Drug Interactions Causing Warfarin Overdose in a Patient with Pancreatic Cancer: A Case Report.

Mistletoe, Viscum album, is a medicinal plant used in complementary medicine in oncology. Patients do not 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 them. This case reports drug interactions leading to bleeding secondary to warfarin overdose. A patient over 75 years of age was treated with nab-paclitaxel and gemcitabine as a first course for 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 anemia with hemoglobinemia of 5.1 g/dL and an international normalized ratio of 7.3, indicating vitamin K antagonist (VKA) overdose. Warfarin was discontinued and the patient received 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 (V. 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. V. 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 of warfarin from its albumin binding sites or the inhibition of CYP3A4 by mistletoe. This adverse drug event was reported to the Regional Pharmacovigilance Center of Strasbourg on June 30, 2021, and registered under the number ST20212767.

Development and validation of a ready-to-use score to prioritise medication reconciliation at patient admission in an orthopaedic and trauma department.

OBJECTIVE: Medication reconciliation (MR) is recognised as an important tool in preventing medication errors such as unintentional discrepancies (UDs). The aim of this study was to identify independent predictive factors of UDs during MR at patient admission to an orthopaedic and trauma department. The secondary objective was to build and validate a ready-to-use score to prioritise patients. METHOD: A retrospective study was performed on 3.5 years of pharmacist-led MR in the orthopaedic and trauma department of a large university teaching hospital. Independent predictors of UD were identified by multivariable logistic regression. A priority score to identify patients at risk of at least one UD was constructed from the odds ratios of the risk factors, and validated in a separate cohort. Performance was assessed with sensitivity, specificity, C-statistic and Hosmer-Lemeshow goodness-of-fit. RESULTS: In total, 888 patients were included and 387 UDs were identified, mainly drug omissions (65.1%). Five independent predictors of UD were identified: age >75 years (OR 2.05, 95% CI 1.41 to 3.00; p<0.001), admission during school holidays (OR 1.69, 95% CI 1.17 to 2.44; p=0.005), female gender (OR 2.20, 95% CI 1.53 to 3.16; p<0.001), emergency hospitalisation (OR 2.05, 95% CI 1.45 to 2.92; p<0.001), and ≥5 medications on the best possible medication history (BPMH) (OR 3.29, 95% CI 2.20 to 4.94; p<0.001). Based on these predictors, a priority score ranging from 0 to 10 was built and internally and externally validated (C statistic 0.72, 95% CI 0.67 to 0.76). CONCLUSIONS: This study confirms the high prevalence of UD in patients admitted to orthopaedic and trauma surgery departments. Five independent predictive factors of UD during MR were identified (female gender, emergency hospitalisation, hospitalisation during school holidays, age ≥75 years, and ≥5 medicines on the BPMH). The developed risk score will help to prioritise MR among patients at risk of medication error and is ready-to-use in other orthopaedic and trauma departments.