Instruction for use: Tizanidine (Tizanidinum)

chemical name 5-Chloro-N- (4,5-dihydro-1H-imidazol-2-yl) -2,1,3-benzothiadiazole-4-amine (as hydrochloride)

Pharmacotherapeutic group:

Drugs affecting neuromuscular transmission

Alpha-adrenoceptor agonists

The nosological classification (ICD-10)

G24.8.0 * Muscle hypertonicity

Increased muscle tone, The spasm of the striated muscles due to organic diseases of the CNS, muscle Spasticity, Painful muscle spasms in spinal diseases, Increased skeletal muscle tone

G35 Multiple sclerosis

Disseminated sclerosis, multiple sclerosis, Relapsing Multiple Sclerosis, Secondary progressive multiple sclerosis, Exacerbation of multiple sclerosis, Mixed forms of multiple sclerosis

G54.1 Disorders of lumbosacral plexus

Sciatica, Neurology radicular origin, spine Pathology, Sciatica lumbosacral, radiculoneuritis

G54.2 Disorders of the cervical roots, not elsewhere classified

Barre -Leu Syndrome, Neck migraine

G80 Cerebral Palsy

Cerebral paralysis, Children's cerebral palsy

G81 Hemiplegia

Hemiparesis

G95.0 Syringomyelia and siringobulbiya

Syringomyelia

G95.9 Disease of spinal cord, unspecified

Degenerative spinal disease, myelopathy funicular, Spinal spastic syndrome, Acquired spinal cord disease, Congenital spinal cord disease

G99.2 Myelopathy in diseases classified elsewhere

Myelopathy, Chronic myelopathy

I64 Stroke, not specified as hemorrhage or infarction

Primary stroke, Stroke, Stroke in the course of, microstroke, stroke, The completed stroke

I67.9 Cerebrovascular disease, unspecified

lacunarity status, Angioneyropatiya, Arterial angiopathy, brain hypoxia, Encephalopathy, cerebral vascular disease and age-related, Coma in violation of cerebral circulation, Metabolic and cerebrovascular disorders, Violation of the blood supply to the brain, Cerebrovascular accidents, Violation of brain functions, Violation of the functions of the cerebral cortex, Violation of cerebral circulation, Cerebrovascular insufficiency, Acute cerebrovascular insufficiency, Acute ischemic attack,The defeat of the brain vessels, The progression of destructive changes in the brain, Disorders of cerebral circulation, The syndrome of cerebral insufficiency, Cerebral vascular insufficiency, Vascular encephalopathy, Vascular diseases of the brain, Vascular brain disorders, Vascular lesions of the brain,Functional brain disorders, Chronic cerebral ischemia, Chronic heart failure,Chronic cerebrovascular insufficiency, Chronic violation of the blood supply to the brain, Cerebral insufficiency, Cerebral organic failure, encephalasthenia, cerebroasthenic syndrome, Cerebrovascular disease,Cerebrovascular pathology, cerebrovascular disease, cerebrovascular disorders, cerebrovascular disorders, Encephalopathy discirculatory

M13.9 Arthritis, unspecified

Arthritis,Purulent arthritis (non-infectious), acute Arthritis,Pain in acute inflammatory diseases of the musculoskeletal system,Pain in chronic inflammatory diseases of the musculoskeletal system,The pain in osteoarthritis, Inflammation in osteoarthritis, Inflammatory arthropathy, Inflammatory and degenerative joint diseases, Inflammatory disease of the musculoskeletal system, Inflammatory joint disease, Inflammatory diseases of the musculoskeletal system, destructive arthritis, The disease of the musculoskeletal system, Diseases of the musculoskeletal system, Diseases of the musculoskeletal system and connective tissue, Infections musculoskeletal system, monoartrit, Non-infectious arthritis, rheumatic arthritis, Osteoarthritis, Acute inflammation of the musculoskeletal tissue, Acute inflammatory diseases of the musculoskeletal system, Acute inflammatory condition of the musculoskeletal system, Acute arthritis, Acute osteoarthritis, Post-traumatic osteoarthritis, Reactive arthritis, Chronic inflammatory diseases of the joints, Chronic arthritis, Chronic inflammatory arthritis, Chronic inflammation of the inner layer of the joint capsule, Chronic inflammation of the joint capsule,Chronic inflammatory disease of the joints, Exudative arthritis

