Mercaptopurine – Uses, Dosage, Side Effects, Drug Interactions

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Mercaptopurine is an antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.

Mercaptopurine Anhydrous is the anhydrous form of mercaptopurine, a thiopurine-derivative antimetabolite with antineoplastic and immunosuppressive activities. Produced through the metabolism of mercaptopurine by hypoxanthine-guanine phosphoribosyltransferase (HGPRT), mercaptopurine metabolites 6-thioguanine-5′-phosphate (6-thioGMP) and 6-the inosine monophosphate (T-IMP) inhibit nucleotide interconversions and de novo purine synthesis, thereby blocking the formation of purine nucleotides and inhibiting DNA synthesis. This agent is also incorporated into DNA in the form of deoxythioguanosine, which results in the disruption of DNA replication. In addition, mercaptopurine is converted to 6-methyl mercaptopurine ribonucleoside (MMPR) by 6-thiopurine methyltransferase; MMPRs are also potent inhibitors of de novo purine synthesis.

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Mercaptopurine is a medication used for cancer and autoimmune diseases. Specifically, it is used to treat acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), Crohn’s disease, and ulcerative colitis. For ALL it is generally used with methotrexate. It is taken by mouth. It is an antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.

Mechanism of action of Mercaptopurine

Mercaptopurine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to thioinosinic acid (TIMP). This intracellular nucleotide inhibits several reactions involving inosinic acid (IMP), including the conversion of IMP to xanthylic acid (XMP) and the conversion of IMP to adenylic acid (AMP) via adenylosuccinate (SAMP). In addition, 6-methylthioinosinate (MTIMP) is formed by the methylation of TIMP. Both TIMP and MTIMP have been reported to inhibit glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis. Experiments indicate that radiolabeled mercaptopurine may be recovered from the DNA in the form of deoxythioguanosine. Some mercaptopurine is converted to nucleotide derivatives of 6-thioguanine (6-TG) by the sequential actions of inosinate (IMP) dehydrogenase and xanthate (XMP) aminase, converting TIMP to thioguanylic acid (TGMP).

Indications of Mercaptopurine

  • Crohn’s disease, 
  • Acute lymphoblastic leukemia
  • Autoimmune hepatitis,
  • Cancer in the primary stage, Cyst, small tumor
  • Inflammatory bowel disease
  • Intestinal arterial insufficiency
  • Ulcerative colitis, maintenance
  • Acute lymphoblastic leukemias
  • Acute promyelocytic leukemia
  • Hepatitis, autoimmune
  • Lymphoma, lymphoblastic
  • Ulcerative colitis
  • Mercaptopurine is approved to be used with other drugs to treat: Acute lymphoblastic leukemia (ALL). It is used as maintenance therapy in adults and children.
  • Mercaptopurine tablets are indicated for maintenance therapy of acute lymphatic (lymphocytic, lymophoblastic) leukemia as part of a combination regimen. The response to this agent depends upon the particular subclassification of acute lymphatic leukemia and the age of the patient (pediatric or adult).
  • Mercaptopurine is not effective prophylaxis or treatment of central nervous system leukemia.
  • Mercaptopurine is also being studied in the treatment of other types of cancer.

Contra-Indications of Mercaptopurine

  • Extreme loss of body water
  • Decreased function of bone marrow
  • Anemia
  • Decreased blood platelets
  • Decreased white blood cells
  • Decreased neutrophils a type of white blood cell
  • Stomach or intestinal ulcer
  • Liver Problems
  • Blockage of normal bile flow
  • Acute inflammation of the pancreas
  • kidney disease with a reduction in kidney function
  • The high amount of bilirubin in the blood
  • Ascites
  • Abnormal liver function tests
  • Pregnancy
  • Thiopurine S-methyltransferase deficiency
  • Hepatosplenic T-cell lymphoma

Dosage of Mercaptopurine

Strengths: 50 mg; 100 mg/5 mL

Acute Lymphoblastic Leukemia

Initial Dosage

  • Oral: 2.5 mg/kg of body weight per day (100 to 200 mg in the average adult). This dose may be continued daily for several weeks or more in some patients. If, after 4 weeks at this dosage, there is no clinical improvement and no definite evidence of leukocyte or platelet depression, the dosage may be increased up to 5 mg/kg daily. A dosage of 2.5 mg/kg per day may result in a rapid fall in leukocyte count within 1 to 2 weeks in some adults with acute lymphatic leukemia and high total leukocyte counts.
  • The total daily dosage may be given at one time. It is calculated to the nearest multiple of 25 mg.

