CONTRAINDICATIONS / PRECAUTIONS
General Information
Fenofibric acid is contraindicated in patients with hypersensitivity to fenofibric acid, choline fenofibrate, or fenofibrate.
Dialysis, renal disease, renal failure, renal impairment
Fenofibric acid is contraindicated in patients with severe renal dysfunction including renal failure or severe renal disease and those on dialysis. Per the manufacturer, fenofibric acid accumulates during chronic therapy in these patients and is not removed by hemodialysis. Fenofibric acid clearance is also reduced in patients with mild to moderate renal impairment. Elevations in serum creatinine have been reported in patients on fenofibrate. These elevations return to baseline upon discontinuation of therapy. The risk of rhabdomyolysis and myositis may be increased in patients with impaired renal function who take fibric acid derivatives. Lower doses should be prescribed in patients who have moderate renal dysfunction.
Cholelithiasis, gallbladder disease
Fenofibric acid is contraindicated in patients with pre-existing gallbladder disease because it may exacerbate this condition. Other fibric acid derivatives, clofibrate and gemfibrozil, have been associated with a higher risk of cholecystitis and cholelithiasis in clinical trials. Fenofibric acid is the active metabolite of fenofibrate. The association between fenofibrate and gallbladder disease is less defined, but post-marketing studies in Europe suggest that the frequency of gallstones may not be significantly increased with therapy. However, fenofibric acid may increase the saturation of cholesterol in the bile, and therefore could potentially lead to cholelithiasis. If gallstones develop, discontinue fenofibric acid.
Biliary cirrhosis, hepatic disease
Fenofibric acid is contraindicated in patients with pre-existing hepatic disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities.
Pancreatitis
Significantly elevated serum triglyceride concentrations (e.g., > 2000 mg/dL) may increase the risk of pancreatitis. The effect of fenofibric acid on this risk has not been adequately studied. Pancreatitis has been reported in patients taking fenofibric acid. Use fenofibric acid with caution in patients at risk for developing pancreatitis.
Cardiac disease
Because of clinical and pharmacologic similarities between fenofibric acid and other fibric acid derivatives, findings of important cardiac trials of gemfibrozil and clofibrate may also be applicable to fenofibrate and fenofibric acid. In the Helsinki Heart Study, men with known heart disease (secondary prevention group) had a higher trend of cardiac deaths with gemfibrozil versus placebo. Total mortality was found to be elevated in the primary prevention group, despite the effectiveness of gemfibrozil in preventing heart disease. In a study conducted by the WHO, patients without coronary heart disease were treated with clofibrate or placebo for 5 years. There was a significant increase in deaths from non-cardiac causes, including malignancy, post-cholecystectomy complications, and pancreatitis in the clofibrate group. All trials included large numbers of patients treated with fibric acid derivatives for several years. No such trials have been performed for fenofibrate or fenofibric acid, and the benefit/risk ratio for primary or secondary cardiac disease, or other non-cardiovascular mortality has not been established. Fenofibric acid should only be used in the treatment of dyslipidemias where the benefit to the patient would outweigh the potential health risks.
Anticoagulant therapy, thromboembolic disease
Caution should be used when fenofibric acid is used in patients with thromboembolic disease. Fenofibric acid is the active metabolite of fenofibrate, and thrombosis has occurred in patients taking fenofibrate. In addition, caution should be used when prescribing fenofibrate or fenofibric acid to patients receiving anticoagulant therapy. Fenofibrate has been shown to potentiate the effects of coumarin-type anticoagulants.
Geriatric
In geriatric volunteers, the oral clearance of fenofibric acid following a single dose was similar to that observed in young adults, suggesting that a similar dosage regimen can be used for geriatric patients. However, the risk of adverse effects from fenofibric acid is greater in patients with impaired renal function. Since geriatric patients have a higher incidence of renal impairment, dose selection for geriatric patients should be based on renal function.
Diabetes mellitus
Patients with diabetes mellitus are at increased risk for serious muscle toxicity, including myopathy and rhabdomyolysis, when treated with fibrate therapy. Additionally, because fenofibrate therapy has been associated with elevations in serum creatinine, renal monitoring should be considered in patients at increased risk for renal impairment including those with diabetes. Of note, fenofibrate was not shown to reduce coronary heart disease morbidity and mortality in 2 large, randomized controlled trials of patients with type 2 diabetes mellitus.
Hypothyroidism
Use fenofibric acid cautiously in those patients with hypothyroidism. The risk for fenofibric acid-associated serious muscle toxicity, including myopathy and rhabdomyolysis, appears to be increased in patients with hypothyroidism.
Pregnancy
Fenofibric acid has been classified as FDA pregnancy risk category C. There are no adequate and well controlled studies in pregnant women. According to the manufacturer, use of fenofibric acid during pregnancy should be avoided unless the potential benefits justify the potential risks to the fetus.
