What Is Tizanidine HCl?

Tizanidine hydrochloride tablets, the indication is that tizanidine hydrochloride tablets are central skeletal muscle relaxation drugs, used to reduce skeletal muscle tension caused by brain and spinal cord trauma, cerebral hemorrhage, encephalitis, and multiple sclerosis. Muscle spasms and muscle rigidity.

Drug Name: Tizanidine hydrochloride tablets

Drug type: Prescription drugs, medicines for medical workers' injuries

Ingredients of Tizanidine Hydrochloride

The main ingredient of this product is tizanidine hydrochloride, and its chemical name is 5-chloro-4- (2-imidazoline-2-amino) -2,1,3-benzylthiothiazine hydrochloride.
Molecular formula: C ₉ H ₈ CIN ₅ S.HCl
Molecular weight: 290.17

Characteristics of Tizanidine Hydrochloride Tablets

This product is white to off-white film.

Tizanidine hydrochloride tablets specifications

4mg / tablet

Tizanidine hydrochloride dosage and dosage

Patients should use a dose adjustment period of 2 to 4 weeks for the first time. The starting dose is 2 to 4 mg each time, once every 6 to 8 hours. The single dose should not exceed 8mg, and the daily dose should not exceed 24mg. The maximum dosage is 36mg daily. Due to the strong first-pass effect of this product, the dose should be individualized when used.

Adverse effects of tizanidine hydrochloride tablets

According to the literature:
1. General adverse events leading to treatment discontinuation: In a multi-dose, placebo-controlled clinical study, 264 patients were given tizanidine and 261 were given a placebo. Several serious adverse events were included in the drug treatment group Adverse reactions occurred more frequently than placebo controls.
In a multiple-dose placebo-controlled study, patients discontinued due to adverse reactions occurred in 45 (17%) of 264 patients receiving tizanidine and 13 of 261 patients receiving placebo (5%). When withdrawing from treatment, they often state two or more reasons to stop taking the medication. The most common adverse events that led to discontinuation were fatigue (3%), lethargy (3%), dry mouth (3%), increased spasm or tension (2%), and dizziness (2%). Among them, fatigue, lethargy / sedation, dry mouth, and dizziness were the most common adverse events associated with tizanidine. Three-quarters of these patients considered these adverse events to be mild-moderate and 1/4 Considered serious; these adverse events were dose-dependent.
2. In the study of 142 subjects who received a single dose of placebo, in addition to the most common adverse events mentioned above, there were hypotension and bradycardia (incidence rate> 2%).
3. Other adverse reactions observed in the study: Adverse events of tizanidine were observed in a clinical study of another 1187 patients. Some of these studies are randomized, double-blind, and some are open studies; some are placebo-controlled studies, and some have no control group; some are outpatients, some are inpatients; and some use a gradually increasing dosing schedule . The final statistical results are divided into systemic adverse events and adverse events of each system based on the COSTART principle. The incidence of common adverse events is more than 1/100, the incidence of rare adverse events is between 1/100 and 1/1000, and the incidence of rare adverse events is 1/1000. It should be noted that although these adverse events occurred during tizanidine treatment, they were not necessarily caused by the drug.
(1) Systemic adverse events: common: fever; rare: allergies, candidiasis, discomfort, abscess, neck pain, sepsis, death; rare: cancer, congenital malformation, suicidal tendency.
(2) Cardiovascular system: rare: vasodilation, orthostatic hypotension, syncope, migraine, arrhythmia; rare: angina pectoris, coronary artery disease, heart failure, myocardial infarction, phlebitis, pulmonary embolism, early ventricle And VT.
(3) Digestive system: common: abdominal pain, diarrhea, indigestion; rare: dysphagia, gallstones, fecal impaction, flatulence, melena, hepatitis; rare: vomiting, gastroenteritis, liver cancer, small intestine Obstruction, liver damage.
(4) Hemolymphatic system: Rare: bruising, hypercholesterolemia, anemia, hyperlipidemia, leukopenia, leukocytosis, sepsis; rare: bruising, purpura, thrombocytopenia, thrombocytosis .
(5) Nutrition and metabolic systems: rare: edema, hypothyroidism, weight loss; rare: adrenal insufficiency, hyperglycemia, hyperkalemia, hyponatremia, hypoproteinemia, and respiratory acid Poisoning.
(6) Skeletal muscle system: common: muscle weakness, back pain; rare: pathological fractures, joint pain, arthritis and bursitis.
(7) Nervous system: common: depression, anxiety, paresthesia; rare: tremor, emotional instability, convulsions, paralysis, abnormal thinking, dizziness, strange dreams, agitation, loss of self-esteem, euphoria, migraine, Loss of sensation, autonomic dysfunction, neuralgia; rare: dementia, neuropathy.
(8) Respiratory system: rare: sinusitis, pneumonia, bronchitis; rare: asthma.
(9) Skin and appendages: common: rash, sweating, skin ulcers; rare: itching, dry skin, hemorrhoids, baldness, urticaria; rare: exfoliation, dermatitis, herpes simplex, shingles, skin cancer.
(10) Special sensations: rare: ear pain, tinnitus, deafness, glaucoma, combined meningitis, eye pain, optic neuritis, otitis media, retinal hemorrhage, visual field defect; rare: iris inflammation, eye atrophy.
(11) Urogenital system: Rare: Urgency, cystitis, urinary retention, menstruation, pyelonephritis, kidney stones, enlarged uterine fibrosis, vaginal candidiasis, vaginitis; rare: proteinuria, diabetes, Hematuria, uterine blood.
4. Drug addiction and dependence: No human studies have been conducted on drug addiction. When monkeys are dosed in a dose-dependent manner, the drug is abruptly discontinued when it exceeds 35 times the maximum human recommended dose (mg / m ² ), which can produce transient withdrawal symptoms. This transient withdrawal symptoms (increased activity, Physical tremors, hostile emotions, cannot be reversed by naloxone.

