ARCOXIA®

etoricoxib
30 mg, 60 mg, 90 mg & 120 mg tablets

What is in this leaflet

This leaflet answers some common questions about ARCOXIA. It does not contain all the
available information. It does not take the place of talking to your doctor or pharmacist. All
medicines have risks and benefits. Your doctor has weighed the risks of you taking
ARCOXIA against the benefits they expect it will have for you. If you have any concerns
about taking this medicine, ask your doctor or pharmacist. Keep this leaflet with the
medicine. You may need to read it again.

What ARCOXIA is used for

ARCOXIA is used for the following:
1 acute and chronic treatment of the signs and symptoms of osteoarthritis (OA) and
rheumatoid arthritis (RA)
2 management of ankylosing spondylitis
3 relief of chronic musculoskeletal pain
4 relief of acute pain
5 to treat acute gouty arthritis

Your doctor will prescribe ARCOXIA for you only after you have used other medicines for
your condition and they have not been suitable for you. Your doctor will want discuss your
treatment with ARCOXIA from time to time. It is important that you use the lowest dose that
controls your pain and you should not take ARCOXIA for longer than necessary. This is
because the risk of heart attacks and strokes might increase after prolonged treatment,
especially with high doses.

Osteoarthritis
Osteoarthritis is a joint disease. It results from the gradual breakdown of the cartilage that
covers the joints and cushions the ends of bones. Symptoms of osteoarthritis include pain,
tenderness, stiffness of one or more joints, and physical disability. The hips and knees are
the most commonly affected joints, but other joints such as those of the hands and spine
may also be affected. Osteoarthritis is more common in women than in men. Many factors
can lead to the development of osteoarthritis including obesity and joint injury (eg. from
sport).

Rheumatoid Arthritis
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling and loss of
function in the joints and inflammation in other body organs.

Ankylosing Spondylitis
Ankylosing spondylitis is an inflammatory disease of the spine and large joints.
Gout
Gout is a disorder characterised by sudden, recurring attacks of pain and inflammation in
one or more joints.

How ARCOXIA works

ARCOXIA belongs to a group of medicines called cyclooxygenase-2 (COX-2) specific
inhibitors (also known as Coxibs). The body produces two similar enzymes called COX-1
and COX-2. COX-1, among other functions, is involved with protecting the stomach, while
COX-2 plays a role in joint inflammation and pain. ARCOXIA reduces pain and inflammation
by blocking COX-2, an enzyme in the body. ARCOXIA does not block COX-1, the enzyme
involved in protecting the stomach from ulcers. Other anti-inflammatory medicines (NSAIDs)
block both COX-1 and COX-2. ARCOXIA relieves pain and inflammation with less risk of
stomach ulcers compared to NSAIDs. However taking aspirin with ARCOXIA may reverse
this benefit (see Before you take ARCOXIA, Taking Other Medicines). In clinical studies, the
risk of developing ulcers on ARCOXIA was lower than with NSAIDs. Some people
developed ulcers whether they were taking ARCOXIA or placebo in these studies; however
the rate was higher on ARCOXIA. If any of the following symptoms: shortness of breath,
chest pains or ankle swelling appear or worsen, stop your treatment with ARCOXIA and
consult a doctor, as soon as is practical. If you have kidney, liver or heart disease, your
doctor will want to appropriately keep a check on you. If you develop any symptoms that
could indicate a severe allergic reaction such as an inability to breathe or a serious skin
reaction you must consult a doctor on an urgent basis. Your doctor will want to discuss your
treatment from time to time. It is important that you use the lowest dose that controls your
pain and you should not take ARCOXIA for longer than necessary. This is because the risk
of heart attacks and strokes might increase after prolonged treatment, especially with high
doses. ARCOXIA can increase blood pressure in some people, especially in high doses,
and this could increase the risk of heart attacks and strokes. Your doctor will want to check
your blood pressure from time to time, to make sure that it is safe to continue treatment.
Your doctor may have prescribed ARCOXIA for another reason. Ask your doctor if you have
any questions about why ARCOXIA has been prescribed for you. ARCOXIA is not addictive.
Before you take ARCOXIA
When you must not take it
Do not take ARCOXIA if:
1 you have an allergy to ARCOXIA or any of the ingredients listed at the end of this
leaflet
2 the packaging is torn or shows signs of tampering
3 the expiry date on the pack has passed. If you take this medicine after the expiry
date has passed, it may not work.
4 you have had heart failure, a heart attack, bypass surgery, chest pain (angina),
narrow or blocked arteries of the extremities (peripheral arterial disease), a stroke or mini
stroke (TIA or transient ischaemic attack)
5 you have high blood pressure that is not well controlled on blood pressure
medication
6 you are having major surgery on your heart or arteries
7 you have serious liver disease.