Breast-feeding
According to the manufacturer, fenofibric acid is contraindicated in women who are breast-feeding. The importance of continued fenofibric acid therapy to the mother should be considered in making the decision whether to discontinue breast-feeding or discontinue the medication. If pharmacotherapy is necessary in the nursing mother, a nonabsorbable resin such as cholestyramine, colesevelam, or colestipol should be considered. These agents do not enter the bloodstream and thusly will not be excreted during lactation. However, resins bind fat-soluble vitamins and prolonged use may result in deficiencies of these vitamins in the mother and her nursing infant.
DRUG INTERACTIONS
Acarbose: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Acetaminophen; Diphenhydramine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as diphenhydramine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diphenhydramine during coadministration with fenofibric acid.
Albiglutide: Fibric acid derivatives may enhance the hypoglycemic effects of incretin mimetics through increased insulin sensitivity and decreased glucagon secretion. Patients receiving this combination should be monitored for changes in glycemic control.
Aliskiren; Valsartan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as valsartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of valsartan during coadministration with fenofibric acid.
Alogliptin: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Alogliptin; Metformin: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Alogliptin; Pioglitazone: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion; monitor for changes in glycemic control and for needed dose adjustments.
Alpha-glucosidase Inhibitors: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Amlodipine; Atorvastatin: Use caution when coadministering atorvastatin and fenofibric acid. Using lower starting and maintenance doses of atorvastatin should be considered. The risk of myopathy increases when HMG-CoA reductase inhibitors are administered concurrently with fibric acid derivatives. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as valsartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of valsartan during coadministration with fenofibric acid.
Amlodipine; Valsartan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as valsartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of valsartan during coadministration with fenofibric acid.
Amoxicillin; Clarithromycin; Lansoprazole: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as lansoprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of lansoprazole during coadministration with fenofibric acid.
Amoxicillin; Clarithromycin; Omeprazole: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibric acid.
Amprenavir: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as amprenavir, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of amprenavir during coadministration with fenofibric acid.
Aspirin, ASA; Carisoprodol: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as carisoprodol, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of carisoprodol during coadministration with fenofibric acid.
Aspirin, ASA; Carisoprodol; Codeine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as carisoprodol, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of carisoprodol during coadministration with fenofibric acid.
Aspirin, ASA; Omeprazole: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibric acid.
Aspirin, ASA; Pravastatin: The risk of myopathy during treatment with other HMG-CoA reductase inhibitors is generally increased with concurrent therapy with fibric acid derivatives. The use of fibrates alone may occasionally be associated with myopathy. Combination therapy with pravastatin and gemfibrozil is generally not recommended. The combined use of pravastatin and fibrates should be avoided unless the benefit of further alterations in lipid levels is likely to outweigh the increased risk of this drug combination. Preliminary data suggest that the addition of gemfibrozil to therapy with pravastatin is not associated with greater reduction in LDL-cholesterol than that achieved with pravastatin alone. Pravastatin and gemfibrozil have been administered together in a study of 290 patients, with two patients developing asymptomatic elevations of CPK; severe myopathy was not observed, although muscle biopsies were not performed. In addition, a trial of pravastatin (40 mg/day) coadministration with gemfibrozil (1200 mg/day) has not been shown to be associated with myopathy, although 4 of 75 patients receiving the combination showed marked CPK elevations versus 1 of 73 patients receiving placebo. A trend has been reported toward more frequent CPK elevations and patient withdrawals due to musculoskeletal symptoms in the group receiving combined treatment as compared to the groups receiving placebo, gemfibrozil, or pravastatin monotherapy. In a crossover study in 20 healthy male volunteers given concomitant single doses of pravastatin and gemfibrozil, there was a significant decrease in urinary excretion and protein binding of pravastatin. In addition, there was a significant increase in AUC, Cmax, and Tmax for the pravastatin metabolite SQ 31,906.
Atorvastatin: Use caution when coadministering atorvastatin and fenofibric acid. Using lower starting and maintenance doses of atorvastatin should be considered. The risk of myopathy increases when HMG-CoA reductase inhibitors are administered concurrently with fibric acid derivatives. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Atorvastatin; Ezetimibe: Use caution when coadministering atorvastatin and fenofibric acid. Using lower starting and maintenance doses of atorvastatin should be considered. The risk of myopathy increases when HMG-CoA reductase inhibitors are administered concurrently with fibric acid derivatives. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. Ezetimibe was approved by the FDA for use in combination with fenofibrate as adjunctive therapy to diet for the treatment of hypercholesterolemia in patients with mixed hyperlipidemia in May 2006. However, the safety and effective use of ezetimibe when coadministered with other fibric acid derivatives such as gemfibrozil or clofibrate has not been established. Until further data are available to support efficacy and safety, ezetimibe is not recommended for use with gemfibrozil. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile. The incidence rates for cholecystectomy have been reported as 0.6% for fenofibrate monotherapy and 1.7% for combination therapy (ezetimibe plus fenofibrate), respectively. According to the manufacturer, the number of patients exposed to combination therapy versus fenofibrate or ezetimibe monotherapy has been inadequate to assess gallbladder disease risk. If cholelithiasis is suspected in a patient receiving ezetimibe and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered. In a pharmacokinetic study, concomitant fenofibrate or gemfibrozil administration increased total ezetimibe concentrations by approximately 1.5- or 1.7-fold, respectively. However, ezetimibe does not affect the pharmacokinetics of fenofibrate or the bioavailability of gemfibrozil.
