whether to administer the medication with food
or without. Clinicians should be mindful of any
physical limitations (i.e. poor eyesight) that a patient
might have that could interfere with accurate and
timely administration of prescribed opioids.
Here are some key ideas to convey to
patients about proper use:46

Read the prescription container label

each time to check dosage
Never use medicines after expiration
date
Never share medicines with others
Do not take a pain medicine with
alcohol or other sedatives
Do not take a pain medicine to
promote sleep
Never break, chew, or crush
medicines, particularly ER/LA
opioid medications
For transdermal products, external
heat, fever, and exertion can
increase absorption, leading to a
potentially fatal overdose

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Transdermal products with metal

foil backings are not safe for use in
MRI scanners
Do not use transdermal products if
they are broken or torn

Safe Storage
Patients need to be reminded that even
children or close relatives can be tempted to use pain
medications they have not been prescribed. Opioids
are often obtained by teens, for example, from unsecured medicine cabinets of family and friends.
If possible, opioid pain medications should
be stored in a locked cabinet or other secure storage
unit. Storage areas should be cool, dry, and out of
direct sunlight. Remind patients not to store
medications in their car, to keep medications in the
original containers, and to avoid storing medications
in the refrigerator or freezer unless specifically
directed to do so by a healthcare provider or
pharmacist.
Proper Disposal
The Office of National Drug Control Policy
currently recommends that unused opioid pain
medications be flushed down a toilet.47 Some states,
however, may have different or more stringent
guidelines. California, for example, instructs
consumers not to flush any medicines down the
toilet or drain. If flushing medicines is not allowed
in your state, instruct patients to follow the
instructions of a pharmacist for disposal or to mix
the medicines with an undesirable substance, such as
used coffee grounds, put the mixture into a
disposable container with a lid or a sealable bag, and
place it in the trash.
Before they are thrown out, personal
information, including the prescription number,
should be removed from empty medication
containers. Patients should also be encouraged to use
any drug take-back programs available in the local
community. [Note: the Drug Enforcement
Administration maintains up-to-date information on
national take-back programs, as well as ways to find
drug collection sites in any given locale.
Information can be accessed at:
www.deadiversion.usdoj.gov/drug_disposal/takebac
k/index.html.]

19

Take-Home Naloxone
In the future it may become more common
to provide patients and their caregivers with the
intranasal preparation of the opioid antagonist
medication naloxone as a way to reverse the
complications associated with accidental overdose.
Although naloxone was FDA-approved in 1971 and
has been used for decades by emergency medical
services personnel, intranasal administration of
naloxone is not currently approved by the FDA for
at-home use as an antidote for opioid overdose so, as
of this writing, this represents an off-label use of this
medication. Numerous studies and community
initiatives have attested to the safety, convenience,
and effectiveness of providing intranasal naloxone to
patients who may be at risk of overmedication or
overdose.48 This includes patients who:

Receive prescriptions of more than 50

mg of morphine equivalent/day
Are being rotated from one opioid to
another when there may be incomplete
cross-tolerance
Are opioid nave and who have been
prescribed methadone or who are rotated
from another opioid to methadone
Are released after emergency medical
care involving opioid intoxication or
poisoning
Have a suspected history of substance
abuse, dependence, or nonmedical
opioid use.
Have known or suspected concurrent
heavy alcohol use
Have a respiratory infection or illness
May have difficulty accessing
emergency medical services

Efforts are underway in several states to

make intranasal naloxone more widely available to
the public and to train health care and emergency
service providers in its use.48
Dealing With Opioid Overdose
Because respiratory depression is the most
serious potential harm from opioids, it is incumbent
on clinicians to fully inform patients of this fact and
educate them (and their home caregivers, if possible)
on recommended steps to take in an emergency.
Respiratory depression might occur because a

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patient takes more than the prescribed amount, either

intentionally or unintentionally, or because the
patient was mistakenly given too much medication
by a caregiver. Point out that respiratory depression
typically takes some time to develop, hence there
will be early warning signs of overdose including:

Intoxicated behaviorconfusion,
slurred speech, stumbling;
Feeling dizzy or faint;
Acting very drowsy or groggy;
Unusual snoring, gasping, or snorting
during sleep; and
Difficulty waking up from sleep or
staying awake.
Patients and their caregivers should be
counseled to immediately call 911 or an emergency
service if they observe any of these warning signs. If
naloxone has been provided for the patient, it should
be administered immediately, which will reverse
respiratory depression and should allow the patient
to begin breathing more normally. If a person has
stopped breathing, artificial respiration/cardiopulmonary resuscitation (CPR, including rescue
breathing) should be begun immediately until
emergency help arrives.
Conclusions
This monograph has summarized best
practices for the responsible prescribing of opioid
pain medications for chronic non-cancer pain. More
detailed information on many of these topics is
available from the resources listed to the right. The
treatment of pain is a dynamic and evolving field,
and clinicians should periodically refresh their
knowledge through reading, attending seminars or
other events, or by taking additional CME courses.
Clinicians face the competing demands of
relieving pain while minimizing potential harm to
both patients and society. The steps and procedures
described in this monograph provide a roadmap and
structure by which clinicians can achieve these twin
goals without incurring undue burdens of time or
energy. Pharmacovigilance simply means that
prescribers apply basic principles of prudent
medicine to the needs of patients in pain. And
because the evidence base for current guidelines
remains sub-optimal, clinicians retain a great deal of
latitude in deciding how that vigilance is best
deployed on a day-to-day basis.

20

Table 5: Specific Drug Information for Extended-Release and Long-Acting Opioid Analgesics (ER/LA opioid
analgesics)
Morphine Sulfate ER
Avinza
Capsules, 30 mg, 45 mg, 60 mg, 75 mg, 90 mg, and 120 mg
Dosing Interval
Once a day
Key Instructions
Initial dose in opioid non-tolerant patients is 30 mg.
Titrate using a minimum of 3-day intervals.
Swallow capsule whole (do not chew, crush, or dissolve).
May open capsule and sprinkle pellets on applesauce for patients who can reliably swallow
without chewing; use immediately.
Maximum daily dose: 1600 mg due to risk of serious renal toxicity by excipient, fumaric
acid.
Specific Drug Interactions Alcoholic beverages or medications containing alcohol may result in the rapid release and
absorption of a potentially fatal dose of morphine.
PGP inhibitors (e.g. quinidine) may increase the absorption/exposure of morphine sulfate
by about two-fold.
Use in Opioid-Tolerant
90 mg and 120 mg capsules are for use in opioid-tolerant patients only.
Patients
Product-Specific Safety
None
Concerns
Buprenorphine
Butrans
Transdermal System, 5 mcg/hr, 10 mcg/hr, 20 mcg/hr
Dosing Interval
One transdermal system every 7 days
Key Instructions

Specific Drug Interactions

Use in Opioid-Tolerant
Patients
Drug-Specific Safety
Concerns
Relative Potency To Oral
Morphine

Initial dose in opioid non-tolerant patients when converting from less than 30 mg morphine
equivalents, and in mild to moderate hepatic impairment - 5 mcg/hr dose.
When converting from 30 mg to 80 mg morphine equivalents - first taper to 30 mg
morphine equivalent, then initiate with 10 mcg/hr dose.
Titrate after a minimum of 72 hours prior to dose adjustment.
Maximum dose: 20 mcg/hr due to risk of QTc prolongation.
Application
o Apply only to sites indicated in the Full Prescribing Information.
o Apply to intact/non-irritated skin.
o Skin may be prepped by clipping hair, washing site with water only
o Rotate site of application a minimum of 3 weeks before reapplying to the
same site.
o Do not cut.
Avoid exposure to heat.
Dispose of used/unused patches by folding the adhesive side together and flushing down
the toilet.
CYP3A4 Inhibitors may increase buprenorphine levels.
CYP3A4 Inducers may decrease buprenorphine levels.
Benzodiazepines may increase respiratory depression.
Class IA and III antiarrythmics, other potentially arrhythmogenic agents, may increase risk
for QTc prolongation and torsade de pointe.
Butrans 10 mcg/hr and 20 mcg/hr transdermal systems are for use in opioid-tolerant patients
only.
QTc prolongation and torsade de pointe.
Hepatotoxicity

Application site skin reactions

Equipotency to oral morphine has not been established.

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21

Table 5 (continued): Specific Drug Information for Extended-Release and Long-Acting Opioid Analgesics (ER/LA
opioid analgesics)
Methadone Hydrochloride
Dolophine
Tablets, 5 mg and 10 mg
Dosing Interval
Every 8 to 12 hours
Key Instructions
Initial dose in opioid non-tolerant patients: 2.5 to 10 mg
Conversion of opioid-tolerant patients using equianalgesic tables can result in overdose and
death. Use low doses according to the table in the full prescribing information.

Specific Drug Interactions

Use in Opioid-Tolerant
Patients
Product-Specific Safety
Concerns

Relative Potency To Oral

Morphine
Duragesic
Dosing Interval
Key Instructions

Specific Drug Interactions

High inter-patient variability in absorption, metabolism, and relative analgesic potency.

Opioid detoxification or maintenance treatment shall only be provided in a federally
certified opioid (addiction) treatment program (Code of Federal Regulations, Title 42, Sec
8).
Pharmacokinetic drug-drug interactions with methadone are complex.
o CYP 450 inducers may increase methadone levels.
o CYP 450 inhibitors may decrease methadone levels.
o Anti-retroviral agents have mixed effects on methadone levels.
Potentially arrhythmogenic agents may increase risk for QTc prolongation and torsade de
pointe.
Benzodiazepines may increase respiratory depression
Refer to full prescribing information.
QTc prolongation and torsade de pointe.
Peak respiratory depression occurs later and persists longer than analgesic effect.
Clearance may increase during pregnancy.
False positive urine drug screens possible.
Varies depending on patients prior opioid experience.
Fentanyl
Transdermal System, 12, 25, 50, 75, and 100 mcg/hr
Every 72 hours (3 days)
Use product specific information for dose conversion from prior opioid
Use 50% of the dose in mild or moderate hepatic or renal impairment, avoid use in severe
hepatic or renal impairment
Application
o Apply to intact/non-irritated/non-irradiated skin on a flat surface.
o Skin may be prepped by clipping hair, washing site with water only
o Rotate site of application.
o Titrate using no less than 72 hour intervals.
o Do not cut.
Avoid exposure to heat.
Avoid accidental contact when holding or caring for children.
Dispose of used/unused patches by folding the adhesive side together and flushing down
the toilet.
Specific contraindications:
Patients who are not opioid-tolerant.
Management of acute or intermittent pain, or in patients who require opioid analgesia for a
short period of time.
Management of post-operative pain, including use after out-patient or day surgery.
Management of mild pain.

CYP3A4 inhibitors may increase fentanyl exposure.

CYP3A4 inducers may decrease fentanyl exposure.

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22

Table 5 (continued): Specific Drug Information for Extended-Release and Long-Acting Opioid Analgesics (ER/LA
opioid analgesics)
Use in Opioid-Tolerant
All doses of Duragesic are indicated for use in opioid-tolerant patients only.
Patients
Product-Specific Safety
Accidental exposure due to secondary exposure to unwashed/unclothed application site.
Concerns
Increased drug exposure with increased core body temperature or fever.
Bradycardia
Application site skin reactions
Relative Potency To Oral
See individual product information for conversion recommendations from prior opioid
Morphine
Morphine Sulfate ER-Naltrexone
Embeda
Capsules, 20 mg/0.8 mg, 30 mg/1.2 mg, 50 mg/2 mg, 60 mg/2.4 mg,
80 mg/3.2 mg, 100 mg/4 mg
Dosing Interval
Once a day or every 12 hours
Key Instructions
Initial dose as first opioid: 20 mg/0.8 mg.
Titrate using a minimum of 3-day intervals.
Swallow capsules whole (do not chew, crush, or dissolve)
Crushing or chewing will release morphine, possibly resulting in fatal overdose, and
naltrexone, possibly resulting in withdrawal symptoms.
May open capsule and sprinkle pellets on applesauce for patients who can reliably swallow
without chewing, use immediately.
Specific Drug Interactions Alcoholic beverages or medications containing alcohol may result in the rapid release and
absorption of a potentially fatal dose of morphine.
PGP inhibitors (e.g. quinidine) may increase the absorption/exposure of morphine sulfate
by about two-fold.
Use in Opioid-Tolerant
Embeda 100 mg/4 mg capsule is for use in opioid-tolerant patients only.
Patients
Product-Specific Safety
None
Concerns
Hydromorphone Hydrochloride
Exalgo
Extended-Release Tablets, 8 mg, 12 mg or 16 mg
Dosing Interval
Once a day
Key Instructions
Use the conversion ratios in the individual product information.
Start patients with moderate hepatic impairment on 25% dose that would be prescribed for
a patient with normal hepatic function.
Start patients with moderate renal impairment on 50%, and patients with severe renal
impairment on 25% of the dose that would be prescribed for a patient with normal renal
function.
Titrate using a minimum of 3 to 4 day intervals.
Swallow tablets whole (do not chew, crush, or dissolve).
Do not use in patients with sulfa allergycontains sodium metabisulfite.
Specific Drug Interactions None
Use in Opioid-Tolerant
All doses of Exalgo are indicated for opioid-tolerant patients only.
Patients
Drug-Specific Adverse
Allergic manifestations to sulfa component.
Reactions
Relative Potency To Oral
Approximately 5:1 oral morphine to hydromorphone oral dose ratio, use conversion
Morphine
recommendations in the individual product information.