If you are not sure whether you should start taking ARCOXIA, talk to your doctor. ARCOXIA
has not been adequately studied in children. Therefore, ARCOXIA should not be given to
children. ARCOXIA works equally well in older and younger adult patients. Adverse
experiences may occur at a higher incidence in older patients compared to younger
patients. If you are elderly (ie over 65 years of age), your doctor will want to appropriately
keep a check on you. No dosage adjustment is necessary for older patients.

Before you start to take it

Tell your doctor if:
• you are pregnant or intend to become pregnant. ARCOXIA is not recommended for use
during late pregnancy. If there is a need to consider using ARCOXIA during your
pregnancy, your doctor will discuss with you the benefits and risks of using it.
• you are breast-feeding or plan to breast-feed. It is not known if ARCOXIA passes into
breast milk. You and your doctor should discuss whether you should stop breast-feeding or
not take ARCOXIA.
• you have or have had any medical conditions, especially the following:
0 history of angina, heart attack or a blocked artery in your heart
1 narrow or blocked arteries of the extremities
2 kidney disease
3 liver disease
4 dehydration, for example by a prolonged bout of vomiting or diarrhoea
5 history of stomach bleeding or ulcers
6 heart failure
7 high blood pressure
8 swelling due to fluid retention
9 • you have had an allergic reaction to aspirin or other anti-inflammatory medicines
(commonly known as NSAIDs). Symptoms of an allergic reaction may include asthma,
pinkish itchy swellings on the skin (hives), runny or blocked nose.
10 • you have an infection. If you take ARCOXIA while you have an infection, it may
hide fever and may make you think, mistakenly, that you are better or that your infection is
less serious than it might be.
11 • you have any allergies to any other medicines or any other substances, such as
foods, preservatives or dyes
12 • you have a history of stroke or mini stroke
1 you have conditions which increase your risk of coronary artery disease or
atherosclerosis such as high blood pressure, diabetes, high cholesterol or smoking.

If you have not told your doctor about any of the above, tell them before you take any
ARCOXIA.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy
without a prescription from your pharmacy, supermarket or health food shop. Some
medicines and ARCOXIA may interfere with each other. These include:
1 warfarin, a medicine used to prevent blood clots
2 rifampicin, an antibiotic used to treat tuberculosis and other infections
3 water pills (diuretics)
4 ACE inhibitors and angiotensin receptor blockers, medicines used to lower high
blood pressure or treat heart failure
5 lithium, a medicine used to treat a certain type of depression
6 birth control pills
7 hormone replacement therapy
8 methotrexate, a medicine used to suppress the immune system

These medicines may be affected by ARCOXIA or may affect how well it works. You may
need different amounts of your medicine, or you may need to take different medicines.

Some medicines should not be taken with ARCOXIA. These include:

1 non-steroidal anti-inflammatory medicines (NSAIDs), used to relieve pain, swelling,
and other symptoms of inflammation
2 aspirin when used regularly for conditions other than to prevent heart attack or stroke
ARCOXIA can be taken with low dose aspirin. If you are currently taking low dose aspirin for
the prevention of a heart attack or stroke, you should continue to do so unless specified by
your Doctor. ARCOXIA cannot replace aspirin for this purpose.

Your doctor or pharmacist has more information on medicines to be careful with or avoid
while taking ARCOXIA.

How to take ARCOXIA

How much to take
Take ARCOXIA only when prescribed by your doctor. For osteoarthritis, the recommended
dose is 30 mg or 60 mg once a day. For rheumatoid arthritis the recommended dose is 90
mg once a day. For ankylosing spondylitis the recommended dose is 90 mg once a day. For
the relief of gout attacks the recommended dose is 120 mg once a day, which should only
be used for the acute painful period. For the relief of chronic musculoskeletal pain the
recommended dose is 60 mg once a day. Doses greater than those recommended for each
condition have either not demonstrated additional efficacy or have not been studied.
Therefore, the daily doses stated above for each condition should not be exceeded.
If you have mild liver disease, you should not take more than 60 mg a day. If you have
moderate liver disease, you should not take more than 60 mg every other day or 30 mg a
day. Follow all directions given to you by your doctor carefully. They may differ from the
information contained in this leaflet. If you do not understand the instructions on the box,
ask your doctor or pharmacist for help.

