Drug-Drug Interaction of Direct Oral Anticoagulants in Geriatric Patients

Relevance. Recently there has been an increase in the population of older people suffering from cardiovascular diseases. At the same time, the need to prescribe effective anticoagulation therapy to prevent thromboembolic complications also increases. Oral anticoagulants (DOACs) are one of the main methods of treatment for such patients; however, this group is characterized by polypharmacy and polymorbidity, which increases the risk of developing drug interactions when using them. Thus, it is necessary to take into account the possible risks of developing side effects of drugs when using DOACs.

Aim to study drug interactions of direct oral anticoagulants in geriatric patients.

Materials and methods. The study was conducted on the basis of the War Veterans Hospital No. 2 of the Moscow City Health Department in the 2nd, 4th, 5th geriatric departments. The study included patients aged 65 and over with chronic kidney disease (CKD) 3B and receiving one of the DOACs (Rivaroxaban (R), Dabigatran etexilate (D), Apixaban (A)). The patients were divided into 3 groups. The sample was made of 109 patients during the hospitalization period from May to June 2023.

Results. 69 patients were enrolled for analysis, the mean age was 81.4 years ingroup P, A and 75.6 years in-group D, 26 men and 40 women. CKD stage 2 — 26, 3A st. — 23, 3B st. 15 patients respectively. The duration of therapy was up to 1 year — 9, from 1 year to 5 years — 44 and from 5 to 10 years — 5 patients. Complications during therapy were noted in five cases in the P, A — epistaxis group. All patients were prescribed an average of 12.04 drugs from various drug groups. The smallest group D was younger in age compared to groups Pand A, this is due to the criterion creatinine clearance, which for D is 30 ml/min and requires cancellation, while for P, A this criterion is 15 ml/min. P and A are metabolized by CYP3A4, and D by glucuronidation enzymes UGT2B15, UGT1A9, UGT2B7, as well as with the participation of P-glycoprotein. Among the drugs used, the following drug interactions were identified: inducer carbamazepine and inhibitors verapamil, amiodarone, dexamethasone, diltiazem, clotrimazole, metronidazole, spironalactone.

Conclusions in older patients, it is necessary to evaluate age, glomerular filtration rate, and duration of DOAC use. When using DOACs, interactions between drugs that are metabolized by cytochrome CYP3A4 and P-glycoprotein should be assessed, which may result in decreased or increased drug concentrations (inducer/inhibitor) and increase the risk of side effects. One of the typical adverse reactions is epistaxis.