Long-Acting Anticoagulant Overdose: Brodifacoum Kinetics and Optimal Vitamin K Dosing

• Published in: Annals of emergency medicine Vol. 36; no. 3; pp. 262 - 267
• Main Authors: Bruno, G.Richard, Howland, Mary Ann, McMeeking, Alex, Hoffman, Robert S.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.09.2000; Elsevier
• Subjects: 4-Hydroxycoumarins - blood; 4-Hydroxycoumarins - pharmacokinetics; 4-Hydroxycoumarins - poisoning; Administration, Oral; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Drug Overdose; Follow-Up Studies; Half-Life; Hemorrhage - chemically induced; Hemorrhage - drug therapy; Humans; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Pesticides, fertilizers and other agrochemicals toxicology; Pharmacology. Drug treatments; Plasma; Rodenticides - blood; Rodenticides - pharmacokinetics; Rodenticides - poisoning; Suicide, Attempted; Toxicology; Vitamin K - administration & dosage; Vitamin K - therapeutic use; Human; Phytomenadione; Hemostatic; Toxicity; Pesticides; Male; Hemopathy; Anticoagulant; Rodenticide; Chemotherapy; Toxicology; Treatment; Adult; Poisoning; Kinetics; Effective dose; Coagulopathy; Vitamin K
• ISSN: 0196-0644; 1097-6760
• DOI: 10.1067/mem.2000.108317

Ingestion of long-acting anticoagulant rodenticides such as brodifacoum can lead to prolonged and life-threatening coagulopathy. A paucity of conflicting information is available on brodifacoum’s half-life and elimination pharmacokinetics. In addition, the optimal dose, duration, and route of administration of vitamin K1 therapy are unknown. We report the case of a 52-year-old man who ingested eight 43-g boxes of a rodenticide (d-Con Mouse-Prufe II; 0.005% brodifacoum; Reckitt & Colman, Wayne, NJ). This case demonstrates that after stabilization with fresh frozen plasma, high-dose oral vitamin K1 therapy (≅7 mg/kg per 24 hours divided every 6 hours) was effective in treating brodifacoum-induced coagulopathy. The concentration of vitamin K1 required for normal coagulation in this case was less than the accepted value of 1 μg/mL, which is derived from a rabbit model. In this case, brodifacoum appears to follow zero-order elimination pharmacokinetics. In future cases of patients with ingestions of long-acting anticoagulants who present with coagulopathy, it may be useful to obtain serial brodifacoum concentrations to determine elimination curves to help predict the duration of oral vitamin K1 therapy. [Bruno GR, Howland MA, McMeeking A, Hoffman RS. Long-acting anticoagulant overdose: brodifacoum kinetics and optimal vitamin K dosing. Ann Emerg Med. September 2000;36:262-267.]