Sirdalud mr caps. with modif.vysv. 6mg 30 pc

Description

Composition
Active substance:
1 capsule contains: tizanidine hydrochloride – 6.864 mg (based on the tizanidine base – 6.000 mg) ;.
Excipients:
Ethylcellulose – 1,000 mg, shellac – 4,000 mg talc – 18.736 mg sugar spheres – 155.400 mg Titanium dioxide – 1,260 mg gelatine – 61.740 mg. Ink composition: dye black iron oxide (E 172) Titanium dioxide (E 171), shellac.
Description:
Hard gelatin capsules №2, with white opaque cap and white opaque body. On the lid inscription gray – Sirdalud, in the case of gray inscription – 6 mg.
Capsule contents: round pellets white or nearly white.
Product form:
Capsules containing 6 mg modified release. 10 capsules in blister (PVC / PVDC or PVC / PE / PVDC), 1, 2 or 3 blisters with instruction for use in a cardboard box.
Contraindications
Hypersensitivity to tizanidine or any other component of the preparation.
Impaired function of the liver and severe.
The simultaneous use of potent inhibitors isoenzyme CYP1A2, such as fluvoxamine or ciprofloxacin.
Not recommended for use in patients with rare hereditary diseases such as lactase deficiency, lactose intolerance, glucose-galactose malabsorption, because the formulation contains lactose.
Experience with the drug in patients younger than 18 years is limited. Use of the drug Sirdalud® MR in this population is not recommended.
Caution: It is recommended to be careful when using in patients older than 65 years, patients with impaired renal function, patients with dysfunction of moderate severity of the liver.
Care must be taken while the application of the drug to the drugs prolong the interval QT (e.g., cisapride, amitriptyline, azithromycin).
Dosage
6 mg
Indications
Skeletal muscle spasticity in neurological diseases such as multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, the consequences of cerebral blood flow and cerebral palsy (patients older than 18 years).
Interaction with other drugs
With the simultaneous application of the drug Sirdalud® MP inhibitors isoenzyme CYP1A2 may increase the concentration of tizanidine in plasma. In turn, an increase in the plasma concentration of tizanidine can lead to symptoms of drug overdose, QT (c) interval including elongation.
Simultaneous use of the drug with Sirdalud® MR isoenzyme inducers of CYP1A2 may lead to a decrease in the concentration of tizanidine in plasma, which could lead to a decrease in therapeutic effect of the drug. Contraindicated in combination with tizanidine
The simultaneous use of tizanidine with fluvoxamine or ciprofloxacin isoenzyme CYP1A2 inhibitors is contraindicated.
In the application of tizanidine with fluvoxamine or ciprofloxacin indicated respectively 33-fold and 10-fold increase in AUC of tizanidine. The result of the simultaneous application may be clinically significant and prolonged hypotension accompanied by sleepiness, dizziness, decreased psychomotor reactions rate (in some cases up to collapse and loss of consciousness).
Not recommended combination with tizanidine
It is not recommended to use simultaneously tizanidine with other inhibitors isoenzyme CYP1A2 – antiarrhythmics (amiodarone, mexiletine, propafenone), cimetidine, certain fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives, ticlopidine.
Combination with tizanidine, requiring compliance with caution
Care must be taken while applying Sirdalud® MR formulation with drugs that prolong the interval QT (e.g., cisapride, amitriptyline, azithromycin).
antihypertensive drugs
Simultaneous use of the drug Sirdalud® MR with antihypertensive agents including diuretics, may sometimes cause a decrease in blood pressure (in some cases up to vascular collapse and loss of consciousness) and bradycardia.
If rapid elimination of the drug after application Sirdalud® MR with antihypertensive drugs mentioned tachycardia development and increased blood pressure, which may in some cases lead to acute cerebral circulation.
rifampicin
Simultaneous administration of tizanidine and rifampicin causes 50% reduction in the concentration of tizanidine in plasma. Consequently, the therapeutic effect of the drug Sirdalud® MR may be reduced, which may have clinical significance for some patients. Avoid prolonged simultaneous use of rifampicin and tizanidine, failing recommended careful dose selection tizanidine (upward).
Smoking tobacco
Systemic bioavailability of tizanidine in smoking patients (more than 10 cigarettes per day) is reduced by about 30%. Long-term therapy with patients in this category may require higher doses of tizanidine than average therapeutic.
Alcohol
During therapy, the drug should avoid alcohol intake, as it may increase the likelihood of adverse events (eg, lowering blood pressure and sedation). Tizanidine may enhance the depressant effect of alcohol on the central nervous system.
