Statins Diltiazem

While rhabdomyolysis from statins is rare, the risk is increased when they are used in combination with agents that share similar metabolic pathways. Atorvastatin is metabolized by CYP3A4, which is inhibited by diltiazem. 

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. 

Cisapride Antihislainines Astemizole V Chlorphcnirainine Calcium channel blockers Amlodipine Diltiazem Felodipine Nifedipine Nisoldipine Nitrendipine Verapamil. . . HMG CoA reductase inhibitors Atorva statin Cerivastatin Lovastalin... 

CYP3A4 Alfentanil Alprazolam Astern izole Carbamazepine Cisapride Cyclosporine Diltiazem Erythromycin Felodipine Fluconazole Itraconazole Ketoconazole Lidocaine Lova statin Midazolam Nifedipine Quinidine Simvastatin Tacrolimus Terfenadine Verapamil... 

Adverse effects are bradycardia, headache, flushing, palpitations and ankle oedema. There is an increased risk of myopathy if diltiazem is used together with statins (see page 77). 

Similarly, the calcium channel blockers verapamil and diltiazem are inhibitors of both CYP3A4 and P-glycoprotein. Substrates of these two pathways, such as statins, may have significant increases in blood concentrations when used with these inhibitors. 

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. 

Gladding P, Pilmore H, Edwards C. Potentially fatal interaction between diltiazem and statins, Am Intern Med (2004) 140,W31. 

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... 

Effect on atorvastatin. In an open study the eoneurrent use of atorvastatin 10 mg daily with eielosporin resulted in a sixfold inerease in atorvastatin levels, when eompared with historieal eontrols not taking ciclosporin. A further analysis of this study has been reported elsewhere. A case of rhabdomyolysis has been deseribed in a woman who took both drugs for 2 months. She had also been taking diltiazem. In a review of the FDA spontaneous reports of statin-assoeiated rhabdomyolysis eovering the period November 1997 to Mareh 2000, eielosporin was potentially implicated in 5 eases of rhabdomyolysis involving atorvastatin. ... 

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