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23

Table 5 (continued): Specific Drug Information for Extended-Release and Long-Acting Opioid Analgesics (ER/LA
opioid analgesics)
Kadian
Dosing Interval
Once a day or every 12 hours
Key Instructions
Product information recommends not using as first opioid.
Titrate using a minimum of 2-day intervals.
Swallow capsules whole (do not chew, crush, or dissolve).
May open capsule and sprinkle pellets on applesauce for patients who can reliably swallow
without chewing, use immediately.
Specific Drug Interactions Alcoholic beverages or medications containing alcohol may result in the rapid release and
absorption of a potentially fatal dose of morphine.
PGP inhibitors (e.g. quinidine) may increase the absorption/exposure of morphine sulfate
by about two-fold.
Use in Opioid-Tolerant
Kadian 100 mg and 200 mg capsules are for use in opioid-tolerant patients.
Patients
Product-Specific Safety
None
Concerns
Morphine Sulfate
MS Contin
Controlled-release Tablets, 15 mg, 30 mg, 60 mg, 100 mg, and 200 mg
Dosing Interval
Every 8 hours or every 12 hours
Key Instructions
Product information recommends not using as first opioid.
Titrate using a minimum of 2-day intervals.
Swallow tablets whole (do not chew, crush, or dissolve).
Specific Drug Interactions PGP inhibitors (e.g. quinidine) may increase the absorption/exposure of morphine sulfate by
about two-fold.
Use in Opioid-Tolerant
MS Contin 100 mg and 200 mg tablet strengths are for use in opioid-tolerant patients only.
Patients
Product-Specific Safety
None
Concerns
Tapentadol
Nucynta ER
Extended-Release Tablets, 50 mg, 100mg, 150 mg, 200 mg, and 250 mg
Dosing Interval
Every 12 hours
Key Instructions
Use 50 mg every 12 hours as initial dose in opioid nontolerant patients
Titrate by 50 mg increments using a minimum of 3-day intervals.
Maximum total daily dose is 500 mg
Swallow tablets whole (do not chew, crush, or dissolve).
Take one tablet at a time and with enough water to ensure complete swallowing
immediately after placing in the mouth.
Dose once daily in moderate hepatic impairment with 100 mg per day maximum
Avoid use in severe hepatic and renal impairment.
Specific Drug Interactions Alcoholic beverages or medications containing alcohol may result in the rapid release and
absorption of a potentially fatal dose of tapentadol.
Contraindicated in patients taking MAOIs.
Use in Opioid-Tolerant
No product-specific considerations.
Patients
Product-Specific Safety
Risk of serotonin syndrome
Concerns
Angioedema
Relative Potency To Oral
Equipotency to oral morphine has not been established.
Morphine

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24

Table 5 (continued): Specific Drug Information for Extended-Release and Long-Acting Opioid Analgesics (ER/LA
opioid analgesics)
Oxymorphone Hydrochloride
Opana ER
ER Tablets, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg, and 40 mg
Dosing Interval
Every 12h dosing, some may benefit from asymmetric (different dose given in AM than in PM)
dosing.
Key Instructions
Use 5 mg every 12 hours as initial dose in opioid non-tolerant patients and patients with
mild hepatic impairment and renal impairment (creatinine clearance < 50 mL/min) and
patients over 65 years of age
Swallow tablets whole (do not chew, crush, or dissolve).
Take one tablet at a time, with enough water to ensure complete swallowing immediately
after placing in the mouth.
Titrate using a minimum of 2-day intervals.
Contraindicated in moderate and severe hepatic impairment.
Specific Drug Interactions Alcoholic beverages or medications containing alcohol may result in the absorption of a
potentially fatal dose of oxymorphone.
Use in Opioid-Tolerant
No product specific considerations.
Patients
Product-Specific Safety
None
Concerns
Relative Potency To Oral
Approximately 3:1 oral morphine to oxymorphone oral dose ratio
Morphine
Oxycodone Hydrochloride
OxyContin
Controlled-release Tablets, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80 mg
Dosing Interval
Every 12 hours
Key Instructions
Opioid-nave patients: initiate treatment with 10 mg every 12 hours.
Titrate using a minimum of 1 to 2 day intervals.
Hepatic impairment: start with one third to one half the usual dosage
Renal impairment (creatinine clearance <60 mL/min): start with one half the usual dosage.
Consider use of other analgesics in patients who have difficulty swallowing or have
underlying GI disorders that may predispose them to obstruction. Swallow tablets whole
(do not chew, crush, or dissolve).
Take one tablet at a time, with enough water to ensure complete swallowing immediately
after placing in the mouth.
Specific Drug Interactions CYP3A4 inhibitors may increase oxycodone exposure.
CYP3A4 inducers may decrease oxycodone exposure.
Use in Opioid-Tolerant
Single dose greater than 40 mg or total daily dose greater than 80 mg are for use in opioidPatients
tolerant patients only.
Product-Specific Safety
Choking, gagging, regurgitation, tablets stuck in the throat, difficulty swallowing the tablet.
Concerns
Contraindicated in patients with gastrointestinal obstruction.
Relative Potency To Oral
Approximately 2:1 oral morphine to oxycodone oral dose ratio.
Morphine
For detailed information, refer to prescribing information available online via DailyMed at www.dailymed.nlm.nih.gov
or Drugs@FDA at www.fda.gov/drugsatfda.
Source: FDA Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 7/9/2012.

InforMed 1-800-237-6999 Fax 1-800-647-1356

25

PatientCounselingDocument(PCD)
Patient Counseling Document on Extended-Release / LongActing Opioid Analgesics

Patient
Name:

Patient
Name:
The DOs and DONTs of
Extended-Release / Long-Acting Opioid Analgesics
DO:

Patient Counseling Document on ExtendedRelease /

Long-Acting Opioid Analgesics

Patient Specific Information

Read the Medication Guide

Take your medicine exactly as prescribed
Store your medicine away from children and in a safe place
Flush unused medicine down the toilet
Call your healthcare provider for medical advice about side
effects. You may report side effects to FDA at 1-800-FDA1088.

Call 911 or your local emergency service right away if:

You take too much medicine

You have trouble breathing, or shortness of breath

A child has taken this medicine

Talk to your healthcare provider:

If the dose you are taking does not control your pain

About any side effects you may be having

About all the medicines you take, including over-the-counter

medicines, vitamins, and dietary supplements
DONT:

Do not give your medicine to others

Do not take medicine unless it was prescribed for you

Do not stop taking your medicine without talking to your

healthcare provider

Do not break, chew, crush, dissolve, or inject your medicine.

If you cannot swallow your medicine whole, talk to your
healthcare provider.

Do not drink alcohol while taking this medicine

For additional information on your medicine go to:
dailymed.nlm.nih.gov

Take this card with you every time you see your
healthcare provider and tell him/her:

Your complete medical and family history, including

any history of substance abuse or mental illness

The cause, severity, and nature of your pain

Your treatment goals

All the medicines you take, including over-thecounter

(non-prescription) medicines, vitamins, and dietary
supplements

Any side effects you may be having

Take your opioid pain medicine exactly as
prescribed by your healthcare provider.

Resources
American Academy of Pain Medicine
painmed.org

National Association of Drug Diversion

Investigators
www.naddi.org

American College of Physicians

doctorsforadults.com

Pain Treatment Topics

www.Pain-Topics.org

American Chronic Pain Association

www.theacpa.org

Opioids911-Safety
www.opioids911.org

Drug Enforcement Administration Diversion

Control Program
www.DEAdiversion.usdoj.gov

United States Food & Drug Administration

(FDA)
www.fda.gov

Federation of State Medical Boards

www.fsmb.org

University of Wisconsin Pain & Policy Studies

Group
www.painpolicy.wisc.edu

The National Association of State Controlled

Substances Authorities
www.nascsa.org

InforMed 1-800-237-6999 Fax 1-800-647-1356

26

References
1
Chou E, Fanciullo GJ, Fine PG, et al. Clinical Guidelines for the
Use of Chronic Opioid Therapy in Chronic Non-cancer Pain. J Pain.
2009;10(2):113-130.
2
Webster LR, Dove B. Avoiding Opioid Abuse While Managing
Pain. Sunrise River Press, North Branch, MN. 2007.
3
Centers for Disease Control and Prevention. Vital Signs: Risk for
Overdose from Methadone Used for Pain ReliefUnited States, 1999-2010.
Morbidity and Mortality Weekly Report. July 3, 2012, Vol. 61.
4
IMS Health. IMS National Prescription Audit. February 23,
2012.
5
Joint meeting of the anesthetic and life support drugs advisory
committee and the drug safety and risk management advisory committee.
Risk evaluation and mitigation strategies for extended-release and longacting opioid analgesic. July 22 and 23, 2010.
6
Substance Abuse and Mental Health Services Administration.
(2010). Results from the 2009 National Survey on Drug Use and Health:
Volume I. Summary of National Findings (Office of Applied Studies,
NSDUH Series H-38A, HHS Publication No. SMA 10-4586Findings).
Rockville, MD.
7
Substance Abuse and Mental Health Services Administration,
Office of Applied Studies. (June 18, 2010). The DAWN Report: Trends in
Emergency Department Visits Involving Nonmedical Use of Narcotic Pain
Relievers. Rockville, MD. Available at:
http://www.samhsa.gov/data/DAWN.aspx.
8
Substance Abuse and Mental Health Services Administration.
Treatment Episode Data Set. Substance Abuse Treatment Admissions
Involving Abuse of Pain Relievers. SAMHSA; 1998 and 2008. July 15, 2010.
9
Centers for Disease Control and Prevention (CDC). Unintentional
drug poisoning in the United States, July 2010. National Center for Injury
Prevention and Control, CDC. Available at:
http://www.cdc.gov/HomeandRecreatonalSafety/pdf/poison-issue-brief.pdf.
Accessed August 28, 2012.
10
U.S. Food and Drug Administration (FDA) news release. FDA
Introduces new safety measures for extended-release and long-acting opioid
medications. July 9, 2012.
11
Executive Office of the President of the United States. Epidemic:
Responding to Americas Prescription Drug Abuse Crisis. 2011. Available at:
http://www.whitehouse.gov/ondcp/prescription-drug-abuse. Accessed:
August 28, 2012.
12
International Association for the Study of Pain. Classification of
chronic pain: Descriptions of chronic pain syndromes and definitions of pain
terms. Prepared by the International Association for the Study of Pain,
Subcommittee on Taxonomy. Pain Suppl S1S226, 1986.
13
Institute of Medicine. Relieving Pain in America: A blueprint for
transforming prevention, care, education, and research. Report Brief. June
2011.
14
NCHS. Health, United States, 2006 with Chartbook on Trends in
the Health of Americans. Hyattsville, MD: U.S. Department of Health and
Human Services; 2006.
15
American Cancer Society (ACS). Cancer Facts and Figures 2012.
Atlanta: ACS; 2012.
16
Food and Drug Administration, CDER Final Blueprint for
Prescriber Continuing Education Program. July 9, 2012.
17
Fishman SM. Responsible Opioid Prescribing: A Clinicians
Guide, 2nd Ed. Waterford Life Sciences. 2012.
18
Goodwin J, Bajwa ZH. Evaluating the patient with chronic pain.
In: Principles and Practice of Pain Medicine 2nd Ed. Warfield CA, and
Bajwa ZH., Eds. 2004. New York, NY, McGraw-Hill Companies, Inc.
19
Goodwin J, Bajwa ZH. Understanding the patient with chronic
pain. In: Principles and Practice of Pain Medicine 2nd Ed. Warfield CA, and
Bajwa ZH., Eds. 2004. New York, NY, McGraw-Hill Companies, Inc. p.58
20
Tang NK, Crane C. Suicidality in chronic pain: a review of the
prevalence, risk factors, and psychological links. Psychological Medicine
2006; 36:575-586.
21
Gourlay D, Heit H. Universal precautions: a matter of mutual
trust and responsibility. Pain Medicine. 2006; 7(2):210-211.
22
Payne R, Anderson E, Arnold R, et al. A Rose by any other
name: pain contracts/agreements. American Journal of Bioethics.
2010;10(11):5-12.
23
Management of Opioid Therapy for Chronic Pain Working
Group. VA/DoD clinical practice guideline for management of opioid
therapy for chronic pain. Washington (DC): Department of Veterans Affairs,
DoD; May 2010.

InforMed 1-800-237-6999 Fax 1-800-647-1356

24
Roskos SE, Keenum AJ, Newman LM, Wallace LS. Literacy
demands and formatting characteristics of opioid contracts in chronic
nonmalignant pain management. Journal of Pain. 2007;8(10):753-758.
25
Center for Professional Practice of Nursing. Guidelines for
preparing patient education handouts. UC Davis Health System. Available at:
http://www.ucdmc.ucdavis.edu/cne/health_education/guide.html. Accessed
July 22, 2011.
26
Fishman SM, Mahajan G, Wilsey BL. Author Response letter to
the editor about article: The trilateral opioid contract: bridging the pain clinic
and the primary care physician through the opioid contract. J Pain Symptom
Manage. 2003;25(5):403.
27
Cleeland CS, Ryan KM. Pain assessment: global use of the Brief
Pain Inventory. Annals of the Academy of Medicine, Singapore. 1994;
23(2):129-138.
28
Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical
Pharmacogenetics Implementation Consortium 9CPIC) guidelines for
codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype.
Clin Pharmacol Ther. 2012;91(2):321-6.
29
Agency Medical Directors Group. Interagency Guideline on
Opioid Dosing for Chronic Non-cancer Pain: An educational aid to improve
care and safety with opioid therapy. 2010 Update.
30
U.S. Food and Drug Administration (FDA). Blueprint for
Prescriber Continuing Education Program. July 9, 2012.
31
Zacharoff KL, McCarberg BH, Reisner L, Venuti SW.
Managing Chronic Pain with Opioids in Primary Care, 2nd Ed. Inflexxion,
nc. Newton MA. 2010.
32
U.S. Food and Drug Administration press release. FDA approves
shared system REMS for TIRF products. December, 2011.
33
Harris G. FDA Plans New Limits on Prescription Painkillers.
New York Times. January 13, 2011.
34
Fishman SM, Wilsey B, Mahajan G, Molina P. Methadone
reincarnated: novel clinical applications with related concerns. Pain
Medicine. 2002;3(4):339-348.
35
Goodnough A, Zezima K. When Childrens Scribbles Hide a
Prison Drug. New York Times. May 26, 2011.
36
American Medical Association (AMA). The physicians role in
medication reconciliation: issues, strategies and safety principles. 2007.
37
Governing Board, Council of State Governments. Resolution on
Prescription Drug Abuse. 2010 National Conference, Providence, RI.
December 6, 2010.
38
The PMP Center of Excellence. Available at
http://pmpexcellence.org. Accessed January 18, 2012.
39
Webster LY, Fine PG. Overdose Deaths Demand a New
Paradigm for Opioid Rotation. Pain Med. 2012;13(4):571-4.
40
Webster LR, et al. Select medical-legal reviews of unintentional
overdose deaths. Presented at 26th Annual Meeting of AAPM; February 3-6,
2010: San Antonio, TX.
41
Centers for Disease Control and Prevention. Increases in
Poisoning and Methadone-Related Deaths: United States, 1999-2005. NCHS
Health & Stats. February, 2008.
42
Dolophine Hydrochloride (Methadone Hydrochloride) Full
Prescribing Information. Roxane Laboratories, Inc. October, 2006.
43
Knotkova H, Fine PG, Portenoy RK. Opioid rotation: The science
and limitations of the equianalgesic dose table. J Pain Symp Mangmnt.
2009;38(3): 426-439.
44
Food and Drug Administration. Public Health Advisory:
Methadone Use for Pain Control May Result in Death and Life-Threatening
Changes in Breathing and Heart Beat. November 27, 2006.
45
Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MC. QTc
interval screening in methadone treatment. Ann Intern Med. 2009;150:387395.
46
U.S. Food and Drug Administration (FDA). Blueprint for
Prescriber Continuing Education Program. July 9, 2012.
47
Office of National Drug Control Policy. Proper Disposal of
Prescription Drugs. October, 2009. Available at:
www.whitehousedrugpolicy.gov. Accessed May 17, 2011.
48
Leavitt SB. Intranasal Naloxone for At-Home Opioid Rescue.
Prac Pain Mngmnt. October, 2010:42-46.

27

Self-Assessment
Choose the best possible answer for each question and mark your answers on the Self-Assessment
answer sheet at the end of this book. There is a required score of 70% or better to receive a Certificate
of completion.
1. Long-acting (LA) and extended-release
(ER) formulations of opioids should
typically not be used for which of the
following?
a. Treating cancer pain.
b. Treating acute pain.
c. Treating end-of-life pain.
d. Treating chronic non-cancer pain.
2. If an organic pathology cannot be found
to explain a patients pain, what should a
clinician infer?
a. The pain is real, though unexplained.
b. The pain is psychosomatic.
c. The patient is seeking opioids for illegal
use.
d. The pain is the result of a mental health
condition.
3.

Which of the following is the appropriate

use of universal precautions as it
applies to patients with chronic pain?
a. Exploring patients HIV status.
b. Having all patients submit to frequent
urine toxicology tests.
c. Being vigilant about the possibility of
misuse or abuse with all patients.

