What is Zanaflex (tizanidine)?

What is Zanaflex (Tizanidine)?

Zanaflex (tizanidine) is a short-acting, centrally acting α2-adrenergic receptor agonist used specifically for managing muscle spasticity associated with upper motor neuron disorders such as multiple sclerosis, stroke, and spinal cord injury. 1

Mechanism of Action

Tizanidine works as an α2-adrenergic receptor agonist in the central nervous system, reducing excessive muscle tone without significantly affecting muscle strength. 1, 2 This distinguishes it from other muscle relaxants that may cause more pronounced weakness. 3

FDA-Approved Indications

• Primary indication: Management of spasticity (increased muscle tone) in patients with upper motor neuron syndromes including multiple sclerosis, stroke, and spinal cord injury. 1, 4
• Important limitation: Tizanidine is a short-acting medication and should be reserved for daily activities and times when relief of spasticity is most important. 1
• Critical contraindication: Tizanidine treats spasticity (increased muscle tone), NOT hypotonia (reduced muscle tone)—using it for hypotonia would worsen the condition. 4, 2

Dosing and Administration

• Starting dose: 2 mg up to three times daily, particularly in older adults. 2
• Titration: Gradual dose adjustment over 2-4 weeks to optimize effect while monitoring for adverse events. 2, 3
• Maximum dose: Older adults rarely tolerate doses greater than 30-40 mg per day, though doses up to 36 mg/day have been used in clinical trials. 2, 3
• Timing strategy: Taking the initial dose at bedtime can help patients tolerate sedation during the titration phase. 5
• Peak effect: Maximum antispastic effects occur within 2 hours of administration. 3

Clinical Efficacy

• Spasticity reduction: Clinical trials demonstrate 21-37% reduction in mean muscle tone scores compared to 4-9% with placebo. 3
• Comparative effectiveness: Tizanidine shows similar efficacy to baclofen (60-82% improvement vs. 60-65% with baclofen) but with less subjective muscle weakness. 3
• Additional benefits: Reduces spasm frequency, clonus, and can improve pain, skin hygiene, and function in patients with spasticity. 2, 4
• Off-label use: Shows efficacy for acute low back pain with muscle spasm when combined with acetaminophen or NSAIDs, though this is not FDA-approved. 2

Critical Safety Considerations

Common Adverse Effects

• Most frequent: Dry mouth and somnolence/drowsiness are the most commonly reported side effects. 3, 6
• CNS effects: Sedation, dizziness, and cognitive effects require monitoring, especially in older adults who have increased fall risk. 2, 5
• Management of dry mouth: Sugar-free gum and frequent water sips can help manage this side effect. 5

Serious Risks

• Hypotension: Can cause significant blood pressure drops, particularly problematic when combined with opioids or other antihypertensive medications. 2, 5
• Hepatotoxicity: Should be avoided in patients with hepatic dysfunction; monitor liver function tests as elevations can occur. 5, 7
• Renal impairment: Clearance is significantly reduced in renal dysfunction, requiring dose adjustments. 2, 5

Drug Interactions

• CYP1A2 inhibitors: Significantly reduce tizanidine clearance, increasing risk of adverse effects. 2, 5
• Opioid combination: Concomitant use with oxycodone or other opioids carries significant hypotension risk through additive blood pressure-lowering effects. 5
• CNS depressants: Combining with pregabalin, quetiapine, duloxetine, or benzodiazepines produces additive sedative effects. 5
• Acetaminophen/NSAID combination: While providing superior pain relief for acute muscle spasms, this increases CNS adverse events 2.44-fold. 2

Discontinuation Protocol

Never abruptly stop tizanidine in long-term users. 2, 5

• Withdrawal risk: Abrupt discontinuation causes withdrawal symptoms including rebound tachycardia, hypertension, hypertonia, and CNS irritability. 2, 5
• Tapering requirement: Dose must be tapered slowly when discontinuing after long-term use. 2, 5

Special Population Considerations

Older Adults

• The American Geriatrics Society recommends particular caution due to increased sedation, fall risk, and orthostatic hypotension. 5
• Monitor specifically for muscle weakness, urinary function changes, cognitive effects, sedation, and orthostasis. 2, 5

Perioperative Use

• Can be continued preoperatively including on the day of surgery, potentially providing benefits including improved postoperative pain control, decreased midazolam requirements, decreased opioid consumption, and hemodynamic stability. 5

Formulation Details

Tizanidine is available as 2 mg and 4 mg tablets containing tizanidine hydrochloride (2.288 mg equivalent to 2 mg base and 4.576 mg equivalent to 4 mg base) with inactive ingredients including colloidal silicon dioxide, lactose monohydrate, microcrystalline cellulose, and stearic acid. 1