Diltiazem interaction with other drugs

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. 

Calcium-channel blockers in current clinical usage affect the slow L-type channel. They are usually classified by their chemical structure, which determines their selectivity for vascular smooth muscle over myocardium, and hence their potential to slow the heart rate (negative inotropic activity) see Table 23. T, (below). Interactions due to additive inotropic effects will therefore apply only to the benzothiazepine (diltiazem) and phenyla-Ikylamine-type (verapamil) calcium-channel blockers, and usually not to the dihydropyridine-type (e.g. nifedipine) calcium-channel blockers. All three types of calcium-channel blocker will have additive hypotensive effects with other drugs with blood-pressure lowering activity. 

Verapamil, diltiazem Nonselective block of L-type calcium channels in vessels and heart Reduced vascular resistance, cardiac rate, and cardiac force results in decreased oxygen demand Prophylaxis of angina, hypertension, others Oral, IV, duration 4-8 h Toxicity Atrioventricular block, acute heart failure constipation, edema Interactions Additive with other cardiac depressants and hypotensive drugs... 

The most common interactions with SSRIs are pharmacokinetic interactions. For example, paroxetine and fluoxetine are potent CYP2D6 inhibitors (Table 30-4). Thus, administration with 2D6 substrates such as TCAs can lead to dramatic and sometimes unpredictable elevations in the tricyclic drug concentration. The result may be toxicity from the TCA. Similarly, fluvoxamine, a CYP3A4 inhibitor, may elevate the levels of concurrently administered substrates for this enzyme such as diltiazem and induce bradycardia or hypotension. Other SSRIs, such as citalopram and escitalopram, are relatively free of pharmacokinetic interactions. The most serious interaction with the SSRIs are pharmacodynamic interactions with MAOIs that produce a serotonin syndrome (see below). 

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. 

Established interactions but of uncertain clinical importance. The manufacturers of nifedipine advise caution when it is used with diltiazem because of possible increases in nifedipine levels. They say a reduction in the dose of nifedipine should be considered. Verapamil is predicted to interact similarly. Information about the use of combinations of other ealei-um-channel blockers appears to be lacking. However, the UK manufacturers of nimodipine advise that if it is used with other antihypertensive drugs, including other calcium-channel bloekers sueh as nifedipine, diltiazem, or verapamil, blood pressure monitoring and eareful dose titration of nimodipine should be carried out with possible reduetion or discontinuation of the other calcium-channel bloeker. 

The clinical relevance of the diltiazem interaction was demonstrated in a 53-year-old man, who developed rhabdomyolysis 3 months after diltiazem 30 mg four times daily was added to established treatment with simvastatin 40 mg daily. Both drugs were discontinued and he recovered over the following 10 days. Other similar cases have also been report-ed.3- 3... 

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. 

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... 

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