Adult: As part of combination chemotherapy maintenance regimen: 1.5-2.5 mg/kg once daily or 50-75 mg/m2 once daily. Dose and treatment duration are based on the combination regimen used and should be carefully adjusted according to individual response and tolerability. Dosage and treatment recommendations may vary among individual products and between countries (refer to specific product guidelines). Child: Same as adult dose.
What are the brands available for Mercaptopurine in Philippines?
Patients receiving allopurinol: Decrease the dose of mercaptopurine by 25-33%.
Pharmacogenomics:
Mercaptopurine is catabolised by thiopurine methyltransferase (TPMT) into an inactive methylmercaptopurine base, thereby reducing the amount of parent drug available to form active thioguanine nucleotides (TGNs). TPMT variant alleles are associated with reduced enzyme activity and significant pharmacological effects on thiopurines. Nudix (nucleoside diphosphate linked moiety X)-type motif 15 (NUDT15) catalyses the conversion of cytotoxic thioguanine triphosphate (TGTP) metabolites into the less toxic thioguanine monophosphate. Deficiencies in NUDT15-mediated degradation of TGTP result in increased TGTP availability for incorporation into DNA, thereby promoting DNA damage and apoptosis. Inherited TPMT deficiency is the primary cause of thiopurine intolerance among Europeans and Africans, whereas risk alleles in NUDT15 are responsible for the majority of thiopurine-induced myelosuppression in Asians and are also common in Hispanic populations. TPMT genotyping or phenotyping, and NUDT15 genotyping may assist in identifying patients at risk of developing toxicity. Testing for NUDT15 and TPMT deficiency should be considered in patients who experience severe bone marrow toxicities or recurrent episodes of myelosuppression.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of November 2018:
Dosage recommendations based on TMPT Phenotypes:
Phenotype and Genotype
Implications
Recommendations
TPMT normal metaboliser
Individuals carrying 2 normal functional alleles e.g. *1/*1
Lower levels of TGN metabolites are observed, with a normal risk of thiopurine-related leucopenia, neutropenia and myelosuppression.
Initiate therapy using the normal starting dose (e.g. 1.5 mg/kg daily or 75 mg/m2 daily), then adjust the mercaptopurine dose, including other combination agents, without special emphasis on mercaptopurine. After each dose adjustment, allow at least 2 weeks to reach steady-state concentrations.
TPMT intermediate metaboliser
Individuals carrying 1 normal functional allele and 1 non-functional allele e.g. *1/*2, *1/*3A, *1/*3B, *1/*3C, *1/*4
Moderate to high levels of TGN metabolites are observed, with an increased risk of thiopurine-related leucopenia, neutropenia, and myelosuppression.
Normal starting dose ≥1.5 mg/kg daily or ≥75 mg/m2 daily: Initiate therapy using 30-80% of normal dose (e.g. initiate at 0.45-1.2 mg/kg daily or 22.5-60 mg/m2 daily), then adjust mercaptopurine dose according to the degree of myelosuppression and disease-specific guidelines. After each dose adjustment, allow 2-4 weeks to reach steady-state concentrations. If myelosuppression occurs, emphasis must be on the reduction of mercaptopurine dose over other agents (depending on other combination therapy). Normal starting dose <1.5 mg/kg daily or <75 mg/m2 daily: Dose reduction may not be recommended.
TPMT possible intermediate metaboliser
Individuals carrying 1 uncertain/unknown functional allele and 1 non-functional allele e.g. *2/*8, *3A/*7
Moderate to high levels of TGN metabolites are observed, with an increased risk of thiopurine-related leucopenia, neutropenia, and myelosuppression.
Normal starting dose ≥1.5 mg/kg daily or ≥75 mg/m2 daily: Initiate therapy using 30-80% of normal dose (e.g. initiate at 0.45-1.2 mg/kg daily or 22.5-60 mg/m2 daily), then adjust mercaptopurine dose according to the degree of myelosuppression and disease-specific guidelines. After each dose adjustment, allow 2-4 weeks to reach steady-state concentrations. If myelosuppression occurs, emphasis must be on the reduction of mercaptopurine dose over other agents (depending on other combination therapy). Normal starting dose <1.5 mg/kg daily or <75 mg/m2 daily: Dose reduction may not be recommended.
