Diltiazem drug interactions

Caution is needed to avoid potential drug interactions. Tamsulosin decreases metabolism of cimetidine and diltiazem. Carbamazepine and phenytoin increase catabolism of a-adrenergic antagonists. 

Other reported potentially significant drug interactions include the combination of verapamil or nifedipine with CBZ, which, at times, can lead to toxicity secondary to increases in CBZ levels, and neurotoxic reactions when verapamil or diltiazem is combined with lithium. 

Cyclosporine has significant nephrotoxicity, and its toxicity can be increased by drug interactions with diltiazem, potassium-sparing diuretics, and other drugs inhibiting CYP3A. Serum creatinine should be closely monitored. Other toxicities include hypertension, hyperkalemia, hepatotoxicity, gingival hyperplasia, and hirsutism. 

Dixit AA, Rao YM. Pharmacokinetic interaction between diltiazem and tolbutamide. Drug Metabol Drug Interact 1999 15(4) 269-77. 

Diltiazem interacts with lovastatin but not with pravastatin (96). In 10 healthy volunteers given lovastatin orally with or without intravenous diltiazem in a randomized, two-way, crossover design, the interaction of diltiazem with lovastatin was primarily a first-pass effect, due to inhibition of CYP3A4 (97). Thus, drug interactions with diltiazem may become evident when a patient is switched from intravenous to oral dosing. 

In another study by the same investigators, 10 healthy volunteers were randomized in a two-way, crossover study either to oral lovastatin or to intravenous diltiazem followed by oral lovastatin. Intravenous diltiazem did not significantly affect the pharmacokinetics of lovastatin (oral AUC, Cmax, tmax, or half-life), suggesting that the interaction does not occur systemically and is primarily a first-pass effect (11). Drug interactions with diltiazem may therefore become evident when a patient is changed from intravenous to oral dosing. 

CYP3A4 inhibitors that have demonstrated P-gp inhibition include erythromycin, itraconazole, cyclosporine, diltiazem, and several protease inhibitors. As a result of considerable overlap with CYP3A4, the true effect of P-gp modulation on drug interactions involving P-gp substrates is unclear. Further, poor differentiation between P gp modulation in the intestine and liver makes it difficult to determine the relative contribution of P-gp to a specific drug interaction. 

Drug interactions Amphotericin B or potassium-wasting diuretics may contribute to digoxin toxicity ACE-I, amiodarone, bepridii, diltiazem.guinidine, and verapamil may increase digoxin levels. 

Caution is needed when cimetidine or diltiazem is used with tamsulosin or other a-adrenergic antagonists, as a drug-drug interaction leads to decreased metabolism of the latter agents. In contrast, carbamazepine and phenytoin may increase hepatic catabolism of... 

Drug Interactions Since sirolimus is a substrate for CYP3A4 and is transported by P-glycoprotein, close attention to interactions with other drugs that are metaboUzed or transported by these proteins is required. As noted above, cyclosporine and sirolimus interact, and their administration should be separated by time. Dose adjustment may be required when sirolimus is coadministered with diltiazem or rifampin. 

Because finasteride and dutasteride are metabolized primarily by CYP3A4, the CYP3A4 inhibitors, such as ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, and ciprofloxacin, may increase the drugs blood levels and, possibly, cause drug-drug interactions. Clinical drug interaction studies have shown no pharmacokinetic or pharmacodynamic interactions between dutasteride and tamsulosin or terazosin, warfarin, digoxin, and cholestyramine. 

Clarke WR, Horn JR, Kawabori I, Gurtel S. Potentially serious drug interactions secondary to high-dose diltiazem used in die treatment of pulmonary hypertension. Pharmacoiherapy... 

Etoh A, Kohno K. Studies on the drug interaction of diltiazem. IV, Relationship between first pass metabolism of various drugs and the absorption enhancing effect of diltiazem. Yakugaku... 

T. T. Levin, M. H. Bakr and T. Nikolova, Case report delirium due to diltiazem-fentanyl CYP3A4 drug interaction, Gen. Hasp. Psychiatry,... 

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