M42 Osteochondrosis

Pain in spinal osteochondrosis, Cervical osteochondrosis, Radicular syndrome in osteochondrosis, intervertebral osteochondrosis, osteochondrosis, Osteochondrosis with radicular syndrome, Osteocondritis of the spine

M47 Spondylosis

Spondyloarthrosis, spondylarthrosis, Diseases of the spinal column, spondylosis

M51.9 Intervertebral disc defeat unspecified

Herniated disk, Diseases of the vertebral discs, Disc protrusion

Slipped disk, Prolapse of intervertebral disc

M53.0 cervical-cranial syndrome

M53.1 neck and shoulder syndrome

Acute shoulder-scapular periarthritis, Shoulder periarthritis, Of shoulder periarthritis, Shoulder periarthritis,frozen shoulder, Periarthritis in humeroscapular area, shoulder hand syndrome

R25.2 Cramp and spasm

Muscle spasms in tetanus, Pain smooth muscle spasm, Pain spasm of smooth muscles (renal and biliary colic, intestinal spasms, dysmenorrhea),Pain spasm of smooth muscles of internal organs, Pain spasm of smooth muscles of internal organs (kidney and biliary colic, intestinal spasms, dysmenorrhea), Painful muscle spasm, mimic spasm, spasticity, Muscle spasms, Muscle spasms of central origin, Muscle spasms, Neurological contracture with spasms, Night cramps in the extremities, Night leg cramps, Symptomatic convulsive state, West syndrome, Smooth muscle spasm, Spasm of vascular smooth muscle, muscle spasm, The spasm of the striated muscles due to organic diseases of the CNS, Skeletal muscle spasm, The spasms of smooth muscles of internal organs, The spasms of skeletal muscles, Spastic condition of striated muscle, Spastic pain, Spasmodic state of smooth muscle, Spasticity skeletal muscle, muscle cramps, convulsions, Leg cramps, Seizures of central origin, convulsive states, Spastic syndrome, Convulsive status in children, Tonic seizures, Cerebral spastic syndrome, Phenomenon jackknife

R52.2 Other constant pain

Pain syndrome, rheumatic origin, Pain at vertebral lesions, Pain in the chamber, Pain for burns, Pain syndrome weak or moderate, Perioperative pain,Moderate to severe pain, Moderately or weakly expressed pain syndrome, Moderate to severe pain, Ear pain of otitis, Neuropathic pain, neuropathic pain

R52.9 Unspecified Pain

Pain after cholecystectomy, Pain shooting, Non-malignant pain, Obstetric and gynecological pain, Pain syndrome, Pain in the postoperative period, Pain in the postoperative period after orthopedic surgery, Pain of inflammatory genesis, Pain than cancer genesis,Pain syndrome after diagnostic procedures, Pain after surgery Diagnostic, Pain after surgery, Pain after orthopedic surgery, Pain after injuries, Pain after the removal of hemorrhoids, Pain after surgery, Pain at the non-rheumatic inflammation of nature, Pain in inflammatory lesions of the peripheral nervous system, Pain in diabetic neuropathy, Pain in acute inflammatory diseases of the musculoskeletal system, Pain when the tendon pathology, Pain smooth muscle spasm, Pain spasm of smooth muscles (renal and biliary colic, intestinal spasms, dysmenorrhea), Pain spasm of smooth muscles of internal organs, Pain spasm of smooth muscles of internal organs (kidney and biliary colic, intestinal spasms, dysmenorrhea), Pain in trauma syndrome,Pain with injuries and after surgical interventions, Pain in chronic inflammatory diseases of the musculoskeletal system, Pain with duodenal ulcer, Pain syndrome in gastric ulcer, Pain syndrome in gastric ulcer and duodenal ulcer, pain, Pain during menstruation, pain syndromes, painful condition, Painful foot fatigue, Sore gums when wearing dentures, Soreness of the cranial nerves exit points, Painful menstrual irregularities, Painful dressings, Painful muscle spasm, Painful teeth growth, pain, Melosalgia, Pain in the area of the surgical wound, Pain in the postoperative period, Pain in the body, Pain after diagnostic procedures, Pain after orthopedic surgery,Pain after surgery, The pains of the flu, Pain in diabetic polyneuropathy, Pain for burns, Pain during sexual intercourse, Pain during diagnostic procedures, Pain during therapeutic procedures, for colds Pain,Pain in sinusitis, Pain in trauma, Pain traumatic, Pain, The pain in the postoperative period, Pain after diagnostic procedures, The pain after sclerotherapy, Pain after surgery, postoperative Pain, Pain postoperative and posttraumatic, posttraumatic pain, Pain when swallowing, Pain in infectious and inflammatory diseases of the upper respiratory tract, The pain of burns, The pain in traumatic muscle injury, Pain in trauma, The pain of tooth extraction, The pain of traumatic origin, Pain caused by spasm of smooth muscles, Expressed pain syndrome, Expressed pain syndrome, traumatic origin, Postoperative pain, postoperative pain, Post-traumatic pain, Post-traumatic pain syndrome, Torpid pain, Traumatic pain, Mild pain, Moderately severe pain, Moderate pain, Polyarthralgia with polymyositis

