Sirdalud MR caps 6mg #30

Sirdalud MR instruction

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Release form, composition and packaging

Modified-release capsules are hard gelatin, size No. 2, with a white opaque lid and a white opaque body, on the lid is an inscription in gray "Sirdalud", on the body is an inscription in gray "6 mg"; the contents of the capsules are round pellets of white or almost white color.
1 caps
tizanidine hydrochloride 6.864 mg
which corresponds to the content of tizanidine base 6 mg
Excipients: ethylcellulose - 1 mg, shellac - 4 mg, talc - 18.736 mg, sugar spheres - 155.4 mg, titanium dioxide - 1.26 mg, gelatin - 61.74 mg.
Ink composition: iron dye black oxide (E172), titanium dioxide (E171), shellac.

pharmachologic effect

Tizanidine is a centrally acting muscle relaxant. The main point of application of its action is in the spinal cord. By stimulating presynaptic α2 receptors, tizanidine inhibits the release of excitatory amino acids that stimulate NMDA receptors. As a result, at the level of the intermediate neurons of the spinal cord, polysynaptic transmission of excitation is suppressed. Since this mechanism is responsible for excessive muscle tone, when it is suppressed, muscle tone decreases. In addition to the muscle relaxant properties, tizanidine also has a central moderate analgesic effect.
Sirdalud MR is effective in chronic spasticity of spinal and cerebral genesis. Reduces spasticity and clonic convulsions, resulting in reduced resistance to passive movements and increases the amount of active movements.
Myorelaxing effect (measured on the Ashworth scale and using the "pendulum" test) and side reactions (decrease in heart rate and lowering blood pressure) of tizanidine depends on the concentration of tizanidine in the blood plasma.

Pharmacokinetics

Suction

When ingestion tizanidine absorbed almost completely. After a single use of Sirdalud MR at a dose of 12 mg, the average Cmax value is reached within 8.5 hours and amounts to 6.6 ng / ml, which corresponds to approximately half of the Cmax value when taking tizanidine tablets in the same daily dose, divided into 3 doses (4 mg 3 times / day), while the total daily exposure (AUC) remains unchanged.
Simultaneous food intake does not affect the pharmacokinetics of tizanidine (when using the drug in the form of capsules with a modified release of 12 mg). Although the Cmax value increases by 1/3 when taken after a meal, this is not clinically significant. No significant effect on absorption (AUC) is noted. Tizanidine in the dose range from 1 mg to 20 mg is characterized by linear pharmacokinetics.

Distribution

The prolonged release of tizanidine from the modified-release capsule dosage form causes a more “soft” pharmacokinetic profile, which ensures the maintenance of a stable therapeutic plasma concentration of tizanidine for 24 hours.
Plasma protein binding is 30%. The average value of Vd in the equilibrium state after i / v injection is 2.6 l / kg.

Metabolism

It is shown that tizanidine is rapidly and to a large extent (more than 95%) metabolized in the liver. In vitro, it has been shown that tizanidine is mainly metabolized by the CYP1A2 isoenzyme. Metabolites are inactive.

Removal

The average T1 / 2 tizanidine from the systemic blood flow is 2-4 hours. It is mainly excreted by the kidneys (approximately 70% of the dose) as metabolites; unchanged - about 4.5%

Pharmacokinetics in special clinical situations

In patients with impaired renal function (CK ≤ 25 ml / min), the average Cmax of tizanidine in plasma is 2 times higher than in healthy volunteers, T1 / 2 reaches 14 h, which leads to an increase (approximately 6 times) of the systemic bioavailability of tizanidine (measured by AUC value).
In patients with impaired liver function, special studies have not been conducted. Since tizanidine is extensively metabolized in the liver by the isoenzyme CYP1A2, impaired liver function can lead to an increase in systemic exposure to tizanidine.
Data on pharmacokinetics in patients over the age of 65 years is 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

Spasticity of skeletal muscles in neurological diseases, including:
- in multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord;
- with the consequences of cerebral circulation disorders;
- with the consequences of cerebral palsy (patients over 18 years old).