How to take it
ARCOXIA comes as tablets. When taking the tablets, swallow them with a glass of water.
Do not halve the tablet.

When to take it
Take your ARCOXIA at about the same time each day. Taking ARCOXIA at the same time
each day will have the best effect. It will also help you remember when to take the dose. It
does not matter if you take ARCOXIA before or after food.

How long to take it

Do not use ARCOXIA for longer than your doctor says.
Your doctor will want to discuss your treatment from time to time. It is important that you use
the lowest dose that controls your pain and you should not take ARCOXIA for longer than
necessary. This is because the risk of heart attacks and strokes might increase after
prolonged treatment, especially with high doses. Depending on your condition, you may
need to take ARCOXIA for a few days or for a longer period. For osteoarthritis and
rheumatoid arthritis ARCOXIA helps relieve your symptoms but it does not cure it. Continue
taking ARCOXIA for as long as your doctor prescribes. For the relief of gout attacks or other
types of pain, ARCOXIA is usually only needed for a few days. If you are not sure how long
to take ARCOXIA, talk to your doctor.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose
when you are meant to. Otherwise, take it as soon as you remember, and then go back to
taking your tablet(s) as you would normally. If you are not sure whether to skip the dose,
talk to your doctor or pharmacist. Do not take a double dose to make up for the dose that
you missed. If you have trouble remembering to take your tablets, ask your pharmacist for
some hints.
If you take too much (overdose)
Immediately telephone your doctor or National Poisons Centre (telephone 0800 POISON or
0800 764 766), or go to accident and emergency at your nearest hospital, if you think that
you or anyone else may have taken too much ARCOXIA. Do this even if there are no signs
of discomfort or poisoning.

While you are using ARCOXIA

Things you must do
If you become pregnant while taking ARCOXIA, tell your doctor immediately. If you get an
infection while taking ARCOXIA, tell your doctor. ARCOXIA may hide fever and may make
you think, mistakenly, that you are better or that your infection is less serious than it might
be.

If you notice any of the following, tell your doctor immediately

1 vomiting blood or material that looks like coffee grounds
2 bleeding from the back passage, black sticky bowel motions (stools), or bloody
diarrhoea

You may need urgent medical attention. If you are about to be started on any new medicine,
tell your doctor and pharmacist that you are taking ARCOXIA.

Things you must not do

Do not give ARCOXIA to anyone else, even if they have the same condition as you.

Things to be careful of
Be careful driving or operating machinery until you know how ARCOXIA affects you. The
effect of ARCOXIA on the ability to drive a car or operate machinery has not been studied,
although it is thought to be unlikely to have any effect on these activities. However, as with
many medicines, ARCOXIA may cause certain adverse effects in some people, including
dizziness and tiredness. Make sure you know how you react to ARCOXIA before you drive
a car or operate machinery.

Things that would be helpful for your osteoarthritis

Some self help measures suggested below may help your condition. Talk to your doctor or
pharmacist about these measures and for more information.
1 Exercise - regular exercise can help reduce pain and disability from osteoarthritis by
increasing muscle strength and reducing the load on joints, but it is important not to overdo
it. Walking is good exercise, however, before starting any exercise, ask your doctor about
the best kind of programme for you.
2 Weight - your doctor may suggest losing some weight to help reduce the strain on
your joints. Some people may need a dietician's help to lose weight.
3 Hot and cold treatments.
4 Using support devices.
Adverse Effects
Tell your doctor or pharmacist as soon as possible if you do not feel well while you are
taking ARCOXIA.
ARCOXIA helps most people with osteoarthritis, rheumatoid arthritis, menstrual pain, gout
or other types of pain, but it may have unwanted adverse effects in a few people. All
medicines can have adverse effects. Sometimes they are serious, most of the time they are
not. You may need medical treatment if you get some of the adverse effects. Ask your
doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice or have any of the following and they worry you:
1 feeling sick (nausea), vomiting
2 heartburn, indigestion, uncomfortable feeling or pain in the stomach
3 mouth ulcers
4 diarrhoea
5 swelling of the legs, ankles or feet
6 high blood pressure
7 headache
8 dizziness
9 unusual tiredness or weakness
10 difficulty sleeping (insomnia)
11 signs of urinary tract infection, including painful burning when passing urine
12 wheezing
13 signs of an infection of the breathing passages, including runny nose, sore throat,
cough

These are the more common adverse effects of ARCOXIA.

