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

Tizanidine Dosage and Treatment Protocol for Muscle Spasms

Initial Dosing

Start tizanidine at 2-4 mg orally up to three times daily, with gradual titration in 2-4 mg increments every 3-7 days to achieve optimal muscle tone reduction while monitoring for hypotension, sedation, and muscle weakness. 1, 2

• Begin with a single 4 mg dose to assess tolerability, as doses below 8 mg have limited efficacy data but the dose-related adverse effects make conservative initiation prudent 2
• The American Geriatrics Society specifically recommends starting at 2 mg up to three times daily in older adults, who rarely tolerate doses exceeding 30-40 mg per day 1
• Maximum effect occurs 1-2 hours post-dose and dissipates between 3-6 hours 2

Dose Titration Protocol

• Increase by 2-4 mg steps over 2-4 weeks to reach the optimal dose that provides satisfactory muscle tone reduction at a tolerated level 2, 3
• Doses can be repeated at 6-8 hour intervals as needed, up to three times in 24 hours 2
• The effective dosage range in clinical trials spans 2-36 mg/day, with optimal doses typically between 8-36 mg daily 3, 4

Maximum Dosing Limits

• Total daily dose must not exceed 36 mg 2
• Single doses exceeding 8 mg and daily doses exceeding 24 mg have limited clinical experience 2
• There is essentially no experience with repeated single daytime doses greater than 12 mg 2

Food Effects and Administration

Prescribers must be aware that switching tizanidine administration between fed and fasted states can cause clinically significant pharmacokinetic differences, potentially resulting in increased adverse events or altered onset of activity. 2

• Food has complex effects on tizanidine absorption and should be administered consistently (always with or always without food) 2

Monitoring Requirements

Monitor for the following during titration and maintenance therapy:

• Hypotension: Can be significant and requires blood pressure monitoring, especially when combined with opioids or other antihypertensives 5, 1
• Sedation and drowsiness: Most common adverse effects occurring in clinical trials 3
• Dry mouth: Frequently reported adverse effect 3
• Muscle weakness: Though less common than with baclofen, assess muscle strength objectively 3, 4
• Urinary function changes 1
• Cognitive effects and orthostasis 1

Critical Safety Considerations

Drug Interactions

• Avoid concurrent use with CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine), which significantly reduce tizanidine clearance and increase adverse effect risk 5, 1
• Exercise extreme caution when combining with opioids like oxycodone due to additive hypotensive effects requiring careful monitoring and potential dose adjustments 5
• Avoid combining with other CNS depressants (pregabalin, quetiapine, duloxetine) due to additive sedative effects 5

Contraindications and Precautions

• Avoid in patients with hepatic or renal dysfunction due to reduced clearance 5, 1
• Use with extreme caution in elderly patients due to significant sedative and hypotensive effects 5
• Never discontinue abruptly in long-term users: Taper slowly to prevent withdrawal symptoms including rebound tachycardia, hypertension, and hypertonia 5, 1

Clinical Context and Efficacy

• Tizanidine reduces muscle tone by 21-37% versus 4-9% with placebo in controlled trials 3
• Improvement in muscle tone occurs in 60-82% of patients, comparable to baclofen (60-65%) and diazepam (60-83%) 3
• Tizanidine is specifically indicated for spasticity (increased muscle tone), not hypotonia (reduced muscle tone) 1
• For chronic stroke patients, tizanidine is preferred over benzodiazepines due to possible deleterious effects of benzodiazepines on stroke recovery 6
• Global tolerability rated as good to excellent in 44-100% of tizanidine recipients versus 38-90% for baclofen and 20-54% for diazepam 3

Treatment Algorithm for Spasticity

Follow this stepwise approach per stroke rehabilitation guidelines 6:

1. First-line: Antispastic positioning, range of motion exercises, stretching, splinting, serial casting several times daily
2. Second-line: Add oral tizanidine (or dantrolene, oral baclofen) for spasticity causing pain, poor skin hygiene, or decreased function
3. Third-line: Consider botulinum toxin or phenol/alcohol injections for selected patients with disabling or painful spasticity
4. Fourth-line: Consider intrathecal baclofen for chronic patients
5. Fifth-line: Consider neurosurgical procedures (selective dorsal rhizotomy, dorsal root entry zone lesions) for refractory cases

Perioperative Management

• Tizanidine can be continued preoperatively including on the day of surgery and may provide benefits including improved postoperative pain control, decreased midazolam requirements, decreased opioid consumption, and hemodynamic stability 5