PURIXAN_- purixan_suspension

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. Exposure-Response Relationships Following a single oral dose of PURIXAN 50 mg under fasted conditions to adult healthy subjects, the median (min en dash max) AUC 0-INF max Absorption max Effect of foods Distribution Elimination 1/2 Metabolism Elimination Specific Populations Pediatrics Patients 2 en dash5hours 2 2 2 Several published studies indicate that patients with reduced TPMT or NUDT15 activity receiving usual doses of mercaptopurine, accumulate excessive cellular concentrations of active 6-TGNs, and are at higher risk for severe myelosuppression [see Warnings and Precautions (5. 1)] [see Dosage and Administration (2. 2) Warnings and Precautions (5.

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 PURIXAN is indicated for the treatment of patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen.

The recommended starting dosage of PURIXAN is 1. 5 mg/kg to 2. 5 mg/kg (50 mg/m 2 2 2. 1 Renal Impairment 2. 6 Hepatic Impairment 2. 7 The recommended starting dose of PURIXAN is 1. 5 mg/kg (50 mg/m 2 2 [see Dosage and Administration (2. Consider testing for TPMT and NUDT15 deficiency in patients who experience severe myelosuppression or repeated episodes of myelosuppression [see Warnings and Precautions (5. 1) Clinical Pharmacology (12. 5)] Homozygous Deficiency in either TPMT or NUDT15 Heterozygous Deficiency in TPMT and/or NUDT15 Renal Impairment [see Uses in Specific Populations (8. 6)] Hepatic Impairment [see Uses in Specific Populations (8. 7)] Reduce the dose of PURIXAN to one-third to one-quarter of the current dosage when coadministered with allopurinol [see Drug Interactions (7. Shake the bottle vigorously for at least 30 seconds to ensure the oral suspension is well mixed. PURIXAN is a pink to brown viscous oral suspension. Wash the oral dispensing syringe with warm ‘soapy’ water and rinse well; Hold the oral dispensing syringe under water and move the plunger up and down several times to make sure the inside of the oral dispensing syringe is clean; Ensure the oral dispensing syringe is completely dry before use of the oral dispensing syringe again; and Store the oral dispensing syringe in a hygienic place with PURIXAN. PURIXAN is a hazardous drug. Follow special handling and disposal procedures. 1 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. Myelosuppression 2. 1 Hepatotoxicity 5. 2 Immunosuppression 5. 3 Treatment Related Malignancies 5. 4 Macrophage Activation Syndrome 5. 5 Embryo-Fetal Toxicity 5. 3 The most consistent, dose-related adverse reaction of PURIXAN is myelosuppression, manifested by anemia, leukopenia, thrombocytopenia, or any combination of these. Monitor CBC and adjust the dosage of PURIXAN for excessive myelosuppression [see Dosage and Administration (2. 1)] [see Dosage and Administration (2. 2) Clinical Pharmacology (12. 5)] [see Drug Interactions (7. 4)] [see Dosage and Administration (2. 4)] Mercaptopurine is hepatotoxic. There are reports of deaths attributed to hepatic necrosis associated with the administration of mercaptopurine. Hepatic injury can occur with any dosage but seems to occur with greater frequency when the recommended dosage is exceeded. In some patients, jaundice has cleared following withdrawal of mercaptopurine and reappeared with rechallenge. Usually, clinically detectable jaundice appears early in the course of treatment (1 to 2 months); however, jaundice has been reported as early as 1 week and as late as 8 years after starting mercaptopurine. The hepatotoxicity has been associated in some cases with anorexia, diarrhea, jaundice, ascites and pruritus. Hepatic encephalopathy has occurred. Monitor serum transaminase levels, alkaline phosphatase, and bilirubin levels at weekly intervals when first beginning therapy and at monthly intervals thereafter. Monitor liver tests more frequently in patients who are receiving PURIXAN with other hepatotoxic drugs [see Drug Interactions (7. 5)] Intrahepatic Cholestasis of Pregnancy [see Indications and Usage (1. 1)] Mercaptopurine is immunosuppressive and may impair the immune response to infectious agents or vaccines. Due to the immunosuppression associated with maintenance chemotherapy for ALL, response to all vaccines may be diminished and there is a risk of infection with live virus vaccines. Consult immunization guidelines for immunocompromised patients. Hepatosplenic T-cell lymphoma has been reported in patients treated with mercaptopurine for inflammatory bowel disease (IBD), an unapproved use. Mercaptopurine is mutagenic in animals and humans, carcinogenic in animals, and may increase the risk of secondary malignancies. Macrophage activation syndrome (MAS) (hemophagocytic lymphohistiocytosis) is a known, life-threatening disorder that may develop in patients with autoimmune conditions, in particular with inflammatory bowel disease (IBD), and there