Sirdalut 2mg 30 tablets — Made in Switzerland — Free Delivery

Pharmacological properties

Pharmacodynamics. Tizanidine is a centrally acting skeletal muscle relaxant. the main point of application of its influence is the spinal cord. by stimulating presynaptic α2-adrenergic receptors, it inhibits the release of amino acids that stimulate n-methyl-d-aspartate receptors (nmda receptors). As a result, polysynaptic signal transmission at the level of interneuronal connections in the spinal cord, which is responsible for excessive muscle tone, is suppressed, and muscle tone is reduced. sirdalud is effective both for acute painful muscle spasms and for chronic spasticity of spinal and cerebral origin. it reduces resistance to passive movement and suppresses spasm and clonic convulsions and improves the strength of active muscle contractions.

Pharmacokinetics

Absorption and distribution. Tizanidine is rapidly absorbed. Cmax in blood plasma is reached approximately 1 hour after application. The average absolute bioavailability is 34%. The average volume of distribution of a steady state (Vss) after intravenous administration is 2.6 l / kg of body weight. Plasma protein binding - 30%. The relatively low deviation of pharmacokinetic parameters (Cmax and AUC) among patients facilitates a reliable preliminary assessment of blood plasma levels after oral administration.

Metabolism / excretion. The preparation undergoes rapid and extensive metabolism in the liver. Tizanidine is metabolized in vitro primarily by CYP 1A2. The metabolites are inactive. They are excreted mainly by the kidneys (70%). The elimination of the total radioactivity (that is, the substance in unchanged form and metabolites) is two-phase, with a fast initial phase (T1 / 2 - 2.5 h) and a slower elimination phase (T1 / 2 - 22 h). Only a small amount of the substance unchanged (about 2.7%) is excreted by the kidneys. The average T½ of a substance unchanged is 2–4 hours.

Pharmacokinetics in certain groups of patients. In patients with renal insufficiency (creatinine clearance 25 ml / min), the average Cmax in blood plasma is twice that in healthy volunteers, and the final T½ increases to approximately 14 hours, resulting in an average AUC increase of 6 times.

No studies have been performed in patients with impaired liver function.

Tizanidine is metabolized by the CYP 1A2 isoenzyme in the liver. In patients with impaired liver function, higher plasma concentrations of the substance may appear.

Sirdalud is contraindicated in persons with severely impaired liver function.

Pharmacokinetic data on 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.

The influence of food. Simultaneous food intake does not affect the pharmacokinetic profile of Sirdalud tablets. Although the Cmax value increases by one third, this is not clinically significant. There was no significant effect on absorption.

Indications

Painful muscle spasm. spasticity due to multiple sclerosis. spasticity due to spinal cord injury. spasticity due to brain damage.

Application

Sirdalud has a narrow therapeutic range and high variability in plasma tizanidine concentration in different patients. therefore, it is important to use it in optimal doses according to the patient's needs. treatment should be started with a low dose of 2 mg, which minimizes the risk of adverse effects from taking the preparation. if necessary, the dose of the preparation can be gradually increased with all the required precautions.

Adults

Relief of painful muscle spasms. Apply 2-4 mg 3 times a day. In severe cases, an additional dose of 2 or 4 mg may be taken before bedtime.

Spasticity in neurological disorders. The dose should be selected individually for each patient.

The initial daily dose should not exceed 6 mg, divided into 3 doses. It can be increased gradually to 2-4 mg 2 times 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

Application in children and adolescents. The experience of using the preparation Sirdalud in children and adolescents is limited, therefore it is not recommended for use in this category of patients.

Use in the elderly. The experience of using the preparation in elderly patients is limited, therefore, caution should be exercised when using the preparation Sirdalud in this category of patients. It is recommended to start treatment with a minimum dose and gradually increase it with caution in "small steps" until the optimal balance of individual tolerance and therapeutic efficacy of the preparation is achieved.

Use in patients with impaired renal function. For patients with impaired renal function (creatinine clearance 25 ml / min), the recommended initial single daily therapeutic dose is 2 mg. The dose is increased gradually and with caution, "in small steps", until the optimal balance of individual tolerance and therapeutic efficacy of the preparation is achieved. In order to increase the therapeutic efficacy, you should first increase a single dose before moving on to a more frequent intake of the preparation during the day.

Use in patients with impaired liver function. Treatment of persons with severely impaired liver function is contraindicated. Sirdalud is largely metabolized in the liver. Sirdalud should be used with caution in the treatment of patients with moderately severe liver dysfunction. Treatment is required to start with a minimum dose, a possible dose increase should be carried out with caution and taking into account the patient's individual tolerance of the preparation Sirdalud.

Interruption of treatment. If it is necessary to interrupt treatment, the dose should be reduced slowly and gradually. This is especially true for patients who have used the preparation in an increased dose for a long time. Thus, the risk of developing a rebound increase in blood pressure and tachycardia is reduced.

Contraindications

Hypersensitivity to tizanidine or any other component of the preparation. severe liver dysfunction. concomitant use of tizanidine with potent cyp 1a2 inhibitors such as fluvoxamine or ciprofloxacin.

