Drug Interactions between famotidine / ibuprofen and omega-3 polyunsaturated fatty acids

MONITOR: Omega-3 fatty acids (e.g., fish oil) may potentiate the pharmacologic effects of anticoagulants and other drugs that affect hemostasis such as platelet inhibitors, thrombin inhibitors, thrombolytic agents, dextran, and nonsteroidal anti-inflammatory drugs (NSAIDs). The exact mechanism of interaction is unknown. Omega-3 fatty acids may possess mild antiplatelet and hypocoagulant activities. In some studies, these substances have been shown to reduce thrombin generation and plasma levels of fibrinogen, prothrombin, and coagulation factors V, VII, and X. Prolongation of bleeding time has been demonstrated, although it did not exceed normal limits and did not produce clinically significant bleeding. In a double-blind, placebo-controlled trial (n=8,179), bleeding events were reported in 11.8% of patients receiving icosapent ethyl compared to 9.9% in the placebo group, most commonly gastrointestinal bleeding, contusion, hematuria, and epistaxis. Serious bleeding events were reported more frequently in icosapent ethyl-treated patients who were also on concomitant antithrombotic therapy (3.4%) compared to placebo-treated patients (2.6%) but occurred at the same rate (0.2%) in patients not on such concomitant therapy. However, the interaction was suspected in a case report of a 67-year-old woman treated with warfarin for 1.5 years who exhibited an increase in INR from 2.8 the previous month to 4.3 approximately one week after doubling her fish oil dosage from 1000 to 2000 mg/day. Prior to the increase, her INR had been stable and therapeutic for 5 months on warfarin 1.5 mg/day. The patient was advised to reduce her fish oil consumption to 1000 mg/day, while her warfarin dose was withheld for one day and then reduced to 1 mg alternating with 1.5 mg per day. Eight days later, her INR was subtherapeutic at 1.6, so the warfarin dosage was increased back to 1.5 mg/day. The patient's INR subsequently returned to therapeutic range.

MANAGEMENT: In general, patients should consult a healthcare provider before taking any herbal or nutritional supplements. Patients using omega-3 fatty acid-containing medicines, including icosapent ethyl, in combination with anticoagulants or other drugs that affect hemostasis should be advised of the potential for increased risk of bleeding complications.

H2 antagonists may alter the pharmacokinetic disposition of some nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data have been varied, even for the same NSAID. The mechanism may involve inhibition of metabolism, changes in gastric pH resulting in altered absorption, and/or reduced urinary elimination of the affected NSAIDs. Statistically significant changes have been small and of limited clinical significance when interactions have been observed.