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MERCAPTOPURINE is a brand name for Mercaptopurine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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…
Verbatim from this product's FDA label. Tap a section to expand.
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. 1 ) • Renal Impairment : Use the lowest recommended starting dose or increase the dosing interval.
6 ) • Hepatic Impairment : Use the lowest recommended starting dose. 5 mg/kg (50 mg/m 2 to 75 mg/m 2 ) orally once daily as part of combination chemotherapy maintenance regimen. Take mercaptopurine oral suspension either consistently with or without food.
After initiating mercaptopurine, monitor complete blood counts (CBC) and adjust the dose to maintain absolute neutrophil count (ANC) at a desirable level and for excessive myelosuppression. Evaluate the bone marrow in patients with prolonged myelosuppression or repeated episodes of myelosuppression to assess leukemia status and marrow cellularity.
2 )] . If a patient misses a dose, instruct the patient to continue with the next scheduled dose. 5 )] . Homozygous Deficiency in either TPMT or NUDT15 Patients with homozygous deficiency of either enzyme typically require 10% or less of the recommended dosage.
Reduce the recommended starting dosage of mercaptopurine in patients who are known to have homozygous TPMT or NUDT15 deficiency. Heterozygous Deficiency in TPMT and/or NUDT15 Reduce the mercaptopurine dosage based on tolerability. Most patients with heterozygous TPMT or NUDT15 deficiency tolerate recommended dosage, but some require dose reduction based on adverse reactions.
Patients who are heterozygous for both TPMT and NUDT15 may require more substantial dose reductions. 3 Dosage Modifications in Renal and Hepatic Impairment Renal Impairment Use the lowest recommended starting dosage for mercaptopurine in patients with renal impairment (CLcr less than 50 mL/min).
6 )] . Hepatic Impairment Use the lowest recommended starting dosage for mercaptopurine in patients with hepatic impairment. 7 )] . 1 )] . 5 Administration Shake the bottle vigorously for at least 30 seconds to ensure the oral suspension is well mixed.
Mercaptopurine oral suspension is a pink to brown viscous oral suspension. Provide a press-in bottle adapter and two oral dispensing syringes (one 1 mL and one 5 mL). Train patients or caregivers on proper handling, storage, administration, disposal and clean-up of accidental spillage prior to initiation of mercaptopurine oral suspension and during each visit to the clinic.
5 )] 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 Hikma Pharmaceuticals USA Inc. gov/medwatch. 1 Clinical Trials Experience 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.
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% of patients included urticaria, hyperuricemia, oral lesions, elevated transaminases, hyperbilirubinemia, hyperpigmentation, infections, and pancreatitis. Oral lesions resemble thrush rather than antifolic ulcerations.
2 )] . Drug fever has been reported with mercaptopurine. 2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of mercaptopurine. 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.
5 WARNINGS AND PRECAUTIONS • 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. 1 ) • Hepatotoxicity : Monitor transaminases, alkaline phosphatase and bilirubin. Withhold mercaptopurine at onset of hepatotoxicity. 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. 3 ) • Treatment Related Malignancies : Aggressive and fatal cases of hepatosplenic T-cell lymphoma have occurred. 4 ) • Macrophage Activation Syndrome : Monitor for and treat promptly; discontinue mercaptopurine.
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. 3 ) • Phenylketonuria : Patients should be informed that mercaptopurine oral suspension contains phenylalanine, a component of aspartame.
015 mg of phenylalanine. 1 Myelosuppression The most consistent, dose-related adverse reaction of mercaptopurine is myelosuppression, manifested by anemia, leukopenia, thrombocytopenia, or any combination of these. 1 )] . 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. 5 )] . 4 )] . 4 )] . 2 Hepatotoxicity Mercaptopurine is hepatotoxic. There are reports of deaths attributed to hepatic necrosis associated with the administration of mercaptopurine.
4 CONTRAINDICATIONS None. • None
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Advise patients and caregivers to use mercaptopurine oral suspension within 8 weeks and properly discard remaining mercaptopurine oral suspension after 8 weeks. Provide instructions regarding which syringe to use and how to administer the specified dose, since mercaptopurine oral suspension is supplied with 1 mL and 5 mL oral dispensing syringes.
Advise patients that the oral dispensing syringe is intended for multiple uses and provide the following instructions: • 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 mercaptopurine oral suspension.
Mercaptopurine is a hazardous drug. Follow special handling and disposal procedures. 1
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. 5 )] or with known pre-existing liver disease.
Withhold mercaptopurine at onset of hepatotoxicity. Intrahepatic Cholestasis of Pregnancy Postmarketing cases of intrahepatic cholestasis of pregnancy (ICP) have been reported in patients with inflammatory bowel disease who received mercaptopurine during pregnancy.
1 )] . Discontinue mercaptopurine if ICP develops in a pregnant woman . 3 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. 4 Treatment Related Malignancies 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. 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. 5 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 mercaptopurine. Monitor for and promptly treat infections such as EBV and cytomegalovirus (CMV), as these are known triggers for MAS. 6 Embryo-Fetal Toxicity Mercaptopurine 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 mercaptopurine and for 6 months after the last dose. 3 )] . 7 Risks in Patients with Phenylketonuria Phenylalanine can be harmful to patients with phenylketonuria (PKU).
Phenylketonuric patients should be informed that mercaptopurine oral suspension contains phenylalanine, a component of aspartame. 015 mg of phenylalanine.