EPERISONE

EPERISONE Hydrochloride

50mg Tablet

DRUG CATEGORY: Muscle Relaxant

BRAND NAME: Myonal

FORMULATION: Each white sugar-coated tablet contains 50mg of eperisone hydrochloride.

PRODUCT DESCRIPTION

1. Dosage form: Sugar-coated tablets

1. Appearance:

• Face: 7.5mm in diameter

• Weight : 162mg

• Thickness: 4.2mm

3. Description: White

INDICATIONS

• Spastic paralysis in the following diseases:
  • Cerebrovascular diseases, spastic spinal paralysis, cervical spondylosis, post-operative sequelae (including cerebrospinal tumor), sequelae to trauma (spinal trauma, head injury), amytrophic lateral sclerosis, cerebral palsy, spinocerebellar degeneration, spinal vascular diseases, and other encephalomyelopathies.

• Improvement of myotonic symptoms in the following diseases:
  • Cervical syndrome, periathritis of the shoulder, lumbago.

• Tension type headache.

DOSAGE AND ADMINISTRATION

The usual adult dose for oral use is 3 tablets (150mg of eperisone hydrochloride) daily in three divided doses after meals. The dose may be adjusted depending on the patient's age and symptoms.

CONTRAINDICATIONS

Patients with a history of hypersensitivity to any ingredients of Eperisone hydrochloride.

PRECAUTIONS

1. Careful Administration

• Patients with a history of drug hypersensitivity

• Patients with hepatic function disorder (Eperisone hydrochloride 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.

DRUG INTERACTIONS

Precautions for co-administration ( Eperisone hydrochloride should be administered with care when co-administered with the following drugs.)

Methocarbamol: It has been reported that disturbance of visual accomodation occurred after the concommitant use of methocarbamol with tolperisone hydrochloride, an analogue compound. Mechanism is unknown.

USE IN ELDERLY

Since the elderly often have a physiological hypofunction, it is advisable to take such measures as the reduction in dosage under careful supervision.

PREGNANCY AND LACTATION

1. Use During Pregnancy
   Eperisone hydrochloride should only be used in pregnant women suspected of being pregnant, if the expected therapeutic benefits are evaluated to outweigh the possible risk of treatment.

1. Use During Lactation
   It is advisable to avoid the administration of Eperisone hydrochloride to nursing mothers. When Eperisone hydrochloride must be used, breastfeeding should be discontinued during treatment. (It has been reported that Eperisone hydrochloride is excreted in breast milk in an animal study in rats.)

PEDIATRIC USE

Safety in children has not been established (insufficient clinical experience).

ADVERSE REACTIONS

Adverse reactions were reported in 416 of 12,315 patients (3.38%). (At the end of the re-examination period)

1. Clinically significant adverse reactions (incidence unknown)

• 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.

• Oculo-muco-cutaneous syndrome (Stevens-Johnson sydrome) 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

	0.1%-5%	<0.1%	Incidence unknown
Hepatic note 1		Elevations of AST (GOT), ALT (GPT) and AI-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 temor 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 measure taken.

Note 2) In the event of such symptoms, treatment should be discontinued.

PHARMACOKINETICS

Blood Concentration

Eperisone hydrochloride was administered orally to 8 healthy adult male volunteers at a single dose of 150 mg/day* for 14 consecutive days and the plasma concentration was determined at days 1, 8 and 14. The time to reach the peak plasma concentration (t_max) ranged from 1.6 to 1.9 hr, the peak plasma concentration (C_max) was 7.5 to 7.9 ng/ml, elimination half-life (t_1/2) 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 to 14 did not significantly vary from those of the first day.

Plasma concentration of eperisone hydrochloride in the course of oral administration at a single dose of 150 mg/day* for 14 consecutive days (means± S.E., n=8)

*A single dose of 150mg is unapproved.

PHARMACOLOGY

1. Skeletal muscle relaxation

• Inhibition of experimentally-induced muscle rigidity
  • Eperisone hydrochloride suppresses intercollicular section-induced decerebrate rigidity (γ-rigidity) and ischemic decerebrate rigidity (α-rigidity) in rats dose-dependently.

• Suppression of spinal reflexes
  • In spinal cats, eperisone hydrochloride suppresses mono- and polysynaptic reflex potentially induced through spinal nerve efferent root stimulation to a similar degree.

• Reduction of muscle spindle via γ-motor neurons.
  • Eperisone of muscle suppresses the activity of afferent fibers (Ia fibers) from human spindles at 20min. After administration. Eperisone hydrochloride suppresses the spontaneous discharge of γ-motor neurons, but does not act directly on muscle spindles in animals. Accordingly, eperisone hydrochloride reduces muscle spindle via the γ-motor neurons.

1. Vasodilation and Augmentation of blood flow

• 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).

• 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.

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 leve.
   
   

3. 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 facilities voluntary movements, such as extension and flexion of the extremities, without reducing the muscular force.

CLINICAL STUDIES

1. Cervical syndrome, periathritis of the shoulder and lumbago
   In open-labeled clinical trials and a double-blind controlled clinical trial undertaken to determine the effects of Eperisone hydrochloride 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%)

1. Spastic paralysis
   In open-labeled clinical trials and a double-blind trial, the usefulness of Eperisone hydrochloride has been established for spastic paralysis associated with diseases such as cerebrovascular disturbance, 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.

STORAGE CONDITION

Eperisone hydrochloride should be stored at temperatures not exceeding 30^oC, and should be protected from moisture after opening package.