MYDOFLEX Film-coated tablet Ref.[11045] Active ingredients: Tolperisone

Hypersensitivity reactions

During post marketing experience with tolperisone the most frequently reported adverse reactions were hypersensitivity reactions. Hypersensitivity reactions 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 hypersensitivity to other drugs or with a history 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.

When prescribing Mydoflex, the physician should inform patient on the risk of sensitisation (see adverse events). The former should be alerted when patient complains of a certain malaise expressing in dysesthesias of the extremities, a sensation of burning or even in skin eruption or dyspnoea, typically when appearing after the first administration (in case patient had a history of tolperisone treatment). In this case the treatment should be stopped immediately and definitively.

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 induction 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 consistent administration in relation to meals is recommended (see also sections 4.2 and 5.2).

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.

No specific interaction studies with Mydoflex were performed so far but no interactions were reported, including with benzodiazepines, NSAIs or analgesics.

For tolperisone no clinical data on exposed pregnancies are available.

Thus – and although animal studies do not indicate direct or indirect harmful effects with respect to pregnancy and embryonal/fœtal development (see §5.3) – tolperison should not be prescribed to pregnant women during the first quarter of pregnancy.

As it is possible that tolperisone and/or its metabolites are excreted in the milk, breast-feeding should be avoided if treatment with Mydoflex appears necessary.

In a study in healthy subjects Mydoflex at doses of one tablet at 50 mg three times a day or 150 mg three times a day did not induce drowsiness and did not prolong reaction time, even after sensitisation of the test by acute alcohol intake. It can therefore be stated that Mydoflex has no or negligible influence on the ability to drive and use machines. In the case of adverse reactions such as sleepiness or dizziness the patient’s ability to concentrate and to react properly may be impaired. In such cases, patients should refrain from driving cars and using machines.

Patients who experience dizziness, somnolence, disturbance in attention, epilepsy, blurred vision or muscular weakness while taking tolperisone should consult his/her doctor.

Less than 5% of patients can be expected to experience adverse reactions. In most cases they are of mild intensity and treatment can be continued, sometimes after reduction of the initial dose.

Following suspected adverse reactions were reported uncommonly (Nb of occurrence of an adverse reaction/Nb of patients exposed >1/1.000, <1/100), rarely (frequency <1/1.000) or very rarely (frequency <1/10.000).

Psychiatric disorders

Uncommon: Impaired concentration

Nervous system

Uncommon: Dizziness, balance difficulty, tremor

Vascular

Uncommon: Hypotension, palpitation

Gastrointestinal

Uncommon: Nausea, vomiting, diarrhoea, abdominal pain, xerostomia, flatulence

Skin

Uncommon: Erythematous rash, urticaria, sudation

General disorders

Uncommon: Fatigue, asthenia, pain

Very rare: Anaphylactic shock, anaphylactoid reaction, larynx oedema

The safety profile of tolperisone containing tablets is supported by data on more than 12,000 patients.
According to these data, the most frequently concerned system organ classes are skin and subcutaneous tissue disorders, general disorders, neurological disorders and gastrointestinal disorders.

In post-marketing data, hypersensitivity reactions associated with tolperisone administration account for about 50-60% of the reported cases. 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)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs Fax: +357 22608649.

Not applicable.