Purinethol (mercaptopurine)

Generic drug: Purinethol

Brand name: mercaptopurine

Purinethol (mercaptopurine) is used to slow the growth of cancer cells. Purinethol is also used to treat certain types of leukemia.

Common side effects of Purinethol include:

• nausea,
• vomiting,
• diarrhea,
• loss of appetite,
• itching or skin rash, or
• darkened skin color.

Temporary hair loss may also occur. Normal hair growth should return after treatment with Purinethol has ended. Tell your doctor if you have unlikely but serious side effects of Purinethol including:

• easy bruising or bleeding,
• dizziness,
• fainting,
• joint pain or swelling,
• tongue or mouth sores or pain,
• unusual tiredness, or
• symptoms of liver disease (such as persistent nausea or vomiting, stomach or abdominal pain, dark urine, yellowing eyes or skin).

Recommended Dosage

• The recommended starting dosage of Purinethol is 1.5 mg/kg to 2.5 mg/kg orally once daily as part of combination chemotherapy maintenance regimen. A recommended dosage for patients less than 17 kg is not achievable, because the only available strength is 50 mg. Take Purinethol either consistently with or without food.
• After initiating Purinethol, monitor complete blood count (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.
• Evaluate thiopurine S-methyltransferase (TPMT) and nucleotide diphosphatase (NUDT15) status in patients with severe myelosuppression or repeated episodes or myelosuppression [see Dosage Modifications in Patients with TPMT and NUDT15 Deficiency below].
• Do not administer to patients who are unable to swallow tablets.
• If a patient misses a dose, instruct the patient to continue with the next scheduled dose.
• Purinethol is a cytotoxic drug. Follow special handling and disposal procedures.

Dosage Modifications In Patients With TPMT And NUDT15 Deficiency

• Consider testing for TPMT and NUDT15 deficiency in patients who experience severe myelosuppression or repeated episodes of myelosuppression.

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 Purinethol in patients who are known to have homozygous TPMT or NUDT15 deficiency.

Heterozygous Deficiency In TPMT And/Or NUDT15

• Reduce the Purinethol dose based on tolerability.
• Most patients with heterozygous TPMT or NUDT15 deficiency tolerate the recommended dosage, but some require a dose reduction based on adverse reactions.
•  Patients who are heterozygous for both TPMT and NUDT15 may require more substantial dose reductions.

Dosage Modifications In Renal And Hepatic Impairment

Renal Impairment

• Use the lowest recommended starting dosage for Purinethol in patients with renal impairment (CLcr less than 50 mL/min).
• Adjust the dosage to maintain absolute neutrophil count (ANC) at a desirable level and for adverse reactions.

Hepatic Impairment

• Use the lowest recommended starting dosage for Purinethol in patients with hepatic impairment.
• Adjust the dosage to maintain absolute neutrophil count (ANC) at a desirable level and for adverse reactions.

Dosage Modification With Concomitant Use Of Allopurinol

• Reduce the dose of Purinethol to one-third to one-quarter of the current dosage when coadministered with allopurinol.

Warfarin

• The concomitant administration of Purinethol 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.

Myelosuppressive Products

• Purinethol can cause myelosuppression. Myelosuppression may be increased when Purinethol 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 Purinethol for excessive myelosuppression.

Aminosalicylates

• Aminosalicylates (e.g., mesalamine, olsalazine or sulfasalazine) may inhibit the TPMT enzyme, which may increase the risk of myelosuppression when coadministered with Purinethol. When aminosalicylates and Purinethol are coadministered, use the lowest possible doses for each drug and monitor more frequently for myelosuppression.

Hepatotoxic Products

• Purinethol can cause hepatotoxicity. Hepatotoxicity may be increased when Purinethol is coadministered with other products that cause hepatotoxicity. Monitor liver tests more frequently in patients who are receiving Purinethol with other hepatotoxic products.

• Purinethol can cause fetal harm when administered to a pregnant woman.
• Pregnant women who receive mercaptopurine have an increased incidence of miscarriage and stillbirth.
• There are no data on the presence of mercaptopurine or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production.
• Because of the potential for serious adverse reactions in the breastfed child, women should not breastfeed during treatment with Purinethol and for 1 week after the last dose.