Enzalutamide and analytical interferences in digoxin assays. (2nd November 2018)

• Record Type: Journal Article
• Authors: Deguigne, Marie; Brunet, Marion; Abbara, Chadi; Turcant, Alain; Le Roux, Gaël; Lelièvre, Bénédicte
• Is Part Of: Clinical toxicology. Volume 56:Number 11(2018)
• Page Start: 1150
• Page End: 1154
• Publication Date: 2018-11-02
• Subjects: Enzalutamide -- digoxin -- immunoassay -- false positive; Toxicology -- Periodicals; Toxicological emergencies -- Periodicals; 615.9
• DOI: 10.1080/15563650.2018.1469758
• Languages: English
• ISSNs: 1556-3650

Abstract

Abstract: Objective: We report two cases of elevated digoxin plasma levels in patients receiving enzalutamide. Cases reported: The first patient, an 84-year-old male treated with enzalutamide, was hospitalized due to deterioration in his general state. Atrial fibrillation was discovered and treatment with digoxin was initiated. Supratherapeutic digoxin concentrations (4 µg/L and 3.5 µg/L 3 days later) led to treatment being stopped despite the lack of clinical or biological signs of overdose. The second patient, an 84-year-old male treated with digoxin and enzalutamide, was hospitalized for the same reasons. Digoxin concentration upon admission was 2.8 μg/L. Despite stopping treatment, digoxin blood levels were observed to have increased on D3 and D7 following admission (3 and 3.6 μg/L, respectively). However, no clinical or biological findings indicated an overdose. Blood samples were sent to the Pharmacology and Toxicology Laboratory for analysis. Methods: The second patient's digoxin plasma level was determined using the chemiluminescent microparticle immunoassay (CMIA®, Abbott, Illinois) method. Enzalutamide levels were determined using HPLC-UV/DAD method. An interference study was performed using different assay methods by adding enzalutamide to control plasma at various concentrations from a Xtandi ® (40mg) capsule. Results: Plasma concentration of digoxin at D7 for patient 2 was identical in both laboratories (3.5 vs. 3.6 µg/L). Enzalutamide was found in the patient's plasma (12, 5 mg/L). Adding 4, 10, 20, and 40 mg/L of enzalutamide to the untreated plasma showed that the plasma concentration of digoxin was positive (from 0.35 to 3.69 µg/L) using the CMIA method. Conclusions: Our results highlight the analytical interferences of enzalutamide with digoxin assays using the CMIA method.