Diltiazem and Lanora Co-Administration
Direct Answer
Diltiazem should NOT be co-administered with ivabradine (Lanora) as this combination is explicitly contraindicated by the American Heart Association. 1
Mechanism and Rationale for Contraindication
The American Heart Association guidelines explicitly state to "avoid use with diltiazem, verapamil, grapefruit juice" when prescribing ivabradine (brand name Lanora). 1 This contraindication exists for two critical pharmacological reasons:
CYP3A4 drug interaction: Ivabradine is a substrate of CYP3A4, and diltiazem is a moderate CYP3A4 inhibitor, which significantly increases ivabradine plasma concentrations and raises the risk of excessive bradycardia. 1, 2
Additive heart rate reduction: Both diltiazem and ivabradine independently reduce heart rate through different mechanisms (diltiazem via AV nodal blockade, ivabradine via If channel inhibition in the sinoatrial node), creating dangerous additive bradycardic effects. 1
Clinical Consequences of This Combination
The combination poses serious risks:
Severe symptomatic bradycardia: The dual mechanism of heart rate reduction can lead to profound, clinically significant bradycardia requiring intervention. 1
Increased risk of heart block: Diltiazem's effects on AV nodal conduction combined with elevated ivabradine levels may precipitate higher-degree AV block. 1, 2
Unpredictable drug levels: The CYP3A4 inhibition by diltiazem makes ivabradine dosing unpredictable and potentially dangerous. 1
Alternative Management Strategies
If a patient requires both heart rate control and the specific indication for ivabradine (typically heart failure with reduced ejection fraction):
Choose one agent: Select either diltiazem OR ivabradine based on the primary indication, not both simultaneously. 1
Consider beta-blockers: For most patients requiring heart rate control, beta-blockers remain first-line and can be safely combined with other therapies when ivabradine is not being used. 1
If diltiazem is essential: Use alternative rate control strategies that don't involve ivabradine, such as optimizing beta-blocker therapy or considering digoxin in appropriate patients. 1, 2
Critical Clinical Pitfall
Never assume that lower doses of either medication make this combination safe. The contraindication is absolute and dose-independent because both the pharmacokinetic interaction (CYP3A4 inhibition) and pharmacodynamic interaction (additive bradycardia) persist regardless of dosing. 1