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Mercaptopurine: Drug information

Mercaptopurine: Drug information
(For additional information see "Mercaptopurine: Patient drug information" and see "Mercaptopurine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Purixan
Brand Names: Canada
  • Purinethol
Pharmacologic Category
  • Antineoplastic Agent, Antimetabolite;
  • Antineoplastic Agent, Antimetabolite (Purine Analog);
  • Immunosuppressant Agent
Dosing: Adult

Note: Consider testing for thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (nucleotide diphosphatase [NUDT15]) deficiency; patients with TPMT or NUDT15 deficiency are at increased risk for severe toxicity at conventional mercaptopurine doses and generally require dose reduction (see Dosage adjustment for TPMT and/or NUDT15 deficiency below) (Ref).

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL): Maintenance: Oral: 1.5 to 2.5 mg/kg once daily (50 to 75 mg/m2 once daily); continue based on blood counts or

Off-label ALL dosing (combination chemotherapy; refer to specific reference for combinations):

Early intensification (two 4-week courses): 60 mg/m2/day days 1 to 14 (Ref).

Interim maintenance (12-week course): 60 mg/m2/day days 1 to 70 (Ref).

Maintenance (prolonged): 50 mg 3 times/day for 2 years (Ref) or 60 mg/m2/day for 2 years from diagnosis (Ref).

AALL0232 (Ref): Patients ≤30 years:

Consolidation: Oral: 60 mg/m2 once daily on days 1 to 14 and 29 to 42 of a 56-day cycle (in combination with cyclophosphamide, cytarabine, vincristine, pegaspargase, and intrathecal methotrexate).

Interim Maintenance 1 and 2: Oral: 25 mg/m2 once daily on days 1 to 56 (in combination with vincristine, high-dose methotrexate, and intrathecal methotrexate).

Maintenance phase: Oral: 75 mg/m2 once daily on days 1 to 84 of an 84-day cycle (in combination with vincristine, steroid, oral methotrexate, and intrathecal methotrexate). Maintenance cycles are repeated for a total duration of 2 years (females) and 3 years (males) from the start of Interim Maintenance I. During Maintenance, the mercaptopurine (and oral methotrexate) dose may be titrated to target absolute neutrophil count (ANC) and platelet count goals.

Acute promyelocytic leukemia, maintenance

Acute promyelocytic leukemia, maintenance (off-label use): 60 mg/m2/day for 1 year (in combination with tretinoin and methotrexate) (Ref).

Crohn disease

Crohn disease (off-label use): Oral:

Maintenance of remission: 0.75 to 1.5 mg/kg/day in combination with an antitumor necrosis factor agent (eg, adalimumab, infliximab) (Ref).

Management after surgical resection: 1.5 mg/kg/day (in combination with metronidazole) for ~18 months after surgery (Ref) or 50 mg once daily for 24 months, beginning prior to discharge from hospital (Ref).

Hepatitis, autoimmune

Hepatitis, autoimmune (off-label use): Note: Reserve for patients with nonresponse or intolerance to first-line treatment. Oral: Initial: 25 mg once daily (in combination with a corticosteroid); may increase to 50 mg once daily as tolerated (Ref).

Lymphoblastic lymphoma

Lymphoblastic lymphoma (off-label use): Maintenance (prolonged): 50 mg 3 times daily for 2 years (Ref).

Ulcerative colitis, remission induction

Ulcerative colitis, remission induction (off-label use): Oral: Initial: 50 mg once daily; titrate up to 1.5 mg/kg/day as tolerated (Ref). Note: Monotherapy is not recommended in patients with moderately to severely active ulcerative colitis (Ref).

Ulcerative colitis, remission maintenance

Ulcerative colitis, remission maintenance (off-label use): Oral: 1 to 1.5 mg/kg/day (Ref).

Dosage adjustment for TPMT and/or NUDT15 deficiency:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines (Ref):

Normal TPMT or NUDT15 activity (wild type): No initial dosage adjustment necessary; adjust dose based on condition being treated. Allow at least 2 weeks after each dosage adjustment to reach steady state. For patients receiving combination therapy, dosage adjustments (of all agents) should be made without any emphasis on mercaptopurine compared to other agents.

TPMT intermediate or possible intermediate metabolizer or NUDT15 intermediate or possible intermediate metabolizer : Initiate mercaptopurine with the dose reduced to 30% to 80% of the usual dose and adjust dose based on the degree of myelosuppression and condition being treated. Allow 2 to 4 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy). If the starting dose is already below the normal recommended dose, dose reduction may not be recommended.