Side effects

Adverse reactions - such as drowsiness, fatigue, dizziness, dry mouth, decreased blood pressure, nausea, disorders of the digestive tract and increased levels of transaminases in the blood plasma - are usually mild and transient in patients using the preparation in low doses, recommended for relief painful muscle spasm.

When taken in doses higher than recommended, to eliminate spasticity, the above adverse reactions occur more often and are more pronounced, but they are rarely so serious as to stop treatment. Also, such side reactions may occur: arterial hypotension, bradycardia, muscle weakness, sleep disturbances, hallucinations and hepatitis.

The appearance of such symptoms has been reported after a sudden discontinuation of tizanidine, especially after long-term treatment and / or taking in high daily doses and / or concomitant therapy with antihypertensive preparations. Under these circumstances, patients may experience hypertension and tachycardia. In some cases, such rebound hypertension can cause a stroke. Therefore, treatment with tizanidine should not be stopped abruptly, but only by a gradual dose reduction.

To assess the incidence of various adverse reactions, the following classification was used: very often (≥1 / 10), often (≥1 / 100, 1/10), infrequently (≥1 / 1000, 1/100), rarely (≥1 / 10 000, 1/1000), very rarely (1/10 000), including individual messages.

Mental disorders: often - insomnia, sleep disturbance.

From the side of the central nervous system: very often - drowsiness, dizziness; frequency unknown - confusion, vertigo.

From the heart: infrequently - bradycardia

From the vascular system: often - arterial hypotension; a slight decrease in blood pressure.

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

Hepatobiliary disorders: often - increased levels of transaminases in the blood plasma.

From the musculoskeletal system: very often - muscle weakness.

General disorders: very often - increased fatigue.

Post-marketing research

Additional adverse reactions to the preparation have been reported in post-marketing studies.

These adverse reactions have been reported from an unspecified number of patients, so it is not possible to reliably estimate their frequency.

From the immune system: hypersensitivity reactions (including anaphylaxis, swelling of the throat, shortness of breath and hives).

Mental disorders: hallucinations, confusion.

From the side of the central nervous system: vertigo.

On the part of the cardiovascular system: syncope.

From the side of the organ of vision: blurred vision.

Hepatobiliary disorders: hepatitis, liver failure.

On the part of the skin and subcutaneous tissue: rash, erythema, itching, dermatitis.

General disorders: asthenia, withdrawal syndrome.

Special instructions

The concomitant use of cyp 1a2 inhibitors with tizanidine is not recommended.

After a sudden discontinuation of the preparation or a rapid dose reduction, patients may experience hypertension and tachycardia. In some cases, such rebound hypertension can cause a stroke. Treatment with tizanidine should not be stopped abruptly, but only by gradually reducing the dose.

For patients with renal insufficiency (creatinine clearance 25 ml / min), the initial dose is 2 mg once a day. The dose should be increased sequentially, in small "steps", taking into account the effectiveness and tolerability. To achieve a more pronounced effect, it is recommended to first increase the dose prescribed 1 time per day, and then increase the frequency of administration.

Liver failure associated with the use of tizanidine has been reported, but this has rarely been reported in patients receiving daily doses up to 12 mg. In this regard, it is recommended to monitor liver function once a month during the first 4 months of therapy in patients using tizanidine at a dose of ≥12 mg, and in patients with clinical symptoms indicating liver failure (for example, nausea, loss of appetite, or increased fatigue unknown etiology). The use of the preparation Sirdalud should be discontinued if the level of ALT or AST in the blood plasma exceeds the upper limit of the norm by ≥3 times for a long period.

It is recommended that patients be closely monitored for 1 or 2 days after taking the first dose of tizanidine. In the case of anaphylaxis or throat edema with anaphylactic shock or shortness of breath, the use of the preparation Sirdalud should be stopped immediately and the patient should be prescribed the necessary treatment.

Arterial hypotension can occur with the use of tizanidine, as well as as a result of preparation interactions with CYP 1A2 inhibitors and / or antihypertensive preparations. Severe forms of arterial hypotension, such as loss of consciousness and circulatory collapse, have been reported.

Use caution when using this preparation with preparations that prolong the Q – T interval (eg, cisapride, amitriptyline, azithromycin).

Caution is necessary for patients with coronary artery disease and / or heart failure. ECG monitoring should be carried out at regular intervals at the beginning of the use of the preparation Sirdalud in these patients.

Patients with myasthenia gravis need to carefully assess the risk / benefit ratio before using this preparation.

The experience of use in children and adolescents is limited, therefore the use of the preparation Sirdalud is not recommended in this category of patients.

Use caution when using this preparation in the elderly.

Sirdalud tablets contain lactose. For patients with rare hereditary diseases - galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption syndrome - Sirdalud tablets are not recommended.

