Sirdalud® MR (Sirdalud® MR)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceTizanidineTizanidine
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    • Dosage form: & nbspmodified release capsules
    Composition:

    1 capsule contains: active substance - tizanidine hydrochloride - 6.864 mg (in terms of gizanidine 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, gelatin - 61,740 mg.

    Ingredients of ink: iron oxide, black oxide, titanium dioxide, shellac.

    Description:Hard gelatin capsules, size 2, with a white opaque lid and white opaque. housing. On the cap there is an inscription of gray color - Sirdalud, on the body there is an inscription of gray color - 6 mg
    Contents of the capsule: round pellets of white or almost white color.
    Pharmacotherapeutic group:Miorelaxant of central action
    ATX: & nbsp

    M.03.B.X   Other muscle relaxants of central action

    M.03.B.X.02   Tizanidine

    Pharmacodynamics:
    Tizanidine-muscle relaxant, the central action.The main point, the application of its action is in the spinal cord. By stimulating presynaptic alpha2-adrenergic receptors, it suppresses the release of excitatory amino acids - which stimulate '
    receptors for N-methyl-D-aspartate (NMDA receptors). As a result, the polysynaptic transmission of excitation is suppressed at the level of the intermediate neurons of the spinal cord. Since this mechanism is responsible for the excess muscle tone, when it is suppressed, the muscle tone decreases. In addition to
    miorelaksiruyuschim-properties, tizanidine also has a central moderately pronounced analgesic effect.
    Sirdalud® MRI is effective for chronic spasticity of spinal and cerebral origin. Reduces spasticity and clonic convulsions, resulting in reduced resistance to passive movements and increases the volume of active movements.
    The miorelaxing effect (measurement on the Ashworth scale and using the "pendulum" test) and side effects (decrease in the heart rate (HR) and blood pressure (BP) reduction) of tizanidine depends on the concentration of tizanidine in the blood plasma.
    Pharmacokinetics:
    Suction
    Tizanidine is absorbed almost completely. The mean maximum concentration (Cmax) (6.6 ng / ml) after a single application of 12 mg of the preparation Sirdalud® MP in capsules is achieved for 8.5 hours and is approximately half the value of Stach when taking tizanidine tablets in a similar daily dose , divided into 3 doses (4 mg 3 times a day), while the total daily exposure (AUC) remains unchanged.
    Distribution.
    The long-term "release" of tizanidine from the dosage form of the modified-release capsule causes a "relaxed" pharmacokinetic profile / that ensures the maintenance of a stable therapeutic concentration of tizanidine in the blood plasma for 24 hours.The average volume of the distribution during the equilibrium period after intravenous administration is 2.6 l / kg.
    The binding with plasma proteins is 30%. " .
    Metabolism.
    It was shown that. tizanidine quickly and to a large extent, (more than 95%). is metabolized in the liver. 'In vitro it has been shown that' tizanidine, is mainly metabolized by the isoenzyme 1A2 of the cytochrome P450 system. Metabolites are inactive.Excretion.
    Tizanidine is excreted mainly by the kidneys (approximately 70%) in the form of
    metabolites: in unchanged form - about 4.5%.
    Tizanidine in the range from 1 mg to 20 mg has a linear pharmacokinetics.
    Features of the pharmacokinetics of individual patents
    Patients with impaired renal function.
    In patients with impaired renal function (creatinine clearance <25 ml / min), the maximum mean concentration of tizanidine in plasma is 2 times higher than in healthy volunteers, the half-life period reaches 14 hours, which leads to an increased (approximately 6-fold) systemic bioavailability of tizanidine (measured by the area of ​​the sub-curve "concentration-time"),
    Patients with impaired hepatic function
    There were no specific studies in this category of patients. As- tizanidine intensively metabolized in the liver by the isoenzyme CYP1A2, a violation of liver function can lead to an increase in systemic exposure to tizanidine.
    Patients over 65 years of age '
    Data on pharmacokinetics in this group of patients are limited.
    Dependence on sex and race
    Sex does not affect the pharmacokinetic properties of thiazanidine.
    The influence of ethnic, and racial affiliation on the pharmacokinetics of tizanidine was not studied.
    Effect of food
    Simultaneous food intake does not affect the pharmacokinetics. tizanidine. Although the maximum concentration increases by 1/3, when the tablet is taken after a meal, it is considered that it is not clinically relevant. There is no significant effect on absorption (AUC).