TPMT poor metabolizer: When used for malignancy, initiate mercaptopurine at a drastically reduced dose (reduce the daily dose by 10-fold and reduce the frequency from once daily to 3 times a week). Adjust dose based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy). When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy.

NUDT15 poor metabolizer: When used for malignancy, initiate mercaptopurine at 10 mg/m2/day. Adjust dose based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy). When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy.

Manufacturer’s labeling:

Heterozygous deficiency (intermediate activity): Reduce the dose based on tolerability; most patients with heterozygous deficiency of TPMT or NUDT15 tolerate recommended doses, although some require dosage reduction. Patients who are heterozygous for both TPMT and NUDT15 may require more substantial dose reductions.

Homozygous deficiency (low or deficient activity): Reduce the mercaptopurine dose to 10% of the usual dose or lower for homozygous deficiency in either TPMT or NUDT15.

Missed dose: If a dose is missed, continue with the next scheduled dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥50 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.

CrCl <50 mL/minute: Initiate with the lowest recommended starting dose or increase the dosing interval to every 36 to 48 hours to avoid accumulation in patients with renal impairment adjust dose to maintain desirable ANC level and for adverse reactions.

Dosing: Hepatic Impairment: Adult

Hepatic impairment at baseline: Initiate with the lowest recommended starting dose; adjust dose to maintain desirable ANC level and for adverse reactions.

Hepatotoxicity during treatment: Withhold therapy.

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).

Dosing: Adjustment for Toxicity: Adult

Adjust dosage for excessive hematologic toxicity.

Dosing: Older Adult

Due to renal decline with age, initiate treatment at the low end of recommended dose range.

Dosing: Pediatric

(For additional information see "Mercaptopurine: Pediatric drug information")

Dosage guidance:

Safety: Consider testing for thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (nucleotide diphosphatase [NUDT15]) deficiency, patients with minimal or no TPMT activity are at increased risk for severe toxicity at conventional mercaptopurine doses and generally require dose reduction (see "Dosage Adjustment for TPMT or NUDT15 Deficiency" below). Pediatric doses presented as mg/m2 and mg/kg; use caution.

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL): Limited data available; multiple regimens/protocols reported; refer to specific protocols.

Standard risk (Ref): Children 1 to <10 years: Consolidation, Interim Maintenance I and Maintenance: Oral: 75 mg/m2 once daily, frequency and duration dependent on protocol phase (in combination with vincristine, steroid, and methotrexate [oral and/or intrathecal]). Maintenance cycles are repeated for a total duration of 2 years (females) and 3 years (males) from the start of Interim Maintenance I. During Maintenance, oral methotrexate and mercaptopurine are adjusted to maintain a target ANC goal (generally 1,000 to 2,000/mm3; varies based on protocol).

High risk (Ref):

Children and Adolescents:

Consolidation: Oral: 60 mg/m2 once daily on days 1 to 14 and 29 to 42 of a 56-day cycle (in combination with cyclophosphamide, cytarabine, vincristine, pegaspargase, and intrathecal methotrexate).

Interim Maintenance 1 and 2: Oral: 25 mg/m2 once daily on days 1 to 56 (in combination with vincristine, high-dose methotrexate, and intrathecal methotrexate).

Maintenance phase: Oral: 75 mg/m2 once daily on days 1 to 84 of an 84-day cycle (in combination with vincristine, steroid, oral methotrexate, and intrathecal methotrexate). Maintenance cycles duration: 2 to 3 years (refer to specific protocol). During Maintenance, the oral methotrexate and mercaptopurine are titrated to a target ANC goal (generally 1,000 to 2,000/mm3; varies based on protocol).

Acute promyelocytic leukemia

Acute promyelocytic leukemia (APL): Limited data available; multiple regimens reported:

Combination with tretinoin: Maintenance phase: Children and Adolescents ≤14 years: Oral: 100 mg/m2/day for 14 days of a 28-day cycle in combination with tretinoin. Cycles were repeated every 28 days for 2 years (Ref).

Combination with tretinoin and methotrexate:

Kutny 2017: AAML0631: Maintenance phase: Children ≥2 years and Adolescents: Oral: 50 mg/m2/day for 9 cycles of 12 weeks in combination with methotrexate and tretinoin.

Ortega 2005: PETHEMA Group: Maintenance phase: Children and Adolescents <17 years: Oral: 50 mg/m2/day for 2 years in combination with methotrexate and tretinoin. Doses of mercaptopurine and methotrexate were decreased by 50% if the WBC count was <3,500 cells/mm3 and discontinued for WBC <2,500/mm3.

Powell 2010: North American Leukemia Intergroup Study C9710: Maintenance phase: Adolescents ≥15 years: Oral: 60 mg/m2/day for 1 year in combination with tretinoin and methotrexate.

