Drug Interactions between aspirin / butalbital / caffeine and B-Nexa

MONITOR: Ginger may potentiate the effects of anticoagulants, platelet inhibitors and thrombolytic agents, possibly increasing the risk of bleeding. Limited data suggest that ginger may decrease platelet aggregation via the inhibition of thromboxane synthetase, although some studies have found no effect on platelet function or thromboxane production or activity. Nevertheless, the interaction was suspected in a 76-year-old patient stabilized on coumarin therapy who developed epistaxis following use of ginger products (pieces of dried ginger, tea from ginger powder) for several weeks. Her INR was greater than 10 (target INR 2.0 to 3.0) and partial thromboplastin time (PTT) was 84.4 seconds (normal less than 35 seconds) upon hospital admission. INR and PTT values normalized after ginger intake was stopped and vitamin K given. In contrast, an investigative study found no significant effect of ginger pretreatment for 7 days on clotting status or the pharmacokinetics or pharmacodynamics of a single 25 mg dose of warfarin in 12 healthy volunteers.

MANAGEMENT: Patients should consult a healthcare provider before taking any herbal or alternative medicine. In patients who have used ginger and ginger supplements extensively prior to receiving anticoagulation, antiplatelet or thrombolytic therapy, the potential for an interaction should be considered. Close clinical and laboratory observation for hematologic complications is recommended. 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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One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

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One small study has suggested that pyridoxine may decrease serum levels of phenobarbital. The mechanism is unknown. Phenobarbital is the only barbiturate specifically implicated in this interaction. However, other barbiturates may behave in a similar fashion. Close observation for altered barbiturate effects is indicated if these drugs must be used together.

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