Can I Take Omega-3 (EPA/DHA) With Dutasteride (Avodart)?

Dutasteride is a 5-alpha reductase inhibitor approved for symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate, alone or with tamsulosin; hair-loss use is off-label [1]. The Avodart label describes a 0.5 mg capsule taken once daily and swallowed whole [1]. Omega-3 products come as over-the-counter dietary supplements, which are not FDA-approved drugs, and as prescription drugs approved to lower very high triglycerides [2][4].

What each label lists as an interaction

The Avodart drug interactions section covers potent, chronic CYP3A4 inhibitors such as ritonavir and advises caution with them because the effect of those inhibitors on dutasteride has not been studied [1]. It reports no effect on the steady-state pharmacokinetics of tamsulosin or terazosin; a fall in dutasteride clearance and higher dutasteride exposure with verapamil or diltiazem that is not considered clinically significant and needs no dose adjustment; no change in dutasteride bioavailability when a 5 mg dose is followed an hour later by 12 g of cholestyramine; no change in digoxin pharmacokinetics; and no change in the steady-state pharmacokinetics of the S- or R-warfarin isomers or in warfarin's effect on prothrombin time after 3 weeks of dutasteride 0.5 mg/day [1].

The prescription omega-3-acid ethyl esters label's interactions section covers one situation: anticoagulants and other drugs that affect coagulation, where it advises periodic monitoring [2]. The same label reports that 4 g/day of omega-3-acid ethyl esters did not affect exposure to simvastatin 80 mg (24 healthy adults), atorvastatin 80 mg (50 healthy adults) or rosuvastatin 40 mg (48 healthy adults) in 14-day trials, and that in vitro studies using human liver microsomes indicated clinically significant cytochrome P450-mediated inhibition by EPA/DHA combinations is not expected in humans [2].

Bleeding: what the omega-3 label says

The omega-3-acid ethyl esters label states that omega-3 acids may prolong bleeding time. Some trials showed prolongation, but the label says the prolongation reported has not exceeded normal limits and did not produce clinically significant bleeding episodes. It also says clinical trials have not thoroughly examined the combination with anticoagulants, and it advises periodic monitoring for patients taking an anticoagulant or another drug that affects coagulation, such as an antiplatelet agent [2].

On the dutasteride side, the Avodart label reports a warfarin study: 3 weeks of dutasteride 0.5 mg/day did not alter the steady-state pharmacokinetics of the S- or R-warfarin isomers or warfarin's effect on prothrombin time [1].

The omega-3-acid ethyl esters label adds a caution for people with known fish or shellfish hypersensitivity and says it is not known whether such people are at higher risk of an allergic reaction [2].

Atrial fibrillation signal with omega-3

The omega-3-acid ethyl esters label describes a trial of 663 people with symptomatic paroxysmal atrial fibrillation (542) or persistent atrial fibrillation (121) who received 8 g/day for 7 days and 4 g/day for the next 23 weeks. First recurrent symptomatic atrial fibrillation or flutter was more frequent on omega-3 in both groups: in the paroxysmal group 141 events (53%) versus 129 (47%) on placebo (HR 1.19, 95% CI 0.93 to 1.35), and in the persistent group 34 (52%) versus 19 (35%) (HR 1.63, 95% CI 0.91 to 2.18). Combined, the HR was 1.25 (95% CI 1.00 to 1.40), and the label describes a possible association, particularly within the first 2 to 3 months [2].

A meta-analysis of 7 cardiovascular outcome trials with 81,210 patients found marine omega-3 associated with more atrial fibrillation (HR 1.25, 95% CI 1.07 to 1.46). The hazard was higher in trials testing more than 1 g/day (HR 1.49, 95% CI 1.04 to 2.15) than in trials testing 1 g/day or less (HR 1.12, 95% CI 1.03 to 1.22), and rose 1.11 per extra gram per day [3].

These studies evaluated omega-3 regimens and did not test omega-3 together with dutasteride, so they do not establish a dutasteride-specific effect [2][3].

Food, dose and half-life

The Avodart label says the capsule may be taken with or without food; food lowers peak concentration by 10% to 15%, a change the label calls not clinically significant [1]. Dutasteride's terminal half-life is about 5 weeks at steady state, with about 65% of steady state reached after 1 month and about 90% after 3 months [1]. The omega-3-acid ethyl esters label describes 4 g/day as a single 4-gram dose or two 2-gram doses, says the capsules were given with meals in clinical studies, and says to swallow them whole [2]. Over-the-counter products can differ, and their EPA plus DHA content varies widely, so the EPA and DHA amounts on the label matter more than the "fish oil" milligram figure.

The doses used in the cardiovascular trials were 1 g/day of marine omega-3 in VITAL, 4 g/day of icosapent ethyl in REDUCE-IT and 4 g/day of omega-3 carboxylic acids in STRENGTH [5][6][7].