Contraindications

- hypersensitivity to tizanidine or to any other component of the drug;
- violation of liver function;
- simultaneous use with strong inhibitors of CYP1A2 isoenzyme, such as fluvoxamine or ciprofloxacin;
- not recommended for patients with rare hereditary diseases such as lactase deficiency, lactose intolerance, glucose-galactose malabsorption, because dosage form contains lactose.
- Patients younger than 18 years old (since experience with the use of the drug in this category of patients is limited).
With caution it is recommended to use the drug in patients over 65 years of age, patients with impaired renal function, patients with impaired liver function of moderate severity; simultaneously with drugs that prolong the QT interval (for example, cisapride, amitriptyline, azithromycin).

Dosage

Tizanidine has a narrow therapeutic index and high variability in the concentration of tizanidine in the blood plasma of patients, so careful selection of the dose is necessary.
The drug is taken orally. The dose and dosage regimen should be selected individually depending on the needs of the patient.
The recommended initial dose is 6 mg (1 capsule) per day. If necessary, the daily dose can be gradually (“steps”) increased - by 6 mg (1 capsule) at intervals of 3-7 days. Usually, the dose range is from 6 mg to 24 mg 1 time / day. 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.
Experience with the use of Sirdalud MR in patients over the age of 65 is limited. It is recommended to begin therapy with a minimum dose with a gradual increase until the optimum ratio of tolerance and efficacy of therapy is achieved.
The use of the drug Sirdalud MR in patients of this category is possible only in cases where the optimal dose was previously titrated when using other dosage forms of tizanidine. Increasing the dose is carried out in small "steps", taking into account tolerability and effectiveness. With insufficient therapeutic effect, it is recommended to first increase the dose, administered 1 time / day, and then increase the frequency of administration.
The use of the drug Sirdalud MR in patients with severely impaired liver function is contraindicated. In patients with moderate hepatic impairment, the drug should be used with caution; It is recommended to start therapy with a minimum dose, with a gradual increase to achieve the optimal ratio of tolerability and efficacy of therapy.

Interruption of treatment

When stopping therapy with Sirdalud MR, in order to reduce the risk of ricochet hypertension and tachycardia, the dose should be slowly reduced until the drug is completely discontinued, especially in patients receiving high doses of the drug for a long time.

Side effects

When taking tizanidine in small doses, recommended for relieving painful muscle spasm, drowsiness, fatigue, dizziness, dry mouth, lowering blood pressure, nausea, gastrointestinal disorders, increased activity of hepatic transaminases were noted. Usually, the above-described adverse reactions are moderate and transient.
When taken in higher doses recommended for the treatment of spasticity, the above adverse reactions (HP) occur more frequently and are more pronounced, but they are rarely so severe that the drug should be withdrawn. In addition, the following phenomena may occur: bradycardia, muscular weakness, insomnia, sleep disturbances, hallucinations, hepatitis.
HPs are grouped according to the classification of organs and organ system MedDRA, within each group are listed in order of decreasing frequency of occurrence. Definition of HP frequency categories: 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.
On the part of the nervous system: very often - drowsiness, dizziness.
On the part of the psyche: often - insomnia, sleep disorders.
Since the cardiovascular system: often - a decrease in blood pressure (in some cases, pronounced, up to collapse and loss of consciousness); infrequently - bradycardia.
On the part of the digestive system: very often - gastrointestinal disorders, dry mouth; often nausea.
From the musculoskeletal system: very often - muscle weakness.
General disorders: very often - increased fatigue.
Laboratory indicators: often - increased activity of hepatic transaminases.
With abrupt cancellation of the drug Sirdalud MR after prolonged treatment and / or taking high doses of the drug (as well as after simultaneous use with antihypertensive drugs), tachycardia and an increase in blood pressure were observed, which in some cases can lead to acute cerebral circulation, therefore, the dose of the drug Sirdalud MR should be reduced gradually until the drug is completely discontinued.
Separate reports on HP according to the use in clinical practice
Since information on HP data was obtained using the spontaneous reporting method and the exact number of patients taking the drug is not determined, it is not possible to estimate the frequency of occurrence of these reactions, and therefore the category “frequency is unknown” is indicated for HP data.
Immune system disorders: hypersensitivity reactions, including anaphylactic reactions, angioedema, and urticaria.
Mental disorders: hallucinations, confusion.
On the part of the nervous system: dizziness.
On the part of the organ of vision: blurred vision.
On the part of the liver and biliary tract: hepatitis, liver failure.
On the part of the skin and subcutaneous tissues: skin rash, erythema, pruritus, dermatitis.
Common disorders: asthenia, withdrawal syndrome.
If any of the side effects indicated in the instruction are aggravated, or the patient has noticed any other side effects not indicated in the instruction, he should inform the doctor about it.

