MYNARAC
INFORMATION FOR MEDICAL STAFF
COMPOSITION:
Tolperisone hydrochloride...................... 150 mg
Excipients q.s....................................... 1 tablet
(Wheat starch, microcrystalline cellulose M101, lactose monohydrate, povidone K30, citric acid monohydrate, crospovidone XL10, colloidal silicon dioxide, talc, stearic acid, sepifilm LP 770, hypromellose 2910 (6cp), hypromellose 2910 (15cp), polyethylene glycol 6000, titanium dioxide, yellow ferric oxide).
PHARMACEUTICAL FORM: Film coated tablet.
PHARMACODYNAMIC PROPERTIES:
ATC code: M03BX04
Tolperisone hydrochloride is a centrally acting muscle relaxant.
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. On the different animal models, tolperisone shows to reduce an increased muscle tone and spasticity increased after brain lost.
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.
PHARMACOKINETIC PROPERTIES:
Tolperisone is well absorbed from the small intestines. Peak plasma concentration appears within 0.5 - 1 hour after oral administration. Due to an intensive first-pass metabolism, the bioavailability of tolperisone is about 20%.
Tolperisone is intensively metabolised by the liver and the kidneys. It is almost exclusively eliminated via the kidneys (>99%) as metabolites which their effects have not been determined.
High-fat meal increases the bioavailability of orally administered tolperisone by approximately 100% and increases the peak plasma concentration by approximately 45% as compared with fasting condition, delaying time to peak by approximately 30 minutes.
PRESENTATION: Box of 6 blisters x 10 film coated tablets.
THERAPEUTIC INDICATIONS:
Symptomatic treatment of post-stroke spasticity in adults.
DOSAGE & ADMINISTRATION:
The recommended dose should be 150 to 450 mg/day, divided into 3 doses, depending on the needs and tolerance of the patient. The medicine should be taken during or after a meal with a glass of water.
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.
Or as prescribed by the physician.
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.
SPECIAL WARNING AND PRECAUTIONS FOR USE:
Cautions should be taken in hepatic and renal and hepatic impairments.
Hypersensitivity reactions:
- During post marketing experience with tolperisone 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.
Pregnancy:
No teratogenic effect of tolperidone was noted in any animal studies.
In rats and rabbits, embryo toxicity occurred after a dose of 500 mg/kg body weight and 250 mg/kg body weight in the respective order. However, these doses are several times higher than the therapeutic dose.
Since there are no human study results available, tolperisone should not be used in pregnancy (especially in the first trimester) unless the intended benefits to the mother outweighs the potential risk to the fetus or infant.
Lactation:
Since there are no data available whether tolperisone is excreted into breast milk, it must not be used during lactation.
The administration of tolperisone is not recommended during breastfeeding.
Effects on ability to drive and use machines: The effect of this medicine on the ability to drive vehicles and operate machinery is unknown.
Patients who experience dizziness, somnolence, and disturbance in attention, epilepsy, blurred vision or muscular weakness while taking the drug should consult a doctor.
INTERACTIONS:
Pharmacokinetic drug interaction studies with 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 metabolic pathways of tolperisone.
The bioavailability of tolperisone is decreased when taken without food, therefore administration with or after a meal is recommended.
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.
Uncommon: weakness, fatigue, headache, dizziness, mild hypotension, nausea, abdominal discomfort. These symptoms usually disappear with dose reduction.
Rare: hypersensitivity reactions (pruritus, erythema, rash, angioedema, anaphylactic shock, dyspnea), and sweating.
Very rare: confusion.
OVERDOSE:
Information on tolperisone overdosage is limited. Tolperisone has broad therapeutic boundaries. The highest daily dose is up to 800 mg without causing any serious poisoning symptoms. An irritation occurred in children at doses of 300 to 600 mg per day. In acute preclinical toxicology studies, high doses of tolperisone may cause ataxia, rigidity - tremors, dyspnea, respiratory paralysis.
There are no specific antidotes. In case of overdose, supportive and symptomatic treatment should be indicated.
Read the directions carefully before use.
Consult the physician for more information.
This drug is for prescription only.
Storage conditions: Store in dry places, not exceeding 300C, protect from light.
