Fenofibrate (Page 2 of 8)
Hepatic Insufficiency
No pharmacokinetic studies have been conducted in patients having hepatic insufficiency.
Drug-Drug Interactions
In vitro studies using human liver microsomes indicate that fenofibrate and fenofibric acid are not inhibitors of cytochrome (CYP) P450 isoforms CYP3A4, CYP2D6, CYP2E1, or CYP1A2. They are weak inhibitors of CYP2C19 and CYP2A6, and mild-to-moderate inhibitors of CYP2C9 at therapeutic concentrations.
Potentiation of coumarin-type anti-coagulants has been observed with prolongation of the prothrombin time/INR.
Bile acid sequestrants have been shown to bind other drugs given concurrently. Therefore, fenofibrate should be taken at least 1 hour before or 4 to 6 hours after a bile acid binding resin to avoid impeding its absorption (see WARNINGS and PRECAUTIONS).
Concomitant administration of a single dose of fenofibrate (administered as 3 X 67 mg fenofibrate micronized capsules) with a single dose of pravastatin (40 mg) in 23 healthy subjects increased the mean Cmax and mean AUC for pravastatin by 13%. The Cmax and AUC of fenofibrate decreased by 2% and 1%, respectively, after concomitant administration of fenofibrate and pravastatin. The mean Cmax and AUC for 3α-hydroxy-iso-pravastatin increased by 29% and 26%, respectively.
Concomitant administration of a single dose of fenofibrate (equivalent to 145 mg fenofibrate) and a single dose of fluvastatin (40 mg) 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 (equivalent to fenofibrate 200 mg) with atorvastatin (20 mg) once daily for 10 days resulted in approximately 17% decrease (range from 67% decrease to 44% increase) 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.
Concomitant administration of fenofibrate (equivalent to fenofibrate 200 mg) once daily for 10 days with glimepiride (1 mg tablet) single dose simultaneously with the last dose of fenofibrate resulted in a 35% increase in mean AUC of glimepiride in healthy subjects. Glimepiride Cmax was not significantly affected by fenofibrate coadministration. There was no statistically significant effect of multiple doses of fenofibrate on glucose nadir or AUC with the baseline glucose concentration as the covariate after glimepiride administration in healthy volunteers. However, glucose concentrations at 24 hours remained statistically significantly lower after pretreatment with fenofibrate than with glimepiride alone. Glimepiride had no significant effect on the pharmacokinetics of fenofibric acid.
Concomitant administration of fenofibrate (54 mg) and metformin (850 mg) three times a day for 10 days resulted in no significant changes in the pharmacokinetics of fenofibric acid and metformin when compared with the two drugs administered alone in healthy subjects.
Concomitant administration of fenofibrate (equivalent to fenofibrate 200 mg) once daily for 14 days with rosiglitazone tablet (rosiglitazone maleate) (8 mg) once daily for 5 days, Day 10 through Day 14, resulted in no significant changes in the pharmacokinetics of fenofibric acid and rosiglitazone when compared with the two drugs administered alone in healthy subjects.
Clinical Trials
Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb)
The effects of fenofibrate at a dose equivalent to 200 mg fenofibrate per day were assessed from four randomized, placebo-controlled, double-blind, parallel-group studies including patients with the following mean baseline lipid values: total-C 306.9 mg/dL; LDL-C 213.8 mg/dL; HDL-C 52.3 mg/dL; and triglycerides 191 mg/dL. Fenofibrate therapy lowered LDL-C, Total-C, and the LDL-C/HDL-C ratio. Fenofibrate therapy also lowered triglycerides and raised HDL-C (see Table 1).
| a Duration of study treatment was 3 to 6 months | ||||
| b p = <0.05 vs. Placebo | ||||
| In a subset of the subjects, measurements of apo B were conducted. Fenofibrate treatment significantly reduced apo B from baseline to endpoint as compared with placebo (-25.1% vs. 2.4%, p<0.0001, n=213 and 143 respectively). | ||||
| Treatment Group | Total-C | LDL-C | HDL-C | TG |
| Pooled Cohort | ||||
| Mean baseline lipid values (n=646) | 306.9 mg/dL | 213.8 mg/dL | 52.3 mg/dL | 191 mg/dL |
| All FEN (n=361) | -18.7%b | -20.6%b | +11%b | -28.9%b |
| Placebo (n=285) | -0.4% | -2.2% | +0.7% | +7.7% |
| Baseline LDL-C > 160 mg/dL and TG < 150 mg/dL (Type IIa) | ||||
| Mean baseline lipid values (n=334) | 307.7 mg/dL | 227.7 mg/dL | 58.1 mg/dL | 101.7 mg/dL |
| All FEN (n=193) | -22.4%b | -31.4%b | +9.8% | -23.5%b |
| Placebo (n=141) | +0.2% | -2.2% | +2.6% | +11.7% |
| Baseline LDL-C > 160 mg/dL and TG ≥ 150 mg/dL (Type IIb) | ||||
| Mean baseline lipid values (n=242) | 312.8 mg/dL | 219.8 mg/dL | 46.7 mg/dL | 231.9 mg/dL |
| All FEN (n=126) | -16.8%b | -20.1%b | +14.6%b | -35.9%b |
| Placebo (n=116) | -3% | -6.6% | +2.3% | +0.9% |
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