What are the contraindications for ivabradine?

Ivabradine Contraindications

Ivabradine is absolutely contraindicated in acute decompensated heart failure, clinically significant hypotension (BP <90/50 mm Hg), sick sinus syndrome, sinoatrial block or 3rd-degree AV block (unless a functioning demand pacemaker is present), clinically significant bradycardia, severe hepatic impairment, pacemaker dependence, and concomitant use of strong CYP3A4 inhibitors. 1

Absolute Contraindications

The FDA drug label clearly delineates the following absolute contraindications 1:

Cardiac Contraindications

• Acute decompensated heart failure - Ivabradine is only for stable, chronic heart failure
• Sick sinus syndrome, sinoatrial block, or 3rd-degree AV block (unless a functioning demand pacemaker is present)
• Clinically significant bradycardia - The drug further slows heart rate by inhibiting the If current
• Pacemaker dependence - When heart rate is maintained exclusively by the pacemaker 1

Hemodynamic Contraindications

• Clinically significant hypotension - Specifically BP <90/50 mm Hg 2, 3

Hepatic Contraindications

• Severe hepatic impairment (Child-Pugh C) - Increased systemic exposure is anticipated 1

Drug Interaction Contraindications

• Concomitant use of strong CYP3A4 inhibitors including boceprevir, clarithromycin, indinavir, itraconazole, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir, telaprevir, posaconazole, and voriconazole 2, 3, 1

Critical Precautions and Relative Contraindications

Drugs to Avoid

Avoid concomitant use with diltiazem, verapamil, and grapefruit juice - These increase ivabradine exposure and contribute to heart rate lowering 2, 3. The 2015 ACC/AHA/HRS guidelines explicitly state to avoid these combinations.

Avoid strong CYP3A4 inducers including carbamazepine, phenytoin, rifampin, and St. John's wort - These reduce ivabradine efficacy 2, 3

Rhythm Requirements

Ivabradine requires sinus rhythm - It is contraindicated in persistent or chronic atrial fibrillation and in patients experiencing 100% atrial pacing 4. However, a history of paroxysmal atrial fibrillation is NOT a contraindication if the patient is in sinus rhythm at least 40% of the time 4.

Pregnancy and Lactation

Ivabradine is contraindicated in pregnancy based on animal data showing embryo-fetal toxicity and cardiac teratogenic effects at exposures 1-3 times the human exposure at maximum recommended doses 1. Advise females of reproductive potential to use effective contraception 1.

Breastfeeding is not recommended - Ivabradine is present in rat milk with milk-to-plasma ratios of 1.5-1.8 1

Conduction Defects

In patients with a history of conduction defects or 2nd-degree AV block, avoid use unless a functioning demand pacemaker is present 1. If ivabradine must be used, initiate at 2.5 mg twice daily rather than the standard 5 mg dose 1.

Common Pitfalls

1. Don't confuse paroxysmal AF with persistent/chronic AF - Paroxysmal AF is acceptable if sinus rhythm is present ≥40% of the time 4

2. Don't combine with other bradycardic agents without caution - Concomitant drugs that exacerbate bradycardia increase risk 2, 3

3. Don't use in unstable patients - Only for stable, chronic heart failure, not acute decompensation 4, 1

4. Monitor for atrial fibrillation development - Ivabradine increases AF risk (5.0% vs 3.9% per patient-year with placebo) and should be discontinued if AF develops 4, 1