mercaptopurine
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Leucemia aguda, incluida leucemia linfoblástica aguda y leucemia promielocítica aguda/M3, dentro de protocolos combinados especializados.
Contraindicaciones
Absolutas
- Hipersensibilidad; administración concomitante de vacuna contra la fiebre amarilla.
Advertencias clínicas
- Controla hemograma antes de cada ciclo y durante el nadir. Aplaza o modifica el ciclo ante mielosupresión; las infecciones y hemorragias pueden ser graves o mortales. — CIMA/AEMPS, ficha técnica 34565
- Evalúa actividad TPMT y considera genotipado NUDT15 antes de iniciar, pero mantén control hematológico estrecho. Vigila hepatotoxicidad y suspende ante toxicidad hepática clínicamente significativa. — CIMA/AEMPS, ficha técnica 34565
Interacciones medicamentosas
- SeveraAlopurinol, oxipurinol o tiopurinol
Mecanismo: La inhibición de xantina oxidasa aumenta marcadamente la exposición a mercaptopurina.
Recomendación: Reduce mercaptopurina al 25 % de la dosis habitual y ajusta por hemograma.
CIMA/AEMPS, ficha técnica 34565
- SeveraFebuxostat
Mecanismo: Puede aumentar de forma peligrosa la exposición a mercaptopurina.
Recomendación: No se recomienda la administración concomitante.
CIMA/AEMPS, ficha técnica 34565
- SeveraVacunas vivas
Mecanismo: La inmunosupresión puede causar infección vacunal diseminada.
Recomendación: No se recomienda administrar vacunas vivas durante la inmunosupresión.
CIMA/AEMPS, ficha técnica 34565
- SeveraRibavirina
Mecanismo: Puede causar mielosupresión intensa con mercaptopurina.
Recomendación: Evita si es posible o intensifica el control hematológico.
CIMA/AEMPS, ficha técnica 34565
- SeveraWarfarina
Mecanismo: Mercaptopurina puede reducir el efecto anticoagulante.
Recomendación: Controla INR y ajusta warfarina según respuesta.
CIMA/AEMPS, ficha técnica 34565
- SeveraAminosalicilatos (olsalazina, mesalazina o sulfasalazina)
Mecanismo: Pueden inhibir TPMT y aumentar la exposición y toxicidad de mercaptopurina.
Recomendación: Considera una dosis menor de mercaptopurina y refuerza el hemograma.
CIMA/AEMPS, ficha técnica 34565
- SeveraMetotrexato
Mecanismo: Metotrexato aumenta la exposición de mercaptopurina; el aumento descrito de AUC es de aproximadamente 31 % con 20 mg/m² por vía oral, 69 % con 2 g/m² IV y 93 % con 5 g/m² IV.
Recomendación: Ajusta mercaptopurina según el protocolo y vigila los leucocitos muy estrechamente.
CIMA/AEMPS, ficha técnica 34565
- ModeradaFenitoína
Mecanismo: Mercaptopurina puede alterar las concentraciones de fenitoína.
Recomendación: Vigila las concentraciones de fenitoína y el control de las convulsiones.
CIMA/AEMPS, ficha técnica 34565
Embarazo y lactancia
Puede causar daño fetal. Las mujeres y los hombres deben usar anticoncepción eficaz durante el tratamiento y durante 3 meses después. No amamantes.
Bibliografía reciente (PubMed)
The outcome of older patients with B-cell acute lymphocytic leukaemia is inferior to that in younger patients due to the adverse disease biology and their inability to tolerate intensive therapy. We aimed to study the long-term outcomes of inotuzumab ozogamicin with or without blinatumomab in combination with low-intensity chemotherapy in these patients. For this open-label phase 2 trial, patients aged 60 years or older with newly diagnosed, Philadelphia-chromosome negative, B-cell acute lymphocytic leukaemia, and an ECOG performance status of 3 or lower were eligible. This study was conducted at the University of Texas MD Anderson Cancer Center. The induction chemotherapy consisted of mini-hyper-CVD and has been published before; inotuzumab ozogamicin was administered intravenously on day 3 of the first four cycles at a dose of 1·3-1·8 mg/m2 in cycle 1, followed by 1·0-1·3 mg/m2 in subsequent cycles (cycles 2-4). Maintenance therapy with dose-reduced POMP (6-mercaptopurine, vincristine, methotrexate, and prednisone) was given for 3 years. From patient 50 onwards, the study protocol was amended to fractionate inotuzumab ozogamicin to a maximum cumulative dose of 2·7 mg/m2 (0·9 mg/m2 during cycle 1 fractionated into 0·6 mg/m2 on day 2 and 0·3 mg/m2 on day 8 of cycle 1, and 0·6 mg/m2 in cycles 2-4 fractionated into 0·3 mg/m2 on day 2 and 0·3 mg/m2 on day 8) followed by blinatumomab for four cycles (cycles 5-8). POMP maintenance was shortened to 12 cycles with one cycle of blinatumomab administered by continuous infusion after every three cycles of POMP. The primary endpoint was progression-free survival and was analysed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT01371630) and the present data is from the newly diagnosed, older subgroup of patients treated on the phase 2 portion of this trial; the trial is still enrolling patients. Between Nov 11, 2011, and March 31, 2022, 80 patients were enrolled and treated (32 female and 48
Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy. This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy. A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decrease