Mercaptopurine

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.

Oral suspension: 2,000 mg/100 mL (20 mg/mL). ( 3 ) Oral Suspension: 2,000 mg/100 mL (20 mg/mL) pink to brown in color.

None None.

Myelosuppression : Monitor complete blood count (CBC) and adjust the dose of MERCAPTOPURINE for excessive myelosuppression. Consider testing in patients with severe myelosuppression or repeated episodes of myelosuppression for thiopurine S-methyltransferase (TPMT) or nucleotide diphosphatase (NUDT15) deficiency. Patients with homozygous-TPMT or homozygous-NUDT15 deficiency may require a dose reduction. ( 2.2, 5.1 ) Hepatotoxicity : Monitor transaminases, alkaline phosphatase and bilirubin. Withhold MERCAPTOPURINE at onset of hepatotoxicity. ( 5.2 ) Immunosuppression :Response to all vaccines may be diminished and there is a risk of infection with live virus vaccines. Consult immunization guidelines for immunocompromised pediatrics. ( 5.3 ) Treatment Related Malignancies : Aggressive and fatal cases of hepatosplenic T-cell lymphoma have occurred. ( 5.4 ) Macrophage Activation Syndrome : Monitor for and treat promptly; discontinue MERCAPTOPURINE. ( 5.5 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1, 8.3 )

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 (5.1) ] 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) ]

Allopurinol : Reduce the dose of MERCAPTOPURINE when co-administered with allopurinol. ( 2.4 , 7.1 ) Warfarin : MERCAPTOPURINE may decrease the anticoagulant effect. Monitor INR and adjust warfarin dose as appropriate. ( 7.2 ) See FDA approved patient labeling and

Lactation : Advise not to breastfeed. ( 8.2 ) Infertility : Can impair fertility. ( 8.3 )

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.