Tolperisone
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Pharmacological properties
tolperisone is a central muscle relaxant. the mechanism of action of tolperisone is not fully understood.
It has a high affinity for nervous tissue, reaching the highest concentrations in the brain stem, spinal cord, and peripheral nervous system.
The most significant effect of tolperisone is its inhibitory effect on the spinal reflex pathway. Probably, this effect, combined with an inhibitory effect on the descending pathways, determines 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. Accordingly, the amplitude and frequency of the action potential decreases.
The inhibitory effect on voltage-gated calcium channels is proved. This suggests that tolperisone not only has a membrane-stabilizing effect, but can also inhibit the release of transmitters.
To top it all, tolperisone has weak properties of α-adrenergic antagonists and has an antimuscarinic effect.
Clinical efficacy and safety. The effectiveness of tolperisone in the treatment of muscle spasm after a stroke has been proven.
In a randomized, double-blind, placebo-controlled study in which 120 patients with muscle spasm after a stroke participated in treatment with tolperisone, a significantly significant decrease in spasticity according to the Ashworth scale was noted, which was the main target indicator. According to the general assessment of the effectiveness of the doctor and researchers, tolperisone was superior to placebo (p0.001). The average improvement on the Ashworth scale was 32% in the general population of patients who were prescribed treatment (intention-to-treat, ITT), and 42% in the subgroup of patients who received tolperisone at a dose of 300-450 mg / day. When evaluating functional test scores, the efficacy of tolperisone was also higher than placebo, but the differences were not statistically significant.
In a randomized, double-blind, comparative study of 48 patients with brain damage, the efficacy of tolperisone according to the Barthel index is comparable to the effectiveness of baclofen. At the same time, tolperisone was superior to baclofen in improvement on the Rivermead Motor Assessment Scale (RMAS).
Data on the effectiveness of tolperisone with increased muscle tone in patients with diseases of the musculoskeletal system other than muscle spasm after a stroke are contradictory. Some studies have shown positive results in terms of some tests, while in other studies, the benefits of tolperisone in such diseases have not been identified.
The safety profile of tolperisone is based on data from clinical studies involving patients with increased muscle tone of various etiologies, as well as data from spontaneous reports of adverse reactions.
Pharmacokinetics After oral administration, tolperisone is well absorbed in the small intestine. Cmax in blood plasma is achieved after 0.5-1.5 hours after administration. Due to the significant metabolism of the first pass, the bioavailability of tolperisone is about 20%. Fatty foods increase the bioavailability of the drug after ingestion by approximately 100%, and Cmax in blood plasma - approximately 45% compared with fasting. Time to reach Cmax while increasing by approximately 30 minutes
Tolperisone is extensively metabolized by the liver and kidneys. The drug is almost completely excreted by the kidneys (99%) in the form of metabolites. The pharmacological activity of metabolites is unknown.
T½ tolperisone after iv administration is about 1.5 hours, after oral administration - about 2.5 hours
Preclinical safety data. Based on data from preclinical studies on the pharmacological safety, toxicity with repeated use, genotoxicity, toxic effects on reproductive function, no specific risk to humans was noted.
Effects in preclinical studies were identified only when taken in doses significantly exceeding the maximum permissible doses for humans, which indicates low significance for clinical use.
In rats and rabbits, embryotoxic changes were detected upon oral administration of the drug at doses of 500 mg / kg body weight and 250 mg / kg body weight, respectively. However, these doses are many times higher than the recommended therapeutic doses for humans.
Indications
P-R: muscle spasticity, including post-stroke spasticity, in cases where the injectable form is the method of choice.
Pills: symptomatic treatment of muscle spasm in adults after a stroke.
Application
Rr. for parenteral administration only.
Use in adults only. The drug is administered intramuscularly at 100 mg 2 times a day or as a slow iv injection of 100 mg once a day.
Injection solution cannot be used in children.
The duration of treatment is determined by the doctor depending on the nature of the course of the disease and the effectiveness of the treatment.
Tablets. The drug should be taken after meals with a glass of water. Inadequate food intake may decrease the bioavailability of tolperisone.
Adults: depending on individual needs and tolerance of 150-450 mg / day in 3 divided doses.
Patients with impaired renal function. The experience of using the drug in patients with kidney damage is limited, in this group of patients a higher incidence of adverse events was noted. In this regard, with moderate renal damage, individual dose titration with careful monitoring of the patients condition and monitoring of renal function is recommended. In severe kidney damage, tolperisone is not recommended.
Patients with impaired liver function. The experience of using the drug in patients with liver damage is limited, in this group of patients a higher incidence of adverse events was noted. In this regard, with moderate liver damage, individual dose titration with careful monitoring of the patients condition and monitoring of liver function is recommended. In severe liver damage, tolperisone is not recommended.
Contraindications
Hypersensitivity to the active substance or similar to its chemical composition Eperisone, or to any of the excipients (for solution - also to other amide local anesthetics). myasthenia gravis. lactation period. for solution - also childrens age.