Tabezidine hydrochloride taboo

Patients allergic to tizanidine hydrochloride and other components are contraindicated.

Precautions for Tizanidine Hydrochloride Tablets

1. Hypotension: Tizanidine is an alpha ₂ receptor agonist (similar to clonidine) and may cause hypotension. A single-dose clinical study showed that two-thirds of patients in the 8 mg tizanidine treatment group had a 20% decrease in systolic or diastolic blood pressure. Hypotension occurred at 1 h after administration, peaked at 2-3 h, and sometimes accompanied by Have bradycardia, hypotension in an upright position, mild headache / dizziness, and very few syncope. This hypotension effect is dose-dependent. When a single dose is greater than 2 mg, blood pressure is monitored. By adjusting the dose and paying close attention to the signs and symptoms of hypotension, the apparent hypotension may be greatly reduced. In addition, the risk of hypotension and orthostatic hypotension is greater when the patient changes from lying to standing. Be more vigilant when using antihypertensive drugs, and should not be combined with other 2 receptor agonists. Patients should be informed during use and brought to their attention.
2. Risk of liver damage: Tizanidine can occasionally cause liver damage. In a clinical study with a control group, liver function tests have increased in nearly 5% of patients taking tizanidine, which is three times higher than the upper limit of normal (if the original baseline value is increased, it is more than two times higher). In the normal control group, only 0.4% of patients had a similar situation. Most cases recovered rapidly after discontinuation of the drug, and there were no reports of its effects. Occasional symptoms such as nausea, vomiting, decreased appetite, and jaundice. After listing, it was found that there were 3 cases of death due to liver failure when taking tizanidine. One 49-year-old male patient, 6 mg once a day, three times a day. Liver jaundice and hepatomegaly appeared after taking 2 weeks. Liver biopsy showed Polycentric necrosis, no eosinophil infiltration, discontinuation of medication, the patient died of liver coma 10 days later; this patient had no evidence of hepatitis B and C, and had only used oxazepam and ranitidine, except for tiza Nitinin, there is no other reason to explain liver damage. In the other 2 cases, drugs that impaired liver function were used at the same time. One patient received carbamazepine and tizanidine 4 mg / day, and cholestatic jaundice occurred after 2 months of treatment. The patient died of pneumonia 20 days later; the other patient used 11 days of tizanidine, during which Dantrolene was also used for 2 weeks before rapid and fatal liver failure. Therefore, after taking tizanidine for 6 months (January, March, June) and after 6 months, according to the specific clinical reality, patients should be regularly tested for transaminase, and the drug should be used in patients with liver damage. Be more cautious.
3. Sedative effects: Clinical studies with multiple doses have shown that 48% of patients reported this adverse event, of which 10% were more serious, while the control group had less than 1%. After the first week of dose adjustment, it reached a peak and remained stable during the administration period; single-dose studies found that the effect was dose-dependent and began to appear within 30 minutes after taking the drug. It reached a peak at 1.5 hours and generally lasted 6 hours. 51% of patients who were too large (16mg) remained drowsy after 6 hours, compared with 13% in the control group or the 8mg dose group. Sedation may interfere with patients' daily activities. Therefore, patients should be informed that the drug has a sedative effect, and some occupations, such as drivers, need to focus on the operation of the patient. Patients should be more vigilant and reminded that if they are taking other drugs with central nervous system inhibitory effects (such as The sedative effect of chloramphenicol, benzodiazepines, ethanol, etc.) will be enhanced.