Crohn disease, remission maintenance

Crohn disease, remission maintenance: Limited data available: Children and Adolescents: Oral: 1 to 1.5 mg/kg/day (Ref).

Hepatitis, autoimmune

Hepatitis, autoimmune (alternative agent): Limited data available: Note: Use should be reserved for patients not responsive or intolerant of other therapies (Ref).

Children and Adolescents: Oral: Initial: 0.5 to 1 mg/kg/day; monitor serum levels and adjust dose accordingly; a higher dose of 1.5 mg/kg/day has also been suggested (Ref).

Ulcerative colitis, remission maintenance

Ulcerative colitis, remission maintenance: Limited data available: Children and Adolescents: Oral: 1 to 1.5 mg/kg/day (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment in TPMT and/or NUDT15 deficiency: Limited data available:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines (Ref):

Normal TPMT or NUDT15 activity (wild type): No initial dosage adjustment necessary; adjust dose based on condition being treated. Allow at least 2 weeks after each dosage adjustment to reach steady state. For patients receiving combination therapy, dosage adjustments (of all agents) should be made without any emphasis on mercaptopurine compared to other agents.

TPMT intermediate or possible intermediate metabolizer or NUDT15 intermediate or possible intermediate metabolizer: Initiate mercaptopurine with the dose reduced to 30% to 80% of the usual dose and adjust dose based on the degree of myelosuppression and condition being treated. Allow 2 to 4 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy). If the starting dose is already below the normal recommended dose, dose reduction may not be recommended.

TPMT poor metabolizer:

• When used for malignancy, initiate mercaptopurine at a drastically reduced dose (reduce the daily dose by 10-fold and reduce the frequency from once daily to 3 times a week). Adjust dose based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy).

• When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy.

NUDT15 poor metabolizer:

• When used for malignancy, initiate mercaptopurine at 10 mg/m2/day. Adjust dose based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy).

• When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy.

Manufacturer's labeling:

Heterozygous deficiency (intermediate activity): Reduce the dose based on tolerability; most patients with heterozygous deficiency of TPMT or NUDT15 tolerate recommended doses, although some require dosage reduction. Patients who are heterozygous for both TPMT and NUDT15 may require more substantial dose reductions.

Homozygous deficiency (low or deficient activity): Reduce the mercaptopurine dose to 10% of the usual dose or lower for homozygous deficiency in either TPMT or NUDT15.

Dosing: Kidney Impairment: Pediatric

Children and Adolescents:

CrCl ≥50 mL/minute: No adjustment required (Ref).

CrCl <50 mL/minute: Initiate with the lowest recommended starting dose or increase the dosing interval to every 36 to 48 hours to avoid accumulation in patients with renal impairment adjust dose to maintain desirable ANC level and for adverse reactions (Ref).

Hemodialysis: Administer every 48 hours (Ref).

Continuous ambulatory peritoneal dialysis (CAPD): Administer every 48 hours (Ref).

Continuous renal replacement therapy (CRRT): Administer every 48 hours (Ref).

Dosing: Hepatic Impairment: Pediatric

Children and Adolescents:

Hepatic impairment at baseline: Initiate with the lowest recommended starting dose; adjust dose to maintain desirable ANC level and for adverse reactions.

Hepatotoxicity during treatment: Withhold therapy.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Dermatologic: Skin rash (5% to 20%)

Gastrointestinal: Anorexia (5% to 20%), diarrhea (5% to 20%), nausea (5% to 20%), vomiting (5% to 20%)

Hematologic & oncologic: Bone marrow depression (dose-related: >20%, including anemia, neutropenia, lymphocytopenia, and thrombocytopenia)

Nervous system: Malaise (5% to 20%)

1% to 10%:

Dermatologic: Hyperpigmentation (<5%), urticaria (<5%)

Endocrine & metabolic: Hyperuricemia (<5%)

Gastrointestinal: Oral lesion (<5%), pancreatitis (<5%)

Hepatic: Hyperbilirubinemia (<5%), increased serum transaminases (<5%)

Infection: Infection (<5%)

Frequency not defined:

Dermatologic: Alopecia

Gastrointestinal: Cholestasis, sprue-like symptoms, stomach pain, stomatitis, ulcerative bowel lesion

Genitourinary: Oligospermia, renal toxicity

Hematologic & oncologic: Granulocytopenia, leukopenia, metastases

Hepatic: Ascites, hepatic encephalopathy, hepatic fibrosis, hepatic injury, hepatic necrosis, hepatomegaly, hepatotoxicity, intrahepatic cholestasis, jaundice, toxic hepatitis

