Instructions for use Mydocalm film-coated tablets 150 mg No. 30
Composition
active ingredient: tolperisone hydrochloride;
1 film-coated tablet contains 150 mg of tolperisone hydrochloride;
excipients:
core: citric acid, monohydrate; colloidal anhydrous silica; stearic acid; talc; microcrystalline cellulose; corn starch; lactose monohydrate;
shell: colloidal anhydrous silica; titanium dioxide (E 171); lactose monohydrate; macrogol 6000; hypromellose.
Dosage form
Film-coated tablets.
Main physicochemical properties: white or almost white, round, biconvex tablets, film-coated, with a characteristic odor, engraved with "150" on one side.
Pharmacotherapeutic group
Muscle relaxants with a central mechanism of action.
ATX code M03V X04.
Pharmacological properties
Pharmacodynamics
Tolperisone is a centrally acting 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 brainstem, spinal cord, and peripheral nervous system.
The most significant effect of tolperisone is its inhibitory effect on the spinal reflex pathway. It is likely that this effect, together with the inhibitory effect on the descending pathways, determines the therapeutic benefit 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 are reduced.
It has been shown to have an inhibitory effect on voltage-gated calcium channels. It is assumed that in addition to its membrane-stabilizing effect, tolperisone may also inhibit mediator release.
To top it all off, tolperisone has some weak alpha-adrenergic antagonist properties and exerts antimuscarinic effects.
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 trial of 120 patients with post-stroke muscle spasm, tolperisone treatment resulted in a highly significant reduction in the primary endpoint of spasticity on the Ashworth scale. Tolperisone was superior to placebo in the overall physician and investigator efficacy assessment (p < 0.001). The mean improvement on the Ashworth scale was 32% in the overall intention-to-treat (ITT) population and 42% in the subgroup of patients receiving tolperisone 300–450 mg/day. Tolperisone was also superior to placebo in functional tests, but the differences were not statistically significant.
In a randomized, double-blind, comparative study of 48 patients with brain injury, the efficacy of tolperisone on the Barthel index was comparable to that of baclofen. At the same time, tolperisone was superior to baclofen in improving the Rivermead Motor Assessment Scale (RMAS).
The evidence for the efficacy of tolperisone in treating increased muscle tone in patients with musculoskeletal conditions other than post-stroke muscle spasm is conflicting. Some studies have reported positive results on some tests, while others have failed to show any benefit of tolperisone in these conditions.
The safety profile of tolperisone is based on data from clinical studies involving patients with increased muscle tone of various etiologies, as well as on data from spontaneous reports of adverse reactions.
Pharmacokinetics
After oral administration, tolperisone is well absorbed in the small intestine. The maximum concentration of the drug in plasma is reached 0.5-1.5 hours after administration. Due to the significant first-pass metabolism, the bioavailability of tolperisone is approximately 20%. Fatty food increases the bioavailability of the drug after oral administration by approximately 100%, and the maximum plasma concentration by approximately 45% compared to fasting. The time to reach the maximum concentration increases by approximately 30 minutes.
Tolperisone is extensively metabolized by the liver and kidneys.
The drug is almost completely excreted by the kidneys (more than 99%) in the form of metabolites.
The pharmacological activity of metabolites is unknown.
The half-life of tolperisone after intravenous administration is about 1.5 hours, after oral administration - about 2.5 hours.
Preclinical safety data
Based on non-clinical data on safety pharmacology, repeated dose toxicity, genotoxicity, and toxicity to reproduction, no specific risk to humans was identified.
Embryotoxic changes were observed in rats and rabbits at oral 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 dose for humans.
Indication
Symptomatic treatment of muscle spasm in adults after stroke.
Contraindication
Hypersensitivity to the active substance or to a chemically similar substance, eperisone, or to any of the excipients. Myasthenia gravis. Breastfeeding.
Interaction with other medicinal products and other types of interactions
Pharmacokinetic studies of drug interactions with dextromethorphan, a CYP2D6 substrate, have demonstrated that co-administration of tolperisone increases plasma concentrations of drugs that are predominantly metabolized by cytochrome CYP2D6, in particular concentrations of thioridazine, tolterodine, venlafaxine, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine.
In vitro studies in human liver microsomes and hepatocytes did not reveal significant inhibition or induction of other CYP isoenzymes (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP1A2, CYP3A4).
It is expected that co-administration with other CYP2D6 substrates and/or other drugs will not increase exposure to tolperisone, due to the diversity of tolperisone metabolic pathways.
When taking tolperisone on an empty stomach, its bioavailability is reduced, therefore, when prescribing the drug, it is recommended to take into account the relationship with food intake.
Although tolperisone is a centrally acting drug, the likelihood of developing a sedative effect when using it is low. In the case of simultaneous administration with other centrally acting muscle relaxants, it is necessary to consider reducing the dose of tolperisone.
Tolperisone potentiates the effects of niflumic acid, therefore, when taken simultaneously with tolperisone, it is advisable to reduce the dose of niflumic acid, as well as other NSAIDs.
Application features
Hypersensitivity reactions
In the post-marketing period, the most frequently observed adverse reactions with tolperisone were hypersensitivity reactions. Their severity ranged from mild skin reactions to severe systemic reactions, including anaphylactic shock. Symptoms of hypersensitivity reactions may include erythema, rash, urticaria, pruritus, angioedema, tachycardia, hypotension or dyspnoea.
