Can tacrolimus (immunosuppressive medication) cause bradycardia (abnormally slow heart rate)?

Tacrolimus and Bradycardia

Yes, tacrolimus can cause bradycardia, though this is an uncommon adverse effect that requires careful monitoring, particularly when combined with other rate-lowering medications.

Direct Cardiac Effects of Tacrolimus

Tacrolimus has documented negative chronotropic (heart rate-slowing) effects on the heart:

• Animal studies demonstrate that clinically relevant doses of tacrolimus (0.1 mg/kg) produce negative chronotropic, inotropic, and dromotropic effects, with cardiovascular effects persisting even after drug infusion cessation despite declining plasma concentrations 1
• A case report documented severe sinus bradycardia (heart rate 42/min) in a renal transplant patient on tacrolimus and diltiazem when ranolazine was added, with complete resolution after stopping ranolazine 2
• The bradycardic effects are believed related to calcium channel blocking properties of tacrolimus 1

Clinical Evidence and Manifestations

Bradycardia from tacrolimus is uncommon but documented in transplant recipients:

• Tacrolimus-induced bradycardia typically presents with fatigue, lethargy, and decreased heart rate, as demonstrated in the case where heart rate dropped to 42/min 2
• More commonly, tacrolimus causes tachyarrhythmias rather than bradycardia, including supraventricular tachycardia and atrial premature complexes 3
• QT prolongation and torsades de pointes represent more serious cardiac complications, particularly with intravenous tacrolimus administration, showing direct linear relationship between arrhythmia and blood tacrolimus levels 4

Critical Drug Interactions

The combination of tacrolimus with other rate-lowering agents significantly increases bradycardia risk:

• Combining tacrolimus with diltiazem (a calcium channel blocker) creates additive negative chronotropic effects 2
• When ozanimod is co-administered with tacrolimus and other immunosuppressants, there is potential for additive immunosuppressive effects, though the primary concern with ozanimod relates to its additive effects on heart rate when combined with beta blockers or calcium channel blockers 5
• The combination of beta blockers or calcium channel blockers with tacrolimus warrants heightened monitoring for bradycardia 6

Monitoring and Management Recommendations

Patients on tacrolimus require cardiovascular surveillance:

• Monitor tacrolimus blood levels closely, as cardiovascular effects may not correlate directly with plasma concentrations and can persist after levels decline 1
• Obtain baseline ECG before initiating tacrolimus to identify pre-existing QT prolongation or conduction abnormalities 4
• Frequent monitoring of heart rate and blood pressure is essential, particularly when initiating therapy or adding medications that affect cardiac conduction 1
• If symptomatic bradycardia develops (heart rate <50/min with symptoms), evaluate for drug interactions and consider dose reduction 2

Clinical Context and Pitfalls

Important considerations when managing tacrolimus-related bradycardia:

• Bradycardia is less common than other tacrolimus cardiac effects (hypertension, QT prolongation, tachyarrhythmias), but remains clinically significant 3, 4, 7
• Reversible myocardial hypertrophy can occur with elevated tacrolimus levels, requiring dose adjustment 7
• The cardiovascular effects of tacrolimus may be enhanced after cessation of infusion despite declining drug levels, necessitating continued monitoring beyond the infusion period 1
• Avoid combining tacrolimus with multiple rate-lowering agents (beta blockers, non-dihydropyridine calcium channel blockers) without careful monitoring 6, 2