Sponsored by an unrestricted educational grant from Valeo Pharma Inc.

Dr. William Robert Mundle, MD, FRCSC, is an obstetrician and director of the Fetal Maternal Medicine clinic at the Windsor Regional
Hospital. In 2001, he founded the High Risk Pregnancy Program and is working closely with local obstetricians and neonatologists
responsible for Windsor's Modied Level III Neonatal Intensive Care Unit. He also works closely with the Windsor Public Health Unit to
provide genetic counselling and amniocentesis along with consultative and comprehensive care for complex obstetrical problems. Dr.
Mundle is an avid speaker and is frequently invited to facilitate workshops in the area of problematic pregnancy management.
Nausea and vomiting of pregnancy (NVP) is the most common
medical condition in pregnancy, with symptoms ranging from mild
to severe. Notably, the severity of symptoms is not correlated with
the impact of NVP on the patients quality of life. Even mild NVP
symptoms can cause signifcant anxiety and distress to some patients.
1
Once other potential causes of nausea or vomiting have been
ruled out and NVP is diagnosed, Diclectin is the standard of
care, specifcally studied and approved for this indication.
1
Te
current SOGC guidelines advocate early treatment of NVP with
Diclectin to assure proper maternal health and to decrease the risk
of NVP progression to hyperemesis gravidarum (HG), a severe
form of persistent vomiting associated with >5% weight loss of pre-
pregnancy weight, electrolyte imbalance and ketonuria. When NVP
is severe, and management with Diclectin is not sufcient, other
of-label therapies can be used for short periods of time to achieve the
desired result and, when vomiting is persistent, to bring the patients
condition to a state in which she is able to tolerate oral medication.
Intravenous hydration and parenteral nutrition may also be indicated
in severe cases. Tis article discusses the management protocol, the
available options, and is based on both the current guidelines and
the discussion that took place at a recent SOGC continuing medical
education program.
TIMELY TREATMENT OF NVP IS IMPORTANT
NVP afects up to 90% of pregnant women
1,2
typically
manifesting itself in the 2nd month of pregnancy, with the severity
reaching its peak between the 7th and 12th week. For most women,
NVP resolves after the 16th week, however up to 20% of women
experience symptoms in the 2nd and 3rd trimesters. Some women
have NVP throughout the entire pregnancy.
3
Te symptoms of NVP afect women diferently, ranging from
mild to severe, and may include nausea, retching, and vomiting.
1,4

For some women, NVP is accompanied by the gastroesophageal
refux. It has been shown that regardless of symptom severity, women
tend to experience anxiety about the efects of NVP on the fetus, have
diminished ability to work and strained family relations.
1
Women
have also requested terminations of otherwise wanted pregnancies
citing severe NVP as the reason.
5
LEARNING OBJECTIVES:
1. Recognize that nausea and vomiting of pregnancy (NVP) has a signicant impact on the quality
of life, health and pregnancy continuation.
2. Understand that early treatment of NVP is safe and recommended by the SOGC guidelines.
3. Identify doxylamine/pyridoxine (Diclectin) as the standard of care for NVP.
4. Review the treatment algorithm with adjuvant and alternative therapies for severe cases of NVP
(including hyperemesis gravidarum).
This newsletter provides a scientic update on the importance, safety and effectiveness of managing nausea and vomiting
of pregnancy. It is based on the contents of an interactive continuing medical education workshop held by The Society of
Obstetricians and Gynaecologists of Canada (SOGC) in Toronto on November 28, 2013.
In about 1% of cases, NVP progresses to HG, with symptoms
so severe that persistent vomiting leads to dehydration, weight loss
of more than 5% of the pre-pregnancy weight, electrolyte imbalance
and ketonuria. Te rate of hospitalization for NVP is as many as
14 per 1000 births.
1
Te latest evidence-based SOGC Clinical Practice Guidelines
on Te Management of Nausea and Vomiting of Pregnancy state
that NVP can and should be managed safely and efectively. Early
treatment with counselling is preferable, after appropriate history-
taking and physical examinations. Other causes of nausea and
vomiting must be ruled out, including gastrointestinal, genitourinary,
central nervous system related, and toxic/metabolic problems.
1