Atropine; Hyoscyamine; Phenobarbital; Scopolamine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as phenobarbital, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of phenobarbital during coadministration with fenofibric acid.
Belladonna Alkaloids; Ergotamine; Phenobarbital: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as phenobarbital, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of phenobarbital during coadministration with fenofibric acid.
Bortezomib: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as bortezomib, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of bortezomib during coadministration with fenofibric acid.
Bosentan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as bosentan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of bosentan during coadministration with fenofibric acid.
Canagliflozin: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Canagliflozin; Metformin: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Candesartan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as candesartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of candesartan during coadministration with fenofibric acid.
Candesartan; Hydrochlorothiazide, HCTZ: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as candesartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of candesartan during coadministration with fenofibric acid.
Carbetapentane; Diphenhydramine; Phenylephrine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as diphenhydramine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diphenhydramine during coadministration with fenofibric acid.
Carisoprodol: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as carisoprodol, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of carisoprodol during coadministration with fenofibric acid.
Celecoxib: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as celecoxib, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of celecoxib during coadministration with fenofibric acid.
Chenodiol: Fibric acid derivatives (i.e., clofibrate and perhaps other lipid-lowering fibrate drugs) increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may counteract the effectiveness of chenodiol.
Chlorpropamide: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as chlorpropamide, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of chlorpropamide during coadministration with fenofibric acid.
Cholestyramine: Based on reported interactions with gemfibrozil, cholestyramine can potentially reduce the oral bioavailability of fenofibric acid if these agents are administered together. Although the presence of a drug interaction is uncertain, patients should take fenofibric acid at least 1 hour before or 4 to 6 hours after cholestyramine to avoid affecting the bioavailability of fenofibric acid.
Citalopram: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as citalopram, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. The manufacturer of citalopram recommends 20 mg/day as the maximum daily dose of citalopram in patients receiving CYP2C19 inhibitors, due to the potential risk for QT prolongation. Monitor the therapeutic effect of citalopram during coadministration with fenofibric acid.
Clomipramine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as clomipramine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of clomipramine during coadministration with fenofibric acid.
Clopidogrel: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as clopidogrel, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of clopidogrel during coadministration with fenofibric acid.
Colchicine: Concurrent administration of colchicine and fibric acid derivatives may result in the development of myotoxicity (i.e., muscle pain and weakness, rhabdomyolysis). The pharmacokinetic and/or pharmacodynamic mechanism of this interaction is not clear; however, both colchicine and fibric acid derivatives are associated with the development of myotoxicity and concurrent use may increase the risk of myotoxicity. If such agents are co-administered, advise patients to report signs and symptoms of myotoxicity including muscle tenderness, pain, or weakness; monitoring creatine phosphokinase may not predict the development of severe myopathy.
Colestipol: Based on reported interactions with gemfibrozil, colestipol can potentially reduce the oral bioavailability of fenofibric acid if these agents are administered together. Although the presence of a drug interaction is uncertain, patients should take fenofibric acid at least 1 hour before or 4 to 6 hours after colestipol to avoid affecting the bioavailability of fenofibric acid.
Dapagliflozin: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion; monitor for changes in glycemic control and for needed dose adjustments. Gemfibrozil increases the systemic exposure of pioglitazone or rosiglitazone. Administration of 600 mg of gemfibrozil twice daily with pioglitazone 30 mg/day resulted in a higher pioglitazone exposure of 226%. If coadministered with a strong CYP2C8 inhibitor like gemfibrozil, the maximum recommended dose of pioglitazone is 15 mg daily.
Dapagliflozin; Metformin: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion; monitor for changes in glycemic control and for needed dose adjustments. Gemfibrozil increases the systemic exposure of pioglitazone or rosiglitazone. Administration of 600 mg of gemfibrozil twice daily with pioglitazone 30 mg/day resulted in a higher pioglitazone exposure of 226%. If coadministered with a strong CYP2C8 inhibitor like gemfibrozil, the maximum recommended dose of pioglitazone is 15 mg daily.
Dextromethorphan; Diphenhydramine; Phenylephrine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as diphenhydramine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diphenhydramine during coadministration with fenofibric acid.
Diazepam: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as diazepam, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diazepam during coadministration with fenofibric acid.
Diclofenac: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as diclofenac, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diclofenac during coadministration with fenofibric acid.
Diclofenac; Misoprostol: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as diclofenac, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diclofenac during coadministration with fenofibric acid.
