Sirdalud MR, 6 mg 30 pcs

Pharmgroup:

Myorelaxant of central action.

Pharmic action:

Tizanidine is a centrally acting muscle relaxant. Its main point of action is in the spinal cord. By stimulating presynaptic α2-receptors in the spinal cord, tizanidine suppresses release of excitatory amino acids which stimulate NMDA-receptors. As a consequence, polysynaptic excitation transmission is inhibited at the level of intermediate spinal cord neurons. Since it is this mechanism that is responsible for excess muscle tone, when it is suppressed, muscle tone is reduced. In addition to its myorelaxant properties, tizanidine also has a moderately pronounced central analgesic effect.

Sirdalud® is effective for both acute painful muscle spasm and chronic spasticity of spinal and cerebral genesis. It reduces spasticity and clonic spasms, as a result of which resistance to passive movements decreases and the volume of active movements increases.

The myorelaxant effect (as measured with the Ashworth scale and pendulum test) and adverse effects (decrease in HR and BP) of Sirdalud® depend on the plasma concentration of the drug.

Pharmacokinetics:

Intake

Tizanidine is absorbed rapidly and almost completely. Cmax in plasma is reached approximately 1 h after taking the drug. Because of the pronounced metabolism during “first passage” through the liver, the average bioavailability is about 34%.

The cmax of tizanidine is 12.3 ng/ml and 15.6 ng/ml after single and multiple doses of tizanidine at a dose of 4 mg, respectively.
Simultaneous intake of food does not affect pharmacokinetics of tizanidine. Although the Cmax value increases by 1/3 when the tablet is taken after a meal, this is not considered to be clinically significant. There is no significant effect on absorption (AUC). Tizanidine in the dose range from 1 mg to 20 mg has linear pharmacokinetics.

Distribution

The binding to plasma proteins is 30%.

Metabolism

Tizanidine is rapidly and largely (about 95%) metabolized in the liver. In vitro it has been shown that tizanidine is mainly metabolized by cytochrome P450 system isoenzyme 1A2. The metabolites are inactive.

The average T1/2 of tizanidine from the systemic bloodstream is 2-4 hours. The drug is excreted primarily by the kidneys (approximately 70% of the dose) as metabolites; a share of unchanged substance is only about 4.5%.

Pharmacokinetics in special clinical cases

. In patients with renal insufficiency (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 h, which leads to increased (approximately 6-fold) systemic bioavailability of tizanidine (measured by AUC)

Pharmacokinetics of tizanidine/p>

There have been no specific studies in patients with impaired liver function.

Tizanidine is primarily metabolized in the liver, by cytochrome CYP1A2; therefore, impairment of liver function may increase systemic exposure to the drug.

There are limited data on pharmacokinetics in patients over 65 years of age.

Gender has no effect on the pharmacokinetic properties of tizanidine.

The effect of ethnicity and race on the pharmacokinetics of tizanidine has not been studied.

Indications

Active ingredient

Composition

1 capsule contains:

the active ingredient:

tizanidine (in hydrochloride form) 6 mg

How to take, the dosage

Sirdalud MR is taken orally.

The dosing regimen should be determined individually.

The initial daily dose is 6 mg (1 capful).

If necessary, the daily dose can be gradually (“steps”) increased – by 6 mg (1 capful) at 3-7 day intervals.

Clinical experience shows that for most patients the optimal dose is 12 mg/day (2 capsules); in rare cases an increase in the daily dose to 24 mg may be required.

Interaction

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

The concomitant use may result in clinically significant and prolonged BP reduction leading to drowsiness, dizziness, and slow psychomotor reactions. Co-administration of tizanidine with other CYP1A2 inhibitors – antiarrhythmic drugs (amiodarone, mexiletine, propafenone), cimetidine, fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives, ticlopidine is not recommended.

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

Special Instructions

Hepatic dysfunction associated with tizanidine has been reported, but rarely when using a daily dose up to 12 mg. In this regard, it is recommended that liver function tests be monitored once a month during the first 4 months of treatment in patients receiving tizanidine at a daily dose of 12 mg or higher, as well as in cases where clinical signs suggestive of liver dysfunction, such as unexplained nausea, anorexia, and fatigue, are observed. If serum ALT and ACT levels are persistently above the upper limit of normal by a factor of 3 or more, Sirdalud should be discontinued.

Because Sirdalud tablets contain lactose, it is not recommended for use in patients with rare hereditary galactose intolerance, severe lactase deficiency, or glucose/galactose malabsorption.

Impact on the ability to drive and operate machinery.

Patients who experience drowsiness or dizziness should refrain from activities requiring high concentration and quick reactions, such as driving vehicles or operating machinery.

Contraindications

Cautions
Simultaneous use of Sirdalud with CYP1A2 inhibitors is not recommended.

Side effects

Cardiovascular system: often – bradycardia, decreased blood pressure.

Gastrointestinal tract: often – dry mouth; rarely – nausea, gastrointestinal disorders.

Liver disorders: rare – increased liver transaminase activity, very rare – hepatitis.

Skeletal and muscular system: rare – muscle weakness.

Others: often – fatigue.

When taking low doses recommended to relieve painful muscle spasm, drowsiness, fatigue, dizziness, dry mouth, decreased blood pressure (BP), nausea, gastrointestinal disturbances, increased liver transaminase activity have been reported. Usually the above described adverse reactions are moderate and transient.

When taking higher doses recommended for the treatment of spasticity, the above adverse reactions occur more frequently and are more severe, but they are rarely so severe that treatment has to be interrupted. In addition, the following may occur: decreased BP, bradycardia, muscle weakness, insomnia, sleep disturbances, hallucinations, and hepatitis.

Overdose

There have been several reports of Cirdalud overdose to date, including a case where the dose taken was 400 mg. In all cases, recovery has been uneventful.

Symptoms: nausea, vomiting, decreased BP, dizziness, drowsiness, miosis, restlessness, respiratory distress, coma.

Treatment. Multiple administration of activated charcoal is recommended for elimination of the drug from the body. Forced diuresis may also accelerate excretion of Sirdalud. Subsequently, symptomatic treatment is carried out.

Pregnancy use

Since there have been no controlled studies of tizanidine use in pregnant women, it should not be used during pregnancy unless the potential benefit exceeds the possible risk.

Tizanidine is excreted with breast milk in insignificant amounts, however, women breast-feeding children should not use the drug.

Similarities