Additionally, the following have been reported:

1 taste alteration
2 high levels of potassium in the blood
3 anxiety
4 depression
5 restlessness
6 drowsiness
7 severe increase in blood pressure
8 confusion
9 hallucinations
10 platelets decreased
11 blurred vision

These are usually the mild adverse effects of ARCOXIA.

Tell your doctor immediately if you notice any of the following:

1 redness of the skin
2 severe skin reactions, which may occur without warning
3 skin rash or itchiness
4 pinkish, itchy swellings on the skin, also called hives or nettlerash
5 severe stomach pain
6 passing little or no urine
These may be serious adverse effects. Some of these may be symptoms of an allergic
reaction to ARCOXIA. You may need urgent medical attention.
If any of the following happen, stop taking ARCOXIA and tell your doctor immediately
or go to Accident and Emergency at your nearest hospital:
1 swelling of the face, lips, tongue or throat which may cause difficulty in swallowing or
breathing (hypersensitivity reactions, anaphylactic/anaphylactoid reactions including shock)
2 abnormal rhythm of the heart (atrial fibrillation and arrhythmia)
3 heart failure
4 palpitations (fast or irregular heart beats)
5 feeling of tightness, pressure or heaviness in the chest (angina)
6 yellowing of the skin and eyes (jaundice)
7 serious kidney problems
8 serious liver problems
9 stomach ulcers that may become serious and may bleed, and may occur at any time
during use and without warning
10 vomiting blood or material that looks like coffee grounds
11 bleeding from the back passage, black sticky bowel motions (stools), or bloody
diarrhoea
12 shortness of breath, wheezing, or trouble breathing

These may be serious adverse effects. You may need urgent medical attention. Other
adverse effects not listed above may also occur in some patients. Tell your doctor if you
notice any other effects. Do not be alarmed by this list of possible adverse effects. You may
not experience any of them.

After using ARCOXIA

Storage
Keep your tablets in the blister pack until it is time to take them. If you take the tablets out of
the blister pack they may not keep well. Keep ARCOXIA in a cool dry place where the
temperature stays below 30°C. Do not store it or any other medicine in the bathroom or
near a sink. Do not leave it in the car or on window sills. Heat and dampness can destroy
some medicines. Keep it where children cannot reach it. A locked cupboard at least one-
and-a-half metres above the ground is a good place to store medicines.

Disposal
If your doctor tells you to stop taking ARCOXIA, or the tablets have passed their expiry
date, ask your pharmacist what to do with any that are left over.

Product description
What it looks like
ARCOXIA comes as four strengths of tablets:
1 30 mg tablet - a blue green apple shaped biconvex film coated tablet debossed 101
on one side and ACX 30 on the other, and comes in boxes of 10 tablets and 30 tablets.
2 60 mg tablet - a dark green apple shaped biconvex film coated tablet debossed 200
on one side and ARCOXIA 60 on the other, and comes in boxes of 30 tablets.
1 90 mg tablet - a white apple shaped biconvex film coated tablet debossed 202 on
one side and ARCOXIA 90 on the other, and comes in boxes of 30 tablets.
2 120 mg tablet - a pale green apple shaped biconvex film coated tablet debossed 204
on one side and ARCOXIA 120 on the other, and comes in boxes of 10 tablets.

Ingredients

Active ingredient:
ARCOXIA 30 mg tablet contains 30 mg etoricoxib. ARCOXIA 60 mg tablet contains 60 mg
etoricoxib. ARCOXIA 90 mg tablet contains 90 mg etoricoxib. ARCOXIA 120 mg tablet
contains 120 mg etoricoxib.

