Instructions Tizalud tablets 2 mg blister No. 30
Composition
active ingredient: tizanidine;
1 tablet contains tizanidine 2 mg;
excipients: microcrystalline cellulose, anhydrous lactose, colloidal anhydrous silicon dioxide, stearic acid.
Dosage form
Pills.
Main physicochemical properties: round tablets with a flat surface with beveled edges and a score, white or almost white in color.
Pharmacotherapeutic group
Centrally acting muscle relaxants. ATX code M03B X02.
Pharmacological properties
Pharmacodynamics
Tizanidine is a centrally acting skeletal muscle relaxant. Its primary site of action is the spinal cord. By stimulating presynaptic α2-adrenoceptors, it inhibits the release of amino acids that stimulate N-methyl-D-aspartate receptors (NMDA receptors). As a result, polysynaptic signaling at the level of interneuronal connections in the spinal cord, which is responsible for excessive muscle tone, is inhibited, and muscle tone is reduced. Tizanidine is effective in both acute painful muscle spasms and chronic spasticity of spinal and cerebral origin. It reduces resistance to passive movements, suppresses spasm and clonic seizures, and improves the strength of active muscle contractions.
Pharmacokinetics
Absorption and distribution. Tizanidine is rapidly absorbed. Peak plasma concentrations are reached approximately 1 hour after administration. The mean absolute bioavailability is 34%. The mean steady-state volume of distribution (Vss) after intravenous administration is 2.6 L/kg. Plasma protein binding is 30%.
The relatively low inter-patient variation in pharmacokinetic parameters (Cmax and AUC) facilitates reliable preliminary estimation of plasma levels after oral administration.
Metabolism/Excretion: The drug undergoes rapid and extensive metabolism in the liver.
Tizanidine is metabolized in vitro mainly by CYP1A2. The metabolites are inactive. They are excreted mainly by the kidneys (70%). The elimination of total radioactivity (i.e., parent compound and metabolites) is biphasic, with a rapid initial phase (half-life t1/2 = 2.5 hours) and a slower elimination phase (t1/2 = 22 hours). Only a small amount of parent compound (about 2.7%) is excreted by the kidneys. The mean half-life of parent compound is 2-4 hours.
Pharmacokinetics in specific patient groups. In patients with renal insufficiency (creatinine clearance less than 25 ml/min), the average maximum plasma concentration is 2 times higher than in healthy volunteers, and the terminal half-life is prolonged to approximately 14 hours, resulting in an average 6-fold increase in the area under the concentration-time curve (AUC).
Studies in patients with hepatic impairment have not been conducted.
Tizanidine is metabolized by the CYP1A2 isoenzyme in the liver. Patients with impaired liver function may experience higher plasma concentrations of the substance.
Tizalud is contraindicated in patients with severe hepatic impairment.
Pharmacokinetic data in elderly patients are limited.
Gender does not affect the pharmacokinetic properties of tizanidine.
The effect of ethnicity and race on the pharmacokinetics of tizanidine has not been studied.
Food effects. Concomitant food intake does not affect the pharmacokinetic profile of Tizalud tablets. Although the maximum concentration value increases by one third, this is not clinically significant. No significant effect on absorption was observed.
Indication
Painful muscle spasm. Spasticity due to multiple sclerosis. Spasticity due to spinal cord injuries. Spasticity due to brain injuries.
Contraindication
Hypersensitivity to tizanidine or to any of the excipients of the drug. Severe hepatic impairment. Concomitant use of tizanidine with potent CYP1A2 inhibitors such as fluvoxamine or ciprofloxacin.
Interaction with other medicinal products and other types of interactions
Concomitant use of known CYP1A2 inhibitors may increase tizanidine plasma levels. Increased tizanidine plasma levels may lead to symptoms of overdose, such as QT prolongation.
Concomitant use of known CYP1A2 inducers may reduce tizanidine plasma levels. Decreased tizanidine plasma levels may lead to a reduced therapeutic effect of Tizalud.
Concomitant use of tizanidine with other CYP1A2 inhibitors, such as antiarrhythmics (amiodarone, mexiletine, propafenone), cimetidine, some fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives and ticlopidine, is not recommended. Increased plasma levels of tizanidine may cause symptoms of overdose, including QT prolongation.
Concomitant use of Tizanidine with antihypertensive drugs, including diuretics, may occasionally cause hypotension and bradycardia. Rebound hypertension and rebound tachycardia have been observed in some patients receiving concomitant antihypertensive drugs when tizanidine is abruptly withdrawn. In isolated cases, rebound hypertension may lead to stroke.