S06 Intracranial injury

Traumatic brain injury, Traumatic brain injury with a predominantly stem lesion level, Condition after traumatic brain injury,Brain Injury, skull Injuries, brain injury, Brain Contusion, Craniocerebral trauma, Traumatic brain injury,TBI, traumatic brain injury, The traumas of head injury, The consequence of traumatic brain injury, The consequence of TBI, Cranial trauma, Traumatic brain injury, Traumatic encephalasthenia, concussion

Z100 * CLASS XXII Surgical practice

Abdominal surgery, adenomectomy, Amputation, Coronary angioplasty, Angioplasty of the carotid arteries, Antiseptic skin treatment for wounds, Antiseptic Hand, Appendectomy, atherectomy, Balloon coronary angioplasty, Vaginal hysterectomy, The coronary bypass, Interventions in the vagina and cervix, Interventions on the bladder, Intervention in the mouth, Restoration and reconstructive surgery, Hand hygiene of medical personnel, Gynecologic surgery, Gynecological intervention, Gynecological surgery, Hypovolemic shock during operations, Disinfection of purulent wounds, Disinfection of wounds edges, Diagnostic intervention, Diagnostic procedures, Cervical Diathermocoagulation, Long-surgery, Replacing the fistula catheters, Infection in orthopedic surgery, Artificial heart valve, cystectomy, Short-term outpatient surgery, Short-term operation, Short surgical procedures, Krikotireotomiya, Blood loss during surgery, Bleeding during surgery and in the postoperative period, Kuldotsentez, laser photocoagulation, laser coagulation, retinal laser coagulation, Laparoscopy, Laparoscopy in Gynecology, CSF fistula, Small gynecological operations, Small surgical procedures, Mastectomy and subsequent plastic, mediastinotomy, Microsurgical operations on the ear, Mukogingivalnye operation, suturing, Minor surgery, neurosurgical operation, Immobilization of the eyeball in ophthalmic surgery, testectomy, pancreatectomy, Perikardektomiya, The period of rehabilitation after surgery, The period of, convalescence after surgery, Percutaneous transluminal coronary angioplasty, Pleural thoracentesis, Pneumonia postoperative and posttraumatic, Preparation for surgical procedures, Preparation for surgery, Preparation of the surgeon's hands before surgery, Preparation of the colon for surgical procedures, Postoperative aspiration pneumonia in neurosurgical and thoracic surgery, Postoperative nausea, Postoperative bleeding, postoperative granuloma, postoperative shock, The early postoperative period, myocardial revascularization, Radiectomy, gastric Resection, bowel resection, uterine Resection, liver Resection, enterectomy, Resection of part of the stomach, Reocclusion of the operated vessel, Bonding tissues during surgical procedures, Removal of sutures, Condition after eye surgery, Condition after surgery, Condition after surgery in the nasal cavity, Condition after gastrectomy, Status after resection of the small intestine, Condition after tonsillectomy, Condition after removal of the duodenum, Condition after phlebectomy, Vascular surgery, Splenectomy, Sterilization of surgical instruments, Sterilization of surgical instruments, sternotomy, Dental surgery, Dental intervention in periodontal tissues, strumectomy, Tonsillectomy, Thoracic surgery, total gastrectomy, Transdermal intravascular coronary angioplasty, Transurethral resection, Turbinektomiya, Removal of a tooth, cataract surgery, Removal of cysts, tonsillectomy, Removal of fibroids, Removing the mobile primary teeth, Removing polyps, Removing broken tooth, Removal of the uterus body, Removal of sutures, Urethrotomy, Fistula likvoroprovodyaschih ways, Frontoetmoidogaymorotomiya, Surgical infection, Surgical treatment of chronic limb ulcersm, Surgery, The surgery in the anal area, The surgery on the colon, Surgical practice, The surgical procedure, Surgical interventions, Surgery on the gastrointestinal tract, Surgical procedures on the urinary tract, Surgical procedures on the urinary system, Surgical intervention of the genitourinary system, Surgical procedures on the heart, Surgical manipulation, surgery, Surgery on the veins, Surgical intervention, Vascular surgery, Surgical treatment of thrombosis, cholecystectomy, Partial gastric resection, transabdominal hysterectomy, Percutaneous transluminal coronary angioplasty, Percutaneous transluminal angioplasty, Coronary artery bypass, tooth Extirpation, Extirpation of milk teeth, pulpectomy, pulsative cardiopulmonary bypass, tooth Extraction, teeth Extraction, cataract extraction, Electrocoagulation, endourological intervention, episiotomy, Etmoidotomiya, Complications after tooth extraction