Diphenhydramine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as diphenhydramine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diphenhydramine during coadministration with fenofibric acid.
Diphenhydramine; Hydrocodone; Phenylephrine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as diphenhydramine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diphenhydramine during coadministration with fenofibric acid.
Diphenhydramine; Ibuprofen: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as ibuprofen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of ibuprofen during coadministration with fenofibric acid. At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as diphenhydramine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diphenhydramine during coadministration with fenofibric acid.
Diphenhydramine; Naproxen: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as naproxen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of naproxen during coadministration with fenofibric acid. At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as diphenhydramine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diphenhydramine during coadministration with fenofibric acid.
Diphenhydramine; Phenylephrine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as diphenhydramine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diphenhydramine during coadministration with fenofibric acid.
Dronabinol, THC: Use caution if coadministration of dronabinol with fenofibric acid is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; fenofibric acid is a weak-to-moderate inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dulaglutide: Fibric acid derivatives may enhance the hypoglycemic effects of incretin mimetics through increased insulin sensitivity and decreased glucagon secretion. Patients receiving this combination should be monitored for changes in glycemic control.
Empagliflozin: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Empagliflozin; Linagliptin: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents, such as linagliptin, should be monitored for changes in glycemic control.
Empagliflozin; Metformin: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Escitalopram: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as escitalopram, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of escitalopram during coadministration with fenofibric acid.
Esomeprazole; Naproxen: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as naproxen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of naproxen during coadministration with fenofibric acid.
Etravirine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as etravirine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of etravirine during coadministration with fenofibric acid.
Everolimus: When possible, optimal lipid control should be achieved before starting a patient on everolimus. Immunosuppressants such as everolimus, especially when used along with cyclosporine, can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine. Because renal excretion is the primary elimination route of drugs of the fibrate class (e.g., fenofibric acid, fenofibrate, and gemfibrozi) there is a risk that an interaction will lead to deterioration of renal function. Deterioration of renal function increases the risk for myopathy and rhabomyolysis with fibrate agent lipid-lowering therapy. Carefully monitor for renal function deterioration and symptoms of myopathy when agents of the fibrate class are used in combination with everolimus or other immunosuppressants. Creatinine phosphokinase (CPK) levels should be assessed in patients reporting symptoms of muscle toxicity, and the fibrate should be discontinued if markedly elevated CPK levels occur or myopathy or myositis is suspected or diagnosed.
Exenatide: Fibric acid derivatives may enhance the hypoglycemic effects of incretin mimetics through increased insulin sensitivity and decreased glucagon secretion. Patients receiving this combination should be monitored for changes in glycemic control.
Ezetimibe: Ezetimibe was approved by the FDA for use in combination with fenofibrate as adjunctive therapy to diet for the treatment of hypercholesterolemia in patients with mixed hyperlipidemia in May 2006. However, the safety and effective use of ezetimibe when coadministered with other fibric acid derivatives such as gemfibrozil or clofibrate has not been established. Until further data are available to support efficacy and safety, ezetimibe is not recommended for use with gemfibrozil. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile. The incidence rates for cholecystectomy have been reported as 0.6% for fenofibrate monotherapy and 1.7% for combination therapy (ezetimibe plus fenofibrate), respectively. According to the manufacturer, the number of patients exposed to combination therapy versus fenofibrate or ezetimibe monotherapy has been inadequate to assess gallbladder disease risk. If cholelithiasis is suspected in a patient receiving ezetimibe and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered. In a pharmacokinetic study, concomitant fenofibrate or gemfibrozil administration increased total ezetimibe concentrations by approximately 1.5- or 1.7-fold, respectively. However, ezetimibe does not affect the pharmacokinetics of fenofibrate or the bioavailability of gemfibrozil.
Ezetimibe; Simvastatin: Fenofibric Acid and simvastatin should administered concomitantly only with caution. Fenofibric Acid may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. This risk of myopathy, rhabdomyolysis, and acute renal failure is increased with higher doses of simvastatin. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. Ezetimibe was approved by the FDA for use in combination with fenofibrate as adjunctive therapy to diet for the treatment of hypercholesterolemia in patients with mixed hyperlipidemia in May 2006. However, the safety and effective use of ezetimibe when coadministered with other fibric acid derivatives such as gemfibrozil or clofibrate has not been established. Until further data are available to support efficacy and safety, ezetimibe is not recommended for use with gemfibrozil. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile. The incidence rates for cholecystectomy have been reported as 0.6% for fenofibrate monotherapy and 1.7% for combination therapy (ezetimibe plus fenofibrate), respectively. According to the manufacturer, the number of patients exposed to combination therapy versus fenofibrate or ezetimibe monotherapy has been inadequate to assess gallbladder disease risk. If cholelithiasis is suspected in a patient receiving ezetimibe and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered. In a pharmacokinetic study, concomitant fenofibrate or gemfibrozil administration increased total ezetimibe concentrations by approximately 1.5- or 1.7-fold, respectively. However, ezetimibe does not affect the pharmacokinetics of fenofibrate or the bioavailability of gemfibrozil.
