Tolizor, 150 mg capsules 30 pcs

Tolperizone is a myorelaxant of central action. The mechanism of action is not fully elucidated. Tolperizone has high affinity to the nervous tissue, reaching the highest concentrations in the brain stem, spinal cord and peripheral nervous system.

The main effect of tolperizone is mediated by inhibition of spinal reflex arcs. This effect, together with the elimination of the facilitation of excitation conduction along the descending pathways, probably provides the therapeutic effect of tolperisone. The chemical structure of tolperizone is similar to that of lidocaine.

Like lidocaine, it has a membrane stabilizing effect and reduces electrical excitability of motor neurons and primary afferent fibers.

Tolperizone dose-dependently inhibits the activity of potential-dependent sodium channels.

Accordingly, the amplitude and frequency of action potential is reduced. A suppressive effect on potential-dependent calcium channels has been proven. It is assumed that in addition to its membrane-stabilizing effect, tolperizone may also inhibit mediator release. Tolperizone has some weak a-adrenergic antagonist properties and antimuscarinic action.

Indications

Symptomatic treatment of stroke-induced spasticity in adults.

Active ingredient

Tolperizon

Composition

Active ingredient:

tolperizone hydrochloride -150.00 mg;

excipients:

microcrystalline cellulose – 70.00 mg;

lactose monohydrate (milk sugar) – 43.50 mg;

Croscarmellose sodium – 12.00 mg;

Hypromellose – 3.00 mg;

Citric acid monohydrate – 4.50 mg;

Magnesium stearate -2.00 mg.

Capsule body composition: iron oxide black dye – 0,0500%; titanium dioxide – 2,0000%; water – 14,50%; gelatin – up to 100%.

Capsule cap: quinoline yellow dye – 0.7500%; sunset yellow dye – 0.0059%; titanium dioxide – 2.0000%; water – 14.50%; gelatin – up to 100%.

How to take, the dosage

Orally, after a meal, without chewing, without opening the capsule, with a small amount of water. Bioavailability of Tolperizone is reduced when taken on an empty stomach.

The drug dose is adjusted according to the individual patient’s needs and tolerance of the drug.

50 mg 3 times a day, gradually increasing the dose to 150 mg 3 times a day.

Recommended daily dose is 150-450 mg divided into 3 parts.

Patients with renal impairment

Experience in using tolperizone in patients with renal impairment is limited, adverse reactions occurred more often in this category of patients. Therefore, in patients with moderate renal impairment the dose of tolperizone should be adjusted, with close monitoring of the patient’s health status and control of renal function. The use of the drug is not recommended in patients with severe renal failure.

Patients with hepatic impairment

Experience of tolperizone use in patients with hepatic impairment is limited, adverse reactions occurred more often in this category of patients. Therefore, in patients with moderate liver dysfunction it is necessary to adjust the dose of tolperizone with close monitoring of the patient’s health status and control of liver function. The use of the drug is not recommended in patients with severe hepatic impairment.

Interaction

Studies of pharmacokinetic drug interaction with the marker substrate of CYP2D6 isoenzyme dextromethorphan have shown that concomitant use of tolperizone may increase blood levels of drugs that are metabolized primarily by CYP2D6 isoenzyme (thioridazone, tolterodine, venlafaxine, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivololol, perphenazine).

No significant inhibition or induction of other CYP isoenzymes (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP1A2, CYP3A4) was found in laboratory experiments on human liver microsomes and human hepatocytes. Due to the variety of metabolic pathways of tolperizone, increased exposure of tolperizone when concomitant use of substrates of the
CYP2D6 isoenzyme and/or other drugs is not expected.

The bioavailability of tolperizone is reduced when taken on an empty stomach.

Although Tolperizone is a central acting drug, its sedative effect is very low. When concomitant use with other central myorelaxants, the dose of tolperizone should be reduced. Tolperizone enhances the effect of niflumic acid, therefore, reduction of the dose of niflumic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs) should be considered during concomitant use.

Special Instructions

The most common adverse reactions are hypersensitivity reactions. Allergic reactions range from mild skin to severe systemic, including anaphylactic shock.

