6-mercaptopurine


mercaptopurine (6-mercaptopurine, 6-MP)

Purinethol, Puri-Nethol (UK)

Pharmacologic class: Antimetabolite

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Don't give drug unless diagnosis of acute lymphatic leukemia is confirmed and responsible physician knows how to assess response to chemotherapy.

Action

Inhibits DNA and RNA synthesis, suppressing growth of certain cancer cells

Availability

Tablets: 50 mg

Indications and dosages

➣ Maintenance therapy for acute lymphatic (lymphocytic, lymphoblastic) leukemia

Adults and children: On complete hematologic remission, 1.5 to 2.5 mg/kg/day P.O. as a single dose (combined with other agents as prescribed).

Contraindications

• Hypersensitivity to drug or its components

• Prior resistance to drug or thioguanine

• Breastfeeding

Precautions

Use cautiously in:

• renal or hepatic impairment

• decreased platelet or neutrophil counts after chemotherapy or radiation

• inherited thiopurine methyltransferase deficiency

• pregnant patients.

Administration

• Follow facility protocols regarding proper handling and disposal of drug.

See Don't handle drug if you are pregnant.

• Be aware that total daily dosage is calculated to nearest multiple of 25 mg and given once daily.

See Be aware that when mercaptopurine is given with allopurinol, mercaptopurine dosage must be reduced to one-third to one-fourth of usual dosage to avoid severe toxicity.

See Withdraw drug immediately if white blood cell (WBC) or platelet count falls rapidly or steeply.

Adverse reactions

GI: nausea, vomiting, anorexia, diarrhea, GI ulcers, painful oral ulcers, pancreatitis

Hematologic: anemia, leukopenia, thrombocytopenia

Hepatic: jaundice, hepatotoxicity

Metabolic: hyperuricemia

Skin: rash, hyperpigmentation

Interactions

Drug-drug. Allopurinol (more than 300 mg), aminosalicylate derivatives (mesalazine, olsalazine, sulfasalazine): increased bone marrow depression

Warfarin: decreased anticoagulant effect

Drug-diagnostic tests. Hemoglobin, platelets, red blood cells, uric acid, WBCs: increased values

Patient monitoring

See Watch for signs and symptoms of hepatotoxicity.

• Monitor weekly CBC with white cell differential and platelet count.

• Assess bone marrow aspiration and biopsy results, as necessary, to aid assessment of disease progression, resistance to therapy, and drug-induced marrow hypoplasia.

• Monitor serum uric acid level.

• Evaluate fluid intake and output.

• Monitor liver function tests and bilirubin level weekly at start of therapy, then monthly.

Patient teaching

See Instruct patient to immediately report fever, sore throat, increased bleeding or bruising, or signs or symptoms of liver problems (right-sided abdominal pain, yellowing of skin or eyes, nausea, vomiting, clay-colored stools, or dark urine).

• Advise both male and female patients to use reliable contraception.

• Encourage patient to maintain adequate fluid intake.

• Caution patient not to get vaccinations without consulting prescriber.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

6-mer·cap·to·pu·rine (Shy),

(mer-kap'tō-pyūr'ēn), An analogue of hypoxanthine and of adenine; an antineoplastic agent.

mercaptopurine

An antimetabolic chemotherapeutic structural analogue (thiol replaces 6-hydroxyl) of hypoxanthine, which is activated by hypoxanthine phosphoribosyl transferase and converted in vivo to thioinosinic acid, a competitive inhibitor in purine synthesis that targets rapidly dividing cells (e.g., in ALL, AML). The wide variation in 6-MP bioavailability and suboptimal doses during maintenance regimens are attributable causes for the high incidence of relapse in children with ALL in remission.
Adverse effects
Myelosuppression, anorexia, nausea, vomiting, jaundice.