MR SIRDALUD

Active material: Tizanidin
When ATH: M03BX02
CCF: Muscle relaxants centrally acting
ICD-10 codes (testimony): G35, G80, G95.9, I69, R25.2
When CSF: 02.10.01
Manufacturer: NOVARTIS PHARMA AG (Switzerland)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Modified release capsule hard gelatin, size №2, with white opaque cap and white opaque body, gray inscription on the lid “Sirdalud”, gray inscription on the body “6 mg”; contents of capsules – Round pellets of white to slightly yellow-brown.

Excipients: ethyl cellulose, shellac, talc, corn starch, sucrose, Titanium dioxide, iron oxide black, gelatin.

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.

Pharmacological action

Muscle relaxants centrally acting. The main point of the application, its action is in the spinal cord. Стимулируя пресинаптические a₂-receptors, tizanidine inhibits the release of excitatory amino acids, stimulus receptors, sensitive to N-methyl-D-aspartate (NMDA-receptors). Consequently, at the intermediate level of the spinal cord neurons are suppressed polysynaptic excitation transfer. Since this mechanism is responsible for excessive muscle tone, when you attempt to suppress muscle tone decreases. In addition to the muscle relaxant properties, tizanidine also has a central analgesic effect Moderate.

Sirdalud^® MRI is effective for chronic spasticity of spinal and cerebral origin. It reduces spasticity and clonic convulsions, thereby reducing the resistance to passive movements and increases the amount of active movements.

Pharmacokinetics

Absorption

When administered tizanidine absorbed almost completely. The average value of C_max It reached within 8.5 h and is about half the value of C_max while taking Sirdalud tablets^® in the same daily dose of, razdelennoy of 3 admission, provided that the total exposure (AUC) It remains unchanged.

Distribution

Sustained release dosage forms of tizanidine capsules modified release causes “softened” pharmacokinetic profile, that provides a stable therapeutic concentration of tizanidine in plasma for 24 no.

Plasma protein binding is 30%.

Metabolism

Tizanidine rapidly and largely metabolised in the liver. In vitro it was shown, that tizanidine are mainly metabolized by CYP1A2 isoenzyme. The metabolites are inactive.

Deduction

Tizanidine appears mainly kidneys (about 70% dose) as metabolites; the share unchanged substance accounts for only about 2.7%.

Pharmacokinetics in special clinical situations

Gender does not affect the pharmacokinetic parameters of tizanidine.

Testimony

- Spasticity of skeletal muscles in neurological diseases (eg, at rasseânnom sclerosis, Chronic myelopathy, degenerative diseases of the spinal cord, consequences of cerebral circulation and cerebral palsy / older patients 18 years/).

Dosage regimen

The drug is prescribed inside. The dosage regimen should be installed individually.

The initial daily dose is 6 mg (1 caps.). If necessary, the daily dose can be gradually (“steps”) increase – on 6 mg (1 caps.) intervals 3-7 days. Clinical experience shows, that for most patients, the optimal dose is 12 mg / day (2 caps.); In rare cases, it may be necessary to increase the daily dose to 24 mg.

Treatment patients with renal insufficiency (CC < 25 ml / min) it is recommended to start with taking the drug Sirdalud^® dose 2 mg 1 time / day. Increasing doses of conduct small “steps”, taking into account the tolerability and effectiveness. If you need to get a more pronounced effect, it is recommended to increase the dose, appointive 1 time / day, then increase the multiplicity of purposes.

Side effect

Adverse reactions are distributed in accordance with the frequency of occurrence. To assess the frequency of adverse reactions, the following criteria: Often (≥10%); often (by ≥1% to <10%); sometimes (by ≥0.1% to <1%); rarely (of ≥0.01% to <0.1%); rarely (<0.01%, including isolated reports). In one group, the frequency of occurrence of adverse reactions are ranked in order of importance.

From the nervous system: often – drowsiness, weakness, dizziness; rarely – hallucinations, insomnia, sleep disorders.

Cardio-vascular system: often – bradycardia, decrease in blood pressure; in some cases – marked reduction in blood pressure up to the collapse and loss of consciousness.

From the digestive system: often – dry mouth; rarely – nausea, gastrointestinal disorders, increase in liver transaminases; rarely – hepatitis, hepatic failure.

On the part of the musculoskeletal system: rarely – muscular weakness.

Other: often – fatigue.

When taken in small doses, recommended for the relief of painful muscle spasms, marked drowsiness, fatigue, dizziness, dry mouth, decrease in blood pressure, nausea, gastrointestinal disorders, increase in liver transaminases. Typically, the above reactions are mild and transient.

