Can you overdose on tizanidine (muscle relaxant)?

Tizanidine Overdose: Risks and Management

Yes, you can overdose on tizanidine, and it can be potentially life-threatening with symptoms including severe sedation, respiratory depression, bradycardia, and hypotension requiring intensive medical support. 1

Pharmacology and Mechanism of Action

Tizanidine is an α2-adrenergic receptor agonist that functions as a centrally acting muscle relaxant. It is structurally related to clonidine but has fewer cardiovascular effects at therapeutic doses. As a spasmolytic agent, it works by increasing presynaptic inhibition of motor neurons, resulting in reduced muscle tone and spasticity. 2

Overdose Presentation

Tizanidine overdose manifests with a predictable constellation of symptoms:

• Central nervous system effects:

  • Depressed consciousness (somnolence, stupor, coma)
  • Lethargy (most common symptom)
  • Confusion
  • Agitation

• Cardiovascular effects:

  • Bradycardia
  • Hypotension (can be severe)

• Respiratory effects:

  • Respiratory depression
  • Respiratory failure in severe cases 1, 3

Dose-Response Relationship in Overdose

The severity of overdose symptoms correlates with the amount ingested:

• Doses as low as 28mg have been associated with hypotension in vulnerable individuals
• Coma has been reported with doses between 60-120mg
• Fatal overdoses have occurred, particularly when combined with other CNS depressants 3

In a retrospective review of 45 tizanidine overdose cases:

• Mean ingested dose was 72mg
• Lethargy occurred in 84% of patients
• Bradycardia in 31%
• Hypotension in 18%
• Coma in 4% 3

Risk Factors for Severe Overdose

Several factors increase the risk of severe tizanidine toxicity:

1. Concomitant use of other CNS depressants - particularly opioids, benzodiazepines, or alcohol

2. Drug interactions - especially with CYP1A2 inhibitors such as:

   • Ciprofloxacin (contraindicated)
   • Fluvoxamine (contraindicated)
   • Oral contraceptives
   • Amiodarone
   • Verapamil
   • Cimetidine
   • Famotidine 2

3. Pre-existing conditions:

   • Hepatic dysfunction
   • Renal impairment
   • Advanced age 2

Management of Tizanidine Overdose

Treatment is primarily supportive:

1. Airway management - ensuring adequate ventilation is critical
2. Cardiovascular support - may require vasopressors for hypotension
3. Monitoring - close observation of vital signs and mental status
4. Naloxone - generally ineffective for tizanidine overdose 3

Most cases resolve within 1-3 days with appropriate supportive care. 1

Prevention and Risk Reduction

To minimize overdose risk:

• Start with low doses and titrate slowly
• Use caution when prescribing to elderly patients or those with hepatic/renal dysfunction
• Avoid combining with other CNS depressants when possible
• Be aware of drug interactions, particularly with CYP1A2 inhibitors
• Educate patients about proper dosing and potential risks 2

Special Considerations

If discontinuing tizanidine in patients on long-term therapy, taper slowly to avoid withdrawal symptoms including rebound tachycardia, hypertension, and hypertonia. 2

For any suspected overdose, contact a poison control center immediately for the most current management recommendations. 1