Extremely high levels of TGN metabolites are observed, leading to possible fatal toxicity without dose reduction and with a significantly increased risk of thiopurine-related leucopenia, neutropenia and myelosuppression.
Malignant conditions: Initiate therapy using a drastically reduced dose and frequency. Decrease the daily dose by 10-fold and adjust the frequency to 3 times weekly instead of once daily (e.g. 10 mg/m2 daily given just 3 times weekly), then adjust mercaptopurine dose according to the degree of myelosuppression and disease-specific guidelines. After each dose adjustment, allow 4-6 weeks to reach steady-state concentrations. If myelosuppression occurs, emphasis must be on the reduction of mercaptopurine dose over other agents (depending on other combination therapy). Non-malignant conditions: Consider alternative non-thiopurine immunosuppressant.
Dosage recommendations based on NUDT15 Phenotypes:
Phenotype and Genotype
Implications
Recommendations
NUDT15 normal metaboliser
Individuals carrying 2 normal functional alleles e.g. *1/*1
Normal risk of thiopurine-related leucopenia, neutropenia and myelosuppression.
Initiate therapy using the normal starting dose (e.g. 1.5 mg/kg daily or 75 mg/m2 daily), then adjust the mercaptopurine dose, including other combination agents, without special emphasis on mercaptopurine. After each dose adjustment, allow at least 2 weeks to reach steady-state concentrations.
NUDT15 intermediate metaboliser
Individuals carrying 1 normal functional allele and 1 non-functional allele e.g. *1/*2, *1/*3
Increased risk of thiopurine-related leucopenia, neutropenia and myelosuppression.
Normal starting dose ≥1.5 mg/kg daily or ≥75 mg/m2 daily: Initiate therapy using 30-80% of normal dose (e.g. initiate at 0.45-1.2 mg/kg daily or 22.5-60 mg/m2 daily), then adjust mercaptopurine dose according to the degree of myelosuppression and disease-specific guidelines. After each dose adjustment, allow 2-4 weeks to reach steady-state concentrations. If myelosuppression occurs, emphasis must be on the reduction of mercaptopurine dose over other agents (depending on other combination therapy). Normal starting dose <1.5 mg/kg daily or <75 mg/m2 daily: Dose reduction may not be recommended.
NUDT15 possible intermediate metaboliser
Individuals carrying 1 uncertain functional and 1 non-functional allele e.g. *2/*5, *3/*6
Increased risk of thiopurine-related leucopenia, neutropenia and myelosuppression.
Normal starting dose ≥1.5 mg/kg daily or ≥75 mg/m2 daily: Initiate therapy using 30-80% of normal dose (e.g. initiate at 0.45-1.2 mg/kg daily or 22.5-60 mg/m2 daily), then adjust mercaptopurine dose according to the degree of myelosuppression and disease-specific guidelines. After each dose adjustment, allow 2-4 weeks to reach steady-state concentrations. If myelosuppression occurs, emphasis must be on the reduction of mercaptopurine dose over other agents (depending on other combination therapy). Normal starting dose <1.5 mg/kg daily or <75 mg/m2 daily: Dose reduction may not be recommended.
NUDT15 poor metaboliser
Individuals carrying 2 non-functional alleles e.g. *2/*2, *2/*3, *3/*3
Significantly increased risk of thiopurine-related leucopenia, neutropenia and myelosuppression.
Malignant conditions: Initiate therapy at 10 mg/m2 daily, then adjust mercaptopurine dose according to the degree of myelosuppression and disease-specific guidelines. After each dose adjustment, allow 4-6 weeks to reach steady-state concentrations. If myelosuppression occurs, emphasis must be on the reduction of mercaptopurine dose over other agents (depending on other combination therapy). Non-malignant conditions: Consider alternative non-thiopurine immunosuppressant.
Dosage recommendations based on combination of TPMT and NUDT15 phenotypes from CPIC update as of March 2024:
Phenotype Combination
Recommendations
TPMT normal metaboliser and NUDT15 normal metaboliser
Initiate therapy using the normal starting dose (e.g. 1.5 mg/kg daily or 75 mg/m2 daily), then adjust the mercaptopurine dose, including other combination agents, without special emphasis on mercaptopurine. After each dose adjustment, allow at least 2 weeks to reach steady-state concentrations.
