Lipid-regulating drug interactions

1. Acipimox + Colestyramine Colestyramine does not appear to affect the pharmacokinetics of acipimox significantly. 2. Colestyramine + Food Food does not interact with colestyramine. 3. Ezetimibe + Ciclosporin Ciclosporin may greatly elevate ezetimibe levels, and the combination should be used with caution. 4. Fibrates + Bile acid sequestrants Colestyramine does not alter the pharmacokinetics of clofibrate when given at the same time, and similarly colestipol does not alter the pharmacokinetics of clofibrate or fenofibrate. Colestipol can reduce the absorption of gemfibrozil if given at the same time, but not if separated by 2 hours. 5.Fibrates + Diuretics Treatment with clofibrate in patients with nephrotic syndrome receiving furosemide (frusemide) has sometimes led to marked diuresis and severe and disabling muscular symptoms. An isolated report describes rhabdomyolysis in a patient on bezafibrate and furosemide. 6. Fibrates + Ezetimibe Ezetimibe did not alter fenofibrate pharmacokinetics. Fenofibrate and gemfibrozil may modestly increase ezetimibe levels, although this is unlikely to be clinically relevant. The makers currently advise against concurrent use, because of the theoretical increased risk of gallstone formation. 7. Fibrates + Rifampicin (Rifampin) Preliminary evidence shows that rifampicin can reduce the plasma levels of the active metabolite of clofibrate, but rifampicin apparently has no effect on gemfibrozil. 8. Fibrates; Ciprofibrate + Ibuprofen An isolated report describes acute renal failure and rhabdomyolysis in a patient on ciprofibrate when ibuprofen was added.

9. Fibrates; Clofibrate + Oral contraceptives Oral contraceptives increase the loss of clofibrate from the body, but the significance of this is unclear. 10. Fibrates; Clofibrate + Probenecid Plasma clofibrate levels can be approximately doubled by probenecid, but the clinical significance of this is unclear. 11. Fibrates; Gemfibrozil + Antacids Antacids can reduce the absorption of gemfibrozil. 12. Fibrates; Gemfibrozil + Psyllium Psyllium causes a small, but almost certainly clinically unimportant, reduction in the absorption of gemfibrozil. 13. Nicotinic acid (Niacin) + Aspirin Aspirin reduces the flushing reaction that often occurs with nicotinic acid, but there is some evidence that it can also increase nicotinic acid plasma levels. The importance of this latter reaction is uncertain. 14. Nicotinic acid (Niacin) + Nicotine An isolated report describes an unpleasant flushing reaction that developed in a woman taking nicotinic acid when she started to use nicotine transdermal patches. 15. Statins + ACE inhibitors In clinical trials, the safety and efficacy of statins were not altered by concurrent use of ACE inhibitors as a class. An isolated report describes severe hyperkalaemia in a diabetic when given lisinopril and lovastatin. In one study simvastatin did not alter the pharmacokinetics or ACE-inhibitory activity of the ramipril. 16. Statins + Antacids An aluminium/magnesium hydroxide antacid (Maalox) causes a moderate reduction in the bioavailability of atorvastatin and pravastatin, but this does not appear to reduce their lipidlowering efficacy.

17. Statins + Azole antifungals Fluconazole modestly increases the levels of fluvastatin and rosuvastatin, but not pravastatin. Itraconazole causes a marked rise in the serum levels of atorvastatin, lovastatin, pravastatin and simvastatin, but no change in fluvastatin or rosuvastatin levels. Ketoconazole also has no significant effect on rosuvastatin levels. Rhabdomyolysis has been reported with itraconazole or ketoconazole and simvastatin, and with unnamed azoles and atorvastatin or lovastatin. 18. Statins + Beta blockers Propranolol does not cause any clinically relevant changes to the pharmacokinetics of fluvastatin, lovastatin, pravastatin or simvastatin. In clinical trials, the safety and efficacy of statins were not altered by concurrent use of beta blockers as a class. 19. Statins + Bile acid sequestrants Although colestyramine and colestipol reduce plasma fluvastatin and pravastatin levels, the overall total lipid-lowering effect is increased by concurrent use. Separating their administration minimises this interaction. Colestipol appears to interact with atorvastatin similarly. Colesevelam appears not to interact with lovastatin. 20. Statins + Calcium channel blockers Although marked rises in statin plasma levels have been seen with lovastatin/diltiazem, simvastatin/diltiazem, simvastatin/verapamil, and isolated cases of rhabdomyolysis with atorvastatin/diltiazem and simvastatin/diltiazem, it seems that problems with combinations of statins and calcium channel blockers are rare. 21. Statins + Ciclosporin Ciclosporin can cause marked rises in the plasma levels of fluvastatin, lovastatin, pravastatin and simvastatin, and for some of the statins this had led to the development of serious myopathy (rhabdomyolysis) accompanied by kidney failure. Rhabdomyolysis has also been reported with atorvastatin/ciclosporin. The plasma levels of ciclosporin appear not to be affected by fluvastatin, lovastatin or pravastatin, but some moderate changes have been seen when atorvastatin or simvastatin were used. 22. Statins + Diuretics In clinical trials, the safety and efficacy of statins were not altered by concurrent use of diuretics.

