In the UK, miconazole oral gel is the recommended first line treatment for localised or mild oral candida (oral thrush) infection in children (aged over 4 months) and adults.

Miconazole oral gel is available as two licensed products within the UK:

  • Daktarin Oral Gel (80g)classified as a POM medicine
  • Daktarin Oral Gel Sugar Free 2% (15g) classified as a pharmacy (P) medicine

The interaction between miconazole and warfarin is well established.  Miconazole inhibits several cytochrome P450 isoenzymes including CYP2C9, which is the main isoenzyme involved in the metabolism of warfarin. Inhibition of this isoenzyme reduces warfarin metabolism, leading to an increased anticoagulant effect, increased INR and possible bleeding complications.

A Drug Safety Update (DSU) was published in June 2016 advising of the risk of systemic absorption of miconazole following use of the oral gel and the possibility of an increased anticoagulant effect in patients taking warfarin. Twenty five yellow card reports have been received since the DSU was published bringing the total number of reported possible interactions to 175. The most common outcome of these yellow card reports includes:

  • Increased INR (135 reports)
  • Confusion (23 reports)
  • Haematuria (19 reports)
  • Fatal outcome (3 reports)

A review of the yellow card reports concluded that to minimise potential risks to patients the following changes should be implemented:

  • The use of over the counter miconazole oral gel by patients taking warfarin should be contra-indicated
  • More prominent and explicit warnings and information about the potential for an interaction between miconazole oral gel and warfarin. The risks associated with concomitant use of these products should be specified in the summary of product characteristics (SPC), patient information leaflet, and for OTC miconazole oral gel, the product label (tube and carton)
Advice to Healthcare Professionals

The use of over-the-counter miconazole oral gel by patients taking warfarin is now contra-indicated.

A warning has been included on the tube and outer carton for Daktarin Oral Gel Sugar Free 2% advising that miconazole oral gel should not be used by patients taking warfarin. Pharmacists should be alert to possible confusion that could occur if this product is supplied on prescription to patients also prescribed warfarin.

Additional advice has been provided for prescribers who make the clinical decision that oral miconazole gel is the most appropriate product for a patient prescribed warfarin. This advice includes:

  • Bleeding events, some with fatal outcome, have been reported with the use of miconazole oral gel by patients on warfarin
  • If the concomitant use of miconazole oral gel with an oral anticoagulant, such as warfarin is planned, exercise caution and ensure that you monitor and titrate the anticoagulant effect carefully
  • Advise patients taking prescription only miconazole oral gel and warfarin that if they experience signs of over-anticoagulation, such as sudden unexplained bruising, nosebleeds, or blood in urine, they should stop using miconazole and seek immediate medical attention.