4. The DIRE and the COMM are examples

of which of the following assessments?
a. Quantifying patients pain perceptions.
b. Assessing patient risk of opioid misuse
or abuse.
c. Evaluating risk of physical adverse
reactions to opioids.
d. Determining a reason for opioid pain
medications.

InforMed 1-800-237-6999 Fax 1-800-647-1356

5. All of the following need to be

documented in writing as part of an
overall therapeutic approach to managing
chronic pain patients EXCEPT:
a. Informed consent.
b. Patient/provider agreements.
c. Treatment agreements.
d. Answers to patient questions about
insurance coverage.
6. All of the following are possible
advantages of patient/provider
agreements EXCEPT:
a. Provides a foundation for subsequent
decisions about treatment termination.
b. Can help clinicians identify a patients
level of risk for opioid abuse.
c. Can help avoid misunderstandings
between provider and patient.
d. Can document informed consent.
7. All of the following are examples of
functional goals EXCEPT:
a. Reduced anxiety about pain.
b. Walking around the block.
c. Increased sexual activity.
d. Returning to work.
8. The responsibility for obtaining evidence
of success in meeting a functional goal lies
with which of the following individuals?
a. The clinician.
b. The patients partner.
c. The patient.
d. Law enforcement officers.
9. All of the following are reasonable causes
for discontinuing treatment with an
opioid medication EXCEPT:
a. Healing or resolution of the
pathology/injury.
b. Experience of intolerable side effects.

28

c. Being occasionally late for scheduled

appointments.
d. Evidence of non-medical or
inappropriate use of medications.
10. When opioid treatment is initiated, both
the patient and clinician should view the
commitment as:
a. Short-term trial of therapy
b. A long-term use of opioid therapy
c. A titration of the opioid to reach optimal
pain relief
d. Continued therapy until adequate pain
relief is achieved
11. It can be particularly unsafe to combine
opioids with which of the following other
medicines?
a. Stimulant medications
b. SSRI antidepressants
c. Benzodiazepines or barbiturates
d. Anti-hypertensive medications
12. The duration of action of short-acting
opioids is generally:
a. 10- 60 min.
b. 2 hrs. maximum
c. 2 -4 hrs.
d. 8-10 hrs.
13. Short-acting opioids are most appropriate
and commonly used for which of the
following conditions?
a. Cancer pain
b. Breakthrough pain
c. Background or persistent pain
d. Neuropathic pain

InforMed 1-800-237-6999 Fax 1-800-647-1356

14. Combination products are those that

include an opioid with which of the
following elements?
a. Non-opioid coanalgesic
b. Non-opioid narcotic medication
c. Opioid antagonist to prevent abuse
d. Caffeine
15. What is the typical duration of action of
the different ER/LA opioids?
a. 30 90 min
b. 2- 4 hrs
c. 4 12 hrs
d. 4 72 hrs
16. All of the following are of particular
concern when prescribing an ER/LA
opioid pain medication EXCEPT:
a. Abuse by breaking, chewing, or crushing
tablets
b. Risk of overdose if long-duration drugs
are combined with short-acting
medications
c. Addition of a non-opioid coanalgesic in
the formulation may raise possibility of
liver damage
d. Some opioids with ER/LA
characteristics (i.e. methadone) may
have atypical pharmacokinetics
17. All of the following types of patients need
more frequent or intense monitoring
EXCEPT:
a. Those with a prior history of an
addictive disorder
b. Adherent patients on a stable dose of
opioid
c. Those with comorbid psychiatric
conditions
d. Older adults

29

18. Of the following tools, which one can help

patients pinpoint triggers of
breakthrough pain?
a. Paper or electronic pain diary
b. Pill box organizers
c. Portable EEG monitors
d. Automated systems for sending patients
reminders to take their medications
19. Uncomfortable or unpleasant side effects
(aside from constipation) may potentially
be reduced by which two approaches?
a. Switching to another opioid or taking the
opioid with food
b. Switching to another opioid or using
adjunctive medications to treat
symptoms
c. Adding a non-opioid analgesic or trying
a complimentary therapeutic technique
d. Changing the route of administration or
advising patients to avoid alcohol
consumption
20. All of the following are valid reasons to
pursue opioid rotation EXCEPT:
a. Lack of efficacy
b. Bothersome or unacceptable side effects
c. Desire to prevent the patient from
illegally diverting opioids
d. Change in patients ability to absorb a
medication in its present formulation

InforMed 1-800-237-6999 Fax 1-800-647-1356

21. Which of the following is the APS-AAPM

guideline regarding driving for patients
prescribed opioid medication?
a. Patients taking opioids should not drive
for 1 month after starting them
b. There is no consensus on specifically
how long patients should abstain from
driving
c. Driving is at the discretion of the
clinician
d. There are no driving restrictions
22. One reason that methadone must be
prescribed with particular caution is that:
a. Methadone is only appropriate for opioid
maintenance therapy programs
b. Methadones analgesic half-life is much
shorter than its elimination half-life
c. Methadone has uniquely powerful
respiratory depressive effects
d. Methadone may produce visual
disturbances
23. In 2006, the FDA added a caution to the
black box warning that methadone may
cause which of the following serious
adverse effects?
a. Respiratory depression
b. Cardiac conduction disturbances
c. Myoclonus
d. Renal failure

30

Course:EOL12Credits

OriginalReleaseDate11/2012 LastUpdate09/2013

ExpirationDate:10/31/2015

Pain Management at the End of Life

Audience
This course is designed for all physicians (MD/DO), physician
assistants and nurse practitioners.
Course Objective
The purpose of this course is to update and increase competency
in the application of pain management in palliative care. Course
includes discussion on strategies for optimizing palliative care at
the end of life.
Learning Objectives
Completion of this course will better enable the course participant to:

1.

Explain the difference between palliative care and hospice

care as these terms are understood in the US
2. Describe the process of formulating patient-centered goals
for end-of-life pain management
3. Understand that patients may have different treatment goals
and understandings of the term quality of life
4. Describe ways to assess pain in a patient with reduced or
absent consciousness
5. Describe 2 advantages and 2 disadvantages of opioid pain
medications in the context of end-of-life pain management
6. Explain the advantages and disadvantages of NSAID
medications in the context of end-of-life pain management
7. Describe 4 classes of adjuvant analgesics of potential utility
in managing end-of-life pain
8. Describe 2 interventional (non-analgesic) therapies with
potential utility in managing end-of-life pain
9. Describe 4 complementary/alternative therapies that are used
in end-of-life care settings
10. Explain the Doctrine of Double Effect
11. Understand 3 ways to improve communication with patients
from non-Western cultures

1.
2.
3.

How to Receive Credit

Read the course materials
Complete the self-assessment questions at the end. A score
of 70% is required.
Return your customer information/answer sheet, evaluation,
and payment to Informed by mail, phone, fax or complete
online at course website under NETPASS.

Accreditation Statement
Informed is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide continuing
medical education for physicians.

Faculty
Paul J. Christo, MD, MBA
Associate Professor, The Johns Hopkins University School of
Medicine
Director, Multidisciplinary Pain Fellowship (2003-2011)
Director, Blaustein Pain Treatment Center (2003-2008)
Division of Pain Medicine. Department of Anesthesiology and
Critical Care Medicine
Stephen Braun
Medical Writer
Braun Medical Media
Activity Director
Sarina J. Grosswald, EdD
Director of CME, Informed
SJ Grosswald & Associates
Disclosure
Resolution of Conflicts of Interest
In accordance with the ACCME Standards for Commercial
Support of CME, the Informed implemented mechanisms, prior to
the planning and implementation of this CME activity, to identify
and resolve conflicts of interest for all individuals in a position to
control content of this CME activity.
Staff and Content Validation Reviewer Disclosure
Informed staff involved with this activity and any content
validation reviewers of this activity have reported no relevant
financial relationships with commercial interests.
Planning Committee/Faculty Disclosure
The following faculty and/or planning committee members have
indicated they have no relationship(s) with industry to disclose
relative to the content of this CME activity:
Sarina J. Grosswald, EdD
Stephen Braun
The following faculty and/or planning committee members have
indicated that they have relationship(s) with industry to disclose:
Paul J. Christo, MD, MBA has served on the Advisory
Boards of Ameritox and Quadrant HealthCom and has acted
as a consultant for Actavis, Perrigo, and Chattern, Inc.

Designation of Credit
Informed designates this enduring material for a maximum of 2
AMA PRA Category 1 Credits. Physicians should claim only
the credit commensurate with the extent of their participation in
the activity.
This activity developed without Commercial Support

InforMed 1-800-237-6999 Fax 1-800-647-1356

2013. All rights reserved. These materials, except those in the public
domain, may not be reproduced without permission from InforMed. This
publication is designed to provide general information prepared by
professionals in regard to the subject matter covered. It is provided with the
understanding that InforMed, Inc. is not engaged in rendering legal, medical
or other professional services. Although prepared by professionals, this
publication should not be utilized as a substitute for professional services in
specific situations. If legal advice, medical advice or other expert assistance
is required, the service of a professional should be sought.

31

Pain Management at the End of Life

Introduction
In the past century, life expectancy in the
United States has increased by
approximately 30 years.1 As a consequence,
most people alive today will die at an older
age than in previous years, and most will die
after a period of chronic illness and physical
decline.2 At the same time, studies document
serious deficiencies in the care provided to
dying people, including under treatment of
pain and communication difficulties
between patients, family members, and
health care providers regarding end-of-life
goals.3 Pain management at the end of life
has become a particularly challenging and
fraught issue because of the widespread
recognition in recent years of the problems
with diversion and abuse of opioids, which
continue to be the mainstay analgesics in the
terminal phase of many illnesses.
The full range of issues related to the
responsible prescription of opioids will not
be discussed here, since they are covered in
greater detail in other CME programs related
to this monograph. But opioids are not the
onlynor sometimes the most

appropriatepain medications for patients

at the end of life. This monograph explores
in-depth these analgesic options and many
other issues related to the care and comfort
of patients in this final phase of life.
The types of pain syndromes arising at the
end of life include most of the acute and
chronic pain syndromes clinicians confront
in other patients, and many of the same
diagnostic and therapeutic strategies and
skills are the same or similar. But pain
management at the end of life does raise
some unique clinical and ethical issues and,
hence, these issues are appropriate for a
focused consideration. In addition, the
prospect of severe, unrelieved pain at the
end of life ranks very high among patient
fears. Indeed, as shown in Figure 1, many
people consider the experience of severe
pain to be worse than death, which
underscores the importance of a thorough
clinical understanding this issue.
Palliative Care v. Hospice Care
In the United States, a distinction is made
between palliative care and hospice

Figure1:Percentofsampledadultswhoratedthehypotheticalstate
ofseverepainasworsethandeath.

Source: Patrick DL, Pearlman RA, Starks HE, et al. Validation of preferences for life-sustaining
treatment: implications for advance care planning. Ann Intern Med 1997;127(7):509-17.
InforMed 1-800-237-6999 Fax 1-800-647-1356

32

care.4 Both aim to relieve pain and other

distressing symptoms and attempt, in a
holistic manner, to improve a patients
overall functioning and quality of life. A
guiding principle of both is that dying is a
normal process and that the goal of care is to
neither hasten nor postpone death. Pain
control is seen as one component of a larger
effort that involves caring for the
psychological, emotional, cultural, and
spiritual components of dying, both for the
patient and their loved ones.
In the US, the term hospice care is
reserved for people who are not expected to
live more than 6 months if a disease runs its
normal course.5 Palliative care is a
broader term and encompasses care of
patients who have complicated or advanced
diseases that may, or may not, be lifethreatening. Palliative care may be provided
at any phase of a disease process, whereas
hospice care is provided only in the terminal
phase. This monograph focuses exclusively
on end-of-life care and, hence, will use the
terms hospice care and end-of-life care
synonymously while avoiding the use of
palliative care (even though most of the
principles and practices described here apply
equally to palliative care efforts).
Patient-Centered Treatment Goals
Although pain relief is often considered
and may sometimes bean end unto itself,
it is particularly important for clinicians to
recognize that, at the end of life, pain
management and control of symptoms may
be more appropriately viewed as means of
achieving the more primary goal of
improving or maintaining a patients overall
quality of life. The meaning of quality of
life varies, not just from patient to patient,
but even between the phases of an illness
experienced by a single patient. A focus on
quality of life is important because

InforMed 1-800-237-6999 Fax 1-800-647-1356

sometimes a patient may have priorities that

compete with, or supersede, the relief of
pain. For example, the end of life can be an
extremely important and meaningful time.6
For some patients, mental alertness
sufficient to allow maximal interactions with
loved ones may be more important than
physical comfort. Optimal pain management,
in such cases, may mean lower doses of an
analgesic and the experience, by the patient,
of higher levels of pain. The point is that, at
the end of life, decisions about pain relief
must be more than usually balanced with a
mindful consideration of the patients own
values and desires.
Defining clear patient-centered goals of care
is a first step to developing an optimal pain
management strategy at the end of life.
These goals should be guided by four core
ethical values that apply broadly, but are
particularly important at the end of life:7
1. Autonomy of the patient
2. Beneficence (the physicians
obligation to promote patient
welfare)
3. Justice
4. Non-malfeasance (avoiding harm)
These four values are embodied in the
question at the core of any consideration of
an end-of-life intervention: do the expected
benefits outweigh the expected burdens
from the patients perspective?8 This
question applies as much to minor
interventions such as phlebotomy as to more
complex interventions such as chemotherapy
or surgery.
Answering this question, of course, requires
a clinician to understand what a particular
patient would consider a benefit or a
burden and what the patients goals are
(Table 1). The question also can seldom be
answered with absolute certainty since the

33

outcomes, particularly of complex

interventions, are inherently difficult to
predict. In developing plans of care,
therefore, clinicians must engage with the
patient (or designated surrogate) to carefully
consider the patients values, beliefs, and
priorities. In the end, clinicians can only
provide the best information and estimates
they can. The patient (or surrogate) must
weigh the options and make the decision.
Table 1: Potential Patient-Centered Goals
of Care
Longer life
Symptom relief
Time at home
Ability to travel
Mental clarity
Physical mobility
Ability to interact with loved ones
Minimizing burdens on loves ones
Personal/Spiritual growth
Dignity (though meanings will vary)
Source: Forrow L, Smith HS. Pain Management in End of
Life: Palliative Care. In Principles & Practice of Pain
Medicine, 2nd Ed. Warfield CA and Bajwa ZH Eds. 2004.
McGraw-Hill, New York, NY.