4. Hallucinogenic and psychotic effects: Tizanidine is associated with hallucinogenic effects. In two North American clinical studies, 3% (5/170) of patients reported visual hallucinations or illusions during the first 6 weeks, and most of them were aware that this phenomenon was unreal, and one of them developed hallucinations. Of the patients with mental illness, 1 case of this adverse event lasted more than 2 weeks after discontinuation.
5. Cardiovascular: The long-term toxicity study in dogs (equivalent to the maximum dosage in humans) found that it should cause QT interval prolongation and bradycardia; ECG evaluation has not been performed in controlled clinical studies; and in single-dose controlled studies With a decrease in blood pressure, the pulse rate slows.
6. Ophthalmology: Animal studies equivalent to the maximum recommended clinical dosage found that tizanidine caused dose-dependent retinal degeneration and corneal opacity, but it was not seen in clinical experiments.
7. Application in patients with renal impairment: In patients with impaired renal function (creatinine clearance rate is less than 25mg / min), the clearance rate is reduced by 50%, so special attention should be paid when using it. In these patients, the single dose should be reduced; if a larger dose is required, the single dose can be increased instead of the number of doses; monitoring should be performed at the beginning of use, and general adverse reactions (dry mouth, lethargy, fatigue) , Dizziness) would be an indication of a potential overdose.

Tizanidine hydrochloride tablets for pregnant and lactating women

This product is not fully evaluated for pregnant and lactating women. It is not known whether the drug is secreted by breast milk. However, due to its fat solubility, it may enter milk. Therefore, pregnant women and lactating women should fully weigh the pros and cons before taking the drug. consider.

Tizanidine hydrochloride tablets for children

The safety of medications for children has not been fully evaluated.

Tizanidine hydrochloride tablets for the elderly

This product is mainly excreted in the kidney, so in many cases that make kidney function low, for elderly patients, this drug can continuously increase the blood concentration, so pay attention to reducing the dosage; this product has the effect of lowering blood pressure, and it is used in elderly patients Be careful.

Tizanidine hydrochloride drug interactions

In vitro experimental studies with human liver microsomal cytochrome P450 isoenzymes showed that tizanidine hydrochloride and its metabolites did not affect the metabolism of this enzyme by other drugs.
Tizanidine hydrochloride delayed the peak time of paracetamol by 16 minutes, while paracetamol had no effect on the pharmacokinetic parameters of tizanidine hydrochloride.
Ethanol increased the area under the curve of tizanidine hydrochloride by about 20% and increased the maximum peak concentration by 15%. At the same time, the adverse reactions of tizanidine hydrochloride increased, and the central nervous system inhibitory effects of ethanol and tizanidine hydrochloride were similar. Plus effect.
A retrospective study of single or multiple administrations of 4 mg tizanidine hydrochloride showed that concurrent use of oral contraceptives reduced the clearance rate of tizanidine hydrochloride by 50% compared with patients who did not take concurrent oral contraceptives.