Famotidine; Ibuprofen: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as ibuprofen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of ibuprofen during coadministration with fenofibric acid.
Fluoxetine: As fenofibric acid is a mild-to-moderate inhibitor of CYP2C9 and CYP2C19; while fluoxetine is a substrate of both. Although not formally studied, co-administration may lead to increased fluoxetine plasma concentrations and toxicity. Monitor the therapeutic effect of fluoxetine during coadministration with fenofibric acid.
Fluoxetine; Olanzapine: As fenofibric acid is a mild-to-moderate inhibitor of CYP2C9 and CYP2C19; while fluoxetine is a substrate of both. Although not formally studied, co-administration may lead to increased fluoxetine plasma concentrations and toxicity. Monitor the therapeutic effect of fluoxetine during coadministration with fenofibric acid. At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as olanzapine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of olanzapine during coadministration with fenofibric acid.
Flurbiprofen: As fenofibric acid is a mild-to-moderate inhibitor of CYP2C9; while flurbiprofen is a substrate of CYP2C9. Although not formally studied, co-administration may lead to increased fluriprofen plasma concentrations and toxicity. Monitor the therapeutic effect of flurbiprofen during coadministration with fenofibric acid.
Fluvastatin: Use caution when coadministering fluvastatin and fenofibric acid. The risk of myopathy increases when HMG-Co-A reductase inhibitors ('statins'), including fluvastatin, are administered concurrently with fibric acid derivatives. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Fosamprenavir: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as fosamprenavir, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of fosamprenavir during coadministration with fenofibric acid.
Fosphenytoin: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as phenytoin, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of phenytoin during coadministration with fenofibric acid.
Glimepiride; Pioglitazone: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion; monitor for changes in glycemic control and for needed dose adjustments.
Glimepiride; Rosiglitazone: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Additionally, gemfibrozil has been reported to increase the plasma concentrations of rosiglitazone; the mechanism is probably inhibition of CYP2C8-mediated metabolism of rosiglitazone by gemfibrozil. A randomized crossover trial in healthy volunteers studied the effects of gemfibrozil 600 mg or placebo twice daily for 4 days, with a single 4 mg dose of rosiglitazone administered on day 3. Gemfibrozil increased rosiglitazone mean AUC by 2.3-fold and prolonged the elimination half-life from 3.6 to 7.6 hours. The rosiglitazone Cmax was increased 1.2-fold and the concentration measured 24 hours after dosing was increased 9.8-fold. There are no published reports of the potential clinical effects of this interaction. Concomitant administration of the two drugs may enhance rosiglitazone efficacy, but may also increase the risk of adverse effects. If antidiabetic agents are coadministered with gemfibrozil, it would be prudent to carefully monitor glycemic control and for signs and symptoms of adverse effects; dosage adjustment of antidiabetic agents may be necessary.
Glipizide; Metformin: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Glyburide; Metformin: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Hydrochlorothiazide, HCTZ; Losartan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as losartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of losartan during coadministration with fenofibric acid.
Hydrochlorothiazide, HCTZ; Propranolol: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as propranolol, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of propranolol during coadministration with fenofibric acid.
Hydrochlorothiazide, HCTZ; Valsartan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as valsartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of valsartan during coadministration with fenofibric acid.
Hydrocodone; Ibuprofen: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as ibuprofen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of ibuprofen during coadministration with fenofibric acid.
Ibuprofen: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as ibuprofen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of ibuprofen during coadministration with fenofibric acid.
Ibuprofen; Oxycodone: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as ibuprofen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of ibuprofen during coadministration with fenofibric acid.
Ibuprofen; Pseudoephedrine: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as ibuprofen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of ibuprofen during coadministration with fenofibric acid.
Imatinib, STI-571: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as imatinib, STI-571, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of imatinib during coadministration with fenofibric acid.
Imipramine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as imipramine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of imipramine during coadministration with fenofibric acid.
Incretin Mimetics: Fibric acid derivatives may enhance the hypoglycemic effects of incretin mimetics through increased insulin sensitivity and decreased glucagon secretion. Patients receiving this combination should be monitored for changes in glycemic control.
Indomethacin: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as indomethacin, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of indomethacin during coadministration with fenofibric acid.
Insulin Degludec; Liraglutide: Fibric acid derivatives may enhance the hypoglycemic effects of incretin mimetics through increased insulin sensitivity and decreased glucagon secretion. Patients receiving this combination should be monitored for changes in glycemic control.
Insulin Glargine; Lixisenatide: Fibric acid derivatives may enhance the hypoglycemic effects of incretin mimetics through increased insulin sensitivity and decreased glucagon secretion. Patients receiving this combination should be monitored for changes in glycemic control.