Immunologic: Immunosuppression

Nervous system: Drug fever

Respiratory: Pulmonary fibrosis

Postmarketing:

Cardiovascular: Portal hypertension

Dermatologic: Skin photosensitivity

Endocrine & metabolic: Hypoglycemia

Contraindications

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to mercaptopurine or any component of the formulation; patients whose disease showed prior resistance to mercaptopurine; immunizations with live organism vaccines.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Dose-related leukopenia, thrombocytopenia, and anemia are common; however, may also be indicative of disease progression. Hematologic toxicity may be delayed. Bone marrow may appear hypoplastic (could also appear normal). Monitor blood counts; dose may require modification for severe neutropenia or thrombocytopenia. Monitor for bleeding (due to thrombocytopenia) or infection (due to neutropenia). Profound severe or repeated hematologic toxicity may be indicative of thiopurine methyltransferase (TPMT) deficiency or nudix hydrolase 15 (nucleotide diphosphatase [NUDT15]) deficiency (see “TPMT or NUDT15 deficiency” below); patients who are homozygous for TPMT or NUDT15 deficiency may require substantial dosage reductions. TPMT genotyping or phenotyping or NUDT15 genotyping can identify patients with reduced TPMT or NUDT15 enzyme activity.

• Hepatotoxicity: Hepatotoxicity has been reported, including jaundice, ascites, hepatic necrosis (may be fatal), intrahepatic cholestasis, parenchymal cell necrosis, and/or hepatic encephalopathy; may be due to direct hepatic cell damage or hypersensitivity. While hepatotoxicity or hepatic injury may occur at any dose, dosages exceeding the recommended dose are associated with a higher incidence. Signs of jaundice generally appear early in treatment, after ~1 to 2 months (range: 1 week to 8 years) and may resolve following discontinuation; recurrence with rechallenge has been noted. Monitor liver function tests, including transaminases, alkaline phosphatase, and bilirubin weekly with treatment initiation, then monthly thereafter (monitor more frequently if used in combination with other hepatotoxic drugs or in patients with preexisting hepatic impairment). Reduce initial dose in patients with baseline hepatic impairment; monitor closely for toxicity. Withhold treatment at the onset of hepatotoxicity, or for clinical signs of jaundice (hepatomegaly, anorexia, tenderness), deterioration in liver function tests, toxic hepatitis, or biliary stasis until hepatotoxicity is ruled out.

• Immunosuppression: Mercaptopurine is immunosuppressive; immune responses to infections may be impaired and the risk for infection is increased. Common signs of infection, such as fever and leukocytosis may not occur; lethargy and confusion may be more prominent signs of infection.

• Macrophage activation syndrome: Macrophage activation syndrome (MAS), also known as hemophagocytic lymphohistiocytosis, is a life-threatening disorder which may develop in patients with autoimmune disorders (particularly inflammatory bowel disease); mercaptopurine use for the treatment of autoimmune conditions (off-label use) may cause increased susceptibility to MAS. Discontinue mercaptopurine if MAS develops or is suspected. Monitor; promptly treat infections such as Epstein-Barr virus (EBV) and cytomegalovirus (which are known triggers for MAS).

• Photosensitivity: Minimize sun exposure due to possible photosensitivity.

• Secondary malignancy: Immunosuppressive agents, including mercaptopurine, are associated with the development of lymphoproliferative disorders and other malignancies. In an analysis of T-cell lymphomas associated with TNF blockers (with or without thiopurines) for the treatment of rheumatoid arthritis, Crohn disease, ulcerative colitis, or ankylosing spondylitis (off-label uses for thiopurines), an increase in the incidence of T-cell lymphomas, most commonly mycosis fungoides/Sézary syndrome and hepatosplenic T-cell lymphoma (HSTCL) was reported (Deepak 2013). HSTCL is a rare white blood cell cancer that is usually fatal. Most HSTCL cases occurred in patients treated with a combination of TNF blockers and thiopurines, although cases of HSTCL also occurred in patients receiving azathioprine or mercaptopurine monotherapy. Skin cancers (melanoma and non-melanoma), Kaposi and non-Kaposi sarcomas, and uterine cervical cancer in situ have been reported in patients receiving immunosuppressive treatment (including mercaptopurine); risk of development may be related to the degree and duration of immunosuppression. Partial regression of lymphoproliferative disorders may occur upon therapy discontinuation. Regimens containing multiple immunosuppressants increase the risk of EBV-associated lymphoproliferative disorders; use with caution.

Disease-related concerns:

• Renal impairment: Reduce initial dose or extend dosing interval in patients with renal impairment (CrCl <50 mL/minute). Some renal adverse effects may be minimized with hydration and prophylactic antihyperuricemic therapy.

