Overview
11 DESCRIPTION Mercaptopurine, a nucleoside metabolic inhibitor. The chemical name is 1,7-dihydro-6H-purine-6-thione monohydrate. The molecular formula is C 5 H 4 N 4 S•H 2 O and the molecular weight is 170.20. The structural formula is: Mercaptopurine is a yellow, odorless or practically odorless, crystalline powder. It is practically insoluble in water with pKa 7.8, 11.2.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Mercaptopurine is a purine analog that undergoes intracellular transport and activation to form metabolites including thioguanine nucleotides (TGNs). Incorporation of TGNs into DNA or RNA results in cell-cycle arrest and cell death. TGNs and other mercaptopurine metabolites are also inhibitors of de novo purine synthesis and purine nucleotide interconversions. Mercaptopurine was cytotoxic to proliferating cancer cells in vitro and had antitumor activity in mouse tumor models. It is not known which of the biochemical effects of mercaptopurine and its metabolites are directly or predominantly responsible for cell death. 12.
Indications
- 1 INDICATIONS AND USAGE PURIXAN is a nucleoside metabolic inhibitor indicated for the treatment of patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen.( 1.1 ) 1.1 Acute Lymphoblastic Leukemia PURIXAN is indicated for the treatment of patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen.
Common Doses
- 1.5 mg
- 2.5 mg
- 50 mg
- 75 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended starting dosage of PURIXAN is 1.5 mg/kg to 2.5 mg/kg (50 mg/m 2 to 75 mg/m 2 ) orally once daily as part of a combination chemotherapy maintenance regimen. Adjust dose to maintain desirable absolute neutrophil count and for excessive myelosuppression.( 2.1 ) Renal Impairment : Use the lowest recommended starting dose or increase the dosing interval. ( 2.3, 8.6 ) Hepatic Impairment : Use the lowest recommended starting dose. ( 2.3, 8.7 ) 2.1 Recommended Dosage The recommended starting dose of PURIXAN is 1.5 mg/kg to 2.
Contraindications
- 4 CONTRAINDICATIONS None None.
Side Effects
- 6 ADVERSE REACTIONS The most common adverse reaction (> 20%) is myelosuppression including anemia, neutropenia, lymphopenia and thrombocytopenia. Adverse reactions occurring in 5% to 20% of patients include anorexia, nausea, vomiting, diarrhea, malaise and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rare Disease Therapeutics, Inc., at 1-844-472-7389 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [ see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Allopurinol : Reduce the dose of PURIXAN when co-administered with allopurinol. ( 2.4 , 7.1 ) Warfarin : PURIXAN may decrease the anticoagulant effect. ( 7.2 ) See FDA approved patient labeling and