Mercaptopurine (mercaptopurine 50 mg) Dailymed

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 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. Monitor liver tests more frequently in patients who are receiving Mercaptopurine Tablets with other hepatotoxic products [see Drug Interactions (7.5)] or with known pre-existing liver disease. Withhold Mercaptopurine Tablets 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 Tablets during pregnancy. Mercaptopurine is not indicated for use in inflammatory bowel disease [see Indications and Usage (1.1)]. Discontinue Mercaptopurine Tablets if ICP develops in a pregnant woman.

Mercaptopurine Tablets 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 Tablets and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Mercaptopurine Tablets and for 3 months after the last dose

Mercaptopurine Tablets 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 Tablets and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Mercaptopurine Tablets and for 3 months after the last dose [see Use in Specific Populations (8.1, 8.3)].

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).



Risk Summary Mercaptopurine Tablets can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. Pregnant women who receive mercaptopurine have an increased incidence of miscarriage and stillbirth (see Data). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Women receiving mercaptopurine in the first trimester of pregnancy have an increased incidence of miscarriage; 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. Animal Data Mercaptopurine was embryo-lethal and teratogenic in several animal species (rat, mouse, rabbit, and hamster) at doses less than the recommended human dose.

Mercaptopurine Tablets can cause fetal harm when administered to pregnant women

Mercaptopurine Tablets can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify the pregnancy status in females of reproductive potential prior to initiating Mercaptopurine Tablets [see Use in Specific Populations (8.1)]. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Mercaptopurine Tablets and for 6 months after the last dose. Males Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with Mercaptopurine Tablets and for 3 months after the last dose [see Nonclinical Toxicology (13.1)]. Infertility Females and Males Based on findings from animal studies, Mercaptopurine Tablets can impair female and male fertility [see Nonclinical Toxicology (13.1)]. The long-term effects of mercaptopurine on female and male fertility, including the reversibility have not been studied.

Mercaptopurine is carcinogenic in animals. Mercaptopurine causes chromosomal aberrations in cells derived from animals and humans and induces dominantlethal mutations in the germ cells of male mice. Mercaptopurine can 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