Overview
11 DESCRIPTION Mercaptopurine is a nucleoside metabolic inhibitor. The chemical name is 6 H -purine-6-thione, 1,7-dihydro-, 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, USP is a yellow, crystalline powder; odorless. It is practically insoluble in water and in ether; slightly soluble in ethanol (96%).
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 Mercaptopurine 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 Mercaptopurine 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 mercaptopurine oral suspension 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.
Contraindications
- 4 CONTRAINDICATIONS None. • None
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Myelosuppression [see Warnings and Precautions ( 5.1 )] • Hepatotoxicity [see Warnings and Precautions ( 5.2 )] • Immunosuppression [see Warnings and Precautions ( 5.3 )] • Treatment Related Malignancies [see Warnings and Precautions ( 5.4 )] • Macrophage Activation Syndrome [see Warnings and Precautions ( 5.5 )] The most common adverse reaction (>20%) is myelosuppression, including anemia, neutropenia, lymphopenia and thrombocytopenia.
Interactions
- 7 DRUG INTERACTIONS • Allopurinol : Reduce the dose of mercaptopurine when coadministered with allopurinol. ( 2.4 , 7.1 ) • Warfarin : Mercaptopurine may decrease the anticoagulant effect. ( 7.2 ) 7.1 Allopurinol Allopurinol can inhibit the first-pass oxidative metabolism of mercaptopurine by xanthine oxidase, which can lead to an increased risk of mercaptopurine adverse reactions [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 )] . Reduce the dose of mercaptopurine when coadministered with allopurinol [see Dosage and Administration ( 2.4 )] . 7.