Tolperisonum

General characteristics. Structure:

Active ingredient: 50 mg or 150 mg of Tolperisonum of a hydrochloride in 1 tablet.

Excipients: hydroxypropyl cellulose, кросповидон, citric acid, stearic acid, silicon dioxide colloid anhydrous, magnesium stearate, lactose monohydrate, Opadray of II (including the polyvinyl alcohol which is partially hydrolyzed talc, a macrogoal 3350 (polyethyleneglycol), titanium E 171 dioxide).

Pharmacological properties:

Pharmacodynamics. Tolperisonum is a muscle relaxant of the central action. The mechanism of action of Tolperisonum is completely not found out. It has high affinity to nervous tissue, reaching the greatest concentration in a brain trunk, a spinal cord and a peripheral nervous system.

The main effect of Tolperisonum is connected with braking of spinal reflex arcs. Possibly, this effect, together with elimination of simplification of carrying out excitement on the descending ways, provides therapeutic influence of Tolperisonum.

The chemical structure of Tolperisonum is similar to structure of lidocaine. As well as lidocaine, it possesses membrane stabilizing action and reduces electric excitability of motor neurons and primary afferent fibers. Tolperisonum дозозависимо brakes activity potential - dependent natrium channels. Respectively, amplitude and frequency of action potential decreases.

The oppressing effect on potential - dependent calcium channels was proved. It is supposed that in addition to its membrane stabilizing action, Tolperisonum can slow down emission of a mediator also.

In completion to everything, Tolperisonum has some weak properties of alpha and adrenergic antagonists and antimuskarinovy action.

Pharmacokinetics. After intake Tolperisonum is well soaked up in a small intestine. The maximum concentration in a blood plasma is reached in 0,5-1 hour after reception. Because of the expressed presistemny metabolism bioavailability makes 20%. Food with the high content of fats increases bioavailability of orally appointed Tolperisonum approximately to 100% and increases peak plasma concentration approximately by 45% in comparison with medicine reception on an empty stomach, detaining time of achievement of peak concentration approximately for 30 minutes.

Tolperisonum is intensively metabolized in a liver and kidneys, almost completely (more than 99%) is removed by kidneys in the form of metabolites.

Pharmacological activity of metabolites is unknown.

The elimination half-life after intravenous administration makes about 1,5 hours, after use inside – about 2,5 hours.

Indications to use:

- urgent or prolonged treatment patholologically the raised tone of skeletal muscles at organic neurologic diseases (damage of pyramidal ways, multiple sclerosis, cerebrovascular disturbances, a myelipathy, encephalomyelitis etc.);

- treatment of a muscle hyper tone and the muscular spasms accompanying musculoskeletal system diseases (e.g. a spondylosis, a spondylarthritis, cervical and lumbar syndromes, arthroses of large joints);

- recovery treatment after operative measures in orthopedics and traumatology;

- treatment of obliterating diseases of vessels, and also the syndromes arising owing to disturbance of an innervation of vessels (for example, a Crocq's disease, an intermittent angioneurotic dysbasia);

- specific indications in pediatric practice are Littl's disease and other encephalopathies which are followed by muscular dystonia.

Route of administration and doses:

Inside, after food, without chewing, washing down with a glass of water. The initial dose makes 50 mg 2-3 times a day; the dose is gradually increased to 150 mg by 2-3 times a day.

Data on safety and efficiency of use of Tolperisonum for children are limited.

Medicine is appointed to children with body weight by more than 30 kg (10 years are more senior) in a daily dose of 2-4 mg/kg of body weight, in three steps.

Patients with a renal failure. Data on use for patients with renal failures are limited. Higher frequency of development of side reactions in this group of patients was observed. Patients with a moderate renal failure need to titrate a dose and to observe carefully. Do not recommend use of Tolperisonum for patients with heavy renal failures.

Patients with an abnormal liver function. These uses for patients with abnormal liver functions are limited. Higher frequency of development of side reactions in this group of patients was observed. Patients with a moderate abnormal liver function need to titrate a dose and to observe carefully. Do not recommend use of Tolperisonum for patients with heavy abnormal liver functions.

To apply after food, washing down with a glass of water. It is not recommended to accept on an empty stomach as the insufficient amount of food can reduce bioavailability of Tolperisonum.

Features of use:

Hypersensitivity reactions. During the post-registration period at use of the medicines containing Tolperisonum it was most often reported about development of reactions of hypersensitivity.

Allergic reactions varied from easy skin reactions before heavy system reactions, including an acute anaphylaxis. Symptoms of allergic reaction: erubescence, rash, urticaria, itch, Quincke's disease (Quincke's edema), tachycardia, hypotension and asthma.

Female patients with reactions of hypersensitivity to other drugs or the having allergic reactions in the anamnesis, are subject to higher risk.

In case of the known hypersensitivity to lidocaine it is necessary to observe the increased care during use of Tolperisonum because of possible cross-reactions.

Patients should recommend to be attentive concerning any symptoms of hypersensitivity. If symptoms developed, it is necessary to stop reception of Tolperisonum and to see immediately a doctor. It is not necessary to appoint repeatedly Tolperisonum to patients with the postponed hypersensitivity episode.