Managing pain and other symptoms at the

end of life is just one component of a wider
effort to relieve suffering and help a patient
cope with the emotional and psychological
aspects of dying. Nonetheless, a failure to
manage pain and other symptoms may make
it impossible for the patient to attend to
these important dimensions. Uncontrolled
pain can push all other priorities aside and
sap a persons energy and motivation to
focus on potentially positive goals or
meaningful experiences. A patients
perception that his or her pain cannot be
controlled may also contribute to a broader
feeling that he or she has lost control over
their lives in general, which can precipitate a
downward spiral of depression and/or
hopelessness. Effective pain control, on the
other hand, not only directly reduces
InforMed 1-800-237-6999 Fax 1-800-647-1356

suffering but may allow a patient the energy

and positive attitude needed to engage with
the emotional and psychological aspects of
dying.
Assessing Pain at the End of Life
The end of life is often characterized by a
reduced level of consciousness or complete
lack of consciousness. This can make
assessments of pain very challenging. If a
patient is not alert enough to communicate,
then nonverbal signs or cues must be used to
determine if the patient is experiencing pain
and to what degree an analgesic approach is
effective. In general, even ambiguous signs
of discomfort should usually be treated,
although caution must be exercised in
interpreting such signs.9 Patients who are
actively dying may groan or grunt in ways
that suggest they are in pain, although such
sounds may, in fact, be the normal
expressions attendant to the last moments or
hours of life.
Signs of discomfort that are accompanied by
more rapid breathing or heart rate should be
taken more seriously. Likewise, if physical
stimulation of the patient (i.e. during
bathing) causes signs of discomfort,
increased analgesia may be warranted.
Prolonged rapid breathing (> 20/min.) may
be uncomfortable because of muscle fatigue
and it may therefore be reasonable, even in
the absence of other evidence of discomfort,
to titrate a pain medication with a target
respiratory rate of 15 to 20/minute.10

Treatment Options for Pain Management

at the End of Life
Opioids at the End-of-Life
As noted earlier, the subject of responsible
opioid prescribing is vast and a full
discussion is both beyond the scope of this

34

monograph (refer to Section 1-ER/LA

Opioid REMS Education). Nonetheless,
opioids remain critical to providing effective
analgesia at the end of life and will be
briefly summarized here.11
Opioid formulations are available in such
variety in the US that, typically, a pain
regimen can be tailored to each patient.12
Because there is great between-patient
variability in response to particular opioid
agents no specific agent is superior to
another as first-line therapy. Although
morphine was previously considered the
gold standard, it is now recognized that
the most appropriate agent is the opioid that
works for an individual patient.13 Morphine
and other opioids are available in a wide
range of formulations and routes of
administration, including oral, parenteral,
and rectal delivery. Both rectal and
transdermal routes can be especially
valuable at the end of life when the oral
route is precluded because of reduced or
absent consciousness, difficulty swallowing,
or to reduce the chances of nausea and
vomiting.14 When selecting an opioid,
clinicians should also consider cost, since
expensive agents can place undue burden on
patients and families.
Some opioids may not be appropriate in the
end-of-life setting. For example, meperidine
is not recommended in cancer pain
management due to the neurotoxic effects of
its metabolites.15 In addition, mixed agonistantagonist opioid analgesics, including
butorphanol, nalbuphine, and pentazocine,
are not recommended in cancer pain
management because they are more likely to
cause psychotomimetic effects and they can
precipitate the abstinence syndrome if given
to a patient who is physically dependent on a
pure opioid agonist.
Opioid-related side effects must be

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considered in advance of treatment and steps

must be taken to minimize these effects to
the extent possible, since adverse effects
contribute significantly to analgesic
nonadherence. This is particularly true for
constipation and sedation. Tolerance rarely
develops to constipation and therefore it
must be prevented and, if unsuccessful,
treated aggressively. A prophylactic bowel
regimen that includes a laxative and stool
softener, such as senna and docusate, should
be used, although a recent study suggested
that senna alone was just as effective.16
Bulking agents, such as psyllium, are
ineffective and may exacerbate
gastrointestinal distress unless the patient
can drink significant amounts of fluids.
Methylnaltrexone, an opioid antagonist that
works on receptors in the GI system and is
given subcutaneously, can be used as a
rescue when constipation is clearly related to
opioid therapy.17
Sedation is often attributed to opioid therapy
given at the end of life, although many other
drugs used at this time may be sedating,
including benzodiazepines, antiemetics, and
other agents. Tolerance to opioid-induced
sedation may develop within a few days of
regular use; however, in some cases this
may persist and opioid rotation may be
warranted. A psychostimulant, such as
methylphenidate or dextroamphetamine,
might be added to offset sedative effects,
typically starting at a dose of 5 to 10 mg
once or twice daily. One study found that
with proper timing, the administration of
methylphenidate did not disrupt sleep.18
Nausea and vomiting are relatively common
in opioid-naive individuals. Around-theclock antiemetic therapy instituted at the
beginning of opioid therapy may prevent
this adverse effect.19 The antiemetic can be
weaned in most cases after 2 to 3 days. The
itching that can occur early in the course of

35

opioid treatment may be at least partially

alleviated with antihistamines. Opioid
rotation to a more synthetic agent or an
agent with a different route of administration,
such as oxymorphone or transdermal
fentanyl has also been reported to be helpful.
Other adverse effects, including respiratory
depression, are greatly feared and lead to
clinician underprescribing and reluctance by
patients to take the medication, despite the
rarity of this event in persons with cancer.20
Despite this fear, studies have revealed no
correlation between opioid dose, timing of
opioid administration, and time of death.21,22
Non-steroidal Anti-inflammatory (NSAID)
Analgesics
NSAIDs may be useful in the treatment of
pain conditions mediated by inflammation,
including those caused by cancer, such as
bone metastases.23 NSAIDs typically cause
less nausea than opioids, though this is most
true with low doses. NSAIDS also do not
cause constipation, sedation, or adverse
effects on mental functioning. NSAIDs may,
therefore, be useful for the control of
moderate to severe pain, usually as an
adjunct to opioid analgesic therapy.24 The
addition of NSAIDs to opioids may allow a
reduction in the opioid dose, although such
combinations must be used with care.
Typically, the non-opioid co-analgesic agent,
such as acetaminophen or an NSAID, has a
ceiling dose above which efficacy will
plateau as risk for adverse effects increases.
Thus, combining these products, either as
separately-administered agents or in
combination products, are typically used for
patients who are not expected to need
substantial dose escalations.25 Using a
combination product when dose escalation is
required risks increasing adverse effects
from the non-opioid co-analgesic, even if an
increase of the opioid dose is appropriate. In
such cases, using a pure opioid may be

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preferable. (Single-agent formulations are

available for many types of opioids, such as
morphine, oxycodone, and hydromorphone.)
In 2012, the FDA announced new rules that
limit to 325 mg the amount of
acetaminophen allowed in prescription
opioid combination products in an attempt to
limit liver damage and other ill effects
primarily due to excessive doses of
combined products.26
Contraindications for NSAIDs include
decreased renal function (relatively common
at the end of life) and liver failure. Platelet
dysfunction or other potential bleeding
disorders, common due to cancer or its
treatment, are also contraindications to nonselective NSAIDS because of their
inhibitory effects on platelet aggregation,
with resultant prolonged bleeding time.27
Proton pump inhibitors or misoprostol may
be considered to prevent GI bleeding.28
Attention has recently been focused on the
potential limited efficacy of acetaminophen
in older patients. Although it has been
considered a viable co-analgesic with
opioids, and to be first-line therapy in
elderly patients with musculoskeletal pains
or pain associated with osteoarthritis, the
relative limited efficacy and significant
adverse effects of this agent, particularly
hepatic and renal toxicity, have raised
concerns.29 Additionally, acetaminophen
must be used cautiously in those receiving
cancer chemotherapy because there are case
reports of interactions between anticancer
agents and acetaminophen leading to hepatic
toxicity.30 Reduced doses of 2000 mg/day or
the avoidance of acetaminophen is
recommended in the face of renal
insufficiency or liver failure, and
particularly in individuals with a history of
significant alcohol use.31

36

Table 2. Adjuvant Analgesics for End-of-Life Pain Management

Drug Class

Agent

Antidepressants

Nortriptyline

Route of
Administration
Oral

Desipramine

Oral

Venlafaxine

Oral

Duloxetine
Gabapentin
Pregabalin
Clonazepam
Dexamethasone

Oral
Oral
Oral
Oral
Oral/IV/Sq

Lidocaine

Lidocaine patch
Lidocaine
infusion

Topical
IV/sq

NMDA
antagonists

Ketamine

Oral/iv

Bisphosphonates

Pamidronate
Zoledronic acid
THC (Marinol)
Nabilone
(Cesamet)
THC (Sativex)

IV
IV
Oral
Oral

Anti-epilepsy
drugs
Corticosteroids

Cannabinoids

Oromucosal
spray

Potential adverse
effects
Anticholinergic
effects
Cardiac
arrhythmia
Nausea,
dizziness
Nausea
Dizziness
Dizziness
Sedation
Steroid
psychosis

Erythema (rare)
Perioral
numbness,
cardiac changes
Hallucinations

Pain flare,
osteonecrosis
Dizziness,
nausea,
tachycardia,
euphoria

Indications
Neuropathic pain

Neuropathic pain

Neuropathic pain, cerebral

edema, spinal cord
compression, bone pain,
visceral pain
Neuropathic pain
Intractable neuropathic
pain
Unrelieved neuropathic
pain; need to reduce opioid
dose
Osteolytic bone pain
Nausea, loss of appetite,
spasticity, neuropathic
pain

Currently available in: United Kingdom, Canada, Spain, Germany, Denmark, and New Zealand
As evidenced in some clinical trials; not an FDA-approved indication
Sources: Paice JA, Ferrell B. CA Cancer J Clin. 2011;61-157-182.; Marinol Full Prescribing Information

Adjuvant Analgesics
Although opioid medications are a mainstay
of pain management at the end-of-life, many
other classes of medications have proven to
be effective and, in some cases, preferable to
opioids. Some exert a direct analgesic effect
mediated by non-opioid receptors centrally
or peripherally. Other adjuvant analgesics
have no direct analgesic qualities but may
provide pain relief indirectly by affecting
organs or body systems involved in painful
sensations (Table 2).
Some antidepressant agents appear to exert

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analgesic properties and may be particularly

helpful for neuropathic pain conditions.
Tricyclic antidepressants inhibit reuptake of
norepinephrine and serotonin, which appears
to exert analgesic effects, either directly or
indirectly. These agents have been shown to
provide clinically relevant effects in a
review of analgesic studies conducted in
neuropathic pain conditions, primarily
diabetic neuropathy and other non-cancer
conditions.32 One consensus panel listed this
pharmacologic category as one of several
first-line therapies for neuropathic pain.33
Potential side effects include cardiac

37

arrhythmias, conduction abnormalities,

narrow-angle glaucoma, and clinically
significant prostatic hyperplasia. On the
other hand, the sleep-enhancing and moodelevating effects of these antidepressants
may be of benefit in some patients.
Although little evidence supports an
analgesic effect for SSRIs, some newer
antidepressants, such as the serotoninnorepinephrine reuptake inhibitors have
been shown to be effective in relieving
neuropathic pain, including venlafaxine and
duloxetine.34 These have the added
advantage of alleviating hot flashes, a
common and disturbing symptom,
particularly in breast cancer patients
undergoing hormonal therapy. Care must be
taken in such situation, however, because
duloxetine reduces the bioavailability of
tamoxifen, potentially reducing its
therapeutic efficacy.35
The anti-epilepsy drugs gabapentin and
pregabalin have undergone extensive testing
in many non-cancer neuropathy syndromes,
and a recent review concluded that these
drugs have a clinically meaningful effect.36
The most common adverse effects reported
by patients are dizziness; some patients also
develop fluid retention. Although the data
for the efficacy of other anticonvulsants,
such as lamotrigine, levetiracetam, tiagabine,
topiramate, and lacosamide, are not as
conclusive that those for gabapentin and
pregabalin, existing reports suggest potential
efficacy. As with most adjuvant analgesics,
antiepileptic agents are commonly used in
combination with opioid therapy,
particularly when pain is moderate to severe.
A review of cancer trials found that adjuvant
analgesics added to opioids provide
additional relief, usually within 4 to 8 days,
with the strongest evidence for gabapentin.37
Corticosteroids can play a valuable role in
treating end-of-life pain related to

neuropathic pain syndromes, pain associated

with stretching of the liver capsule due to
metastases, for treating bone pain (due to
their anti-inflammatory effects) as well as
for relieving malignant intestinal
obstruction.38 Dexamethasone produces the
least amount of mineralocorticoid effect and
is available in a variety of delivery forms,
including oral, intravenous, subcutaneous,
and epidural.39
Local anesthetics may be useful in
preventing procedural pain and in relieving
neuropathic pain. Local anesthetics can be
given topically, intravenously,
subcutaneously, or spinally. Both gel and
patch versions of lidocaine have been shown
to reduce the pain of postherpetic
neuropathy and cancer-related neuropathic
pain.40 Intravenous or subcutaneous
lidocaine at 1 to 5 mg/kg administered over
1 hour, followed by a continuous infusion of
1 to 2 mg/kg/hour, has been reported to
reduce intractable neuropathic pain in
patients in inpatient palliative care and home
hospice settings.41
NMDA antagonists (dextromethorphan,
amantadine, and ketamine) are believed to
exert their analgesic effects by blocking
receptors for glutamate and other excitatory
amino acids at the level of the spinal cord.
Ketamine is the most commonly-used agent,
and can be administered orally*,
intravenously, subcutaneously, intranasally,
sublingually, epidurally, and topically. A
general recommendation is to reduce the
opioid dose by approximately 25% to 50%
when starting ketamine to avoid sedation.42
Although a Cochrane review found
insufficient trials to determine its safety and
efficacy in relieving cancer pain, case
reports and small studies suggest that
intravenous or oral ketamine
can be used in adults and children with

InforMed 1-800-237-6999 Fax 1-800-647-1356

Not available in the U.S.