    Indications:
    Spasticity of skeletal muscles in neurological diseases, for example, with (multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, the consequences of cerebral circulation and cerebral palsy (patients over 18 years old).

    Contraindications:
    Hypersensitivity to tizanidine or to another component of the drug.
    Severe liver dysfunction.
    Simultaneous use with potent inhibitors of the CYP1A2 isoenzyme, such as fluvoxamine or ciprofloxacin.
    Deficiency of sucrose / isomaltose, intolerance to fructose, glucose-galactose malabsorption.
    Experience with the drug: in patients under 18 years of age is limited. The use of Sirdalud MR in this population is not recommended.

    Carefully:
    It is advisable to use caution when used in patients over 65 years of age, patients with impaired renal function, moderately affected patients, impaired hepatic function, and congenital QT interval prolongation syndrome.
    Also, care must be taken when taking tizanidine and oral contraceptives simultaneously.
    If you have any of the listed diseases before taking the drug, be sure to consult a doctor.

    Pregnancy and lactation:
    Because controlled trials of tizanidine in pregnant women have not been performed, it should not be used during pregnancy, unless the potential for the mother exceeds the potential risk to the fetus; Since there is no data on the penetration of the drug Sirdalud® MP in breast milk in women, women who breastfeed children, the drug should not be used. ■

    Dosing and Administration:
    The drug is prescribed inside. The dosage regimen should be selected, individually, because tizanidine has a narrow therapeutic range and high variability in plasma concentrations.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, once a day. Clinical experience shows that for most patients the optimal dose is 12 mg once a day (2 capsules); In rare cases, an increase in the daily dose to 24 mg may be required.
    Use in patients over 65 years of age,
    Experience of application. Sirdalud MR in patients over 65 years of age is limited: It is recommended to start therapy with a minimal dose with a gradual increase to achieve the optimal ratio of tolerability and efficacy of therapy.
    Use in patients with impaired renal function.
    Treatment of patients with renal insufficiency with Sirdalud® MR (clearance creatinine less than 25 ml / min) is possible only in those patients who had previously titrated the optimal dose when other tizanidine dosage forms were used. Increase the dose in small "steps", taking into account the portability and effectiveness. '
    If it is necessary to obtain a more pronounced effect, it is recommended first to increase the dose prescribed once a day, after which increase the multiplicity of the appointment.
    Use in patients with impaired liver function.
    The use of Sirdalud® MR in patients with severe liver function is contraindicated.
    In patients with a moderately severe impairment of liver function, the drug should be used with caution, it is recommended to start therapy with a minimal dose with a gradual increase to achieve an optimal ratio of tolerability and efficacy of therapy.
    Interruption of treatment.
    When discontinuing therapy with Sirdalud® MP, in order to reduce the risk of developing a ricochet arterial pressure increase / and tachycardia, the dose should be slowly reduced to (complete, drug discontinuation, c, especially in patients receiving high doses of the drug for a long time.

