Centrally Acting Muscle Relaxant (Alpha-2 Agonist) Pregnancy: Avoid — limited human data; teratogenicity in animal studies at high doses

Tizanidine

Brand names: Zanaflex

Adult dose

Dose: 2–4 mg up to three times daily

Route: Oral

Frequency: Two to three times daily

Max: 36 mg/day in divided doses

Start at 2 mg; titrate slowly; begin at night due to sedation; short-term use preferred; abrupt discontinuation risks rebound hypertension — taper if used >2 weeks

Paediatric dose

Route: N/A

Frequency: N/A

Max: Not recommended under 18 years

No licensed paediatric orthopaedic indication

Dose adjustments

Renal

Use with caution if eGFR <25 mL/min — start at 2 mg and titrate carefully

Hepatic

Contraindicated in significant hepatic impairment — serious hepatotoxicity risk

Clinical pearls

Mechanism: alpha-2 adrenergic agonist selective for spinal receptors — reduces spinal interneuron excitability and polysynaptic reflex activity; produces muscle relaxation without direct peripheral neuromuscular blockade
Acute musculoskeletal spasm: used for lumbar and cervical muscle spasm with significant guarding — typically short 2–5 day courses to break the pain-spasm cycle; adjunct to NSAIDs and physiotherapy
Hepatotoxicity warning (MHRA): LFTs mandatory at baseline and 1, 3, 6 months; approximately 5% develop elevated transaminases; serious hepatotoxicity reported — lower risk with short-term low doses
Critical CYP1A2 drug interactions: fluvoxamine and ciprofloxacin cause massive plasma level increases causing life-threatening hypotension — check full medication list before every prescription; this is the highest priority safety concern with tizanidine
Rebound withdrawal similar to clonidine: tachycardia, hypertension, tremor on abrupt discontinuation — taper slowly if used more than 2 weeks; distinguishes tizanidine from most other muscle relaxants

Contraindications

Hepatic impairment
Concomitant fluvoxamine (CYP1A2 inhibitor — massive tizanidine level increase)
Concomitant ciprofloxacin (CYP1A2)
Hypotension

Side effects

Sedation
Dry mouth
Hypotension (dose-dependent)
Weakness
Dizziness
Hepatotoxicity (rare but serious)
Hallucinations at high doses

Interactions

Fluvoxamine — absolute contraindication (up to 33-fold tizanidine plasma increase causing severe hypotension)
Ciprofloxacin — major CYP1A2 inhibition interaction
Antihypertensives — additive hypotension
Alcohol — enhanced CNS depression
Oral contraceptives — may increase tizanidine levels

Monitoring

LFTs at baseline, 1 month, 3 months, 6 months
Blood pressure
Sedation level
Functional improvement
Signs of hepatotoxicity

Reference: BNFc; BNF 90; MHRA Drug Safety Update (Tizanidine hepatotoxicity); SPC Zanaflex; Cochrane Review (Muscle relaxants for acute low back pain). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Pathways