FDA

Purinethol

Approved 11 Sept 1953OralTablet

Indications

Mercaptopurine tablets is a nucleoside metabolic inhibitor indicated for treatment of adult and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen. (1.1)

1.1Acute Lymphoblastic Leukemia

Mercaptopurine tablets are indicated for treatment of adult and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen.

Contraindications

None. None.

Warnings and precautions

Myelosuppression : Monitor complete blood count (CBC) and adjust the dose of mercaptopurine tablets 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 or homozygous TPMT or NUDT15 deficiency may require a dose reduction. (2.2, 5.1) Hepatotoxicity : Monitor transaminases, alkaline phosphatase and bilirubin.

Withhold mercaptopurine tablets 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 patients. (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 tablets.

(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)

5.1Myelosuppression

The most consistent, dose-related adverse reaction is myelosuppression, manifested by anemia, leukopenia, thrombocytopenia, or any combination of these. Monitor CBC and adjust the dosage of mercaptopurine tablets for excessive myelosuppression [see Dosage and Administration (2.1)] . Consider testing for TPMT or 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.

At a glance

Brand name: Purinethol
Active substance: mercaptopurine
Route: Oral
Dosage form: Tablet
Applicant: Stason Pharms
Status: Prescription
FDA approval: 11 Sept 1953
Application: NDA009053-002

Indications

1.1Acute Lymphoblastic Leukemia

Mercaptopurine tablets are indicated for treatment of adult and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen.

Warnings and precautions

(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)

5.1Myelosuppression

Interactions

Allopurinol : Reduce the dose of mercaptopurine tablets when co-administered with allopurinol. (2.4, 7.1) Warfarin : Mercaptopurine tablets may decrease the anticoagulant effect. (7.2)

7.1Allopurinol

Allopurinol can inhibit the first-pass oxidative metabolism of mercaptopurine by xanthine oxidase, which can lead to an increased risk of mercaptopurine adverse reactions (i.e., myelosuppression, nausea, and vomiting) [see Warnings and Precautions (5.1), Adverse Reactions (6.1)] . Reduce the dose of mercaptopurine tablets when coadministered with allopurinol [see Dosage and Administration (2.4)] .

7.2Warfarin

The concomitant administration of mercaptopurine tablets and 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.

7.3Myelosuppresive Products

Mercaptopurine tablets can cause myelosuppression. Myelosuppression may be increased when mercaptopurine tablets is coadministered with other products that cause myelosuppression. Enhanced myelosuppression has been noted in some patients also receiving trimethoprim-sulfamethoxazole. Monitor the CBC and adjust the dose of mercaptopurine tablets for excessive myelosuppression [see Dosage and Administration (2.1), Warnings and Precautions (5.1)] .

7.4Aminosalicylates Aminosalicylates

(e.g., mesalamine, olsalazine or sulfasalazine) may inhibit the TPMT enzyme, which may increase the risk of myelosuppression when coadministered with mercaptopurine tablets. When aminosalicylates and mercaptopurine tablets are coadministered, use the lowest possible doses for each drug and monitor more frequently for myelosuppression [see Warnings and Precautions (5.1)] .

7.5Hepatotoxic Products

Mercaptopurine tablets can cause hepatotoxicity. Hepatotoxicity may be increased when mercaptopurine tablets is coadministered with other products that cause hepatotoxicity. Monitor liver tests more frequently in patients who are receiving mercaptopurine tablets with other hepatotoxic products [see Warnings and Precautions (5.2)] .

Adverse reactions

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)] The most common adverse reaction (>20%) is myelosuppression, including anemia, leukopenia 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 Florida Pharmaceutical Products, LLC at 1-800-315-0985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical 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, increased transaminases, hyperbilirubinemia, hyperpigmentation, infections, and pancreatitis. Oral lesions resemble thrush rather than antifolic ulcerations. Delayed or late adverse reactions include hepatic fibrosis, hyperbilirubinemia, alopecia, pulmonary fibrosis, oligospermia and secondary malignancies [see Warnings and Precautions (5.1, 5.2)].

Drug fever has been reported with mercaptopurine. Additional adverse reactions that have been reported in patients who have received mercaptopurine include photosensitivity, hypoglycemia, and portal hypertension.

6.2Postmarketing Experience

The following adverse reactions have been identified during postapproval use of mercaptopurine tablets. 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: intrahepatic cholestasis of pregnancy (ICP).

Purinethol

Indications

1.1Acute Lymphoblastic Leukemia

Contraindications

Warnings and precautions

5.1Myelosuppression

At a glance

Two medicines in one question?

Purinethol

Indications

1.1Acute Lymphoblastic Leukemia

Contraindications

Warnings and precautions

5.1Myelosuppression

At a glance

Two medicines in one question?

5.2Hepatoxicity

5.3Immunosuppression

5.4Treatment Related Malignancies Hepatosplenic

5.5Macrophage Activation Syndrome

5.6Embryo-Fetal Toxicity

Interactions

7.1Allopurinol

7.2Warfarin

7.3Myelosuppresive Products

7.4Aminosalicylates Aminosalicylates

7.5Hepatotoxic Products

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information