Insulins: Monitor patients receiving fibric acid derivatives concomitantly with insulin for changes in glycemic control. Fibric acid derivatives may enhance the hypoglycemic effects of insulin or other antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Lacosamide: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as lacosamide, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of lacosamide during coadministration with fenofibric acid.
Lansoprazole: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as lansoprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of lansoprazole during coadministration with fenofibric acid.
Lansoprazole; Naproxen: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as naproxen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of naproxen during coadministration with fenofibric acid. At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as lansoprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of lansoprazole during coadministration with fenofibric acid.
Linagliptin: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents, such as linagliptin, should be monitored for changes in glycemic control.
Linagliptin; Metformin: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents, such as linagliptin, should be monitored for changes in glycemic control.
Liraglutide: Fibric acid derivatives may enhance the hypoglycemic effects of incretin mimetics through increased insulin sensitivity and decreased glucagon secretion. Patients receiving this combination should be monitored for changes in glycemic control.
Lixisenatide: Fibric acid derivatives may enhance the hypoglycemic effects of incretin mimetics through increased insulin sensitivity and decreased glucagon secretion. Patients receiving this combination should be monitored for changes in glycemic control.
Loperamide: The plasma concentration of loperamide, a CYP2C8 substrate, may be increased when administered concurrently with fenofibric acid, a weak inhibitor of CYP2C8. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Loperamide; Simethicone: The plasma concentration of loperamide, a CYP2C8 substrate, may be increased when administered concurrently with fenofibric acid, a weak inhibitor of CYP2C8. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Losartan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as losartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of losartan during coadministration with fenofibric acid.
Lovastatin: Concurrent use of fenofibric acid and lovastatin may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. The serious risk of myopathy and rhabdomyolysis should be weighed carefully against the benefit of further alteration in lipid concentrations by the combined use of fenofibric acid and lovastatin.
Lovastatin; Niacin: Concurrent use of fenofibric acid and lovastatin may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. The serious risk of myopathy and rhabdomyolysis should be weighed carefully against the benefit of further alteration in lipid concentrations by the combined use of fenofibric acid and lovastatin.
Meloxicam: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as meloxicam, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of meloxicam during coadministration with fenofibric acid.
Metformin: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Metformin; Pioglitazone: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion; monitor for changes in glycemic control and for needed dose adjustments.
Metformin; Repaglinide: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Metformin; Rosiglitazone: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Additionally, gemfibrozil has been reported to increase the plasma concentrations of rosiglitazone; the mechanism is probably inhibition of CYP2C8-mediated metabolism of rosiglitazone by gemfibrozil. A randomized crossover trial in healthy volunteers studied the effects of gemfibrozil 600 mg or placebo twice daily for 4 days, with a single 4 mg dose of rosiglitazone administered on day 3. Gemfibrozil increased rosiglitazone mean AUC by 2.3-fold and prolonged the elimination half-life from 3.6 to 7.6 hours. The rosiglitazone Cmax was increased 1.2-fold and the concentration measured 24 hours after dosing was increased 9.8-fold. There are no published reports of the potential clinical effects of this interaction. Concomitant administration of the two drugs may enhance rosiglitazone efficacy, but may also increase the risk of adverse effects. If antidiabetic agents are coadministered with gemfibrozil, it would be prudent to carefully monitor glycemic control and for signs and symptoms of adverse effects; dosage adjustment of antidiabetic agents may be necessary.
Metformin; Saxagliptin: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Metformin; Sitagliptin: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Methadone: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as methadone, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of methadone during coadministration with fenofibric acid.
Miglitol: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Montelukast: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as montelukast, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of montelukast during coadministration with fenofibric acid.
Naproxen: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as naproxen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of naproxen during coadministration with fenofibric acid.
Naproxen; Pseudoephedrine: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as naproxen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of naproxen during coadministration with fenofibric acid.
Naproxen; Sumatriptan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as naproxen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of naproxen during coadministration with fenofibric acid.
Nateglinide: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Nebivolol; Valsartan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as valsartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of valsartan during coadministration with fenofibric acid.
Nelfinavir: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as nelfinavir, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of nelfinavir during coadministration with fenofibric acid.
Niacin; Simvastatin: Fenofibric Acid and simvastatin should administered concomitantly only with caution. Fenofibric Acid may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. This risk of myopathy, rhabdomyolysis, and acute renal failure is increased with higher doses of simvastatin. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Olanzapine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as olanzapine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of olanzapine during coadministration with fenofibric acid.
Omeprazole: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibric acid.
Omeprazole; Sodium Bicarbonate: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibric acid.
Paclitaxel: Paclitaxel is a substrate of CYP2C8, and fenofibric acid is a weak CYP2C8 inhibitor. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy.
Pantoprazole: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as pantoprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of pantoprazole during coadministration with fenofibric acid.
Phenobarbital: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as phenobarbital, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of phenobarbital during coadministration with fenofibric acid.
Phenytoin: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as phenytoin, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of phenytoin during coadministration with fenofibric acid.
Pioglitazone: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion; monitor for changes in glycemic control and for needed dose adjustments.