• TPMT or NUDT15 deficiency: Patients with reduced TPMT or NUDT15 activity have a higher risk of severe myelosuppression with usual doses of thiopurines (eg, mercaptopurine, azathioprine, thioguanine) and may require substantial thiopurine dose reductions. Individuals who are TPMT homozygous or compound heterozygous deficient are at very high risk for severe myelosuppression (Relling 2019). TPMT genotyping or phenotyping and NUDT15 genotyping may assist in identifying patients at risk for developing toxicity. Consider testing for NUDT15 and TPMT deficiency in patients who experience severe bone marrow toxicities or repeated myelosuppressive episodes. Accurate phenotyping (red blood cell TPMT activity) results are not possible in patients who have received recent blood transfusions. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for thiopurine dosing based on TPMT and NUDT15 genotypes (Relling 2019) recommends reduced initial doses for TPMT and NUDT15 intermediate (and possible intermediate) metabolizers (with dosage adjustments based on myelosuppression). For TPMT and NUDT15 poor metabolizers, CPIC guideline recommends considering alternative nonthiopurine agents for nonmalignant conditions and drastically reduced doses if used to treat malignancy. Genetic TPMT deficiency is the primary cause of thiopurine intolerance in Europeans and Africans; NUDT15 risk alleles are associated with a majority of thiopurine intolerance in Asians and are also common in Hispanics (Relling 2019).

Concurrent drug therapy issues:

• Drug-drug interactions: Because azathioprine is metabolized to mercaptopurine, concomitant use with azathioprine may result in a significant increase in hematologic toxicity and profound myelosuppression; avoid concurrent use. Hematologic toxicity may be exacerbated by other medications which inhibit TPMT (eg, mesalamine, olsalazine, sulfasalazine) or by other myelosuppressive drugs.

Special populations:

• Pediatric: Cases of symptomatic hypoglycemia have been reported in children receiving mercaptopurine for the treatment of ALL; cases were reported in children less than 6 years of age or with a low body mass index.

Other warnings/precautions:

• Error-prone terms: To avoid potentially serious dosage errors, the terms “6-mercaptopurine” or “6-MP” should be avoided; use of these terms has been associated with six-fold overdosages.

• Vaccines: Immune response to vaccines may be diminished. Live virus vaccines impose a risk for infection.

Warnings: Additional Pediatric Considerations

The development of secondary hemophagocytic lymphohistiocytosis (HLH), a rare and frequently fatal activation of macrophages which causes phagocytosis of all bone marrow blood cell lines, is increased (100-fold) in pediatric patients diagnosed with inflammatory bowel disease; this risk is further increased with concomitant thiopurine (ie, azathioprine, mercaptopurine) therapy, Epstein-Barr virus, or other possible infections; if patient presents with fever (at least 5 days), cervical lymphadenopathy, and lymphopenia, discontinue immunosuppressive therapy and further diagnostic evaluation for HLH should be performed; diagnostic delay associated with increased mortality (Biank 2011).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Oral:

Purixan: 2000 mg/100 mL (100 mL) [contains aspartame, methylparaben, propylparaben]

Tablet, Oral:

Generic: 50 mg

Generic Equivalent Available: US

May be product dependent

Pricing: US

Suspension (Purixan Oral)

2000 mg/100 mL (per mL): $17.19

Tablets (Mercaptopurine Oral)

50 mg (per each): $4.09 - $8.18

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Purinethol: 50 mg

Generic: 50 mg

Administration: Adult

Oral: Administer at the same time(s) each day. Administer preferably on an empty stomach (Ref); avoid concomitant milk products if possible (Ref). The manufacturer recommends taking consistently either with or without food.

If adherence is limited by administering on an empty stomach in the evening or by avoiding concomitant milk products, simplification of administration (eg, take with food/dairy without regard to time of day) should be considered. In adherent patients (taking mercaptopurine regularly), no association was seen between risk of ALL relapse and mercaptopurine ingestion habits; there was also no association noted with red cell thioguanine nucleotide (TGN) levels and administration with food, dairy, or time of day (Ref).

Suspension: Shake vigorously for at least 30 seconds to ensure suspension is mixed thoroughly (suspension is viscous). Measure dose with an oral dosing syringe (a 1 mL and a 5 mL oral dosing syringe are supplied by the manufacturer) to assure proper dose is administered. Patients and caregivers should be trained on appropriate measuring and administration, handling, storage, disposal, cleanup of accidental spills, and proper cleaning of oral dosing syringe. Use within 8 weeks after opening.

