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Rx Product News: Profile: A Closer Look at New FDA Actions: Trilipix

Caryn Domenici, RPh, and Alka Patel, PharmD
Published Online: Wednesday, April 1, 2009   [ Request Print ]

Both Ms. Domenici and Dr. Patel are pharmacists at Brigham and Women’s Hospital, Boston, Massachusetts.


Abbott Laboratories’ Trilipix

On December 15, 2008, the FDA approved Abbott Laboratories’ Trilipix (fenofibric acid) for use in combination with a hydroxy-3-methylglutaryl coenzyme A reductase inhibitor for cholesterol management.1

Clinical Pharmacology

Trilipix exerts its effects by activating peroxisome proliferator–activated receptor a (PPARa). This then increases lipolysis of triglyceride (TG) particles from plasma by activating lipoprotein lipase and reducing production of an inhibitor of lipoprotein lipase activity, Apo CIII. The resulting decrease in TG produces an alteration in the size and composition of low-density lipoprotein (LDL) from small to larger particles. These larger particles have a stronger affinity for cholesterol receptors and are catabolized rapidly. Activation of PPARa also results in an increase in the synthesis of high-density lipoprotein cholesterol (HDL-C) and Apo AI and AII.2

Pharmacokinetics

Trilipix has once-daily dosing and is well absorbed. It has an absolute bioavailability of 81%, with peak plasma concentrations occurring at 4 to 5 hours, and reaches steady state within 8 days. Trilipix has a half-life of approximately 20 hours and is primarily excreted in the urine.

Dose adjustments are necessary with renal impairment. In patients with severe renal impairment, Trilipix should be avoided. No data are currently available supporting the use of Trilipix in patients with hepatic impairment.2

Clinical Trials

In this phase 3, multicenter, randomized, double-blind, active-controlled study, a total of 657 patients with mixed dyslipidemia (LDL cholesterol .130 mg/ dL, TGs .150 mg/dL, and HDL-C < 40 mg/dL [men] or < 50 mg/dL [women]) were randomized to 12 weeks of treatment with Trilipix + simvastatin (20 or 40 mg) combination therapy; Trilipix monotherapy (135 mg); or simvastatin monotherapy (20, 40, or 80 mg).

Combination therapy resulted in significantly greater increases in HDL-C and decreases in TGs, compared with the corresponding simvastatin monotherapy dose (P <.001) and decreases in LDL-C, compared with Trilipix monotherapy (P <.001).

HDL-C increased 17.8% versus 7.2%, and TGs decreased -37.4% versus -14.2% (Trilipix + simvastatin 20 vs simvastatin 20); LDL-C decreased -24.0% versus -4.0% (Trilipix + simvastatin 20 vs Trilipix); HDL-C increased 18.9% versus 8.5%, and TGs decreased -42.7% versus -22.4% (Trilipix + simvastatin 40 vs simvastatin 40); LDL-C decreased -25.3% versus -4.0% (Trilipix + simvastatin 40 vs Trilipix).3

In a phase 3, multicenter, randomized, double-blind, active-controlled study, a total of 1445 patients with LDL-C .130 mg/dL, TGs .150 mg/dL, and HDL-C < 40 mg/dL ( < 50 mg/dL for women) were randomized to either Trilipix (135 mg), rosuvastatin (10, 20, or 40 mg), or Trilipix + rosuvastatin 10 or 20 mg and treated for 12 weeks.

Combination therapy with Trilipix + rosuvastatin 10 mg resulted in significantly (P <.001) greater improvements in HDL-C (20.3% vs 8.5%) and TGs (-47.1% vs -24.4%), compared with rosuvastatin 10 mg and LDL-C (-37.2% vs -6.5%), compared with Trilipix. Similarly, significantly (P <.001) greater improvements were observed with Trilipix + rosuvastatin 20 mg in HDL-C (19.0% vs 10.3%) and TGs (-42.9% vs -25.6%), compared with rosuvastatin 20 mg and LDL-C (-38.8% vs -6.5%), compared with Trilipix monotherapy.4

In both 12-week treatment studies, combination therapy was generally well tolerated and no cases of rhabdomyolysis were reported.3,4

Contraindications

Trilipix is contraindicated in patients with active liver disease, severe renal impairment (including those receiving dialysis), and preexisting gallbladder disease. Nursing mothers and patients with hypersensitivity to fenofibric acid, choline fenofibrate, or fenofibrate also should not take Trilipix.

Drug Interactions

Caution should be exercised when Trilipix is given in conjunction with oral anticoagulants. Trilipix may potentiate the anticoagulant effects of these agents, resulting in prolongation of the prothrombin time/international normalized ratio. Trilipix should be taken at least 1 hour before, or 4 to 6 hours after, a bile acid resin to avoid decreased absorption. The use of Trilipix with cyclosporine and other potentially nephrotoxic agents should be on a risk versus benefit basis.

References

  1. 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.
  2. Trilipix [package insert]. Chicago, IL: Abbott Laboratories; 2008.
  3. 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.
  4. 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].
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