Crohn’s Disease – Acute stage

  • Oral: 1.0 to 1.5 mg/kg of body weight per day

Crohn’s Disease – Maintenance

  • Oral: 1.0 to 1.5 mg/kg of body weight per day

Ulcerative Colitis – Maintenance

  • Oral: 1.0 to 1.5 mg/kg of body weight per day

Inflammatory Bowel Disease

  • Oral: 1.0 to 1.5 mg/kg of body weight per day

Pediatric Intestinal Arterial Insufficiency

Initial Dosage

  • Oral: 2.5 mg/kg of body weight per day (50 mg in an average 5-year-old child). Pediatric patients with acute leukemia have tolerated this dose without difficulty in most cases; it may be continued daily for several weeks or more in some patients. If, after 4 weeks at this dosage, there is no clinical improvement and no definite evidence of leukocyte or platelet depression, the dosage may be increased up to 5 mg/kg daily. A dosage of 2.5 mg/kg per day may result in a rapid fall in leukocyte count within 1 to 2 weeks in some adults with acute lymphatic leukemia and high total leukocyte counts.
  • The total daily dosage may be given at one time. It is calculated to the nearest multiple of 25 mg.

Side effects of Mercaptopurine

The most common

More common

Less common

Drug Interactions of Mercaptopurine

Mercaptopurine may interact with following drugs, suppliments & may change the drug efficasy

Pregnancy & Lactation of Mercaptopurine

FDA Pregnancy Category D

Pregnancy

There is a possibility of a birth defect if either the man or woman is using mercaptopurine at the time of conception, or if it is taken during pregnancy. Effective birth control should be practiced while using this medication. This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while you or your partner are taking this medication, contact your doctor immediately.

Lactation

This medication passes into breast milk. Because of the risks associated with mercaptopurine, a decision should be made to cease breastfeeding or discontinue the medication, taking into account the importance of the medication to the mother. Women who are taking this medication should not breastfeed.