38

cancer for the relief of intractable

neuropathic pain or to reduce opioid doses.43
Psychotomimetic reactions consisting of
hallucinations, vivid imagery delirium,
confusion, and irrational behavior have been
reported to occur in approximately 12% of
individuals receiving the drug
systemically.44 Adverse effects, including
hallucinations and unpleasant cognitive
sensations, responded to diazepam at a dose
of 1 mg intravenously.45
Bisphosphonates inhibit osteoclast-mediated
bone resorption and alleviate pain related to
metastatic bone disease and multiple
myeloma.46 Pamidronate
disodium has been shown to reduce the pain,
hypercalcemia, and skeletal morbidity
associated with breast cancer and multiple
myeloma.47 Dosing is generally repeated
every 4 weeks and the analgesic effects
occur in 2 to 4 weeks.48 Although some
recent studies have found an association
between long-term use of bisphosphonate
and an increased risk for atypical femoral
fracture, as well as an association between
new use of bisphosphonate and uveitis and
scleritis, these risks are relatively less
important in end-of-life contexts.49,50
In recent years there has been a resurgence
of interest in the use of cannabinoids for the
relief of pain and the end of life. Like
opioids, cannabinoids produce their
pharmacological effects via actions at
specific receptors in the body that are
designed for endogenously produced
compounds with normal regulatory,
homeostatic properties.51 Unlike opioids,
however, there has never been a documented
case of death from cannabis overdose
indeed, cannabis has no known lethal dose.52
The CB1 and CB2 receptors have been
shown to mediate the analgesic effects of
cannabinoids.53 This has allowed for the

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development of more selective agents that

may provide analgesia while minimizing
cognitive or perceptual side effects. Two
oral cannabinoid preparations are FDAapproved and available in the US, and an
oromucosal preparation is available in
Canada and several European countries.
These routes of administration avoid the
potential hazards and dosing uncertainties
involved with inhaled forms of raw cannabis.
A review of the existing literature evaluating
the role of cannabinoids currently approved
for human use suggests that these agents are
moderately effective for neuropathic pain
with adverse effects that are less than or
comparable to existing analgesics.54
Cannabinoids have been shown to exert no
appreciable effects on opioid plasma levels
and may even augment the efficacy of
oxycodone and morphine in patients
suffering from a variety of chronic pain
conditions, potentially allowing a reduction
in the opioid doses used in such patients.55
The authors of a recent review of the role of
cannabinoids in hospice and palliative care
concluded: Many patients in a palliative
care setting who are currently on long-term
opioids for chronic pain could potentially be
treated with either cannabis alone or in
combination with a lower dose of opioids.
From a pharmacological perspective,
cannabinoids are considerably safer than
opioids and have broad applicability in
palliative care.56
Interventional Therapies
A number of different co-analgesic
techniques have been shown to relieve pain
in certain end-of-life patients. Most of the
existing research is relevant, specifically, to
cancer pain though some results may be
more broadly applicable.
Palliative chemotherapy is the use of
antitumor therapy to relieve symptoms

39

associated with malignancy, such as the

reduction of dyspnea in those with lung
cancer. Radiotherapy, given as single or
multiple fractions, can effectively reduce
pain associated with bone metastases or
other lesions.57 When considering these and
other antitumor approaches, patient goals,
performance status, sensitivity of the tumor,
and potential toxicities must be considered.
As always, clear communication with
patients and their families about the goals
and limitations of these therapies is essential.
Other interventional therapies include
selective nerve blocks, vertebroplasty,
kyphoplasty, implantable intrathecal pumps,
and celiac plexus neurolytic block, which
has been shown to be superior to morphine
in patients with pain due to unresectable

pancreatic cancer.58 . Compared to medical

management alone in refractory cancer pain
patients, patients receiving intrathecal
morphine via a pump reported a greater
reduction in pain and toxicity, a significant
decrease in fatigue and elevated level of
consciousness, and even improved
survival.59 (Smith TJ et al. Journal of
Clinical Oncology, 2002). Trigger point
injections or Botulinum toxin injections into
areas of muscle spasticity, tightness, and
pain may provide some relief. Although
used more extensively in migraine treatment
and chronic pain conditions, this has been
used more recently to relieve pain in people
with cancer who experience radiation
fibrosis that causes cervical dystonia,
trigeminal nerve pain, and headache.60

Figure2.PercentageofpatientsreportingusingspecificCAMtherapiesduringstudy
period

Source: Kutner JS, Corbin L. The use of complementary and alternative medicine therapies by patients with
advanced cancer and pain in a hospice setting: a multi-centered, descriptive study. J Palliat Med. 12(1):78. 2009.
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40

Complementary and Alternative Therapies

A wide range of complementary and
alternative therapies (CAT) are commonly
used in end-of-life care (Figure 2). A 2007
NHHCS study found that 41.8% of all
hospice care providers offered some form of
CAT.61 More than half of providers that
offered CAT offered massage, supportive
group therapy, music and pet therapy, and
guided imagery and relaxation.
CAT interventions are aimed at reducing
pain, inducing relaxation, and enhancing a
sense of control over the pain or the
underlying disease. Breathing exercises,
relaxation, imagery, hypnosis, and other
behavioral therapies are among the
modalities shown to be potentially helpful to
patients.62 Physical modalities such as
massage, use of heat or cold, acupuncture,
acupressure, and other physical methods
may be provided in consultation with
physical or occupational therapy. These
treatments can enhance patients sense of
control as well as greatly reduce the family
caregivers sense of helplessness when they
are engaged in pain relief. A 2008 study
found that both massage and simple touch
induced statistically significant
improvements in pain, quality of life, and
physical and emotional symptom distress
over time without increasing analgesic
medication use.63
Psychosocial interventions for end-of-life
pain may include cancer pain education,
hypnosis and imagery based methods, and
coping skills training.64 Educational
programs are one of the most common
interventions to address cancer pain barriers,
and current studies provide high-quality
evidence that pain education is feasible,
cost-effective, and practical in end-of-life
settings.65
Coping skills training may be beneficial for

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patients and family caregivers dealing with

chronic cancer pain, although the dose and
components of a coping skills training
regimen remain uncertain. Other integrative
and behavioral approaches found to be
helpful for managing end-of-life pain are
massage therapy and acupuncture.66
Nutrition and Hydration at the End of
Life
The provision of nutrition and hydration can
become a clinical challenge at the end of life
and can be directly related to the use of
analgesics, particularly in decisions about
the preferred route of analgesic
administration. As with decisions about
analgesia itself, the fundamental question
regarding various alternatives for nutrition
or hydration is whether the potential benefits
outweigh the burdens from the patients
perspective. The patients own expression of
interest should be the primary guide. If a
dying patient shows interest in either food or
fluids, they should never be withheld unless
providing them clearly causes greater
suffering (i.e. in patients for whom oral
feeding causes significant discomfort).67 In
most cases, patients either do not show an
active interest in food or are satisfied with
very small amounts of specific foods (such
as sweet custards or ice cream) which are
well-tolerated. The forced administration of
nutrients, either parenterally or through a
nasogastric or gastrostomy tube, has little or
no benefit to most patients in the last days or
weeks of life, and the placement or
continuation of the required intravenous line
or enteral feeding tube can be burdensome.
Enteral feeding tubes used during the
terminal phase of illness are often more
useful as a means of administering
medications than nutrients.
Concerns about adequate hydration are
frequently misplaced. Relative dehydration

41

can be beneficial during the terminal phase

for the following reasons:68
By decreasing urine output urinary
incontinence or difficulties of using a
bedpan or commode are reduced
Reduced gastrointestinal secretions
may reduce nausea and vomiting
Pain may be improved by a reduction
in tumor edema
Reduction in oropharyngeal and
pulmonary secretions may lead to
reduced airway congestion and
diminished pooling of secretions the
patient cannot clear on his or her
own.
Managing Pain in Intensive Care Units
Several studies show that most US adults
wish to die at home.69 And yet more than
half of deaths occur in hospitals, most with
ICU care.70 When curative approaches are
not expected to be successful, a transition to
primary comfort-focused care and the
withdrawal of ineffective or burdensome
therapies is often necessary. Although
guidelines and detailed strategies have been
developed for analgesic therapy during the
removal of life-sustaining interventions,
communication about what to expect and
how things may proceed remain paramount
to negotiating this care transition.71 Some
patients and families may be able to have
meaningful interactions at the end of life,
and thus brief interruption of sedatives and
analgesics may be reasonable.
Rarely are dying ICU patients able to selfreport information about their pain.72 Thus it
is incumbent on the critical care health
professionals, perhaps with the assistance of
the patients family members, to assess pain
without self-report input from the patient.
Two pain assessment instruments have been
validated for use in the ICU setting: the
Behavioral Pain Scale73 and the Critical-

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Care Pain Observation Tool.74 Both tools

describe specific observations that the
patients ICU care providers (including
family members or loved ones) can make
that, when present, could indicate the patient
is experiencing pain such as grimacing,
rigidity, wincing, shutting of eyes, clenching
of fists, verbalization, and moaning.75
Reports by family members or other people
close to a patient should not be overlooked.
In the Study to Understand Prognosis and
Preference for Outcomes and Risks of
Treatment (SUPPORT) study, surrogates for
patients who could not communicate
verbally had a 73.5% accuracy rate in
estimating presence or absence of the
patients pain.76
Ethical Considerations
A potential barrier to good pain management
at the end of life is the misconception on the
part of providers, family members, or both,
that an escalation of pain medications or
other palliative therapies will unethically
hasten or cause death. Although ethical and
legal consensus upholds the appropriateness
of withdrawing unwanted or unhelpful
therapies to avoid the prolongation of the
dying process and the administration of
medications with the intent of relieving
suffering, such concerns may mitigate
optimal administration of therapies.77 When
providers administer pain medications and
other palliative therapies to a dying patient,
the intent should explicitly be on relief of
symptoms, and communication with the
family must stress this goal, even if the
possibility exists that such treatments could
hasten death.78
The doctrine of double effect draws a clear
distinction between the aggressive palliation
of pain with the intent to relieve suffering
and the active and purposeful hastening of
death, and the alleviation of pain is ethically
justifiable as long as the caregivers primary

42

intent is alleviating suffering.79 (The

doctrine of double effect holds that an act
that might have a good or bad effect is
ethical if the nature of the act is morally
good or neutral and the intent of the act is
good even if there is potential for bad
effect.)80 Health-care providers should
communicate this strategy with patient and
families, document the reason for and
titration of agents used for the alleviation of
pain, and they should consider engaging the
family members in discussions of the
processes used to avoid under- or
overtreatment of pain.
Contrary to fears among patient and their
families, research suggests that aggressive
pain management at the end of life does not
necessarily shorten life. In fact, pain
management may be life-prolonging by
decreasing the systemic effects of
uncontrolled pain that can compromise vital
organ function.81
If a patient experiences intense pain,
discomfort or other undesirable states at the
end of life despite the best efforts of pain
management providers, palliative sedation
(also known as terminal, continuous,
controlled, or deep-sleep sedation) is an
option.82 Palliative sedation is the
intentional sedation of a patient suffering
uncontrollable refractory symptoms in the
last days of life to the point of almost, or
complete, unconsciousness and maintaining
sedation until deathbut not intentionally
causing death.83 Although palliative sedation
may bring intolerable suffering to an end
and allow people to die peacefully, it
nonetheless can be challenging to put into
practice and has been criticized as slow
euthanasia.84
Acknowledging the inherently complex and
subjective nature of decisions about
palliative sedation, guidelines have

InforMed 1-800-237-6999 Fax 1-800-647-1356

nonetheless been developed to help guide

responsible use of this alternative. Many
guidelines state that palliative sedation
should only be considered when:85,86,87
The patient is terminally ill
Death is expected within hours or
days
The patient is suffering acute
symptoms unresponsive to therapy
Consent is obtained from the patient
or his/her proxy
The withdrawal of food and water is
discussed
Families are informed that the
patient will likely not regain
consciousness and will die
Causing death is not the intention
even though it may not be possible to
achieve adequate symptom control
except at the risk of shortening the
patients life
The degree to which palliative sedation is
used, and the manner in which it is used,
must, in the end, be a matter of clinical
judgment on the part of individual
physicians.
Caring for Families
Although the needs of a patient must
necessarily be a clinicians priority, the
needs and concerns of family members must
also be addressed. Family members or loved
ones often need counseling, education, and
other support because they are often
centrally involved in caring for the patient.
But the death of a loved one is consequential
at the least and, more often, is overtly
traumatic. Family members often remember
vividly the last days of their loved ones life,
especially whether or not the loved one
appeared to be comfortable. These
perceptions may profoundly influence not
only their own emotional state and the
course of their grieving process, but also
how they approach their own death.88 In

43

addition, grief can exert well-documented

impacts on physical and mental health,
raising the risk for depression, sleep
disorders, increased use of alcohol and other
drugs, and suicide.89 A physicians
discomfort or uncertainty about what to say
or do when encountering a bereaved relative
or loved one must be overcome in favor of
taking active steps to provide support. The
following are some suggested strategies for
communicating with bereaved loved ones or
family members.90
Use the name of the deceased when
talking to the bereaved
Talk about the deceased, and, if
appropriate, say it was a honor to
know him or her and that you will
miss him or her
Ask the bereaved if they have any
questions about the final illness or
treatment at the end of life
Ask how the bereaved is feeling
since the death of the deceases, or
how the deceaseds death is affecting
them
Say I cant imagine what youre
going through (even if you have
experienced the death of a loved one
yourself)
Say Im sorry, or Im sorry she/he
is gone
Effective Approaches to Cultural
Differences
Communicating effectively with both
patients and their loved ones requires an
awareness of some of the cultural
differences that can create unexpected
barriers or misunderstandings. End-of-life
discussions are particularly challenging
because of their emotional and interpersonal
intensity. Many physicians are unfamiliar
with common cultural variations regarding
physician-patient communication, medical
decision making, and attitudes about formal
documents such as code status guidelines

InforMed 1-800-237-6999 Fax 1-800-647-1356

and advance directives.91

Although cultural differences certainly exist,
generalizations about specific cultures are
not always applicable to specific patients
because there is wide variation in the ways
that individuals adhere or adopt the
stereotypical beliefs, values, or attitudes of a
particular culture. In fact, research suggests
that when compared with whites of
European descent, ethnic minorities exhibit
greater variability in their cultural beliefs an
preferences.92
Clinicians should be aware that different
cultures may place different emphasisor
disagree completelywith the four guiding
principles of ethical medical conduct
described earlier in this monograph. For
example, in the United States, legal
documents such as advance directives and
durable powers of attorney are strategies to
prolong autonomy in situations in which
patients can no longer represent themselves.
Other cultures, however, de-emphasize
autonomy, perceiving it as isolating rather
than empowering. These non-Western
cultures believe that communities and
families, not individuals alone, are affected
by life-threatening illnesses and the
accompanying medical decisions.93 Cultures
valuing non-malfeasance (doing no harm)
may try to protect patients from the
emotional and physical harm caused by
directly addressing death and end-of-life
care. Many Asian and Native American
cultures value beneficence (physicians
obligation to promote patient welfare) by
encouraging patient hope, even in the face of
terminal illness. Patient or family member
preferences for nondisclosure of medical
information and family-centered decision
making may also be surprising to Americantrained physicians.
Physicians may improve their rapport with

44

ethnically diverse patients simply by

showing interest in their cultural heritage
(Table 3).

preferences and be in a better position to

provide effective, culturally sensitive endof-life care.

Table 3 : Potential Questions Pertaining to

Cultural Differences in End-of-Life Care
Some people want to know everything about
their medical condition, and others do not. What
is your preference?
Do you prefer to make medical decisions about
future tests or treatments for yourself, or would
you prefer that someone else make them for
you?
To patients who request that the physician
discuss their condition with family members:
Would you be more comfortable if I spoke with
your (brother, son, daughter) alone, or would
you like to be present? If the patient chooses
not to be present: If you change your mind at
any point and would like more information,
please let me know. I will answer any questions
you have. (This exchange should be
documented in the medical record.)
When discussing medical issues with family
members, particularly through a translator, it is
often helpful to confirm their understanding: I
want to be sure that I am explaining your
mothers treatment options accurately. Could
you explain to me what you understand about
your mothers condition and the treatment that
we are recommending?
Is there anything that would be helpful for me
to know about how your family/community/
religious faith views serious illness and
treatment?
Sometimes people are uncomfortable
discussing these issues with a doctor who is of a
different race or cultural background. Are you
comfortable with me treating you? Will you
please let me know if there is anything about
your background that would be helpful for me to
know in working with you or your (mother,
father, sister, brother)?

Conclusions
Expert pain management in the terminal
phase of life requires clinicians to employ
the full range of pain assessment, diagnosis,
treatment, and management used for patients
with acute or chronic non-life-threatening
pain. But, in addition, clinicians must be
aware of and knowledgeable about the many
unique physiological, emotional, and
cultural components that come into play at
the end of life. As it is in other phases of life,
pain management at the end of life is highly
dynamic. Ongoing comprehensive pain
assessment is necessary to detect changes in
pain such as the development of painful
bone metastasis, resolution of treatable
causes such as infections, or worsened
neuropathic or visceral pain due to tumor
growth. Careful refinement of pain
management regimens are often required at
the end of life and may include changes in
the route of analgesics if patients can no
longer take oral medications, the need to
rotate opioids, or the addition of agents such
as steroids for a pain crisis (as in
pathological fracture).

