Sirdalud (Tizanidine)

1 tablet contains: 

Tizanidine is a central muscle relaxant. The main point of application of its action is in the spinal cord. By stimulating presynaptic α2 receptors in the spinal cord, tizanidine inhibits the release of excitatory amino acids that stimulate NMDA receptors. 

As a result, the polysynaptic transmission of excitation is suppressed at the level of intermediate neurons of the spinal cord. Since it is this mechanism that is responsible for excess muscle tone, when it is suppressed, muscle tone decreases. In addition to muscle relaxant properties, tizanidine also has a mild central analgesic effect.

Sirdalud® is effective both in acute painful muscle spasm and in chronic spasticity of spinal and cerebral origin. Reduces spasticity and clonic convulsions, as a result of which resistance to passive movements decreases and the volume of active movements increases.

The muscle relaxant effect (measurement on the Ashworth scale and using the “pendulum” test) and side effects (decrease in heart rate and blood pressure) of Sirdalud® preparation depend on the concentration of the drug in blood plasma.

Pharmacokinetics

Suction

Tizanidine is absorbed rapidly and almost completely. Cmax in plasma is reached approximately 1 hour after taking the drug. Due to the pronounced metabolism during the "first passage" through the liver, the average bioavailability is about 34%.

The max of tizanidine is 12.3 ng / ml and 15.6 ng / ml after a single and multiple doses of tizanidine in a dose of 4 mg, respectively.

Simultaneous eating does not affect the pharmacokinetics of tizanidine. Although the Cmax value increases by 1/3 when the pill is taken after meals, it is believed that this is not clinically significant. Significant effect on absorption (AUC) is not observed. Tizanidine in the dose range from 1 mg to 20 mg has a linear pharmacokinetics.

Distribution

Plasma protein binding is 30%.

Metabolism

Tizanidine is rapidly and to a large extent (about 95%) metabolized in the liver. In vitro, it was shown that tizanidine is mainly metabolized by the isoenzyme 1A2 of the cytochrome P450 system. Metabolites are inactive.

Breeding

The average T1 / 2 value of tizanidine from the systemic circulation is 2-4 hours. The drug is excreted mainly by the kidneys (approximately 70% of the dose) in the form of metabolites; unchanged substance accounts for only about 4.5%.

Pharmacokinetics in special clinical cases

In patients with renal failure (creatinine clearance ≤ 25 ml / min), the average Cmax of the drug in plasma is 2 times higher than in healthy volunteers, and the final T1 / 2 reaches 14 hours, which leads to an increased (about 6 times) systemic bioavailability tizanidine (measured by AUC) /

No specific studies have been conducted in patients with impaired liver function.

Tizanidine is predominantly metabolized in the liver by cytochrome CYP1A2, therefore, impaired liver function can lead to increased systemic exposure to the drug.

Pharmacokinetics data for patients over 65 years of age are limited.

Sex does not affect the pharmacokinetic properties of tizanidine.

The effect of ethnic and racial affiliation on the pharmacokinetics of tizanidine has not been studied.

• Painful muscle spasms in diseases of the spine (including osteochondrosis, spondylosis, syringomyelia, hemiplegia, cervical and lumbar syndromes); 

• After surgery for a herniated disc or osteoarthritis of the thigh,

• Spastic state of skeletal muscles caused by neurological diseases: multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, cerebrovascular accident, stroke, craniocerebral trauma, cerebral palsy, seizures of central origin.

Impaired liver function, hypersensitivity to the drug Sirdalud.

From the cardiovascular system: often - bradycardia, lowering blood pressure.

From the gastrointestinal tract: often - dry mouth; rarely - nausea, gastrointestinal upset.

On the part of the liver: rarely - increased activity of hepatic transaminases, very rarely - hepatitis.

From the musculoskeletal system: rarely - muscle weakness.

Other: often - fatigue.

When taking small doses recommended for the relief of painful muscle spasm, drowsiness, fatigue, dizziness, dry mouth, decreased blood pressure (BP), nausea, gastrointestinal upsets, increased liver transaminases were noted. Usually the above-described adverse reactions are mild and transient.

When taking the higher doses recommended for the treatment of spasticity, the above side reactions occur more often and are more pronounced, but they are rarely so severe that the treatment had to be interrupted. In addition, the following phenomena may occur: decreased blood pressure, bradycardia, muscle weakness, insomnia, sleep disturbances, hallucinations, hepatitis.

The simultaneous use of tizanidine with fluvoxamine or ciprofloxacin, which are inhibitors of cytochrome P450 1A2, is contraindicated. The simultaneous use of tizanidine with fluvoxamine or ciprofloxacin leads to a 33-fold or 10-fold increase in the AUC of tizanidine, respectively.

The result of the combined use may be a clinically significant and prolonged decrease in blood pressure, leading to drowsiness, dizziness, inhibited psychomotor reactions. The simultaneous administration of tizanidine with other inhibitors of CYP1A2 antiarrhythmic drugs (amiodarone, mexiletine, propafenone), cimetidine, fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives, ticlopid is not recommended.

The simultaneous administration of Sirdalud with antihypertensive drugs, including diuretics, can sometimes cause a decrease in blood pressure and bradycardia. Alcohol or sedatives may increase the sedative effect of Sirdalud.

Inside. The dosage regimen should be selected individually.

With painful muscle spasm, the drug Sirdalud is prescribed in a dose of 2 or 4 mg 3 times a day. In severe cases, 2 or 4 mg may be taken before bedtime.

With skeletal muscle spasticity due to neurological diseases, the dose should be selected individually. The initial daily dose should not exceed 6 mg, divided into 3 doses. The dose can be increased gradually, by 2–4 mg, at intervals of 3-4 to 7 days. Usually, the optimal therapeutic effect is achieved with a daily dose of 12 to 24 mg, divided into 3 to 4 doses at regular intervals. Do not exceed a dose of 36 mg per day.

Use in patients with renal failure. Treatment of patients with renal failure (Cl creatinine

To date, several reports of an overdose of Sirdalud have been received, including the case when the accepted dose was 400 mg. In all cases, the recovery was uneventful.

Symptoms: nausea, vomiting, decreased blood pressure, dizziness, drowsiness, miosis, anxiety, respiratory failure, coma.

Treatment. For the removal of the drug from the body, repeated administration of activated carbon is recommended. Forced diuresis may also accelerate the excretion of Sirdalud. In the future, symptomatic treatment is performed.

Cases of liver dysfunction associated with tizanidine have been reported, however, with a daily dose of up to 12 mg, these cases have been rare. In this regard, it is recommended to monitor functional liver tests once a month in the first 4 months of treatment in those patients who are prescribed tizanidine in a daily dose of 12 mg or higher, as well as in cases where clinical signs are observed suggesting impaired liver function, - such as unexplained nausea, anorexia, feeling tired. In the case when the serum ALT and ACT levels persistently exceed the upper limit of normal by 3 times or more, the use of Sirdalud should be discontinued.

Since lactose is part of Sirdalud tablets, it is not recommended to use the drug in patients with rare hereditary galactose intolerance, with severe lactase deficiency or glucose / galactose malabsorption.

Influence on the ability to drive a car and work with mechanisms. Patients with drowsiness or dizziness should refrain from the types of work that require a high concentration of attention and a quick reaction, for example, driving vehicles or working with machines and mechanisms.

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