Other drugs
Sedatives, hypnotics (benzodiazepines, baclofen) and other drugs such as H1-receptor blockers gistaminnovyh may also increase sedation tizanidine. Avoid taking the drug Sirdalud® MR other alpha2 agonists (e.g., clonidine), due to the potential gain of hypotensive effect.
Overdose
By now, a few reports of overdose tizanidine, including the case where the received dose was 400 mg. In all cases, recovery was uneventful.
Symptoms include nausea, vomiting, decreased blood pressure, lengthening the interval QT (c), dizziness, drowsiness, miosis, anxiety, respiratory failure, coma.
Treatment. For removing multiple dose recommended tizanidine activated carbon from the body. Forced diuresis also may accelerate the excretion of tizanidine. Subsequently symptomatic treatment.
pharmachologic effect
Pharmacological group:
Muscle relaxants centrally acting.
Pharmacodynamics:
Tizanidine – muscle relaxant central action. The main point of application of its action is in the spinal cord. Stimulating the presynaptic alpha2 adrenoceptors, it suppresses the release of excitatory amino acids, which stimulate the receptors to N-methyl-D-aspartate (NMDA-receptors). Consequently, at the level of intermediate neurons of the spinal cord is suppressed polysynaptic transmit excitation. Since this mechanism is responsible for excessive muscle tone, the muscle tone in its suppression is reduced. In addition to the muscle relaxant properties, tizanidine also has central moderately pronounced analgesic effect.
Tizanidine is effective for chronic spasticity of spinal and cerebral origin. Decreases spasticity and clonic convulsions, thereby reducing resistance to passive movement, and increases the amount of active movements.
Muscle relaxant effect (measured by the Ashworth scale and using a “pendulum” test) and side effects (lowering of heart rate (HR) and blood pressure reduction (AD)) of the drug depends on the concentration of tizanidine in plasma.
Pharmacokinetics:
Suction
Tizanidine absorbed almost completely. The mean value of the maximum concentration (Cmax) (6,6 ng / ml) after a single application of 12 mg drug Sirdalud® MR capsules achieved within 8.5 hours and is approximately half the Cmax value when receiving tizanidine tablets in the same daily dose, divided into 3 doses (4 mg three times a day), the total daily exposure (AUC) remains unchanged.
Distribution
Prolonged release of tizanidine modified release capsules causes a “soft” pharmacokinetic profile that provides stable therapeutic concentration of tizanidine in plasma for 24 hours.
The mean volume of distribution at steady state after intravenous administration of 2.6 l / kg.
Binding to plasma proteins is 30%.
Metabolism
It is shown that tizanidine rapidly and substantially (about 95%) is metabolized in the liver. In vitro demonstrated that tizanidine is mainly metabolized isoenzyme CYP1A2 of cytochrome P450. The metabolites are inactive.
breeding
The average half-life of tizanidine systemic circulation is 2-4 hours, removing is carried out mainly by the kidneys (approximately 70%) in the form of metabolites: in unmodified form – about 4.5%.
Tizanidine in the range from 1 mg to 20 mg has linear pharmacokinetics.
Effect of food
Simultaneous food intake has no effect on the pharmacokinetics of tizanidine after receiving 4 mg as a 12 mg tablet or a capsule with a modified release formulation. Although the C max value is increased by 1/3 when taking pills after a meal, it is not clinically significant. Significant effect on absorption (AUC) is not marked.
Pharmacokinetics in specific patient groups
Patients with impaired renal function
In patients with impaired renal function (creatinine clearance (CC)
Patients with impaired liver function
Specific studies in patients of this category have been conducted. Since tizanidine primarily metabolized in the liver isoenzyme CYP1A2, liver dysfunction can lead to an increase in systemic exposure tizanidine.
Patients older than 65 years
Pharmacokinetic data from this group of patients is limited.
Dependence on sex and race
Gender does not affect the pharmacokinetic properties of tizanidine.
The influence of ethnicity and race on the pharmacokinetics of tizanidine has not been studied.
Pregnancy and breast-feeding
Pregnancy
Since the controlled trial of tizanidine in pregnant women have not been conducted, it should not be used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus. In animal studies revealed no teratogenic effects. When applied in doses 10 and 30 mg / kg per day in animals an increase gestation, reported cases of prenatal and postnatal fetal loss, and growth retardation. When applying the above dosages expressed in females observed signs of sedation and muscle relaxation. Based on body surface area, these doses exceeding the maximum recommended human dose (0.72 mg / kg per day) in 2.2 and 6.7 times.
Breast-feeding
In animal studies, tizanidine stood out in small amounts with the milk of lactating females. Do not apply the drug during breast-feeding, as there is no data on the penetration of tizanidine passes into breast milk in humans.
