What is the appropriate tizanidine dose for a healthy 80‑kg adult?

Tizanidine Dosing for an 80 kg Adult

For an 80 kg healthy adult, initiate tizanidine at 2–4 mg orally at bedtime, then titrate by 2–4 mg every 1–7 days to an effective dose, typically 24–36 mg per day divided into three doses, with an absolute maximum of 36 mg per day. 1, 2

Initial Dosing Strategy

• Start with 2–4 mg orally at bedtime to allow sedation to occur during sleep and minimize daytime adverse effects during the titration phase. 1, 3
• The FDA label specifies beginning with single oral doses of 4 mg due to the dose-related nature of common adverse events, though 2 mg is often used in practice for better tolerability. 2

Titration Protocol

• Increase the dose gradually by 2–4 mg increments every 1–7 days according to tolerability and clinical response. 1
• Doses can be repeated at 6–8 hour intervals as needed, up to three doses in 24 hours. 2
• The titration period typically spans 2–4 weeks to reach the optimal individualized dose. 4

Target Therapeutic Dose

• Most patients achieve optimal spasticity control with 24–36 mg per day, divided into three 8 mg doses every 8 hours. 1
• Single doses of 8 mg reduce muscle tone for several hours, with peak effect at 1–2 hours and dissipation between 3–6 hours. 2
• The absolute maximum daily dose is 36 mg; there is essentially no experience with repeated single daytime doses greater than 12 mg or total daily doses exceeding 36 mg. 1, 2

Weight-Based Considerations

• Body weight does not directly determine tizanidine dosing, as wide interpatient variability in effective plasma concentrations means the optimal dosage must be titrated individually based on clinical response and tolerability rather than weight. 4
• For an 80 kg adult without hepatic or renal impairment, standard adult dosing applies without weight-based adjustment. 1

Critical Safety Considerations

Adverse Effects to Monitor

• Hypotension, asthenia, dizziness, and fatigue are the most frequently reported adverse effects at therapeutic doses. 1
• Dry mouth and somnolence/drowsiness occur commonly but are generally manageable with supportive measures. 4
• Hepatotoxicity is a recognized risk requiring periodic liver function monitoring. 1

Important Drug Interactions

• Contraindicated with ciprofloxacin and fluvoxamine due to significantly reduced clearance via CYP1A2 inhibition. 1
• Other CYP1A2 inhibitors (e.g., oral contraceptives) markedly increase tizanidine plasma levels and adverse effects. 1
• Concurrent methadone raises the risk of QTc interval prolongation, necessitating cardiac monitoring. 1
• Concurrent opioids (e.g., oxycodone) carry significant risk of additive hypotension requiring careful monitoring. 3

Food Effects

• Food has complex effects on tizanidine pharmacokinetics that may result in clinically significant differences when switching administration between fed and fasted states, potentially causing increased adverse events or altered onset of activity. 2

Common Pitfalls to Avoid

• Do not abruptly discontinue in patients treated long-term (>9 weeks); taper slowly to prevent withdrawal symptoms including rebound tachycardia, hypertension, and hypertonia. 1, 3
• Avoid use in hepatic or renal dysfunction due to heightened sedative and hypotensive effects; if unavoidable, dose reduction and intensive monitoring are required. 1
• Do not exceed 36 mg per day as safety data beyond this dose are lacking. 1, 2