Centrally Acting Muscle Relaxant (Alpha-2 Agonist) Pregnancy: The safety of tizanidine in pregnancy has not been established — it should not be used in pregnant women unless the benefit clearly outweighs the risk. The safety in breast-fed infants is not known and tizanidine and/or its metabolites have been found in rodent milk, so it should not be used in nursing mothers unless the benefit clearly outweighs the risk.

Tizanidine

Brand names: Zanaflex

Tizanidine is a centrally acting alpha-2 adrenergic agonist used as a skeletal muscle relaxant for painful muscle spasm and spasticity.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Spasm of the skeletal muscles: 2–4 mg three times daily; in severe cases an extra dose of 2–4 mg may be given, preferably late in the evening to reduce the sedative effect

Route: Oral

Frequency: Three times daily (plus one optional extra evening dose in severe cases)

Max: For spasticity due to neurological disorders the total daily dose should not exceed 36 mg. No separate maximum is stated for skeletal muscle spasm beyond 2–4 mg three times daily plus an extra 2–4 mg dose in severe cases.

Tizanidine has a narrow therapeutic index and high inter-patient variability in plasma concentrations, so the dose must be adjusted individually; a low starting dose of 2 mg three times daily can reduce the risk of side effects, and the dose should be increased gradually and with caution according to individual need and therapeutic response. OTHER INDICATION in §4.2 — spasticity due to neurological disorders: initial daily dose should not exceed 6 mg in 3 divided doses, increased in steps of 2–4 mg at intervals of half or a full week; the optimum therapeutic response is usually achieved with 12–24 mg daily divided into 3–4 equal doses; total daily dose should not exceed 36 mg. HEPATIC: contraindicated in severe hepatic impairment; use with caution in mild and moderate impairment with the lowest possible starting dose and small increments. Liver function tests should be monitored monthly for the first four months in patients receiving 12 mg daily or more, or with symptoms suggestive of hepatic dysfunction; discontinue if SGPT/SGOT are persistently above three times the upper limit of normal. Elderly: experience is limited — start as low as possible and increase in small increments according to tolerability and efficacy. DISCONTINUATION: decrease the dose slowly (2–4 mg per day), particularly after high doses (20–28 mg daily) for long periods (9 weeks or more) or with concomitant narcotics, to prevent rebound hypertension, tachycardia and hypertonia. PAEDIATRIC: safety and efficacy in children and adolescents under 18 years have not been established, data are limited and tizanidine cannot be recommended for use in children and adolescents. PROVENANCE: fetched eMC product is Tizagelan 2 mg tablets. §4.5 (interactions) was not part of the fetched bundle; §4.4 and §4.8 were truncated at the source-fetch limit.

Dose adjustments

Renal

In patients with renal impairment (creatinine clearance below 25 mL/min) treatment should be started with 2 mg once daily with slow titration to the effective dose; dosage increases should be in increments of no more than 2 mg according to tolerability and effectiveness, and it is advisable to slowly increase the once-daily dose before increasing the frequency of administration. Clearance is reduced by more than 50% — monitor renal function and watch closely for dry mouth, somnolence, asthenia and dizziness as indicators of potential overdose.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients
Severe hepatic impairment
Concomitant use of tizanidine with potent CYP1A2 inhibitors such as fluvoxamine or ciprofloxacin

Side effects

Somnolence, drowsiness, dizziness and fatigue (very common/common) — usually not severe enough to require discontinuation with slow upward titration
Dry mouth, gastrointestinal disturbances and nausea (very common/common); vomiting, abdominal pain, constipation
Hypotension (common); bradycardia and tachycardia (uncommon); syncope and QT prolongation (post-marketing)
Hepatic enzymes increased (common); hepatitis and hepatic failure (post-marketing)
Muscular weakness, asthenia and withdrawal syndrome (rebound hypertension, tachycardia and hypertonia after sudden withdrawal of chronic treatment)
Insomnia and sleep disorders, confusion, hallucinations (self-limiting, invariably in patients concurrently taking potentially hallucinogenic substances such as antidepressants)

Interactions

Potent CYP1A2 inhibitors such as fluvoxamine or ciprofloxacin — concomitant use is contraindicated (§4.3/§4.4)
Other CYP1A2 inhibitors — adverse reactions such as hypotension, bradycardia or excessive drowsiness can occur; concomitant use should be avoided unless the necessity for tizanidine therapy is clinically evident, in which case use with caution (§4.4)
Full §4.5 interaction section was not retrieved in this bundle — check the SPC directly before relying on this list

Clinical monograph

How it works

By stimulating central alpha-2 adrenoceptors it reduces excitatory neurotransmitter release at spinal interneurons, decreasing motor neuron firing and muscle tone.

Prescribing in practice

Contraindicated with potent CYP1A2 inhibitors such as fluvoxamine and ciprofloxacin, which markedly raise tizanidine levels and can cause profound hypotension and sedation.
Titrate gradually and avoid abrupt withdrawal, which can cause rebound hypertension, tachycardia and increased spasticity.
Causes dose-related hypotension, sedation and dry mouth, and requires caution with other antihypertensives or CNS depressants.

Monitoring

Monitor liver function and blood pressure, particularly during dose titration and with interacting medicines.

Counselling the patient

May cause drowsiness and dizziness, especially on standing; take care driving until you know how it affects you.
Do not stop the medicine suddenly without advice.
Report yellowing of the skin or eyes or persistent nausea.

Evidence & guidelines

Tizanidine is recognised in UK references for muscle spasticity, with prescribing shaped by its CYP1A2 interactions and hepatic monitoring requirements.

Reference: MHRA Drug Safety Update (Tizanidine hepatotoxicity); SPC Zanaflex; Cochrane Review (Muscle relaxants for acute low back pain); Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Pathways