Pregnancy test
Before starting the application with the stored Sirdalud® reproductive potential of the drug in patients advised to get pregnancy test result.
Effect on Fertility
In the studies the animals were observed adverse effect on the fertility of male animals and female when using tizanidine in a dose of 10 mg / kg per day, and 3 mg / kg / day, respectively. It noted a decrease fertility in males receiving tizanidine in a dose exceeding 30 mg / kg per day, and female individuals – at a dose greater than 10 mg / kg per day. Based on body surface area, these doses exceeding the maximum recommended human dose (0.72 mg / kg per day) in 2.2 and 6.7 times. In applying these doses maternal effects observed behavioral and clinical symptoms include severe sedation, decrease in body weight and ataxia.
Conditions of supply of pharmacies
Prescription.
side effects
At lower doses recommended for the relief of painful muscle spasms, marked drowsiness, fatigue, dizziness, dry mouth, decreased blood pressure, nausea, gastrointestinal disorders, elevation of liver transaminases. Usually, the above side reactions are mild and transient.
At higher doses recommended for the treatment of spasticity above undesirable reactions (HP) arise more and more pronounced, but rarely requires discontinuation due to gravity. Additionally, you may experience the following effects: hypotension, bradycardia, muscle weakness, insomnia, sleep disturbances, hallucinations, hepatitis.
HP grouped according to the classification MedDRA organs and organ systems, within each group are listed in order of decreasing frequency of occurrence. The following criteria for evaluation of HF frequencies used are very often (> 1/10); often (by> 1/100,
special instructions
In applying the drug Sirdalud® MR blood pressure reduction may occur, and as a result of drug interactions with inhibitors of CYP1A2 isoenzyme and / or antihypertensive agents. Marked reduction in blood pressure can lead to unconsciousness and vascular collapse.
Reported cases of liver dysfunction associated with tizanidine, but when using a daily dose of 12 mg of these cases were rare. In this connection, it is recommended to control the functional “liver function tests” 1 once a month during the first 4 months of treatment in those patients receiving tizanidine at a daily dose of 12 mg and above, as well as in cases where the clinical signs suggestive of dysfunction liver, such as unexplained nausea, anorexia, fatigue. In the case where the activity of alanine aminotransferase and aspartate aminotransferase in serum consistently exceeds the upper normal limit is 3 times or more, the use of the preparation should be discontinued Sirdalud® MR.
Contraception
Should inform patients with preservation of reproductive potential of adverse effects of the drug on the developing fetus, identified in animal studies. During application of the preparation, as well as within 1 day after stopping treatment patients with preserved reproductive potential use reliable methods of contraception (long-term and with proper use of which the pregnancy rate is
Patients who have a background in the use of the drug is marked drowsiness should be advised to refrain from activities that require high concentration and quick reaction, for example, management of vehicles and mechanisms.
Storage conditions
At a temperature not exceeding 25 C. The drug should be kept out of reach of children.
Dosing and Administration
Tizanidine has a narrow therapeutic index and a high variability in the plasma concentration, however requires careful dose selection.
The drug is taken orally. The dose and dosing regimen should be individualized, depending on each patient’s needs.
The recommended initial dose of 6 mg (1 capsule) per day; if necessary, the daily dose may be increased incrementally from a “step” 6 mg (1 capsule) at intervals of 3-7 days. Typically, dose range is from 6 mg to 24 mg once a day. Clinical experience shows that for most patients, the optimal dose is 12 mg once a day (2 capsules); In rare cases, it may be necessary to increase the daily dosage to 24 mg.
Use in patients older than 65 years
Experience with the drug Sirdalud® MR in patients aged over 65 years is limited. It is recommended to start treatment with the lowest dose with gradual increase to achieve the optimum ratio of tolerability and efficacy of therapy.
The use in patients with impaired renal function
Use of the drug Sirdalud® MR patients in this category is only possible after prior selection tizanidine dose drugs in other dosage forms. Increasing doses carried small “steps”, in view of tolerability and efficacy. When insufficient therapeutic effect is recommended to first increase the daily dose for single dose and then increased dosing frequency.
The use in patients with impaired liver function
Use of the drug Sirdalud® MR in patients with impaired hepatic function is contraindicated severe.
In patients with impaired liver function moderate drug should be used with caution; recommended to initiate therapy with the lowest dose with a gradual increase until the optimum ratio of tolerability and efficacy of therapy.
treatment interruption
Upon termination of drug therapy Sirdalud® MR, in order to reduce the risk of rebound hypertension and tachycardia should be slowly reduce the dose until complete withdrawal of the drug, especially in patients receiving high doses of the drug over a long time.
Information
Appearance may differ from that depicted in the picture. There are contraindications. You need to read the manual or consult with a specialist