TPMT normal metaboliser and NUDT15 possible intermediate/intermediate metaboliser or NUDT15 normal metaboliser and TPMT possible intermediate/intermediate metaboliser
Normal starting dose ≥1.5 mg/kg daily or ≥75 mg/m2 daily: Initiate therapy using 30-80% of normal dose (e.g. initiate at 0.45-1.2 mg/kg daily or 22.5-60 mg/m2 daily), then adjust mercaptopurine dose according to the degree of myelosuppression and disease-specific guidelines. After each dose adjustment, allow 2-4 weeks to reach steady-state concentrations. If myelosuppression occurs, emphasis must be on the reduction of mercaptopurine dose over other agents (depending on other combination therapy). Normal starting dose <1.5 mg/kg daily or <75 mg/m2 daily: Dose reduction may not be recommended.
TPMT possible intermediate/intermediate metaboliser and NUDT15 possible intermediate/intermediate metaboliser
Normal starting dose ≥1.5 mg/kg daily or ≥75 mg/m2 daily: Initiate therapy using 20-50% of normal dose (e.g. initiate at 0.3-0.75 mg/kg daily or 15-37.5 mg/m2 daily), then adjust mercaptopurine dose according to the degree of myelosuppression and disease-specific guidelines. After each dose adjustment, allow 2-4 weeks to reach steady-state concentrations. If myelosuppression occurs, emphasis must be on the reduction of mercaptopurine dose over other agents (depending on other combination therapy). Normal starting dose 0.75 mg/kg daily or <37.5 mg/m2 daily: Dose reduction may not be recommended.
TPMT normal/possible intermediate/intermediate metaboliser and NUDT15 poor metaboliser
Malignant conditions: Initiate therapy at 10 mg/m2 daily, then adjust mercaptopurine dose according to the degree of myelosuppression and disease-specific guidelines. After each dose adjustment, allow 4-6 weeks to reach steady-state concentrations. If myelosuppression occurs, emphasis must be on the reduction of mercaptopurine dose over other agents (depending on other combination therapy). Non-malignant conditions: Consider alternative non-thiopurine immunosuppressant.
NUDT15 normal/possible intermediate/intermediate/poor metaboliser and TPMT poor metaboliser
Malignant conditions: Initiate therapy using a drastically reduced dose and frequency. Decrease the daily dose by 10-fold and adjust the frequency to 3 times weekly instead of once daily (e.g. 10 mg/m2 daily given just 3 times weekly), then adjust mercaptopurine dose according to the degree of myelosuppression and disease-specific guidelines. After each dose adjustment, allow 4-6 weeks to reach steady-state concentrations. If myelosuppression occurs, emphasis must be on the reduction of mercaptopurine dose over other agents (depending on other combination therapy). Non-malignant conditions: Consider alternative non-thiopurine immunosuppressant.
Follow the guidelines corresponding to the specific determinate phenotype; use the more stringent determinate phenotype for dosage adjustment (e.g. if the patient is a TPMT normal metaboliser and a NUDT15 poor metaboliser, follow the instructions for a NUDT15 poor metaboliser). Dosage or treatment recommendations may vary among countries. Refer to local guidelines for the appropriate clinical recommendations.
Renal Impairment
Dose reduction may be needed.
Hepatic Impairment
Dose reduction may be needed.
Administration
Mercaptopurine May be taken with or without food. Oral susp: Shake well before use.
Special Precautions
Patient with autoimmune conditions (e.g. inflammatory bowel disease), history of exposure to varicella-zoster virus. Concomitant administration with xanthine oxidase inhibitors (e.g. allopurinol, febuxostat) and live vaccines. Mercaptopurine is available in different formulations that are not bioequivalent; close haematological monitoring is recommended when switching between formulations. TPMT or NUDT15 normal, intermediate, possible intermediate, and poor metabolisers. Hepatic and renal impairment. Children. Pregnancy (avoid use, particularly during the 1st trimester) and lactation.
