Tisalud (Tablets) Instructions for Use

Marketing Authorization Holder

Veropharm, JSC (Russia)

ATC Code

M03BX02 (Tizanidine)

Active Substance

Tizanidine

Dosage Forms

	Tisalud	Tablets 2 mg: 30 pcs.
		Tablets 4 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Tablets white or white with a yellowish tint, round, biconvex, with a score.

Excipients: anhydrous lactose (lactopress) – 117.012 mg, microcrystalline cellulose (MCC 102) – 14 mg, sodium starch glycolate type A (primogel) – 4.2 mg, magnesium stearate – 2.5 mg.

10 pcs. – blister packs (3) – cardboard packs.

Tablets white or white with a yellowish tint, round, biconvex, with a score.

Excipients: anhydrous lactose (lactopress) – 234.024 mg, microcrystalline cellulose (MCC 102) – 28 mg, sodium starch glycolate type A (primogel) – 8.4 mg, magnesium stearate – 5 mg.

10 pcs. – blister packs (3) – cardboard packs.

Clinical-Pharmacological Group

Centrally acting muscle relaxant

Pharmacotherapeutic Group

Centrally-acting muscle relaxant

Pharmacological Action

Centrally acting muscle relaxant. Its primary site of action is in the spinal cord. By stimulating presynaptic α₂-adrenoceptors, it inhibits the release of excitatory amino acids that stimulate N-methyl-D-aspartate (NMDA) receptors. As a result, polysynaptic transmission of excitation is suppressed at the level of the spinal cord interneurons. Since this mechanism is responsible for excessive muscle tone, its suppression leads to a reduction in muscle tone. In addition to its muscle relaxant properties, Tizanidine also has a moderately pronounced central analgesic effect.

Tizanidine is effective in chronic spasticity of spinal and cerebral origin. It reduces spasticity and clonic convulsions, thereby decreasing resistance to passive movements and increasing the range of active movements.

Pharmacokinetics

After oral administration, Tizanidine is rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability is about 34%. Plasma protein binding is 30%.

Tizanidine is rapidly and extensively (about 95%) metabolized in the liver. In vitro, Tizanidine is metabolized mainly by the cytochrome P450 isoenzyme CYP1A2. The metabolites are inactive.

The T_1/2 averages 2-4 hours. It is excreted by the kidneys (approximately 70% of the dose) as metabolites, with about 4.5% excreted unchanged.

Indications

Spastic condition of skeletal muscles caused by neurological diseases (multiple sclerosis, chronic myelopathy, stroke, degenerative diseases of the spinal cord). Painful spasm of skeletal muscles due to spinal lesions (cervical and lumbar syndromes) or occurring after surgery (for herniated disc or hip osteoarthritis).

ICD codes

Dosage Regimen

Determine the dose, regimen, and duration of therapy individually based on the clinical situation and severity of spasticity.

Initiate treatment with a low dose and titrate gradually to achieve the desired therapeutic effect.

For the 2 mg tablet, start with 2 mg or 4 mg as a single dose. For the 4 mg tablet, initiate with 4 mg as a single dose.

Administer the total daily dose in three or four divided doses.

Increase the dose in 2 mg or 4 mg increments at intervals of no less than 3 to 4 days.

The maximum recommended single dose is 12 mg.

Do not exceed the maximum total daily dose of 36 mg.

For painful muscle spasms associated with spinal conditions, the usual effective dose ranges from 6 mg to 12 mg daily.

For the management of chronic spasticity of neurological origin, the usual effective maintenance dose ranges from 12 mg to 24 mg daily.

In elderly patients over 65 years and patients with renal or moderate hepatic impairment, initiate therapy at the lowest possible dose and titrate cautiously.

When discontinuing treatment, especially after long-term use or high doses, gradually reduce the dose to minimize the risk of withdrawal effects such as tachycardia and hypertension.

Adverse Reactions

Nervous system disorders: very common – drowsiness, dizziness.

Psychiatric disorders: common – insomnia, sleep disorders; frequency unknown – hallucinations, confusion.

Cardiovascular system disorders: common – decreased blood pressure (in some cases pronounced, up to vascular collapse and loss of consciousness); uncommon – bradycardia.

Digestive system disorders: very common – dyspeptic phenomena, dry mouth; common – nausea.

Hepatobiliary disorders: frequency unknown – hepatitis, liver failure.