Tyroid function should be assessed, as 60% of women with HG are
found to have either subclinical or mildly clinical hyperthyroidism.
6

Further, pregnancy needs to be confrmed and idiopathic NVP
needs to be distinguished from NVP of known etiology, such as
hydatidiform mole.
1
A DOXYLAMINE/PYRIDOXINE COMBINATION IS THE
STANDARD OF CARE FOR NVP
According to the SOGC Clinical Practice Guidelines, a delayed-
release combination of Diclectin (10 mg antihistamine doxylamine
succinate and 10 mg vitamin B
6
, also known as pyridoxine
hydrochloride) is the standard of care for NVP. It is the only anti-
nauseant specifcally indicated for use in pregnant women. Vast
clinical experience with more than 33 million pregnancies worldwide,
including many epidemiological studies designed to detect
teratogenicity, and 2 meta-analyses showed no increase in the risk of
malformations in comparison to pregnancies where a combination of
doxylamine, pyridoxine, with or without dicyclomine, was not used.
7
According to the product monograph
7
, the best way to initiate
Diclectin is with 4 delayed-release tablets per day: 2 taken at bedtime
to control nausea and vomiting occurring in the morning, and
additionally one tablet in the morning and one in the mid-afternoon
to control the symptoms throughout the day (See Figure 1). Diclectin
is a delayed-release formulation that works best when taken 4 to 6
hours before it is needed. It should be taken on a daily basis. Te
delay in action may be prolonged when tablets are taken with food.
DISCUSSION OF THE LATEST SOGC GUIDELINES AND CURRENT PRACTICES
MANAGING NAUSEA AND
VOMITING OF PREGNANCY
By Dr. William Mundle, MD, FRCSC
Te dose of Diclectin can be individualized according to the
timing, frequency, duration and severity of NVP symptoms. Most
patients experience the worst symptoms in the morning, however
this may be diferent for other patients. When NVP is not adequately
controlled with 4 tablets, the dose can be increased up to 12 tablets
per day.
8

