Estudio observacional prospectivo sobre interacciones medicamentosas en pacientes onco-hematológicos

Resumo

The knowledge and a suitable management of drug interactions improve the quality, safety and efficiency of treatments administered to patients. Objectives: 1. To determine the prevalence of potential drug-drug interactions (DDIs) in treatments from onco-haematological inpatients, distinguishing three population groups (paediatric patients, oncological adult patients and haematological adult patients). Two databases were used, Micromedex¿ and Drug Interaction Facts¿ (DIF¿). 2. To determine the incidence density of potential DDIs in treatments from onco-haematological patients in the same population groups. 3. To describe the characteristics of patients, treatments and detected potential DDIs. 4. To determine the risk factors associated with the presence of both total and clinically relevant DDIs by each population group and database. 5. To compare the agreement between both databases regarding to identified potential DDIs and their severity rating. 6. To describe the most frequent clinically relevant DDIs and to propose pharmacological alternatives or risk reduction strategies. Methodology: A prospective, observational and descriptive study was carried out during a 12 weeks period, to detect potential DDIs in medical treatments from onco-haematological inpatients, both adults and children, regardless antineoplastic treatment were administered to patients. Apart from treatment sheets, demographical, clinical and analytical data were recorded. Each medication list was screened through Micromedex¿ and DIF¿. All identified potential DDIs were recorded and graded by their level of severity and scientific evidence, with a description of the pharmacological mechanism and their effects. Any DDI detected by each database was considered a potential DDI. A clinically relevant DDI (CR-DDI) was defined according to the level of severity irrespective to the scientific evidence: " For Micromedex¿ database, those DDIs classified as contraindicated, major and moderate. " For DIF¿, those DDIs classified as major and moderate. A descriptive analysis, both quantitative and qualitative, of demographical, clinical and analytical data was carried out. A list of prescribed drugs and both total and clinically relevant identified DDIs by each database was executed too. Logistic and linear regression models were used to identify risk factors associated with DDIs, well as probability of DDI occurrence (presence/absence), well as to obtain an equation that determine the number of potential DDIs according to associated risk factors. When comparing both databases, and in the context of commonly detected DDIs, kappa statistic was used to evaluate the agreement between their assigned severity ratings. Results: A total of 1,166 treatment sheets, belonging to 341 patients, were analysed. The total number of identified DDIs was 3,155 by Micromedex¿ and 1,989 by DIF¿. Results for the main objectives were described as follows: " Oncology Department: prevalence of medical orders with any potential DDI was 81.69% and 48.21% by Micromedex¿ and DIF¿ respectively; and prevalence of treatments with any potential CR-DDI was 80.97% and 32.62%, respectively. Mean incidence density considering all potential DDIs was 222.77 and 102.08 DDI per 100 treatments-day; regarding to CR-DDIs, 218.63 and 61.72 DDIs per 100 treatments-day, respectively. " Haematology Department: prevalence of medical orders with any potential DDI was 74.45% and 69.40% by Micromedex¿ and DIF¿ respectively; and prevalence of treatments with any potential CR-DDI was 74.13% and 56.78%, respectively. Mean incidence density considering all potential DDIs was 437.28 and 331.95 DDIs per 100 treatments-day; regarding to CR-DDIs, 428.51 and 240.53 DDIs per 100 treatments-day, respectively. " Onco-haematological Paediatric Section: prevalence of medical orders with any potential DDI was 56.67% and 58.00% by Micromedex¿ and DIF¿ respectively; and prevalence of treatments with any potential CR-DDI was 44.67% and 51.33%, respectively. Mean incidence density considering all potential DDIs was 155.70 and 153.82 DDIs per 100 treatments-day; regarding to CR-DDIs, 121.04 and 118.12 DDIs per 100 treatments-day, respectively. Globally, the main risk factor associated with the presence of DDIs was the drugs number, sometimes as total prescribed drugs, others as non-antineoplastic drugs, or even both. Several differences were observed when comparing both databases, such as the ability to detect any potential DDI finding a weak congruence (k=0.372 by total DDIs and k=0.253 regarding to CR-DDIs; p<0.0001 in both instances), or analyzing the reliability of severity ratings in the context of commonly detected DDIs by both databases, finding a null congruence (k=-0.062; p<0.002). Given their potential severity and frequency, we would like to highlight the following DDIs: combinations of central nervous system depressants; increased risk of extrapyramidal reactions when antiemetics are associated; serotoninergic syndrome when 2 serotoninergic agents are co-administered; QT interval prolongation, especially if some drugs are combined, such as azole antifungals, 5-HT3 antagonists, antipsychotics, fluoroquinolones and tricyclic antidepressants; and an increase or a decrease in serum concentrations of immunosuppressant agents. Conclusions: Prevalence and incidence density of DDIs were elevated, considering both databases and all three population groups. There are important differences between databases, so the congruence of severity ratings was low. This fact makes difficult a proposal based on alternative drugs and the establishment of risk reduction strategies.