Adverse Reactions
Significant: Myelosuppression manifested by anaemia, leucopenia, thrombocytopenia (dose-related); hepatotoxicity (e.g. jaundice, ascites, intrahepatic cholestasis [including intrahepatic cholestasis of pregnancy], parenchymal cell necrosis, hepatic encephalopathy); immunosuppression, increased risk for infection; secondary malignancies (e.g. melanoma and non-melanoma skin cancers, Kaposi and non-Kaposi sarcoma); photosensitivity. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, oral lesions, pancreatitis. General disorders and administration site conditions: Malaise. Hepatobiliary disorders: Hyperbilirubinaemia. Investigations: Increased serum transaminases. Metabolism and nutrition disorders: Anorexia, hyperuricaemia. Skin and subcutaneous tissue disorders: Rash, urticaria, hyperpigmentation. Potentially Fatal: Hepatic necrosis; development of macrophage activation syndrome (MAS) in patients with autoimmune conditions (particularly inflammatory bowel disease).
Women of childbearing potential and males with female partners of childbearing potential must use effective contraception during therapy and for 3 months after treatment. Breastfeeding is not recommended during therapy and for 1 week after the last dose. Avoid or minimise exposure to sunlight (including UV light); if exposure cannot be avoided, use sunscreens or wear protective clothing.
Monitoring Parameters
Verify pregnancy status in women of childbearing potential and consider TPMT genotyping or phenotyping, and NUDT15 genotyping before treatment initiation. Hepatitis B virus screening including HBsAg, hepatitis B core antibody, total Ig or IgG, and antibody to HBsAg is recommended before or at the beginning of systemic anticancer therapy. Monitor CBC with differential (initially at weekly intervals, or more frequently depending on clinical status), LFTs such as transaminases, alkaline phosphatase, or bilirubin (initially at weekly intervals, then monthly, or more frequently to those with hepatic impairment), and renal function. Perform bone marrow examination (particularly in patients with prolonged or repeated myelosuppression) and urinalysis. Assess for signs and symptoms of photosensitivity reactions, infection, malignancy, and bleeding.
Overdosage
Symptoms: Nausea, vomiting, diarrhoea, anorexia, gastroenteritis, myelosuppression, and liver dysfunction. Management: Supportive treatment. Closely monitor blood counts and institute blood transfusion if necessary.
Drug Interactions
Xanthine oxidase inhibitors (e.g. allopurinol, febuxostat) may decrease the metabolism and increase the serum concentration of mercaptopurine. May reduce the immune response to vaccines and increase the risk of infection, particularly from live vaccines. May increase the risk of myelosuppression with aminosalicylates (e.g. mesalazine, olsalazine, sulfasalazine), trimethoprim-sulfamethoxazole, ribavirin, and other myelosuppressive agents. May diminish the anticoagulant effect of warfarin. Increased risk of hepatotoxicity with other hepatotoxic agents.
Food Interaction
Food may slightly reduce the systemic exposure of mercaptopurine. May decrease plasma concentration with milk or any dairy products.
Action
Description: Mechanism of Action: Mercaptopurine, a purine analogue, is an antimetabolite antineoplastic agent that acts specifically in the S phase of the cell cycle. It requires intracellular transport and activation to form metabolites, including thioguanine nucleotides, which incorporate into DNA and RNA, resulting in cell death and cell-cycle arrest. Pharmacokinetics: Absorption: Variably and incompletely absorbed from the gastrointestinal tract. Food may slightly reduce the systemic exposure. Distribution: Widely distributed in tissues and throughout body water. Crosses the blood-brain barrier. Plasma protein binding: Approx 19%. Metabolism: Rapidly and extensively metabolised in the liver via thiol methylation by thiopurine S-methyltransferase (TPMT) into methyl-mercaptopurine (inactive metabolite), and via oxidation by xanthine oxidase into 6-thiouric acid (inactive metabolite); undergoes first-pass metabolism. Excretion: Via urine (46%, as unchanged drug and metabolites). Elimination half-life: <2 hours.
Chemical Structure
Mercaptopurine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 667490, Mercaptopurine. https://pubchem.ncbi.nlm.nih.gov/compound/Mercaptopurine. Accessed May 28, 2025.
Storage
Store below 25ºC. Oral susp: Use within 8 weeks after 1st opening. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
Sign Out
Continue with Google