Valheart Drug Interactions

CYP3A4 Inhibitors: Concomitant use with potent CYP3A4 inhibitors such as azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, oral erythromycin, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir), and nefazodone is contraindicated because of substantial increases in ivabradine exposure and risks of excessive bradycardia.
Concomitant use of ivabradine with moderate CYP3A4 inhibitors with their own heart rate reducing properties (i.e., diltiazem or verapamil) is also contraindicated because of increased ivabradine exposure and additive effects on heart rate.
Concomitant use with other moderate CYP3A4 inhibitors (e.g., fluconazole) may be considered at the starting dose of 2.5 mg twice a day and if resting heart rate is above 70 bpm, with monitoring of heart rate.
CYP3A4 Inducers (e.g., St. John's Wort, rifampicin, barbiturates, phenytoin): Concomitant use with a CYP3A4 inducer may decrease ivabradine exposure. Ivabradine may be initiated and titrated with the usual recommended doses. Close heart rate monitoring is recommended if treatment with the CYP3A4 inducer needs to be interrupted, ivabradine dosing may need to be reduced.
QT Prolonging Agents: Concomitant use with cardiovascular QT prolonging agents (e.g., quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone) and non-cardiovascular QT prolonging agents (e.g., pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, intravenous erythromycin) should be avoided since QT prolongation may be exacerbated by heart rate reduction. If the combination appears necessary, close cardiac monitoring (12-lead ECG) is required.
Negative Chronotropes: Concomitant use with drugs that slow heart rate (e.g., digoxin, beta-blockers) increases the risk of bradycardia. Monitor patients taking ivabradine with other negative chronotropes.
Potassium-depleting Diuretics (e.g., furosemide, hydrochlorothiazide, indapamide): Hypokalemia can increase the risk of arrhythmia. As ivabradine may cause bradycardia, the resulting combination of hypokalemia and bradycardia is a predisposing factor to the onset of severe arrhythmias, especially in patients with long QT syndrome, whether congenital or substance-induced.
Grapefruit Juice: Coadministration with grapefruit juice increased ivabradine exposure by 2-fold. Therefore, grapefruit juice should be avoided during treatment with ivabradine.
Other Drugs: Coadministration of ivabradine did not result in a clinically significant interaction with proton pump inhibitors (omeprazole, lansoprazole), sildenafil, HMG-CoA reductase inhibitors (simvastatin), dihydropyridine calcium channel blockers (amlodipine, lacidipine), aspirin, and warfarin.