Piroxicam: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as piroxicam, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of piroxicam during coadministration with fenofibric acid.
Pitavastatin: The use of fibrates alone, including fenofibrate, may occasionally be associated with myositis, myopathy, or rhabdomyolysis. Concurrent use of fenofibrate and HMG-CoA reductase inhibitors (Statins) has been associated with increases in creatine kinase (CK), an increased risk of rhabdomyolysis, and myoglobinuria leading to acute renal failure. In a single-dose drug interaction study in 23 healthy adults, concomitant administration of fenofibrate (201 mg) with pravastatin (40 mg) resulted in an increase in the mean Cmax and AUC values for pravastatin by 13%. The mean Cmax and AUC for 3-alpha-hydroxy-iso-pravastatin increased by 29% and 26%, respectively. In another drug interaction study, the coadministration of fenofibrate and pravastatin (40 mg) for 10 days resulted in an increase in the mean Cmax and AUC values for pravastatin by 36% and 28%, respectively, and for the metabolite, 3-alpha-hydroxy-iso-pravastatin, by 55% and 39%, respectively. The coadministration of a single dose of fenofibrate and a single dose of fluvastatin resulted in a small increase (approximately 15% to 16%) in exposure to (+)3R,5S-fluvastatin, the active enantiomer of fluvastatin. A single dose of either pravastatin or fluvastatin had no clinically important effect on the pharmacokinetics of fenofibric acid. Concomitant administration of fenofibrate with atorvastatin 20 mg once daily for 10 days resulted in a 17% decrease in atorvastatin AUC values in 22 healthy males. The atorvastatin Cmax values were not significantly affected by fenofibrate. The pharmacokinetics of fenofibric acid were not significantly affected by atorvastatin. Based on studies in other fibrate treated patients, myopathy can occur from 3 weeks to several months after initiating the combined therapy. The combined use of fenofibrate and HMG-CoA reductase inhibitors should be avoided unless the benefit of further alterations in lipid levels is likely to outweigh the increased risk of this drug combination. It is unknown whether any potential benefit in blood lipids derived from concomitant use would outweigh the potential risks. If fenofibrate and HMG-CoA reductase inhibitors are prescribed together, serum CK levels should be monitored closely during the initial weeks of therapy, but there is no assurance that periodic CK levels will prevent the occurrence of myopathy or renal dysfunction. Patients on fenofibrate should be instructed to report any complaints of muscle pain, tenderness, or weakness to their health care professional immediately. Patients complaining of muscle pain, tenderness, or weakness should have prompt medical evaluation for myopathy, including CK level determination. If myopathy or myositis is suspected or diagnosed, fenofibrate should be stopped.
Pramlintide: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Pravastatin: The risk of myopathy during treatment with other HMG-CoA reductase inhibitors is generally increased with concurrent therapy with fibric acid derivatives. The use of fibrates alone may occasionally be associated with myopathy. Combination therapy with pravastatin and gemfibrozil is generally not recommended. The combined use of pravastatin and fibrates should be avoided unless the benefit of further alterations in lipid levels is likely to outweigh the increased risk of this drug combination. Preliminary data suggest that the addition of gemfibrozil to therapy with pravastatin is not associated with greater reduction in LDL-cholesterol than that achieved with pravastatin alone. Pravastatin and gemfibrozil have been administered together in a study of 290 patients, with two patients developing asymptomatic elevations of CPK; severe myopathy was not observed, although muscle biopsies were not performed. In addition, a trial of pravastatin (40 mg/day) coadministration with gemfibrozil (1200 mg/day) has not been shown to be associated with myopathy, although 4 of 75 patients receiving the combination showed marked CPK elevations versus 1 of 73 patients receiving placebo. A trend has been reported toward more frequent CPK elevations and patient withdrawals due to musculoskeletal symptoms in the group receiving combined treatment as compared to the groups receiving placebo, gemfibrozil, or pravastatin monotherapy. In a crossover study in 20 healthy male volunteers given concomitant single doses of pravastatin and gemfibrozil, there was a significant decrease in urinary excretion and protein binding of pravastatin. In addition, there was a significant increase in AUC, Cmax, and Tmax for the pravastatin metabolite SQ 31,906.
Primidone: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as primidone, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of primidone during coadministration with fenofibric acid.
Propranolol: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as propranolol, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of propranolol during coadministration with fenofibric acid.
Quinine: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as quinine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of quinine during coadministration with fenofibric acid.
Rabeprazole: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as rabeprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of rabeprazole during coadministration with fenofibric acid.
Raltegravir: Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as fibric acid derivatives.
Ramelteon: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as ramelteon, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of ramelteon during coadministration with fenofibric acid.
Red Yeast Rice: Since compounds in red yeast rice are chemically similar to and possess actions similar to lovastatin, patients should avoid this dietary supplement if they currently take drugs known to increase the risk of myopathy (e.g., fibric acid derivatives (gemfibrozil, fenofibrate, clofibrate)) when coadministered with HMG-CoA reductase inhibitors.
