What is the recommended dosage and treatment protocol for Tizanidine (Zanaflex) for muscle spasms?

Tizanidine Dosage and Treatment Protocol for Muscle Spasms

For muscle spasms, tizanidine should be started at 2-4 mg orally at bedtime and gradually titrated up to 8 mg every 8 hours as needed, not exceeding a total daily dose of 36 mg. 1

Mechanism and Pharmacology

Tizanidine is an α2-adrenergic receptor agonist and centrally acting muscle relaxant. It is a clonidine derivative but with fewer cardiovascular effects. Key pharmacological properties include:

• Peak effect occurs at 1-2 hours after administration
• Effects dissipate between 3-6 hours
• Food has complex effects on tizanidine pharmacokinetics that can affect onset and side effect profile 1

Dosing Algorithm

1. Initial dosing:

   • Start with 2-4 mg orally at bedtime 2, 1
   • This lower starting dose helps minimize adverse effects while assessing tolerability

2. Titration:

   • Increase by 2-4 mg increments every 1-3 days 2, 1
   • Titrate to optimal effect (satisfactory muscle tone reduction at a tolerated dose)

3. Maintenance dosing:

   • Can be administered every 6-8 hours as needed
   • Maximum of three doses in 24 hours
   • Maximum single dose: typically 8 mg (though doses up to 12 mg have been used)
   • Maximum daily dose: 36 mg 1

4. Duration of treatment:

   • For acute muscle spasms: Short-term use (days to weeks)
   • For chronic spasticity: May require long-term therapy with periodic reassessment

Special Considerations

Hepatic/Renal Impairment

• Dose reduction and monitoring recommended for patients with hepatic or renal impairment 2

Drug Interactions

• Contraindicated with CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine)
• Use cautiously with:
  • Oral contraceptives
  • Acyclovir
  • Amiodarone
  • Verapamil
  • Mexiletine
  • Propafenone
  • Cimetidine
  • Famotidine 2

Discontinuation

• If used long-term, taper slowly to avoid withdrawal symptoms
• Abrupt discontinuation can lead to rebound tachycardia, hypertension, and hypertonia 2

Efficacy

• Studies show 20-37% reduction in muscle tone scores versus 4-9% with placebo 3
• Maximum effects typically occur within 2 hours of administration 3
• In back pain studies, patients experienced initial relief by day 2 of treatment and complete relief after approximately 4 days 4

Adverse Effects

Common adverse effects include:

• Sedation/drowsiness (dose-dependent)
• Dry mouth
• Dizziness
• Hypotension
• Asthenia
• Hepatotoxicity (monitor liver function) 2, 3

Clinical Pearls

1. Tizanidine has shown comparable efficacy to baclofen but with a more favorable side effect profile, particularly regarding subjective muscle weakness 3

2. Consider timing of doses to minimize daytime sedation - evening dosing may be preferable for patients who experience significant drowsiness

3. Perioperative benefit: Tizanidine has shown improvement in postoperative pain control, decreased midazolam requirements, decreased opioid consumption, and improved hemodynamic stability 2

4. Unlike some other muscle relaxants (e.g., carisoprodol), tizanidine is not associated with significant abuse potential

5. Avoid use in elderly patients and those with significant hepatic or renal dysfunction due to increased risk of sedation and hypotension 2