Is there any risk of interaction between warfarin and herbal remedies containing omega-3 or garlic?

Fråga: Is there any risk of interaction between warfarin and herbal remedies containing omega-3 or garlic?<br><br>The question concerns a patient treated with warfarin (Waran) for atrial fibrillation. The patient wants to take omega-3 capsules and garlic capsules.

Sammanfattning: Concomitant treatment with warfarin and omega-3 and/or garlic capsules should preferably be avoided, as both the risk, with a possible influence on thrombocyte aggregation indicated in the literature, and the benefit of these combinations are difficult to evaluate.

Svar: In general, interaction studies between drugs and natural remedies are scarce.<br><br>It has previously been reported that polyunsaturated fatty acids, such as omega-3, can prolong the time of bleeding as well as reduce thrombocytes aggregation (1).<br><br>An updated literature search revealed one placebo-controlled, randomised study with eleven patients, that studied the effect of fish oil on the INR in patients treated with warfarin. Three patients received 3000 mg fish oil (180 mg omega-3 per 1000 mg), three patients 6000 mg fish oil and five received placebo for four weeks. The INR did not change significantly and none of the patients required any warfarin dosage change. No bleedings were reported (2).<br><br>One case report of an increased INR, in a patient with concomitant treatment with warfarin and fish oil, has been published. After increasing the dose of fish oil from 1000 mg to 2000 mg, the INR increased from 2.8 to 4.3. The patient was also taking other drugs known to affect coagulation, vitamin E and acetylsalicylic acid. However, no change in dosage had been done for these. The patient did not experience any adverse effects (3).<br><br>No interaction studies with warfarin and garlic have been found in the literature. Only one brief report with increased INR in two patients treated with garlic and warfarin has been published. No information about doses and timeframes were mentioned (4).<br><br>However, it has been shown that garlic can inhibit thrombocyte aggregation (5, 6). In a double-blind, placebo-controlled study with 60 patients having a constantly increased spontaneous platelet aggregation, the effect of garlic on platelet aggregation was studied. After a run-in phase of one week the patients were randomised to either receive 800 mg garlic (n=30) or placebo (n=30) for four weeks followed by four weeks of a drug-free period. The ratio of platelet aggregates decreased by 10% and spontaneous platelet aggregation by 56%. After the drug-free period, the values went back to normal. In the placebo group, no changes were seen (5). Other small studies have also shown effects of garlic on platelet aggregation and fibrinolytic activity (6,7,8).<br><br>In the Swedish adverse drug reactions register there are four reports of interactions between warfarin and omega-3. One case is described, with a man having an INR that was difficult to control, with values up to 4.5. Besides warfarin he had been taking omega-3. When omega-3 was withdrawn his INR decreased and was thereafter stable. No such reports have been found for warfarin and garlic (9).<div id="referenser" style="display:none;">Drugline no 15608 (year 1998)<br>Bender NK, Kraynak MA, Chiquette E, Linn WD, Clark GM, Bussey HI. Effects of marine fish oils on the anticoagulation status of patients receiving chronic warfarin therapy. J Thromb Thrombolysis 1998;5:257-61.<br>Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother 2004;38:50-3.<br>Sunter WH. Warfarin and garlic (letter). Pharmaceut J 1991;246:722.<br>Kieselwetter H, Jung F, Jung EM, Mrowietz C, Koscielny J, Wenzel E. Effect of garlic on platelet aggregation in patients with increased risk of juvenile ischaemic attack. Eur J Clin Pharmacol 1993;45:333-6.<br>Legnani C, Frascaro M, Guazzaloca G, Ludovici S, Cesarano G, Coccheri S. Effects of a dried garlic preparation on fibrinolysis and platelet aggregation in healthy subjects. Arzneimittelforschung 1993;43(2):119-22.<br>Harenberg J, Giese C, Zimmermann R. Effect of dried garlic on blood coagulation, fibrinolysis, platelet aggrgation and serum cholesterol levels in patients with hyperlipoproteinemia. Atherosclerosis 1988;74:247-9.<br>Warfarin. Drugdex(R) System; Thomson MICROMEDEX, Greenwood Village, Colorado (cited 2004-10-26)<br>Swedis (cited 2004-11-04)</div>