Inactive ingredients:
30 mg, 60 mg, 90 mg and 120 mg tablets
1 calcium hydrogen phosphate (anhydrous)
2 carnauba wax
3 microcrystalline cellulose
4 lactose monohydrate
5 croscarmellose sodium
6 hypromellose
7 magnesium stearate
8 titanium dioxide
9 glycerol triacetate
10 The 30 mg, 60 mg and 120 mg tablets also contain yellow ferric oxide and indigo
carmine lake.

ARCOXIA does not contain gluten, sucrose, tartrazine or any other azo dyes.

Manufacturer/Supplier
ARCOXIA is marketed in New Zealand by: Merck Sharp & Dohme (New Zealand) Limited P
O Box 99 851 Newmarket Auckland NEW ZEALAND Tel: 0800 500 673 This leaflet was
prepared inJune 2010 CP-ACX- 0510(010610) ®Registered Trademark of Merck Sharp &
Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA Copyright ©
2010 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station,
NJ, USA All Rights Reserved
How does Etoricoxib work?
As per the FDA information, Etoricoxib works by blocking the production of Prostaglandins, chemicals in the
body which cause pain, swelling and inflammation. It contains non-steroidal anti-inflammatory chemical that
blocks the action of Cyclo-oxygenase is involved in producing prostaglandins, in response to injury or
certain diseases. Since no cyclo-oxygenase is produced in the body, then no prostaglandins are produced to
cause inflammation in the body.
Side Effects of Etoricoxib
The doctor will monitor your blood pressure when putting you on medication for Etoricoxib. Other side
effects of Etoricoxib are headaches, dizziness and fluid retention in the body. Overdose of Etoricoxib can
lead to serious repercussions. The drug also causes gastrointestinal effects such as abdominal pain,
diarrhoea, gas, indigestion and nausea. Some of the uncommon symptoms reported by the patients were
depression, tingling sensation, altered taste, anxiety, weight gain and change in appetite. People with
diabetes, hypertension, and high cholesterol or have a tendency to smoke showed greater susceptibility of
suffering a stroke or a heart attack.
Guidelines before taking Etoricoxib
The drug is not recommended for pregnant females or breast feeding mothers. If you have stomach
problems like reflux or indigestion, you should tell your doctor about it. Other problems like related to
kidney, heart, liver high blood pressure, diabetes, porphyries or any inflammatory bowel disease should also
be reported to the doctor before beginning medication for Etoricoxib. The medication works faster if it is
taken without food or empty stomach.
What are the common dosages of Arcoxia?
The dosage for taking Etoricoxib largely depends upon what you are being treated for. Usually the
recommended dose of the tablets is once daily. Do not take over dose of the drug. If you miss you dose,
continue with your daily schedule by skipping the dose. Do not try to repeat the dose.
Eisai Co., Ltd. 1
Revised: October 2010 (11th version) Standard Commodity Classification No. of Japan
871249
- For improvement of myotonic symptoms -
Myonal→ Tablets 50 mg
Myonal→ Granules 10 %
<Eperisone hydrochloride preparation>
Prescription drug
Tablets 50 mg Granules 10 %
Approval No. 15700AMZ01120000 15700AMZ01121000
Date of listing in the NHI reimbursement price Feb 1983 Feb 1983
Date of initial marketing in Japan Feb 1983 Feb 1983
Date of latest reexamination Dec 1991
Date of latest approval of indications May 1985
Storage
MYONAL should be stored at room temperature.
Press-through packages of MYONAL tablet should be protected from light after opening outer
package. (Light may occur discoloration of the
tablets.)
MYONAL tablets in bottle package should be protected from light and moisture after opening
the cap of bottle. (Light and moisture may occur
discoloration of the tablets.)
MYONAL granules in bottle should be protected from moisture after opening the cap of bottle.
(MYONAL granules absorb moisture easily.)
Expiration date
MYONAL should be used before the expiration date indicated on the package or label.
Caution : Use only as directed by a physician.
