| Pharmacogenetics of warfarin |
Pharmacogenetics is genetic testing to optimise prescribing for individual patients. Warfarin is a potential candidate for pharmacogenetic testing as it is commonly used, has a narrow therapeutic window and its mechanism of action and elimination pathways involve receptors and enzymes that are polymorphic. Polymorphism is found in vitamin K epoxide reductase and cytochrome P450 2C9. Pharmacogenetic testing is not yet routine because alone it does not predict all the variability in a patient's response to warfarin so its contribution to improved clinical outcomes is uncertain.
Key words:anticoagulation, cytochrome P450 system, vitamin K.
(Aust Prescr 2009;32:80)
The international normalised ratio (INR) is a simple test commonly used by dentists to gauge the likelihood that a patient taking warfarin will have excessive haemorrhage following tooth extraction. There is a clearly defined range of INR values within which simple local post-extraction measures, such as suturing, pressure and tranexamic acid mouth rinses, are adequate to control bleeding. Patients within this range can continue warfarin.1
The large variation in INR values, related to genetic and dietary factors, particularly the intake of vitamin K, reinforces the need to have this test undertaken shortly before the dental procedure.
The metabolism of warfarin can be reduced by azole antifungals such as miconazole. Topical oral miconazole can profoundly increase the INR and thus the risk of bleeding due to overanticoagulation.2,3 Similarly metronidazole, which is commonly used in the management of oral infections, can greatly increase the INR. Dentists therefore need to review patients' current medication before prescribing any drugs, even those topically applied, for possible interactions with warfarin.
References
- Therapeutic Guidelines: Oral and Dental. Version 1. Melbourne:Therapeutic Guidelines Limited; 2007.
- Pemberton MN, Oliver RJ, Theaker ED. Miconazole oral gel and drug interactions. Br Dent J 2004;196:529-31.
- Morgan L. Topical drug with systemic risk. Aust Prescr 2003;26:35.
