What is the maximum recommended dose of tizanidine (Zanaflex)?

Tizanidine Maximum Dose

The maximum recommended dose of tizanidine is 36 mg per day, though older adults rarely tolerate doses greater than 30-40 mg per day. 1

Standard Dosing Parameters

• Starting dose: 2 mg up to three times daily, with gradual titration to achieve optimal effect while monitoring for side effects 1
• Maximum daily dose: 36 mg/day has been used in clinical trials, though wide interpatient variability in effective plasma concentrations means optimal dosage must be titrated over 2 to 4 weeks for each patient 2
• Typical dosage range: 2 to 36 mg/day, with dosages divided into multiple administrations throughout the day 2

Special Population Considerations

Older Adults

• Older adults rarely tolerate doses greater than 30-40 mg per day 1
• The American Geriatrics Society recommends starting at 2 mg up to three times daily with careful monitoring for sedation, somnolence, orthostasis, muscle weakness, urinary function issues, and cognitive effects 1

Renal or Hepatic Impairment

• Avoid tizanidine in patients with hepatic or renal dysfunction due to significantly reduced clearance and increased risk of adverse effects 3
• For patients with moderate renal impairment who must use tizanidine, a starting dose of 2 mg twice daily is within appropriate parameters 4

Clinical Achievement of Maximum Dose

• In clinical trials, only 10 of 47 patients (21%) were able to reach the maximum daily dosage of 36 mg 5
• Maximum effects occur within 2 hours of administration 2
• The titration phase typically spans 2 to 4 weeks to reach optimal dosing 2, 6

Critical Safety Warnings at Higher Doses

• Hypotension risk: Tizanidine can cause significant hypotension, which requires monitoring, particularly at higher doses 3, 1
• Drug interactions: Tizanidine clearance is significantly reduced when given with CYP1A2 inhibitors, increasing risk of adverse effects and potentially requiring dose reduction 3
• Discontinuation: Never abruptly discontinue in long-term users; taper slowly to prevent withdrawal symptoms including rebound tachycardia, hypertension, and hypertonia 3, 1

Common Adverse Effects

• The most frequent side effects are somnolence (62%) and dizziness (32%), with dry mouth also commonly reported 2, 5
• Adverse events were reported in 91% of tizanidine-treated patients in controlled trials, with 13% discontinuing treatment due to side effects 6