CONTRAINDICATIONS (MYONAL is contraindicated
in the following patients.)
Patients with a history of hypersensitivity to any ingredients
of MYONAL.
DESCRIPTION
1. Composition
Tablets 50 mg:
Each white, sugar-coated tablet contains 50 mg of eperisone
hydrochloride.
It contains carnauba wax, carmellose, hydrated silicon
dioxide, microcrystalline cellulose, titanium oxide,
stearic acid, calcium stearate, sucrose, talc, precipitated
calcium carbonate, corn starch, white shellac, hydroxypropylcellulose,
pullulan, povidone and macrogol
6000 as inactive ingredients.
Granules 10%:
Each gram of white to yellowish white granules contains
100 mg of eperisone hydrochloride.
It contains carmellose, light anhydrous silicic acid, talc,
corn starch, lactose hydrate, povidone, polyvinylacetal
diethylaminoacetate and macrogol 6000 as inactive ingredients.
2. Product description
Brand Appearance
name
Dosage form
and identification
code Face Reverse Lateral
Description
Sugar-coated
MYONAL tablets
Tablets
50mg
Diameter
(mm)
7.5
Weight
(mg)
162
Thickness
(mm)
4.2
White
MYONAL
Granules
10%
Granules
White to yellowish
white,
coated granules
having a
faint characteristic
odor
INDICATIONS
⋅ Improvement of myotonic conditions caused by the following
diseases:
Neck-shoulder-arm syndrome, scapulohumeral periarthritis
and low back pain
⋅ Spastic paralysis caused by the following diseases:
Cerebrovascular disorders, spastic spinal paralysis, cervical
spondylosis, sequela of surgical trauma (including cerebrospinal
tumor), sequela of trauma (spinal injury and head
injury), amyotrophic lateral sclerosis, infantile cerebral
palsy, spinocerebellar degeneration, spinal vascular disorders,
subacute myelo-optico neuropathy (SMON) and other
encephalomyelopathies
2 Eisai Co., Ltd.
DOSAGE AND ADMINISTRATION
Tablets 50 mg:
The usual adult dosage for oral use is 3 tablets (150 mg of
eperisone hydrochloride) daily in three divided doses after
meals.
The dosage may be adjusted depending on the patient’s age
and symptoms.
Granules 10%:
The usual adult dosage for oral use is 1.5 g (150 mg of
eperisone hydrochloride) daily in three divided doses after
meals.
The dosage may be adjusted depending on the patient’s age
and symptoms.
PRECAUTIONS
1. Careful Administration (MYONAL should be administered
with care in the following patients.)
(1) Patients with a history of drug hypersensitivity
(2) Patients with hepatic function disorder
[MYONAL may aggravate hepatic function.]
2. Important Precautions
Weakness, light-headedness, sleepiness or other symptoms
may occur. In the event of such symptoms, the dosage
should be reduced or treatment discontinued. Patients
should be cautioned against engaging in potentially hazardous
activities requiring alertness, such as operating machinery
or driving a car.
3. Drug Interactions
Precautions for coadministration (MYONAL should be
administered with care when coadministered with the following
drugs.)
Drugs Signs, Symptoms, and
Treatment
Mechanism and
Risk Factors
Methocarbamol It has been reported that disturbance
of visual accommodation
occurred after the concomitant
use of methocarbamol
with tolperizone hydrochloride,
an analogue compound.
Mechanism unknown
4. Adverse Reactions
Adverse reactions were reported in 416 of 12,315 patients
(3.38%). (At the end of the reexamination period)
(1) Clinically significant adverse reactions (incidence
unknown)
1) Shock and anaphylactoid reactions
Since shock and anaphylactoid reactions may occur, patients
should be carefully observed. In the event of
symptoms such as redness, itching, urticaria, edema of
the face or other parts and dyspnea etc., treatment should
be discontinued and appropriate measures taken.
2) Oculo-muco-cutaneous syndrome (Stevens-Johnson
syndrome) and toxic epidermal necrolysis (Lyell
syndrome)
Serious dermatopathy such as oculo-muco-cutaneous
syndrome (Stevens-Johnson syndrome) or toxic epidermal
necrolysis (Lyell syndrome) may occur. Patients
should be carefully observed, treatment discontinued
