Contraindications: Potent CYP3A4 inhibitors eg, azole antifungals, macrolide antibiotics, HIV PIs & nefazodone. Increased ivabradine exposure & additional heart rate reduction of 5 bpm w/ moderate CYP3A4 inhibitors. Enhanced depressant effect on BP, heart rate, myocardial contractility & AV conduction w/ IV Ca channel blockers eg, verapamil or diltiazem. Not recommended: Ivabradine: QT prolongation may be exacerbated by heart rate reduction w/ cardiovascular QT prolonging drugs (eg, quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone), non-cardiovascular QT prolonging drugs (eg, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, IV erythromycin). Increased exposure w/ grapefruit juice. Metoprolol: Decreased plasma conc w/ barbituric acid derivatives. May increase risk of rebound HTN w/ centrally-acting antihypertensive agents (eg, clonidine). May increase -ve inotropic effect & atrial conduction time w/ class 1 antiarrhythmics (eg, quinidine, tocainide, procainamide, aimaline, amiodarone, flecainide & disopyramide). Precautions: Ivabradine: Increased risk of arrhythmia w/ K-depleting diuretics; fluconazole; decreased exposure w/ CYP3A4 inducers (eg, rifampicin, barbiturates, phenytoin, St. John's wort). Metoprolol: Plasma conc lowering w/ rifampicin; increased plasma conc w/ cimetidine, alcohol & hydralazine. Plasma conc increase w/ SSRI (eg, paroxetine, fluoxetine & sertraline), diphenhydramine, hydroxychloroquine, celecoxib, terbinafine, neuroleptics, propafenone. Inhibitory effect on CYP2D6 w/ amiodarone & quinidine. Reduced elimination of lidocaine. Enhanced bradycardic effect w/ inhalation anesth. May enhance hypotensive effect w/ nitrates, digoxin. May result in bradycardia & enhanced hypotensive effect w/ β-receptor blockers or MAOIs. Adrenaline; parasympathomimetics; reduced antihypertensive effects w/ NSAIDs; increased hypoglycemic effects w/ insulin & oral antidiabetics. To be taken into consideration: Ivabradine: Increased plasma conc w/ CYP3A4 inhibitors. Decreased plasma conc w/ CYP3A4 inducers. Metoprolol: Additive effects w/ TCA & neuroleptics; additive bradycardiac effects w/ mefloquine; increased antihypertensive effects w/ IV dipyridamole. Increased hypotensive effects w/ urology α-blockers; increased vasoconstrictive effects w/ ergotamine; enhancement of neuromuscular block w/ skeletal muscle relaxant; may impede compensatory CV reactions associated w/ hypotension or shock w/ floctafenine; increased plasma conc w/ antacid.