Sirdalud MR, modified-release capsules 6mg 30pcs

Composition

1 capsule contains:

Active ingredient:

tizanidine (in the form of hydrochloride) 6 mg

Pharmacological action

Pharmaceutical Group:

a central-acting muscle relaxant.

Pharmaceutical action:  

Tizanidine is a central-acting muscle relaxant. The main point of application of its action is located in the spinal cord. By stimulating presynaptic a2 receptors in the spinal cord, tizanidine suppresses the release of excitatory amino acids that stimulate NMDA receptors. As a result, polysynaptic transmission of arousal is suppressed at the level of intermediate neurons in the spinal cord. Since this mechanism is responsible for excessive muscle tone, when it is suppressed, muscle tone decreases. In addition to its muscle-relaxing properties, tizanidine also has a moderate central analgesic effect.

Sirdalud® is effective for both acute painful muscle spasms and chronic spinal and cerebral spasticity. Reduces spasticity and clonic seizures, which reduces resistance to passive movements and increases the volume of active movements.

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

Pharmacokinetics:  

Suction

Tizanidine is absorbed quickly and almost completely. Cmax in plasma is reached approximately 1 h after taking the drug. Due to the pronounced metabolism during the “first pass” through the liver, the average bioavailability value is about 34%.

The cmax of tizanidine is 12.3 ng / ml and 15.6 ng / ml after a single and multiple 4 mg dose of tizanidine, respectively. Concomitant food intake does not affect the 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

Binding to plasma proteins is 30%.

Metabolism

Tizanidine is rapidly and significantly (about 95%) metabolized in the liver. It has been shown in vitro that tizanidine is mainly metabolized by cytochrome P450 isoenzyme 1 A 2. Metabolites are inactive.

Deduction

The average T1 / 2 value of tizanidine from the systemic circulation is 2-4 hours. The drug is mainly excreted by the kidneys (approximately 70% of the dose) in the form of metabolites; the share of unchanged substance accounts for 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 hours, which leads to an increased (approximately 6-fold) systemic bioavailability of tizanidine (measured by AUC)

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

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

Data on pharmacokinetics in patients over 65 years of age 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.

Indications

• Painful muscle spasms in diseases of the spine (including osteochondrosis, spondylosis, syringomyelia, hemiplegia, cervical and lumbar syndromes);
• After surgery for a herniated disc or hip osteoarthritis,
• Spastic state of skeletal muscles caused by neurological diseases: multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, cerebral circulation disorders, stroke, traumatic brain injuries, cerebral palsy, convulsions of central origin.

Use during pregnancy and lactation

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

Tizanidine is excreted in breast milk in small amounts, however, women who breastfeed children, the drug should not be used.

Contraindications

• Hypersensitivity to tizanidine or to any other component of the drug.
• Severe liver function disorders.
• Concomitant use with fluvoxamine or ciprofloxacin.

With caution, simultaneous use of Sirdalud with CYP1A2 inhibitors is not recommended.

Side effects

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

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

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

Musculoskeletal disorders: rarely-muscle weakness.

Other: often-fatigue.

Drowsiness, fatigue, dizziness, dry mouth, decreased blood pressure (BP), nausea, gastrointestinal disorders, and increased activity of hepatic transaminases were observed when taking small doses recommended for relieving painful muscle spasms. Usually, the above-described adverse reactions are moderate and transient.

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

Interaction

Concomitant use of tizanidine with fluvoxamine or ciprofloxacin, which are cytochrome P450-1 and 2 inhibitors, is contraindicated. Concomitant use of tizanidine with fluvoxamine or ciprofloxacin resulted in a 33-fold or 10-fold increase in tizanidine AUC, respectively.

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

Concomitant use 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.

How to take, course of use and dosage

Sirdalud MR is taken orally.

The dosage regimen should be set individually.

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

If necessary, the daily dose can be increased gradually (in” steps”) — by 6 mg (1 capsule) at intervals of 3-7 days.

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

Overdose

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

Symptoms: nausea, vomiting, decreased blood pressure, dizziness, drowsiness, miosis, restlessness, respiratory disorders, coma.

Treatment. To remove the drug from the body, repeated use of activated carbon is recommended. Forced diuresis may also accelerate the elimination of Sirdalud. In the future, symptomatic treatment is carried out.

Special instructions

Cases of tizanidine-related hepatic impairment have been reported, but these cases were rare with a daily dose of up to 12 mg. In this regard, it is recommended to monitor liver function tests once a month for the first 4 months of treatment in those patients who are prescribed tizanidine at a daily dose of 12 mg or higher, as well as in cases where there are clinical signs that suggest impaired liver function, such as unexplained nausea, anorexia, fatigue. If serum ALT and ACT levels persistently exceed the upper limit of normal by 3 times or more, Sirdalud should be discontinued.

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

Influence on the ability to drive a car and work with mechanisms.

Patients who experience drowsiness or dizziness should refrain from activities that require high concentration and rapid response, such as driving vehicles or working with machines and mechanisms.

Form of production

Modified-release capsules

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Tizanidine

Conditions of release from pharmacies

By prescription

Dosage form

long-acting capsule