Source: Searight HR, Gafford J. Cultural Diversity at the End of

Life: Issues and Guidelines for Family Physicians. Am Fam
Physician. 2005;71(3):515-22.

By using patient-centered questions, and by

including interpreters as necessary,
physicians can develop a richer
understanding of patients health care
InforMed 1-800-237-6999 Fax 1-800-647-1356

Clinicians should seek expert consultation

from pain services or palliative care teams
for complex cases or when pain appears to
be refractory to all efforts. Early referral to
hospice care may allow time for a carefully
planned pain regimen to ensure comfort at
the end of life. The other symptoms that can
accompany the end of life, such as dyspnea,
agitation, delirium, and anxiety, each need
to be carefully assessed and treated with
coordinated interventions. Fortunately, a
wide array of analgesics, interventional
strategies, adjuvant medications, varied
routes of administration, and complementary
and alternative therapies exist that, if used

45

cooperatively and effectively, can greatly

improve the chances that patients and their
families will experience death without

trauma, suffering, or unrelieved pain.

Resources
American Academy of Hospice and Palliative Medicine - http://www.aahpm.org
American Cancer Society - http://www.cancer.org or
American Pain Society - http://www.ampainsoc.org
American Society for Pain Management Nursing - http://www.aspmn.org
City of Hope Pain & Palliative Care Resource Center - http://prc.coh.org
Hospice and Palliative Nurses Association - http://www.hpna.org
References
[Note: some references are duplicated to avoid confusion and errors with manuscript superscripts during the editing and revising process and to
facilitate medical/legal review.]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34

Centers for Disease Control and Prevention. Ten great public health achievements United States, 1900-1999. MMWR Morb Mortal Wkly Rep.
1999;48(12):241-3.
Lunney JR, Lynn J, Foley DJ, Lipson S, Guralnik JM. Patterns of functional decline at the end of life. JAMA. 2003;289(18):2387-92.
Rao JK, Abraham LA, Anderson LA. Novel approach, using end-of-life issues, for identifying items for public health surveillance. Prev Chronic Dis.
2009;6(2):1-8.
Family Caregivers Guide to Hospice and Palliative Care. 2010 United Hospital Fund. Next Step in Care series.
Family Caregivers Guide to Hospice and Palliative Care. 2010 United Hospital Fund. Next Step in Care series.
Byock I. Dying Well: The Prospect for Growth at the End of Life. Riverhead Books. New York. 1997.
Beauchamp TL, Childress JF. Principles of biomedical ethics. 5th ed. Oxford, UK: Oxford University Press, 2001
Forrow L, Smith HS. Pain Management in End of Life: Palliative Care. In Principles & Practice of Pain Medicine, 2nd Ed. Warfield CA and Bajwa
ZH Eds. 2004. McGraw-Hill, New York, NY.
Forrow L, Smith HS. Pain Management in End of Life: Palliative Care. In Principles & Practice of Pain Medicine, 2nd Ed. Warfield CA and Bajwa
ZH Eds. 2004. McGraw-Hill, New York, NY.
Forrow L, Smith HS. Pain Management in End of Life: Palliative Care. In Principles & Practice of Pain Medicine, 2nd Ed. Warfield CA and Bajwa
ZH Eds. 2004. McGraw-Hill, New York, NY.
Paice JA, Ferrell B. The Management of Cancer Pain. CA Cancer J Clin. 2011;61-157-182.
Abrahm JL. 2005. A Physicians Guide to Pain and Symptom Management in Cancer Patients. Baltimore, MD: Johns Hopkins Univ. Press. 2nd ed.
Paice JA, Ferrell B. The Management of Cancer Pain. CA Cancer J Clin. 2011;61-157-182.
Mercadante S. Intravenous morphine for management of cancer pain. Lancet Oncol. 2010;11:484-489.
Kaiko RF, Foley KM, Grabinski PY, et al. Central nervous system excitatory effects of meperidine in cancer patients. Ann Neurol. 1983;13:180-185.
Hawley PH, Byeon JJ. A comparison of sennosides-based bowel protocols with and without docusate in hospitalized patients with cancer. J Palliat
Med. 2008;11:575-581.
Portenoy RK, Thomas J, Moehl Boatwright ML, et al. Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients
with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. J Pain Symptom Manage. 2008;35:458-468.
Bruera E, Driver L, Barnes EA, et al. Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: a
preliminary report. J Clin Oncol. 2003;21:4439-4443.
Paice JA, Ferrell B. The Management of Cancer Pain. CA Cancer J Clin. 2011;61-157-182.
Paice JA, Ferrell B. The Management of Cancer Pain. CA Cancer J Clin. 2011;61-157-182.
Morita T, Tsunoda J, Inoue S, Chihara S. Effects of high dose opioids and sedatives on survival in terminally ill cancer patients. J Pain Symptom
Manage. 2001;21:282-289.
Sykes N, Thorns A. The use of opioids and sedatives at the end of life. Lancet Oncol. 2003;4:312-318.
Paice JA, Ferrell B. The Management of Cancer Pain. CA Cancer J Clin. 2011;61-157-182.
McNicol E, Strassels SA, Goudas L, Lau J, Carr DB. NSAIDS or paracetamol, alone or combined with opioids, for cancer pain. Cochrane Database
Syst Rev. 2005;(1):CD005180.
Fishman SM. Responsible Opioid Prescribing: A Clinicians Guide, 2nd Ed. Waterford Life Sciences. 2012 (in press).
Harris G. FDA Plans New Limits on Prescription Painkillers. New York Times. January 13, 2011.
Rainsford KD. Anti-inflammatory drugs in the 21st century. Subcell Biochem. 2007; 42:3-27.
Schlansky B, Hwang JH. Prevention of nonsteroidal anti-inflammatory drug-induced gastropathy. J Gastroenterol. 2009;44(suppl 19):44-52.
American Geriatrics Society Panel on Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent
pain in older persons. J AmGeriatr Soc. 2009;57:1331-1346.
Ridruejo E, Cacchione R, Villamil AG, Marciano S, Gadano AC, Mando OG. Imatinibinduced fatal acute liver failure. World J Gastroenterol.
2007;13:6608-6611.
Swarm R, Abernethy AP, Anghelescu DL, et al. Adult cancer pain. J Natl Compr Canc Netw. 2010;8:1046-1086.
Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010;150:573-581.
Dworkin RH, OConnor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain.
2007;132:237-251.
Durand JP, Goldwasser F. Dramatic recovery of paclitaxel-disabling neurosensory toxicity following treatment with venlafaxine. Anticancer Drugs.
2002;13:777-780.

InforMed 1-800-237-6999 Fax 1-800-647-1356

46

35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80

Goetz MP, Knox SK, Suman VJ, et al. The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res
Treat. 2007;101:113-121.
Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010;150:573-581.
Bennett MI. Effectiveness of antiepileptic or antidepressant drugs when added to opioids for cancer pain: systematic review. Palliat Med.
2011;25(5):553-9.
Wooldridge JE, Anderson CM, Perry MC. Corticosteroids in advanced cancer. Oncology (Williston Park). 2001;15:225-234; discussion 234-236.
Paice JA, Ferrell B. The Management of Cancer Pain. CA Cancer J Clin. 2011;61-157-182.
Fleming JA, OConnor BD. Use of lidocaine patches for neuropathic pain in a comprehensive cancer centre. Pain Res Manag. 2009;14:381-388.
Ferrini R, Paice JA. How to initiate and monitor infusional lidocaine for severe and/or neuropathic pain. J Support Oncol. 2004;2:90-94.
Paice JA, Ferrell B. The Management of Cancer Pain. CA Cancer J Clin. 2011;61-157-182.
Bell R, Eccleston C, Kalso E. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev. 2003;(1):CD003351.
Kastrup EK, Hebel SK, Rivard R (eds.). Drug facts and Comparisons. 1998.
Mercadante S, Arcuri E, Tirelli W, Casuccio A. Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized,
controlled, double-blind, crossover, double-dose study. J Pain Symptom Manage. 2000;20:246-252.
Wong R, Wiffen PJ. Bisphosphonates for the relief of pain secondary to bone metastases. Cochrane Database Syst Rev. 2002;(2):CD002068.
Groff L, Zecca E, De Conno F, et al. The role of disodium pamidronate in the management of bone pain due to malignancy. Palliat Med.
2001;15:297-307.
Paice JA, Ferrell B. The Management of Cancer Pain. CA Cancer J Clin. 2011;61-157-182.
Meier RPH et al. Increasing occurrence of atypical femoral fractures associated with bisphosphonate use. Arch Intern Med. 2012 May 21; [e-pub
ahead of print].
Etminan M et al. Inflammatory ocular adverse events with the use of oral bisphosphonates: A retrospective cohort study. CMAJ. 2012;184:E431.
Carter GT, Flanagan AM, Earleywine M, et al. Cannabis in Palliative Medicine: Improving Care and Reducing opioid-Related Morbidity. Am J Hosp
& Pall Med. 2011;28(5):297-303.
Aggarwal SK, Kyashna-Tocha M, Carter GT. Dosing medical marijuana: rational guidelines on trial in Washington State. Med Gen Med.
2007;9(3):52.
Rahn EJ, Zvonok AM, Thakur GA, Khanolkar AD, Makriyannis A, Hohmann AG. Selective activation of cannabinoid CB2 receptors suppresses
neuropathic nociception induced by treatment with the chemotherapeutic agent paclitaxel in rats. J Pharmacol Exp Ther. 2008;327:584-591.
Ashton JC, Milligan ED. Cannabinoids for the treatment of neuropathic pain: clinical evidence. Curr Opin Investig Drugs. 2008;9:65-75.
Abrams, D.I., Couey, P., Shade, S.B., Kelly, M.E. & Benowitz, N.L. Cannabinoidopioid interaction in chronic pain. Clin. Pharmacol. Ther.
2011;90:844851.
Carter GT, Flanagan AM, Earleywine M, et al. Cannabis in Palliative Medicine: Improving Care and Reducing opioid-Related Morbidity. Am J Hosp
& Pall Med. 2011;28(5):297-303.
Culleton S, Kwok S, Chow E. Radiotherapy for pain. Clin Oncol (R Coll Radiol). 2011;23(6):399-406.
Zhang CL, Zhang TJ, Guo YN, et al. Effect of neurolytic celiac plexus block guided by computerized tomography on pancreatic cancer pain. Dig Dis
Sci. 2008;53:856-860.
Smith TJ et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory
cancer pain: impact on pain, drug-related toxicity, and survival. Journal of Clinical Oncology. 2002;20(19):4040-9.
Stubblefield MD, Levine A, Custodio CM, Fitzpatrick T. The role of botulinum toxin type A in the radiation fibrosis syndrome: a preliminary report.
Arch Phys Med Rehabil. 2008;89:417-421.
Bercovitz A, Sengupta M, Jones A, Harris-Kojetin LD. Complementary and Alternative Therapies in Hospice: The National Home and Hospice Care
Survey: United States, 2007. National health statistics reports; no 33. Hyattsville, MD: National Center for Health Statistics. 2010.
Paice JA, Ferrell B. The Management of Cancer Pain. CA Cancer J Clin. 2011;61-157-182.
Kutner JS, Smith MC, Corbin L, et al. Massage Therapy vs. Simple Touch to Improve Pain and Mood in Patients with Advanced Cancer: A
Randomized Trial. Ann Intern Med. 2008;149(6):369-379.
Keefe FJ, Abernethy AP, C Campbell L. Psychological approaches to understanding and treating disease-related pain. Annu Rev Psychol.
2005;56:601-630.
Keefe FJ, Abernethy AP, C Campbell L. Psychological approaches to understanding and treating disease-related pain. Annu Rev Psychol.
2005;56:601-630.
Cassileth BR, Keefe FJ. Integrative and behavioral approaches to the treatment of cancer-related neuropathic pain. Oncologist. 2010;15(suppl 2):1923.
Forrow L, Smith HS. Pain Management in End of Life: Palliative Care. In Principles & Practice of Pain Medicine, 2nd Ed. Warfield CA and Bajwa
ZH Eds. 2004. McGraw-Hill, New York, NY.
Forrow L, Smith HS. Pain Management in End of Life: Palliative Care. In Principles & Practice of Pain Medicine, 2nd Ed. Warfield CA and Bajwa
ZH Eds. 2004. McGraw-Hill, New York, NY.
Weitzen S, Teno JM, Fennell M, et al. Factors associated with site of death: a national study of where people die. MedCare. 2003;41:323335.
Angus DC, Barnato AE, Linde-Zwirble WT, et al. Use of intensive care at the end of life in the United States: an epidemiologic study. Crit Care Med.
2004;32:638643
Mularski RA, Puntillo K, Erstad BL, et al. Pain Management Within the Palliative and End-of-Life Care Experience in the ICU. Chest.
2009;135:1360-1369.
Mularski RA, Puntillo K, Erstad BL, et al. Pain Management Within the Palliative and End-of-Life Care Experience in the ICU. Chest.
2009;135:1360-1369.
Payen JF, Bru O, Bosson JL, et al. Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med. 2001; 29:2258
2263.
Gelinas C, Fillion L, Puntillo KA, et al. Validation of the Critical-Care Pain Observation Tool in adult patients. Am J Crit Care. 2006; 15:420427.
Puntillo KA, Morris AB, Thompson CL, et al. Pain behaviors observed during six common procedures: results from Thunder Project II. Crit Care
Med. 2004;32:421427.
Desbiens NA, Mueller-Rizner N. How well do surrogates assess the pain of seriously ill patients? Crit Care Med. 2000;28:13471352.
Beauchamp TL, Childress JF. Principles of biomedical ethics. 5th ed. Oxford, UK: Oxford University Press, 2001
Mularski RA, Puntillo K, Erstad BL, et al. Pain Management Within the Palliative and End-of-Life Care Experience in the ICU. Chest.
2009;135:1360-1369.
Forrow L, Smith HS. Pain Management in End of Life: Palliative Care. In Principles & Practice of Pain Medicine, 2nd Ed. Warfield CA and Bajwa
ZH Eds. 2004. McGraw-Hill, New York, NY.
Forrow L, Smith HS. Pain Management in End of Life: Palliative Care. In Principles & Practice of Pain Medicine, 2nd Ed. Warfield CA and Bajwa
ZH Eds. 2004. McGraw-Hill, New York, NY.