Administration: Pediatric

Oral: Administer at the same time(s) each day, preferably on an empty stomach (Ref); avoid concomitant milk products if possible (Ref).

Acute lymphoblastic leukemia (ALL): Administration in the evening has demonstrated superior outcome; administration with food did not significantly affect outcome (Ref).

If adherence is limited by administering on an empty stomach in the evening or by avoiding concomitant milk products, simplification of administration (eg, take with food/dairy without regard to time of day) should be considered. In adherent patients (taking mercaptopurine regularly), no association was seen between risk of ALL relapse and mercaptopurine ingestion habits; there was also no association noted with red cell thioguanine nucleotide (TGN) levels and administration with food, dairy, or time of day (Ref).

Suspension: Shake well for at least 30 seconds to ensure suspension is mixed thoroughly (suspension is viscous). Measure dose with an oral dosing syringe (a 1 mL and a 5 mL oral dosing syringe are supplied by the manufacturer) to assure proper dose is administered. If oral syringe is intended to be re-used, wash with warm soapy water and rinse well (hold syringe under water and move plunger several times to ensure inside of syringe is clean); allow to dry completely. Patients and caregivers should be trained on appropriate measuring and administration, handling, storage, disposal, cleanup of accidental spills, and proper cleaning of oral dosing syringe. Use within 8 weeks after opening.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Acute lymphoblastic leukemia: Treatment of acute lymphoblastic leukemia (ALL), as part of a combination chemotherapy maintenance regimen.

Use: Off-Label: Adult

Acute promyelocytic leukemia, maintenance; Crohn disease; Hepatitis, autoimmune; Lymphoblastic lymphoma; Ulcerative colitis (remission induction); Ulcerative colitis (remission maintenance)

Medication Safety Issues
Sound-alike/look-alike issues:

Mercaptopurine may be confused with methotrexate

Purinethol [DSC] may be confused with propylthiouracil

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

International issues:

Mercaptopurine may be confused with mercaptamine [multiple international markets]

Other safety concerns:

To avoid potentially serious dosage errors, the terms “6-mercaptopurine” or “6-MP” should be avoided; use of these terms has been associated with sixfold overdosages.

Azathioprine is metabolized to mercaptopurine; concurrent use of these commercially-available products has resulted in profound myelosuppression.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Thiopurine Analogs. 5-Aminosalicylic Acid Derivatives may increase serum concentrations of the active metabolite(s) of Thiopurine Analogs. Specifically, exposure to the active 6-thioguanine nucleotides (6-TGN) may be increased. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Allopurinol: May increase the serum concentration of Mercaptopurine. Allopurinol may also promote formation of active thioguanine nucleotides. Management: Reduce the mercaptopurine dose to one third to one quarter of the usual dose if used with allopurinol, and monitor closely for systemic toxicity. Risk D: Consider therapy modification

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Anti-TNF Agents: May enhance the adverse/toxic effect of Thiopurine Analogs. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. Risk C: Monitor therapy

AzaTHIOprine: May enhance the myelosuppressive effect of Mercaptopurine. Risk X: Avoid combination

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

DOXOrubicin (Conventional): May enhance the hepatotoxic effect of Mercaptopurine. Risk C: Monitor therapy

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Febuxostat: May increase the serum concentration of Mercaptopurine. Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

Methotrexate: May increase the serum concentration of Mercaptopurine. Conversely, intracellular concentrations of thioguanine nucleotides may be decreased with the combination. Risk C: Monitor therapy

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification

Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy

Sulfamethoxazole: May enhance the myelosuppressive effect of Mercaptopurine. Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Trimethoprim: May enhance the myelosuppressive effect of Mercaptopurine. Risk C: Monitor therapy

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Vitamin K Antagonists (eg, warfarin): Mercaptopurine may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Verify pregnancy status in females of reproductive potential prior to initiating therapy.

Mercaptopurine is approved for use as part of combination maintenance therapy for acute lymphoblastic leukemia. Product labeling recommends females of reproductive potential use effective contraception during mercaptopurine treatment and for 6 months after the last mercaptopurine dose. Males with female partners of reproductive potential should be advised to use effective contraception during therapy and for 3 months after the last dose of mercaptopurine.

Mercaptopurine is also used (off label) for the treatment of ulcerative colitis and Crohn disease; monotherapy use for these indications may be continued in patients planning a pregnancy (Bermejo 2018). Mercaptopurine does not decrease fertility in patients with inflammatory bowel disease (AGA [Mahadevan 2019]; Bermejo 2018).