Women with a history of hypersensitivity to other drugs or allergic conditions are at higher risk of hypersensitivity reactions when taking tolperisone.
Patients should be advised to be vigilant for possible symptoms of allergy. Patients should be informed that if symptoms of allergy occur, they should stop taking tolperisone and seek immediate medical attention.
After an episode of hypersensitivity to tolperisone, the drug should not be re-administered.
This medicine contains lactose monohydrate. Patients with lactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Ability to influence reaction speed when driving vehicles or 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 or working with other mechanisms.
Use during pregnancy or breastfeeding
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, Mydocalm should not be used during pregnancy.
Since it is not known whether tolperisone passes into breast milk, the use of Mydocalm during breastfeeding is contraindicated.
Method of administration and doses
The drug should be taken after meals, with 1 glass of water. Insufficient food intake may reduce the bioavailability of tolperisone.
Adults: depending on individual needs and tolerance - 150-450 mg per day in 3 divided doses.
Patients with renal impairment
Experience in patients with renal impairment is limited, and a higher incidence of adverse effects has been reported in such patients. Therefore, in patients with moderate renal impairment, individual dose titration with careful monitoring of the patient's condition and renal function is recommended. In patients with severe renal impairment, tolperisone is not recommended.
Patients with liver dysfunction
Experience with the use of the drug in patients with liver damage is limited, a higher frequency of adverse events was noted in such patients. In this regard, in moderate liver damage, individual dose titration with careful monitoring of the patient's condition and control of liver function is recommended. In severe liver damage, tolperisone is not recommended.
Children
The safety and effectiveness of tolperisone in children have not been studied.
Overdose
Symptoms of overdose may mainly include drowsiness, gastrointestinal symptoms (nausea, vomiting, epigastric pain), tachycardia, hypertension, bradykinesia and vertigo. In severe cases, convulsions and coma have been reported.
There is no specific antidote for tolperisone. In case of overdose, symptomatic treatment is recommended.
Adverse reactions
The safety profile of tolperisone tablets is based on data from more than 12,000 patients. According to these data, the most common adverse reactions were skin and subcutaneous tissue disorders, systemic disorders, nervous system disorders and digestive system disorders.
According to post-marketing surveillance, approximately 50-60% of adverse reactions associated with tolperisone are hypersensitivity reactions. Most of these reactions were minor and self-limiting. Life-threatening hypersensitivity reactions have occurred in isolated cases.
Adverse reactions are listed by system organ class according to the MedDRA Medical Dictionary of Regulatory Activities using the following MedDRA frequency definitions: uncommon (≥ 1/1000, < 1/100), uncommon (≥ 1/10,000, < 1/1000), rare (< 1/10,000), unknown frequency (cannot be estimated from the available data).
| Organ system classes | Infrequent (≥1/1000, <1/100) | Single (≥1/10000, <1/1000) | Rare (<1/10000) |
| Blood and lymphatic system disorders | | | Anemia Lymphadenopathy |
| Immune system disorders | | Hypersensitivity reaction Anaphylactic reaction | Anaphylactic shock |
| Nutritional and metabolic disorders | Anorexia | | Polydipsia |
| Mental disorders | Insomnia Sleep disturbances | Decreased activity Depression | Confusion of consciousness |
| Nervous system disorders | Headache Dizziness Drowsiness | Attention deficit disorder Tremor Convulsions Hypoesthesia Paresthesia Lethargy (increased drowsiness) | |
| Visual impairment | | Vision impairment | |
| Hearing and balance disorders | | Tinnitus Vertigo | |
| Cardiac disorders | | Angina pectoris Tachycardia Rapid heartbeat Lowering blood pressure | Bradycardia |
| Vascular disorders | Hypotension | Skin hyperemia | |
| Respiratory, thoracic and mediastinal disorders | | Difficulty breathing Nosebleed Rapid breathing | |
| Gastrointestinal disorders | Feeling of discomfort in the stomach Diarrhea Dryness of the oral mucosa Dyspepsia Nausea | Epigastric pain Constipation Flatulence Vomiting | |
| Liver and biliary tract disorders | | Mild liver damage | |
| Skin and subcutaneous tissue disorders | | Allergic dermatitis Hyperhidrosis Itch Urticaria Rash | |
| Musculoskeletal and connective tissue disorders | Muscle weakness Myalgia Pain in the extremities | Feeling of discomfort in the extremities | Osteopenia |
| Renal and urinary disorders | | Enuresis Proteinuria | |
| General disorders and administration site conditions | Asthenia Discomfort Increased fatigue | Feeling intoxicated Feeling hot Irritability Thirst | Feeling of discomfort in the chest |
| Laboratory indicators | | Lowering blood pressure Increased bilirubin concentration in the blood Change in liver enzyme activity Decreased platelet count Leukocytosis | Increased creatinine concentration in the blood |
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 30 °C.
Keep the medicine out of the reach of children!
Packaging
10 tablets in a blister; 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
JSC "Gedeon Richter".
Location of the manufacturer and its business address
H-1103, Budapest, Demrei Street 19-21, Hungary.
