MERCAPTOPURINE
Clinical safety rating: avoid
Contraindicated (not allowed)
Mercaptopurine is a prodrug that is converted to 6-thioguanine nucleotides, which inhibit de novo purine synthesis and DNA replication by incorporating into DNA and RNA. It also inhibits purine nucleotide interconversions via feedback inhibition of amidophosphoribosyltransferase.
| Metabolism | Hepatic metabolism via xanthine oxidase (XO) to 6-thiouric acid (inactive); also metabolized by thiopurine S-methyltransferase (TPMT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT). |
| Excretion | Renal: 20-30% as unchanged drug; biliary/fecal: minor; extensive hepatic metabolism to active and inactive metabolites. |
| Half-life | Terminal elimination half-life: 1.5-3 hours (variable); for active metabolites (e.g., 6-thioguanine nucleotides) half-life is 5-7 days, which correlates with myelosuppression. |
| Protein binding | Approximately 20-30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.5-1.0 L/kg, indicating distribution into total body water with some tissue binding. |
| Bioavailability | Oral: 5-37% (highly variable, due to first-pass metabolism; mean ~16%). |
| Onset of Action | Oral: 1-2 weeks for therapeutic effect in leukemia; up to 2-3 months for immunosuppression in inflammatory bowel disease. |
| Duration of Action | Duration: variable; myelosuppression may persist for 2-4 weeks after discontinuation due to intracellular metabolites. |
| Molecular Weight | 152.18 |
1.5 to 2.5 mg/kg orally once daily; maintenance 1.5 to 2.5 mg/kg orally once daily.
| Dosage form | SUSPENSION |
| Renal impairment | GFR 50-80 mL/min: reduce dose by 25%; GFR 10-50 mL/min: reduce dose by 50%; GFR <10 mL/min: avoid or reduce dose by 75%. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: avoid use or reduce dose by 50%. |
| Pediatric use | Initial 2.5 mg/kg orally once daily; maintenance 1.5 to 2.5 mg/kg orally once daily; maximum 5 mg/kg/day. |
| Geriatric use | Start at lower end of dosing range (1.5 mg/kg orally once daily) due to potential decreased renal and hepatic function; monitor for myelosuppression. |
| 1st trimester | Use only if clearly needed. Known teratogen in animals; limited human data. Risk of fetal malformations, spontaneous abortion. |
| 2nd trimester | Use only if clearly needed. Potential for fetal growth restriction, prematurity, anemia, immunosuppression. |
| 3rd trimester | Use only if clearly needed. Risk of neonatal myelosuppression, anemia, thrombocytopenia, infection. |
Clinical note
Allopurinol inhibits xanthine oxidase increasing levels of active metabolites leading to severe myelosuppression Myelosuppression is dose-related and requires frequent CBC monitoring.
| Placental transfer | Significant placental transfer documented. Fetal concentrations similar to maternal levels. |
| Breastfeeding | Excreted into breast milk in low concentrations. Use with caution, monitor infant for signs of myelosuppression (anemia, thrombocytopenia, infection). The American Academy of Pediatrics considers it compatible with breastfeeding. |
■ FDA Black Box Warning
Myelosuppression: Mercaptopurine can cause severe bone marrow suppression, including fatal myelosuppression. Monitor blood counts regularly, especially during the first month of therapy. Reduce or discontinue dose if toxicity occurs.
| Common Effects | Myelosuppression |
| Serious Effects |
Hypersensitivity to mercaptopurine or any componentPrior resistance to mercaptopurine or thioguanineSevere hepatic impairmentSevere myelosuppression (unless due to malignancy)Concurrent therapy with allopurinol (unless dose adjusted)
| Precautions | Myelosuppression (particularly leukopenia, thrombocytopenia, anemia), hepatotoxicity (elevated liver enzymes, jaundice, hepatic necrosis), increased risk of infection, pancreatitis, hypersensitivity reactions, immunosuppression-related malignancies (e.g., lymphoma), interaction with allopurinol (reduce mercaptopurine dose by 65-75%), TPMT deficiency (increased toxicity, consider genotyping). |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: Associated with congenital malformations including cleft palate, skeletal anomalies, and myelosuppression. Second/third trimesters: Risk of fetal growth restriction, premature birth, and neonatal immunosuppression. |
| Fetal Monitoring | Maternal: Complete blood count weekly, liver function tests, creatinine, uric acid. Fetal: Serial ultrasound for growth and anatomy, fetal echocardiogram at 18-22 weeks. |
| Fertility Effects | May cause reversible oligospermia or azoospermia in males and menstrual irregularities or ovarian failure in females. Dose-dependent. |
| Food/Dietary |
| Avoid raw or undercooked foods to reduce infection risk. No specific food-drug interactions; maintain adequate hydration. |
| Clinical Pearls | Monitor CBC and LFTs weekly during induction, then monthly. Check TPMT genotype before initiation to predict toxicity. Avoid allopurinol unless dose reduced by 65-75% due to severe myelosuppression risk. Use with caution in pregnancy (category D). |
| Patient Advice | Take exactly as prescribed; do not stop or change dose without consulting doctor. · Avoid live vaccines (e.g., MMR, varicella) during treatment. · Report any signs of infection (fever, sore throat), unexplained bruising/bleeding, jaundice, or dark urine immediately. · Do not take allopurinol or other medications without doctor approval. · Use effective contraception during therapy and for at least 3 months after stopping. |