TOGETHER FOR HEALTH

TOPXOL 150 05/07/2011

Packing: Box of 10 blisters of 10 film coated tablets.

Active substances: Tolperisone hydrochloride 150 mg.

   TOPXOL 150


 

Tolperisone hydrochloride

Film coated tablet 

COMPOSITION

Each tablet contains:

Each film coated tablet contains:

Active ingredient: Tolperisone hydrochloride             150 mg.

PHARMACODYNAMICS AND PHARMACOKINETICS

Pharmacodynamics

Tolperisone hydrochloride, a piperidine derivative, is a centrally acting muscle relaxant. Its mode of action is complex. Owing to its membrane-stabilising and local anaesthetic effects, tolperisone inhibits the conduction in primary afferent nerve fibres and motoneurons whereby it inhibits spinal mono- and polysynaptic reflexes. The secondary mechanism is inhibition of synaptic Ca2+ influx whereby it inhibits transmitter release. In the brain stem, tolperisone inhibits the reticulospinal tracts.

Tolperisone improves peripheral blood flow. The favourable circulatory effects are independent of those seen in the central nervous system. They are probably related to the weak spasmolytic and antiadrenergic effects of tolperisone.

Pharmacokinetics

When administered orally, tolperisone is well absorbed from the small intestines. Peak plasma concentration appears within 0.5-1 hour after ingestion. Due to an intensive first-pass metabolism, the bioavailability of tolperisone is about 20%. High-fat meal increases the bioavailability of orally administered tolperisone by approx. 100% and increases the peak plasma concentration by approx. 45% as compared with fasting condition, delaying time to peak by approx. 30 minutes.

Tolperisone is intensively metabolised by the liver and the kidneys. It is almost exclusively eliminated via the kidneys (>99%) as metabolites.

INDICATIONS

Symptomatic treatment of post-stroke spasticity in adults.

RECOMMENDED DOSE AND MODE OF ADMINISTRATION

+ Method of administration

The medicine should be taken during or after meals.

+ Dosage

Adults: The daily dose by mouth is 150-450 mg divided in 3 equal portions according to the individual needs and tolerance of the patient.

Children under 6 years: The daily dose by mouth is 5-10 mg/kg body weight divided in 3 equal portions. Children 6-14 years: the daily dose by mouth is 4-12 mg/kg body weight divided in 3 equal portions.

Special population

Patients with renal impairment: Experience in patients with renal impairment is limited. However, a higher frequency of adverse events has been observed in this patient group. Therefore, individual titration with close monitoring of the patient’s condition and renal function is recommended in patients with moderate renal impairment. Use of tolperisone is not recommended in patients with severe renal impairment.

Patients with hepatic impairment: Experience in patients with hepatic impairment is limited. However, a higher frequency of adverse events has been observed in this patient group. Therefore, individual titration with close monitoring of the patient’s condition and hepatic function is recommended in patients with moderate hepatic impairment. Use of tolperisone is not recommended in patients with severe hepatic impairment.

Pediatric population: The safety and efficacy of tolperisone in children have not been established.

CONTRAINDICATIONS

Patients with hypersensitivity to the active substance tolperisone or to the chemically similar eperisone or to any ingredient of the medicine.

Patients with myasthenia.

Relative contraindications: Pregnancy, especially in the 1st trimester. Tolperisone is not recommended during the period of breastfeeding.

WARNINGS AND PRECAUTIONS

Hypersensitivity reactions

-    During posr marketing experience with tolperison the most frequently reported adverse reactions were hypersensitivity reactions which ranged from mild skin reactions to severe systemic reactions including anaphylactic shock. Symptoms may include erythema, rash, urticaria, pruritus, angioedema, tachycardia, hypotension or dyspnoea.

-    Females, patients with a history of hypersensitivity to other drugs or of allergy may be at a higher risk.

-    In case of a known hypersensitivity to lidocaine increased caution during the administration of tolperisone because of possible cross-reactions is warranted.

-    Patients should be advised to remain vigilant for any symptoms compatible with hypersensitivity and to stop tolperisone and seek medical advice immediately if such symptoms occur.

-    Tolperisone must not be re-administered after an episode of hypersensitivity to tolperisone.

Use in pregnancy and lactation: Due to the absence of relevant clinical data, tolperisone should not be used in pregnancy (particularly not in the 1st  trimester) unless its expected benefits would undoubtedly outweigh any possible embryotoxicity. Since it is not known whether tolperisone is excreted with breast milk or not, the administration of tolperisone is not recommended during breastfeeding.

Effects on the ability to drive or operate machinery: Patients who experience dizziness, somnolence, disturbance in attention, epilepsy, blurred vision or muscular weakness while taking tolperisone should consult his/her doctor.

INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION

Tolperisone may enhance the CNS effects of methocarbamol.

Tolperisone may enhance the effects of other neuromuscular blocking agents.

Tolperisone potentiates the effect of nifluminic acid, therefore reduction of the dose of nifluminic acid should be considered in case of co-administration.

Pharmacokinetic drug interaction studies with the CYP2D6 substrate dextromethorphan indicate that tolperisone co-administration may increase the blood levels of drugs which are metabolised dominantly by CYP2D6 such as thioridazine, tolterodine, venlafaxine, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine.

In vitro experiments in human liver microsomes and human hepatocytes did not suggest significant inhibition or introduction of other CYP isoenzymes (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP1A2, CYP3A4).

Increase in tolperisone exposure is not expected after concomitant administration of CYP2D6 substrates and/or other drugs due to the diversity of the mtabolic pathways of tolperisone.

The bioavailability of tolperisone is decreased when taken without food, therefore administration with or after meals is recommended.

Although tolperisone is a centrally acting compound, its potential to cause sedation is low.

In the case of co-administration with  other centrally acting muscle relaxants, the dose reduction of tolperisone should be considered.

Tolperisone potentiates the effect of niflumic acid, therefore reduction of the dose of niflumic acid or other NSAID should be considered in case of co-administration.

UNDESIRABLE EFFECTS

The most frequently reported adverse reactions are skin and subcutaneous tissue disorders, general disorders, neurological disorders and gastrointestinal disorders.

Hypersensitivity reactions: The majority of the cases express non-serious and self-limiting conditions. Life-threatening hypersensitivity reactions are reported very rarely.

Confusion (very rare).

Hyperhidrosis (rare).

Stop use and ask a doctor if unusual new symptoms occur.

Inform your physician in case of any adverse reaction related to drug use.

OVERDOSE AND TREATMENT

Symptoms: Information on tolperisone overdosage in human is limited.

Treatment: There are no specific antidotes. In case of overdose, supportive and symptomatic treatment should be indicated.

DOSAGE FORMS AND PACKAGING AVAILABLE

Box of 3 blisters of 10 film coated tablets.

Box of 10 blisters of 10 film coated tablets.

STORAGE:

Store at the temperature not more than 30oC, in a dry place, protect from light.

SPECIFICATION: Manufacturer’s.

SHELF-LIFE: 36 months from manufacturing date.

PRESCRIPTION ONLY

KEEP OUT OF REACH OF CHILDREN

READ CAREFULLY THE LEAFLET BEFORE USE

FOR MORE INFORMATION, CONSULT YOUR PHYSICIAN

Manufactured by: GLOMED PHARMACEUTICAL Co., Inc.

Address: 35 Tu Do Boulevard, Vietnam – Singapore Industrial Park, Thuan An, Binh Duong.

Tel: 0650.3768824;  Fax: 0650.3769095.

© 2011 GLOMED PHARMACEUTICAL Co., INC