    Side effects:
    'Undesirable reactions are distributed, according to the frequency of occurrence. The following criteria were used to estimate the frequency: very often. (> 1/10); often (from>, �?
    '- 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000) .1; '('
    , Disturbances from the nervous system: very often - drowsiness, dizziness. -
    Disorders of the psyche: often - insomnia, sleep disorders
    Disorders from the heart: infrequent bradycardia. , - : ,
    Violations from the vessels: often - lowering blood pressure (in some cases, expressed, up to collapse and loss of consciousness). .
    Disorders from the digestive system ', very often - gastrointestinal disorders; dry mouth; often nausea.
    Disorders from the musculoskeletal and connective tissue: very often -
    muscle weakness.
    General disorders and, violations at the injection site: very often - increased fatigue.
    Laboratory and instrumental data: often an increase in the activity of liver transaminases.
    When taking small doses, recommended to stop the painful muscle spasm, there was drowsiness, increased fatigue, dizziness, dry mouth, lowering blood pressure (BP), nausea, gastrointestinal disorders, increased activity of "liver" transaminases. Usually the above-described adverse reactions are moderately expressed and transient.
    At reception of higher. doses recommended. for treatment, spasticity, the above-mentioned adverse reactions appear more often and more pronounced, however they are; rarely are so severe that the treatment had to be interrupted.In addition, the following can occur: a decrease in blood pressure, bradycardia, muscle weakness,
    insomnia, sleep disturbances, hallucinations, hepatitis.
    With a sharp reversal of the drug Sirdalud® MP after prolonged treatment-and / or intake, high doses of the drug (and also after simultaneous application together with antihypertensive drugs), "the development of tachycardia and increased blood pressure, which in some cases can lead to acute disruption, cerebral circulation so the dose of the drug Sirdalud MR should be reduced, gradually until the drug is completely discontinued.
    Separate messages about. undesirable phenomena according to postmarketing application data. , - \
    On the background of therapy with the drug Sirdalud® MR, the following adverse events were noted in clinical practice, without indication of a cause-and-effect relationship with the use of the drug (the frequency of AE was not established)
    Disorders of the psyche: the frequency is unknown - hallucinations, confusion. '
    Disorders from the nervous system: frequency unknown - vertigo
    "Disturbances from the side of the organ of vision: the frequency is unknown - blurred vision. Disorders from the liver and bile ducts: the frequency is unknown -
    hepatitis, hepatic insufficiency.
    General disorders and disorders at the site of administration: frequency unknown - asthenia,
    withdrawal syndrome
    With a sharp cancellation. preparation of Sirdalud® MR, cases of a ricochet
    increase in 'blood pressure and tachycardia; in some cases, ricochet increase in blood pressure caused an acute impairment of cerebral circulation.


    If any of the side effects indicated in the manual are aggravated, or if you notice any other side effects that are not listed in the instructions, tell your doctor.

    Overdose:
    By now, several reports have been received of the overdose of tizanidine, including the case when the dose taken was 400 mg. In all cases, the recovery did not go away.
    Symptoms: nausea, vomiting, decreased blood pressure, lengthening of the interval QT (c), dizziness.
    drowsiness, miosis, anxiety, dumping, coma
    Treatment. To remove tizanidine from the body it is recommended to take multiple activated carbon. Forced diuresis may also accelerate the excretion of tizanidine. In the future, symptomatic treatment is carried out.
    Interaction:

    With the use of Sirdalud MP together with inhibitors of the isoenzyme CYP1A2, an increase in the concentration of tizanidine in the blood plasma is possible. In turn, an increase in the concentration of tizanidine in the plasma can lead to symptoms of overdose, including. to an extension of the interval QTfrom.

    Joint use of the drug Sirdalud® MR with inductors of the isoenzyme CYP1A2 can lead to a decrease in the concentration of tizanidine in the plasma. A reduced concentration of tizanidine in plasma can lead to a decrease in the therapeutic effect of the drug Sirdalud® MR.

    Contraindicated combinations of the drug Sirdalud® MR

    The simultaneous use of tizanidine with fluvoxamine or ciprofloxacin, inhibitors of the isoenzyme CYP1A2, is contraindicated.

