Is it safe to prescribe a 90-day supply of tizanidine (Zanaflex) for a patient with a history of muscle spasms, likely due to a neurological disorder?

Can You Order a 90-Day Supply of Tizanidine?

Yes, you can order a 90-day supply of tizanidine, but this should be reserved for patients with chronic spasticity from established neurological conditions (stroke, multiple sclerosis, spinal cord injury) who have already been titrated to a stable, effective dose and are being monitored for long-term safety concerns including hepatotoxicity and withdrawal risk.

Clinical Context for 90-Day Prescriptions

FDA-Approved Indications Suitable for Extended Supply

• Tizanidine is FDA-approved for spasticity associated with upper motor neuron syndromes including stroke, multiple sclerosis, and spinal cord injury 1
• The American Heart Association specifically recommends tizanidine for chronic stroke patients with spasticity resulting in pain, poor skin hygiene, or decreased function 2, 1
• Clinical studies demonstrate maintained antispastic efficacy over 8 weeks, with effectiveness improving rather than diminishing over time in patients with multiple sclerosis 3

When 90-Day Supply is NOT Appropriate

• Acute conditions: The American College of Physicians recommends skeletal muscle relaxants including tizanidine for short-term use only in acute low back pain 4
• Initial titration phase: The FDA label specifies that optimal dosage must be titrated over 2-4 weeks for each patient, with doses starting at 4 mg and increasing gradually in 2-4 mg steps 5
• Unstable patients: Those not yet established on a stable dose or experiencing adverse effects require closer monitoring 4

Critical Safety Monitoring Requirements for Extended Prescriptions

Hepatotoxicity Surveillance

• Use tizanidine with extreme caution or avoid entirely in patients with hepatic dysfunction due to risk of hepatotoxicity and reduced clearance 4
• Monitor liver function tests, as abnormal results occurred in 3% of patients in controlled trials 5

Withdrawal Risk Management

• Never allow abrupt discontinuation: Taper slowly to prevent withdrawal symptoms including tachycardia, hypertension, rebound hypertonia, hallucinations, decorticate posture, and tremors 4, 1, 6
• A 90-day supply creates risk if the patient runs out unexpectedly or stops taking the medication without medical supervision 6

Cardiovascular Monitoring

• Tizanidine can cause significant hypotension requiring monitoring 4, 1
• Reduction in pulse rate and QT prolongation have been documented 5
• Monitor blood pressure and heart rate, particularly when combining with other antihypertensive medications 4

Dosing Considerations for Extended Prescriptions

Maximum Safe Dosing

• The FDA label states total daily dose should not exceed 36 mg, with essentially no experience with repeated single daytime doses greater than 12 mg or total daily doses exceeding 36 mg 5
• Older adults rarely tolerate doses greater than 30-40 mg per day 4

Special Population Adjustments

• Renal impairment: Reduce individual doses (not frequency) in patients with creatinine clearance <25 mL/min, as clearance is reduced by more than 50% 5
• Women on oral contraceptives: Clearance is reduced by approximately 50%, requiring dose reduction 5
• Elderly patients: Start with 2 mg up to three times daily with gradual titration 4

Drug Interaction Screening Before Extended Supply

Contraindicated Combinations

• Concomitant use with CYP1A2 inhibitors is contraindicated due to significantly increased tizanidine levels 4
• Avoid concomitant use with methadone due to increased risk of QTc prolongation 4

Additive CNS Depression

• Sedation is additive when combined with baclofen, benzodiazepines, or alcohol 5
• Alcohol increases tizanidine AUC by 20% and Cmax by 15%, associated with increased side effects 5

Common Pitfalls to Avoid

• Prescribing for acute pain without established chronic spasticity: This contradicts guideline recommendations for short-term use only in acute conditions 4, 7
• Failing to educate about food effects: Food has complex effects on tizanidine pharmacokinetics that may result in increased adverse events or delayed/more rapid onset of activity when switching between fed and fasted states 5
• Not providing withdrawal prevention plan: Patients must understand never to stop abruptly and to contact you before running out 5
• Inadequate baseline and ongoing monitoring: Liver function, blood pressure, and CNS effects require surveillance 4, 5