Concomitant use of Tizanidine with rifampicin may result in a 50% decrease in tizanidine concentrations. Thus, the therapeutic effect may be reduced when rifampicin is used during Tizanidine therapy, which may be clinically significant in some patients. Prolonged concomitant use should be avoided, and if necessary, dosage adjustments should be made with great caution.
The use of the drug Tizalud leads to a 30% reduction in the systemic exposure of tizanidine in men who smoke (more than 10 cigarettes per day). Long-term use of the drug in men who smoke a lot requires the appointment of higher doses of the drug.
The simultaneous use of the drug Tizalud and other centrally acting drugs (for example, sedatives and hypnotics (benzodiazepine or baclofen), some antihistamines and analgesics, psychotropic drugs, narcotic drugs) may enhance the effects of each drug and enhance the hypnotic effect of Tizalud. This applies, in particular, to the simultaneous use of alcohol, which may unpredictably change or enhance the effect of Tizalud and increase the risk of adverse reactions, so you should refrain from drinking alcohol.
The use of Tizalud with α2-adrenergic agonists (e.g. clonidine) should be avoided due to their potential additive hypotensive effect.
Application features
Concomitant use of CYP1A2 inhibitors with tizanidine is not recommended.
After abrupt withdrawal of the drug or rapid dose reduction, patients may experience hypertension and tachycardia. In some cases, such rebound hypertension may lead to stroke. Tizanidine treatment should not be discontinued abruptly, but only by gradually reducing the dose.
For patients with renal insufficiency (creatinine clearance < 25 ml/min), the recommended initial dose is 2 mg once daily. The dose should be increased gradually, in small "steps", taking into account efficacy and tolerability. To achieve a more pronounced effect, it is recommended to first increase the dose, which is prescribed 1 time per day, and then increase the frequency of administration.
Hepatic failure has been reported with tizanidine, but has been rare in patients receiving daily doses up to 12 mg. Therefore, it is recommended that liver function be monitored monthly for the first four months of therapy in patients receiving tizanidine at doses of 12 mg or higher and in patients with clinical symptoms suggestive of hepatic failure (e.g. nausea, loss of appetite, or unexplained fatigue). Tizanidine should be discontinued if serum ALT or AST levels exceed 3 times the upper limit of normal for a prolonged period.
Hypotension may occur during the use of tizanidine, as well as as a result of drug interactions with CYP1A2 inhibitors and/or antihypertensive drugs.
Severe forms of arterial hypotension, such as loss of consciousness and circulatory collapse, have been reported.
Caution should be exercised when using this medicinal product with drugs that prolong the QT interval (e.g. cisapride, amitriptyline, azithromycin).
Caution is required in patients with ischemic heart disease and/or heart failure. ECG monitoring should be performed at regular intervals when initiating Tizalud in such patients.
Before using this medicine in patients with myasthenia gravis, the risk-benefit ratio should be carefully assessed.
Experience in children and adolescents is limited, therefore the use of Tizalud is not recommended in this category of patients.
Caution should be exercised when using this medicine in elderly patients.
Tizalud tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Tizalud tablets.
Ability to influence reaction speed when driving vehicles or other mechanisms
Tizanidine may cause drowsiness, dizziness and/or hypotension, thus impairing the patient's ability to drive or operate machinery.
The risks increase with simultaneous alcohol consumption.
Therefore, you should refrain from activities that require high concentration of attention and quick reactions, such as driving vehicles or working with machines and mechanisms.
Use during pregnancy or breastfeeding
Pregnancy. Data on the use of Tizalud in pregnant women are limited, therefore it should not be prescribed during pregnancy, except in cases where the potential benefit to the mother outweighs the possible risk to the fetus.
Breastfeeding. It has been established that tizanidine penetrates into breast milk in small amounts. Therefore, the drug should not be prescribed to women who are breastfeeding.
Fertility: Available data indicate that tizanidine administered at doses of 10 mg/kg/day to male rats and 3 mg/kg/day to female rats did not impair fertility. Impaired fertility was observed in male rats administered tizanidine at doses of 30 mg/kg/day and in female rats administered tizanidine at doses of 10 mg/kg/day. Sedation, weight loss, and ataxia were also observed at these doses.
