Mercaptopurine
6-mercaptopurine
Also known as: Purinethol · Flocofil · Ismipur · Mercaptina · Puri-Nethol · Varimer · 6-mercaptopurine · 6-MP · 6MP · mercaptopurinum · NSC-755 · purinethiol · WR-2785
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| As an immunosuppressant in combination with corticosteroids for treating bullous pemphigoid | 2.2 mg/kg | PO | once daily (q24h), then q48h | — | 🌎 NA |
| For erosive, immune-mediated polyarthritis in combination with corticosteroids | 2 mg/kg | PO | once daily (q24h) for 14-21 days, then q48h (every other day) | 14-21 days initially | 🌎 NA |
| For treatment of immune-mediated diseases or acute lymphocytic and granulocytic leukemias | 50 mg/m2 | PO | once daily (q24h) to effect, then every other day (q48h) or as needed | — | 🌎 NA |
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Mercaptopurine (6-MP) is a thiopurine antineoplastic and immunosuppressive agent.
Clinical Pearls & Pharmacology:
- It is closely related to azathioprine, which is actually a prodrug that is rapidly converted to mercaptopurine in the body.
- While rarely used as a first-line agent in veterinary medicine, it serves as a valuable adjunctive therapy for lymphosarcoma, acute leukemias, and severe immune-mediated diseases such as rheumatoid arthritis or refractory autoimmune conditions (e.g., unresponsive ulcerative colitis/inflammatory bowel disease).
- Because it is a cytotoxic agent, it requires careful handling and rigorous patient monitoring for bone marrow suppression and hepatotoxicity.
Mechanism of action
Mercaptopurine is an inactive prodrug that requires intracellular activation to exert its cytotoxic and immunosuppressive effects.
- Mercaptopurine enters the cell and is converted by the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) → thioinosinic acid (TIMP).
- TIMP acts as a purine antagonist, inhibiting multiple enzymes required for de novo purine synthesis.
- False nucleotides are incorporated into DNA and RNA → inhibition of nucleic acid synthesis → cell cycle arrest and apoptosis.
- It primarily affects rapidly dividing cells, strongly inhibiting humoral immunity (B-cell function) and, to a lesser extent, cell-mediated immunity.
Safety & warnings
Contraindications
- Hypersensitivity to mercaptopurine
- Pregnancy (teratogenic and mutagenic)
Adverse effects
- Nausea
- Anorexia
- Vomiting
- Diarrhea
- Bone marrow suppression (leukopenia, thrombocytopenia, anemia)
- Hepatotoxicity
- Pancreatitis
- Gastrointestinal ulceration (including oral ulcers)
- Dermatologic reactions
Precautions
Risk vs. Benefit Warning: Use with extreme caution in patients with pre-existing hepatic dysfunction, bone marrow depression, active infections, renal function impairment (dosage adjustment required), or a history of urate urinary stones.
- Teratogenicity: Mercaptopurine is mutagenic and teratogenic (FDA Category D). Do not use in pregnant animals unless the benefit strictly outweighs the risk.
- Nursing: Unknown if excreted in milk; use milk replacer for nursing bitches or queens.
- Laboratory Interference: May cause falsely elevated serum glucose and uric acid values on SMA 12/60 analyzers.
Drug interactions
Decreases hepatic metabolism of mercaptopurine via xanthine oxidase inhibition. Dose of mercaptopurine must be drastically reduced (to 1/4-1/3 of usual dose) if used concurrently.
May increase the risk for mercaptopurine toxicity.
Increased risk of hepatotoxicity; use cautiously together.
Increased risk of severe infection due to additive immunosuppression.
Additive bone marrow depression; use with extreme caution.
Increased risk of vaccine-induced infection; use with caution or avoid during therapy.
Mercaptopurine may reduce the anticoagulant effect of warfarin.
Monitoring
- Hemograms (including platelets): Monitor closely; initially every 1-2 weeks, then every 1-2 months on maintenance therapy. (Note: If WBC drops to 5,000-7,000 cells/mm3, consider reducing dose by 25%. If WBC drops below 5,000 cells/mm3, discontinue until leukopenia resolves).
- Liver function tests (ALT, AST, ALP, Bilirubin)
- Serum amylase (if pancreatitis is suspected)
- Clinical efficacy and signs of toxicity
Pharmacokinetics
Absorption
Variable and incomplete after oral dosing.
Distribution
Distributed throughout total body water. Crosses the blood-brain barrier, but not in levels significant enough to treat CNS neoplasms. Unknown if it enters milk.
Metabolism
Rapidly metabolized in the liver via the enzyme xanthine oxidase to 6-thiouric acid.
Elimination
Principally excreted in the urine as the parent compound and metabolites.
Overdose
Toxicity may present acutely (severe GI effects like vomiting and diarrhea) or be delayed (bone marrow depression, hepatotoxicity, gastroenteritis).
- Treatment: If ingestion was recent, use standard protocols to empty the GI tract (emesis, activated charcoal). Provide aggressive supportive care (IV fluids, antiemetics, broad-spectrum antibiotics if neutropenic, and potentially blood transfusions for severe myelosuppression).
Available products
Formulations
- Tablets
Human-labeled
- Mercaptopurine Tablets: 50 mg; Purinethol® (Gate Pharmaceuticals); generic (Par)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store tablets at room temperature in well-closed containers.
Client information
- Safe Handling: This is a potent immunosuppressive and anti-cancer drug. Wash your hands thoroughly after administering the tablets. Pregnant women or immunocompromised individuals should avoid handling this medication.
- Watch for Toxicity: Contact your veterinarian immediately if your pet exhibits signs of abnormal bleeding, bruising, loss of appetite, vomiting, diarrhea, or signs of infection (such as fever or extreme lethargy).
- Strict Monitoring: Your pet will require frequent blood tests to ensure the drug is not damaging their bone marrow or liver. Do not skip these appointments.
- Long-term Risks: Be aware that long-term use of immunosuppressants carries a risk of severe toxicity, including an increased susceptibility to infections or the development of secondary cancers.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.