mercaptopurine
Regulatory sources consulted
Approved indications
- Acute leukemia, including acute lymphoblastic leukemia and acute promyelocytic/M3 leukemia, within specialized combination protocols.
Contraindications
Absolute
- Hypersensitivity; concomitant yellow-fever vaccine.
Clinical warnings
- Monitor blood counts before each cycle and through the nadir. Delay or modify the cycle for myelosuppression; infections and bleeding may be severe or fatal. — CIMA/AEMPS, ficha técnica 34565
- Assess TPMT activity and consider NUDT15 genotyping before treatment, while maintaining close blood-count monitoring. Monitor hepatotoxicity and discontinue for clinically significant liver toxicity. — CIMA/AEMPS, ficha técnica 34565
Drug interactions
- HighAllopurinol, oxipurinol, or thiopurinol
Mechanism: Xanthine-oxidase inhibition markedly increases mercaptopurine exposure.
Recommendation: Reduce mercaptopurine to 25% of the usual dose and adjust by blood counts.
CIMA/AEMPS, ficha técnica 34565
- HighFebuxostat
Mechanism: It may dangerously increase mercaptopurine exposure.
Recommendation: Concomitant administration is not recommended.
CIMA/AEMPS, ficha técnica 34565
- HighLive vaccines
Mechanism: Immunosuppression may cause disseminated vaccine infection.
Recommendation: Live vaccines are not recommended during immunosuppression.
CIMA/AEMPS, ficha técnica 34565
- HighRibavirin
Mechanism: It may cause profound myelosuppression with mercaptopurine.
Recommendation: Avoid when possible or intensify hematologic monitoring.
CIMA/AEMPS, ficha técnica 34565
- HighWarfarin
Mechanism: Mercaptopurine may reduce the anticoagulant effect.
Recommendation: Monitor INR and adjust warfarin according to response.
CIMA/AEMPS, ficha técnica 34565
- HighAminosalicylates (olsalazine, mesalazine, or sulfasalazine)
Mechanism: They may inhibit TPMT and increase mercaptopurine exposure and toxicity.
Recommendation: Consider a lower mercaptopurine dose and intensify blood-count monitoring.
CIMA/AEMPS, ficha técnica 34565
- HighMethotrexate
Mechanism: Methotrexate increases mercaptopurine exposure; the reported AUC increase is about 31% with 20 mg/m² orally, 69% with 2 g/m² IV, and 93% with 5 g/m² IV.
Recommendation: Adjust mercaptopurine according to protocol and monitor leukocytes very closely.
CIMA/AEMPS, ficha técnica 34565
- ModeratePhenytoin
Mechanism: Mercaptopurine may alter phenytoin concentrations.
Recommendation: Monitor phenytoin concentrations and seizure control.
CIMA/AEMPS, ficha técnica 34565
Pregnancy and lactation
It may cause fetal harm. Women and men must use effective contraception during treatment and for 3 months afterward. Do not breastfeed.
Recent literature (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