FAQ

  • Mercaptopurine is used in combination with other medicines as a maintenance treatment of acute lymphoblastic leukemia. It belongs to the group of medicines known as antimetabolites. Mercaptopurine interferes with the growth of cancer cells, which are eventually destroyed.
What is another name for mercaptopurine?
  • Mercaptopurine is the generic name for the trade name drug Purinethol or Purixan. In some cases, healthcare professionals may use the trade name Purinethol®, Purixan® or other names 6-Mercaptopurine and 6-MP when referring to the generic drug name mercaptopurine.
  • Mercaptopurine is a medication used in the management and treatment of acute lymphoblastic leukemia. It is in the class of medications known as purine antagonists
  • Azathioprine and mercaptopurine are chemically closely related. Azathioprine is converted to mercaptopurine in the body and both medications act in a very similar way. Although they are similar, some people who cannot tolerate azathioprine because of side effects may still be able to take mercaptopurine
  • In the view of the clinical efficacy, results achieved by 6-MP treatment can be compared with azathioprine. Considering bioequivalence, 6-MP shows the same efficacy as half (0.75-1.5 mg/kg per day) of the daily dose of AZA (1.5-2.5 mg/kg per day)[19]
  • How it works:This medication belongs to a class of drugs called immunomodulators. It helps to reduce irritation and swelling (inflammation) in the intestines. It also decreases the long-term need for steroids. For that reason, it is sometimes referred to as a “steroid-sparing” drug
  • Both 6-MP and Aza are well-known causes of drug-induced liver injury. At least 4 patterns of injury have been associated with their use. The first, and most common, is transient and usually asymptomatic elevations in serum enzymes, mostly ALT and AST, that occurs in 5–15% of treated subjects.
  • You take mercaptopurine in the evening, with food or on an empty stomach. But whichever you choose, you should do the same thing each day. You should drink some water after taking the liquid. You should not take tablets or liquid at the same time as milk or dairy products
  • Research suggests that the effectiveness of azathioprine and mercaptopurine does not diminish over time. While guidelines state that stopping treatment may be considered after four years for patients remaining in remission, many experts now believe thiopurine treatment should be continued indefinitely
  • Cases of hepatosplenic T-cell lymphoma have been reported in patients treated with mercaptopurine for inflammatory bowel disease, for which mercaptopurine is not approved. Mercaptopurine is mutagenic in animals and humans, carcinogenic in animals, and may increase the risk of secondary malignancies
  • MERCAPTOPURINE, 6-MP (mer kap toe PYOOR een) is a chemotherapy drug. It interferes with the growth of cancer cells and can reduce immune system activity. It is used to treat certain types of acute leukemia
  • This medicine may increase your risk of getting certain types of cancer, including skin cancer and cervical cancer. Some teenagers and young adults with Crohn’s disease or ulcerative colitis developed a rare type of cancer called hepatosplenic T-cell lymphoma (HSTCL)
  • Mercaptopurine is in a class of medications called purine antagonists. It works by stopping the growth of cancer cells.
  • Mechanisms of action is Specifically, Mercaptopurine is a purine antimetabolite or purine antagonist as such inhibits DNA synthesis by inhibiting the production of the purine containing nucleotides, adenine and guanine thus halting DNA synthesis
  • Mercaptopurine works to reduce inflammation in the body by targeting the immune system. 6MP is given at a lower dose than azathioprine. It may take up to 6 months for the 6MP to start working effectively. Your doctor may want you to continue taking other medicines during this time to help manage your disease
  • Mercaptopurine can also lead to a distinctive acute, clinically apparent liver injury that usually presents with fatigue and jaundice and a cholestatic or mixed pattern of serum enzyme elevations 1 to 6 months after starting therapy, but sometimes later, particularly following an increase in dose
  • The authors found that treatment with 6MP did not affect sperm morphology or sperm production compared with controls. However, pregnancy rates were inversely related to escalating doses of 6MP
  • Both Azathioprine and 6-Mercaptopurine (6-MP) belong to a group of drugs called thiopurines which are immunosuppressants. Thiopurines work by suppressing inflammation and slowing down the body’s immune response. They are also used to avoid rejection following organ transplantation.
  • Steady-state concentrations were reached after 4 weeks, indicating a half-life of approximately 5 days for both 6-TGN and 6-MMPR; the concentrations were 368 (CI95% 284-452) and 2837 (CI95% 2101-3573) pmol/8 x 10 RBCs, respectively
  • Mercaptopurine can affect your kidneys. Drink plenty of liquids to keep your kidneys working properly. You may be given other medication to help prevent serious side effects on your kidneys. Keep using this medicine for as long as your doctor has prescribed.
  • Your hair may become thin, brittle, or may fall out. This typically begins two to three weeks after treatment starts. This hair loss can be all body hair, including pubic, underarm, legs/arms, eyelashes, and nose hairs. The use of scarves, wigs, hats and hairpieces may help.
  • With regard to fathers taking thiopurines, one study suggests azathioprine and mercaptopurine do not reduce sperm quality, but some manufacturers say mercaptopurine may occasionally cause temporary reductions in sperm counts
  • Azathioprine and mercaptopurine have been associated with a number of liver abnormalities, including hepatitis, veno-occlusive disease, nodular regenerative hyperplasia, and peliosis hepatitis.
  • Weight gain isn’t a common side effect of mercaptopurine (Purinethol). Talk to your provider if you experience notable changes in weight while you’re taking this medication and are concerned
  • Possible Side Effects (More Common) may raise your risk of infection, make you tired and weak (fatigue), and raise your risk of bleeding. Soreness of the mouth and throat may happen with high doses of this drug.
  • Mercaptopurine and milk
  • Both in vivo and in vitro studies have demonstrated that drinking cow’s milk while taking mercaptopurine decreases its bioavailability and may result in clinically significant interactions. Consequently, experts suggest refraining from drinking cow’s milk around the time of taking the drug.
  • You should not take mercaptopurine tablets or liquid with milk or dairy products. Take it: at least 1 hour before having milk or dairy products. at least 2 hours after having milk or dairy products.
