Miconazole oral gel and warfarin interaction
From Mr D. J. Buck
I write to express increasing concern of a lack of awareness among pharmacists and other healthcare professionals regarding the significant interaction between miconazole oral gel and warfarin (PJ, 28 April 2012, p527).
The most recent case our hospital was involved with was a 42-year-old male patient with a history of multiple venous thromboembolism events, hence his long-term warfarin treatment. He also has a history of a subarachnoid haemorrhage requiring significant neurosurgical intervention. He was started on miconazole oral gel for a simple case of oral thrush, and attended our anticoagulant clinic several weeks later, where he was found to have an international normalised ratio of 16. The patient was admitted to hospital and his INR was reversed with vitamin K and his anticoagulation subsequently successfully reintroduced.
This is not the first incidence we have experienced of this interaction and, over the past few years, we have seen at least three cases with INR results above 10. One resulted in a small gastrointestinal haemorrhage and another in a patient suffering haematuria. These cases required at least a brief hospital admission for the reversal of the high INR.
Miconazole is a potent inhibitor of the metabolism of warfarin by the cytochrome p450 isosyme CYP2C9.1 This interaction is
well documented within literature2,3 and standard references sources,4 and cases have been reported by professionals in periodicals previously to raise awareness.5,6
The risk of bleeding in these patients cannot, in my mind, be overstated and it seems it will only be a matter of time before we see further serious consequences from this interaction. It is clear that miconazole oral gel should never be used concomitantly with warfarin, especially when, in most circumstances, there is a far more suitable alternative.
Pharmacists need to exercise caution not only when selling miconazole over the counter, but also when dispensing prescriptions for patients already on warfarin. In most of the cases we have seen the miconazole has been prescribed by GPs, not bought over the counter.
Specialist Pharmacist — Anticoagulation
Royal Albert Edward Infirmary
1 O’ Reilly RA, Goulart DA, Kunze KL et al. Mechanisms of the stereoselective interaction between miconazole and racemic warfarin in human subjects. Clinical Pharmacology and Therapeutics 1992;51:656–67.
2 Silingardi M, Ghirarduzzi A, Tincani E et al. Miconazole oral gel potentiates warfarin anticoagulant activity. Thrombosis and Haemostasis 2000;83:794–5.
3 Miki A, Ohtani H, Sawada Y. Warfarin and miconazole oral gel interactions: analysis and therapy recommendations based on clinical data and a pharmacokinetic model. Journal of Clinical Pharmacy and Therapeutics 2011;36:642–50.
4 Baxter K (ed), Stockley’s drug interactions. London: Pharmaceutical Press. Available at: www.medicinescomplete.com (accessed 26 April 2012).
5 Baker S. Miconazole oral gel and warfarin. The Pharmaceutical Journal 2008;280:308.
6 Pemberton MN. Derangement of warfarin anticoagulation by miconazole oral gel. British Dental Journal 1998;184:68–9.
Citation: The Pharmaceutical Journal URI: 11100542