IJCS | Volume 32, Nº2, March/April 2019

114 Figure 2 - Drug interactions and Time in Therapeutic Range (TTR) of a cohort of warfarin users (n = 68) in Ijui, Brazil. Table 1 - Stratification of vitamin K consumption among warfarin users (n = 68) attending public health centers of Ijui, Brazil Consumption Vitamin K n (%) a Very low 10 (14.7) Low 53 (77.9) Moderate 5 (7.4) Elevated - a number of patients. Colet et al. Adverse events in warfarin users Int J Cardiovasc Sci. 2019;32(2)110-117 Original Article neither followed in an anticoagulation outpatient clinic nor followed for pharmacotherapy, and hence weremore vulnerable to drug interactions. The most cited drugs and drug classes that have the potential to interact with warfarin are antibiotics, 18,19 ant i coagul ant s (hepar i n and enoxapar i n) , 7,17 diuretics (spironolactone), 17 betablockers, 17,20 proton- pump inhibitors, 7,18,21 nonsteroidal inflammatory drugs, 8,17,18,22 serotonin selective reuptake inhibitors, 19 amiodarone, 22 paracetamol, 8,14,19 simvastatin, 7 tramadol, 7 levothyroxine. 21 All these drugs were prescribed and taken by our study group. Many patients who reported bleeding and thromboembolism episodes were exposed to omeprazole, simvastatin and paracetamol. These drugs interact with warfarin by means of competition for the cytochrome P450 metabolism. Nearly 30% of our patients had CYP2C9 polymorphism (data not shown), which would increase the risk for drug interactions. A careful evaluation of risks and benefits would be useful in prescribing simvastatin to anticoagulated patients, due to high severity of the interaction of this drug with warfarin and questionable benefit for patients with low cardiovascular risk. 23 Three patients with low cardiovascular risk were taking simvastatin, who may benefit from simvastatin deprescribing. Deprescribing is the process of discontinuing drugs when existing or potential harms outweigh the benefits, considering patient’s need of treatment, level of functioning, life expectancy, values, and preferences. Deprescribing should be a patient-centered intervention; it is not free of uncertainties, and requires shared decision making, informed patient consent, and close monitoring of effects. 24 With respect to omeprazole, it would be prudent to advise patients about safe limits of its use, since important increases in INR may occur during one to two weeks of initiation of moderate/high doses (2-4 g/day) of omeprazole. 10 For omeprazole users, INR monitoring should be performed, with necessary changes in the dosage, or even discontinuation of treatment, aiming to maintain INR at desirable levels. 10 Similar to simvastatin, the use of both omeprazole 25 and paracetamol 26 have been pointed out as excessive and irrational, emphasizing the need to evaluate the real need for its use.