Сирдалуд®

General characteristics. Structure:

Active agent - тизанидин (in the form of a hydrochloride) 2 mg or 4 mg; excipients: silicon dioxide colloid anhydrous, stearic acid, cellulose microcrystallic, lactoses monohydrate.

Description: Tablets of 2 mg: from white till almost white color, round, flat tablets with slanted edges, on one party it is squeezed out risk and the OZ code. Tablets of 4 mg: from white till almost white color, round, flat tablets with slanted edges, on one party the crossing risks, on another - the RL code.

Pharmacological properties:

Tizanidin - a muscle relaxant of the central action. The main point of application of its action is in a spinal cord. Stimulating presynaptic alfa2-receptors, it suppresses release of exciting amino acids which stimulate receptors to N-methyl-D-aspartate (NMDA receptors). Thereof at the level of interneuronels of a spinal cord there is a suppression of polisinaptichesky transfer of excitement. As this mechanism is responsible for an excess muscle tone, at its suppression the muscle tone decreases. In addition to myorelaxation properties, тизанидин renders also central moderately expressed analgeziruyushchy effect.

Sirdalud is effective both at an acute painful muscular spasm, and at chronic spasticity of spinal and cerebral genesis. Reduces spasticity and clonic spasms owing to what resistance to the passive movements decreases and the volume of active movements increases.

Pharmacokinetics

Absorption.
Tizanidin is soaked up quickly and almost completely. The maximum concentration in plasma (Cmax) is reached approximately in 1 hour after administration of drug. Because of the expressed metabolism at "the first passing" through a liver average value of bioavailability makes about 34%.

Distribution.
Average value of volume of distribution in the period of an equilibrium fortune at intravenous administration of drug makes 2.6 l/kg. Linkng with proteins of plasma makes 30%. In the range of doses from 4 to 20 mg the pharmacokinetics of a tizanidin has linear character. Considering low interindividual variability of pharmacokinetic parameters (in particular, such as Cmax and area under a curve "concentration time" / AUC/), at reception of a tizanidin inside it is possible to predict reliably values of its concentration in plasma. A floor does not influence pharmacokinetic parameters of a tizanidin.

Metabolism.
It was shown what тизанидин is quickly and substantially metabolized in a liver. In vitro was shown that тизанидин is generally metabolized by an isoenzyme 1A2 of system of P450 cytochrome. Metabolites are inactive.

Removal.
Average value of an elimination half-life of a tizanidin makes 2-4 h of a system blood-groove. Drug is removed preferential by kidneys (about 70% of a dose) in the form of metabolites; about 2.7% fall to the share of not changed substance.

Features of pharmacokinetics at separate groups of patients
It was established that at patients with a renal failure (clearance of creatinine less than 25 ml/min.) average Cmax value exceeded this indicator at healthy volunteers twice, and the final elimination half-life was extended approximately till 14 o'clock therefore AUC increased on average by 6 times.

Influence of food
The concomitant use of food does not influence pharmacokinetics of a tizanidin. Though Cmax value increases on 1/3, it is considered that it is not clinically significant. The significant effect on absorption (AUC) is not noted.

Indications to use:

Painful muscular spasm:

connected with static and functional diseases of a backbone (cervical and lumbar syndromes);
after surgical interventions, for example, concerning hernia of an intervertebral disk or an osteoarthrosis of a hip joint.
Spasticity of skeletal muscles at neurologic diseases, for example, at multiple sclerosis, a chronic myelipathy, degenerative diseases of a spinal cord, effects of disturbances of cerebral circulation and cerebral palsy (patients are more senior than 18 years).

Route of administration and doses:

Drug is appointed inside. The mode of dosing should be selected individually. At a painful muscular spasm appoint Sirdalud in a dose 2 mg or 4 mg 3 times a day. In hard cases before going to bed it is possible to accept in addition 2 mg or 4 mg. At the spasticity of skeletal muscles caused by neurologic diseases, the dose should be selected individually.

The initial daily dose should not exceed 6 mg divided into 3 receptions. The dose can be raised gradually, on 2-4 mg, bucketed from 3-4 to 7 days. Usually optimum therapeutic effect is reached at the daily dose from 12 to 24 mg divided into 3 or 4 receptions at regular intervals. It is not necessary to exceed a dose of 36 mg a day.

Use for patients with a renal failure
Treatment of patients with a renal failure (clearance of creatinine less than 25 ml/min.) is recommended to begin with a dose 2 mg once a day. Increase in a dose is carried out by small "steps", taking into account portability and efficiency. If it is necessary to gain more expressed effect, it is recommended to increase at first the dose appointed 1 time a day then increase frequency rate of appointment.

Features of use:

It was reported about cases of the abnormal liver functions connected with tizanidiny, however at use of a daily dose to 12 mg these cases were noted seldom. In this regard it is recommended to control functional hepatic trials in the first 4 months of treatment at those patients to whom it is appointed тизанидин in a daily dose of 12 mg and above once a month and also when the clinical signs allowing to assume an abnormal liver function are observed, - such as inexplicable nausea, anorexia, feeling of fatigue. In case the ALT and ACT levels in serum with firmness exceed the upper bound of norm by 3 times and more, Sirdalud's use should be stopped.