Shelf-life: 36 months from the manufacturing date.
DATE OF REVISION OF THE TEXT: July 24, 2028
INFORMATION FOR THE USER
Read all of this leaflet carefully before you start taking this medicine.
Keep out of reach of children
Immediately tell your doctor or pharmacist of undesired effects encountered during the treatment.
The drug is for prescriptions only.
QUALITATIVE AND QUANTITATIVE COMPOSITION:
Tolperisone hydrochloride...................... 150 mg
Excipients q.s....................................... 1 tablet
Product description: A round, film-coated, yellow tablet, plain on both surfaces, intact edges.
PRESENTATION: Box of 6 blisters x 10 film coated tablets
WHAT THE DRUG IS USED FOR:
Symptomatic treatment of post-stroke spasticity in adults.
HOW TO TAKE THIS MEDICINE:
The recommended dose should be 150 to 450 mg/day, divided into 3 doses, depending on the needs and tolerance of the patient. The medicine should be taken during or after a meal with a glass of water.
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.
Or as prescribed by the physician.
WHEN NOT TO TAKE THIS MEDICINE:
Patients with hypersensitivity to the active substance tolperisone or to the chemically similar eperisone or to any ingredient of the medicine.
Patients with myasthenia.
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.
Uncommon: weakness, fatigue, headache, dizziness, mild hypotension, nausea, abdominal discomfort. These symptoms usually disappear with dose reduction.
Rare: hypersensitivity reactions (pruritus, erythema, rash, angioedema, anaphylactic shock, dyspnea), and sweating.
Very rare: confusion.
Inform your physician about any adverse effects occur during the treatment.
WHICH MEDICINE OR FOOD SHOULD BE AVOIDED WHILE TAKING THIS MEDICINE:
Pharmacokinetic drug interaction studies with 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, 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 metabolic pathways of tolperisone.
The bioavailability of tolperisone is decreased when taken without food, therefore administration with or after a meal is recommended.
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.
WHAT SHOULD YOU DO IF YOU MISS A DOSE:
The following dose should be taken as directed. Do not use extra medicine to make up the missed dose to avoid overdose.
HOW TO STORE THIS MEDICINE: Store in dry places, not exceeding 300C, protect from light.
SIGNS AND SYMPTOMS OF DRUG OVERDOSE:
Information on tolperisone overdosage is limited. Tolperison has broad therapeutic boundaries. The highest daily dose is up to 800 mg without causing any serious poisoning symptoms. An irritation oocurred in children at doses of 300 to 600 mg per day. In acute preclinical toxicology studies, high doses of tolperison may cause ataxia, rigidity - tremors, dyspnea, respiratory paralysis.
WHAT TO DO IF OVERDOSE:
There are no specific antidotes. In case of overdose, supportive and symptomatic treatment should be indicated.
WHAT ARE THE PRECAUTIONS WHEN TAKING THIS MEDICINE:
Cautions should be taken in hepatic and renal and hepatic impairments.
Hypersensitivity reactions:
- During post marketing experience with tolperisone 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.
Pregnancy:
No teratogenic effect of tolperidone was noted in any animal studies.
In rats and rabbits, embryo toxicity occurred after a dose of 500 mg/kg body weight and 250 mg/kg body weight in the respective order. However, these doses are several times higher than the therapeutic dose.
Since there are no human study results available, tolperisone should not be used in pregnancy (especially in the first trimester) unless the intended benefits to the mother outweighs the potential risk to the fetus or infant.
Lactation:
Since there are no data available whether tolperisone is excreted into breast milk, it must not be used during lactation.
The administration of tolperisone is not recommended during breastfeeding.
Effects on ability to drive and use machines: The effect of this medicine on the ability to drive vehicles and operate machinery is unknown.
Patients who experience dizziness, somnolence, and disturbance in attention, epilepsy, blurred vision or muscular weakness while taking the drug should consult a doctor.
WHEN YOU SHOULD MEET YOUR DOCTOR OR PHARMACIST:
If you need further information, please consult your doctor or pharmacist.
SHELF-LIFE: 36 months from the manufacturing date.
DATE OF REVISION OF THE TEXT: July 24, 2018