America's First Exclusively Orphan Drug Company:
  • Rare Disease Therapeutics, Inc.

About PURIXAN®

Indication

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

Liquid Formulation

PURIXAN offers patients and healthcare professionals a liquid formulation as an alternative to the mercaptopurine tablet for precise dosing based on the individual patient’s dosing needs.

  • Mercaptopurine is a cornerstone of all maintenance therapy drug regimens for acute lymphoblastic leukemia (ALL).1
  • Until recently, the only marketed formulation of mercaptopurine has been a 50-mg tablet.
    • However, solid oral dosage forms may be ineffective for many children because they have difficulty swallowing tablets and capsules.2
    • Fixed doses are impractical because the dose varies according to the size of the child.2
    • More than 90% of pediatricians reported that a drug’s taste and palatability were the greatest barriers to compliant treatment.2
  • For children, PURIXAN addresses common concerns relating to treatment with a tablet.

Comparison between PURIXAN and the tablet form of mercaptopurine

The bioavailability of PURIXAN is equivalent to that of the tablet form of mercaptopurine, as measured by the AUC (area under the concentration curve).

  • The mean ratio of the AUCs for PURIXAN and mercaptopurine tablets is 114%, with a 90% confidence interval of 108%–121%. 3
  • The accepted target range of AUC ratios for equivalence is 80%–125%.3

Predictability

PURIXAN performs more consistently and predictably than the mercaptopurine tablet.

  • PURIXAN had substantially lower between-subject variability in maximum plasma concentrations (46% vs 69% coefficient of variation).3

Consistent Absorption

PURIXAN reduced the variability in the absorption of mercaptopurine, proving itself to be a dependable and reliable alternative to the tablet.3

 

fredictability-chart

Flexibility and Accuracy

PURIXAN provides dosing flexibility and accuracy for precise dosing.

PURIXAN 20 mg/mL oral suspension provides an accuracy of 2 mg and an opportunity to administer the product in a way that may be more acceptable to children.2

flexibility-chart

  1. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006;354:166-178.
  2. Mennella JA, Spector AC, Reed DR, Coldwell SE. The bad taste of medicines: overview of basic research on bitter taste. Clin There. 2013;35:1225-1246.
  3. Mulla H, Leary A, White P, Pandya H. A step toward more accurate dosing for mercaptopurine in childhood acute lymphoblastic leukemia. J Clin Pharmacol. 2012;52:1610-1613.
  4. WHO growth chart for children. http://www.who.int/childgrowth/standards/en/. Accessed April 16, 2020.
  5. PURIXAN (mercaptopurine) oral suspension [package insert]. Franklin, TN: Rare Disease Therapeutics, Inc.; April 2020.
INDICATION

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

IMPORTANT SAFETY INFORMATION
Contraindications

None.

Warnings and Precautions

Myelosuppression

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.

Consider testing for thiopurine S-methyltransferase (TPMT) or nucleotide diphosphatase (NUDT15) deficiency in patients with severe myelosuppression or repeated episodes of myelosuppression. TPMT genotyping or phenotyping (red blood cell TPMT activity) and NUDT15 genotyping can identify patients who have reduced activity of these enzymes. Patients with homozygous TPMT or NUDT15 deficiency may require a dose reduction.

Myelosuppression can be exacerbated by coadministration with allopurinol, aminosalicylates or other products that cause myelosuppression. Reduce the dosage of PURIXAN when coadministered with allopurinol.

Hepatotoxicity

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.

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 or with known pre-existing liver disease. Withhold PURIXAN at onset of hepatotoxicity.

Immunosuppression

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.

Treatment Related Malignancies

Patients receiving immunosuppressive therapy, including mercaptopurine, are at an increased risk of developing lymphoproliferative disorders and other malignancies, notably skin cancers (melanoma and non-melanoma), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ. The increased risk appears to be related to the degree and duration of immunosuppression. It has been reported that discontinuation of immunosuppression may provide partial regression of the lymphoproliferative disorder.

A treatment regimen containing multiple immunosuppressants (including thiopurines) should therefore be used with caution as this could lead to lymphoproliferative disorders, some with reported fatalities. A combination of multiple immunosuppressants, given concomitantly increases the risk of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders.

Macrophage Activation Syndrome

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.

Embryo-Fetal Toxicity

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.

Adverse Reactions

Based on multicenter cooperative group ALL trials, the most common adverse reaction occurring in > 20% of patients was myelosuppression, including anemia, neutropenia, lymphopenia and thrombocytopenia. Adverse reactions occurring in 5% to 20% of patients included anorexia, nausea, vomiting, diarrhea, malaise, and rash. Adverse reactions occurring in 5% to 20% of patients included anorexia, nausea, vomiting, diarrhea, malaise, and rash. Adverse reactions occurring in < 5% of patients included urticaria, hyperuricemia, oral lesions, elevated transaminases, hyperbilirubinemia, hyperpigmentation, infections, and pancreatitis. Oral lesions resemble thrush rather than antifolic ulcerations. Delayed or late toxicities include hepatic fibrosis, hyperbilirubinemia, alopecia, pulmonary fibrosis, oligospermia and secondary malignancies.

USE IN SPECIFIC POPULATIONS
  • Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with PURIXAN and for 1 week after the last dose.
  • Pediatric Use: 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.
  • Renal Impairment: 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.
  • Hepatic Impairment: Use the lowest recommended starting dosage for PURIXAN in patients with hepatic impairment. Adjust the dose to maintain absolute neutrophil count (ANC) at a desirable level and for adverse reactions.

 

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.

Withhold PURIXAN immediately if severe or life-threatening adverse reactions occur during treatment. If a patient is seen immediately following an accidental overdosage, it may be useful to induce emesis.

 

Please see complete Prescribing Information.

To report SUSPECTED ADVERSE REACTIONS, contact Rare Disease Therapeutics, Inc., at 1-844-472-7389 or by email at safety@raretx.com, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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