    When using Sirdalud® MR with fluvoxamine or ciprofloxacin, respectively, a 33-fold and 10-fold increase in the TUCANO AUC, respectively. The result of a combined application may be a clinically significant and prolonged decrease in blood pressure, accompanied by drowsiness, dizziness, decreased speed of psychomotor reactions (in some cases, up to collapse and loss of consciousness).

    Unsupported combinations

    It is not recommended to appoint tizanidine together with other inhibitors of the isoenzyme CYP1A2 - antiarrhythmic agents (amiodarone, mexiletine, propafenone), cimetidine, certain fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives, ticlonidine.

    Combinations that require caution

    Care must be taken when using the drug Sirdalud® MR with drugs that extend the QT interval (eg, cisapride, amitriptyline, azithromycin).

    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 a sharp withdrawal of the drug Sirdalud® MR after application together with antihypertensive drugs, the development of tachycardia and increased blood pressure, in some cases leading to acute impairment of cerebral circulation.

    Simultaneous administration of the drug Sirdalud® MR and rifampicin leads to a decrease in the concentration of tizaidin in blood plasma by 50%.As a consequence, a decrease in the therapeutic effect of the drug Sirdalud® MR, which can be of clinical importance for some patients. Avoid prolonged combined use of rifampicin and tizanidine; if this combination is necessary, then a careful selection of the dose of tizanidine (upward) is recommended.

    Other medicines. Sedative, hypnotics (benzodiazepine, baclofen), as well as histamine H blockers1receptors, can also enhance the sedative effect of tizanidine.

    You should avoid taking Sirdalud® MR with other alpha2-adrenomimetics (for example, with clonidine) due to the potential increase in the hypotensive effect.

    Smoking. Systemic bioavailability of Sirdalud® MP in smokers men (more than 10 cigarettes a day) is reduced by about 30%. Long-term therapy with Sirdalud® MR smoking men may require higher doses than average therapeutic doses.

    Alcohol. During therapy with the drug Sirdalud® MR patients should avoid alcohol use, because it can increase the likelihood of developing adverse events (eg, lowering blood pressure and inhibition). Sirdalud®MP can increase the inhibitory effect of alcohol on the central nervous system.

    Special instructions:

    When using Sirdalud® MR may decrease blood pressure, as well as as a result of drug interaction with inhibitors of the isoenzyme CYP1A2 and / or antihypertensive drugs. A pronounced decrease in blood pressure can lead to loss of consciousness and collapse.

    Sirdalud® MR has a sedative effect, can cause hallucinations.

    Reported cases of violations of liver function associated with tizanidine, but with a daily dose of up to 12 mg, these cases were rare. In this regard, it is recommended to monitor functional liver function tests once a month in the first 4 months of treatment in those patients who are assigned tizanidine in a daily dose of 12 mg and above, as well as in those cases when there are clinical signs suggesting a violation of liver function, such as nausea, anorexia, a feeling of fatigue. In the case when the levels of ALT and AST in the serum persistently exceed the VGN by 3 times or more, the use of Sirdalud MR should be discontinued.


    Effect on the ability to drive transp. cf. and fur:

    Impact on the ability to drive vehicles and manage mechanisms

    Patients who are drowsy during the use of the drug should be advised to refrain from activities requiring high concentration of attention and quick reaction, for example, driving vehicles or working with machines and mechanisms.

    Form release / dosage:
    Capsules with modified release of 6 mg for 10 pcs. in blister (PVC / PVDC / Al), 1, 2, 3 blisters together with instructions for use in a cardboard bundle.

    Packaging:
    Capsules with modified release of 6 mg for 10 pcs. in blister (PVC / PVDC / Al), 1, 2, 3 blisters together with instructions for use in a cardboard bundle.

    Storage conditions:
    At a temperature of no higher than 25 ° C.
    The drug should be stored out of the reach of children.

    Shelf life:
    3 years
    The drug should not be used after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LS-002605
    Date of registration:04.11.2011
    The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland
    Manufacturer: & nbsp
    Information update date: & nbsp29.08.2015
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