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 eperis-
one 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, hy-
droxypropylcellulose, 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 in-
gredients.
INDICATIONS
⋅Improvement of myotonic conditions caused by the follow-ing 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 cere-brospinal tumor), sequela of trauma (spinal injury and head injury), amyotrophic lateral sclerosis, infantile cerebral palsy, spinocere
bellar degeneration, spinal vascular disor-ders, subacute myelo-optico neuropathy (SMON) and other encephalomyelopathies
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 adminis-
tered 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 haz-ardous activities requiring alertness, such as operating ma-chinery or driving a car.
3.  Drug Interactions
Precautions for coadministration (MYONAL should be administered with care when coadministered with the fol-lowing drugs.)
Drugs Signs, Symptoms, and
Treatment Mechanism and Risk Factors
Methocarbamol It has been reported that dis-
turbance of visual accommoda-
tion occurred after the con-
comitant 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, pa-
tients 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 epi-
dermal necrolysis (Lyell syndrome) may occur. Pa-
tients should be carefully observed, treatment discon-
tinued 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
tablet英文(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 ex-
tremities
Gastrointestinal Nausea/vomiting,
ano-
rexia, stomach discom-
fort, abdominal pain,
diarrhea, constipation
and thirst
Stomatitis and
feeling of enlarged
abdomen
Urinary  Urinary
retention,
urinary inconti-
nence and feeling
of residual urine
General Weakness,
light-headedness and
generalized fatigue
Muscle hypotonia
and dizziness
Others Hot flushes Diaphoresis and
edema
Note 1) S ince 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) I n 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 pos-
sible 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)
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 concen-tration (t max) ranged from 1.6 to 1.9 hr, the peak plasma con-centration (c max) 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 concen-tration-time curve (AUC) was 19.7 to 21.1 ng ⋅ hr/mL. The plasma concentration profiles of eperisone hydrochloride de-termined 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 periar-
thritis and low back pain
In open labeled clinical trials and a double blind controlled clinical trial undertaken to determine the effects of MYO-NAL on myotonic symptoms associated with these dis-eases, 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 cere-brovascular disturbances, spastic spinal paralysis or cervi-cal spondylosis. Improvement rates for rigidity and stiff-ness 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 sec-
tion-induced decerebrate rigidity (γ-rigidity) and
ischemic decerebrate rigidity (α-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 γ-motor
neurons
Eperisone hydrochloride suppresses the activity of af-
ferent nerve fibers (Ia fibers) from human muscle spin-
dles at 20 min after administration. Eperisone hydro-
chloride suppresses the spontaneous discharge of
γ-motor neurons, but does not act directly on muscle
spindles in animals. Accordingly, eperisone hydrochlo-
ride reduces muscle spindle sensitivity via the γ-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 vas-
cular smooth muscle and muscular sympatholytic ac-
tions (in humans). 10, 11)
(2)  Augmentation of blood flow
Eperisone hydrochloride increases the volume of blood
flow in skin, muscle, external and internal carotid ar-
teries 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 hy-
drochloride. 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 im-
proves the cybex torque curve and electromyogram and fa-
cilitates 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
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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REQUEST FOR DRUG INFORMATION SHOULD BE  MADE TO:
Customer Information Service Free Dial: 0120-419-497 Eisai Co., Ltd.
Manufactured and marketed by:  Eisai Co., Ltd.
6-10, Koishikawa 4-chome, Bunkyo-ku, Tokyo, 112-8088

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