Tizanidine Dosage for Adults
Start tizanidine at 2-4 mg orally as a single dose, with gradual titration in 2-4 mg increments every 3-7 days to achieve optimal spasticity control, up to a maximum of 36 mg per day divided into three doses. 1
Initial Dosing
- Begin with 4 mg orally as a single dose, as doses less than 8 mg have limited efficacy data but the dose-related adverse effects make starting at 4 mg prudent 1
- For older adults or those with persistent pain, start at 2 mg up to three times daily to minimize sedation, hypotension, and cognitive effects 2
- The effect peaks at 1-2 hours and dissipates between 3-6 hours after administration 1
Dose Titration
- Increase gradually in 2-4 mg steps to achieve satisfactory reduction of muscle tone at a tolerated dose 1
- Titration should occur over 2-4 weeks due to wide interpatient variability in effective plasma concentrations 3
- Doses can be repeated at 6-8 hour intervals as needed, up to three doses in 24 hours 1
Maximum Dosing
- Total daily dose should not exceed 36 mg 1
- Single doses exceeding 8 mg and daily doses exceeding 24 mg have limited clinical experience 1
- There is essentially no experience with repeated single daytime doses greater than 12 mg 1
- In clinical trials, dosages of 2-36 mg/day have been used, with only 21% of patients able to reach the maximum 36 mg daily dose 3, 4
Special Populations
Older Adults (≥65 years)
- Limit to 2 mg up to three times daily (maximum 6 mg/day initially) 2
- Older persons rarely tolerate doses greater than 30-40 mg per day 2
- Monitor closely for muscle weakness, urinary dysfunction, cognitive effects, sedation, and orthostasis 2
Hepatic or Renal Impairment
- Avoid tizanidine in patients with hepatic or renal dysfunction due to significant sedative and hypotensive effects 2
- Dose reduction and monitoring are recommended for both hepatic and renal impairment 2
Administration Considerations
Food Effects
- Food has complex effects on tizanidine pharmacokinetics that may result in clinically significant differences when switching between fed and fasted states 1
- These changes may result in increased adverse events or delayed/more rapid onset of activity 1
- Maintain consistent administration relative to meals to avoid variability 1
Perioperative Management
- Continue tizanidine preoperatively including the day of surgery 2
- Abrupt discontinuation risks withdrawal symptoms including rebound tachycardia, hypertension, and hypertonia 2
- If discontinuation is necessary in long-term users, taper the dose slowly 2
Clinical Efficacy Data
- In stroke-related spasticity, tizanidine demonstrated significant improvement with mean daily doses of 18 mg (range 2-24 mg) over 16 weeks 4
- For chronic daily headache prophylaxis, mean effective dose was 18 mg/day (median 20 mg, range 2-24 mg) divided into three doses 5
- Antispastic efficacy shows reduction in muscle tone scores of 21-37% versus 4-9% for placebo 3
- In back pain with muscle spasm, initial pain relief occurred on day 2 of treatment with complete relief after 4 days using the lowest recommended doses 6
Critical Safety Monitoring
Hypotension Risk
- Two-thirds of patients taking 8 mg experience a 20% reduction in diastolic or systolic blood pressure within 1 hour of dosing 1
- The hypotensive effect is dose-related and occurs with doses ≥2 mg 1
- Monitor for bradycardia, orthostatic hypotension, lightheadedness, dizziness, and rarely syncope 1
- Do not use with other α2-adrenergic agonists or concurrent antihypertensive therapy without extreme caution 1
Hepatotoxicity
- Monitor aminotransferase levels during the first 6 months of treatment 1
- Approximately 5% of patients develop liver function test elevations >3 times upper limit of normal 1
- Three deaths associated with liver failure have been reported in postmarketing experience 1
Drug Interactions
- Contraindicated with ciprofloxacin and fluvoxamine due to significantly reduced clearance 2
- Significant hypotension, bradycardia, and sedation can occur with CYP1A2 inhibitors including oral contraceptives, acyclovir, amiodarone, verapamil, cimetidine, and famotidine 2
- Increased risk of prolonged QTc when prescribed with methadone 2