What is the recommended dosing for Tizanidine (a muscle relaxant)?

Tizanidine Dosing Recommendations

The recommended dosing for tizanidine starts with 4 mg orally and gradually increases in 2-4 mg steps to achieve optimal muscle tone reduction, with a maximum of 36 mg daily divided into three doses taken at 6-8 hour intervals. 1

Initial Dosing and Titration

• Begin with a single oral dose of 4 mg, as the dose-related nature of tizanidine's common adverse effects makes it prudent to start at this level 1
• Gradually increase the dose in 2-4 mg increments to achieve optimal effect (satisfactory reduction of muscle tone at a tolerated dose) 1
• The dose can be repeated at 6-8 hour intervals, as needed, up to three times daily 1
• Titration should be individualized over 2-4 weeks to find the optimal dose due to wide interpatient variability in effective plasma concentrations 2

Maximum Dosing

• Total daily dose should not exceed 36 mg 1
• Experience with single doses exceeding 8 mg and daily doses exceeding 24 mg is limited 1
• There is essentially no experience with repeated, single daytime doses greater than 12 mg 1

Pharmacokinetic Considerations

• Maximum effects occur within 1-2 hours of administration 2
• Effects typically dissipate between 3-6 hours after dosing 1
• Food has complex effects on tizanidine pharmacokinetics that may result in clinically significant differences when switching administration between fed and fasted states 1
• These changes may result in increased adverse events or delayed/more rapid onset of activity 1

Clinical Efficacy

• A single 8 mg oral dose reduces muscle tone in patients with spasticity for several hours 1
• Studies show reduction in mean muscle tone scores of 21-37% with tizanidine versus 4-9% with placebo 2
• Improvement in muscle tone occurs in 60-82% of tizanidine recipients 2
• Tizanidine is effective for treating spasticity resulting in pain, poor skin hygiene, or decreased function in chronic stroke patients 3

Adverse Effects and Precautions

• Most common adverse effects include dose-dependent sedation, drowsiness, dizziness, ataxia, and dry mouth 3, 2
• Tizanidine should be avoided in patients with hepatic or renal dysfunction and in elderly patients due to significant sedative and hypotensive effects 3
• Tizanidine clearance is significantly reduced when given with CYP1A2 inhibitors (ciprofloxacin, fluvoxamine, oral contraceptives, acyclovir, amiodarone, verapamil, mexiletine, propafenone, cimetidine, famotidine) 3
• If tizanidine needs to be discontinued in a patient who uses the medication long-term, the dose should be tapered slowly due to risk of withdrawal and rebound tachycardia, hypertension, and hypertonia 3
• Subjective muscle weakness appears to be less of a problem with tizanidine than with other muscle relaxants like baclofen 2

Special Considerations

• Tizanidine can be continued preoperatively including on the day of surgical procedure 3
• Tizanidine may provide perioperative benefits including improved postoperative pain control, decreased midazolam requirements, decreased opioid consumption, and hemodynamic stability 3
• Tizanidine is preferred over diazepam or other benzodiazepines during stroke recovery due to possible deleterious effects of benzodiazepines on recovery 3

Clinical Response Timeline

• Initial pain relief (in back pain studies) typically occurs by the second day of treatment 4
• Complete pain relief may be achieved after approximately 4 days of treatment 4
• For chronic conditions, clinical effects may be more delayed 4