Tizanidine Contraindications
The only absolute contraindication to tizanidine is known hypersensitivity to tizanidine or its ingredients. 1
Absolute Contraindication
- Known hypersensitivity to tizanidine or any of its ingredients is the sole FDA-listed contraindication. 1
Critical Relative Contraindications and High-Risk Situations
While not absolute contraindications, the following situations warrant extreme caution or avoidance:
Hepatic and Renal Dysfunction
- Tizanidine should be avoided in patients with hepatic or renal dysfunction due to significantly reduced drug clearance and increased risk of serious adverse effects. 2
- Case reports document severe liver, renal, and cardiovascular failure following tizanidine overdose, particularly when compounded by dehydration or comorbidities. 3
Concurrent CYP1A2 Inhibitor Use
- Concomitant use of CYP1A2 inhibitors (such as fluvoxamine, ciprofloxacin, or other fluoroquinolones) dramatically increases tizanidine plasma concentrations and can cause life-threatening hypotension. 4, 2, 5
- This interaction effectively represents a practical contraindication due to the narrow therapeutic window and risk of severe adverse effects. 5
Elderly Patients
- The American Academy of Neurology and American Geriatrics Society recommend avoiding tizanidine in elderly patients due to significant sedative and hypotensive effects that increase fall risk. 2
- Older adults rarely tolerate doses greater than 30-40 mg per day and are at heightened risk for sedation, somnolence, and orthostatic hypotension. 4, 2
Important Clinical Warnings
Cardiovascular Risks
- Tizanidine causes significant hypotension requiring careful monitoring, particularly when combined with other blood pressure-lowering medications such as opioids. 4, 2
- Tizanidine can prolong the QT interval by blocking the rapid component of the delayed rectifier potassium current (IKr), potentially causing cardiac arrhythmias. 6
- Patients with cardiovascular instability or those taking QT-prolonging medications require heightened vigilance. 6
Drug Interactions Requiring Caution
- Combining tizanidine with opioids (such as oxycodone) carries significant risk of additive hypotension and excessive sedation. 2
- Concurrent use with other CNS depressants (benzodiazepines, pregabalin, quetiapine, duloxetine) produces additive sedative effects. 2
- Adding tizanidine to acetaminophen increases CNS adverse events 2.44-fold, primarily sedation and dizziness. 7
Pediatric Use
- Tizanidine use in pediatric populations is off-label, and case reports demonstrate that overdose can result in severe multi-organ failure, especially when combined with dehydration or malnutrition. 3
Common Pitfalls to Avoid
- Never discontinue tizanidine abruptly in long-term users—taper slowly to prevent withdrawal symptoms including tachycardia, hypertension, and rebound hypertonia. 4, 7, 2
- Do not confuse spasticity (increased muscle tone) with hypotonia (reduced muscle tone)—tizanidine is specifically indicated for spasticity and inappropriate for hypotonia. 4, 7
- Avoid polypharmacy situations without careful review of all medications for potential interactions, particularly CYP1A2 inhibitors. 2, 5
- Do not use tizanidine as first-line therapy in older adults when the American Geriatrics Society suggests baclofen or benzodiazepines may be more appropriate for true muscle spasm. 2