Tizanidine

# Tizanidine ## Overview Tizanidine is a centrally acting alpha-2 adrenergic agonist. It reduces spasticity by increasing presynaptic inhibition of motor neurons. Onset of action is 30–60 minutes; peak effect at 1–2 hours; half-life ~2.5 hours. **Caution:** Hypotensive and sedative effects are dose-dependent and can be significant at higher doses. ## Primary Indications - Management of spasticity associated with multiple sclerosis or spinal cord injury - Not indicated for spasticity due to rheumatic conditions or stroke (off-label use with caution) ## Adult Dosing **Individualize gradually.** - **Initial:** 2 mg orally every 6–8 hours as needed; may increase by 2–4 mg per dose at 1–2 week intervals - **Usual therapeutic range:** 8–16 mg/day divided 3–4 times daily - **Maximum single dose:** 8 mg - **Maximum total daily dose:** 36 mg (seldom required; higher risk of adverse effects) Titrate to effect; lower doses may be effective. **Do not stop abruptly**—taper to avoid rebound hypertension and tachycardia. ## Pediatric Dosing Limited data; no FDA-approved pediatric indication. - **Children (12–17 years):** Doses extrapolated from adult experience—start 1–2 mg every 6–8 hours; maximum 8 mg single dose, 24 mg/day. - **Children <12 years:** Dosing not well established; consult pediatric neurology specialist. Use only if benefit clearly outweighs risks. ## Dose Adjustments - **Renal impairment (CrCl <25 mL/min):** Start with 2 mg once daily; increase slowly (max 8 mg/day). - **Hepatic impairment:** Avoid use if significant liver disease. - **Elderly:** Start at lowest dose (2 mg once daily); titrate cautiously. ## Contraindications - Hypersensitivity to tizanidine or any component - Hepatic impairment (Child-Pugh C) - Concurrent use with strong CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine)—contraindicated due to risk of severe hypotension, sedation, and QT prolongation ## Adverse Effects **Common:** Drowsiness, sedation, dry mouth, dizziness, fatigue, hypotension, bradycardia. **Serious:** Hepatotoxicity (rare), hallucinations, prolonged QT interval (dose-related), severe hypotension when combined with CYP1A2 inhibitors. **Withdrawal:** Rebound hypertension, tachycardia, clonus, and anxiety if abruptly stopped. ## Key Drug Interactions - **CYP1A2 inhibitors** (ciprofloxacin, fluvoxamine, zileuton, cimetidine, oral contraceptives) — **contraindicated** with strong inhibitors - **Other CNS depressants** (alcohol, benzodiazepines, opioids) — additive sedation - **Antihypertensives** (especially diuretics, ACEi, ARBs) — increased risk of hypotension and bradycardia - **Digoxin** — limited interaction; monitor heart rate if co-used ## Monitoring - **Blood pressure and heart rate** at baseline and during dose changes - **Liver function tests** (ALT, AST) at baseline, 1 month, then every 6 months - **Sedation level/mental status** regularly - In prolonged use: withdrawal signs if holding or discontinuing ## Clinical Pearls - **Administer with food?** High-fat meal increases absorption variability; take consistently with respect to meals. - **Maximize timing:** Titrate to sleep-related spasticity using larger dose at night if sedation is a problem. - **Beware of cumulative effects:** Combine with baclofen or gabapentin with extreme caution—respiratory depression possible. - **Discontinuation:** Taper over 2–4 weeks to avoid rebound. - **Not first-line in pediatric care**—other agents (baclofen, botulinum toxin) often preferred. --- *This information is for educational purposes only. Always verify current prescribing information from a reliable formulary or drug reference (e.g., FDA prescribing information, local hospital guidelines) before making clinical decisions.*