Tizanidine

Tizanidine is a central alpha-2 adrenergic agonist used for spasticity from multiple sclerosis and spinal cord disease, and off-label for muscle spasm. It causes sedation, hypotension and dry mouth, can injure the liver, and is contraindicated with strong inhibitors of its metabolism.

Mechanism. Agonist at alpha-2 adrenergic receptors in the spinal cord, reducing release of excitatory neurotransmitters and spinal reflex activity.

Pharmacokinetics. Bioavailability about 40% and half-life about 2.5 hours. It is metabolised mainly by cytochrome P450 1A2. Food affects absorption differently for tablets and capsules.

First-line and alternative use. Spasticity, especially when daytime spasms need short-acting cover, or when baclofen is not tolerated.

• Adults, oral tizanidine: 2 mg once daily (often at night), then increase by 2 mg every 3 to 7 days. Usual maintenance 12 to 24 mg daily in three or four divided doses. Maximum 36 mg daily, with no single dose over 12 mg.

• Use for short-term cover: 2 to 4 mg for specific times of day when spasticity interferes with activity.

• Off-label for painful muscle spasm: same start, rarely beyond 8 to 12 mg daily.

Kidney, liver, weight and age.

• Kidney: creatinine clearance under 25 mL/min, start 2 mg once daily and increase slowly.

• Liver: contraindicated in severe impairment; in mild to moderate impairment, use lower doses and monitor liver enzymes.

• Older adults: start 2 mg once daily and titrate slowly.

Contraindications. Severe hepatic impairment, concurrent fluvoxamine or ciprofloxacin, and hypersensitivity.

Serious adverse effects. Hepatotoxicity, hypotension and syncope, bradycardia, hallucinations, QT prolongation, and rebound hypertension and tachycardia on abrupt withdrawal.

Common adverse effects. Drowsiness, dry mouth, dizziness, asthenia and nausea.

Interactions. Fluvoxamine and ciprofloxacin (strong cytochrome P450 1A2 inhibitors) are contraindicated, and other inhibitors (some oral contraceptives, cimetidine) raise levels. Antihypertensives add hypotension. Alcohol and sedatives add drowsiness. QT-prolonging drugs add risk.

Common prescribing errors. Prescribing with ciprofloxacin. Fast titration. Missing liver tests. Abrupt withdrawal.

Special groups.

• Pregnancy: avoid unless essential.

• Breastfeeding: avoid.

• Older adults: higher risk of hypotension and falls.

Formulations. Tablets 2 and 4 mg. Capsules 2, 4 and 6 mg in some markets. Take consistently with or without food, as tablets and capsules differ in their food effect.

Monitoring.

• Baseline liver function, then at 1, 3 and 6 months, and when symptoms suggest liver injury.

• Blood pressure, pulse, sedation and spasticity at each review.

Stopping. Taper over 1 to 2 weeks, particularly after high doses or long use, to avoid rebound hypertension.

Referral and escalation. Refer for poor control, liver enzyme elevation, or hallucinations.