Method of administration and doses
Tizalud has a narrow therapeutic range and high variability of tizanidine plasma concentrations in different patients. Therefore, it is important to use optimal doses according to the patient's needs. Treatment should be started with a low dose of 2 mg, which makes the risk of undesirable effects from taking the drug minimal. If necessary, the dose of the drug should be gradually increased, observing all necessary precautions.
Adults
Relieving painful muscle spasms
Use 2-4 mg 3 times daily. In severe cases, an additional dose of 2 or 4 mg may be taken at bedtime.
Spasticity in neurological disorders
The dose must be selected individually for each patient.
The initial daily dose should not exceed 6 mg, divided into 3 doses. It can be increased to 2-4 mg twice gradually at intervals of 3-7 days. Usually the optimal therapeutic effect is achieved with a daily dose of 12-24 mg, divided into 3 or 4 doses.
The total daily dose of 36 mg should not be exceeded.
Special patient populations
Use in children and adolescents
Experience with the use of Tizalud in children and adolescents is limited, therefore the drug is not recommended for use in children and adolescents.
Use in elderly patients
Experience with the use of the drug in elderly patients is limited, therefore caution should be exercised when using Tizalud in this category of patients. It is recommended to start treatment with the lowest dose and gradually increase it with caution in "small steps" until the optimal ratio of individual tolerability and therapeutic efficacy of the drug is achieved.
Use in patients with renal impairment
For patients with impaired renal function (CC < 25 ml/min), the recommended initial single daily therapeutic dose is 2 mg. The dose should be increased gradually and with caution in small steps, until the optimal ratio of individual tolerability and therapeutic efficacy of the drug is achieved. In order to increase therapeutic efficacy, a single dose should first be increased before switching to a more frequent daily dose.
Use in patients with impaired liver function
Treatment of patients with severe liver dysfunction is contraindicated. Tizalud is extensively metabolized in the liver. The drug should be used with caution in the treatment of patients with moderately impaired liver function. Treatment should be initiated at the lowest dosage; possible dose increases should be made with caution and taking into account the patient's individual tolerance to Tizalud.
Treatment interruption
If it is necessary to discontinue treatment with the drug, the dose should be reduced slowly and gradually. This is especially true for patients who have been receiving an increased dose of the drug for a long time. This reduces the risk of developing a rebound increase in blood pressure and tachycardia.
Children
Experience with the use of the drug in pediatrics is limited. Tizalud is not recommended for use in children.
Overdose
Very few reports of overdose with Tizalud have been received.
Symptoms: nausea, vomiting, hypotension, bradycardia, QT prolongation, dizziness, miosis, respiratory distress, coma, restlessness, drowsiness.
Treatment: multiple high-dose administration of activated charcoal is recommended to remove the drug from the body. Forced diuresis may accelerate drug elimination. Symptomatic treatment should be continued.
Adverse reactions
Adverse reactions – such as drowsiness, fatigue, dizziness, dry mouth, low blood pressure, nausea, gastrointestinal disturbances and increased serum transaminase levels – are usually mild and transient in patients taking the low doses recommended for the relief of painful muscle spasm.
At doses higher than those recommended for the treatment of spasticity, the above adverse reactions occur more frequently and more pronouncedly, but they are rarely serious enough to require discontinuation of treatment. The following adverse reactions may also occur: hypotension, bradycardia, muscle weakness, sleep disturbances, hallucinations and hepatitis.
The occurrence of such symptoms has been reported after abrupt withdrawal of tizanidine, particularly after long-term treatment and/or high daily doses and/or concomitant therapy with antihypertensive drugs. In such circumstances, patients may develop hypertension and tachycardia. In isolated cases, such rebound hypertension may lead to stroke. Therefore, treatment with tizanidine should not be discontinued abruptly, but only by gradual dose reduction.
Psychiatric: insomnia, sleep disorders; hallucinations.
From the side of the central nervous system: drowsiness, dizziness; confusion, vertigo.
Cardiovascular system: hypotension; bradycardia; syncope.
Gastrointestinal: dry mouth, gastrointestinal pain, gastrointestinal disorders; nausea.
On the part of the hepatobiliary system: increased serum transaminase levels; acute hepatitis, liver failure.
Musculoskeletal system: muscle weakness.
General disorders: increased fatigue; asthenia, withdrawal syndrome, possible occurrence of hypersensitivity reactions.
From the organs of vision: blurred vision.
Investigations: decreased blood pressure, increased transaminase levels.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
JSC "KYIV VITAMIN FACTORY".
Location of the manufacturer and its business address
04073, Ukraine, Kyiv, Kopylivska St., 38.
