Drug Interactions between Aggrenox and Nutr-E-Sol

MONITOR: Vitamin E may potentiate the effects of anticoagulants and platelet inhibitors. Vitamin E is thought to inhibit the oxidation of reduced vitamin K and interfere with the functions of vitamin K-dependent clotting factors. These effects appear to be dose-dependent and greater in individuals with preexisting vitamin K deficiency. In one study, administration of vitamin E 42 units/day for one month increased the hypoprothrombinemic effect of a single dose of dicumarol in 3 healthy volunteers, as demonstrated by a decrease in prothrombin activity from 52% to 33% thirty-six hours postdose. The interaction was also suspected in a patient who developed ecchymoses and hematuria following two months of vitamin E supplementation at a dosage of 800 to 1200 units/day while taking warfarin. In contrast, two studies found no significant effect of vitamin E on the hypoprothrombinemic effect of chronic warfarin therapy when administered at relatively high dosages (800 or 1200 units/day) to 21 subjects for one month or at low dosages (100 or 400 units/day) to 12 subjects for four weeks. With respect to antiplatelet activities, data from in vitro and ex vivo human studies suggest that vitamin E can inhibit collagen-induced platelet activation and protein kinase C-dependent platelet aggregation. Clinically significant antiplatelet effects have not been consistently observed in published studies, particularly at dosages below 400 units/day. However, there have been isolated reports of excessive bleeding in surgical patients who had taken vitamin E regularly prior to surgery, and one controlled clinical trial found that supplementation with only 50 mg/day of vitamin E resulted in an increase in subarachnoid hemorrhage in male smokers aged 55 to 74 years (n=409). In a random sampling of that same population of male smokers, gingival bleeding was also more common in subjects who received vitamin E with aspirin compared to those who received either agent alone or neither.

MANAGEMENT: Patients should consult a healthcare provider before taking any nutritional supplements like vitamin E. Close clinical and laboratory observation for hematologic complications may be appropriate when vitamin E supplementation at dosages greater than 400 units/day is initiated in patients stabilized on anticoagulant or antiplatelet therapy. The dose of the anticoagulant or antiplatelet drug may require adjustment during and after treatment with vitamin E. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

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MONITOR: Vitamin E may potentiate the effects of anticoagulants and platelet inhibitors. Vitamin E is thought to inhibit the oxidation of reduced vitamin K and interfere with the functions of vitamin K-dependent clotting factors. These effects appear to be dose-dependent and greater in individuals with preexisting vitamin K deficiency. In one study, administration of vitamin E 42 units/day for one month increased the hypoprothrombinemic effect of a single dose of dicumarol in 3 healthy volunteers, as demonstrated by a decrease in prothrombin activity from 52% to 33% thirty-six hours postdose. The interaction was also suspected in a patient who developed ecchymoses and hematuria following two months of vitamin E supplementation at a dosage of 800 to 1200 units/day while taking warfarin. In contrast, two studies found no significant effect of vitamin E on the hypoprothrombinemic effect of chronic warfarin therapy when administered at relatively high dosages (800 or 1200 units/day) to 21 subjects for one month or at low dosages (100 or 400 units/day) to 12 subjects for four weeks. With respect to antiplatelet activities, data from in vitro and ex vivo human studies suggest that vitamin E can inhibit collagen-induced platelet activation and protein kinase C-dependent platelet aggregation. Clinically significant antiplatelet effects have not been consistently observed in published studies, particularly at dosages below 400 units/day. However, there have been isolated reports of excessive bleeding in surgical patients who had taken vitamin E regularly prior to surgery, and one controlled clinical trial found that supplementation with only 50 mg/day of vitamin E resulted in an increase in subarachnoid hemorrhage in male smokers aged 55 to 74 years (n=409). In a random sampling of that same population of male smokers, gingival bleeding was also more common in subjects who received vitamin E with aspirin compared to those who received either agent alone or neither.

MANAGEMENT: Patients should consult a healthcare provider before taking any nutritional supplements like vitamin E. Close clinical and laboratory observation for hematologic complications may be appropriate when vitamin E supplementation at dosages greater than 400 units/day is initiated in patients stabilized on anticoagulant or antiplatelet therapy. The dose of the anticoagulant or antiplatelet drug may require adjustment during and after treatment with vitamin E. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

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