Musculoskeletal and connective tissue disorders: very common – muscle weakness.

Investigations: common – increased activity of liver transaminases.

Immune system disorders: hypersensitivity reactions (including anaphylactic reactions, angioedema, urticaria).

Skin and subcutaneous tissue disorders: frequency unknown – skin rash, erythema, skin itching, dermatitis.

General disorders and administration site conditions: very common – increased fatigue; frequency unknown – asthenia, withdrawal syndrome, blurred vision.

Contraindications

Hypersensitivity to tizanidine; severe liver dysfunction; simultaneous use with potent inhibitors of the CYP1A2 isoenzyme (such as fluvoxamine or ciprofloxacin); children and adolescents under 18 years of age.

With caution in patients over 65 years of age, patients with impaired renal function, patients with moderate liver dysfunction. Caution should be exercised when used concomitantly with drugs that prolong the QT interval (e.g., cisapride, amitriptyline, azithromycin).

Use in Pregnancy and Lactation

During pregnancy, should be used only after consultation with a doctor, in cases where the intended benefit to the mother outweighs the potential risk to the fetus or infant.

Contraindicated for use during lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in patients with severe liver dysfunction. Use with caution in patients with moderate liver dysfunction. It is recommended to start therapy with the minimum dose, with gradual increase until the optimal balance of tolerability and efficacy of therapy is achieved.

Use in Renal Impairment

Use with caution in patients with impaired renal function. It is recommended to start therapy with the minimum dose, with gradual increase until the optimal balance of tolerability and efficacy of therapy is achieved.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in patients over 65 years of age. It is recommended to start therapy with the minimum dose, with gradual increase until the optimal balance of tolerability and efficacy of therapy is achieved.

Special Precautions

When discontinuing tizanidine therapy, to reduce the risk of rebound arterial hypertension and tachycardia, its dose should be slowly reduced until complete withdrawal in patients receiving Tizanidine in high doses for a long time.

Abrupt withdrawal of tizanidine after prolonged treatment and/or high-dose use, as well as after simultaneous use with antihypertensive drugs, has been observed to cause tachycardia and increased blood pressure, which in some cases can lead to acute cerebrovascular accident; therefore, the dose of tizanidine should be gradually reduced until complete withdrawal.

When using tizanidine, it is recommended to monitor liver function tests once a month for the first 4 months of treatment in patients receiving Tizanidine at a daily dose of 12 mg and above, as well as in cases where clinical signs suggestive of liver dysfunction (such as unexplained nausea, anorexia, feeling of fatigue) are observed. In cases where serum ALT and AST activity persistently exceed the upper limit of normal by 3 times or more, tizanidine should be discontinued.

During the use of tizanidine and for 1 day after its discontinuation, women with preserved reproductive potential should use reliable methods of contraception.

Influence on the ability to drive vehicles and mechanisms

During the use of tizanidine, patients should exercise caution when driving vehicles and operating machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Concomitant use of tizanidine with inhibitors of the CYP1A2 isoenzyme may increase the plasma concentration of tizanidine, which in turn may lead to symptoms of overdose, including prolongation of the QT(c) interval.

Concomitant use of tizanidine with inducers of the CYP1A2 isoenzyme may decrease the plasma concentration of tizanidine, which may lead to a reduction in its therapeutic effect.

When tizanidine is used concomitantly with fluvoxamine or ciprofloxacin, a 33-fold and 10-fold increase in the AUC of tizanidine is observed, respectively. The result of concomitant use may be clinically significant and prolonged arterial hypotension, accompanied by drowsiness, dizziness, and decreased speed of psychomotor reactions (in some cases up to collapse and loss of consciousness).

Concomitant use of tizanidine with antihypertensive drugs, including diuretics, may cause decreased blood pressure (in some cases up to vascular collapse and loss of consciousness) and bradycardia.

Concomitant use with tizanidine of sedatives, hypnotics (benzodiazepines, baclofen), histamine H₁-receptor blockers may enhance the sedative effect of tizanidine.

Concomitant use of tizanidine and rifampicin leads to a 50% decrease in the plasma concentration of tizanidine.

Concomitant use of ethanol, drugs with sedative effects enhances the sedative effect of tizanidine.

The systemic bioavailability of tizanidine in smoking patients (more than 10 cigarettes per day) is reduced by approximately 30%.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.