Section 09 · Monograph

Tizanidine

Reviewed Nov 2026FDA label

ZanaflexAlpha-2 agonist

Indications

Management of spasticity (FDA-approved indication) — the only two drugs in this class approved specifically for 'spasticity' are tizanidine and dantrolene; tizanidine is indicated for the acute and intermittent management of increased muscle tone associated with spasticity in adults.FDA-labeled

Chronic daily headache / tension-type headache prophylaxis (studied in double-blind trials, not FDA-approved).Off-label
Adjunct for myofascial pain syndromes.Off-label
Adjunct in fibromyalgia-associated muscle tightness (limited evidence).Off-label

Central alpha-2 adrenergic receptor agonist (structurally related to clonidine).
Reduces spasticity by increasing presynaptic inhibition of motor neurons in the spinal cord, presumed to work at the level of the spinal interneurons to reduce excitatory input to alpha motor neurons.
Acts predominantly at spinal (and to a lesser degree supraspinal) sites to inhibit polysynaptic reflexes, which are believed to be responsible for excess muscle tone.
Has no direct effect on skeletal muscle fibers or the neuromuscular junction.

Adult, spasticity: initiate 2 mg orally, may repeat every 6-8 hours as needed, up to 3 doses/24 hr.
Titrate in increments of 2-4 mg per dose, at intervals of 1-4 days, based on response and tolerability, until satisfactory reduction of spasticity.
Maximum recommended single dose 16 mg (single doses >16 mg not adequately studied); maximum total daily dose 36 mg.
Capsule vs tablet: capsule contents sprinkled on food produce different absorption (higher Cmax) than an intact capsule taken without food or a tablet taken with food — do not interchange formulations/administration conditions without accounting for altered bioavailability.
Discontinuation: taper gradually (e.g., decrease by 2-4 mg/day) when stopping after chronic use to reduce risk of rebound hypertension, tachycardia, and increased spasticity/muscle tone.
Elderly: clearance is significantly reduced in older patients (especially older men); use lower starting doses and titrate cautiously.

Renal impairment (CrCl <25 mL/min): reduced clearance — titrate slowly and monitor closely as dose increases; consider lower doses.

Hepatic impairment: use is not recommended in hepatically impaired patients; if used, start at 2 mg and titrate cautiously with close monitoring of liver enzymes and clinical response.

Concomitant use with potent CYP1A2 inhibitors: fluvoxamine or ciprofloxacin (contraindicated — coadministration produces markedly increased tizanidine exposure with severe hypotension and sedation).
Known hypersensitivity to tizanidine or any component of the formulation.

Strong CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) — contraindicated; can raise tizanidine levels ~10-fold and ~7-fold respectively, causing severe hypotension and sedation.
Moderate/weak CYP1A2 inhibitors (e.g., oral contraceptives, cimetidine, certain fluoroquinolones, acyclovir, famotidine) — coadministration should generally be avoided; if necessary, use the lowest tizanidine dose and titrate based on tolerability.
CNS depressants (alcohol, benzodiazepines, opioids, other sedatives) — additive CNS depression and sedation.
Antihypertensive agents (including other alpha-2 agonists such as clonidine) — additive hypotensive effects; avoid concomitant use of multiple alpha-2 agonists.
Digoxin — tizanidine may enhance hypotensive/bradycardic effects; monitor.

Very common (>10%): dry mouth, somnolence/drowsiness, asthenia (weakness, fatigue), dizziness.
Common: hypotension (orthostatic), bradycardia, transient elevations in liver transaminases (ALT/AST), constipation, urinary tract infection.
Serious: symptomatic hypotension/syncope (especially with dose increases or coadministration of CYP1A2 inhibitors/antihypertensives), hepatotoxicity (rare cases of liver failure reported), hallucinations/psychotic-like symptoms, sedation impairing driving/operating machinery, withdrawal effects (rebound hypertension, tachycardia, increased spasticity) with abrupt discontinuation after prolonged use.

Liver function tests (ALT/AST) at baseline, and at 1, 3, and 6 months, then periodically, especially during dose titration to higher maintenance doses.
Blood pressure and heart rate, particularly at initiation and with dose increases, and in patients on antihypertensives.
Renal function (adjust monitoring frequency/dosing in renal impairment).
Sedation level and mental status (hallucinations, confusion).
Signs/symptoms of withdrawal if discontinuing after chronic therapy — taper rather than stop abruptly.

Pregnancy: no adequate, well-controlled human studies; animal reproduction studies showed adverse effects (decreased fetal/pup weight, delayed skeletal ossification) at doses associated with maternal toxicity. Use only if the potential benefit justifies the potential risk to the fetus.
Lactation: not known whether tizanidine is excreted in human milk; excreted in animal milk. Because of the potential for serious adverse reactions in a nursing infant (sedation, hypotension), a decision should be made whether to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother.