mercaptopurine
Sources réglementaires consultées
Indications approuvées
- Leucémie aiguë, notamment leucémie aiguë lymphoblastique et leucémie aiguë promyélocytaire/M3, dans des protocoles spécialisés en association.
Contre-indications
Absolues
- Hypersensibilité ; vaccin antiamaril concomitant.
Mises en garde cliniques
- Surveiller la numération avant chaque cycle et pendant le nadir. Différer ou modifier le cycle en cas de myélosuppression ; les infections et hémorragies peuvent être graves ou mortelles. — CIMA/AEMPS, ficha técnica 34565
- Évaluer l’activité TPMT et envisager le génotypage NUDT15 avant le traitement, tout en maintenant une surveillance hématologique étroite. Surveiller l’hépatotoxicité et arrêter en cas de toxicité hépatique cliniquement significative. — CIMA/AEMPS, ficha técnica 34565
Interactions médicamenteuses
- SévèreAllopurinol, oxipurinol ou thiopurinol
Mécanisme: L’inhibition de la xanthine oxydase augmente fortement l’exposition à la mercaptopurine.
Recommandation: Réduire la mercaptopurine à 25 % de la dose habituelle et ajuster selon la numération.
CIMA/AEMPS, ficha técnica 34565
- SévèreFébuxostat
Mécanisme: Peut augmenter dangereusement l’exposition à la mercaptopurine.
Recommandation: L’administration concomitante n’est pas recommandée.
CIMA/AEMPS, ficha técnica 34565
- SévèreVaccins vivants
Mécanisme: L’immunosuppression peut provoquer une infection vaccinale disséminée.
Recommandation: Les vaccins vivants ne sont pas recommandés pendant l’immunosuppression.
CIMA/AEMPS, ficha técnica 34565
- SévèreRibavirine
Mécanisme: Peut provoquer une myélosuppression intense avec la mercaptopurine.
Recommandation: Éviter si possible ou renforcer la surveillance hématologique.
CIMA/AEMPS, ficha técnica 34565
- SévèreWarfarine
Mécanisme: La mercaptopurine peut réduire l’effet anticoagulant.
Recommandation: Surveiller l’INR et ajuster la warfarine selon la réponse.
CIMA/AEMPS, ficha técnica 34565
- SévèreAminosalicylés (olsalazine, mésalazine ou sulfasalazine)
Mécanisme: Ils peuvent inhiber la TPMT et augmenter l’exposition et la toxicité de la mercaptopurine.
Recommandation: Envisager une dose plus faible de mercaptopurine et renforcer la surveillance de la numération.
CIMA/AEMPS, ficha técnica 34565
- SévèreMéthotrexate
Mécanisme: Le méthotrexate augmente l’exposition à la mercaptopurine ; l’augmentation rapportée de l’ASC est d’environ 31 % avec 20 mg/m² par voie orale, 69 % avec 2 g/m² IV et 93 % avec 5 g/m² IV.
Recommandation: Ajuster la mercaptopurine selon le protocole et surveiller très étroitement les leucocytes.
CIMA/AEMPS, ficha técnica 34565
- ModéréePhénytoïne
Mécanisme: La mercaptopurine peut modifier les concentrations de phénytoïne.
Recommandation: Surveiller les concentrations de phénytoïne et le contrôle des crises.
CIMA/AEMPS, ficha técnica 34565
Grossesse et allaitement
Peut provoquer une atteinte fœtale. Les femmes et les hommes doivent utiliser une contraception efficace pendant le traitement et pendant 3 mois après. Ne pas allaiter.
Bibliographie récente (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