When receiving the higher doses, recommended for the treatment of spasticity, above adverse reactions occur more frequently and are more pronounced, however, they are rarely so severe, that the treatment had to be interrupted. Additionally, you may experience the following phenomena: decrease in blood pressure, bradycardia, muscular weakness, insomnia, sleep disturbance, hallucinations, hepatitis.

Contraindications

- Expressed human liver;

- Simultaneous use with potent inhibitors of CYP1A2 isoenzymes (incl. fluvoxamine or ciprofloxacin);

- Hypersensitivity to tizanidine or any other component of the drug.

Application sirdalud^® MR in children is not recommended, tk. experience with the drug in children is limited.

Pregnancy and lactation

Since the controlled trial of tizanidine in pregnant women were not conducted, it should not be used during pregnancy, except, when the potential benefits outweigh the potential risks.

Tizanidine is excreted in breast milk in small amounts. Nonetheless, women, breastfeeding children, the drug should not be used.

Cautions

Reported cases of liver dysfunction, associated with tizanidine, However, when applying the daily dose to 12 mg of these cases have been rare. In this connection, it is recommended to monitor liver function tests 1 once a month during the first 4 months of treatment in patients, which is assigned a daily dose of tizanidine 12 mg and higher, and where, when clinical signs, suggestive of hepatic dysfunction, such as unexplained nausea,, anorexia, feeling tired. When, when the levels of ALT and AST in serum consistently over ULN in 3 or more times, use sirdalud^® MR should be discontinued.

Do not abruptly cancel Sirdalud^® MR, the dose is gradually reduced.

With a sharp lifting sirdalud^® LL after prolonged treatment and / or receiving high doses (and after the simultaneous application of antihypertensive drugs) It noted the development of tachycardia and increased blood pressure, in some cases, could lead to the acute stroke.

Use caution when applying sirdalud^® MR in patients with renal insufficiency. When using Sirdalud MR in patients with renal insufficiency (CC less than 25 ml / min) necessary correction mode.

Use caution when applying sirdalud^® MP in elderly patients. Experience with sirdalud^® MP in elderly patients is limited. Based on the pharmacokinetic data suggest, In some cases, the renal clearance of these patients may be considerably reduced.

Use in Pediatrics

Experience in the use of the drug in children is limited. Therefore, the use sirdalud^® MR in these patients is not recommended.

Effects on ability to drive vehicles and management mechanisms

With the development of drowsiness, dizziness or blood pressure lowering therapy with sirdalud^® MR should refrain from the types of work, require high concentration of attention and fast reaction, eg, driving or using machinery.

Overdose

So far received several reports of overdose sirdalud^® MR, including the case, when the dose was adopted 400 mg.

Symptoms: nausea, vomiting, decrease in blood pressure, QT prolongation_from, dizziness, drowsiness, mioz, anxiety, respiratory failure, coma.

Treatment: to remove the drug from the body is recommended gastric lavage and repeated appointment of activated carbon. Forced diuresis and, perhaps, accelerate the elimination of tizanidine. In the future, symptomatic therapy.

Drug Interactions

In applying sirdalud^® MP inhibitors with isoenzyme CYP1A2 may increase the concentration of tizanidine in plasma.

Concomitant use of tizanidine with fluvoxamine or ciprofloxacin, isoenzyme inhibitors of cytochrome P450 1A2, leads respectively to a 33-fold or 10-fold increase in AUC tizanidine. The result of the combined application may be clinically significant and lasting reduction of blood pressure, leading to sleepiness, weakness, retarded psychomotor reactions (in some cases up to collapse and loss of consciousness). Concomitant use of tizanidine with fluvoxamine or ciprofloxacin – contraindicated.

We do not recommend co-administration of tizanidine with other inhibitors of the CYP1A2 - antiarrhythmic drugs (Amiodarone, mexiletine, propafenone), cimetidine, ftorxinolonami (эnoksatsin, pefloxacin, Ciprofloxacin, norfloxacin), rofekoksiʙom, oral contraceptives, ticlopidine.

With increasing concentrations of tizanidine in blood plasma may prolong the QT interval_from, characteristic of drug overdose.

Simultaneous with the appointment sirdalud^® MR with antihypertensive drugs, including diuretics, It can sometimes cause a decrease in blood pressure (in some cases up to collapse and loss of consciousness) and bradycardia.

Ethanol or sedatives may enhance the sedative effect sirdalud^® MR, it is not recommended the simultaneous use of other sedative drugs and / or alcohol.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 3 year.