The maximum plasma concentration is reached about 1 hour after ingestion. Due to the pronounced metabolism in “first pass” through the liver bioavailability is the average value of about 34%. Side effects of anastrozole protein binding is 30%. In the dose range from 4 to 20 mg tizanidine pharmacokinetics is linear.
Between the individual variability of pharmacokinetic parameters is low. Gender does not affect the pharmacokinetics of tizanidine. It is metabolized in the liver, mainly izofermenom 1A2 cytochrome P450. The metabolites are inactive. The half-life is 2-4 hours. Write mainly kidneys as metabolites, a small portion – unchanged. In patients with renal impairment (creatinine clearance less than 25 mL / min), the average value of the maximum plasma concentration is 2 times greater than the rate in healthy volunteers, and elimination half period lengthened to 14 hours.
Simultaneous food intake has no clinically meaningful effect on the pharmacokinetics of tizanidine.
Indications for use:
- painful muscle spasms associated with static and functional disorders of the spine, as well as after surgery;
- spasticity of the skeletal muscles during nevralogicheskih diseases (multiple sclerosis, chronic myelopathy, degenerative spinal cord disease, cerebrovascular accidents, cerebral palsy (in patients older than 18 years).
- severely impaired liver function,
- hypersensitivity to any component side effects of anastrozole of the drug,
- simultaneous use with fluvoxamine,
- age of 18 years (due to lack of data)
- pregnancy and lactation.
renal impairment, advanced age, concurrent use inhibitors (anti-arrhythmic drugs (amiodarone, mexiletine, propafenone), cimetidine, fluoroquinolones, rofecoxib, oral contraceptives, ticlopidine).
Dosage and administration:
With painful muscle spasms: 2-4 mg three times a day. In severe cases, before bedtime in addition take 2-4 mg.
When spasticity of the skeletal muscles: the initial daily dose should not exceed 6 mg, divided into 3 doses. The dose may be increased gradually to 4.2 mg at intervals of 3-7 days. Optimum therapeutic benefit is achieved at a daily dose of 12-24 mg divided by 3-4 hours at regular intervals.
The maximum daily dose of 36 mg.
In patients with renal failure is recommended to begin treatment with a dose of 2 mg once daily. Increasing the dose should be gradual, focusing on tolerability and efficacy. In case of need to increase the dose, the dosage is increased first to be assigned to one time per day, then increased dosing frequency.
Drowsiness, weakness, dizziness, a slight decrease in blood pressure, dry mouth, nausea, gastrointestinal disorders, passing increase in liver transaminases.
When taking the drug in higher side effects of anastrozole doses, further, there may be: lower blood pressure, bradycardia, muscle weakness, insomnia, sleep disorders, hallucinations, acute hepatitis (very rarely), anxiety.
Symptoms include nausea, vomiting, decreased blood pressure, dizziness, drowsiness, cramps, anxiety, respiratory failure, coma.
Treatment: multiple appointment of activated charcoal is recommended to remove the drug from the body. Forced diuresis also may accelerate the excretion of tizanidine. Subsequently, symptomatic therapy.
Interaction with other drugs:
The simultaneous use of fluvoxamine leads to 33-fold increase in area under the curve “concentration-time” tizanidine. As a result, developing long-lowering blood pressure, drowsiness, weakness and lethargy.
With simultaneous use of tizanidine with antihypertensive drugs (including a diuretic) may develop arterial gipogenzii and bradycardia.
Sedatives and ethanol, may increase the sedative action of tizanidine.
Simultaneous use of oral contraceptives leads to a significant decrease in clearance of tizanidine.
It reported liver problems associated with taking tizanidine, but the application of a daily dose to 12 mg of these cases were rare. In this connection, it is recommended to control hepatic function tests 1 time per month during the first 4 months of treatment, and if the levels of side effects of anastrozole in serum staunchly upper limit of normal 3 times or more, the use of tizanidine should be discontinued.
Patients who marked drowsiness should refrain from the types of jobs that require high concentration and speed of psychomotor reactions (eg driving vehicles or using machines and mechanisms).