Introduction
Zanaflex (tizanidine hydrochloride) is a centrally acting alpha-2 adrenergic agonist approved by the FDA for the management of spasticity. It is commonly prescribed to reduce increased muscle tone associated with conditions such as multiple sclerosis, spinal cord injury, and other neurological disorders. Unlike other muscle relaxants, Zanaflex primarily acts on the central nervous system rather than directly on skeletal muscle.
Mechanism of Action
Tizanidine exerts its effects through agonism of alpha-2 adrenergic receptors in the central nervous system. This action results in presynaptic inhibition of motor neurons, reducing the release of excitatory neurotransmitters (particularly glutamate and aspartate) in spinal interneurons. The net effect is reduced facilitation of spinal motor neurons, leading to decreased muscle tone and spasticity without directly affecting neuromuscular function.
Indications
- Management of spasticity
- FDA-approved for treatment of spasticity associated with multiple sclerosis and spinal cord injury
- Off-label uses may include treatment of tension headaches, low back pain, and certain neuromuscular conditions (evidence varies)
Dosage and Administration
Initial dose: 2-4 mg orally every 6-8 hours as needed Titration: May increase gradually by 2-4 mg daily increments Maximum dose: 36 mg per day in divided doses (not to exceed three doses daily) Administration: May be taken with or without food (note: food affects absorption) Special populations:- Renal impairment (CrCl < 25 mL/min): Use with caution, consider lower doses
- Hepatic impairment: Contraindicated in significant hepatic impairment
- Elderly: Start with lower doses due to increased sensitivity
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapid but incomplete oral bioavailability (approximately 40%); food decreases Cmax by 30% and increases Tmax Distribution: Volume of distribution: 2.4 L/kg; Protein binding: 30% Metabolism: Extensive hepatic metabolism via CYP1A2; forms inactive metabolites Elimination: Half-life: 2.5 hours; primarily renal excretion (60%) with fecal elimination (20%) Special considerations: Linear pharmacokinetics at doses below 12 mg; non-linear at higher dosesContraindications
- Hypersensitivity to tizanidine or any component of the formulation
- Concurrent use with potent CYP1A2 inhibitors (fluvoxamine, ciprofloxacin)
- Significant hepatic impairment
Warnings and Precautions
Black Box Warning: None Sedation: May cause significant sedation; caution patients about operating machinery Hypotension: Can cause dose-related hypotension; monitor blood pressure Hepatotoxicity: Monitor liver function tests; discontinue if ALT/AST > 3x ULN Withdrawal: Abrupt discontinuation may cause rebound hypertension, tachycardia, and hypertonia Psychiatric effects: Hallucinations and delusions reported Ophthalmologic effects: May cause dry eyes; caution in patients with dry eye syndromeDrug Interactions
Major interactions:- CYP1A2 inhibitors (fluvoxamine, ciprofloxacin): Contraindicated - increases tizanidine concentrations 30-fold
- Other CNS depressants (alcohol, benzodiazepines, opioids): Additive sedation
- Antihypertensives: Additive hypotensive effects
- Oral contraceptives: May decrease tizanidine clearance
- CYP1A2 inducers (smoking, omeprazole): May decrease efficacy
- Acyclovir: May increase tizanidine concentrations
Adverse Effects
Common (≥10%):- Dry mouth (49%)
- Somnolence (48%)
- Asthenia (41%)
- Dizziness (16%)
- Hypotension
- Bradycardia
- Hallucinations
- Elevated liver enzymes
- Hepatotoxicity
- Severe hypotension
- Syncope
- Psychotic symptoms
Monitoring Parameters
- Blood pressure (especially during dose titration)
- Liver function tests (baseline and periodically)
- Renal function
- Degree of spasticity improvement
- Sedation level
- Signs of hypotension
- Mental status changes
Patient Education
- Take exactly as prescribed; do not exceed recommended dosage
- Avoid alcohol and other CNS depressants
- Rise slowly from sitting/lying position to prevent dizziness
- Do not drive or operate machinery until effects are known
- Report signs of liver problems (yellowing skin, dark urine, abdominal pain)
- Do not stop abruptly; taper under medical supervision
- Inform all healthcare providers about Zanaflex use
- Note that food affects drug absorption
References
1. FDA Prescribing Information: Zanaflex (tizanidine hydrochloride) tablets 2. Nance PW, et al. Efficacy and safety of tizanidine in the treatment of spasticity in patients with spinal cord injury. Neurology. 1994;44(11 Suppl 9):S44-S52 3. Wagstaff AJ, et al. Tizanidine: A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997;53(3):435-452 4. Micromedex Solutions: Tizanidine Drug Monograph 5. Lexicomp Online: Tizanidine Professional Drug Information 6. Clinical Pharmacology: Tizanidine Monograph 7. Gelber DA, et al. Open-label dose-titration safety and efficacy study of tizanidine hydrochloride in the treatment of spasticity associated with chronic stroke. Stroke. 2001;32(8):1841-1846
This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical guidance.