Tolizor capsules 50mg, 30pcs

Composition

Active antimatter elements: Tolperisone hydrochloride 50 mg

Excipients: microcrystalline cellulose-55.22 mg, lactose monohydrate (milk sugar) – 34.33 mg, croscarmellose sodium-6.32 mg, hypromellose-1.58 mg, citric acid monohydrate-1.5 mg, magnesium stearate-1.05 mg

Pharmacological action

Pharmacotherapy group: muscle relaxant of central action. ATX code: M 03 BX 04 Pharmacological properties

Pharmacodynamics

Tolperisone is a centrally acting muscle relaxant. The mechanism of action is not fully understood. Tolperisone has a high affinity for nervous tissue, reaching the highest concentrations in the brain stem, spinal cord and peripheral nervous system. The main effect of Tolperisone is mediated by inhibition of spinal reflex arcs. Probably, this effect, together with the elimination of facilitation of arousal along the descending pathways, provides the therapeutic effect of Tolperisone. The chemical structure of tolperisone is similar to that of lidocaine. Like lidocaine, it has a membrane-stabilizing effect and reduces the electrical excitability of motor neurons and primary afferent fibers.

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

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

Pharmacokinetics

After oral use, Tolperisone is well absorbed in the small intestine. The maximum plasma concentration is observed 0.5-1 h after use. Due to the pronounced presystemic metabolism, bioavailability is about 20%. Fat-rich foods increase the bioavailability of oral Tolperisone to about 100% and increase the maximum plasma concentration by about 45% compared to fasting, delaying the time to reach the maximum concentration by about 30 minutes. Tolperisone is extensively metabolized in the liver and kidneys. The compound is almost completely (more than 99%) excreted by the kidneys in the form of metabolites. The pharmacological activity of the metabolites is unknown. The half-life after oral use is about 2.5 hours.

Indications

Symptomatic treatment of spasticity in adults due to stroke.

Use during pregnancy and lactation

Pregnancy

No teratogenic effects of Tolperisone were detected in experimental animal studies. Due to the lack of significant clinical data, Tolperisone should not be used during pregnancy (especially in the first trimester), unless the expected benefit definitely justifies the potential risk to the fetus.

Breast-feeding period

Since there are no data on the excretion of Tolperisone in breast milk, the use of the drug during breast-feeding is contraindicated.

Contraindications

• hypersensitivity to any of the components of the drug;
• myasthenia gravis;
• age up to 18 years;
• breastfeeding;
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Side effects

The safety profile of Tolperisone is confirmed by data from more than 12,000 patients. According to these data, the most frequent disorders were skin and subcutaneous tissue disorders, general disorders, and disorders of the nervous system and gastrointestinal tract.

In the post-marketing period, hypersensitivity reactions accounted for about 50-60% of all adverse reactions. Most of the adverse reactions were not serious and went away on their own. Life-threatening hypersensitivity reactions were reported very rarely.

Adverse reactions are listed below according to MedDRA classification and frequency: infrequent (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (

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

From the immune system: rarely-hypersensitivity reactions, anaphylactic reactions; very rarely-anaphylactic shock.

From the side of metabolism and nutrition: infrequently – anorexia; very rarely-polydipsia.

Mental disorders: infrequently – sleep disturbance, insomnia; rarely-weakness, depression; very rarely-confusion.

Nervous system disorders: infrequently-headache, dizziness, drowsiness; rarely-attention deficit disorder, tremor, convulsions, malaise, paresthesia, lethargy.

From the side of the visual organ: rarely-decreased visual acuity.

Hearing disorders and labyrinth disorders: rarely-tinnitus, vertigo.

From the cardiovascular system: infrequently-hypotension; rarely-angina pectoris, tachycardia, palpitations, “flushes” of blood to the face; very rarely-bradycardia.

Respiratory system disorders: rarely-shortness of breath, nosebleeds, rapid breathing.

From the digestive system: infrequently-abdominal discomfort, dyspepsia, diarrhea, dry mouth, nausea; rarely-epigastric pain, constipation, flatulence, vomiting.

Liver and biliary tract disorders: rarely-moderate hepatic insufficiency.

Skin and subcutaneous tissue disorders: rarely-allergic dermatitis, excessive sweating, pruritus, skin rash, urticaria.

Musculoskeletal disorders: infrequently-muscle weakness, muscle pain, pain in the extremities; rarely – discomfort in the extremities; very rarely-osteopenia.

From the urinary system: rarely-enuresis, proteinuria.