Pregnancy Considerations

Mercaptopurine may cause fetal harm if administered during pregnancy. An increased risk of miscarriage has been noted with mercaptopurine administration during the first trimester; adverse events, including miscarriage and stillbirth, have also been noted with second and third trimester use. Mercaptopurine is approved for use as part of combination therapy for acute lymphoblastic leukemia. Information is available following use for leukemia during pregnancy; outcomes may be influenced by concomitant medications (NTP 2013; Ticku 2013).

Mercaptopurine is also used (off label) for the treatment of ulcerative colitis and Crohn disease. The risk of adverse fetal events is decreased with monotherapy. In addition, maternal use to maintain remission may improve pregnancy outcomes. Females with inflammatory bowel disease who are on maintenance therapy with mercaptopurine monotherapy may continue treatment during pregnancy. Initiating treatment during pregnancy is not recommended. Combination therapy is also not recommended (AGA [Mahadevan 2019]; Puchner 2019; Restellini 2020).

The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy; the guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (Peccatori 2013).

Data collection to monitor outcomes following exposure to medications during pregnancy is ongoing. A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499). Women exposed to medications during pregnancy for the treatment of an autoimmune disease (eg, Crohn disease) may contact the OTIS Autoimmune Diseases Study (877-311-8972).

Breastfeeding Considerations

Mercaptopurine may be present in breast milk.

A case report describes maternal use of mercaptopurine 50 mg daily for the treatment of Crohn disease throughout pregnancy. One month prior to delivery, intracellular concentrations of 6-thioguanine and 6-methylmercaptopurine (6MMP) were detected in maternal blood samples obtained 2 and 4 hours after a maternal dose. A single breast milk sample was obtained 1 day after delivery, 4 hours after the maternal mercaptopurine dose. Mercaptopurine, 6-thioguanine, and 6MMP were undetectable in the breast milk sample (Ter Horst 2019). Mercaptopurine is the active metabolite of azathioprine. Following administration of azathioprine, mercaptopurine can be detected in breast milk (Gardiner 2006).

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 week after the last mercaptopurine dose. When used as monotherapy for the treatment of inflammatory bowel disease, mercaptopurine is considered to be compatible with breastfeeding (AGA [Mahadevan 2019]; Bermejo 2018).Waiting for 4 hours after the maternal dose to breastfeed may decrease potential exposure to the infant (Puchner 2019; Restellini 2020; ter Horst 2019).

Monitoring Parameters

CBC with differential (weekly initially, although clinical status may require increased frequency), bone marrow exam (to evaluate leukemia status and marrow cellularity in patients with prolonged or repeated myelosuppression), liver function tests (transaminases, alkaline phosphatase, and bilirubin; weekly initially, then monthly; monitor more frequently if on concomitant hepatotoxic agents or in patients with preexisting hepatic impairment), renal function, urinalysis. Evaluate pregnancy status prior to use in females of reproductive potential. Monitor for signs/symptoms of macrophage activating syndrome or photosensitivity reactions. Monitor adherence.

Thiopurine S-methyltransferase (TPMT) genotyping or phenotyping: Consider testing for TPMT deficiency, particularly in patients with abnormally low CBC unresponsive to dose reduction. TPMT genotyping or phenotyping may assist in identifying patients at risk for developing toxicity (Relling 2019).

Nudix hydrolase 15 (NUDT15) genotyping: Consider genotyping for NUDT15 deficiency in patients who experience severe bone marrow toxicities or repeated myelosuppressive episodes. NUDT15 genotyping may assist in identifying patients at risk for developing toxicity (Relling 2019).

Crohn disease or ulcerative colitis (off-label uses): Monitor CBC with differential weekly for 1 month, then biweekly for 1 month, followed by monitoring every 1 to 2 months throughout the course of therapy. LFTs should be assessed every 3 months. Monitor for signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss).

Oncology uses: The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Mercaptopurine is a purine antagonist which inhibits DNA and RNA synthesis; acts as false metabolite and is incorporated into DNA and RNA, eventually inhibiting their synthesis; specific for the S phase of the cell cycle

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Variable and incomplete (~50% of a dose is absorbed); Cmax of suspension is 34% higher than the tablet.

Distribution: Vd: ~0.9 L/kg; CNS penetration is poor.

Protein binding: ~19%.

Metabolism: Hepatic and in GI mucosa; hepatically via xanthine oxidase and methylation via thiopurine methyltransferase to sulfate conjugates, 6-thiouric acid, and other inactive compounds; first-pass effect.

Half-life elimination: Suspension: Median: 1.3 hours (range: 0.9 to 5.4 hours).

Time to peak, serum: Suspension: Median: Children: 1 to 3 hours, Adults: 0.75 hours (range: 0.33 to 2.5 hours).