As lactose is a part of tablets of Sirdalud, it is not recommended to use drug at patients with rare hereditary intolerance of a galactose, with heavy lactose insufficiency or malabsorption of a glucose/galactose.

Influence on ability to drive the car and to work with mechanisms. Patients at whom drowsiness or dizziness are noted should refrain from types of the works demanding high concentration of attention and bystry reaction, for example, of driving of vehicles or work with cars and mechanisms.

Side effects:

Undesirable reactions are distributed according to emergence frequency. For assessment of frequency of development of undesirable reactions the following criteria are used: very often (> 1/10); often (from> 1/100, <1/10); sometimes (> 1/1000, <1/100); seldom (> 1/10000, <1/1000); very seldom (<1/10000), including separate messages. From a nervous system: often - drowsiness, dizziness; seldom - hallucinations, sleeplessness, sleep disorders.

From cardiovascular system: often - bradycardia, lowering of arterial pressure.

From digestive tract: often - dryness in a mouth; seldom - nausea, gastrointestinal frustration.

From a liver: seldom - increase in activity of hepatic transaminases, is very rare - hepatitis.

From skeletal and muscular system: seldom - muscular weakness.

Others: often - fatigue.

At reception of the small doses recommended for stopping of a painful muscular spasm drowsiness, fatigue, dizziness, dryness in a mouth, a lowering of arterial pressure (ABP), nausea, gastrointestinal frustration, increase in activity of hepatic transaminases were noted. Usually above described side reactions are moderately expressed and is passing.

At reception of higher doses recommended for spasticity treatment, above-mentioned side reactions arise more often and are more expressed, however they seldom are so heavy that treatment had to be interrupted. Besides, there can be following phenomena: decrease in the ABP, bradycardia, muscular weakness, sleeplessness, sleep disorders, hallucinations, hepatitis.

Interaction with other medicines:

Simultaneous use of a tizanidin with fluvoksaminy or ciprofloxacin which are inhibitors of P450 1A2 cytochrome, contraindicated. Simultaneous use of a tizanidin with fluvoksaminy or ciprofloxacin leads respectively to 33-fold or 10-fold increase in AUC of a tizanidin, respectively. Clinically significant and long decrease in the ABP resulting in drowsiness, dizziness, the slowed-down psychomotor reactions can appear result of the combined use. Do not recommend co-administration of a tizanidin with other CYP1A2 inhibitors - antiarrhytmic drugs (Amiodaronum, мексилетин, пропафенон), Cimetidinum, ftorkhinolona (эноксацин, пефлоксацин, norfloxacin), rofekoksiby, oral contraceptives, tiklopidiny.

Co-administration of Sirdalud with anti-hypertensive drugs, including diuretic, can sometimes cause decrease in the ABP and bradycardia. Alcohol or sedative drugs can strengthen sedative action of Sirdalud.

Contraindications:

Hypersensitivity to a tizanidin or to any other component of drug.
The expressed abnormal liver functions.
Simultaneous use with fluvoksaminy or ciprofloxacin.
With care
Simultaneous use of Sirdalud with CYP1A2 inhibitors is not recommended.

Use for children
Experience of use of drug for children is limited. Sirdalud's use for children is not recommended.

Use at a renal failure and/or at patients of advanced age
At Sirdalud's use for patients with a renal failure (clearance of creatinine less than 25 ml/min.) correction of the mode of dosing is necessary. Experience of use of Sirdalud for patients of advanced age is limited. On the basis of pharmacokinetic data it is possible to assume that in certain cases the renal clearance at these patients can be considerable it is reduced. It is necessary to be careful at Sirdalud's use for patients with a renal failure and elderly patients.

Use at pregnancy and in the period of a lactation.
As controlled researches of use of a tizanidin for pregnant women were not conducted, it should not be applied during pregnancy unless the potential advantage exceeds possible risk. Tizanidin is allocated with breast milk in insignificant quantities, nevertheless, to the women nursing children, drug should not be used.

Overdose:

Several messages on Sirdalud's overdose are so far received, including a case when the accepted dose made 400 mg. Recovery took place in all cases without features.

Symptoms: nausea, vomiting, decrease in the ABP, dizziness, drowsiness, miosis, concern, disturbance of breath, lump.

Treatment. For removal of drug from an organism repeated purpose of absorbent carbon is recommended. The artificial diuresis also, perhaps, will accelerate Sirdalud's removal. Further carry out a symptomatic treatment.

Storage conditions:

At a temperature not above 25 °C. Drug should be stored in the place, unavailable to children.
List B. Period of validity of 5 years. Drug should not be used after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

10 tablets in the blister. 3 blisters together with the application instruction in a cardboard pack.