Tizanidine hydrochloride overdose

It has been reported that a 46-year-old male patient with sclerosis had a coma immediately after taking 100 tablets (4mg / tablet) of tizanidine. He had no dilated nystagmus during physical examination, and the patient developed Cheyme-Stokes-like breathing. Significant respiratory depression, forced diuresis by gastric lavage and furosemide and mannitol, the patient awoke after a few hours, no sequelae, and laboratory tests were normal.
For this reason, if an overdose occurs, the airway should be ensured first, followed by monitoring of the respiratory and circulatory systems.

Pharmacology and toxicology of tizanidine hydrochloride tablets

Pharmacological effect Tizanib is a central ₂ adrenergic receptor agonist, which may reduce tonic spasticity by enhancing the prominent pre-inhibition of motor neurons. Animal tests have shown that tizanidine has no direct effect on skeletal muscle fibers and neuromuscular junctions, and has a weak effect on single synaptic spinal cord reflex. Tizanidine has the strongest effects on multiple synaptic pathways, and these effects are thought to be related to reduced facilitation of spinal motor neurons.
Toxicological studies for genotoxicity:
Tizanidine Ames test, mammalian gene mutation test, Chinese hamster cell chromosome aberration test, mouse bone marrow micronucleus test, Chinese hamster bone marrow micronucleus test and cytogenetic test, mouse dominant lethal mutagenesis test and mouse Out-of-program DNA synthesis tests were negative.
Reproductive toxicity:
Male rats were given tizanidine 10 mg / kg, and female rats were given 3 mg / kg (calculated as mg / m ² , equivalent to 2.7 times and 1 times the maximum human recommended dose, respectively). No effect on fertility was seen. When male rats were given tizanidine 30 mg / kg and female rats were given 10 mg / kg, fertility decreased, and the mother showed sedation, weight loss, and dyskinesia. Rats were given 3 mg / kg of tizanidine and 30 mg / kg of rabbits (calculated as mg / m ² , equivalent to 1 and 16 times the maximum human recommended amount, respectively), and no teratogenic effects were seen. Administration of 1 to 8 times the maximum recommended dose of tizanidine can prolong the gestation period of rats, leading to increased loss of perinatal pups and delayed development. Rabbits given tizanidine at a dose of 1 mg / kg and higher increased loss of embryos after implantation.
Carcinogenicity:
The mice were orally given tizanidine at a dose of 16 mg / kg for 78 consecutive weeks, and the rats were orally given tizanidine at a dose of 9 mg / kg for 104 consecutive weeks (calculated as mg / m ² , which are equivalent to the human maximum). 2 times and 2.5 times the recommended amount), no significant increase in tumor incidence.

Pharmacokinetics of Tizanidine Hydrochloride Tablets

Tizanidine hydrochloride is well absorbed orally, and its absolute oral bioavailability is 40% (CV = 24%). The time to reach the peak concentration after oral administration is 1.5h (CV = 40%); food can increase the peak plasma concentration (Cmax) after oral administration of the drug by nearly 1/3, and shorten the peak time by nearly 40min, but it does not affect Total gastrointestinal absorption of the drug. Tizanidine hydrochloride is widely distributed in vivo, and the Vd of healthy volunteers when intravenously administered is stable is 2.4 L / kg (CV = 21%). The drug and plasma protein binding rate is about 30%, and there is no obvious concentration dependence in the therapeutic dose range. The liver has a large first pass elimination effect on the drug, and about 95% of the drug is metabolized by the liver after administration, and the metabolites have no significant activity. Tizanidine hydrochloride plasma elimination half-life (T _1/2 ) is about 2.5 hours (CV = 33%), and its T _1/2 of its metabolites is 20-40 hours. About 20% of tizanidine hydrochloride is excreted through the intestine, and more than 60% of the drug is excreted by the kidney, of which the original excreta is only 3%. Poor renal function significantly affects the excretion of the drug; when the creatinine clearance is less than 1.5L / At h, the rate of renal excretion of the drug was reduced by more than 50%, and the plasma elimination half-life of the drug was prolonged by an average of 13.6 hours.

Tizanidine Hydrochloride Tablets Storage

Sealed

Packaging of Tizanidine Hydrochloride Tablets

6 pieces / board / box, 2 × 6 pieces / board / box, aluminum plastic packaging.

Validity of Tizanidine Hydrochloride Tablets

Tentative 24 months ^[1]