Fibrates Warfarin

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. 

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... 

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. 

FIBRATES ANTICOAGULANTS-ORAL T efficacy of warfarin and phenindione Uncertain postulated that fibrates displace anticoagulants from their binding sites Monitor INR closely... 

Lipid-lowering drugs. Fibrates, and some statins, enhance anticoagulant effect. Colestyramine is best avoided for it may impair the absorption of both warfarin and vitamin K. 

The use of statins and probably fibrates should be suspended during daptomycin use because of the possible increased risk of muscle toxicity. Daptomycin does not appear to interact with warfarin, but its use may result in falsely elevated prothrombin times. NSAIDs may reduce daptomycin excretion and concurrent use may increase the risks of renal impairment... 

Uncertain. Clofibrate can displace warfarin from its plasma protein binding sites, but this does not adequately explain the interaetion. Another suggestion is that the fibrates have an additive pharmacodynamic effect. Altered metabolism may also account for the interaetion with ciprofibrate, since this decreased the clearance of 5-warfarin. However, this did not occur with clofibrate or gemfibrozil. ... 

Schelleman H, Bilker WB, Brensinger CM, Wan F, Yang YX, Hennessy S. Fibrate/ statin initiation in warfarin users and gastrointestinal bleeding risk. Am J Med 2010 123(2) 151-7. 

Fibrates An interaction of gemfibrozil with warfarin has been described in a 62-year-old man, whose INR rose to 5.8 within 3 weeks of the addition of gemfibrozil 600 mg bd. The authors recommended a dosage reduction of 20% and close monitoring during administration of this combination [39. ... 

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