Side effects
The safety profile of tablets containing tolperisone is based on data on more than 12 thousand patients. in accordance with these data, the most frequent adverse reactions such as disorders of the skin and subcutaneous tissue, systemic disorders, disorders of the nervous and digestive systems.
According to post-marketing observation, about 50-60% of cases of adverse reactions associated with taking tolperisone are hypersensitivity reactions. Most of these reactions were not serious and took place on their own. Hypersensitivity reactions that pose a threat to life have occurred in isolated cases.
Adverse reactions are given by organ system classes according to the MedDRA Medical Dictionary of Regulatory Activity using MedDRA frequency definitions: very often (≥1 / 10), often (≥1 / 100, 1/10) infrequently (≥1 / 1000, 1/100) , rarely (≥1 / 10,000, 1/100), very rarely (1/10 000), the frequency is unknown (cannot be estimated from the available data).
| Organ system classes | Often (≥1 / 100, 1/10) | Infrequently (≥1 / 1000, 1/100) | Rarely (≥1 / 10,000, 1/100) | Very rare (1/10 000) |
|---|---|---|---|---|
| On the part of the blood system and lymphatic system | Anemia, lymphadenopathy | |||
| From the immune system | Hypersensitivity reactions, anaphylactic reactions | Anaphylactic shock | ||
| From the side of nutrition and metabolism | Anorexia | Polydipsia | ||
| Mental disorders | Insomnia, sleep disturbance | Decreased activity, depression | Confusion | |
| From the nervous system | Headache, dizziness, drowsiness | Attention disorder, tremors, convulsions, hypoesthesia, paresthesia, lethargy (increased drowsiness) | ||
| On the part of the organ of vision | Visual impairment | |||
| On the part of the organ of hearing and balance | Tinnitus, vertigo (dizziness) | |||
| From the heart | Angina pectoris, tachycardia, decreased blood pressure | Bradycardia | ||
| From the vessels | Arterial hypotension | Hyperemia of the skin | ||
| From the respiratory system, chest and mediastinal organs | Shortness of breath, nosebleeds, shortness of breath | |||
| From the digestive system | Abdominal discomfort, diarrhea, dry oral mucosa, dyspepsia, nausea | Epigastric pain, constipation, flatulence, vomiting | ||
| On the part of the liver and biliary tract | Mild liver damage | |||
| On the part of the skin and subcutaneous tissue | Allergic dermatitis, hyperhidrosis, pruritus, urticaria, rash | |||
| From the musculoskeletal system and connective tissue | Muscle weakness, myalgia, pain in the limbs | Discomfort in limbs | Osteopenia | |
| From the kidneys and urinary tract | Enuresis, proteinuria | |||
| General disorders and complications at the place of reference | Hyperemia of the skin at the injection site | Asthenia, discomfort, fatigue | Sensations of intoxication, sensation of heat, irritability, thirst | Chest discomfort |
| Laboratory indicators | A decrease in blood pressure, an increase in the concentration of bilirubin in the blood, a change in the activity of liver enzymes, a decrease in the number of platelets, leukocytosis | Increased blood creatinine concentration |
The frequency is unknown (cannot be determined from the available data) - changes in the injection site.
special instructions
The injection form of the drug is not prescribed for children!
Hypersensitivity reactions. In the post-marketing period, with the use of tolperisone, hypersensitivity reactions were most often observed. Their severity varies from mild skin reactions to severe systemic reactions, including anaphylactic shock. Symptoms of hypersensitivity reactions may include erythema, rash, urticaria, pruritus, angioedema, tachycardia, arterial hypotension, or shortness of breath.
Women with a history of hypersensitivity to other drugs or allergic conditions have a higher risk of hypersensitivity reactions when taking tolperisone.
Patients should be advised to closely monitor their condition to identify possible symptoms of allergies. Patients should be aware that when allergy symptoms appear, stop taking tolperisone and seek medical help immediately.
After an episode of hypersensitivity to tolperisone, the drug cannot be re-prescribed.
The tablet preparation contains lactose monohydrate. With lactose intolerance, Sami lactase deficiency (Lapp lactase deficiency) or glucose-galactose malabsorption, this drug should not be used.
The drug in the form of a solution contains lidocaine, therefore, with known hypersensitivity to lidocaine and other amide local anesthetics, Midokalm for injection should not be used due to the possibility of developing cross-allergic reactions.
Use during pregnancy and lactation. According to animal studies, tolperisone does not have a teratogenic effect.
Due to the lack of significant clinical data on the use of this drug, Midokalm should not be used during pregnancy.
Since it is not known whether tolperisone passes into breast milk, the use of the drug Midocal during lactation is contraindicated.
Children. Solution for injection Midokalm not used in children. The safety and effectiveness of the drug in the form of tablets in children has not been studied.
The ability to influence the reaction rate when driving vehicles and working with other mechanisms. Given the possibility of developing symptoms such as dizziness, drowsiness, impaired attention, epilepsy, blurred vision, the drug should be used with caution when driving vehicles or working with other mechanisms.
Interactions
Pharmacokinetic studies of drugs
938 Items
2020-07-30
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