What is the appropriate dosing for 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. This dosing recommendation is based on the provided evidence [ 1 ], which outlines the appropriate dosing schedule for Tizanidine.

Key Considerations

• The medication should be titrated gradually to minimize side effects, with a focus on nighttime dosing initially to reduce daytime sedation.
• Patients with hepatic and renal impairment require dose reduction and monitoring.
• Concomitant use with CYP1A2 inhibitors, such as oral contraceptives, or methadone, necessitates caution due to potential increased risk of prolonged QTc.
• Common adverse effects include sedation, hypotension, dry mouth, asthenia, dizziness, somnolence, and hepatotoxicity.

Dosing and Administration

• The usual dosing range is up to 8 mg every 8 hours, with the maximum recommended daily dose not explicitly stated in the provided evidence but generally considered to be up to 36 mg in clinical practice.
• Food can affect the absorption of Tizanidine, so it should be taken consistently with or without food.
• Abrupt discontinuation should be avoided, and the medication should be tapered gradually to prevent rebound effects.

Special Populations

• Pregnancy class C and potential infant risk during breastfeeding cannot be ruled out, necessitating careful consideration in these populations.
• Caution is advised in patients with a history of cardiovascular disease due to the potential for hypotension and other cardiovascular effects.

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 appropriate dosing for Tizanidine (Zanaflex) is:

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

From the Research

Dosing Information for 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 having been used in clinical trials 3.
• The initial recommended dose of modified release tizanidine is one capsule per day of 6 mg, which may be increased gradually to 24 mg 4.
• Doses should be started at a low dose and gradually titrated to effect 5.
• In clinical studies, tizanidine produced a significant reduction in spastic muscle tone compared with placebo treatment, with a 20% mean reduction in muscle tone achieved within the effective dose range of 24 to 36 mg given daily in three doses 6.

Special Considerations

• Tizanidine is not approved for use in pediatric patients, and its use in this population is considered off-label 7.
• Tizanidine overdose can result in serious complications, including liver, renal, and cardiovascular failure, which can be worsened by patient comorbidities 7.
• The most common adverse effects associated with tizanidine are dry mouth and somnolence/drowsiness 3.
• Tizanidine can also cause hypotension, which is a frequent adverse effect 7.

Administration and Pharmacokinetics

• Maximum effects of tizanidine occur within 2 hours of administration 3.
• The relative bioavailability of the modified release formulation is similar to that of conventional tablets and is unaffected by food 4.
• Tizanidine achieves its maximum effect on spasticity within 1 week of the start of treatment, and the benefit is maintained for at least 1 week after discontinuation of therapy 6.