In addition, they have been shown to reduce the risk of death, recurrent myocardial infarction and thromboembolic events such as stroke [2]. Despite their benefits and widespread use, many challenges are faced when using warfarin. These include variable inter-patient

warfarin dose response due to age, co-morbidities, liver function, albumin level, genetic polymorphism in enzymes, and numerous drug-drug/drug-diet interactions [1, 3–5]. Consequently, close monitoring using the international normalized ratio (INR) and patient specific dosing must be applied when utilizing warfarin [5]. Because https://www.selleckchem.com/products/AC-220.html of its pharmacokinetic and metabolic profile, warfarin is prone to having drug-drug interactions affecting the intensity of monitoring and clinical efficacy. Warfarin is a racemic mixture of both R and S enantiomers. The enantiomers differ in that R-warfarin is less potent and has a longer half-life when compared to S-warfarin. In addition, R-warfarin is metabolized by the enzymes cytochrome P450 (CYP) 1A2 and CYP 3A4, whereas BIX 1294 molecular weight S-warfarin is metabolized by CYP 2C9 [6]. It is noted that rifampicin is a potent and nonspecific inducer of the hepatic CYP450 oxidative enzyme system. Although it is recognized that

rifampicin causes marked enzyme induction of CYP 3A4, it is still considered to have an enhanced effect on the metabolism of both enantiomers [7]. Importantly, the accelerated clearance can lead to compromised efficacy and reduced anticoagulant effects of warfarin [8]. The clinically significant alterations in the INR can create the need for more intense monitoring and large warfarin dose adjustments. Currently, only seven case reports have been published describing the interaction between warfarin and rifampicin, all of which come from the developed world where tuberculosis (TB) rates are much lower [5, 9–14]. Due to its efficacy and relative affordability, rifampicin is part of the first line regimen for treatment of TB [15]. With an increased prevalence of TB Resveratrol in developing countries, it is likely that there is increased use of rifampicin,

and thus, more concern for the potential drug–drug interactions with warfarin in these settings. According to a study carried out on the global burden of TB, 10 of the 22 countries with the highest incidence rates per capita of TB are in Africa. In the same report, Kenya is ranked 15th in the list of 22 high-burden TB countries, with an incidence of 288 per 100,000 population [16]. The Kenya National Leprosy and TB Treatment Guidelines (2009) recommend the use of rifampicin, isoniazid, ethambutol and pyrazinamide as first line therapy for 2 months, followed by 4 months of rifampicin and isoniazid. In Kenya, all TB medications in the standard medication regimen are provided for free by the ministry of health in the form of fixed dose combinations.