Calmirex tabs tablets 150mg, # 30

Symptomatic treatment of stroke-related spasticity in adults.

Inside, after a meal, without chewing, without breaking the tablet, with a small amount of water. The bioavailability of tolperisone decreases when taken on an empty stomach. 50 mg 3 times a day, gradually increasing the dose to 150 mg 3 times a day.

Patients with renal impairment

Experience with the use of tolperisone in patients with renal insufficiency is limited, in this category of patients, adverse reactions often occurred. Therefore, in patients with moderate renal impairment, it is necessary to select a dose of tolperisone, with careful monitoring of the patient's health and control of renal function. In severe kidney damage, the appointment of tolperisone is not recommended.

Patients with hepatic impairment

The experience of using tolperisone in patients with hepatic impairment is limited, in this category of patients adverse reactions often occurred. Therefore, in patients with moderate hepatic dysfunction, it is necessary to select a dose of tolperisone, with careful monitoring of the patient's health and control of liver function. In severe liver damage, the appointment of tolperisone is not recommended.

One 150 mg tablet contains:

Active ingredient: tolperisone 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.

Shell composition: hypromellose - 4.80 mg, macrogol - 4000 - 1.20 mg, titanium dioxide - 2.00 mg.

• Hypersensitivity to any component of the drug.

• Myasthenia gravis.

• Children under 18 years of age. Breast-feeding.

• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

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 the spinal reflex arcs. Probably, this effect, together with the elimination of the facilitation of the conduction of excitation 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 voltage-gated sodium channels. Respectively,the amplitude and frequency of the action potential decreases. An inhibitory effect on voltage-gated calcium channels has been proven. It is assumed that, in addition to its membrane-stabilizing action, tolperisone may also inhibit the release of the mediator. Tolperisone has some weak properties of ?-adrenergic antagonists and antimuscarinic action.

Pharmacokinetics

After oral administration, tolperisone is well absorbed in the small intestine. The maximum plasma concentration is observed 0.5-1 hour after administration. Due to the pronounced presystemic metabolism, bioavailability is about 20%. Fat-rich food increases the bioavailability of ingested tolperisone to about 100% and increases the maximum plasma concentration by about 45% compared to taking the drug on an empty stomach, 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 administration is about 2.5 hours.

Application during pregnancy and during breastfeeding

Pregnancy

In experimental studies on animals, no teratogenic effects of tolperisone have been revealed. 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.

Breastfeeding period

Since there are no data on the release of tolperisone in breast milk, its use during breastfeeding is contraindicated.

Side effect

From the side of the blood and lymphatic system: 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.

From the side of the psyche: infrequently - sleep disturbance, insomnia; rarely - weakness, depression; very rarely - confusion.

From the nervous system: infrequently - headache, dizziness, drowsiness; rarely - attention deficit disorder, tremor, epilepsy, paresthesia, convulsions, malaise, lethargy.

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

On the part of the organ of hearing: rarely - tinnitus, vertigo.

From the side of the cardiovascular system: infrequently - arterial hypotension; rarely - angina pectoris, tachycardia, palpitations, 'hot flushes' of blood to the face; very rarely - bradycardia.

From the respiratory system: rarely - shortness of breath, epistaxis, tachypnea.

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

From the liver and biliary tract: rarely - moderate hepatic failure.

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

From the musculoskeletal system and connective tissue: infrequently - muscle pain, muscle weakness, pain in the limbs; rarely - discomfort in the limbs; very rarely - osteopenia.

From the side of the kidneys and urinary tract: rarely - enuresis, proteinuria.

General disorders: infrequently - asthenia, fatigue, malaise; rarely - a feeling of intoxication, a feeling of warmth, irritability, thirst; very rarely - chest discomfort.

Laboratory indicators: rarely - hyperbilirubinemia, abnormal liver function, thrombocytopenia, leukocytosis; very rarely - hypercreatininemia.

* As part of post-marketing monitoring, angioedema, including edema of the face and lips, has been reported (frequency unknown).

Overdose

Data on overdose of tolperisone are few.

In preclinical acute toxicity studies, high doses of tolperisone caused ataxia, tonic-clonic seizures, dyspnea, and respiratory paralysis. Tolperisone has no specific antidote. In case of overdose, symptomatic and supportive treatment is recommended.

Interaction with other medicinal products

Studies of pharmacokinetic drug interactions with a marker substrate of the CYP2D6 isoenzyme dextromethorphan have shown that the simultaneous use of tolperisone can increase the blood levels of drugs that are metabolized mainly by the CYP2D6 isoenzyme (thioridazone, tolterodine, venlafaxine, atomoxetine, desipramine.

In laboratory experiments on human liver microsomes and human hepatocytes, significant inhibition or induction of other CYP isoenzymes (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP1A2, CYP3A4) was not found.

Due to the variety of metabolic pathways of tolperisone, an increase in the exposure of tolperisone with the simultaneous use of substrates of the CYP2D6 isoenzyme and (or) other drugs is not expected.

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. With simultaneous use with other centrally acting muscle relaxants, the dose of tolperisone should be reduced.

Tolperisone enhances the effect of niflumic acid, therefore, with simultaneous use, a decrease in the dose of niflumic acid or other non-steroidal anti-inflammatory drugs (NSAIDs) should be considered.

special instructions

The most common adverse reactions are hypersensitivity reactions. Allergic reactions range from mild cutaneous to severe systemic reactions, including anaphylactic shock. Symptoms of an allergic reaction: redness, rash, urticaria, itching, angioedema (angioedema), tachycardia, arterial hypotension and shortness of breath.

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

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

Patients should be alert to any symptoms of hypersensitivity. If symptoms occur, you should immediately stop taking tolperisone and immediately consult a doctor. Tolperisone 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

KALMIREXЃ tabs does not affect the ability to drive vehicles and mechanisms.

Patients who experience dizziness, drowsiness, impaired attention, convulsions, blurred vision or muscle weakness while taking the drug should consult a doctor!