Overdose with Sirdalud MR

To date, several reports of an overdose of tizanidine have been received, including the case when the accepted dose was 400 mg.
Symptoms: nausea, vomiting, decreased blood pressure, prolonged QTc interval, dizziness, drowsiness, miosis, anxiety, respiratory failure, coma.
Treatment: for the removal of the drug from the body, repeated gastric lavage and the appointment of activated charcoal is recommended. Forced diuresis may also accelerate the elimination of tizanidine. In the future, conduct symptomatic therapy.

Drug interaction

With simultaneous use of the drug Sirdalud MR with inhibitors of the isoenzyme CYP1A2 may increase the concentration of tizanidine in the blood plasma. In turn, an increase in plasma tizanidine concentration can lead to symptoms of overdose, including to prolong the QTc interval.
The simultaneous use of the drug Sirdalud MR with inducers of the isoenzyme CYP1A2 can lead to a decrease in the concentration of tizanidine in plasma. A reduced plasma concentration of tizanidine can lead to a decrease in the therapeutic effect of Sirdalud MR.

Contraindications combination drug Sirdalud MR

The simultaneous use of tizanidine with fluvoxamine or ciprofloxacin, inhibitors of the isoenzyme CYP1A2, is contraindicated.
When using the drug tizanidine with fluvoxamine or ciprofloxacin, a 33-fold and 10-fold increase in AUC of tizanidine, respectively, is observed, respectively. The result of simultaneous use may be a clinically significant and prolonged decrease in blood pressure, accompanied by drowsiness, dizziness, a decrease in the speed of psychomotor reactions (in some cases, up to collapse and loss of consciousness).
Not recommended combinations of the drug Sirdalud MR
It is not recommended to use tizanidine in conjunction with other inhibitors of the isoenzyme CYP1A2 - antiarrhythmic agents (amiodarone, mexiletin, propafenone), cimetidine, some fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoksibom, oral contraceptive means, teclonidine.

Combinations that require caution

Care must be taken when using the drug Sirdalud MR with drugs that prolong the QT interval (for example, cisapride, amitriptyline, azithromycin).

Antihypertensive drugs

The simultaneous use of the drug Sirdalud MR with antihypertensive drugs, including diuretics, can sometimes cause a decrease in blood pressure (in some cases up to collapse and loss of consciousness) and bradycardia.
With the abrupt cancellation of the drug Sirdalud MR, after the use of antihypertensive drugs, the development of tachycardia and an increase in blood pressure were noted, in some cases leading to acute cerebral circulation disturbance.
Rifampicin
Simultaneous use of the drug Sirdalud MR and rifampicin leads to a decrease in the concentration of tizanidine in the blood plasma by 50%. As a consequence, it is possible to reduce the therapeutic effect of the drug Sirdalud MR, which may be of clinical importance for some patients. Long-term co-administration of rifampicin and tizanidine should be avoided; if this combination is necessary, then careful selection of the dose of tizanidine is recommended (upwards).
Other medicines. Sedative, hypnotic drugs (benzodiazepine, baclofen), as well as histamine H1 receptor blockers, may also increase the sedative effect of tizanidine.
Sirdalud MR should be avoided with other alpha2-adrenomimetics (for example, clonidine) due to the potential enhancement of the hypotensive effect.
Smoking
Systemic bioavailability of the drug Sirdalud MR in male smokers (more than 10 cigarettes per day) is reduced by about 30%. Long-term therapy with Sirdalud MR smokers may require higher doses than the average therapeutic ones.
Alcohol. During therapy with Sirdalud MR, patients should avoid drinking alcohol, because it may increase the likelihood of adverse events (for example, lowering blood pressure and inhibition). Sirdalud MR may increase the inhibitory effect of alcohol on the central nervous system.

