Tolperil-Zdorovye tab. of p/o of 150 mg No. 30

Pharmacological properties

Pharmacodynamics. muscle relaxant of the central action. the mechanism of action is caused by braking of conductivity of impulses of primary afferent fibers and motor neurons that leads to blockade spinal mono - and polisinaptichesky reflexes. by slowing down of receipt sa2 + in synapses again interferes with discharge of mediators. slows down carrying out excitement on a reticulospinal way. increases a peripheral blood stream irrespective of influence of central nervous system. development of this effect can be connected with weak spasmolytic and anti-adrenergic effect of Tolperisonum.

Pharmacokinetics. At intake it is well soaked up in a small intestine, is exposed to intensive metabolism in a liver and kidneys. The C _max is reached in 0.5-1 h; owing to considerable primary metabolism the bioavailability is about 20%. It is intensively metabolized in a liver and kidneys. T _½ after introduction in/in makes about 1.5 h. It is allocated with kidneys, it is almost exclusive (99%) in the form of metabolites which pharmacological activity is unknown.

Indication

Pathological hyper tone and spasms of striated muscles owing to organic diseases of central nervous system (including damage of pyramidal ways, multiple sclerosis, a stroke, a myelipathy, encephalomyelitis).

Gipertonus of muscles, a spasm of muscles, muscular contractures owing to musculoskeletal system diseases (spondylosis, a spondylarthrosis, a cervical and lumbar syndrome, arthrosis of big joints); recovery therapy after orthopedic and traumatologic operations.

Disease, followed by a spasm of arteries and disturbance of an innervation of vessels (for example Crocq's disease, Sharko's syndrome).

Littl's Disease and encephalopathy at children which is followed by dystonia.

Use

Tablet: the mode of dosing and duration of a course of therapy are appointed individually, depending on a course, efficiency and shipping of therapy. to adults and children 14 years are aged more senior appoint 150–450 mg/days, having distributed on 3 receptions.

to Children with the body weight of 30 kg: on 5 mg/kg of body weight a day, having distributed on 3 receptions.

to Children at the age of 6–14 years: on 2–4 mg/kg/days, having distributed on 3 receptions.

Solution for injections: adult in oil — on 1 ml 2 times a day or in/in slowly — on 1 ml of 1 times a day.

Contraindication

Increased individual sensitivity to medicament components, a heavy myasthenia, the period of pregnancy and feeding by a breast, children's age.

For medicament in the form of tablets a relative contraindication: pregnancy period, especially the I trimester.

Usually medicament is well transferred by

, side reactions are observed only at 2–3% of patients:

from central nervous system: muscle weakness, headache;

from a GIT: nausea, vomiting, sensation of discomfort in a stomach;

from a cardiovascular system: arterial hypotension;

allergic reactions: in isolated cases — a skin itching, an erythema, a small tortoiseshell, a Quincke's disease, an acute anaphylaxis, dispnoe.

Special instructions

Considering existence in composition of medicament of lidocaine, before use it is necessary to carry out sensitivity test to lidocaine.

For prevention of complications needs to use medicament strictly according to indications, especially in heart, pulmonary failure, diseases of kidneys and a liver, OH in the anamnesis, hematologic diseases.

List of planned researches of a condition of bodies and systems before appointment and at long use of medicament is defined by the doctor.

Period of pregnancy and feeding by a breast. Due to the lack of clinical trials of use of medicament during pregnancy, especially in the I trimester, use it is possible, only if the expected advantage for mother exceeds potential risk for a fruit.

Data relatively penetrations of a tolperizon into breast milk are absent therefore in need of administration of medicament during feeding, breastfeeding needs to be stopped.

Children. In the form of tablets, medicament is used at children with body weight 30 kg on appointment and under control of the doctor. Solution cannot be applied to injections at children.

Influence on ability to run vehicles and to work with difficult mechanisms. At control of vehicles and work with other mechanisms it is necessary to consider a possibility of emergence of such side reactions as arterial hypotension and muscle weakness at administration of medicament in the form of solution. In the form of tablets — data are absent.

Interaction

Drug strengthens effect of niflyuminovy acid therefore at simultaneous use it is necessary to lower doses of niflyuminovy acid.

Despite the central mechanism of action, tolperizon does not render sedation therefore it can be applied in a combination with sedative, sleeping, tranquilizing medicines. Does not strengthen influence of alcohol on central nervous system.

Overdose

Data on overdose. tolperizon possesses the high therapeutic index. the case of reception by children in 600 mg of medicament during which special serious toxic symptoms were not noted is described. in certain cases at children observed acrimony after intake of 300-600 mg of medicament a day.

Treatment: symptomatic and maintenance therapy. There is no specific antidote.

Tablet to store

in original packing at a temperature not above 25 °C; solution for injections — at a temperature of 2-8 °C.