  • However there is a risk of relapsing if you stop taking azathioprine or mercaptopurine. Around 1 in 5 people with Crohn’s and 1 in 10 with Ulcerative Colitis are at risk of relapsing within a year of stopping treatment.
  • It is important to take Mercaptopurine in the evening to make the medicine more effective. If you take more Mercaptopurine than you should, you may feel sick, vomit or have diarrhoea
  • Adults—Dose is based on body weight and must be determined by your doctor. At first, 1.5 to 2.5 milligrams (mg) per kilogram (kg) of body weight per day, taken as a single dose. Your doctor may adjust your dose as needed and tolerated. Children—Use and dos
  • Abstract. 6-Mercaptopurine (6-MP) has an important role in the treatment of inflammatory bowel disease. Its most frequent short-term complication has proven to be pancreatitis, which we have now seen in 13 of 400 (3.25%) patients (12 Crohn’s disease, 1 ulcerative colitis) and which we here describe
  • Mercaptopurine is a prodrug that must first be activated to form thioguanine nucleotides (TGNs), of which 6-thioguanine triphosphate (6-TGTP) is the major active metabolite. Two of the enzymes involved in the complex pathway of these metabolites are thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15).
  • Exactly 70 years ago [1951] mercaptopurine was discovered by Gertrude Elion as a novel treatment option for acute leukaemia. A total of three thiopurines (also thioguanine [1950] and azathioprine [1957]) were developed over time
  • Take as a daily dose at the same time each day. Preferable to take on an empty stomach (1 hour before or 2 hours after meals)
  • Very bad and sometimes life-threatening blood and bone marrow problems like anemia, low platelet counts, or low white blood cell counts have happened with this drug. Change in dose or even stopping the drug may be needed if any of these side effects happen.
  • 6-mercaptopurine is an active cytotoxic agent and should be used only under the direction of physician experienced in the administration of such agents.
  • Mercaptopurine can reduce the production of white and red blood cells. Your physician will likely want to conduct regular blood tests to ensure there is no damage to your bone marrow. You may also be tested for TPMT deficiency, which can affect your immune system.
  • Aminosalicylates. Aminosalicylates, also known as 5-ASAs, are medicines that help to reduce inflammation. This in turn allows damaged tissue to heal. They’re usually the first treatment option for mild or moderate ulcerative colitis.
  • 6-mercaptopurine is a mainstay of acute lymphoblastic leukemia treatment. It has a narrow therapeutic window, dictated by its metabolite, thioguanine and 6-methylmercaptopurine. Skin manifestations usually consist of mild facial rash or hypersensitivity exanthems.
  • It is known that immunosuppressive drugs can affect male sexual health and reproduction via multiple mechanisms: by altering reproductive hormone secretion and/or action, by disrupting spermatogenesis or sperm motility and by causing sexual dysfunction (Sasaki et al., 2011).
  • Other medicines can often be used to treat inflammatory conditions during pregnancy. However, azathioprine and mercaptopurine are usually considered to be among the safest options, as several studies have shown that they do not harm the baby.
More common
  • Black, tarry stools.
  • clay colored stools.
  • cough or hoarseness.
  • decreased appetite.
  • fever or chills.
  • headache.
  • nausea, vomiting.
  • rash, itchy skin.
  • Azathioprine has been used for IBD for over 30 years. Mercaptopurine is a newer drug and tends to be prescribed less frequently in the UK. A number of studies have found that these drugs can help to reduce symptoms and maintain remission in about six out 10 people with UC and seven out of 10 people with Crohn’s.
  • It may be 3 to 12 weeks before you notice any benefits, but it is working during this period. Mercaptopurine may need to be taken for several years. Regular blood tests will be taken to check that your bone marrow and liver is working properly and not being affected by this medicine.
  • You take mercaptopurine in the evening, with food or on an empty stomach. But whichever you choose, you should do the same thing each day. You should drink some water after taking the liquid. You should not take tablets or liquid at the same time as milk or dairy products.
  • Mercaptopurine is the generic name for the trade name drug Purinethol or Purixan. In some cases, health care professionals may use the trade name Purinethol®, Purixan® or other names 6-Mercaptopurine and 6-MP when referring to the generic drug name mercaptopurine.
  • How it works:This medication belongs to a class of drugs called immunomodulators. It helps to reduce irritation and swelling (inflammation) in the intestines. It also decreases the long-term need for steroids. For that reason, it is sometimes referred to as a “steroid-sparing” drug.
  • Research suggests that the effectiveness of azathioprine and mercaptopurine does not diminish over time. While guidelines state that stopping treatment may be considered after four years for patients remaining in remission, many experts now believe thiopurine treatment should be continued indefinitely.
  • Mercaptopurine is a medication used in the management and treatment of acute lymphoblastic leukemia. It is in the class of medications known as purine antagonists.
  • MERCAPTOPURINE, 6-MP (mer kap toe PYOOR een) is a chemotherapy drug. It interferes with the growth of cancer cells and can reduce immune system activity. It is used to treat certain types of acute leukemia.
  • Both Azathioprine and 6-Mercaptopurine (6-MP) belong to a group of drugs called thiopurines which are immunosuppressants. Thiopurines work by suppressing inflammation and slowing down the body’s immune response. They are also used to avoid rejection following organ transplantation.
  • Mercaptopurine can affect your kidneys. Drink plenty of liquids to keep your kidneys working properly. You may be given other medication to help prevent serious side effects on your kidneys. Keep using this medicine for as long as your doctor has prescribed.
  • This medicine may increase your risk of getting certain types of cancer, including skin cancer and cervical cancer. Some teenagers and young adults with Crohn’s disease or ulcerative colitis developed a rare type of cancer called hepatosplenic T-cell lymphoma (HSTCL).
  • Fasting hypoglycemia is a known complication of mercaptopurine (6MP) maintenance therapy for acute lymphoblastic leukemia (ALL). It is associated with high levels of the methylated metabolite 6-methyl-mercaptopurine (6MMP). Symptoms of hypoglycemia include morning tremulousness, nausea, and vomiting

References

 

Mercaptopurine