Code CAS 51322-75-9

Characteristic

White or almost white crystalline powder, odorless or with a faint characteristic odor. Slightly soluble in water and methanol, water solubility decreases with increasing pH, molecular weight - 290.2.

Pharmacological Properties of TizanidinePharmachologic effect
muscle relaxant, central.

pharmacodynamics

Tizanidine - muscle relaxant central action. Stimulate presynaptic alpha2 adrenoceptors spinal cord, suppressing neurotransmitter release amino acids that stimulate the receptors to N-methyl-D-aspartate (NMDA receptors) that leads to excitation transfer inhibition polysynaptic spinal cord in performing regulation of skeletal muscle tone. Since this mechanism is responsible for excessive muscle tone, the muscle tone decreases in its suppression.

It reduces muscle stiffness during passive movements, thereby reducing the resistance to passive movements and increases the amount of active movements; reduces clonic spasms, as well as increases the strength of the arbitrary nature of contractions of skeletal muscles.

Pharmacokinetics

Suction

When administered tizanidine absorbed rapidly and almost completely. Tmax tizanidine in plasma is "1 hour after administration. Because the average value expressed metabolic bioavailability is about 34%.

Tizanidine Cmax of 12.3 and 15.6 ng / mL after single and multiple administration of 4 mg, respectively.

Distribution

Average value Vd - 2,6 l / kg. Plasma protein binding is 30%. In the dose range from 20 mg to 4 is linear pharmacokinetics. Given the low inter-individual variability of pharmacokinetic parameters (in particular, C max and AUC), while taking into tizanidine can reliably predict the value of its concentration in plasma.

Metabolism

Tizanidine metabolized rapidly and substantially in the liver (approximately 95%) with the formation of inactive metabolites. In vitro it was shown that tizanidine is mainly metabolized isoenzyme CYP1A2.

breeding

The average value of T1 / 2 of tizanidine from the circulation system is 2-4 hours. Tizanidine excreted mainly by the kidneys (approximately 70% of dose) in the form of metabolites at a fraction of unchanged substance accounts for about 4.5%.

Special groups paiientov

Impaired renal function. In patients with renal insufficiency (Cl creatinine ≤25 ml / min), the average Cmax plasma tizanidine 2 times higher than that in healthy volunteers and its final T1 / 2 as high as 14 hours, which results in increased (about 6 times) system tizanidine bioavailability (as measured by AUC).

Abnormal liver function. No specific studies have been conducted in these patients. Since tizanidine is extensively metabolized in the liver by isoenzyme CYP1A2, impaired hepatic function may lead to increased systemic exposure of tizanidine.

Patients older than 65 years. Data on the pharmacokinetics of tizanidine in this group of patients is limited.

Gender and race. Gender does not affect the pharmacokinetic parameters of tizanidine.

Influence of ethnicity and race on the pharmacokinetics of tizanidine has not been studied.

Effect of meal

Food does not affect the pharmacokinetics of tizanidine (although the value Cmax increased by 1.3, it is considered that it is not clinically significant, significant effect on absorption (AUC) were observed).

Indications for Tizanidine
Painful muscle spasms in spinal diseases (including low back pain, spondylosis, syringomyelia, hemiplegia, cervical and lumbar syndromes), following surgery for a herniated intervertebral disc or osteoarthritis of the hip, spasticity and pain caused by neurological diseases: multiple sclerosis, chronic myelopathy, degenerative diseases spinal cord injury, cerebrovascular accident, stroke, traumatic brain injury, cerebral palsy, seizures of central origin.

