Dilzem Drug Interactions

Due to the potential for additive effects, caution and careful titration are warranted in patients concomitantly receiving any agent(s) known to affect cardiac contractility and/or conduction.
Diltiazem undergoes biotransformation by cytochrome P450 3A4 (CYP3A4), mixed function oxidase. Diltiazem may competitively inhibit the metabolism of concomitant drugs that undergo the same route of biotransformation, thus increasing their plasma concentration. The extent of interaction and potentiation of effects depend on the variability of effect on CYP3A4.
Lomitapide: Diltiazem may increase lomitapide plasma concentrations through CYP3A4 inhibition leading to increased risk of elevations in liver enzymes (see Contraindications).
Ivabradine: Diltiazem and ivabradine are both associated with a heart rate lowering effect. Furthermore, concomitant use of diltiazem with ivabradine increases exposure (C_max, AUC) of ivabradine due to CYP3A4 inhibition, which may result in an additional heart rate lowering effect. Therefore, their concurrent use is not recommended.
Beta-Blockers: There are few controlled studies on the effectiveness of the concomitant use of diltiazem and beta-blockers or of the safety of this combination in patients with impaired ventricular function or conduction abnormalities.
Administration of diltiazem hydrochloride concomitantly with propranolol in normal volunteers resulted in increased propranolol levels in all subjects, and the bioavailability of propranolol was increased approximately 50%. If combination therapy is initiated or withdrawn in conjunction with propranolol, an adjustment of the propranolol dose may be warranted (see Precautions).
H₂ Antagonists: A study in healthy volunteers has shown a significant increase in peak diltiazem plasma levels (58%) and area under curve (AUC) (53%) after a 1-week course of cimetidine at 1200 mg/day and diltiazem 60 mg/day. Ranitidine produced smaller, non-significant increases. Patients receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with cimetidine. An adjustment in the diltiazem dose may be warranted.
Digitalis: Since there have been conflicting results regarding the effect on digoxin levels, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing diltiazem therapy to avoid possible over- or under-digitalization.
Anesthetics: The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with anesthetics may be potentiated by calcium channel blockers. When used concomitantly, anesthetics and calcium blockers should be titrated carefully.
Ciclosporin: In patients with renal transplant receiving both medications concomitantly, diltiazem increases the plasma level of ciclosporin by as much as 30%. Therefore, the dosage of ciclosporin must be reduced when administering diltiazem and ciclosporin concomitantly.
Carbamazepine: Concomitant use of diltiazem and carbamazepine may enhance the plasma levels of carbamazepine and consequently the risk of toxicity.
Erythromycin: Concurrent use of diltiazem with erythromycin should be avoided by persons at risk for heart irregularities or those with long QT manifestations.
Warfarin, Rifampin, Lithium: There have been reports in the literature of diltiazem interactions with warfarin, rifampin or lithium.
Statins: Diltiazem is an inhibitor of CYP3A4 and has been shown to increase significantly the AUC of some statins. The risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 may be increased with concomitant use of diltiazem. When possible, use a non-CYP3A4-metabolized statin together with diltiazem; otherwise, dose adjustments for both diltiazem and the statin should be considered along with close monitoring for signs and symptoms of any statin-related adverse events.
Mechanistic Target of Rapamycin (mTOR) Inhibitors: Sirolimus C_max and AUC were increased 1.4, and 1.6 fold, respectively following simultaneous oral administration of 10 mg of sirolimus oral solution and 120 mg of diltiazem to 18 healthy volunteers. Sirolimus did not affect the pharmacokinetics of either diltiazem or its metabolites desacetyldiltiazem and desmethyldiltiazem. Diltiazem may increase everolimus blood concentrations by decreasing metabolism via CYP3A4 or the efflux of everolimus from intestinal cells. In addition, sirolimus is a principal metabolite of temsirolimus with an equally potency. A dose reduction of mTOR inhibitor such as sirolimus, temsirolimus, and everolimus, may be necessary if diltiazem is co-administered.