ORIGINAL ARTICLE Drug-to-drug interactions of tyrosine kinase inhibitors in chronic myeloid leukemia patients. Is it a real problem? Santiago Osorio 1,2 & Vicente Escudero-Vilaplana 2,3 & Ignacio Gómez-Centurión 1,2 & Raúl Pérez-López 4 & Rosa Ayala 5 & Ferrán Vall-Llovera 6 & Valentín García-Gutierrez 7 & María Teresa Gómez Casares 8 & José David González San Miguel 9 & José-Ángel Hernández-Rivas 10 & Fermín Sánchez-Guijo 11 & Ana Belén Martínez-García 12 & Lucia Villalón 13 & Venancio Conesa-García 14 & Alicia Rodriguez 15 & Felipe Casado 16 & Xandra Garcia-Gonzalez 2,3 & María Nieves Sáez Perdomo 8 & Úrsula Baños 15 & Juan Luis Steegmann 17 & On behalf of the CML Spanish Group (GELMC) Received: 8 April 2018 /Accepted: 20 June 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract 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. * Santiago Osorio sanosorio2000@gmail.com 1 Servicio de Hematología, Hospital General Universitario Gregorio Marañón, Madrid, Spain 2 Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain 3 Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Madrid, Spain 4 Servicio de Hematología, Hospital Universitario Clínico Virgen de la Arrixaca, Murcia, Spain 5 Servicio de Hematología, Hospital Universitario 12 de Octubre, Madrid, Spain 6 Servicio de Hematología, Hospital Universitari Mútua Terrassa, Terrassa, Spain 7 Servicio de Hematología, Hospital Universitario Ramón y Cajal, Madrid, Spain 8 Servicio de Hematología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain 9 Servicio de Hematología, Complejo Hospitalario Universitario Insular Materno Infantil de Canarias, Las Palmas de Gran Canaria, Spain 10 Servicio de Hematología, Hospital Universitario Infanta Leonor, Madrid, Spain 11 Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain 12 Servicio de Hematología, Hospital General Universitario Santa Lucía, Cartagena, Murcia, Spain 13 Servicio de Hematología, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain 14 Servicio de Hematología, Hospital General Universitario de Elche, Elche, Alicante, Spain 15 Servicio de Hematología, Hospital Universitario Virgen Macarena, Sevilla, Spain 16 Servicio de Hematología, Hospital Virgen de la Salud, Toledo, Spain 17 Servicio de Hematología, Hospital Universitario de la Princesa, Madrid, Spain Annals of Hematology https://doi.org/10.1007/s00277-018-3413-7