Drug-to-drug interactions of tyrosine kinase inhibitors in chronic myeloid leukemia patients. Is it a real problem?

With tyrosine kinase inhibitors (TKI), chronic myeloid leukemia (CML) patients are achieving similar rates of survival to the general population and some treatment aspects such as adherence and drug-to-drug interactions (DDI) are becoming increasingly important. Our aim was to investigate the frequency and real clinical consequences of DDI between TKI and concurrent medications in CML. We performed a retrospective multicenter study including 105 patients receiving 134 TKI treatments. Sixty-three patients (60%) had at least one potential DDI. The mean number of concomitant medications was 4.8 (0-19). The mean number of DDI by TKI treatment was 1.2 (0-8); it increased with the number of concomitant medications and age in a significant manner. A total of 159 DDI were detected, involving 55 different drugs. The most common drug classes involved were proton pump inhibitors, statins, and antidepressants. A DDI-related clinical effect (toxicity and/or lack of efficacy) was suspected during the common course of patient follow-up in only five patients (4.7%). This number increased to 20% when data were centrally reviewed. Most of the adverse events (AE) attributed to DDIs were mild. The most common were diarrhea, vomiting, edema, cramps, and transaminitis. Nilotinib and dasatinib showed a tendency towards a higher risk of DDI compared with imatinib. There were no significant differences in AE frequency or in treatment response between patients with or without DDI. Due to their frequency, and their potential to cause clinically relevant effects, DDI are an important aspect of CML management.

Adherence to antiemetic guidelines and control of chemotherapy-induced nausea and vomiting (CINV) in a large hospital.

PURPOSE: The aim of the study was to determine the antiemetic prescription adherence both to the protocol of our hospital and to international recommendations, as well as to analyze the relationship between this adherence and the incidence of nausea and vomiting (NV) and between the adherence and patients' individual risk. METHODS: This is a four-month observational study which included antiemetic prescriptions for adult cancer patients. Prescriptions were considered adherent or not to hospital protocol and also to international guidelines. Patients were given a form to record the NV they suffered and this was to be returned at their next appointment. RESULTS: A total of 102 prescriptions were analyzed. Taking into account the hospital protocol, 59% and 54% were correct (acute and delayed phase, respectively). Of those considered outside the protocol, 24% and 13% did follow international guidelines. In the delayed phase, complete response was achieved in 76% and 72% of the patients, with compliant and non-compliant prescriptions, respectively (82% and 90% in the acute phase). Adherence to the hospital protocol was higher in patients under 50 years old (p = 0.015) and in those without previous experience of NV (p = 0.010). Adherence to international guidelines was higher in female patients (p = 0.023). CONCLUSION: Our study confirms low adherence with both local and international recommendations for antiemetic prescriptions. However, we could not prove that adherence involves a CINV reduction. Adherence did not seem to be influenced by the doctor's perception of the patient's risk of emesis.

Influence of pharmaceutical care on the delayed emesis associated with chemotherapy.

BACKGROUND: Complete control of emesis during chemotherapy remains to be achieved. This could be improved by increasing adherence to medicines and recommendations. OBJECTIVE: The aim of this study was to analyse the effects of pharmaceutical care on the incidence of delayed chemotherapy-induced nausea and vomiting (CINV) in adult cancer outpatients. METHOD: This is a longitudinal prospective intervention study. Patients included were those who received a new cancer intravenous treatment. We compared complete response (no vomiting and no rescue treatment) and the incidence of nausea in the control group (CG) and in the intervention group (IG), as well as patients' adherence. Pharmaceutical intervention consisted of: reviewing the antiemetic protocol and giving some recommendations to the patients. RESULTS: 102 patients were studied. In the delayed phase complete response was achieved in 84.8 % of the patients in the IG, compared with 69.6 % in the control group [absolute risk reduction (ARR), 15.2 %; p = 0.144]. Regarding absence of vomiting, the difference was higher (71.0 CG vs 97.0 % IG, ARR, 26.0%; p = 0.002). Absence of delayed nausea were also better in the IG (61 vs. 52 %). Compliant patients increased from 59 to 76 %. CONCLUSION: The intervention of a pharmacist reduced the incidence of delayed CINV and improved medication adherence.