Contraindications for Tizanidine

Hypersensitivity to tizanidine; severe liver function; simultaneous use with potent inhibitors of CYP1A2 isoenzyme (fluvoxamine and ciprofloxacin), alpha2-adrenergic agonists; pregnancy; breastfeeding; children under 18 years (effectiveness and safety have been established).

Restrictions apply

Moderately severely impaired liver function; hypotension; bradycardia; congenital long QT syndrome interval; age over 65 years. It is necessary to regularly monitor the laboratory parameters of the functional state of the heart and ECG monitoring.

Renal failure and / or old age

Patients with renal insufficiency (Cl creatinine ≤25 mL / min) requires correction dosing regime. Experience with tizanidine in elderly patients is limited. Based on the pharmacokinetic data it can be assumed that in some cases the renal clearance of these patients can be significantly reduced. Caution should be exercised when using tizanidine in patients with renal insufficiency and in elderly patients.

Also, care must be taken while taking tizanidine with oral contraceptive drugs, anti-arrhythmic drugs, cimetidine, norfloxacin, rofecoxib, ticlopidine, digoxin, beta-blockers, sedative drugs, ethanol, diuretics and antihypertensive drugs (see. "Interaction").

Pregnancy and breast-feeding

Since the use of tizanidine controlled studies in pregnant women have not been conducted, it should not be used during pregnancy.

At the time of treatment tizanidine should stop breastfeeding because No data on its penetration into breast milk.

Category effects on the fetus by FDA - C.

Side effect of Tizanidine

The frequency of side effects listed below, defined respectively WHO classification: very common (≥10%); frequently (≥1%, <10%); infrequently (≥0,1%, <1%); rarely (≥0,01%, <0,1%); very rare (<0.01%) including isolated reports; Frequency not known (can not be estimated using the available data).

From the nervous system: very often - drowsiness, dizziness.

On the part of the psyche: often - insomnia, hallucinations, sleep disturbances.

From the CCC: often - a reduction of blood pressure (in some cases expressed, up to the collapse and loss of consciousness); infrequently - bradycardia.

From the digestive system: very often - dry mouth, gastrointestinal disorders; often - nausea.

Laboratory tests: often - increased activity of microsomal liver enzymes.

From the musculoskeletal system: very often - muscle weakness.

Skin and subcutaneous tissue disorders: allergic reaction (eg rash).

General disorders: often - fatigue, withdrawal syndrome.

With a sharp lifting of tizanidine after prolonged treatment and / or high-dose (as well as after the simultaneous application with antihypertensive drugs) noted tachycardia development and increase in blood pressure that can in some cases result in acute ischemic stroke, so the dose of tizanidine should be reduced gradually to the full the abolition of the drugs.

Anecdotal reports of adverse events according to the application in clinical practice

Against the background of tizanidine therapy in clinical practice, the following adverse events were observed without any indication of a causal link with the use of this drug (adverse events has not been established).

On the part of the psyche: the frequency is unknown - hallucinations, anxiety, confusion.

From the nervous system: the frequency is unknown - vertigo.

From a sight organ: the frequency is unknown - blurred vision.

On the part of the liver and biliary tract: the frequency is unknown - acute hepatitis, liver failure.

General disorders: frequency not known - fatigue, withdrawal syndrome.

Interaction

With simultaneous use of tizanidine and isoenzyme CYP1A2 inhibitors may increase concentrations of tizanidine in plasma. In turn, the increase in the plasma concentration of tizanidine can lead to symptoms of an overdose of the drug, including prolongation of the QTc interval.

Concomitant use of inducers of CYP1A2 isoenzyme may reduce the levels of tizanidine in plasma. Reduced levels of tizanidine in plasma may lead to a reduction of its therapeutic effect.

Tizanidine is contraindicated in combination

Concomitant use of tizanidine with fluvoxamine or ciprofloxacin, which are inhibitors of isoenzyme CYP1A2, is contraindicated.

In the application of tizanidine with fluvoxamine or ciprofloxacin is celebrated 33-fold and 10-fold increase in tizanidine AUC, respectively. The result of combined use may prove to be clinically significant and sustained reduction in blood pressure is accompanied by sleepiness, dizziness, decreased psychomotor speed reactions (in some cases up to the collapse and loss of consciousness).