Relevant information

Tolperil — modern medicament which is intended for treatment of various spastic disorders of striated muscles (that is muscles which we can consciously control). it is widely applied in modern out-patient and stationary neurology, rehabilitology, orthopedics, sports medicine. enter the list of diseases in which this medicament is shown:

• the pathological increase in a tone or spasms of skeletal muscles connected with disturbance of their innervation (injuries of a spinal cord, multiple sclerosis, a myelipathy, etc.);

• the spastic paresis and paralyzes which arose as a result of a brain stroke/heart attack (Liptak J., 2013). In heavy postinsultny spastic dystonias the injection way of introduction is preferable. Encephalitis, encephalomyelitis or myelites of infectious origin belong to the same category. They are caused by neurotropic viruses or are a consequence of neuroallergic reactions to a toxaemia;

• during rehabilitation after injuries of a spinal cord often there are pain and constraint in muscles which severity decreases at reception Tolperil (Bajaj P., 2003);

• the hyper tone, a spasm or contractures of muscles developing owing to degenerative or inflammatory diseases of the musculoskeletal system (for example a spondylarthrosis, a lumbago) (Prabhoo R., 2011). Sometimes the spasm or a muscular contracture accompany arthrosis of large joints — knee (Dömötör E., 1979), coxofemoral (O.A. Kaplunov, 2017) — in view of long inflammatory process with a painful afferent impulsation the local pathological reflex is formed;

• the spinal and oral automatism connected with acute or chronic disorders of cerebral circulation;

• myofascial pain (F.I. Devlikamova., 2018), connected with injuries or psychoneurological disorders, it is facilitated thanks to spasmolytic and sedative effects Tolperil (Dulin J., 1998);

• the spasms and fastsikulyation caused by overdose of substances stimulators, including nicotine (Fujii Y., 1979);

• acceleration of rehabilitation after orthopedic operations — against the background of reception Tolperil becomes simpler development of muscles and joints;

• the headache of myogenetic character connected with a spasm of muscles of a neck (Csányi L., 1989);

• static vertebralny syndrome (Ya.Yu. Zakharov, 2007);

• disorders of a peripheral blood-groove caused by disturbance of an innervation of vessels (the alternating lameness, a Crocq's disease, a Raynaud's disease, a diabetic angiopatiya, a diffusion scleroderma, an obliterating thromboangitis). Tolperisonum use is especially relevant if disturbances of blood circulation result from a spasm in skeletal muscles after physical activity;

• the specific indication for prescribing of medicament in pediatrics is Littl's disease (spastic dystonia — the most widely known form of cerebral palsy) and also the other encephalopathies (virus, metabolic, traumatic) children's age which are followed by dystonia of muscles.

Tolperil is issued both in tableted, and in an injection form. One tablet contains active ingredient of Tolperisonum a hydrochloride in a dose of 50 or 150 mg. The injection form represents ampoules with ready solution which 1 ml contains 100 mg of Tolperisonum of a hydrochloride. For simplification of morbidity at pricks in solution the hydrochloride is also added to concentration of 2.5 mg on 1 ml of lidocaine.

Tolperisonum-3-(1-piperidinit)-1-propanon a hydrochloride (2-metil-1-(4 methylphenyl)) - the hydrochloride was synthesized in 1956 and began to be used in clinical practice since 1960 (Tekes K., 2014) for treatment of spasms of skeletal muscles. It is a muscle relaxant of the central action from group of N-cholinolytics. Reduction in the rate of carrying out impulses on primary afferent fibers and motor neurons is the cornerstone of the mechanism of its action. Tolperisonum the hydrochloride modulates ion-exchange processes in the myelinized axons (Hinck D., 2001). Delay of receipt of calcium ions in a synaptic gap leads to secondary oppression of emission of mediators. Stabilization of potential on synaptic membranes and mestnoanesteziruyushchy action is led to blocking spinal mono - and polisinaptichesky reflexes, and in it its mechanism is similar to lidocaine (Fels G., 2006). Thus carrying out exciting impulses on a reticulospinal path is slowed down. Systemically improves peripheric circulation thanks to spasmolytic and anti-adrenergic effects. Besides, for Tolperisonum the antimuskarinovy action is peculiar.

hydrochloride as a part of an injection form is designed to exponentiate membrane stabilizing effect of Tolperisonum and also to facilitate administration of drug.

