What is the recommended dosing for tizanidine (Zanaflex)?

Tizanidine Dosing

Start tizanidine at 4 mg as a single oral dose, increase gradually in 2-4 mg increments to achieve optimal muscle tone reduction at a tolerated dose, with doses repeated every 6-8 hours as needed, up to three doses in 24 hours, not exceeding a total daily dose of 36 mg. 1

Standard Dosing Protocol

Initial Dosing:

• Begin with 4 mg orally as the starting single dose 1
• Although 8 mg is the dose proven effective in controlled trials for reducing muscle tone, the dose-related adverse events make 4 mg the prudent starting point 1
• Peak effect occurs at 1-2 hours, with duration of 3-6 hours 1

Titration Schedule:

• Increase gradually in 2-4 mg steps to achieve satisfactory muscle tone reduction at a tolerated dose 1
• Titration typically occurs over 2-4 weeks 2
• Doses can be repeated at 6-8 hour intervals as needed 1

Maximum Dosing:

• Maximum of three doses per 24-hour period 1
• Total daily dose should not exceed 36 mg 1
• Clinical experience with single doses exceeding 8 mg and daily doses exceeding 24 mg is limited 1
• Essentially no experience exists with repeated single daytime doses greater than 12 mg or total daily doses greater than 36 mg 1

Special Population Dosing

Older Adults (≥65 years):

• Start at 2 mg up to three times daily 3, 4
• Titrate gradually while monitoring for muscle weakness, urinary dysfunction, cognitive effects, sedation, and orthostatic hypotension 4
• Older adults rarely tolerate doses greater than 30-40 mg per day 4

Renal Impairment:

• For moderate renal impairment, start at 2 mg twice daily 3
• Use with caution due to reduced clearance 4
• Monitor closely for adverse effects and adjust dose accordingly 4

Hepatic Impairment:

• Use with extreme caution or avoid entirely 5
• Significantly reduced clearance increases risk of adverse effects 5

Critical Dosing Considerations

Food Effects:

• Food has complex effects on tizanidine pharmacokinetics that may result in clinically significant differences 1
• Switching administration between fed and fasted states can increase adverse events or alter onset of activity 1
• Maintain consistent administration relative to meals 1

Drug Interactions:

• Avoid concurrent use with CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine), which significantly reduce tizanidine clearance and increase toxicity risk 5
• Exercise caution when combining with other CNS depressants or antihypertensives due to additive sedative and hypotensive effects 5

Discontinuation Protocol

Tapering Requirements:

• Never discontinue abruptly in long-term users 4, 5
• Taper dose slowly to prevent withdrawal symptoms including rebound tachycardia, hypertension, and hypertonia 4, 5

Monitoring Parameters

Essential Monitoring:

• Blood pressure (significant hypotension risk) 3, 4
• Sedation and cognitive effects 4
• Muscle weakness (though less common than with baclofen) 2
• Liver function in patients with hepatic concerns 5
• Orthostatic vital signs, particularly in older adults 4

Clinical Pearls

Timing Strategy:

• Consider administering initial doses at bedtime to allow sedation to occur during sleep, particularly during titration 5
• This approach can improve tolerability during the dose-adjustment phase 5

Common Adverse Effects:

• Dry mouth (manage with sugar-free gum and frequent water sips) 5
• Somnolence/drowsiness (most common, reported in 47% of patients) 6
• Dizziness (24% of patients) 6
• These effects are dose-related and typically reversible 7