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Article / Publication Details
Abstract
Mistletoe, Viscum album, is a medicinal plant used in complementary medicine in oncology. Patients don’t necessarily mention to their oncologist this phytotherapeutic treatment which may be responsible for unsuspected drug interactions. Some patients are adept at taking medicinal plants, a practice often unknown to health professionals who take care of it. This case reports drugs interactions leading to bleeding secondary to warfarin overdose. A patient over 75 years old was treated with nab-paclitaxel and gemcitabine a first course for a metastatic pancreatic adenocarcinoma (day 0). He was also treated with warfarin for atrial fibrillation. At day 3, he reported faintness and melena. At day 5, the biological assessment revealed an anemia with an hemoglobinemia of 5.1 g/dL and an International Normalized Ratio (INR) of 7.3, indicating a Vitamin K Antagonist (VKA) overdose. Warfarin was discontinued and the patient received a vitamin K supplementation and transfusions. The final diagnosis was an anemic syndrome due to gastrointestinal bleeding secondary to VKA overdose. Based on the chronology, a drug interaction between chemotherapy and warfarin was first suspected. Then, the patient interview found out that he self-medicated with subcutaneous injections of mistletoe extracts: 10 mg on day 0 and on day 2. Nab-paclitaxel can displace warfarin from its albumin binding sites and increase the free and active concentration of warfarin. Mistletoe extracts (Viscum album ) are used as complementary medicine in oncology. Warfarin is predominantly metabolized in the liver by 1A2, 2C9 and 3A4 cytochrome P450 (CYP) isoforms. An inhibitor of these cytochromes prevents the degradation of warfarin into inactive metabolites, leading to accumulation or even overdose of this narrow therapeutic index VKA. Nab-paclitaxel and gemcitabine do not act on these cytochromes. Viscum album is a cytochrome P450 3A4 inhibitor which therefore probably led to an increase in exposure to warfarin. Thus, there are two pharmacokinetic hypotheses that may explain warfarin overdose: the displacement warfarin from its albumin binding sites or the inhibition of CYP3A4 by mistletoe.
S. Karger AG, Basel
Article / Publication Details
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