Tablet Tolpiril after use inside are easily soaked up by a mucous membrane of a small intestine. The C _max active ingredient in blood is reached pretty fast — in 30–60 min., however the bioavailability of medicament is about 20%. It is connected with the fact that Tolperisonum the hydrochloride quickly contacts blood albumine (Rabbani G., 2018) and also his considerable primary metabolism on the way methyl hydroxylation. It is necessary to consider that the bioavailability of Tolperisonum sharply increases practically up to 100% at use together with greasy food (in comparison with medicament use on an empty stomach). Also time of achievement of the C _max medicament in blood to 30 min. lasts, and the _{level C of max} active ingredient increases by 45%. It is finally metabolized by microsomal P450 cytochrome of hepatocytes then hydroxymethyl-Tolperisonum is excreted by kidneys (Dalmadi B., 2003). At the same time the T _½ at reception of the tableted form Tolperil makes about 2.5 h. If the medicament is administered intravenously, the T _½ makes about 90 min.

If at the patient the consciousness and a deglutitory reflex, Tolperil are not broken appoint inside. It is recommended to use medicament after a meal and to wash down with a glass of clear water. It is desirable to combine use of medicament with meal as on an empty stomach medicament is acquired worse.

is selected individually in the range of 150–450 mg/days and is divided into 3 receptions.

For treatment of children at the age of 6–14 years the dose is selected at the rate of 2–4 mg/kg of body weight and is divided into 3 receptions within a day.

can use Drug for treatment of children aged 6 years are younger provided that the mass of their body is more than 30 kg. At the same time the daily dose of medicament makes 5 mg/kg of body weight.

At children's age in cortical and stem cerebral disorders appoint an injection form Tolperil . The medicament is administered or intramusculary in number of 100 mg of active ingredient with an interval of 12 h, or intravenously in a dose of 100 mg of active ingredient bolyusno with a frequency of 1 time/days

Duration of a course of administration of medicament is defined by the attending physician, being guided by the nature of a disease and individual reaction of the patient to drug.

Direct contraindication to reception Tolperil is the myasthenia gravis — the specific decrease in a muscle tone connected with disturbance of transfer of a neuromuscular impulse.

Besides, it is impossible to use medicament at persons with the increased individual sensitivity to amide mestnoanesteziruyushchy means, N-holinoblokatoram or to other components Tolperil .

Relative contraindication to administration of medicament is pregnancy, especially the first 12 weeks. During the II-III trimester of pregnancy Tolperil to appoint admissible when the expected advantage exceeds possible risks. Drug is not used at children with body weight by less than 30 kg.

In a heavy renal or liver failure Tolperil is not appointed as there is information on increase in number of its undesirable side effects.

Considering property Tolperila, as well as other muscle relaxants, to oppress function of respiratory muscles, bronchial asthma is also a relative contraindication to its use.

Knows that Tolperil is characterized by the wide therapeutic index. There are messages as about overdose manifestations (drowsiness, slackness, the dispeptic phenomena) at a daily dose of 300-600 mg, and about lack of symptoms of overdose at single (accidental or intended) reception of 600 mg.

Symptoms of overdose Tolperil include an ataxy, drowsiness, dizziness, toniko-clonic spasms, respiratory depression up to a stop (Sporkert F., 2012). As specific antidotes are absent, treatment of overdose assumes gastric lavage, symptomatic therapy and maintenance of vital functions.

At use of Tolperisonum of a hydrochloride are quite often observed various side effects. First of all, it is necessary to consider development of an allergy and reactions of hypersensitivity (Glück J., 2011). Manifestations belong to symptoms of allergic reactions skin (urticaria, rash, an itching) and system (a Quincke's disease, tachycardia, an asthma, a lowering of arterial pressure), up to anaphylactic (Ribi C., 2003). At the same time risk of development of such reactions increases at women with intolerance of other medicaments in the anamnesis.

to patients that at appearance of an allergy the administration of medicament needs to be stopped immediately, to see a doctor. Further it is recommended to pick up medicament with other active ingredients.

In addition, during reception Tolperil I can be observed disorders from other functional systems. Most often note such neurologic disorders: dizziness, general weakness, drowsiness, depression, paresthesias, asthenia, headache, sonitus, disorders of vision.

Collateral influence on a cardiovascular system takes such forms: the speeded-up notable heartbeat, decrease in the ABP, erubescence. Besides, anemia, breath difficulty, the dispeptic phenomena (nausea, vomiting, dryness in a mouth, upper abdomens pain), enuresis, pain/sensation of discomfort in extremities can be observed. At use Tolperil such changes in blood test as decrease in hemoglobin, increase in bilirubin and activity of liver enzymes can arise.

Tolperil in the form of tablets as excipient contains lactose which can cause diarrhea, a meteorism and other manifestations of a lactose intolerance.

Tolperisonum the hydrochloride strengthens effect of niflumovy acid and NPVP therefore at the combined use the decrease in their dose can be required. Especially it belongs to NPVP which are widely applied in musculoskeletal system pathology.

by means of CYP enzyme 2D6, its simultaneous use with medicaments which are metabolized in the same way (metoprolol, nebivolol, desipramine, Perfenazinum, venlafaxin, dextromethorphan, tolterodin, thioridazine), leads to increase in concentration of the last in blood.