Not recommended combinations of tizanidine

Do not appoint tizanidine together with other inhibitors of CYP1A2 isoenzyme - antiarrhythmic drugs (amiodarone, mexiletine, propafenone), cimetidine, some fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives, ticlopidine.

Combinations requiring compliance with caution

Care should be taken when used together with tizanidine drugs prolong the interval QT (eg cisapride, amitriptyline, azithromycin).

Antihypertensive drugs

Concomitant use of tizanidine with antihypertensive drugs, including diuretics, can sometimes cause a marked reduction of blood pressure (in some cases up to the collapse and loss of consciousness) and bradycardia.

With a sharp lifting of tizanidine after use with antihypertensive drugs mentioned tachycardia development and increase in blood pressure, in some cases, could lead to acute stroke.

Rifampicin

Simultaneous treatment with tizanidine and rifampicin results in a 50% decrease in tizanidine concentration in blood plasma. As a result, the therapeutic effect of tizanidine may decline, which could have clinical relevance for some patients. Avoid prolonged joint use of rifampicin and tizanidine, when it is impossible recommended careful selection of the dose of tizanidine (increased).

Smoking

Systemic bioavailability of tizanidine male smokers (more than 10 cigarettes a day) reduced by approximately 30%. Long-term therapy tizanidine male smokers may require higher doses than the average therapeutic.

ethanol

During therapy should avoid taking tizanidine ethanol because it may increase the likelihood of adverse events (such as reduction of blood pressure and sedation). Tizanidine may enhance the inhibitory effect of ethanol on the CNS.

Other drugs

Sedatives, hypnotics drugs (benzodiazepines, baclofen) and other drugs, such as antihistamines, can also enhance the sedative effect of tizanidine.

Avoid receiving tizanidine with other alpha2-adrenergic agonists (such as clonidine) because of the potential gain hypotensive effect.

The food (see. "Pharmacokinetics").

Overdose of Tizanidine
To date, there are cases of tizanidine overdose, including the case where the dose taken was 400 mg. In all cases, recovery was uneventful.

Symptoms include nausea, vomiting, marked reduction in blood pressure, QTc prolongation, dizziness, drowsiness, cramps, anxiety, respiratory failure, coma.

Treatment: to remove from the body of tizanidine is recommended gastric lavage, repeated appointment of activated charcoal, drinking large amounts of fluids. Carrying out forced diuresis may also speed up the elimination of tizanidine. Subsequently, symptomatic treatment.

Routes of administration

Inside.

Precautions matter of tizanidine

Hypotension may occur during treatment with tizanidine, but also as a result of interaction with inhibitors of the CYP1A2 isoenzyme and / or antihypertensive drugs. The marked decrease in blood pressure can lead to loss of consciousness and collapse.

Reported cases of liver dysfunction associated with tizanidine, but the application of a daily dose to 12 mg of these cases were rare. In this regard, it is recommended to monitor liver function tests 1 every month during the first 4 months of treatment in patients who are assigned tizanidine in a daily dose of 12 mg and above, as well as in cases where there are clinical signs suggestive of liver dysfunction - such as unexplained nausea, anorexia, fatigue. In the case where the ACT and ALT levels in serum exceed stable ULN 3 times or more, the use of tizanidine should be discontinued.

During treatment should refrain from the use of ethanol.

Patients older than 65 years. Experience with tizanidine in patients aged 65 years and older is limited. It is recommended to start treatment with the lowest dose with gradual increase to achieve the optimum ratio of tolerability and efficacy.

Renal insufficiency. Patients with renal insufficiency (Cl creatinine ≤25 mL / min) the recommended initial dose - 1 mg 2 times a day. Increasing doses are gradually slow in view of portability and efficiency. If you want to get a more pronounced effect, it is recommended to increase the dose to be assigned to one time per day, then increase the multiplicity of purposes.

Abnormal liver function. The use of tizanidine in patients with severe hepatic impairment is contraindicated.

Interruption of treatment

Upon termination of tizanidine therapy to reduce the risk of rebound increase in blood pressure and tachycardia, should slowly reduce the dose to the complete abolition of drugs, especially in patients receiving high doses of tizanidine in a long time.

Effects on ability to drive and use machines. Due to the profile of adverse reactions, it is recommended to refrain from activities that require high concentration and quick reactions, such as driving a vehicle or using machinery.