General disorders and reactions at the injection site: infrequently-asthenia, discomfort, feeling of fatigue; rarely – feeling of intoxication, feeling of heat, irritability, thirst; very rarely-chest discomfort.

From the side of laboratory parameters: rarely-hyperbilirubinemia, changes in the activity of liver enzymes, thrombocytopenia, leukocytosis; very rarely-hypercreatininemia.

* Angioedema, including facial and lip edema, has been reported in post-marketing monitoring (frequency unknown).

If any of the reactions indicated in the instructions are aggravated or any other adverse reactions are noted that are not specified in the instructions, the patient should inform the doctor about this.

Interaction

Studies of the pharmacokinetic drug interaction with the marker substrate of the CYP2D6 isoenzyme dextromethorphan have shown that simultaneous use of Tolperisone can increase the blood content of drugs that are mainly metabolized by the CYP2D6 isoenzyme (thioridazone, tolterodine, venlafaxine, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine).

No significant inhibition or induction of other CYP isoenzymes (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP1A2, and CYP3A4) was found in laboratory experiments on human liver microsomes and human hepatocytes.

Due to the diversity of tolperisone’s metabolic pathways, no increase in tolperisone exposure is expected with concomitant use of CYP2D6 substrates and/or other drugs.

The bioavailability of tolperisone decreases when taken on an empty stomach.

Despite the fact that Tolperisone is a centrally acting drug, its sedative effect is very low. When used concomitantly with other centrally acting muscle relaxants, the dose of tolperisone should be reduced.

Tolperisone enhances the effect of niflumic acid, so when used simultaneously, a reduction in the dose of niflumic acid or other NSAIDs should be considered.

How to take, course of use and dosage

The drug is taken orally, after a meal, without chewing, without opening the capsule, with a small amount of water. The bioavailability of tolperisone decreases when taken on an empty stomach.

The dose of the drug is selected based on the individual needs of the patient and the tolerability of the drug.

Assign 50 mg 3 times / day, gradually increasing the dose to 150 mg 3 times/day. The recommended daily dose is 150-450 mg divided into three doses.

Experience of using Tolperisone in patients with renal insufficiency However, this category of patients experienced more frequent adverse reactions. Therefore, in patients with moderate renal impairment, it is necessary to select the dose of Tolperisone, with careful monitoring of the patient’s health and monitoring of renal function. The use of the drug is not recommended in patients with severe renal insufficiency.

Experience of using Tolperisone in patients with hepatic insufficiency However, this category of patients experienced more frequent adverse reactions. Therefore, in patients with moderate hepatic impairment, it is necessary to select the dose of Tolperisone, with careful monitoring of the patient’s health and monitoring of liver function. The use of the drug is not recommended in patients with severe hepatic insufficiency.

Overdose

Data on Tolperisone overdose are scarce. In preclinical acute toxicity studies, high doses of Tolperisone have caused ataxia, tonic-clonic seizures, shortness of breath, and respiratory paralysis. Tolperisone does not have a specific antidote.In case of overdose, symptomatic and supportive treatment is recommended.

Special instructions

The most common adverse reactions are hypersensitivity reactions.

Allergic reactions range from mild skin reactions to severe systemic reactions, including anaphylactic shock. Symptoms of an allergic reaction include redness, rash, urticaria, pruritus, angioedema (angioedema), tachycardia, hypotension, and shortness of breath.

Female patients with a history of hypersensitivity reactions to other medications or allergic reactions are at a higher risk.

In the case of known hypersensitivity to lidocaine, increased caution should be exercised when using Tolperisone due to possible cross-reactions.

Patients should be alert for any symptoms of hypersensitivity. If symptoms occur, you should immediately stop taking Tolperisone and immediately consult a doctor. Do not re-prescribe Tolperisone after an episode of hypersensitivity to a drug containing it.

Influence on the ability to drive vehicles and mechanisms

Tolizor does not affect the ability to drive vehicles and mechanisms. Patients who experience dizziness, drowsiness, impaired attention, seizures, visual impairment, or muscle weakness while taking the drug should consult a doctor.

Storage conditions

The drug should be stored out of the reach of children, protected from light at a temperature not exceeding 25°C.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Tolperisone

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For children over 3 years of age, For adults as prescribed by a doctor, For children as prescribed by a doctor

Indications

Consequences of Stroke, Arthrosis and Arthritis, Lumbago, Sciatica, Osteoarthritis, Muscle spasm