23. Statins + Everolimus Everolimus did not alter the pharmacokinetics or HMG-CoA reductase activity of atorvastatin or pravastatin to a clinically relevant extent in a single-dose study in healthy subjects. Everolimus pharmacokinetics were unaltered by the statins. 1 24. Statins + Ezetimibe Ezetimibe does not appear to interact adversely with atorvastatin, fluvastatin, lovastatin or simvastatin. 25. Statins + Fibrates The plasma levels of lovastatin and simvastatin are increased by gemfibrozil. Serious myopathy and/or rhabdomyolysis (one fatal case) have been reported. There is also an isolated case of rhabdomyolysis with atorvastatin/gemfibrozil. One report describes a rise in plasma pravastatin levels caused by gemfibrozil but no pharmacokinetic interactions occur with fluvastatin/gemfibrozil, lovastatin/bezafibrate, pravastatin/fenofibrate, or rosuvastatin/fenofibrate. 26. Statins + Grapefruit juice Large amounts of grapefruit juice markedly increase the plasma levels of lovastatin and simvastatin, but only modestly affect the plasma levels of atorvastatin. Pravastatin seems not to interact. 27. Statins + H2-blockers No clinically significant interaction appears to occur between cimetidine and atorvastatin, fluvastatin, or pravastatin, or between ranitidine and fluvastatin. 28. Statins + HIV-Protease inhibitors The levels of atorvastatin and simvastatin appear to be markedly increased by lopinavir/ritonavir, nelfinavir, ritonavir and ritonavir/saquinavir. Pravastatin seems only moderately affected. Two cases of rhabdomyolysis have been attributed to ritonavir used with simvastatin. 29. Statins + Macrolide antibacterials Erythromycin causes a very marked increase in the serum levels of lovastatin and a minor increase in atorvastatin levels, but it does not interact pharmacokinetically with pravastatin. Cases of acute rhabdomyolysis have been reported with lovastatin/azithromycin, lovastatin/clarithromycin, lovastatin/erythromycin and simvastatin/roxithromycin.

Macrolide antibacterials have also been potentially implicated in cases with atorvastatin and pravastatin. No significant pharmacokinetic interaction has been seen between atorvastatin/azithromycin. Atorvastatin levels are modestly raised by clarithromycin and there are some changes in lovastatin levels with roxithromycin. 30. Statins + Nefazodone Nefazodone has been implicated in cases of muscle toxicity and rhabdomyolysis in two patients on simvastatin, two patients on lovastatin, and one patient on pravastatin. 31. Statins + Nicotinic acid (Niacin) Two cases of rhabdomyolysis and one case of myositis have been reported in patients on lovastatin and nicotinic acid (niacin). 32. Statins + Orlistat No clinically relevant interaction has been seen between orlistat and either atorvastatin or pravastatin. 33. Statins + Phenytoin In an isolated case, phenytoin reduced the cholesterol lowering effect of simvastatin, fluvastatin and atorvastatin. 34. Statins + Rifampicin (Rifampin) Rifampicin lowers the serum levels of fluvastatin and simvastatin. 35. Statins + Sildenafil A man on simvastatin developed symptoms of rhabdomyolysis after taking a single dose of sildenafil. Atorvastatin and sildenafil do not appear to interact pharmacokinetically. 36. Statins + St Johns wort (Hypericum perforatum) St Johns wort modestly decreases the plasma level of simvastatin, but not pravastatin. 37. Statins + Tacrolimus An isolated case of rhabdomyolysis occurred following the concurrent use of tacrolimus and simvastatin. 38.Statins; Atorvastatin + Delavirdine A man developed rhabdomyolysis after taking atorvastatin and delavirdine concurrently.

39. Statins; Cerivastatin + Miscellaneous drugs Cerivastatin has now been withdrawn by the makers because of severe muscle toxicity, but its interactions are briefly listed here for completeness. 40. Statins; Lovastatin + Cilostazol Cilostazol increases the serum levels of lovastatin, and lovastatin slightly reduces the levels of cilostazol. 42. Statins; Lovastatin + Danazol and Doxycycline Severe rhabdomyolysis and myoglobinuria developed in a man on lovastatin about two months after danazol was added. A short course of doxycycline may have had some part to play in what happened. 43. Statins; Lovastatin + Fibre or Pectin Pectin and oat bran can reduce the cholesterol-lowering effects of lovastatin. 44. Statins; Pravastatin + Aspirin Aspirin 324 mg did not significantly affect the pharmacokinetics of a single 20-mg dose of pravastatin. 1 45. Statins; Pravastatin + Mianserin An isolated report describes rhabdomyolysis attributed to the long-term concurrent use of pravastatin and mianserin, triggered by a cold. 46. Statins; Pravastatin + Probucol No clinically significant changes in the bioavailability of a single 20-mg dose of pravastatin was seen in 20 healthy subjects given 500 mg probucol. 1 47. Statins; Simvastatin + Bosentan Bosentan modestly reduces the AUC of simvastatin and its active metabolite, which could lead to a reduction in simvastatin efficacy. 48. Statins; Simvastatin + Imatinib Imatinib raises simvastatin serum levels, increasing the risk of toxicity. 49. Statins; Simvastatin + Irbesartan

Irbesartan appears not to alter the pharmacokinetics of simvastatin.