Drug interactions between acetaminophen/salicylamide and Miradon

anisindione ↔ salicylamide

Applies to:Miradon (anisindione) and acetaminophen/salicylamide

GENERALLY AVOID: Theoretically, salicylates may potentiate the effects of anticoagulants and increase the risk of bleeding. Salicylates interfere with the action of vitamin K and induce a dose-dependent alteration in hepatic synthesis of coagulation factors VII, IX and X, occasionally increasing the prothrombin time. While these effects are generally slight for most salicylates (except aspirin) at recommended dosages, they may be of clinical significance when combined with the inhibitory effects of anticoagulants on the clotting cascade. Moreover, salicylates are known to cause dose-related gastrointestinal bleeding, which may be complicated by anticoagulant therapy.

MANAGEMENT: Until further data are available, products containing salicylates, especially if given chronically or in high dosages, should preferably be avoided in patients receiving anticoagulants. Close clinical and laboratory observation for bleeding complications is recommended if concurrent therapy is necessary. The same precaution should be observed with the use of salicylate-related agents such as salicylamide because of their structural and pharmacological similarities. Ambulatory 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. Patients should also be counseled to avoid any other over-the-counter salicylate products.

acetaminophen ↔ anisindione

Applies to:acetaminophen/salicylamide and Miradon (anisindione)

Acetaminophen (APAP) may potentiate the hypoprothrombinemic effect of warfarin and other oral anticoagulants, although data are somewhat conflicting and the mechanism of interaction is unknown. The interaction has generally been associated with prolonged ingestion of relatively high APAP dosages (greater than 1.3 g/day continuously for greater than 1 week) but not with brief, intermittent exposures of average doses. Reported increases in prothrombin time or INR from most studies were often small but statistically significant, although there have been isolated case reports citing bleeding episodes and clinically significant alterations in coagulation parameters. In contrast, one retrospective study found no significant effect of APAP 2000 to 2500 mg/day on the anticoagulant effect of phenprocoumon, and another study reported no effect of APAP 4 g/day for 2 weeks on single-dose warfarin pharmacokinetics and pharmacodynamics in healthy volunteers. Due to the lack of safer alternatives, acetaminophen is considered the analgesic and antipyretic drug of choice for patients receiving oral anticoagulant therapy. However, caution is recommended during concomitant therapy, particularly if high dosages of APAP are used for a prolonged period. 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.