special instructions

With the use of the drug Sirdalud MR may decrease blood pressure, as well as the result of drug interactions with inhibitors of the isoenzyme CYP1A2 and / or antihypertensive drugs. A pronounced decrease in blood pressure can lead to loss of consciousness and collapse.
It was reported cases of dysfunction of the liver associated with tizanidine, but when using a daily dose of up to 12 mg, these cases were rarely observed. In this regard, it is recommended to monitor functional liver function tests 1 time per month in the first 4 months of treatment in those patients who are prescribed tizanidine in a daily dose of 12 mg and above, as well as in cases where there are clinical signs suggesting impaired liver function, such as nausea, anorexia, feeling tired. In the case when serum ALT and AST levels persistently exceed VGN by 3 times or more, the use of Sirdalud MR should be discontinued.
Influence on ability to drive vehicles and mechanisms
Patients who have drowsiness on the background of the use of the drug should be advised to refrain from activities that require high concentration of attention and quick reactions, such as driving vehicles or working with machines and mechanisms.

Pregnancy and lactation

Since controlled studies on the use of tizanidine in pregnant women have not been conducted, it should not be used during pregnancy, unless the potential benefit outweighs the possible risk.
In studies in animals, no teratogenicity was detected. When used in doses of 10 and 30 mg / kg / day in animals, an increase in the period of gestation was observed, cases of prenatal and postnatal loss of the fetus were recorded, as well as delayed fetal development. When using the above doses in females, there were marked signs of muscle relaxation and sedative action. Based on the surface area of ​​the body, the indicated doses exceeded the maximum recommended dose for humans (0.72 mg / kg / day) 2.2 and 6.7 times.
In animal studies, tizanidine was excreted in small amounts with milk from lactating females. Sirdalud MR should not be used during lactation (breastfeeding), because no data on the penetration of tizanidine into human breast milk.
Contraception. Patients with preserved reproductive potential should be informed about the adverse effect of the drug on the developing fetus, as revealed in animal studies. During the use of the drug, as well as within 1 day after stopping the drug, patients with a preserved reproductive potential should use reliable methods of contraception (with proper and long-term use of which the pregnancy rate is <1%).
Pregnancy test. Before starting the use of Sirdalud MR in patients with preserved reproductive potential, it is recommended to obtain a pregnancy test result.
Impact on fertility. In studies in animals there was no adverse effect on fertility in males and females when using tizanidine at a dose of 10 mg / kg / day. A decrease in fertility was noted in males who received tizanidine at a dose exceeding 30 mg / kg / day, and in females at a dose exceeding 10 mg / kg / day. Based on the surface area of ​​the body, the indicated doses exceeded the maximum recommended dose for humans (0.72 mg / kg / day) 2.2 and 6.7 times. When using the indicated doses on the part of the mother, behavioral effects and clinical signs were observed, including a pronounced sedative effect, weight loss and ataxia.

In case of impaired renal function

Care should be taken Sirdalud MR in patients with renal insufficiency.

With abnormal liver function

Contraindicated in marked disorders of the liver.

Use in old age

Care should be taken when using the drug Sirdalud MR in elderly patients. Experience with the use of the drug Sirdalud MR in elderly patients is limited. Based on the pharmacokinetic data, it can be assumed that in some cases the renal clearance in these patients may be significantly reduced.

Pharmacy sales terms

You don't need a prescription to buy Sirdalud MR.

Terms and conditions of storage

The drug should be stored out of reach of children at a temperature not exceeding 25 ° C. Shelf life - 3 years.