This medicine contains lactoses monohydrate. To patients with rare hereditary intolerance of a galactose, deficit of lactase of Lapp or glyukozo-galaktozny malabsorption, it is not necessary to accept this medicine.

Use during pregnancy and in the period of a lactation. At pregnancy and feeding by a breast use of drug is contraindicated. Use during a lactation is not recommended as it is unknown whether Tolperisonum gets into breast milk.

Influence on ability to driving of motor transport and to control of mechanisms. Patients at whom after reception of medicine dizziness was observed drowsiness, disturbance of attention, a spasm, a visual disturbance or muscular weakness, have to see a doctor. At emergence of the specified frustration it is necessary to refrain from driving of the car and work with moving mechanisms.

Side effects:

Frequency of emergence of side reactions: infrequently (> 1/1000 to 1/100 cases); seldom (> 1/10 000 to 1/1000 cases); very seldom (1/10 000 to <10 000 cases).

Disturbances from blood and lymphatic system: very seldom: anemia, lymphadenopathy.

Disturbances from immune system: seldom: hypersensitivity reactions, anaphylactic reaction; very seldom: acute anaphylaxis.

Disturbances of food and metabolism: infrequently: anorexia; very seldom: polydipsia.

Mental disturbances: infrequently: sleeplessness, sleep disorder; seldom: decrease of the activity, depression.

Disturbances from a nervous system: infrequently: headache, dizziness, drowsiness; seldom: disturbance of attention, tremor, spasms, hyposensitivity, paresthesia, pathological catalepsy; very seldom: confusion of consciousness.

Disturbances from an organ of sight: seldom: sight misting.

Disturbances from acoustic organs and balance: seldom: sonitus, dizziness.

Cardiological disturbances: seldom: stenocardia, tachycardia, heart consciousness; very seldom: bradycardia.

Disturbances from vascular system: infrequently: arterial hypotension; rare: pathological flush.

Respiratory, thoracic and mediastinal disturbances: seldom: диспноэ, nasal bleeding, tachypnea.

Disturbances from the alimentary system: infrequently: discomfort in a stomach, diarrhea, dryness in a mouth, dyspepsia, nausea; seldom: pain in epigastriums, a lock, a meteorism, vomiting.

Disturbances from gepatobiliarny system: seldom: easy disturbances from a liver.

Disturbances from skin and hypodermic cellulose: seldom: allergic dermatitis, the increased perspiration, an itch, urticaria, rashes.

Disturbances from an urinary system: seldom: enuresis, proteinuria.

Disturbances from a musculoskeletal system and connecting fabric: infrequently: muscular weakness, mialgiya, extremity pain; seldom: discomfort in extremities; very seldom: osteosinging.

System disturbances and complications in an injection site: infrequently: adynamy, indisposition, fatigue; seldom: feeling of intoxication, feeling of heat, irritability, thirst; very seldom: discomfort in a thorax.

Aberration, revealed in laboratory researches: seldom: a lowering of arterial pressure, increase in concentration of bilirubin in blood, change of activity of liver enzymes, decrease in number of thrombocytes, increase in number of leukocytes; very seldom: increase in content of creatinine of blood.

According to post-marketing use of the medicines containing Tolperisonum messages on cases developments of a Quincke's disease are gained.

Interaction with other medicines:

Researches of pharmacokinetic interaction of medicines with marker CYP2D6 substrate dextromethorphan showed that simultaneous use of Tolperisonum can increase the level of content in blood of medicines which are metabolized preferential CYP2D6 (thioridazine, толтеродин, венлафаксин, атомоксетин, desipramine, dextromethorphan, метопролол, небиволол, Perfenazinum).

Laboratory experiments on microsomes of a liver of the person and human hepatocytes did not cause considerable inhibition or induction of other isoenzymes of CYP (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP1A2, CYP3A4).

Do not assume increase in influence of Tolperisonum at simultaneous use of CYP2D6 substrates and/or other drugs in connection with a variety of metabolic ways of Tolperisonum.

Bioavailability of Tolperisonum goes down if to accept it on an empty stomach.

Though Tolperisonum is drug of the central action, sedation its very low. In case of co-administration with other muscle relaxants of the central action, the dose of Tolperisonum should be reduced.

Tolperisonum strengthens effect of niflumovy acid therefore at simultaneous use it is necessary to consider a dose decline of niflumovy acid or other non-steroidal anti-inflammatory drugs.

Contraindications:

Hypersensitivity to Tolperisonum or other similar chemicals, and also to auxiliary components. Myasthenia, heavy abnormal liver functions and/or kidneys, pregnancy, lactation period.

Overdose:

Data on overdose by Tolperisonum are not numerous. Tolperisonum possesses a wide therapeutic interval.

In preclinical trials of acute toxicity high doses caused an ataxy, toniko-clonic spasms, диспноэ and respiratory paralysis.

In case of overdose the symptomatic and supporting treatment is recommended. There is no specific antidote.

Storage conditions:

In the place protected from light and moisture, at a temperature from 15 ºС to 25 ºС. A period of validity - 2 years. Medicine cannot be used after the termination of the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging; in packaging No. 10х3.