Other safety alerts
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| The United Kingdom: Topical miconazole, including oral gel: reminder of potential for serious interactions with warfarin |
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The Medicines and Healthcare products Regulatory Agency (MHRA) advised that in view of reports of serious bleeding events in patients taking miconazole and warfarin, the MHRA is considering further measures to minimise the risk of potentially serious interactions between miconazole and warfarin.
Healthcare professionals are reminded that miconazole, including the topical gel formulation, can enhance the anticoagulant effect of warfarin—if miconazole and warfarin are used concurrently, the anticoagulant effect should be carefully monitored and, if necessary, the dose of warfarin reduced. Patients should be advised to tell their doctor or pharmacist if they are receiving warfarin before using products that contain miconazole (including those available without prescription), and to seek medical advice if they notice signs of over-anticoagulation during treatment, such as sudden unexplained bruising, nosebleeds or blood in the urine.
Miconazole (Daktarin, Daktacort) is an antifungal indicated for prevention and treatment of various infections of the mouth, throat, skin, nails, or genitals. It is usually applied topically as a cream, ointment, powder, or oral gel. Some products are available without a prescription.
Warfarin is an oral anticoagulant that has been widely used since the 1950s for prophylaxis of thromboembolic events. Daily dose depends on individual requirements, and patients receiving long-term therapy require regular coagulation tests.
The potential for drug interactions between miconazole and warfarin is well established. The mechanism is understood to be inhibition by miconazole of one of the main cytochrome P450 isozymes involved in warfarin metabolism (CYP2C9), resulting in reduced warfarin clearance and an enhanced anticoagulant effect.
In the UK, prescribing information for products that contain miconazole warns that because miconazole inhibits CYP2C9, caution should be exercised for patients on oral anticoagulants such as warfarin, and the anticoagulant effect monitored (warfarin dose reduction may be needed). Patient Information Leaflets for miconazole products advise users to tell their doctor or pharmacist if they are taking warfarin.
Up to 13 April 2016, the MHRA has received 146 Yellow Cards that report possible drug interactions between miconazole and warfarin. Most reports (128, 88%) concerned the oral gel form of miconazole. The most frequently reported events were: increased international normalised ratio (INR, 111 reports); contusion (21); haematuria (17); and epistaxis (8). Approximately half of the 146 cases reported an INR increase above 10—ie, the patient was at significantly increased risk of bleeding events (noting that the target INR range for a patient on long-term warfarin therapy is usually between 2 and 3). In 3 cases, a fatal outcome was reported as a result of a haemorrhagic event.
The MHRA is currently reviewing available data for this interaction to determine whether further measures are required to minimise the risks to patients. This review follows a coroner’s report of a death, which may have been partly due to the coadministration of miconazole oral gel and warfarin. Further advice will be communicated as appropriate when the review is complete.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/topical-miconazole-including-oral-gel-reminder-of-potential-for-serious-interactions-with-warfarin
In Hong Kong, there are 93 registered pharmaceutical products containing miconazole, and 18 registered pharmaceutical products containing warfarin. So far, the Department of Health (DH) has not received any adverse drug reaction case resulting from coadministration of topical miconazole and warfarin. In view of the above MHRA announcement, letters to local healthcare professionals to draw their attention to the risk will be issued. As the MHRA is currently reviewing available data for this interaction to determine whether further measures are required, DH will remain vigilant on the conclusion of the evaluation and safety updates by other overseas drug regulatory authorities for consideration of any action deemed necessary.
Ends/ Thursday, June 16, 2016
Issued at HKT 15:00
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