InforMed 1-800-237-6999 Fax 1-800-647-1356

47

81
82
83
84
85
86
87
88
89

90
91
92
93

Edwards MJ. Opioids and benzodiazepines appear paradoxically to delay inevitable death after ventilator withdrawal. J Palliat Care. 2005;21:299
302.
Mularski RA, Puntillo K, Erstad BL, et al. Pain Management Within the Palliative and End-of-Life Care Experience in the ICU. Chest.
2009;135:1360-1369.
Bruce A, Boston P. Relieving existential suffering through palliative sedation: discussion of an uneasy practice. J Adv Nurs. 2011;67(12):2732-2740.
Battin M.P. Terminal sedation: pulling the sheet over our eyes. Hastings Center Report. 2008;38(5):2730.
Peppin J.F. Intractable symptoms and palliative sedation at the end of life. Christian Bioethics: Non-ecumenical Studies in Medical Morality.
2003;9(2):343355.
Verkerk M., van Wijlick E., Legemaate J. & de Graeff A. A national guideline for palliative sedation in the Netherlands. Journal of Pain & Symptom
Management. 2007;34(6):666670.
Crenshaw J. Palliative sedation for existential pain. Journal of Hospice & Palliative Nursing. 2009;11(2):101108.
Prigerson HG, Jacobs SC. Caring for bereaved patients. JAMA. 2001;286:1369.
Stroebe MS, Hansson RO, Stroebe W, Schut H. Introduction: concepts and issues in contemporary research on bereavement. In: Stroebe MS,
Hansson RO, Stroebe W, Schut H, eds. Handbook of Bereavement Research: Consequences, Coping and Care. Washington, DC. American
Psychological Association. 2001:8.
Prigerson HG, Jacobs SC. Caring for bereaved patients. JAMA. 2001;286:1369.
Searight HR, Gafford J. Cultural Diversity at the End of Life: Issues and Guidelines for Family Physicians. Am Fam Physician. 2005;71(3):515-22.
Blackhall LJ, Murphy ST, Frank G, Michel V, Azen S. Ethnicity and attitudes toward patient autonomy. JAMA. 1995;274:820-5.
Candib LM. Truth telling and advance planning at the end of life: problems with autonomy in a multicultural world. Fam Syst Health. 2002;20:21328.

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48

Self-Assessment
Choose the best possible answer for each question and mark your answers on the SelfAssessment answer sheet at the end of this book. There is a required score of 70% or better to
receive a Certificate of completion.
24. A sample of older well adults
considered having which of the
following conditions as worse than
death?
a. Alzheimer Disease
b. Severe pain
c. Heart attack
d. Stroke
25. Which of the following correctly
describes the distinction between
palliative care and hospice care?
a. Hospice care is a broader term than
palliative care as it includes the
family
b. Palliative care focuses only on pain
control
c. Hospice care is reserved only for
patients who are not expected to live
more than 6 months
d. Palliative care is reserved for
patients with life-threatening
diseases
26. Which statement is most true about
pain relief at the end of life?
a. Pain relief is the primary treatment
goal at the end of life
b. The goal of treatment should be zero
pain for the patient
c. Patients typically ask for maximum
pain relief
d. Some patients choose less pain relief
in exchange for mental alertness

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27. Of the following, the most reliable

option for determining if a patient,
who is not alert enough to
communicate, is experiencing pain
would be:
a. Physician clinical opinion
b. Any patient grunts or groans
c. Signs of discomfort accompanied by
more rapid breathing
d. Tolerance of higher dose of
analgesic
28. For end-of-life pain management,
which of the following is correct about
first-line opioid therapy?
a. Morphine is the drug of choice
b. Meperidine is appropriate for all
patients
c. No specific agent is superior to
another
d. Opioids are not appropriate when
oral route is precluded
29. Unwarranted fear of what potential
side effect of opioid analgesics can
lead to underprescribing by clinicians
and/or under use by patients?
a. Respiratory depression
b. Sedation
c. Nausea
d. Constipation
30. Which analgesic must be used
cautiously in patients receiving cancer
chemotherapy?
a. Ibuprofen
b. Acetaminophen
c. Aspirin
d. Naproxen

49

31. Which of the following is not a

possible adjuvant medication used to
help control pain at the end of life?
a. Antidepressants
b. Corticosteroids
c. NMDA antagonists
d. Psychostimulants

35. What condition of a patient may be

beneficial during the terminal phase
of an illness?
a. Hyperglycemia
b. Hypoglycemia
c. Relative dehydration
d. Bradycardia

32. Which class of analgesic has received

increasing attention in recent years as
a possible way to control pain and
reduce the concurrent dose of opioid
analgesics?
a. Cannabinoids
b. Bisphosphonates
c. Psychostimulants
d. Neuroleptics

36. Contrary to fears among some

patients and/or family members, what
action or treatment does not
necessarily shorten life?
a. Placement in a long-term care
facility
b. Removal of feeding tubes
c. Aggressive pain management
d. CPR

33. Which fundamental question should

guide decisions about ways to provide
nutrition and/or hydration at the end
of life?
a. Will withholding of nutrition and/or
hydration hasten death?
b. Will nutrition and/or hydration
prolong life?
c. Do the potential benefits outweigh
the potential burdens from the
patients perspective?
d. Do the potential benefits outweigh
the potential burdens from the
perspective of the primary clinical
caregivers?

37. Which of the following is an example

of how a clinician can show support
for a bereaved relative or loved one?
a. Silently put an arm around the
bereaved person
b. Use the name of the deceased in
conversation and, if appropriate, say
it was an honor to know him or her
c. Leave interactions with bereaved
relatives to nursing staff
d. Offer the name and contact
information of an on-staff spiritual
advisor or religious representative

34. Enteral feeding tubes used during the

terminal phase of illness may be
primarily useful as a means of
_________________.
a. Assessing gastrointestinal motility
b. Administering medications
c. Administering nutrition
d. Providing hydration

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38. How might clinicians improve their

cultural sensitivity around end-of-life
issues?
a. Allow family members to have
continuous access to the patient
b. Listen to family members concerns,
but continue to provide standard
medical care to the patient
c. If family members dont understand
a medical explanation, repeat the
explanation more slowly and clearly
d. Use patient-centered questions and
use interpreters if needed

50

Course:SDL1Credits OriginalReleaseDate11/2012 LastUpdate09/2013

ExpirationDate:10/31/2015

Self-Directed Searching & Learning

Audience
This course is designed for all physicians (MD/DO), physician
assistants and nurse practitioners required to document lifelong
continuous professional development.
Course Objective
The purpose of the course is to improve competency in
conducting online self-directed learning, including strategies that
facilitates searching, learning, knowledge retention and
application in practice. The course also details how healthcare
professionals can document self-directed search and learn for
CME credits.
Learning Objectives
Completion of this course will better enable the course participant to:

1.
2.
3.
4.

1.
2.
3.

Identify the characteristics of self-directed learning.

Recognize the importance of self-directed learning to
professional development.
Identify the elements of Internet searching and learning.
Use searching and learning to earn AMA PRA Category 1
Credit(s)TM.
How to Receive Credit
Read the course materials
Complete the self-assessment questions at the end. A score
of 70% is required.
Return your customer information/answer sheet, evaluation,
and payment to Informed by mail, phone, fax or complete
online at course website under NETPASS.

Faculty
Stephen Braun
Medical Writer
Braun Medical Media
Activity Director
Sarina J. Grosswald, EdD
Director of CME, Informed
SJ Grosswald & Associates
Disclosure
Resolution of Conflicts of Interest
In accordance with the ACCME Standards for Commercial
Support of CME, the Informed implemented mechanisms, prior to
the planning and implementation of this CME activity, to identify
and resolve conflicts of interest for all individuals in a position to
control content of this CME activity.
Staff and Content Validation Reviewer Disclosure
Informed staff involved with this activity and any content
validation reviewers of this activity have reported no relevant
financial relationships with commercial interests.
Planning Committee/Faculty Disclosure
The following faculty and/or planning committee members have
indicated they have no relationship(s) with industry to disclose
relative to the content of this CME activity:
Sarina J. Grosswald, EdD
Stephen Braun

Accreditation Statement
Informed is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide continuing
medical education for physicians.
Designation of Credit
Informed designates this enduring material for a maximum of 1
AMA PRA Category 1 Credit. Physicians should claim only the
credit commensurate with the extent of their participation in the
activity.
This activity developed without Commercial Support

2013. All rights reserved. These materials, except those in the public
domain, may not be reproduced without permission from InforMed. This
publication is designed to provide general information prepared by
professionals in regard to the subject matter covered. It is provided with the
understanding that InforMed, Inc. is not engaged in rendering legal, medical
or other professional services. Although prepared by professionals, this
publication should not be utilized as a substitute for professional services in
specific situations. If legal advice, medical advice or other expert assistance
is required, the service of a professional should be sought.

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51

Self-Directed Searching & Learning

CHALLENGE YOURSELF TO GET IN FRONT OF THE TECHNOLOGY CURVE.
Physicians have and will continue to engage and direct their own learning to reaffirm and gain new knowledge that is utilized in their
practice of medicine to safely improve patient outcomes. The internet has become an integral medium for self-directed learning by
physicians. It may take less than a minute to verify drug interactions, a few minutes to check a clinical guideline or query MEDLINE,
longer to read a journal article or view your specialty society updates. Perhaps you listen to a podcast from a nationally recognized
expert, view a video from a medical school faculty member, blog in a clinical area or have a collegial discussion in a social network.
Document this internet usage and earn AMA PRA Category 1 Credit(s)TM to fulfill all of your state licensure requirements and parts of
your MOC requirements. Now with Internet Searching and Learning, you can learn how simple it is to use and then utilize the Internet
to gain a comparative benefit for the time you already spend on all of these efforts. Start earning CME credits the next time you go
online. This year, challenge yourself to get in front of the technology curve. When you get ready to renew your license you will be
pleasantly surprised by the amount of credits youve earned.
What motivates us to learn?

Self-Directed Learning and Professional Development

This paper focuses on the physician as a learner. All of us

have some natural motivation to learn. The primary
motivation for physicians is the desire to accomplish some
specific task or resolve a particular problem. It is these tasks
or problems that will send us to books or journals, the howto guides, and yes, on occasion even to the manual that
comes with our new gadget.
These situations not only motivate us to learn, but also
increase the chances that we remember and apply what we
learned. Learning that is undertaken in this way is referred to
as self-directed learning (SDL). The physician is actively
involved in the learning process and in making decisions about
what is learned, how its learned, when the learning takes
place, and how it is applied. The physician is the decisionmaker for meeting his or her own learning needs.

Continuous professional development or lifelong learning

is recognized as an important component of physician
competency. The American Board of Medical Specialties has
incorporated this expectation in a program called Maintenance
of Certification (MOC), which is being adopted by most, if not
all, medical societies that offer specialty certification.

What Distinguishes Self-Directed Learning from Other

Types of Learning?
It is important to distinguish the concept of self-directed
learning from independent learning. Independent learning is a
specific type of instructional method in which the individual
learns alone. Self-directed learning, in contrast, is a process
that encompasses a wide range of methods and approaches for
meeting different learning needs and preferred learning styles,
making use of any available resources.
For example, a physician might be working
independently, defining what is to be learned, setting the
learning objectives, identifying a specific source of learning
(such as a book, journal, or self-assessment module), then
applying the new knowledge to patient care and assessing the
change in performance or patient outcome. In another
situation, self-directed learning might involve the help of a
facilitator to identify a workshop, seminar or conference that
includes learning objectives and formats that meet the
physicians needs and preferred learning style. In either case,
the learning is centered on the physicians individual needs.
Self-directed learning can be formally or informally
structured. In order for SDL to be a certified CME activity
and to qualify for AMA PRA Category 1 Credit or AAFP
Prescribed credit, it must be formally structured. That means
it must have several specifically-documented components.
Those components are 1) a definition of the learning need or
specific problem being explored, 2) identification of sources
used for the educational experience, and 3) evaluation of the
learning experience and/or learning outcomes.
InforMed 1-800-237-6999 Fax 1-800-647-1356

Characteristics of Self-Directed Learning

Learner takes responsibility for what, how and when

learning takes place
Alone or with assistance, the learner:
o Identifies and assesses learning needs
o Sets priorities
o Defines goal of learning
o Selects learning formats and activities
o Evaluates the outcomes
Can make use of any form of learning format or
opportunity
Can be done alone or with others

MOC is based on the premise that physician specialists

should be measured not merely by the fact that they have been
certified, but also on how well they stay current in their
profession. The program incorporates continuous professional
development as a formal means of measuring a physicians
continued competency, rather than merely the requirement of
passing an examination every six to ten years.
MOC focuses on six general competencies that include
four component categories. The six competencies are:

Patient care

Medical knowledge

Practice-based learning and improvement

Interpersonal and communications skills

Professionalism

Systems-based practice
These competencies are patient-centered, driven by the
goal of improving the overall care and safety of patients.
The four component categories are:
Part I:
Professional Standing
Part II:
Lifelong Learning and SelfAssessment
Part III:
Cognitive Expertise
Part IV:
Practice Performance Assessment
52

These component categories provide the criteria model

for specialty recertification, placing emphasis on self-directed
and lifelong learning relevant to the physicians clinical
practice. CME is the primary source of continuing
professional development.
State licensing boards are similarly moving toward
requiring that CME be patient driven. States are defining that
CME specifically be in the area of physicians clinical
practices and reflect the professional focus of the physician to
meet the health care needs of the public. A review of these
model rules indicates two criteria; credits must (1) be in the
physician's practice area; (2) reflect the physician's
professional needs in order to meet the public's health care
needs.
Consequently, self-directed, or individual-directed
learning is becoming vital to a physicians continuing medical
education, ensuring that learning is based on the specific
informational needs of a physicians own clinical practice.
Internet Searching & Learning
A process in which the learner:

Identifies a problem in practice

Accesses content in search for an answer from Internet
sources
Is not following a specific structure

Internet Searching & Learning CME

The Internet provides an invaluable tool for self-directed
learning. It is often the first resource that we turn to for quick
answers to immediate questions or problems. When were
looking for information, we just Google it. When the time
spent exploring the Internet is relevant to a physicians clinical
practice, and is confined to noncommercial and unbiased
sources, that time can be credited toward AMA PRA Category
1 Credit. This search process is referred to as Internet
Searching and Learning (ISL). ISL is structured, self-directed
online learning on topics specific to the clinical practice.
Learning from this type of activity is driven by a reflective
process in which the physician identifies clinical questions, the
sources consulted, and the application to practice.
ISL is dynamic, meeting immediate practice-based needs.
It is also referred to as just-in-time learning because it is
accessible to the physician at the time he or she needs the
information. You may be with a patient or on a consultation
call when a question arises. You can turn to your desktop,
laptop or phone or any internet-access device (tablet, PDA)
and get an immediate answer to your question in a matter of
minutes.
What allows this search for information to qualify for
AMA PRA Category 1 Credit(s) is documentation and
reflection. This does not need to be completed at the time of
your immediate search. Initially, it may take only two or three
minutes to find the answer you need. Later you can return to
research the question more deeply, and reflect on what you
discover and how it relates to your practice and your patients.
InforMed 1-800-237-6999 Fax 1-800-647-1356

