What is the treatment for tizanidine (Zanaflex) overdose presenting with bradycardia?

Treatment of Tizanidine Overdose with Bradycardia

Tizanidine overdose presenting with bradycardia should be managed primarily with supportive care, including airway protection, cardiovascular monitoring, and vasopressor support when hemodynamically unstable, as the drug's alpha-2 agonist effects cause bradycardia and hypotension similar to clonidine toxicity. 1

Initial Management and Monitoring

• Ensure airway adequacy immediately, as altered mental status and respiratory depression are common; intubation may be required in severe cases 1, 2
• Establish continuous cardiac monitoring for heart rate, rhythm, and blood pressure, as bradycardia can be profound (heart rates as low as 19-30 bpm reported) 2, 3
• Secure reliable IV access for medication administration 4
• Monitor mental status closely, as lethargy, confusion, stupor, and coma are frequent manifestations 1, 2

The FDA label explicitly states that tizanidine overdose management is similar to clonidine overdose due to their shared alpha-2 agonist mechanism 1. Clinical effects typically resolve within 1-3 days with appropriate supportive therapy 1.

Pharmacologic Treatment for Bradycardia

First-Line: Atropine

• Administer atropine 0.5-1 mg IV (may repeat every 3-5 minutes to maximum 3 mg) for symptomatic bradycardia 4
• Atropine is reasonable for bradycardia associated with symptoms or hemodynamic compromise, though treatment failures can occur 4

Second-Line: Vasopressors and Inotropes

• Use vasopressors for persistent hypotension despite atropine, particularly when bradycardia contributes to hemodynamic instability 4
• Norepinephrine is preferred based on evidence from similar alpha-2 agonist toxicity (doses up to 100 mcg/min in adults may be needed) 4, 5
• Dopamine 5-20 mcg/kg/min IV starting at 5 mcg/kg/min, increasing by 5 mcg/kg/min every 2 minutes 4
• Epinephrine 2-10 mcg/min IV or 0.1-0.5 mcg/kg/min titrated to effect 4

A case report demonstrated successful use of norepinephrine infusion to maintain hemodynamic stability in tizanidine overdose with bradycardia and shock 5.

Beta-Agonists (Use with Caution)

• Isoproterenol 20-60 mcg IV bolus or infusion of 1-20 mcg/min may be considered in patients at low likelihood of coronary ischemia 4
• Dobutamine may be considered as an alternative beta-agonist 4

Important caveat: Monitor for potential ischemic chest pain and arrhythmias with beta-agonist therapy, particularly at higher doses 4.

Electrical Pacing

• Consider transcutaneous or transvenous pacing for profound symptomatic bradycardia unresponsive to pharmacologic therapy 4, 3
• One case report documented a 93-year-old requiring transvenous pacing for heart rate of 19 bpm after a single 4 mg dose, ultimately receiving a permanent pacemaker 3
• Electrical pacing may be reasonable but is not always effective, particularly with significant vasodilatory shock 4

Naloxone: Not Recommended

• Naloxone is ineffective for tizanidine overdose; in a case series of 7 patients receiving naloxone, 5 had no response and only 1 showed arousal 2
• Do not delay appropriate supportive care by attempting naloxone administration

Special Populations and Considerations

Elderly Patients

• Exercise extreme caution in elderly patients, who may develop profound bradycardia even from therapeutic doses 3
• The lowest reported dose causing severe bradycardia requiring pacing was a single 4 mg dose in a 93-year-old 3

Renal Dysfunction

• Anticipate prolonged effects in patients with renal impairment, as tizanidine clearance is reduced 4, 6
• One hemodialysis patient developed severe bradycardia (47 bpm, maximum RR interval 3720 msec) with elevated trough levels (1.78 ng/mL) on therapeutic dosing 6

Pediatric Patients

• Doses as low as 16 mg can cause bradycardia and drowsiness in young children 2
• Doses ≥1.6 mg/kg/day can cause liver, renal, and cardiovascular failure, particularly when combined with dehydration 7
• Single tablet ingestions (2-4 mg) typically cause only mild drowsiness in children <6 years 2

Long-Term Monitoring

• Continue cardiac monitoring for at least 24-48 hours after symptom resolution, as myocardial toxicity can be prolonged 5
• One case report documented severe fatty metabolic disorder, sympathetic denervation, and non-sustained ventricular tachycardia persisting 30 days post-overdose, with complete recovery requiring one year 5
• Monitor for arrhythmias during recovery period, particularly in patients with severe initial presentation 5

Outcomes

• Prognosis is generally good with supportive care; all 45 patients in the largest case series recovered without residual complications 2
• Mean dose ingested was 72 mg (range not specified), with hypotension occurring at doses as low as 28 mg 2
• Fatalities have occurred in intentional overdoses, particularly when combined with other CNS depressants 1