mercaptopurine (6-MP)
Purinethol

Available forms
Available by prescription only
Tablets (scored): 50 mg

Indications and dosages
  Dosages and indications may vary. Check current literature for recommended protocols.
 Acute lymphoblastic leukemia (in children), chronic myelocytic leukemia. Adults: 2.5 mg/kg P.O. daily as a single dose, increased to 5 mg/kg daily (only if, after 4 weeks, there’s no clinical improvement or signs of toxicity). Or, 80 to 100 mg/m² daily. Maintenance dose is 1.5 to 2.5 mg/kg daily.
Children: 2.5 mg/kg P.O. daily. Or, 70 mg/m² daily. Maintenance dose is 1.5 to 2.5 mg/kg daily.
 Acute myeloblastic leukemia. Adults: 500 mg/m² daily P.O. in combination with other therapies.

Pharmacodynamics
Antineoplastic action: Mercaptopurine is converted intracellularly to its active form, which exerts its cytotoxic antimetabolic effects by competing for an enzyme required for purine synthesis. This results in inhibition of DNA and RNA synthesis. Cross-resistance exists between mercaptopurine and thioguanine.

Pharmacokinetics
Absorption: Absorption is incomplete and variable; about 50% of a dose is absorbed.
Distribution: Distributes widely into total body water. Drug crosses the blood-brain barrier, but the CSF level is too low for treatment of meningeal leukemias.
Metabolism: Extensively metabolized in the liver. It appears to undergo extensive first-pass metabolism, contributing to its low bioavailability.
Excretion: Excreted in urine.

Contraindications and precautions
Contraindicated in patients whose disease has shown resistance to drug. Use cautiously in pregnant patients, patients with depressed neutrophil or platelet counts after chemotherapy or radiation therapy, and patients with impaired renal or hepatic function.

Interactions
Drug-drug. Allopurinol at doses of 300 to 600 mg daily: Increases toxic effects of mercaptopurine, especially myelosuppression. Reduce dosage by 25% to 30% when giving with allopurinol.
Co-trimoxazole: Enhances marrow suppression. Use together cautiously.
Hepatotoxic drugs: Increases potential for hepatotoxicity. Use together cautiously.
Warfarin: Decreases anticoagulant activity of warfarin. Monitor PT and INR.

Adverse reactions
GI: nausea, vomiting, anorexia, painful oral ulcers, diarrhea, pancreatitis, GI ulceration.
Hematologic: leukopenia, thrombocytopenia, anemia.
Hepatic: jaundice, hepatotoxicity.
Metabolic: hyperuricemia.
Skin: rash, hyperpigmentation.

Effects on lab test results
• May increase uric acid levels.
• May decrease hemoglobin and WBC, RBC, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include myelosuppression, nausea, vomiting, and hepatic necrosis.
 Treatment is usually supportive and includes transfusion of blood components and antiemetics. Hemodialysis is thought to be of marginal use because of the rapid intracellular incorporation of mercaptopurine into active metabolites with long persistence.

Special considerations
• Investigational uses include prevention of rejection of homografts, treatment of various autoimmune diseases, treatment of Crohn’s disease, and treatment of chronic active hepatitis.
• Drug is sometimes called 6-mercaptopurine or 6-MP.
• Dose modifications may be required following chemotherapy or radiation therapy or if patient has depressed neutrophil or platelet counts or impaired hepatic or renal function.
• Hepatic dysfunction is reversible when drug is stopped. Watch for jaundice, clay-colored stools, and frothy dark urine, and stop drug if hepatic tenderness occurs. Monitor hepatic function during start of therapy.
• Avoid all I.M. injections when platelet count is less than 100,000/mm³.
• Monitor weekly blood counts; watch for precipitous decline. Hematologic adverse effects may persist for several days after the drug is discontinued.
• Monitor intake and output. Encourage patient to drink about 3 quarts (3 L) of fluid per day.
• Monitor hepatic function and hematologic values weekly during therapy.
• Monitor serum uric acid levels. If allopurinol is needed, use very cautiously.
• Observe patient for signs of bleeding and infection.
• Drug may also cause falsely elevated serum glucose and uric acid values when sequential multiple analyzer is used.
• Store tablets at room temperature and protect from light.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. However, because of the potential for serious adverse reactions, mutagenicity, and carcinogenicity in the infant, breast-feeding isn’t recommended.
Pediatric patients
• Adverse GI reactions are less common in children than in adults.

Patient education
• Warn patient that improvement may take 2 to 4 weeks or longer.
• Tell patient to continue drug despite nausea and vomiting.
• Instruct patient to immediately report vomiting that occurs shortly after taking a dose.
• Warn patient to avoid alcoholic beverages while taking drug.
• Urge patient to ensure adequate fluid intake to increase urine output and facilitate the excretion of uric acid.
• Advise patient to avoid exposure to people with infections. Tell patient to immediately report signs of unusual bleeding or infection.
• Advise women of childbearing age not to become pregnant while taking drug.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use