Will omega-3 fatty acids interact with medications?

While the long chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are derived from dietary (primarily marine) sources, they are still theoretically capable of interacting with other pharmacologic compounds to alter bioactivity. The following data are available on omega-3 fatty acids and drug interactions:

  1. Anticoagulation- Two case reports suggest that in certain circumstances, the addition of EPA and DHA to warfarin may further prolong the bleeding time 1,2. However, the preponderance of the evidence obtained from clinical trials 3 suggests that adding even very high doses of omega-3 fatty acids to various anticoagulants (e.g. aspirin, warfarin, heparin, dipyradimole) does not increase the risk of bleeding complications. Therefore, individuals receiving warfarin in combination with omega-3 fatty acids should simply have their international normalized ratio (INR) checked periodically.
  2. HMG-CoA Reductase Inhibitors- Rigorous crossover studies have found that high dose (i.e. 4 grams) omega-3 fatty acids do not alter the pharmacokinetics (e.g. rate and extent of exposure) of either simvastatin or atorvastatin 4,5.
  3. Cytochrome P450-Dependent Activities- Rat studies have demonstrated that omega-3 fatty acids can increase hepatic concentrations of cytochrome P450 and activities of various P450 enzymes. Two reports in humans suggest that DHA and EPA may modify levels of the P450-dependent medications cyclosporine and saquinavir 6,7. Further confirmatory work is required in this area.

References

  1. Jalili M, Dehpour AR. Extremely prolonged INR associated with warfarin in combination with both trazodone and omega-3 fatty acids. Arch Med Res 2007;38:901-4.
  2. Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother 2004;38:50-2.
  3. Harris WS. Expert opinion: omega-3 fatty acids and bleeding-cause for concern? Am J Cardiol 2007;19:44C-46C.
  4. McKenney JM, Swearingen D, Di Spirito M, Doyle R, Pantaleon C, Kling D, Shalwitz RA. Study of the pharmacokinetic interaction between simvastatin and prescription omega-3-acid ethyl esters. J Clin Pharmacol 2006;46:785-91.
  5. Di Spirito M, Morelli G, Doyle RT, Johnson J, McKenney J. Effect of omega-3-acid ethyl esters on steady-state plasma pharmacokinetics of atorvastatin in healthy adults. Expert Opin Pharmacother 2008;9:2939-45.
  6. Busnach G, Stragliotto E, Minetti E, Perego A, Brando B, Broggi ML, Civati G: Effect of n-3 polyunsaturated fatty acids on cyclosporine pharmacokinetics in kidney graft recipients: a randomized placebo-controlled study. J Nephrol 1998;11:87-93.
  7. Hirunpanich V, Sato H. Docosahexaenoic acid (DHA) inhibits saquinavir metabolism in-vitro and enhances its bioavailability in rats. J Pharm Pharmacol 2006;58:651-8.

Key Points

  • There is little information regarding drug interactions and omega-3 fatty acids.
  • Even at high doses, omega-3 fatty acids have not been associated in clinical studies with elevated bleeding risk.
  • Because omega-3 fatty acids could affect cytochrome P450-dependent activities, drug levels should be periodically monitored in patients on combination therapy.