Simvastatin Calcium-channel blockers

Drugs that may affect repaglinide include CYP 450 inhibitors (eg, clarithromycin, erythromycin, ketoconazole, miconazole), CYP 450 inducers (eg, barbiturates, carbamazepine, rifampin), beta blockers, calcium channel blockers, chloramphenicol, corticosteroids, coumarins, estrogens, gemfibrozil, isoniazid, itraconazole, levonorgestrel and ethinyl estradiol, MAOIs, nicotinic acid, NSAIDs, oral contraceptives, phenothiazines, phenytoin, probenecid, salicylates, simvastatin, sulfonamides, sympathomimetics, thiazides and other diuretics, and thyroid products. 

In a meta-analysis of megatrials of simvastatin, the overall incidence of myopathy was 0.025% the same proportion of those with myositis had used calcium channel blockers as the proportion overall, suggesting that there is no important interaction between these two groups of drugs (32). 

CALCIUM CHANNEL BLOCKERS STATINS t plasma levels of atorvastatin, lovastatin and simvastatin case reports of myopathy when atorvastatin and simvastatin are co-administered with diltiazem or verapamil Uncertain, but postulated to be due to inhibition of CYP3A4-mediated metabolism of statins in the intestinal wall. Also, diltiazem and verapamil inhibit intestinal P-gp, which may t the bioavailability of statins Watch for side-effects of statins. It has been suggested that the dose of simvastatin should not exceed 20 mg when given with verapamil, and 40 mg when given with diltiazem... 

D Rifampin significantly reduces the plasma concentrations of the calcium channel blockers verapamil, diltiazem, and nifedipine. Diltiazem is a substrate of Gi P3A4 and rifampin is an inducer of CYP3A4. Rifampin does not interact with metoprolol, aspirin, pravastatin, or nitroglycerin. However, if the patient had been on another HMG-CoA reductase inhibitor such as atorvastatin, lova-statin, or simvastatin instead of pravastatin, rifampin would have reduced the plasma concentrations of these agents since they are also metabolized via CYP3A4. 

CYP3A4 alprazolam, calcium channel blockers, cisapride, clarithromycin, cyclosporin A, erythromycin, HIV protease inhibitors, lidocaine, midazolam, simvastatin, terfenadine carbamazepine, dexamethsone, phenobarbital, phenytoin, rifampicin, St John s wort cimetidine, erythromycin, grapefruit juice, HIV protease inhibitors, itraconazole, ketoconazole... 

Marked rises in statin plasma levels have been seen when lovastatin or simvastatin were given with diltiazem, and when simvastatin was given with verapamil. Isolated cases of rhabdomyolysis have occurred as a result of these interactions. However, overall, it seems that problems with combinations of statins and calcium-channel blockers (particularly the dihydropyridine-type) are rare. 

Information is limited, but what is known suggests that the concurrent use of these drugs is normally uneventful. Even with those pairs of drugs where the increases in plasma levels are quite large (such as when simvastatin was given with diltiazem or verapamil) problems seem to be very rare. Indeed an analysis of the 4S study and the Heart Protection Study (which used maximum simvastatin doses of 40 mg) found no evidence that the concurrent use of a calcium-channel blocker increases the risk of myopathy. Therefore concurrent use need not be avoided, but it has been suggested that treatment with a statin in a patient taking diltiazem (and probably verapamil) should be started with the lowest possible dose and titrated upwards, or, if diltiazem (or verapamil) is started, the dose of the... 

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