What is the recommended dose and frequency of Tizanidine (Zanaflex)?

From the Guidelines

Tizanidine should be started with 2 mg orally at night and, if well tolerated, increased by 2-4 mg every day up to 8 mg every 8 hours, with careful consideration of its potential side effects and interactions, particularly when prescribed in conjunction with other medications like methadone 1. The dosing of Tizanidine is crucial for managing its side effects while achieving the desired therapeutic effect.

• Key considerations include: + Starting dose: 2 mg orally at night + Dose escalation: Increase by 2-4 mg every day as needed and tolerated + Maximum dose: Up to 8 mg every 8 hours + Potential side effects: Sedation, hypotension, dry mouth, asthenia, dizziness, somnolence, hepatotoxicity + Important interactions: Concomitant use with methadone increases the risk of prolonged QTc, and CYP1A2 inhibitors (e.g., oral contraceptives) require dose reduction and monitoring Given the potential for significant side effects and interactions, careful monitoring and gradual dose adjustments are essential when prescribing Tizanidine, especially in patients with hepatic or renal impairment, or those who are pregnant or breastfeeding 1.
• Monitoring parameters should include: + Blood pressure + Liver function tests + Renal function tests + QTc interval (especially when used with methadone) By carefully managing the dose and monitoring for potential side effects and interactions, healthcare providers can optimize the therapeutic benefits of Tizanidine while minimizing its risks 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION A single oral dose of 8 mg of tizanidine reduces muscle tone in patients with spasticity for a period of several hours. The effect peaks at approximately 1 to 2 hours and dissipates between 3 to 6 hours. Effects are dose-related Although single doses of less than 8 mg have not been demonstrated to be effective in controlled clinical studies, the dose-related nature of tizanidine’s common adverse events make it prudent to begin treatment with single oral doses of 4 mg. Increase the dose gradually (2 mg to 4 mg steps) to optimum effect (satisfactory reduction of muscle tone at a tolerated dose) The dose can be repeated at 6 to 8 hour intervals, as needed, to a maximum of three doses in 24 hours. The total daily dose should not exceed 36 mg.

The recommended dose and frequency of Tizanidine (Zanaflex) is:

• Initial dose: 4 mg
• Dose increment: 2 mg to 4 mg steps
• Dosing interval: 6 to 8 hours
• Maximum daily doses: 3 doses in 24 hours
• Maximum total daily dose: 36 mg 2

From the Research

Recommended Dose and Frequency of Tizanidine (Zanaflex)

• The optimal dosage of tizanidine must be titrated over 2 to 4 weeks for each patient, with dosages of 2 to 36 mg/day used in clinical trials 3.
• The dose should be started at a low level and gradually titrated to effect 4.
• The optimal daily dose of tizanidine was between 8 and 36 mg in a double-blind comparative trial with baclofen 5.
• In an open-label dose-titration safety and efficacy study, tizanidine was administered starting at 2 mg/d and slowly titrated to a maximum of 36 mg/d 6.

Administration and Efficacy

• Maximum effects of tizanidine occur within 2 hours of administration 3.
• Tizanidine has been shown to be clinically effective in the management of spasticity caused by multiple sclerosis, acquired brain injury, or spinal cord injury 4.
• Tizanidine results in quick pain relief, with initial relief on the 2nd day of treatment and complete relief after 4 days, in patients with back pain accompanied by muscle spasm 7.

Safety and Tolerability

• The most common adverse effects associated with tizanidine are dry mouth and somnolence/drowsiness 3.
• Tizanidine is well tolerated, with adverse effects rare (<6%) and transient 7.
• The most frequent side effects of tizanidine in the treatment of stroke-related spasticity were somnolence (62%) and dizziness (32%) 6.