Papers

Drug points: Potentiation of warfarin anticoagulant activity by miconazole oral gel

BMJ 1997; 314 doi: https://doi.org/10.1136/bmj.314.7077.349a (Published 01 February 1997) Cite this as: BMJ 1997;314:349
  1. S Ariyaratnama,
  2. N S Thakkera,
  3. P Sloana,
  4. MH Thornhilla
  1. a University Dental Hospital of Manchester, Manchester M15 6FH

    Miconazole is a synthetic imidazole with broad spectrum activity against pathogenic fungi and Gram positive bacteria. When given systemically it also inhibits several microsomal P-450 isoenzymes, including P-4502C9, the isoenzyme primarily responsible for 7-hydroxylation of warfarin that terminates its anticoagulant effect.1 However, miconazole is poorly absorbed from the gut and its formulation as an oral gel is thought to result in negligible absorption.2 3 Indeed, it is now available over the counter.

    The use of miconazole oral gel in a 73 year old man resulted in loss of anticoagulant control. He had been given warfarin two years previously after coronary bypass surgery and his condition was well controlled with 1-3 mg daily. Other treatment included twice daily metoprolol 50 mg, diltiazem 90 mg, aspirin 75 mg, and isosorbide 40 mg, plus once daily omeprazole 40 mg. In January 1995 he was prescribed miconazole oral gel 125 mg (5 ml) four times daily for oral candidiasis. Before this his international normalised ratio was 1.5. When repeated two weeks later, while still using the oral gel, it was over 10. The miconazole gel and warfarin were immediately withdrawn and two weeks later the international normalised ratio had reduced to 3. Warfarin was reintroduced at 2 mg daily and the ratio remained well controlled in the range 2-3. There was no other change in the patient's drug treatment.

    Two previous cases have been reported of miconazole oral gel potentiating the action of warfarin.4 5 Potentiation has also occurred with the oral anticoagulants nicoumalone6 7 and phenindione.8 Together they indicate that the oral gel may be sufficiently absorbed to interact with other drugs. Indeed, the British National Formulary now carries an appendix note that the gel may be absorbed. No such warning is contained in the drug packaging or datasheet, however. It is important, therefore, that patients taking warfarin and doctors, dentists, and pharmacists are made aware of this important interaction.

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