What is the recommended dosage of Zanaflex (tizanidine) for an adult patient with muscle spasms, considering potential interactions and individual response?

Zanaflex (Tizanidine) Dosage for Muscle Spasms

Start tizanidine at 4 mg as a single dose, increase gradually in 2-4 mg increments to achieve optimal muscle tone reduction while minimizing side effects, with doses repeated every 6-8 hours as needed up to three times daily, not exceeding 36 mg total per day. 1

Initial Dosing Strategy

• Begin with 4 mg orally as the starting single dose, as doses less than 8 mg have not been demonstrated effective in controlled trials, but the dose-related adverse events make this prudent initial approach necessary 1

• Consider starting at 2 mg three times daily in older adults (rather than single doses), as they rarely tolerate doses greater than 30-40 mg per day and are at higher risk for sedation, hypotension, and cognitive effects 2, 3

• Taking the initial dose at bedtime can help patients tolerate sedation during the titration phase, as sedation occurs during sleep 2

Dose Titration and Timing

• Increase the dose gradually in 2-4 mg steps to achieve satisfactory muscle tone reduction at a tolerated dose 1

• Peak effect occurs 1-2 hours after administration, with effects dissipating between 3-6 hours, making the timing of doses critical for symptom control 1

• Repeat doses every 6-8 hours as needed, up to a maximum of three doses in 24 hours 1

• Maximum daily dose is 36 mg, though experience with repeated single daytime doses greater than 12 mg or total daily doses exceeding 36 mg is limited 1

Effective Dose Range

• Single doses of 8 mg reduce muscle tone for several hours in patients with spasticity, representing the evidence-based effective dose 1

• Optimal dosages range from 2-36 mg daily based on clinical trials, with wide interpatient variability requiring individual titration over 2-4 weeks 4

• In clinical studies, patients were titrated up to maximally tolerated doses or 36 mg daily given in three unequal doses (e.g., 10 mg morning and afternoon, 16 mg at night) 1

Critical Food Interaction

• Food significantly alters tizanidine pharmacokinetics: when taken with food, peak plasma concentration increases by approximately 30% and time to peak increases by 25 minutes 1

• Do not switch between fed and fasted administration without careful monitoring, as these pharmacokinetic differences may result in increased adverse events or altered onset of activity 1

• Prescribers must be thoroughly familiar with kinetic changes associated with fed versus fasted states before making any administration changes 1

Special Population Considerations

Older Adults

• Start at 2 mg up to three times daily to minimize sedation, hypotension, and cognitive effects 2, 3

• Monitor closely for muscle weakness, urinary dysfunction, cognitive effects, sedation, and orthostasis in all older patients 2

• Elderly patients clear tizanidine four times slower than younger subjects, requiring lower doses 1

Renal Impairment

• Tizanidine clearance is reduced by more than 50% in elderly patients with creatinine clearance <25 mL/min, leading to longer clinical effect duration 1

• Use with caution and reduce doses in renally impaired patients 3, 1

Hepatic Impairment

• Avoid tizanidine in patients with hepatic dysfunction due to significant sedative and hypotensive effects 2, 3

Dangerous Drug Interactions

• Tizanidine is absolutely contraindicated with ciprofloxacin and fluvoxamine due to significantly reduced clearance causing severe hypotension, bradycardia, and sedation 3

• CYP1A2 inhibitors significantly reduce tizanidine clearance, increasing adverse effect risk 2, 3

• Concomitant use with oxycodone or other opioids carries significant hypotension risk due to additive blood pressure-lowering effects requiring careful monitoring 2

• Women taking oral contraceptives have 50% lower tizanidine clearance, requiring dose adjustments 1

• Risk of prolonged QTc when combined with methadone 3

Discontinuation Protocol

• Never abruptly discontinue tizanidine in long-term users—taper the dose slowly to prevent withdrawal symptoms including rebound tachycardia, hypertension, and hypertonia 2, 3

• Continue tizanidine preoperatively, including the day of surgery, to avoid withdrawal symptoms and potentially gain perioperative benefits including improved pain control and hemodynamic stability 2, 3

Monitoring Requirements

• Monitor blood pressure regularly, as hypotension can be significant and is dose-related 2, 5

• Assess for excessive sedation, which may accompany hypotension 2

• In older adults, monitor for muscle weakness, urinary function changes, cognitive effects, sedation, and orthostatic hypotension 2

Common Pitfalls to Avoid

• Do not use tizanidine for hypotonia (reduced muscle tone)—it is specifically for treating spasticity (increased muscle tone) 5

• Avoid in patients with hepatic or renal dysfunction due to reduced clearance and increased adverse effects 2, 3

• Do not combine with CYP1A2 inhibitors without significant dose reduction and monitoring 2, 3

• Recognize that 16 mg doses produce larger effects but with more common and severe adverse events including hypotension compared to 8 mg 1

Combination Therapy Considerations

• Combining tizanidine with acetaminophen provides superior short-term pain relief for acute muscle spasms and back pain, though this increases CNS side effects (sedation, dizziness) 2.44-fold 5

• Tizanidine is preferred over benzodiazepines during stroke recovery due to possible deleterious effects of benzodiazepines on recovery 2

• Consider multimodal analgesia to reduce opioid requirements when pain control is the primary goal 2