Biomaterial Database

Do all histamine2-antagonists cause a warfarin drug interaction? 1989

E K Hussey, and G E Dukes

School of Pharmacy, University of North Carolina, Chapel Hill 27599.

Cimetidine, the first marketed histamine2-receptor antagonist, has been shown to decrease the clearance of warfarin consistently through inhibition of cytochrome P-450 metabolism. The clinical significance of this drug-drug interaction has been questioned due to: (1) the lowering of the warfarin therapeutic range, (2) the lowering of the total daily therapeutic cimetidine dosage, (3) the advent of once-daily cimetidine dosing, and (4) the demonstration that the clearance of the less active warfarin R-enantiomer is decreased to a greater extent than the more active S-enantiomer. Ranitidine has been implicated in both increasing and decreasing warfarin's hypoprothrombinemic-effect (noted in the warfarin package insert), despite the majority of investigations demonstrating no warfarin clearance changes. Careful examination of the implicating data indicates that the majority of the warfarin pharmacodynamic and pharmacokinetic variance that occurs with combined ranitidine-warfarin therapy cannot be attributed to a drug-drug interaction. No data are available to implicate the newer histamine2-antagonists, famotidine and nizatidine, in causing a decrease in warfarin metabolism.

UI	MeSH Term	Description	Entries
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D006635	Histamine H2 Antagonists	Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.	Antihistaminics, H2,H2 Receptor Blockader,Histamine H2 Antagonist,Histamine H2 Blocker,Histamine H2 Receptor Antagonist,Histamine H2 Receptor Antagonists,Histamine H2 Receptor Blockader,Histamine H2 Receptor Blockaders,Antagonists, Histamine H2,Blockaders, Histamine H2 Receptor,H2 Receptor Blockaders,Histamine H2 Blockers,Receptor Antagonists, Histamine H2,Receptor Blockaders, H2,Antagonist, Histamine H2,Blockader, H2 Receptor,Blockaders, H2 Receptor,Blocker, Histamine H2,Blockers, Histamine H2,H2 Antagonist, Histamine,H2 Antagonists, Histamine,H2 Antihistaminics,H2 Blocker, Histamine,H2 Blockers, Histamine,Receptor Blockader, H2
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014859	Warfarin	An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.	4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one,Aldocumar,Apo-Warfarin,Coumadin,Coumadine,Gen-Warfarin,Marevan,Tedicumar,Warfant,Warfarin Potassium,Warfarin Sodium,Potassium, Warfarin,Sodium, Warfarin