What is Zanaflex (tizanidine)?

What is Zanaflex (Tizanidine)?

Zanaflex (tizanidine) is a short-acting, centrally acting alpha-2 adrenergic receptor agonist used as a muscle relaxant specifically for managing spasticity (increased muscle tone) associated with upper motor neuron disorders such as multiple sclerosis, stroke, and spinal cord injury. 1, 2

Mechanism of Action and Pharmacology

• Tizanidine works by stimulating alpha-2 adrenergic receptors in the central nervous system, reducing excessive muscle tone without significantly affecting muscle strength 1, 3
• The medication has a short duration of effect, with maximum effects occurring within 2 hours of administration 2, 3
• Treatment should be reserved for daily activities and times when relief of spasticity is most important due to its short-acting nature 2

FDA-Approved Indications

• Tizanidine is FDA-approved for treating spasticity associated with upper motor neuron syndromes including stroke, multiple sclerosis, and spinal cord injury 4
• The American Heart Association recommends tizanidine for chronic stroke patients whose spasticity causes pain, poor skin hygiene, or decreased function 1

Clinical Efficacy

• Placebo-controlled trials demonstrate reduction in mean muscle tone scores of 21-37% with tizanidine versus 4-9% with placebo 3
• Improvement in muscle tone occurs in 60-82% of tizanidine recipients, with comparable efficacy to baclofen (60-65%) and diazepam (60-83%) 3
• Spasm frequency and clonus are also reduced by tizanidine treatment 3

Dosing Guidelines

• The American Geriatrics Society recommends starting at 2 mg up to three times daily, with gradual titration to achieve optimal effect 1
• Dosages of 2-36 mg/day have been used in clinical trials, with wide interpatient variability requiring individualized titration over 2-4 weeks 3
• Older adults rarely tolerate doses greater than 30-40 mg per day 1

Common Adverse Effects

• The most frequent side effects are dry mouth and somnolence/drowsiness 3
• Tizanidine can cause significant hypotension requiring monitoring 1
• Global tolerability is assessed as good to excellent in 44-100% of patients, compared to 38-90% with baclofen and 20-54% with diazepam 3

Critical Safety Considerations

• Avoid abrupt discontinuation in long-term users; taper slowly to prevent withdrawal symptoms including tachycardia, hypertension, and hypertonia 1
• Concomitant use with CYP1A2 inhibitors (ciprofloxacin, fluvoxamine) is absolutely contraindicated due to marked reduction in tizanidine clearance and risk of severe toxicity 5
• Use with extreme caution or avoid entirely in hepatic dysfunction due to hepatotoxicity risk and reduced clearance 1
• Dose reduction and careful monitoring required in renal impairment 1

Important Clinical Distinctions

• Tizanidine is specifically for treating spasticity (increased muscle tone), NOT hypotonia (reduced muscle tone) 1, 4
• Unlike benzodiazepines, tizanidine is not contraindicated during stroke recovery 1
• Subjective muscle weakness is reported less often with tizanidine than with baclofen or diazepam 3

Off-Label Uses

• The American College of Physicians recognizes tizanidine as an option for short-term relief of acute low back pain, though this is not FDA-approved 1
• When used for low back pain, treatment duration in clinical trials was typically 2 weeks or less 1
• Combining tizanidine with paracetamol provides superior short-term pain relief for acute muscle spasms, though this increases CNS side effects 2.44-fold 5

Treatment Algorithm Position

• After conservative measures (positioning, passive stretching, range-of-motion exercises) have been tried, tizanidine serves as a second-line pharmacologic intervention for spasticity 1
• When oral agents including tizanidine fail to achieve adequate control, escalate to more invasive options such as botulinum toxin injections, intrathecal baclofen, or neurosurgical procedures 1