When assessing efectiveness, ask the patient if she is taking
Diclectin every day as prescribed, since the efect cannot be achieved
if the medication is taken on an as-needed basis. Diclectin is not
a traditional anti-nauseant drug which acts right away. It must be
taken continuously to achieve and maintain its anti-nauseant efect.
Taking Diclectin throughout the day allows for blood levels to be
maintained to achieve the desired result.
Some patients report drowsiness due to doxylamine.
7
For most
patients the side efects are minor and temporary. Pyridoxine is
generally recognized as having no adverse efects.
7
An interesting question is whether Diclectin can be taken rectally
or vaginally. It is not the case because the coating of Diclectin tablets
is specifcally formulated to dissolve in pH=6 (duodenum). Te
vaginal pH is approximately 4.
TREATING REFRACTORY NVP
When Diclectin is insufcient, additional antihistamines, such
as dimenhydrinate (Gravol), may be added (See Figure 1). Gravol
is inexpensive and available in many forms, such as suppositories and
intravenously (IV).
If the patient has persistent vomiting and is dehydrated,
hydration treatment with IV fuid replacement should be initiated
(See Figure 1). Gravol (dimenhydrinate, 50 mg [in 50 mL of
saline, over 20 min] q46h IV) and IV multivitamins should be
added to the infusion. After one week of diminished nutritional
intake, micronutrient supplementation is required. Vitamin
supplementation can be given vaginally, which is less costly than
IV. However, pregnant women tend to be anxious about vaginal
administration and its impact on the baby.
Potassium defciency is the main electrolyte problem in NVP,
hence potassium supplementation is also necessary. Further, glucose
is the main substrate babies use for energy and metabolism, hence
glucose should be added to the isotonic IV solution. If a patient is
concerned about nutrition and wishes to eat despite vomiting, she
can do so. However, it is best to wait for the medication to take efect
and for the vomiting to subside.
Once the patient is able to tolerate oral agents, any of the following
can be added (the list is in order of proven fetal safety): chlorpromazine,
prochlorperazine, promethazine, or metoclopramide.
1
Promethazine
is a 1
st
generation antihistamine while the other 3 options control
nausea by blocking dopamine receptors in the brain.
Steroids, such as dexamethasone, are frequently used for
chemotherapy-induced nausea and can be extremely efective.
However, in pregnancy, steroids should be the last resort as they
increase the risk of oral clefts in the frst 10 weeks of gestation. When
NVP is refractory to all other options, dexamethasone can be given
for 24-48 hours to bring the patient to a level at which she can
tolerate other agents.
Tamsulosin hydrochloride and ondansetron can also be efective,
but these options are not currently indicated in pregnancy due to the
lack of safety data.
ADJUVANT THERAPIES FOR NVP SYMPTOMS
Some women with NVP will experience gastroesophageal refux
and will beneft from antacids, H2 receptor antagonists (such as
cimetidine) and proton pump inhibitors (such as omeprazole).
1
Ginger therapy, acupuncture and acupressure may be used by
patients who desire more natural options. Ginger may be efective
(less than 1000 mg/day), however its safety has not been confrmed
in clinical trials. Also, natural product preparations are unregulated
for purity and composition. Hence, large quantity of ginger is not
recommended as a treatment for NVP by the current SOGC Clinical
Practice Guidelines.
CONCLUSION
NVP is a serious condition which has safe and efective
management options. Early treatment may prevent nutritional
defciencies, alleviate stress and prevent complications. Diclectin is
the standard of care with other pharmacological options available for
short-term management of refractory and/or severe NVP cases.
If you wish to receive this newsletter by email, please contact Anna Liachenko, MSc @ 514-435-7860 or anna@z-zinc.com. Publisher received an unrestricted
educational grant from Duchesnay Inc. Dr. Mundle was invited by the SOGC to facilitate the workshop and did not receive a honorarium from Duchesnay Inc. Opinions
expressed in this article represent those of Dr. Mundle and participants of the SOGC workshop and do not represent opinions of the SOGC, publisher or sponsor.
FIGURE . Nausea and vomiting of pregnancy: treatment algorithm
(If no improvement, proceed to next step)

Doxylamine/pyridoxine (Diclectin)
- z tablets at bedtime, 1 in the morning, and 1 in the afternoon
- Vaximum 4 tablets/day
- Adjust schedule and dose according to the severity of symptoms

If patient is dehydrated, start rehydration treatment:

- intravenous (lv) fluid replacement
- lv multivitamin supplementation
- Limenhydrinate 0 mg (in 0 mL of saline, over z0 min) q4oh lv

Add dimenhydrinate
- up to z00 mg/d when taking 4 doxylamine/pyridoxine tablets/d

Or promethazine
- to 10 mg qo-8h po or pr

Add any of the following (|n oreer o( roven (ete| se(ety).

- chlorpromazine
- prochlorperazine
- promethazine
- metoclopramide

Add methylprednisolone (note. stero|es mey |ncreese tne r|sr (or ore| c|efts |n
rst 10 weers o( estet|on)
NOTES:
a
Theuseof this algorithmassumes that other causes of NVPhavebeenruledout.
a
At anytimeyoumayaddanyor all:
- yr|eox|ne - |ner - Pe ecuressure/ecuuncture
Adapted from SOGC Clinical Practice Guidelines. Obstet Gynaecol Can 2002; 24(10):817-23.
Permission to reprint has been provided courtesy of the SOGC.
REFERENCES:
1. Arsenault MY et al. SOGC Clinical Practice Guidelines. Obstet Gynaecol Can 2002;
24(10):817-23.
2. Gadsby R et al. Br J Gen Pract 1993; 43:2458.
3. Einarson A et al. Can Fam Phys 2007; 53:2109-11.
4. Koren G et al. How to survive morning sickness successfully. Motherisk.org.
5. Mazzotta P et al. Can Fam Phys 1997; 43:10557.
6. Colin JF. Gastroenterol Clin Biol 1994; 18:378-80.
7.
Pr
Diclectin product monograph 2013.
8. Atanackovic G et al. J Clin Pharmacol 2001; 41:842-5.