FIBRATE DOSING

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• Kidney disease
• AHA recommendations
• The AHA 2013 cholesterol treatment guidelines state that serum creatinine should be checked before, within 3 months of initiation, and every 6 months thereafter in patients receiving fenofibrates. If GFR is < 30 ml/min, fenofibrates should not be used. If GFR is 30 - 59 ml/min, the dose of fenofibrate should not exceed 54 mg/day [19]
• Antara®
• CrCl 30 - 89 ml/min: starting dose is 43 mg/day. Titrate as tolerated.
• CrCl < 30 ml/min: DO NOT USE
• Fenoglide®
• CrCl 30 - 89 ml/min: starting dose is 40 mg/day. Titrate as tolerated.
• CrCl < 30 ml/min: DO NOT USE
• Lipofen®
• CrCl 30 - 89 ml/min: starting dose is 50 mg/day. Titrate as tolerated.
• CrCl < 30 ml/min: DO NOT USE
• Lofibra® capsule
• CrCl 30 - 89 ml/min: starting dose is 67 mg/day. Titrate as tolerated.
• CrCl < 30 ml/min: DO NOT USE
• Lofibra® tablet
• CrCl 30 - 89 ml/min: starting dose is 54 mg/day. Titrate as tolerated.
• CrCl < 30 ml/min: DO NOT USE
• Lopid®
• CrCl 30 - 89 ml/min: has not been studied
• CrCl < 30 ml/min: DO NOT USE
• Tricor®
• CrCl 30 - 89 ml/min: starting dose is 48 mg/day. Titrate as tolerated.
• CrCl < 30 ml/min: DO NOT USE
• Triglide®
• CrCl ≤ 89 ml/min: DO NOT USE
• Trilipix®
• CrCl 30 - 89 ml/min: starting dose is 45 mg/day. Titrate as tolerated.
• CrCl < 30 ml/min: DO NOT USE

• Liver disease
• Fibrates have not been studied in liver disease and are contraindicated in patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities

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• DRUG INTERACTIONS

• NOTE: The drug interactions presented here are NOT all-inclusive. Other interactions may exist. Drug interaction checkers provide the most efficient and practical way to check for interactions among multiple medications. A free interaction checker is available from Drugs.com (see Drugs.com interactions checker).


• All fibrates
• Bile Acid Sequestrants (Questran®, Welchol®) - bile acid sequestrants may interfere with the absorption of fibrates. Fibrates should be taken 1 hour before or 4 hours after bile acid sequestrants. [5,6,7]
• Colchicine (Colcrys®) - muscle toxicity including rhabdomyolysis has been reported in patients taking fenofibrates with colchicine. Use caution when prescribing together.
• Ezetimibe (Zetia®) - ezetimibe and fibrates increase cholesterol excretion into the bile, raising the risk of gallstones in susceptible patients. Furthermore, gemfibrozil and fenofibrate increase ezetimibe exposure. Use caution when combining.
• Immunosuppressants - immunosuppressants such as cyclosporine and tacrolimus can be nephrotoxic and may reduce the elimination of fibrates. Use caution when combining.
• Warfarin (Coumadin®) - fibrates may interfere with warfarin therapy. Monitor INR levels when adding fibrates to warfarin. [5,6,7]


• Gemfibrozil (Lopid®)
• CYP2C8 substrates - gemfibrozil is a CYP2C8 strong inhibitor, and it may increase exposure to CYP2C8 substrates
• Dasabuvir (Viekira Pak™) - DO NOT COMBINE. Gemfibrozil increases dasabuvir exposure.
• Enzalutamide (Xtandi®) - gemfibrozil increases enzalutamide exposure, raising the risk of seizures. The enzalutamide dose should be reduced when taken with gemfibrozil.
• Glitazones (pioglitazone, rosiglitazone, Actos®, Avandia®) - gemfibrozil increases pioglitazone and rosiglitazone exposure. The pioglitazone dose should not exceed 15 mg when taken with gemfibrozil.
• OATP1B1 substrates - gemfibrozil is an OATP1B1 inhibitor, and it may increase exposure to OATP1B1 substrates.
• Repaglinide (Prandin®) - DO NOT COMBINE. Gemfibrozil increases repaglinide exposure.
• Selexipag (Uptravi®) - DO NOT COMBINE. Gemfibrozil has been shown to double selexipag levels and increase exposure to its active metabolite 11-fold.
• Statins (Lipitor®, Zocor®, Crestor®, etc)
• Simvastatin: DO NOT COMBINE
• Rosuvastatin: Gemfibrozil should not be taken with rosuvastatin. If concomitant use cannot be avoided, rosuvastatin dosing should start at 5 mg once daily and not exceed 10 mg/day.
• Other statins: combining gemfibrozil with a statin increases the risk of muscle toxicity (rhabdomyolysis) and should generally be avoided. If a statin-fibrate combination is necessary, fenofibrates are preferred, as they have been used safely with statins several trials. [1,2]

• Metabolism and clearance
• Gemfibrozil (Lopid®)
• CYP2C8 - strong inhibitor
• CYP2C9 - inhibitor
• CYP2C19 - inhibitor
• CYP1A2 - inhibitor
• OATP1B1 - inhibitor
• UGT1A1 and 1A3 - inhibitor


• Fenofibrate (Antara®, Fenoglide®, Lipofen®, Lofibra®, Tricor®, Triglide®)
• CYP2C9 - mild-moderate inhibitor
• CYP2C8 - weak inhibitor
• CYP2C19 - weak inhibitor
• CYP2A6 - weak inhibitor


• Fenofibric acid (Trilipix®)
• CYP2C9 - mild-moderate inhibitor
• CYP2C8 - weak inhibitor
• CYP2C19 - weak inhibitor
• CYP2A6 - weak inhibitor

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• PRICE ($) INFO

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• BIBLIOGRAPHY

• Manufacturer's Package insert
• 1 - PMID 16310551
• 2 - PMID 20228404