Use during pregnancy and lactation

Women of childbearing age. Women of childbearing age who are sexually active should have a pregnancy test before starting treatment with Sirdalud. Women of childbearing age should be advised that animal studies indicate that Sirdalud adversely affects the fetus. Women of childbearing age who are sexually active should use effective methods of contraception (methods that allow pregnancy in less than 1% of cases) throughout the entire period of treatment with Sirdalud and within 1 day after stopping treatment with the preparation.

Pregnancy. Data on the use of the preparation Sirdalud in pregnant women are limited, so it should not be prescribed during pregnancy, except in cases where the potential benefit to the mother outweighs the possible risk to the fetus.

Lactation. When using tizanidine in rats and rabbits, no teratogenic effects were observed. Experiments on animals have shown that tizanidine passes into breast milk in small quantities. Therefore, women who are breastfeeding should not prescribe the preparation.

Fertility There was no impairment of fertility in male rats receiving the preparation at a dose of 10 mg / kg / day and in female rats receiving the preparation at a dose of 3 mg / kg / day. A decrease in fertility was found in male rats receiving the preparation at a dose of 30 mg / kg / day and in female rats receiving the preparation at a dose of 10 mg / kg / day. When using the preparation in these doses, sedation, weight loss and ataxia were also noted.

Children. The experience of using the preparation in pediatrics is limited. It is not recommended to prescribe Sirdalud to children.

The ability to influence the reaction rate when driving or working with other mechanisms. Tizanidine can cause drowsiness, dizziness and / or arterial hypotension, thus impairing the patient's ability to drive vehicles or operate machinery. The risks increase with the simultaneous use of alcohol.

Therefore, one should refrain from activities that require a high concentration of attention and quick reactions, for example, driving vehicles or working with machines and mechanisms.

Interactions

Concomitant use of known cyp 1a2 inhibitors can increase plasma levels of tizanidine. an increase in the level of tizanidine in blood plasma can lead to the appearance of symptoms of an overdose, such as a prolongation of the q – t interval.

The simultaneous use of known inducers of CYP 1A2 can reduce the level of tizanidine in the blood plasma. A decrease in the level of tizanidine in blood plasma can lead to a decrease in the therapeutic effect of Sirdalud.

Concomitant use of potent CYP 1A2 inhibitors such as fluvoxamine or ciprofloxacin with tizanidine is contraindicated. The simultaneous use of tizanidine with fluvoxamine increases the AUC of tizanidine by 33 times, while the simultaneous use of tizanidine with ciprofloxacin increases the AUC of tizanidine by 10 times. This can lead to a clinically significant and long-term decrease in blood pressure, accompanied by drowsiness, dizziness, and decreased psychomotor performance.

Concomitant use of tizanidine with other CYP 1A2 inhibitors such as antiarrhythmics (amiodarone, mexiletine, propafenone), cimetidine, some fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives and ticlopidine is not recommended.

An increase in the level of tizanidine in blood plasma can cause symptoms of an overdose, including a prolongation of the Q – T interval.

The simultaneous use of the preparation Sirdalud with antihypertensive preparations, including diuretics, can sometimes cause arterial hypotension and bradycardia. In some patients who used simultaneous treatment with antihypertensive preparations, rebound hypertension and rebound tachycardia were noted with abrupt withdrawal of tizanidine. In some cases, rebound hypertension can cause a stroke.

The combined use of the preparation Sirdalud with rifampicin can lead to a 50% decrease in the concentration of tizanidine. Thus, the therapeutic effect can be reduced with the use of rifampicin during therapy with Sirdalud, which may be clinically significant for some patients. Long-term simultaneous use should be avoided, and if necessary, it is required to very carefully adjust the dose.

The use of the preparation Sirdalud leads to a 30% decrease in the systemic effect of tizanidine in smokers (more than 10 cigarettes per day). Long-term use of the preparation in patients who smoke a lot requires the use of the preparation in higher doses.

The simultaneous use of the preparation Sirdalud and other preparations of central action (for example, sedatives and hypnotics (benzodiazepine or baclofen), some antihistamines and analgesics, psychotropic preparations, narcotics) can increase the severity of the effects of each of the preparations and enhance the hypnotic effect of Sirdalud. This applies, in particular, to the simultaneous use of alcohol, which can unpredictably change or enhance the effect of Sirdalud and increase the risk of adverse reactions, so you should refrain from drinking alcohol.

The use of the preparation Sirdalud simultaneously with α2-adrenergic agonists (for example, with clonidine) should be avoided due to their potential additive hypotensive effect.

Overdose

There have been very few reports of overdose of the preparation sirdalud. in all patients who have reported isolated cases of overdose of this preparation, including 1 patient who took 400 mg of sirdalud, the recovery was uneventful.

Symptoms: nausea, vomiting, hypotension, bradycardia, prolongation of the Q – T interval, dizziness, miosis, respiratory distress, coma, anxiety, drowsiness.

Treatment. To remove the preparation from the body, multiple use of activated carbon in high doses is recommended. Forced diuresis may speed up the elimination of the preparation. In the future, symptomatic treatment should be carried out.

Storage conditions

At a temperature not exceeding 25 ° c.