"The U.S. Food and Drug Administration today expanded the approved use of Imbruvica (ibrutinib) for chronic lymphocytic leukemia (CLL) patients who have received at least one previous therapy.
CLL is a rare blood and bone marrow disease"...
The most consistent, dose-related toxicity of PURIXAN is bone marrow suppression, manifested by anemia, leukopenia, thrombocytopenia, or any combination of these. Monitor CBC and adjust the dose of PURIXAN for severe neutropenia and thrombocytopenia.
Evaluate patients with repeated severe myelosuppression for thiopurine S-methyltransferase (TPMT) deficiency. Patients with homozygous-TPMT deficiency require substantial dose reductions of PURIXAN [see DOSAGE AND ADMINISTRATION, and CLINICAL PHARMACOLOGY].
Avoid the concurrent use of allopurinol and PURIXAN. Concomitant allopurinol and PURIXAN can result in a significant increase in bone marrow toxicity. Myelosuppression can be exacerbated by coadministration with drugs that inhibit TPMT (e.g., olsalazine, mesalamine, or sulfasalazine) or drugs whose primary or secondary toxicity is myelosuppression [see DRUG INTERACTIONS].
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 the start of treatment with mercaptopurine. The hepatotoxicity has been associated in some cases with anorexia, diarrhea, jaundice and ascites. 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 function more frequently in patients who are receiving mercaptopurine with other hepatotoxic drugs or with known pre-existing liver disease. Interrupt PURIXAN in patients with onset of clinical or laboratory evidence of hepatotoxicity.
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 children.
PURIXAN can cause fetal harm when administered to a pregnant woman. Women receiving PURIXAN in the first trimester of pregnancy have an increased incidence of abortion. Adverse embryo-fetal findings were reported in women receiving mercaptopurine after the first trimester of pregnancy and included abortion and stillbirth.
There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to a fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving PURIXAN [see Use in Specific Populations].
Treatment Related Malignancies
Cases of hepatosplenic T-cell lymphoma have been reported in patients treated with mercaptopurine for inflammatory bowel disease, for which mercaptopurine is not approved. Mercaptopurine is mutagenic in animals and humans, carcinogenic in animals, and may increase the risk of secondary malignancies.
Monitor the following laboratory tests in patients receiving PURIXAN: Complete blood counts (CBCs), transaminases, and bilirubin. Evaluate the bone marrow in patients with prolonged or repeated marrow suppression to assess leukemia status and marrow cellularity. Evaluate TPMT status in patients with clinical or laboratory evidence of severe bone marrow toxicity, or repeated episodes of myelosuppression.
Patient Counseling Information
See FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use).
Prior to initiation of Purixan and on each visit to the clinic, train patients or caregivers on proper handling, storage, administration, and disposal and clean-up of accidental spillage of the medication. Specifically, since Purixan is supplied with 1 mL and 5 mL oral dispensing syringes, provide appropriate instructions regarding which syringe to use and how to administer a specified dose.
Inform patients and caregivers that the major toxicities of PURIXAN are related to myelosuppression, hepatotoxicity, and gastrointestinal toxicity. Advise patients to contact their physician if they experience fever, sore throat, jaundice, nausea, vomiting, signs of local infection, bleeding from any site, or symptoms suggestive of anemia.
Inform women of childbearing potential to avoid becoming pregnant.
See FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use).
Inform patients and caregivers to select the 1 mL or 5 mL syringe whichever is appropriate to deliver the correct dose.
Inform patients and caregivers to shake the bottle vigorously for at least 30 seconds to ensure the oral suspension is well mixed. PURIXAN (mercaptopurine) oral suspension is pink in color but because it contains a natural fruit extract, the color of the suspension may vary from pink to brown. Instruct patients and caregivers that once opened, PURIXAN should be used within 6 weeks.
Inform patients and caregivers that the oral dispensing syringe is intended for multiple use: 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 for dosing; and store the oral dispensing syringe in a hygienic place with the medicine.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Mercaptopurine is carcinogenic in animals and humans.
Mercaptopurine may impair fertility. In mice, surviving female offspring of mothers who received chronic low doses of mercaptopurine during pregnancy were found sterile, or if they became pregnant, had smaller litters and more dead fetuses as compared to control animals.
Use In Specific Populations
Pregnancy Category D [see WARNINGS AND PRECAUTIONS].
PURIXAN can cause fetal harm when administered to a pregnant woman. Women receiving PURIXAN have an increased incidence of abortion and stillbirth. Advise women to avoid becoming pregnant while receiving PURIXAN. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Women receiving mercaptopurine in the first trimester of pregnancy have an increased incidence of abortion; the risk of malformation in offspring surviving first trimester exposure is not known. In a series of 28 women receiving mercaptopurine after the first trimester of pregnancy, 3 mothers died prior to delivery, 1 delivered a stillborn child, and 1 aborted; there were no cases of macroscopically abnormal fetuses.
Mercaptopurine was embryo-lethal and teratogenic in several animal species (rat, mouse, rabbit, and hamster).
It is not known whether mercaptopurine is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from mercaptopurine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
The safety and effectiveness of mercaptopurine for the treatment of ALL in pediatric patients have not been established in adequate and well-controlled trials. The evidence for efficacy of mercaptopurine is derived from the published literature and clinical experience. The toxicities of mercaptopurine are similar in adults and children.
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 other drug therapy.
No formal clinical or pharmacokinetic studies have been conducted in patients with renal impairment.
Starting at the low end of the PURIXAN dosing range, or increasing the dosing interval to 36-48 hours can be considered in patients with baseline renal impairment. Subsequent PURIXAN doses should be adjusted based on efficacy and toxicity [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
No formal clinical or pharmacokinetic studies have been conducted in patients with hepatic impairment.
Mercaptopurine is hepatotoxic. In patients with baseline hepatic impairment, starting at the low end of the PURIXAN dose range should be considered and patients should be monitored for toxicity [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 4/12/2016
Additional Purixan Information
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