How Searching and Learning Meets the

Physicians Needs
Highly Relevant
The CME activity is unique to your individual learning or
information need, to help you find solutions to your clinical
problems.
Effective
The learning applies directly and immediately to your
practice and your patients. Dynamic, real- world application
leads to greater learning.
Individually-Directed and Convenient
The educational activity is driven by you, for your needs
and on your schedule. You decide the topic you want to
pursue and the depth the content. And you do it when and
where its convenient for you.
Simple and Easy
Directus tracks your search, documents the process, and
allows you to print your CME certificate right from your own
computer or mobile device.
Using Directus
Directus is an example of an application for turning your
search into a self-directed CME activity for which you earn
AMA PRA Category 1 Credit. It provides the structure for
this process by documenting the educational activity and
planned outcome, capturing your search efforts and evaluating
your actual outcome. It does not confine you to a specific set
of websites or databases. Rather, it allows you to search freely
throughout the Internet using the sources you know and trust
to be authoritative, unbiased and free from commercial
interests. (Heres how it works. Go to www.directus.cme.edu,
view the demo to get all the benefits of this tool, register, then
download and install the utility program on to your computer.
A small icon will appear in your toolbar and just click on it to
start Directus.)
Lets follow a specific patient care situation to see how
the application turns your patients question into your
individually directed CME.
Bill Johnson is a 57-year-old patient who comes to the
office for annual blood pressure screening because of familial
risk. Today he mentions that his father is beginning to
showing signs of difficulty with short term memory. Bill has
several pages of printed information about the connection
between high blood pressure and Alzheimers, and asks about
this.
Step 1: Define
You decide to search for literature about hyper-tension
and Alzheimers. To earn AMA PRA Category 1 Credit for
your search, you must document the clinical question or
information you are seeking (identify your educational need),
record the sources consulted (the learning activity), and
evaluate the outcome of your search.
Learning begins by identifying the educational need. This
may be accomplished formally through an audit of medical
records or from results of quality assurance processes. More
53

informal identification of a learning need may arise from

everyday interactions such as the specific patient issue raised
by Bill Johnson in our example; or the desire to review the
most recent research about a new drug or procedure or from
conversations with colleagues.
The application allows you to document your educational
need by asking Why are you conducting this research?
Then, to more specifically define the problem or question, and
help you focus your search asks, What is the question /
problem / topic of your research? Most important to CME
is the use in clinical practice of what is learned. So to
conclude Step 1 and complete the identification of the learning
need, it asks What will be the result of your research?
By answering these questions (see Figure 1), you have
defined the purposes and goal of your learning activity.
Figure 1 shows the response to these questions for the search
pertaining to Bill Johnsons inquiry. We will explore the
relationship of hypertension and Alzheimers disease. Next,
we click submit to record our responses.
Step 2: Research
You are now ready to begin your research. The window
(see Figure 2) will appear on your screen. You can minimize
this window, but do not close it because that will close the
program. With the application running in the background, you
can conduct your search as usual. Open your web browser, if
not already open, and begin your research. Use professional

and peer-reviewed data sources. You might begin by going to

Pub Med, the search engine for National Library of Medicine,
Google Scholar, or to Cochrane, and enter the search terms
(e.g. Hypertension and Alzheimers).
This application will keep track of the sites you visit and
the time spent, which is then used to claim CME credit. You
can Pause your search at anytime and Resume later. For
example, you might find the initial information you need
within a few minutes in order to respond to Mr. Johnson while
he is still in the office. Then you can return later to read the
full text of a journal article, print out an article, or continue
searching. Whenever youve completed your research, return
to Directus and select the FINISH button.
Step 3: Evaluate
At the conclusion of the search, you are asked to evaluate
the success of the research in finding the answer to your
question or the information you were seeking. By answering
How well did your research meet your expected result?
you evaluate the results of your individually-directed learning
(see Figure 3).
Finally, you are asked about the outcome of the learning
activity in the last question, What do you plan to do as a
result of what you learned? Will what you found lead to a
change in practice? Did you identify a need for additional
information from other sources or raise interest in further
researching this or a related topic?

Figure1

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54

Figure2

Figure3

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55

Figure4
Figure4

After completing the evaluation, you are ready to submit

your self-directed learning activity for CME credit. The
application has kept track of the time spent on the search
process and gives this information in the time box. In the box
underneath the time box, you can enter the total time you wish
to claim for CME. The total time you spend on the CME
activity may differ somewhat from the exact search time
calculated by the application. You deduct time spent on nonCME qualifying sites. Like all certified CME activities, the
time credited toward CME cannot include visits to commercial
sites or sites that display advertisements. Though these sites
may provide useful information, they are not included in the
calculation of CME credits. You can make this adjustment
manually or you can review the search TIME LOG and
remove any non-qualifying sites by checking the box next to
the listed sites. The search time will be recalculated to reflect
this adjustment. Then just click the submit button to have
Directus record your responses and youre done.
Reflection Time and Viewing Your CME Activities
You may have decided that instead of taking the time to
read a journal article online, you preferred to print the article
and read it later or you may spend additional time analyzing
your research. Learning sometimes requires a reflection period
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and this additional time can also be claimed for AMA PRA
Category 1 Credit. At present, the maximum amount of
time that you can claim is 30 minutes for each individual CME
activity. To claim this credit you simply return to
directus.cme.edu, login and your CME history will be
displayed which contains every individually-directed CME
activity you have claimed for credit. Simply click on the
Activity Title (which in our example was Hypertension and
Alzheimers), to display the activity record with all the
information captured by Directus (see Figure 4). The only
thing that you can change on the activity record is the actual
amount of time claimed for CME credit. You can deduct time
either manually or by making adjustments in the time log.
Likewise you can claim up to 30 minutes for reflection time.
FORECAST
CME is in the midst of transformation with its outcome being
directed by a number of stakeholders, with particular input
from three. First, The American Board of Medical Specialtys
maintenance of certification (MOC) emphasis on life-long,
self-directed learning relevant to a physicians practice. Next,
the Federation of State Medical Boards model for
maintenance of licensure (MOL) concurrency that physicians
satisfying the requirements of MOC have also substantially
56

fulfilled the requirements for MOL. Finally, state medical

boards requirements for physician CME to be patient driven
and within the scope of a physicians practice. Expected
outcomes are expected to include, physicians will: 1) engage
in critical self-assessments; 2) participate in CME that
addresses identified practice/performance gaps; 3) measure
and adjust to improve their performance and document this
process.
Under this regulatory movement, for continuous quality and
performance improvement, expectations are that physicians
will engage in a more profound self-assessment, participate in
CME that addresses identified practice/performance gaps,
measure, document, and provide evidence to support these
processes. This type of primary source documentation and
corresponding verification can burden both physicians and
regulatory entities. Self-directed CME through Searching and
Learning provides a solid tool for physicians to meet or
exceed the expectations of regulators. This method allows
physicians to automatically engage, record, demonstrate,
document, and report their learning experiences. Its ease of
use, modular platform, and adaptability for technology growth
can place physicians ahead of the yield curve for themselves
and regulators. Physicians already engage this process. Think
of yourself, relative to how you engage in Searching and
Learning, then look at Table 1 and see yourself in the data.
Ask yourself how easily you could fulfill your CME
requirements for state licensure, MOC, and MOL? Take a
couple of minutes to reflect.
PATH
This year, challenge yourself to incorporate self-directed
Searching and Learning, through any certified educational
activity that provides cross-utilization, platforms and natural
adaptability to your individual learning preferences. As a
professional courtesy, to get you started and establish a
benchmark comparison, this years subscription fee for
Directus is waived. On page 60 you can opt out or we will
send you temporary password and userid via e-mail to begin
earning CME credits the next time you go online. You can
change your password and userid at any time after you have
installed the program on your computer. You may install the
program on more than one computer but only receive credit
from the program running on a sole computer at any time*.

Table 1: Searching and Learning is for All Physicians

Who?

Online Search is for All Ages.

Physicians <45 years old:

How?

15 hours per week

online-professional
purposes
82% daily search
engine use
77% of online time
is for clinical
decisions

Physicians >55 years old:

9 hours per week

online-professional
purposes
84% daily search
engine use
64% of online time
is for clinical
decisions

Physicians Use Search Information For:

Searched for more information online 68%

Shared information with a patient 67%
Changed or made a treatment decision 55%
Shared information with a colleague 38%

When? Physicians Use the Following Opportunities to

Search For Clinical Information:

77% between consults

70% after work or on weekends
56% on breaks for meals
41% during consults

What Types of Videos Do Physicians Watch Online?

Lectures 55%
Disease and Condition Information 43%
Demonstrations of Medical Procedures 40%
Health News 37%

References

Available only for new subscribers throughout the year 2013.

Access code sent via email upon completion of this program.
All individuals with subscriptions agree to be billed $95 in
February for annual unlimited use.

InforMed 1-800-237-6999 Fax 1-800-647-1356

American Medical Association. The Physicians Recognition Award

and Credit System. Chicago: AMA, 2006.
Bennett, NL, Casebeer LL, Shimin Z, Kristofco R. Information-seeking
behaviors and reflective practice. Journal of Continuing Education in the
Health Professions, 2006:26(2), p120-127.
Houle, CO. Continuing Learning in the Professions. San Francisco:
Jossey-Bass, 1980.
Knowles, MS. Self-Directed Learning: A Guide for Learners and
Teachers. Chicago: Association Press, 1975.
Google/Manhattan Research. Screen to Script: The Doctors Digital
Path to Treatment. June 2012.
thinkhealth With Google, "Connecting With Physicians Online:
Searching for Answers," November 2009

57

Self-Assessment
Choose the best possible answer for each question and mark your answers on the Self-Assessment answer sheet at the end
of this book. There is a required score of 70% or better to receive a Certificate of completion.

39. All of the following describe self-directed

learning (SDL) EXCEPT:
a. Learning is always done alone
b. Includes a wide variety of formats
c. Learner defines educational objectives
d. Learner selects the educational activity
40. The primary emphasis of the
Maintenance of Competence (MOC)
program is on
a. Expansion of number of CME credits
required
b. Completion of certification examination
c. Continuous professional development
d. Creation of mentoring programs
41. Many states are adding the requirement
that CME include which of the following
components?
a. Attendance at least one professional
meeting per year
b. Specific focus in the physicians area of
practice
c. Patient satisfaction data
d. Independent learning

43. ISL serves as a CME tool for Internet

searches by doing which of the following?
a. Providing a form for the learner to cut
and paste URL sites visited
b. Tracking and documenting the search
process
c. Creating a post-test for searches
d. Blocking commercial sites
44. In order to claim a CME activity using
ISL, the learner must do all of the
following EXCEPT:
a. Identify the purpose of the search
b. Identify the outcome of the search
c. Complete the search in a single sitting
d. Evaluate the success of the search
process
45. When using ISL for CME credit the
learner must:
a. Claim only the time calculated by the
computer
b. Write a brief description of the learning
plan
c. Deduct time of commercial sites visited
d. Visit a specified set of sites

42. Internet searching and learning (ISL) is a

CME format that makes use of which of
the following resources?
a. Internet
b. Journal clubs
c. Patient consultation
d. Consultation with peers

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58

2014-2015 NEW JERSEY UPDATE

FOR PHYSICIANS

SELF-ASSESSMENT ANSWERS
Mark One Answer Per Question

SELF-ASSESSMENT ANSWER SHEET

RETURN CERTIFICATE TO (please print):

First

Middle

Last

Board License Number

DEA Number

Mailing Address

City

State

Zip Code

Office Telephone Number

Office Fax Number

E-mail Address

Specialty

REMITTANCE AMOUNT
COURSE FEE

$50.00

ER/LA Opioid REMS Education (see pp 28-30)

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Pain Management at the End of Life (see pp 49-50)

PAYMENT METHODS

Check enclosed made payable to INFORMED

VISA

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American Express

Discover

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Exp. Date

Signature

Total Payment

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Self-Directed Searching & Learning (see page 58)

* Location of Card ID
Internal Use Only

NJ1415

See inside the back cover for instructions

on how to submit your Course
Participation Online or by
Mail, Phone, or Fax.
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39

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Yes, I want to use DIRECTUS to claim of to

100 AMA PRA Category 1 creditsTM.
Check here to opt out of FREE use of
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59

Evaluation Form
Please read the following questions, in their context, and provide
a response based on the content of this educational activity.
1. Current knowledge is information you already know, weighed,
considered or incorporated prior to starting this activity.
For this overall educational activity, I: (choose only one)
only reaffirmed my current knowledge.
gained new knowledge I will weigh, consider or incorporate
in my practice of medicine.
ER/LA OPIOID REMS EDUCATION
For 2-6, with regard to opioids and controlled substances, (A) did the
content provide any knowledge that you will weigh, consider, or
incorporate in your practice and (B) do you expect this to improve
your patients outcomes?
PART A
PART B
Knowledge
Outcomes
Yes
Yes
2. Assessing patients for treatment.
No
No
Initiating therapy, modifying
Yes
Yes
3. dose, and discontinuing use in
No
No
treating patients.
Yes
Yes
4. Managing ongoing therapy.
No
No
Counseling patients and
caregivers about the safe use of
Yes
Yes
5.
and including proper storage and No
No
disposal of the drug.
Familiarity with general and
Yes
Yes
6. product-specific drug
No
No
information.
7. Identify a specific change, if any, you will make in your practice
related to prescribing opioids or other controlled substances.
8. Describe with one word or short phrase any barrier to making that
change.

9. Have you treated or managed patients on ER/LA opioids in the

past twelve months?
Yes

13. Describe in a word or short phrase any barrier to making that

change.

SELF-DIRECTED LEARNING
For 14-15, (A) did the content provide any knowledge that you will
weigh, consider, or incorporate in your practice and (B) do you
expect this to improve your patients outcomes?
PART A
PART B
Knowledge
Outcomes
Using the internet for self Yes
Yes
14.
directed learning.
No
No
Increasing CME credit hours
Yes
Yes
15. you claim for self-directed
No
No
learning.
Please read the following questions, in their context, and provide
a response based on the content of this educational activity.
17. If CME participant records are going paperless (electronic
transmission), what is your preference for administrator and privacy?
A. Administrator
Regulatory (e.g., Federal, State, other agencies)
Special Interest (e.g., AMA, AAFP, AOA, ACCME)
Physicians and CME providers
Other
B. Privacy - Disclosure of any data is under the control of:
Administrator
Physician
Physician and Administrator only with authorization by physician
18. Any national CME system will require a Unique Identifier Code
(UIC) for all participants. Which is the most convenient for you and
which would you feel most comfortable using?
convenience

Soc. Sec. #
St. Med Lic. #
DEA#
NPI#
ME#
Other

comfort

No

PAIN MANAGEMENT AT THE END OF LIFE

For 9-11, (A) did the content provide any knowledge that you will
weigh, consider, or incorporate in your practice and (B) do you
expect this to improve your patients outcomes?
PART A
PART B
Knowledge Outcomes
How you formulate patient Yes
Yes
9. centered goals for end-of-life pain
No
No
management.
How you assess pain in a patient
Yes
Yes
10. with reduced or absent
No
No
consciousness.
How you communicate with
Yes
Yes
11.
patients from non-Western cultures. No
No
12. Identify a specific change, if any, will you make in your practice
related to screening for and treating patients affected by pain at the
end of their lives.
NJ1415

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e
Now theres a way to earn CME CREDIT for the time spent
researching topics and areas of interest SPECIFIC TO YOU

Large Scope of Eligible Activities

Use of Peer Reviewed

Databases (Medline,
Cochran, etc.)
Professional or PracticeSpecific sources (Webcast,
Podcast, Journal Articles,
Specialty Updates Via
Email)
Many More Indexed
Activities!
WHAT IS DIRECTUS? An application that enables you to conduct online
search and learn activities to earn AMA PRA Category 1 creditsTM. Read Part 3 of
this monograph for all the details and get an extra hour of credit COMPLETELY FREE.

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Satisfies New End-of-Life CME Requirement for License Renewal

AMA PRA Category 1 CreditsTM

InforMed is accredited by the Accreditation Council for Continuing Medical Education (ACCME)
to provide continuing medical education for physicians.
InforMed has been providing high-quality CME activities to physicians and physician
assistants for over 40 years. InforMed specializes in developing quality educational
activities to ensure that physicians meet mandatory CME requirements.