Can tizanidine cause bradycardia?

Can Tizanidine Cause Bradycardia?

Yes, tizanidine can cause bradycardia, and this is a well-documented adverse effect that occurs through its mechanism as an α2-adrenergic agonist, similar to clonidine. 1

Mechanism and Incidence

Tizanidine's bradycardic effects stem from its α2-adrenergic agonist properties, which reduce sympathetic outflow and can directly slow heart rate 1. The FDA drug label explicitly warns that hypotension associated with tizanidine dosing is "associated, at times, with bradycardia, orthostatic hypotension, lightheadedness/dizziness and rarely syncope" 1.

In controlled clinical trials, bradycardia was reported as an adverse event requiring monitoring 1. A single-dose placebo-controlled study documented bradycardia rates of 16% with 8 mg doses and 10% with 16 mg doses, compared to 0% with placebo 1.

Clinical Evidence of Severity

Bradycardia from tizanidine can be severe and life-threatening, particularly in vulnerable populations:

• A case report documented profound symptomatic bradycardia (heart rate of 19 bpm with atrial fibrillation) requiring transvenous pacing after a single 4 mg dose in a 93-year-old woman 2
• In a retrospective overdose series, bradycardia occurred in 14 of 45 patients, with the lowest dose associated with bradycardia being 16 mg in a 2-year-old child 3
• A hemodialysis patient developed severe symptomatic bradycardia (47 bpm average, maximum RR interval 3720 msec) on 3 mg/day, which resolved after discontinuation 4
• Overdose cases have demonstrated sinus bradycardia with rates as low as 30 bpm, often accompanied by hypotension 5

High-Risk Populations and Drug Interactions

Elderly patients and those with renal dysfunction are at substantially increased risk 6, 7, 8. The American Geriatrics Society specifically recommends caution with tizanidine in older adults due to sedation and cardiovascular effects 6, 7.

Critical drug interactions that potentiate bradycardia include:

• CYP1A2 inhibitors (ciprofloxacin, fluvoxamine): These dramatically increase tizanidine plasma concentrations, leading to enhanced bradycardic and hypotensive effects 6, 9. A disproportionality analysis found significantly elevated reporting odds ratios for hypotension with ciprofloxacin (ROR 28.1) and fluvoxamine (ROR 36.9) 9
• Other heart rate-lowering medications: Beta-blockers and calcium channel blockers can have additive effects on heart rate when combined with tizanidine 10
• Opioids: Concomitant use with oxycodone and other opioids increases risk of hypotension and bradycardia through additive central mechanisms 6

Monitoring and Management Recommendations

Before initiating tizanidine:

• Screen for concurrent medications, especially CYP1A2 inhibitors, beta-blockers, calcium channel blockers, and opioids 6, 9
• Assess baseline heart rate and blood pressure 1
• Use extreme caution in elderly patients, those with renal or hepatic dysfunction 6, 7, 1

During treatment:

• Monitor vital signs closely, particularly during dose titration 1
• The hypotensive and bradycardic effects are dose-related and typically occur within 1 hour of dosing, peaking at 2-3 hours 1
• Start with low doses (2 mg up to three times daily) in older adults or those with renal impairment 7, 8
• Monitor for orthostatic hypotension when patients move from supine to upright positions 1

If discontinuation is necessary:

• Never abruptly discontinue in long-term users—taper slowly to prevent withdrawal symptoms including rebound tachycardia and hypertension 6, 7, 8, 1

Critical Clinical Pitfalls

The most dangerous scenario occurs when tizanidine is prescribed without screening for CYP1A2 inhibitors, particularly ciprofloxacin, which is commonly prescribed for urinary tract infections 9. This combination can lead to severe bradycardia even at therapeutic tizanidine doses 2, 4, 9.

Single therapeutic doses can cause clinically significant bradycardia in susceptible individuals, particularly the elderly, making the assumption that "low doses are safe" potentially hazardous 2, 4.