By Michael O’Riordan
June 8, 2010 (Maywood, Illinois) — A new review warns physicians to be aware of the potential for drug and dietary interactions with the emerging oral anticoagulants . At present, there are few documented interactions with the new drugs, including dabigatran (Pradaxa, Boehringer Ingelheim), rivaroxaban (Xarelto, Johnson & Johnson), and apixaban (Bristol-Myers Squibb/Pfizer), but considering the extensive food and drug interactions with warfarin, caution should be taken with the new agents, according to researchers.
“Many unknowns remain as to how the new oral anticoagulants will behave in the real-world patient population,” write authors Drs Jeanine Walenga and Cafer Adiguzel (Loyola University Medical Center, Maywood, IL) in the June 2010 issue of the International Journal of Clinical Practice. “As evaluations of the new oral anticoagulants continue, the issue of drug interactions needs to be properly evaluated, particularly as some of the interacting drugs are used to treat potentially life-threatening conditions.”
One recent study reported by heartwire showed that the safety of warfarin, a vitamin-K antagonist, can be compromised by many popular herbal and nonherbal supplements. In fact, eight of the 10 most widely used supplements interact with warfarin, and many of these are associated with significant changes in the international normalized ratio (INR). Cranberry, garlic, ginkgo, and saw palmetto have been linked to increased rates of bleeding, whereas others have been shown to cause changes in prothrombin times, which would result in a need to alter warfarin doses.
Little Known About Food, But Caution Still Needed
In their review, Walenga and Adiguzel note that the new and emerging oral anticoagulants have a “rapid onset of action and a predictable anticoagulant effect,” but little is known about potential interactions with food. They point out the various physiological parameters can alter the pharmacokinetics of orally administered drugs, such as changes in gastric pH balance and intestinal motility and binding, and these can be affected by eating and taking the drugs at the same time.
Regarding drug interactions, dabigatran is contraindicated with quinidine, a drug used to treat cardiac arrhythmias and malaria. Caution should also be used when dabigatran is prescribed in combination with inhibitors or inducers of P-glycoprotein (P-GP), such as amiodarone, clarithromycin, and rifampin. Rivaroxaban, as well as possibly apixaban, is contraindicated with drugs that inhibit both cytochrome P450 3A4 (CYP3A4) and P-GP pathways, such as azole antimycotics, ritonavir, and clarithromycin, among others. Caution should be exercised prescribing rivaroxaban with a drug that inhibits either the CYP3A4 only or P-GP pathway only.
One over-the-counter supplement that the reviewers highlight as a possible problem with the new oral anticoagulants is St John’s wort, a herb taken frequently for depression. St John’s wort is known to reduce the anticoagulant effect of warfarin.
There is also risk of bleeding when using the new oral anticoagulants in combination with an antiplatelet agent, such as clopidogrel, or nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin.
“In addition to drug and food interactions, it is equally important to consider liver, kidney, and other common disease states that the US population experiences, particularly if these patients have been excluded from clinical trials,” write Walenga and Adiguzel. Although dabigatran and rivaroxaban are contraindicated in patients with severe liver impairment, they might inadvertently be given to patients in whom clinical symptoms are not pronounced, a population that has not been extensively studied.
The reviewers recommend clinicians use caution with the new drugs in older patients, particularly since this population often has long-term comorbid conditions.