Reporting of adverse incidents is mandatory in Denmark. All reported adverse incidents are made anonymously, and stored in an encrypted database. It is the purpose of this descriptive study to describe the severity of adverse medication incidents caused by oral anticoagulants in hospitals. All moderate, severe and fatal reports concerning non‐vitamin K antagonist oral anticoagulants were analyzed from date of marketing until July 8 2014. The data collection for warfarin was from January 1 2014 until July 8 2014. Three independent specialists in clinical pharmacology evaluated the severity of incident outcomes. A total of 147 adverse medication incidents were analyzed, and showed that de facto or potentially fatal and serious incidents were most frequently associated with sector change (admission to or discharge from hospital, or undergoing surgery) and resulted from insufficient or excess dosing. Physicians should be aware when prescribing and changing anticoagulant therapy to avoid severe or fatal incidents.

Treatment of patients with metastatic renal cell carcinoma with pazopanib has been associated with an increased probability of developing liver toxicity in the presence of polymorphisms in the gene UGT1A1 (uridine diphosphate glucuronosyltransferase 1A1), leading to treatment interruptions and permanent discontinuation. We have demonstrated that UGT1A1-guided dosing can manage pazopanib-induced liver toxicity and also that UGT1A1 polymorphisms are associated with improved outcomes, despite pazopanib interruption and substantial dose reductions. Background: Pazopanib can induce liver toxicity in patients with metastatic renal cell carcinoma (mRCC). We assessed the effect of a TA repeat polymorphism in the UGT1A1 (uridine diphosphate glucuronosyltransferase 1A1) gene encoding uridine diphosphate glucuronosyltransferase 1A1 on liver toxicity, dose reductions, and patient outcomes. Patients and Methods: Patients with mRCC treated with first-line pazopanib developing liver toxicity underwent genotyping for the UGT1A1 polymorphism. Liver toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.0. Progression-free survival and overall survival were assessed using the Kaplan-Meier and log-rank methods. Results: Of 261 patients, 34 (13%) had developed liver toxicity after a median of 29 days (range, 5-155 days). Grade 4, 3, and 2 alanine aminotransferase or bilirubin had increased in 2 (6%), 17 (50%), and 8 (24%) patients, respectively. The UGT1A1 assessment demonstrated that 18 patients (53%) had TA6/TA7, 7 (21%) had TA7/TA7, and 9 (26%) had wild-type TA6/TA6. The UGT1A1 polymorphism was associated with improved median progression-free survival (TA6/TA6, 5.5 months; TA6/TA7, 34.2 months; TA7/TA7, 22.3 months; unknown UGT1A1 status, 9.2 months; UGT1A1 polymorphisms combined vs. unknown status, P ¼ .021). UGT1A1 polymorphism was associated with improved median overall survival (TA6/TA6, 8.1 months, TA6/TA7 or TA7/TA7 not reached, unknown UGT1A1 status, 16.6 months; UGT1A1 polymorphisms combined vs. unknown status, P ¼ .033). Patients with UGT1A1 polymorphism safely resumed pazopanib at ultra-low doses determined by the degree of liver toxicity and UGT1A1 polymorphism. Conclusions: UGT1A1 polymorphisms were associated with improved outcomes, despite pazopanib interruption and dose reductions. UGT1A1 assessment could improve the management of pazopanibinduced liver toxicity in patients with mRCC.

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Venous thromboembolism (VTE) is a frequent complication of cancer, and management of cancer-associated thrombosis (CAT) is challenging due to increased risks of bleeding and recurrent VTE. Recent trials have shown an acceptable efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of CAT compared to low-molecular weight heparin. Although DOACs provide an effective and convenient treatment option in CAT, the need to assess the risk of drug–drug interactions (DDI) with antineoplastic therapies poses a barrier to their use in clinical practice. With the aim of supporting the assessment of CAT patients for treatment with DOAC, this review provides a comprehensive overview of the compatibility of antineoplastic therapies with the individual DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban). Using several data sources, we characterized 100 widely used antineoplastic agents with regard to their effect on p-glycoprotein and cytochrome P450, both important in the transport and elimination of DOACs. This enabled us to evaluate 400 “DOAC-antineoplastic agent”-pairs regarding their likelihood to interact (unlikely, potential, or likely), ultimately leading to clinical recommendations on the appropriateness of concomitant use for each pair. A potential or likely DDI was identified for 12% of the evaluated pairs. For nearly all antineoplastic agents, at least one DOAC was considered compatible.

We present a case of a 64-year-old man with Crohn's disease who developed parkinsonism after starting treatment with infliximab (Remicade). The patient had a 30-year history of Crohn's disease with previous surgical procedures and treatment with methotrexate. Treatment was augmented with infliximab, and 3 days after the first dose of 400 mg, a resting tremor began in the left leg. Over 4 months, symptoms progressed and now involved the right leg as well as both hands. There was no clinical effect of infliximab treatment, and the treatment was withdrawn 4 months later. The patient then experienced gradual, but continual, improvement of the resting tremor after withdrawal of infliximab. To the best of our knowledge, this is the first case report describing a patient developing parkinsonism after starting treatment with infliximab, with symptoms remitting on discontinuation.