Rosiglitazone: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Additionally, gemfibrozil has been reported to increase the plasma concentrations of rosiglitazone; the mechanism is probably inhibition of CYP2C8-mediated metabolism of rosiglitazone by gemfibrozil. A randomized crossover trial in healthy volunteers studied the effects of gemfibrozil 600 mg or placebo twice daily for 4 days, with a single 4 mg dose of rosiglitazone administered on day 3. Gemfibrozil increased rosiglitazone mean AUC by 2.3-fold and prolonged the elimination half-life from 3.6 to 7.6 hours. The rosiglitazone Cmax was increased 1.2-fold and the concentration measured 24 hours after dosing was increased 9.8-fold. There are no published reports of the potential clinical effects of this interaction. Concomitant administration of the two drugs may enhance rosiglitazone efficacy, but may also increase the risk of adverse effects. If antidiabetic agents are coadministered with gemfibrozil, it would be prudent to carefully monitor glycemic control and for signs and symptoms of adverse effects; dosage adjustment of antidiabetic agents may be necessary.
Rosuvastatin: HMG-CoA reductase inhibitors have been administered safely with fibric acid derivatives in some patients; however the risk of potential myopathy is considerably higher during concurrent therapy. Combination therapy with HMG-CoA reductase inhibitors, such as rosuvastatin and gemfibrozil has been associated with a significantly enhanced risk of myopathy and rhabdomyolysis. When possible, avoid concurrent use of HMG-reductase inhibitors with fibrates. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. If rosuvastatin must be used concurrently with gemfibrozil, limit the rosuvastatin dose to 10 mg/day.
Sacubitril; Valsartan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as valsartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of valsartan during coadministration with fenofibric acid.
Saxagliptin: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Sertraline: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as sertraline, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of sertraline during coadministration with fenofibric acid.
Sildenafil: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as sildenafil , has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of sildenafil during coadministration with fenofibric acid.
Simvastatin: Fenofibric Acid and simvastatin should administered concomitantly only with caution. Fenofibric Acid may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. This risk of myopathy, rhabdomyolysis, and acute renal failure is increased with higher doses of simvastatin. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Simvastatin; Sitagliptin: Fenofibric Acid and simvastatin should administered concomitantly only with caution. Fenofibric Acid may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. This risk of myopathy, rhabdomyolysis, and acute renal failure is increased with higher doses of simvastatin. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Sitagliptin: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as sulfamethoxazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of sulfamethoxazole during coadministration with fenofibric acid.
Telbivudine: The risk of myopathy may be increased if a fibric acid derivative is coadministered with telbivudine. Monitor patients for any signs or symptoms of unexplained muscle pain, tenderness, or weakness, particularly during periods of upward dosage titration.
Thalidomide: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as thalidomide, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of thalidomide during coadministration with fenofibric acid.
Torsemide: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as torsemide, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of torsemide during coadministration with fenofibric acid.
Ursodeoxycholic Acid, Ursodiol: Fibric acid derivatives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may counteract the effectiveness of ursodeoxycholic acid, ursodiol.
Valdecoxib: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as valdecoxib, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of valdecoxib during coadministration with fenofibric acid.
Valsartan: At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as valsartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of valsartan during coadministration with fenofibric acid.
Voriconazole: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates such as voriconazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of voriconazole during coadministration with fenofibric acid.
Warfarin: Fenofibric acid potentiates the effects of warfarin and other oral anticoagulants, resulting in increased prothrombin times. Fibrates have been shown to decrease vitamin K dependent coagulation factor synthesis. Since these drugs are also highly protein-bound, it is possible that fenofibric acid displaces warfarin from protein-binding sites as a potential mechanism. Case reports of significant effects on warfarin exist for all fibrate drugs. Fenofibric acid is the active metabolite of fenofibrate. Three clinical case reports of fenofibrate and warfarin interactions have been reported in post-marketing surveillance of fenofibrate in the US and Europe. In one case, a male (47 years) who had been stable over a course of 20 weeks on his prescribed warfarin dose was admitted to the hospital one week after beginning treatment for hypertriglyceridemia with fenofibrate 201 mg/day. He presented with epigastric discomfort and hematuria. His INR on admission was > 8.5 (previously stabilized at 2 to 2.5 prior to fenofibrate). The patient received treatment with phytonadione and discontinuation of the medications. He was discharged 2 days later, but agreed to be rechallenged under a controlled protocol to confirm the interaction of the fenofibrate with his warfarin. After stabilization of his warfarin dose for 3 weeks, fenofibrate was restarted, and the patient was rechallenged on 2 occasions. Both times, an increase in INR above the therapeutic range occurred. In order to prevent bleeding complications, patients receiving warfarin concomitantly with fenofibric acid should have frequent INR determinations until it has been determined that the INR has been stabilized. A reduction in warfarin dose may be necessary.