MERCAPTOPURINE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Allopurinol inhibits xanthine oxidase increasing levels of active metabolites leading to severe myelosuppression Myelosuppression is dose-related and requires frequent CBC monitoring.

Breastfeeding	Contraindicated due to potential for neonatal immunosuppression and unknown M/P ratio. Use alternative therapy.
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

Warnings & precautions

■ 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.

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

Hypersensitivity to mercaptopurine, severe leukopenia or thrombocytopenia, severe hepatic impairment, pregnancy (especially first trimester - teratogenic; use only if benefit outweighs risk), lactation (discontinue nursing or drug).

Clinical Precautions

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).

Clinical Tips & Counseling

Drug interactions

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