Fibrates interactions

Interactions Antacids ciclosporin colestipol druas metabolized bv cytochrome P450 3A4 fibrates oral-contraceptiyes warfarin niacin erythromycin diaoxin azole-antifunaals... 

Action HMG-CoA reductase inhibitor Dose 5-40 mg PO daily max 5 mg/d w/cyclosporine, 10 mg/d w/gemfibrozil or CrCl <30 mL/min (avoid Al-/Mg-based antacids for 2 h after) Caution [X, /-] Contra Active Uvct Dz, unej lained t LFT Disp Tabs SE Myalgia, constipation, asthenia, abd pain, N, myopathy, rarely rhabdomyolysis Interactions t Effects OF warfarin t risk of myopathy W/ cyclosporine, fibrates, niacin, statins EMS t Effects of warfarin concurrent EtOH use can t risk of liver tox Asian pts have an t risk of advise effects OD Unlikely to cause life-threatening Sxs... 

The fibrates potentiate the actions of the coumarin anticoagulants, such as warfarin, so care should be taken to reduce the dose of simultaneously administered anticoagulants, and plasma prothrombin should be frequently measured until the level stabilizes. As mentioned earlier, great care should be given to combining a statin with a fibrate, since this combination may increase the risk of myositis and perhaps rhabdomyolysis. Table 23.4 summarizes major interactions of drugs that lower cholesterol. 

Myopathy caused by drug interactions The incidence and severity of myopathy are increased by concomitant administration of HMG-CoA reductase inhibitors with drugs that can cause myopathy when given alone, such as gemfibrozil and other fibrates, and lipid-lowering doses (greater than or equal to 1 g/day) of niacin (nicotonic acid). 

Drug Interactions Gemfibrozil Niacin Erythromycin Cholestyramine Digoxin Cimetidine/ranitidine/ omeprazole Rifampicin Warfarin Itraconazole Gemfibrozil Niacin Erythromycin Propranolol Digoxin Warfarin Antacids Colestipol Digoxin Erythromycin Oral contraceptives Fibrates Niacin Azole antifungals... 

Simvastatin (Zocor) [Anrilipemic/HMG-CoA Reductase Inhibitor] Uses X Cholesterol Action HMG-CoA reductase inhibitor Dose Adults. 5-80 mg PO w/ meals X in renal insuff Peds. 10-17 y 10 mg, 40 mg/daily max Caution [X, —] Avoid concurrent use of gemfibrozil Contra PRG, liver Dz Disp Tabs 5,10, 20, 40, 80 mg SE HA, GI upset, myalgia, myopathy (muscle pain, tenderness or weakness w/ creatine kinase 10 x ULN), Hep Interactions T Effects OF digoxin, warfarin T risk of myopathy/iiiabdomyolysis W/ amiodarone, cyclosporine, CYP3A4 inhibitors, fibrates, HIV protease inhibitors, macrolides, niacin, verapamil, grapefruit juice X effects W/ cholestyramine, colestipol, fluvas-tatin, isradipine, propranolol EMS T Effects of warfarin use amiodarone and... 

Susceptibility factors Drug-drug interactions (for example, with fibrates)... 

Ballantine CM, Davidson MH. Possible differences between fibrates in pharmacokinetic interactions with statins. Arch. Intern. Med., 2003, 163, 2394. 

The British National Formulary (BNF) recommends that fibrates or nicotinic acid should not be combined with statins because of the potential for myopathy and rhabdomyolysis with this combination [54]. This is widely discussed in the medical literature. Numerous deaths have been reported and the high mortality associated with concurrent use of cerivastatin and gemfibrozil was partly instrumental in the decision to withdraw cerivastatin from the market in 2001 [34]. It appears that the high mortality in patients using concurrent gemfibrozil and cerivastatin was due to interactions at the level of glucuronidation, CYP2C8 inhibition and OATP inhibition [17, 55]. 

Fibrates should be used cautiously with warfarin and other coumarins, as the INR may rise significantly. The dose of anticoagulant should be reduced by 50% and then adjusted to INR or PT, using serial measurements [1, 28]. This is in addition to the effect of fibrates on haemoglobin, fibrinogen and antithrombin III, and the interaction may be related to displacement of warfarin from protein-binding site [28]. Fatalities have been reported. 

Corsini A, Bellosta S, Davidson MH (2005) Pharmacokinetic interactions between statins and fibrates. Am J Cardiol 96 44K-9K. 

TOLBUTAMIDE FIBRATES Fibrates may t efficacy of sulphonylureas Uncertain postulated that fibrates displace sulphonylureas from plasma proteins and l their hepatic metabolism. In addition, fenofibrate may inhibit CYP2C9-mediated metabolism of tolbutamide Monitor blood glucose levels closely. Warn patients about hypoglycaemia - For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia... 

The increased risk of myopathy observed during concomitant treatment with statins and fibrates may be partly pharmacokinetic in origin. In interactions between fibrates and statins there may be differences between... 

Clinically important, potentially hazardous interactions with fibrates, statins... 

Vu-Dac, N., Schoonjans, K., Laine, B., Fruchart, J. C., Auwerx, J., and Staels, B. (1994). Negative regulation of the human apolipoprotein A-I promoter by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element J Biol Chem 269, 31012-31018. 

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