Rx Product News: Profile: A Closer Look at New FDA Actions: Trilipix
Trilipix has been approved by the FDA, the first and only fibrate indicated for use in combination with a statin for cholesterol management.
Both Ms. Domenici and Dr. Patel arepharmacists at Brigham and Women’sHospital, Boston, Massachusetts.
Abbott Laboratories’ Trilipix
On December 15, 2008, the FDAapproved Abbott Laboratories’ Trilipix(fenofibric acid) for use in combinationwith a hydroxy-3-methylglutarylcoenzyme A reductase inhibitor forcholesterol management.1
Trilipix exerts its effects by activatingperoxisome proliferator–activatedreceptor a (PPARa). This then increaseslipolysis of triglyceride (TG) particlesfrom plasma by activating lipoproteinlipase and reducing production of aninhibitor of lipoprotein lipase activity,Apo CIII. The resulting decrease in TGproduces an alteration in the size andcomposition of low-density lipoprotein(LDL) from small to larger particles.These larger particles have a strongeraffinity for cholesterol receptors andare catabolized rapidly. Activation ofPPARa also results in an increase inthe synthesis of high-density lipoproteincholesterol (HDL-C) and Apo AIand AII.2
Trilipix has once-daily dosing and iswell absorbed. It has an absolute bioavailabilityof 81%, with peak plasmaconcentrations occurring at 4 to 5hours, and reaches steady state within8 days. Trilipix has a half-life ofapproximately 20 hours and is primarilyexcreted in the urine.
Dose adjustments are necessarywith renal impairment. In patients withsevere renal impairment, Trilipix shouldbe avoided. No data are currently availablesupporting the use of Trilipix inpatients with hepatic impairment.2
In this phase 3, multicenter, randomized,double-blind, active-controlledstudy, a total of 657 patients with mixeddyslipidemia (LDL cholesterol .130 mg/dL, TGs .150 mg/dL, and HDL-C < 40mg/dL [men] or < 50 mg/dL [women])were randomized to 12 weeks of treatmentwith Trilipix + simvastatin (20 or40 mg) combination therapy; Trilipixmonotherapy (135 mg); or simvastatinmonotherapy (20, 40, or 80 mg).
Combination therapy resulted in significantlygreater increases in HDL-Cand decreases in TGs, compared withthe corresponding simvastatin monotherapydose (P <.001) and decreasesin LDL-C, compared with Trilipixmonotherapy (P <.001).
HDL-C increased 17.8% versus 7.2%,and TGs decreased -37.4% versus -14.2%(Trilipix + simvastatin 20 vs simvastatin20); LDL-C decreased -24.0% versus-4.0% (Trilipix + simvastatin 20 vsTrilipix); HDL-C increased 18.9% versus8.5%, and TGs decreased -42.7% versus-22.4% (Trilipix + simvastatin 40 vs simvastatin40); LDL-C decreased -25.3%versus -4.0% (Trilipix + simvastatin 40vs Trilipix).3
In a phase 3, multicenter, randomized,double-blind, active-controlledstudy, a total of 1445 patients withLDL-C .130 mg/dL, TGs .150 mg/dL,and HDL-C < 40 mg/dL ( < 50 mg/dL forwomen) were randomized to eitherTrilipix (135 mg), rosuvastatin (10, 20,or 40 mg), or Trilipix + rosuvastatin 10or 20 mg and treated for 12 weeks.
Combination therapy with Trilipix+ rosuvastatin 10 mg resulted in significantly(P <.001) greater improvementsin HDL-C (20.3% vs 8.5%) andTGs (-47.1% vs -24.4%), compared withrosuvastatin 10 mg and LDL-C (-37.2%vs -6.5%), compared with Trilipix. Similarly,significantly (P <.001) greaterimprovements were observed withTrilipix + rosuvastatin 20 mg in HDL-C(19.0% vs 10.3%) and TGs (-42.9% vs-25.6%), compared with rosuvastatin 20mg and LDL-C (-38.8% vs -6.5%), comparedwith Trilipix monotherapy.4
In both 12-week treatment studies,combination therapy was generallywell tolerated and no cases of rhabdomyolysiswere reported.3,4
Trilipix is contraindicated in patientswith active liver disease, severe renalimpairment (including those receivingdialysis), and preexisting gallbladderdisease. Nursing mothers and patientswith hypersensitivity to fenofibric acid,choline fenofibrate, or fenofibrate alsoshould not take Trilipix.
Caution should be exercised whenTrilipix is given in conjunction withoral anticoagulants. Trilipix maypotentiate the anticoagulant effectsof these agents, resulting in prolongationof the prothrombin time/internationalnormalized ratio. Trilipix shouldbe taken at least 1 hour before, or 4to 6 hours after, a bile acid resin toavoid decreased absorption. The useof Trilipix with cyclosporine and otherpotentially nephrotoxic agents shouldbe on a risk versus benefit basis.
- Abbott receives FDA approval for Trilipix (fenobric acid), first and only fibrate indicated for use in combination with a statin for cholesterol management [press release]. www.abbott.com/global/url/pressRelease/ en_US/60.5:5/Press_Release_0660.htm.
- Trilipix [package insert]. Chicago, IL: Abbott Laboratories; 2008.
- Mohiuddin SM, Pepine CJ, Kelly MT, et al. Efficacy and safety of ABT-335 (fenofibric acid) in combination with simvastatin in patients with mixed dyslipidemia: a phase 3, randomized, controlled study. Am Heart J. 2009;157(1):195-203.
- Jones PH, Davidson MH, Kashyap ML, et al. Efficacy and safety of ABT-335 (fenofibric acid) in combination with rosuvastatin in patients with mixed dyslipidemia: a phase 3 study. Atherosclerosis. 2008; Oct 5 [e-pub ahead of print].