The symptoms of allergic reactions include redness, rash, urticaria, pruritus, angioedema (Quincke’s edema), tachycardia, arterial hypotension and shortness of breath.

Patients who are female and have a history of hypersensitivity reactions to other drugs or allergic reactions are at higher risk.

In patients with known hypersensitivity to lidocaine, extra caution should be exercised when using tolperizone because of possible cross-reactions.

Patients should be alert for any symptoms of hypersensitivity.
If symptoms occur, stop taking tolperizone immediately and seek immediate medical attention. Tolperizone should not be re-prescribed after an episode of hypersensitivity to a drug containing it.

The effect of the drug on the ability to drive vehicles and mechanisms

Tolizor does not affect the ability to drive vehicles and mechanisms. Patients who have experienced dizziness, somnolence, impaired attention, seizures, visual impairment or muscle weakness while taking the drug should see their physician!

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Contraindications

Hypersensitivity to any of the drug components.

Myasthenia gravis.

Children under 18 years of age.

Breast-feeding.

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Side effects

The safety profile of the drug tolperisone is confirmed by the data of use in more than 12,000 patients. According to these data, skin and subcutaneous tissue disorders, general, neurological and gastrointestinal disorders were described most frequently.

In the post-registration period the number of reports on the development of hypersensitivity reactions associated with the use of tolperizone was about 50-60% of all reports received. In most cases, these were non-serious adverse reactions. Life-threatening allergic reactions were very rarely reported.

The frequency of adverse reactions is classified according to World Health Organization recommendations, characterized as: very frequently (>1/10), frequently (>1/100, < 1/10), infrequently (>1/1000, < 1/100), rarely (>1/10000, < 1/1000), very rarely (< 1/10000), including isolated cases, frequency unknown (cannot be calculated from available data).

Blood and lymphatic system disorders: very rarely – anemia, lymphadenopathy.

Immune system disorders: rare – hypersensitivity reactions*, anaphylactic reactions, very rare – anaphylactic shock.

Metabolism and nutrition: infrequent – anorexia; very rare – polydipsia.

Mental: infrequent – sleep disturbance, insomnia, rarely – weakness, depression, very rare – confusion.

Nervous system: infrequent – headache, dizziness, somnolence; rare – attention deficit syndrome, tremor, seizures, paresthesia, malaise, lethargy.

Visually: rare – decreased visual acuity.

Hearing: rare – tinnitus, vertigo.

Cardio-vascular system: infrequent – hypotension, rarely – angina, tachycardia, palpitations, “rushes” of blood to the face, very rarely – bradycardia.

Respiratory system: rare – shortness of breath, nasal bleeding, tachypnea.

Gastro-intestinal tract: infrequent – abdominal discomfort, dyspepsia, diarrhea, dry mouth, nausea, rarely – epigastric pain, constipation, flatulence, vomiting.

Liver and biliary tract: rarely – moderate hepatic insufficiency.

Skin and subcutaneous tissue: rare – allergic dermatitis, hyperhidrosis, itching, skin rash, urticaria.

Musculoskeletal and connective tissue: infrequent – muscle pain, muscle weakness, pain in the extremities, rarely – discomfort in the extremities, very rare – osteopenia.

Renal and urinary tract: rare – enuresis, proteinuria.

General disorders and reactions in the injection site: infrequent – asthenia, fatigue, malaise, rarely – a feeling of intoxication, a feeling of warmth, irritability, thirst; very rare – discomfort in the chest.

Laboratory parameters: rare – hyperbilirubinemia, liver function abnormalities, thrombocytopenia, leukocytosis; very rare – hypercreatininemia.

* Angioneurotic edema, including facial and lip edema (frequency is unknown) was reported during post-registration monitoring.

Overdose

There are few data on tolperizone overdose.

In preclinical studies of acute toxicity high doses of tolperizone caused ataxia, tonic-clonic seizures, dyspnea and respiratory paralysis.

Tolperizone has no specific antidote.

In case of overdose symptomatic and supportive treatment is recommended.

Similarities

Midocalm, Tolperizone-OBL, Tolperizone, Calmirex