Can I Take Omega-3 (EPA/DHA) with Fosamax (Alendronate)?

What is known about taking them together

The Fosamax label is specific about the glass and the clock. Alendronate is taken on arising, with 6 to 8 ounces of plain water, at least 30 minutes before the first food, beverage or medication of the day, and the patient stays upright for at least 30 minutes and until after the first food [1]. Other beverages, including mineral water, food and some medications reduce absorption, and the label warns that not following these instructions can increase esophageal adverse effects [1].

The label's interaction statements name calcium supplements and other multivalent-cation products, antacids, coffee, juice and food, with the instruction to wait at least one-half hour after alendronate before any other oral medication, food or drink other than plain water [1]. Fish oil is not named there.

Why the timing matters

Alendronate's oral bioavailability is about 0.64% in women when the dose is taken after an overnight fast and two hours before a standardized breakfast [1]. The label's own measurements show how much food and drink shift that number. Coffee or orange juice taken with the dose reduced bioavailability by about 60%, and a standardized breakfast taken with or up to 2 hours after the dose made absorption negligible [1].

Dosing 0.5 or 1 hour before breakfast reduced bioavailability by about 40% compared with dosing 2 hours before eating. Even so, alendronate was effective in trials when taken at least 30 minutes before breakfast (49 postmenopausal women, 10 mg dose) [1].

What the omega-3 side contributes

Over-the-counter fish oil is a dietary supplement, not an FDA-approved drug [4]. Prescription omega-3 products are drugs. Omega-3-acid ethyl esters (EPA plus DHA) is labeled only as an adjunct to diet for severe hypertriglyceridemia of 500 mg/dL or higher, and its label states that the effect on cardiovascular mortality and morbidity has not been determined [2]. The label gives the dose as 4 g a day, as one 4-gram dose or two 2-gram doses, swallowed whole, and notes it was given with meals in clinical studies [2]. HealthRX.com lists omega-3 fish oil softgels among supplement options.

Bleeding is the warning that matters most if other drugs are in the picture. The omega-3-acid ethyl esters label says omega-3 acids may prolong bleeding time, that the prolongation reported in the trials cited did not exceed normal limits and did not produce clinically significant bleeding, and that people taking an anticoagulant or antiplatelet drug should be monitored periodically [2].

Higher doses also carry an atrial fibrillation signal. The same label describes a possible association with more frequent recurrence of symptomatic atrial fibrillation or flutter in people with paroxysmal or persistent atrial fibrillation, particularly in the first 2 to 3 months; in a 663-person trial the combined hazard ratio was 1.25 (95% CI 1.00 to 1.40) [2]. A 2021 meta-analysis of 7 cardiovascular outcome trials and 81,210 patients found an overall hazard ratio of 1.25 for atrial fibrillation, rising to 1.49 in trials testing more than 1 g a day and 1.12 at 1 g a day or less [3].

Does fish oil do anything for bone?

A key fracture trial of alendronate, the Fracture Intervention Trial, enrolled 2,027 postmenopausal women with at least one vertebral fracture and followed them for 36 months. New morphometric vertebral fractures occurred in 8.0% on alendronate versus 15.0% on placebo (relative risk 0.53, 95% CI 0.41 to 0.68) [5].

For omega-3, a 2012 systematic review found 10 randomized trials with skeletal outcomes. None had fracture as an outcome, four reported favorable effects on bone mineral density or bone turnover markers (three of those delivered omega-3 with high-calcium foods or supplements), five found no difference between groups, and the authors said strong conclusions were limited by the small number and modest size of the trials [6].

A practical morning

1. On waking, take alendronate with 6 to 8 ounces of plain water [1].
2. Stay upright, sitting or standing, for at least 30 minutes and until after the first food of the day; do not lie down [1].
3. Fish oil can follow with that first meal. The omega-3-acid ethyl esters label notes that it was given with meals in clinical studies [2].
4. If a weekly alendronate dose is missed, the label says to take one dose the morning after remembering, never two doses on the same day, then return to the usual chosen day [1].