Mercaptopurine

Mercaptopurine is a prescription medication used for the treatment of acute lymphatic leukemia.

• Mercaptopurine is available under the following different brand names: Purinethol, Purixan, 6Mercaptopurine, 6MP

Adult and pediatric dosage

Tablet

• 50mg

Oral suspension

• 20mg/mL

Acute Lymphatic Leukemia

Adult dosage

• Induction: 2.5 mg/kg orally every day; usually 100-200 mg orally every day in an average adult (other agents preferred)  
• May increase by 5 mg/kg/day after 4 weeks
• Maintenance: 1.5-2.5 mg/kg orally every day
• Reduce dose by 75% if concomitant allopurinol administration

Pediatric dosage

• Starting dose: 1.25-2.5 mg/kg (50-75 mg/m²) orally every day  
• Maintenance: 1.5-2.5 mg/kg orally every day in combination with methotrexate
• Reduce dose by 75% if concomitant allopurinol administration

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Mercaptopurine include:

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

Serious side effects of Mercaptopurine include:

• 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).

Rare side effects of Mercaptopurine include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Mercaptopurine has severe interactions with the following drug:
  • febuxostat
• Mercaptopurine has serious interactions with at least 30 other drugs.
• Mercaptopurine has moderate interactions with at least 69 other drugs.
• Mercaptopurine has minor interactions with the following drugs:
  • benazepril
  • maitake
  • taurine
  • vitamin A
  • vitamin E

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Mercaptopurine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Mercaptopurine?”

Cautions

• Renal impairment
• Recommended that evaluation of hemoglobin or hematocrit, total white blood cell count and differential count, and quantitative platelet count be obtained weekly while the patient is on therapy
• Macrophage activation syndrome (MAS) (hemophagocytic lymphohistiocytosis) a life-threatening disorder, may develop in patients with autoimmune conditions, in particular with inflammatory bowel disease (IBD); there could potentially be an increased susceptibility to developing the condition with the use of mercaptopurine (an unapproved use); if MAS occurs, or is suspected, discontinue therapy; monitor for and promptly treat infections such as EBV and cytomegalovirus (CMV), as these are known triggers for MAS
• Drug fever is very rarely reported; before attributing fever to the drug, make every attempt to exclude more common causes of pyrexia, such as sepsis, in patients with acute leukemia
• Mercaptopurine is immunosuppressive and may impair the immune response to infectious agents or vaccines; due to 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
• Hepatotoxicity
  • Mercaptopurine is hepatotoxic; there are reports of deaths attributed to hepatic necrosis associated with administration of the drug; 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 the 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, 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 tests more frequently in patients who are receiving therapy with other hepatotoxic products or with known pre-existing liver disease; withhold therapy at the onset of hepatotoxicity
• Myelosuppression
  • The most consistent, dose-related adverse reaction is myelosuppression, manifested by anemia, leukopenia, thrombocytopenia, or any combination of these; monitor CBC and adjust dosage for excessive myelosuppression
  • Bone marrow examination may be useful for the evaluation of marrow status; the decision to increase, decrease, continue, or discontinue a given dosage must be based upon the degree of severity and rapidity with which changes are occurring; in many instances, particularly during the induction phase of acute leukemia, complete blood counts will need to be done more frequently than once weekly in order to evaluate the effect of therapy
  • Myelosuppression can be exacerbated by coadministration with allopurinol, aminosalicylates, or other products that cause myelosuppression; reduce the dose by 75% (ie, give a quarter dose) when used concurrently with allopurinol
  • Increased risk of bone marrow toxicity; evaluate patients with repeated severe myelosuppression for thiopurine S-methyltransferase (TPMT) or nucleotide diphosphatase (NUDT15) deficiency; TPMT genotyping or phenotyping (red blood cell TPMT activity) and NUDT15 genotyping can identify patients who have reduced activity of these enzymes; patients with homozygous TPMT or NUDT15 deficiency require substantial dosage reductions of the drug
  • 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; increased risk appears to be related to degree and duration of immunosuppression; discontinuation of immunosuppression reported to provide partial regression of lymphoproliferative disorder; a treatment regimen containing multiple immunosuppressants (including thiopurines) should 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
• Hepatosplenic T-cell lymphomas
  • Rare postmarketing cases were reported primarily in adolescent and young adult patients with Crohn's disease and ulcerative colitis treated with TNF blockers
  • Reports have also included a patient being treated for psoriasis and 2 patients being treated for rheumatoid arthritis
  • HSTCL is an aggressive, rare type of T-cell lymphoma (usually fatal)
  • Most reported cases with TNF blockers have occurred with concomitant treatment with azathioprine or 6-mercaptopurine, although there have been cases reported receiving azathioprine or mercaptopurine alone
  • The following HSTCL cases have been identified in the FDA Adverse Event Reporting System (AERS) database, the literature, and the HSTCL Cancer Survivors' Network: infliximab (20), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0), azathioprine (12), and mercaptopurine (3)

Pregnancy and Lactation

• Therapy can cause fetal harm when administered to a pregnant woman; pregnant women who receive mercaptopurine have an increased incidence of miscarriage and stillbirth; advise pregnant women of the potential risk to the fetus
• Verify pregnancy status in females of reproductive potential prior to initiating therapy
• Reproductive potential
  • Females: Advise females of reproductive potential to use effective contraception during treatment 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 PURIXAN and for 3 months after the last dose
• Infertility
  • Females and males: Based on findings from animal studies, drugs can impair female and male fertility; the long-term effects on female and male fertility, including the reversibility, have not been studied
• Lactation
  • There are no data on the presence of mercaptopurine or metabolites in human milk, effects on the breastfed child, or on milk production; because of the potential for serious adverse reactions