and appropriate measures taken, in the event of
symptoms such as fever, erythema, blistering, itching,
ocular congestion or stomatitis, etc.
(2) Other adverse reactions
5% > ≥ 0.1% <0.1% Incidence
unknown
Hepatic note 1) Elevation of AST
(GOT), ALT(GPT)
and Al-P, etc.
Renal note 1)
Proteinuria and
Elevation of BUN,
etc.
Hematologic note 1) Anemia
Hypersensitivity note 2) Rash Pruritus erythema
exudativum
multiforme
Psychoneurologic Sleepiness, insomnia,
headache and numbness
in the extremities
Stiffness and
tremor in the extremities
Gastrointestinal Nausea/vomiting, anorexia,
stomach discomfort,
abdominal pain,
diarrhea, constipation
and thirst
Stomatitis and
feeling of enlarged
abdomen
Urinary Urinary retention,
urinary incontinence
and feeling
of residual urine
General Weakness,
light-headedness and
generalized fatigue
Muscle hypotonia
and dizziness
Others Hot flushes Diaphoresis and
edema
Note 1) Since these symptoms may occur, patients should be
carefully observed. In the event of such abnormalities,
treatment should be discontinued and appropriate
measures taken.
Note 2) In the event of such symptoms, treatment should be
discontinued.
5. Use in the Elderly
Since the elderly often have a physiological hypofunction,
it is advisable to take measures, such as reduction in dosage
under careful supervision.
6. Use during Pregnancy, Delivery or Lactation
(1) MYONAL should only be used in pregnant women or
women suspected of being pregnant, if the expected
therapeutic benefits are evaluated to outweigh the possible
risk of treatment.
[The safety of MYONAL in pregnant women has not
been established.]
(2) It is advisable to avoid the administration of MYONAL
to nursing mothers. When MYONAL must be used,
breast feeding should be discontinued during treatment.
[It has been reported that MYONAL is excreted in
breast milk in an animal study (in rats).]
7. Pediatric Use
Safety in children has not been established (insufficient
clinical experience).
8. Precautions concerning Use
Caution in handing over drug (tablets)
Eisai Co., Ltd. 3
For drugs that are dispensed in a press-through package
(PTP), instruct the patient to remove the drug from the
package prior to use. [It has been reported that, if the PTP
sheet is swallowed, the sharp corners of the sheet may
puncture the esophageal mucosa, causing perforation and
resulting in serious complications such as mediastinitis.]
PHARMACOKINETICS
Blood concentration
Eperisone hydrochloride was administered orally to 8 healthy
adult male volunteers at a single dose of 150 mg/day note) for 14
consecutive days and the plasma concentration was determined
at days 1, 8 and 14. The time to reach the peak plasma concentration
(tmax) ranged from 1.6 to 1.9 hr, the peak plasma concentration
(cmax) was 7.5 to 7.9 ng/mL, elimination half-life
(t1/2) was 1.6 to 1.8 hr, and the area under the plasma concentration-
time curve (AUC) was 19.7 to 21.1 ng ⋅ hr/mL. The
plasma concentration profiles of eperisone hydrochloride determined
at days 8 and 14 did not significantly vary from those
of the first day. 1)
Plasma concentration of eperisone hydrochloride in the
course of oral administration at a single dose of 150note)
mg/day for 14 consecutive days (means ± S.E., n=8)
Note) A single dose of 150 mg is unapproved.
CLINICAL STUDIES
1. Neck-shoulder-arm syndrome, scapulohumeral periarthritis
and low back pain
In open labeled clinical trials and a double blind controlled
clinical trial undertaken to determine the effects of MYONAL
on myotonic symptoms associated with these diseases,
an efficacy rate of 52.1% (234/449) was achieved.
(When fairly effective responses are included, the efficacy
rate was as high as 80.4%.) 2 - 4)
2. Spastic paralysis
In open labeled clinical trials and a double blind clinical
trial, the usefulness of MYONAL has been established for
spastic paralysis associated with diseases such as cerebrovascular
disturbances, spastic spinal paralysis or cervical
spondylosis. Improvement rates for rigidity and stiffness
