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Therapeutic Classification: antineoplastics

Pharmacologic Classification: antimetabolites

• Acute lymphoblastic leukemia (ALL) (with other agents)

Unlabeled Use:

• Treatment of:
  • Some lymphomas,
  • Polycythemia vera,
  • Crohn's disease,
  • Psoriatic arthritis.

• Disrupts DNA and RNA synthesis (cell-cycle S phase–specific).

• Death of rapidly proliferating cells, especially malignant ones.
• Also has immunosuppressant properties.

Absorption: Variably and incompletely (5–50%) absorbed after oral administration.

Distribution: Widely distributed throughout total body water.

Metabolism/Excretion: Metabolized by liver. Converted to inactive metabolite by thiopurine methyltransferase (TPMT); nucleotide diphosphatase [NUDT15] is also involved in inactivation process. Nearly 50% is excreted unchanged by the kidneys.

Half-life: Three phases — 45 min, 2.5 hr, 10 hr.

(effects on blood counts)

Contraindicated in:

• Hypersensitivity
• Severe hepatic impairment
• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Infections
• ↓bone marrow reserve
• Patients with homozygous TPMT enzyme deficiency or nucleotide diphosphatase (NUDT15) deficiency (substantial dose ↓ are required to avoid hematologic adverse events)
• Rep: Women of reproductive potential
• Geri: ↑risk of adverse reactions.

CNS: weakness.

Derm: alopecia, hyperpigmentation.

Endo: gonadal suppression, oligospermia.

GI: HEPATOTOXICITY, anorexia, diarrhea, nausea, vomiting.

Hemat: MACROPHAGE ACTIVATION SYNDROME, anemia, leukopenia, thrombocytopenia.

Metab: hyperuricemia.

Misc: HEPATOSPLENIC T-CELL LYMPHOMA, SECONDARY MALIGNANCY, fever.

Drug-Drug:

• Allopurinol↓ metabolism and ↑ risk of toxicity from mercaptopurine (↓ dose of mercaptopurine to 25–33% of the usual dose).
• A similar effect may occur with olsalazine sulfasalazine andmesalamine.
• May ↑ risk of bleeding with warfarin.
• ↑risk of hepatotoxicity with other hepatotoxic agents.
• ↑bone marrow depression with trimethoprim/sulfamethoxazole, other antineoplastics, or radiation therapy.
• May alter the effect of warfarin.
• ↓antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Drug-Natural Products:

• Concomitant use with echinacea and melatonin may interfere with immunosuppression.

• PO (Adults): 1.5–2.5 mg/kg/day as a single dose.
• PO (Children): 2.5 mg/kg/day (75 mg/m²) single dose or divided doses (dose should be rounded to the nearest 25 mg).

(Generic available)

• Tablets: 50 mg;
• Oral suspension (raspberry flavor): 20 mg/mL;

• Monitor BP, pulse, respiratory rate, and temperature frequently during therapy. Report significant changes.
• Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae; guaiac stools, urine, and emesis) and avoid IM injections and rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension. If severe myelosuppression occurs, consider testing for genetic metabolic abnormality.
• Monitor intake and output ratios and inform health care professional if significant discrepancies occur. Encourage fluid intake of 2000–3000 mL/day. Allopurinol and alkalinization of the urine may be used to decrease serum uric acid levels and to help prevent urate stone formation.
• Assess patient’s nutritional status. Anorexia and weight loss can be decreased by feeding light, frequent meals. Nausea and vomiting can be minimized by administering an antiemetic at least 1 hr before receiving medication.

• Verify negative pregnancy test before starting therapy.
  • Monitor CBC and differential before and weekly during therapy. May cause leukopenia, thrombocytopenia, and anemia. Notify health care professional if a sudden drop in values occurs. Leukopenia and thrombocytopenia are usually mild, occur 5–6 days after initiation of therapy, and persist for approximately 7 days after discontinuation of therapy.
  • Evaluate TPMT and NUDT15 status in patients with severe myelosuppression or repeated episodes of myelosuppression. In patients with homozygous deficiency, may reduce dose by 10% of recommended dose. Reduce starting dose in patients with known deficiency. In patients with heterozygous deficiency, reduce dose based on tolerability. Most patients with deficiency tolerate recommended dose, but may require dose reduction based on adverse reactions. Patients who are heterozygous for both TPMT and NUDT15 may require more substantial dose reductions.
  • Monitor hepatic function (AST, ALT, alkaline phosphatase, LDH, and bilirubin) weekly during early therapy and monthly thereafter. Hepatotoxicity has occurred between 1 wk and 8 yr of dosing.
  • Monitor renal function (BUN, serum creatinine) and serum uric acid concentrations before and periodically during therapy. May cause ↑ uric acid.
  • Serum glucose and uric acid levels may show false ↑ when sequential multiple analyzer is used to determine values.

• High Alert:Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order and dose calculations.
• Do not confuse with Purinethol (mercaptopurine) with propylthiouracil.
• The dose of mercaptopurine should be reduced to 1/3– 1/4 the usual dose in patients receiving concurrent allopurinol to decrease the risk of toxic effects of mercaptopurine.
• PO: Administer medication with meals. Tablets may be crushed if patient has difficulty swallowing.
  • Shake suspension for at least 30 seconds to make sure well mixed; suspension is pink to brown and viscous. Use oral syringe for accurate dose; wash and dry syringe between doses. Stable for 6 wks after opening.

• Instruct patient to take medication as directed. If a dose is missed, omit and take next dose as scheduled; do not double dose.
• Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
• Instruct patient to report yellowing of anorexia, diarrhea, jaundice, ascites, skin or eyes, dark-colored urine, clay-colored stools, abdominal pain, flank or joint pain, or swelling of feet or legs to health care professional promptly.
• Instruct patient not to receive any vaccinations without advice of health care professional.
• Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during therapy and for at least 6 mo after last dose and to avoid breastfeeding during and for 1 wk after last dose of therapy. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose. May impair male and female fertility.
• Emphasize the need for periodic lab tests to monitor for side effects.

• Remission of acute leukemia. Patients may receive subsequent doses if hematologic profiles are within normal ranges and patients do not demonstrate serious side effects.

Purinethol, Purixan

NDC Code^*

• 0054- West-Ward Pharmaceuticals Corp.
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    • 0054-4581-11- 25 TABLET in 1 BOTTLE, PLASTIC (0054-4581-11)

• 0054- West-Ward Pharmaceuticals Corp.
  • 0054-4581- Mercaptopurine
    • 0054-4581-27- 250 TABLET in 1 BOTTLE, PLASTIC (0054-4581-27)

• 0378- Mylan Pharmaceuticals Inc.
  • 0378-3547- Mercaptopurine
    • 0378-3547-25- 250 TABLET in 1 BOTTLE, PLASTIC (0378-3547-25)

• 0378- Mylan Pharmaceuticals Inc.
  • 0378-3547- Mercaptopurine
    • 0378-3547-52- 25 TABLET in 1 BOTTLE, PLASTIC (0378-3547-52)

• 69076- Quinn Pharmaceuticals, LLC
  • 69076-913- Mercaptopurine
    • 69076-913-02- 25 TABLET in 1 BOTTLE, PLASTIC (69076-913-02)

• 69076- Quinn Pharmaceuticals, LLC
  • 69076-913- Mercaptopurine
    • 69076-913-25- 250 TABLET in 1 BOTTLE, PLASTIC (69076-913-25)