Excretion: Urine (46% as mercaptopurine and metabolites).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Renal impairment may result in slower elimination of parent drug and metabolites, and a greater cumulative effect.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Purinethol;
  • (AR) Argentina: Mercaptopurina | Puri nethol | Purinethol | Varimer;
  • (AT) Austria: Puri nethol | Xaluprine;
  • (AU) Australia: Allmercap | Mercaptopurine link | Purinethol;
  • (BD) Bangladesh: Purinethol;
  • (BE) Belgium: Puri nethol;
  • (BG) Bulgaria: Puri nethol;
  • (BR) Brazil: Purinethol;
  • (CH) Switzerland: Puri nethol;
  • (CL) Chile: Purinethol;
  • (CO) Colombia: Empurine | Kapto | Purinethol;
  • (CZ) Czech Republic: Puri nethol | Xaluprine;
  • (DE) Germany: Medipurin | Mercaptopurin holsten | Puri nethol | Purinethol | Xaluprine;
  • (DO) Dominican Republic: Merpurine | Purinethol;
  • (EC) Ecuador: Mercaptopurina;
  • (EE) Estonia: Merkaptopurin | Puri nethol | Xaluprine;
  • (EG) Egypt: Purinethol;
  • (ES) Spain: Mercaptopurina | Mercaptopurina silver | Mercaptopurina tillomed;
  • (FI) Finland: Mercaptopurin orion | Merkaptopurin | Puri nethol | Xaluprine;
  • (FR) France: Mercaptopurine Dci | Purinethol | Xaluprine;
  • (GB) United Kingdom: Hanixol | Puri nethol | Xaluprine;
  • (GR) Greece: Mercaptopurin | Mercaptopurinum | Puri nethol | Xaluprine;
  • (HK) Hong Kong: Allmercap mercaptopurine | Puri nethol;
  • (HU) Hungary: Purinethol | Xaluprine;
  • (IE) Ireland: Puri nethol | Xaluprine;
  • (IL) Israel: Puri nethol;
  • (IN) India: 6 mp | Captomer | Empurine | Puri nethol | Purinetone;
  • (IT) Italy: Purinethol | Xaluprine;
  • (JO) Jordan: Purinethol;
  • (JP) Japan: Classen | Pro;
  • (KE) Kenya: Purinethol;
  • (KR) Korea, Republic of: Catoprine | Purinethol | Purinetone | Union mercaptopurine;
  • (LB) Lebanon: Puri nethol;
  • (LT) Lithuania: Mercaptopurin | Merkaptopurin | Puri nethol | Xaluprine;
  • (LU) Luxembourg: Puri nethol;
  • (LV) Latvia: Merkaptopurin | Puri nethol | Purinethol;
  • (MA) Morocco: Purinethol;
  • (MX) Mexico: Mercaptopurina | Purinethol;
  • (MY) Malaysia: Empurine | Puri nethol;
  • (NL) Netherlands: Mercaptopurine bmodesto | Puri nethol | Purinethol | Xaluprine;
  • (NO) Norway: Puri nethol | Purimmun | Xaluprine;
  • (NZ) New Zealand: Allmercap | Purinethol;
  • (PE) Peru: Mervitae | Purinethol | Varimer;
  • (PH) Philippines: Capmerin | Empurine | Purinethol;
  • (PK) Pakistan: Mercaprine;
  • (PL) Poland: Mercaptopurin | Purinethol | Xaluprine;
  • (PR) Puerto Rico: Purinethol;
  • (PT) Portugal: Mercaptopurina;
  • (PY) Paraguay: Mercaptopurina d.a. carrion | Purinethol | Varimer;
  • (QA) Qatar: Puri-Nethol;
  • (RU) Russian Federation: Mercaptopurin | Mercaptopurine nativ | Puri nethol;
  • (SA) Saudi Arabia: Purinethol;
  • (SE) Sweden: Merkaptopurin ebb | Puri nethol | Purimmun | Purinethol | Xaluprine;
  • (SG) Singapore: Purinethol | Purinetone;
  • (SI) Slovenia: Purinethol | Xaluprine;
  • (SK) Slovakia: Puri nethol | Xaluprine;
  • (TH) Thailand: Empurine | Puri nethol | Purinetone;
  • (TN) Tunisia: Purinethol;
  • (TR) Turkey: Mercaptopurin | Merpurin | Purinethol;
  • (TW) Taiwan: Merkaptopurine | Merpurine | Puri nethol;
  • (UA) Ukraine: Merkaptopurine | Puri nethol;
  • (UY) Uruguay: Puri nethol | Purinethol;
  • (ZA) South Africa: Purinethol
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