in patients with spastic paralysis were 42.3%
(197/466) and 45.1% (174/386), respectively. 5 - 7)
PHARMACOLOGY
1. Skeletal muscle relaxation
(1) Inhibition of experimentally-induced muscle rigidity
Eperisone hydrochloride suppresses intercollicular section-
induced decerebrate rigidity (-rigidity) and
ischemic decerebrate rigidity (〈-rigidity) in rats
dose-dependently. 8)
(2) Suppression of spinal reflexes
In spinal cats, eperisone hydrochloride suppresses
mono and poly-synaptic reflex potentials induced
through spinal nerve efferent root stimulation to a
similar degree. 8)
(3) Reduction of muscle spindle sensitivity via -motor
neurons
Eperisone hydrochloride suppresses the activity of afferent
nerve fibers (Ia fibers) from human muscle spindles
at 20 min after administration. Eperisone hydrochloride
suppresses the spontaneous discharge of
-motor neurons, but does not act directly on muscle
spindles in animals. Accordingly, eperisone hydrochloride
reduces muscle spindle sensitivity via the -motor
neurons. 8, 9)
2. Vasodilatation and Augmentation of blood flow
(1) Vasodilatory action
Eperisone hydrochloride dilates the blood vessels due
to Ca++-antagonistic action (in guinea pigs) on the vascular
smooth muscle and muscular sympatholytic actions
(in humans). 10, 11)
(2) Augmentation of blood flow
Eperisone hydrochloride increases the volume of blood
flow in skin, muscle, external and internal carotid arteries
and vertebral arteries in humans, monkeys and
dogs. 12 - 15)
3. Analgesic action and inhibition of the pain reflex in the
spinal cord
When eperisone hydrochloride is perfused into the spinal
cord of rats, a tail pinch-induced pain reflex is suppressed,
but the reflex returns with the withdrawal of eperisone hydrochloride.
This suggests that eperisone hydrochloride
possesses an analgesic action at the spinal cord level. 16)
4. Facilitation of voluntary movement
When eperisone hydrochloride is used in the treatment of
spastic paralysis in patients with cerebral apoplexy, it improves
the cybex torque curve and electromyogram and facilitates
voluntary movements, such as extension and flexion
of the extremities, without reducing the muscular force. 17)
PHYSICOCHEMISTRY
Nonproprietary name: Eperisone Hydrochloride (JAN)
Eperisone (INN)
Chemical name:
(2RS)-1-(4-Ethylphenyl)-2-methyl-3-piperidin-1-ylpropan-1-
one monohydrochloride
Molecular formula: C17H25NO ⋅ HCl
Molecular weight: 295.85
4 Eisai Co., Ltd.
Structural formula:
and enantiomer
Description:
Eperisone hydrochloride occurs as a white, crystalline
powder. It is freely soluble in water, in methanol and in
acetic acid (100), soluble in ethanol (99.5).
A solution of eperisone hydrochloride in methanol (1 in
100) shows no optical rotation.
Melting point: About 167°C (decomposition)
PACKAGING
MYONAL Tablets 50 mg:
Boxes of 100, 210 (21Tabs.⋅ 10), 1,000, 1,050 (21 Tabs.
⋅ 50), 3,000 and 3,150 (21Tabs.⋅ 150) in press-through
packages, and bottles of 500
MYONAL Granules 10%: Cans of 100 g
REFERENCES
1) Tanaka S. et al.: Clin. Report, 16, 6423, 1982.
2) Hanai K. et al.: Jap. J. Clin. Exp. Med., 60, 2049, 1983.
3) Tawara T. et al.: Prog. Med., 3, 1703, 1983.
4) Tsuyama N. et al.: Clin. Eval., 12, 231, 1984.
5) Kuroiwa Y. et al.: ibid., 9, 391, 1981.
6) Kobayashi I. et al.: Med. Consult. New Remed.,
19, 1493, 1982.
7) Tohgi H. et al.: ibid., 19, 2073, 1982.
8) Tanaka K. et al.: Folia pharmacol. japon.,
77, 511, 1981.
9) Mano T. et al.: Brain Nerve, 33, 237, 1981.
10) Fujioka M. et al.: J. Pharmacol. Exp. Ther., 235, 757,
1985.
11) Iwase S. et al.: Electroenceph. Clin. Neurophysiol, 66,
S49, 1987.
12) Motomura K. et al.: Biomed. Thermography, 9, 142,
1989.
13) Nanao K. et al.: 73th Folia pharmacol. japon. Abs.
Kinki, 1988.
14) Sugimoto H. et al.: Clin. Report, 21, 4882, 1987.
15) Mano T. et al.: 8th AOCN Satellite Symposium, 95,
1991.
16) Ishizuki M. et al.: J. Jpn. Orthop. Assoc., 63, S1238,
1989.
17) Watanabe S. et al.: Jap. J. Clin. Exp. Med., 58, 1610,
1981.
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