Adults

Initial dose is 2 mg orally once daily, gradually increased by 2-4 mg increments at 3-7 day intervals. The usual dose is 2-4 mg three times daily. Maximum recommended dose is 36 mg per day.

Elderly

Start with lower doses (e.g., 2 mg once daily) and titrate slowly due to potential for increased sensitivity and reduced renal clearance.

Renal_impairment

For patients with creatinine clearance <25 mL/min, initiate with 2 mg once daily and titrate slowly. Discontinue if benefit is not achieved with low doses.

Onset

Onset of action typically occurs within 1-2 hours.

Excretion

Approximately 60% of the dose is excreted via the kidneys after 24 hours. Renal clearance is the primary route.

Half life

The elimination half-life is approximately 2.5 hours (range 1.5-4 hours).

Absorption

Rapidly and almost completely absorbed from the gastrointestinal tract. Absolute bioavailability is about 40% due to first-pass metabolism.

Metabolism

Extensively metabolized in the liver, primarily by the cytochrome P450 1A2 (CYP1A2) isoenzyme.

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CYP1A2 Inhibitors (e.g., fluvoxamine, ciprofloxacin): Concomitant use is contraindicated due to significantly increased tizanidine levels, leading to severe hypotension, drowsiness, and psychomotor impairment.

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Oral Contraceptives: May increase tizanidine exposure by inhibiting CYP1A2.

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Alcohol and other CNS depressants: Increased risk of sedation and hypotension.

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Antihypertensives: Increased risk of hypotension and bradycardia.