could potentially be an increased susceptibility for developing the condition with the use of mercaptopurine (an unapproved use). If MAS occurs, or is suspected, discontinue PURIXAN. Monitor for and promptly treat infections such as EBV and cytomegalovirus (CMV), as these are known triggers for MAS. PURIXAN can cause fetal harm when administered to a pregnant woman. An increased incidence of miscarriage has been reported in women who received mercaptopurine in the first trimester of pregnancy. Adverse embryo-fetal findings, including miscarriage and stillbirth, have been reported in women who received mercaptopurine after the first trimester of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with PURIXAN and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PURIXAN and for 3 months after the last dose [see Use in Specific Populations (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. 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. 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) Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. [see Warnings and Precautions (5. 2)] The following adverse reactions have been identified during postapproval use of PURIXAN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions include: photosensitivity, hypoglycemia, portal hypertension, intrahepatic cholestasis of pregnancy (ICP), pellagra, and erythema nodosum. Allopurinol 2. 1 Warfarin 7. 2 See FDA approved patient labeling and 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. 4)] The coadministration of PURIXAN with warfarin may decrease the anticoagulant effectiveness of warfarin. Monitor the international normalized ratio (INR) in patients receiving warfarin and adjust the warfarin dosage as appropriate. PURIXAN can cause myelosuppression. Myelosuppression may be increased when PURIXAN is coadministered with other drugs that cause myelosuppression. Enhanced myelosuppression has been noted in some patients receiving trimethoprim-sulfamethoxazole. Monitor the CBC and adjust the dose of PURIXAN for excessive myelosuppression [see Dosage and Administration (2. 1) Warnings and Precautions (5. 1)] Aminosalicylates (e. , mesalamine, olsalazine or sulfasalazine) may inhibit the TPMT enzyme, which may increase the risk of myelosuppression when coadministered with PURIXAN. When aminosalicylates and PURIXAN are coadministered, use the lowest possible doses for each drug and monitor more frequently for myelosuppression [see Warnings and Precautions (5. 1)] PURIXAN can cause hepatotoxicity. Hepatotoxicity may be increased when PURIXAN is coadministered with other products that cause hepatotoxicity. Monitor liver tests more frequently in patients who are receiving PURIXAN with other hepatotoxic products [see Warnings and Precautions (5. 2)] PURIXAN dosage may need adjustment when administered concomitantly with high dose methotrexate [see Warnings and Precautions (5. 1)] [see Clinical Pharmacology (12. 3)] [see Clinical Pharmacology (12. 3)] Lactation (8. 2) Infertility (8. 3) Risk Summary [see Clinical Pharmacology (12. 1)] see Data Data Human Data Animal Data Risk Summary PURIXAN can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8. 1)] Pregnancy Testing [see Use in Specific Populations (8. 1)] Contraception Females Males [see Nonclinical Toxicology (13. 1)] Infertility Females and Males [see Nonclinical Toxicology (13. 1)] Safety and effectiveness of PURIXAN has been established in pediatric patients. Use of PURIXAN in pediatrics is supported by evidence from the published literature and clinical experience. Symptomatic hypoglycemia has been reported in pediatric patients with ALL receiving mercaptopurine. Reported cases were in pediatrics less than 6 years or with a low body mass index. Clinical studies of mercaptopurine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or another drug therapy. Use the lowest recommended starting dosage for PURIXAN or increase the dosing interval to every 36 to 48 hours in patients with renal impairment (CLcr less than 50 mL/min). Adjust the dose to maintain absolute neutrophil count (ANC) at a desirable level and for adverse reactions [see Dosage and Administration (2. 3)] Use the lowest recommended starting dosage for PURIXAN in patients with hepatic impairment.

Warnings and Precautions, Hepatotoxicity ( 5.2 7/2024

OVERDOSAGE
Signs and symptoms of mercaptopurine overdosage may be immediate (anorexia, nausea, vomiting, and diarrhea) or delayed (myelosuppression, liver dysfunction, and gastroenteritis). Dialysis cannot be expected to clear mercaptopurine. Hemodialysis is thought to be of marginal use due to the rapid intracellular incorporation of mercaptopurine into active metabolites with long persistence.
NONCLINICAL TOXICOLOGY
Mercaptopurine is carcinogenic in animals.
REFERENCES
1. OSHA Hazardous Drugs. OSHA.

Nova Laboratories, Ltd

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