PURIXAN

Purine Analogs

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
Emetic Risk
Pediatrics
Doses 4.2 mg/kg/dose or lower: Low
Administer routine antiemetic prophylaxis prior to treatment.

Take mercaptopurine tablets orally either consistently with or without with food as a single daily dose.
Do not administer in patients who cannot swallow tablets or patients weighing less than 17 kg.
If a dose is missed, skip that dose and take the next dose at the next scheduled time.

Take mercaptopurine solution orally either consistently with or without with food as a single daily dose.
Prior to starting therapy and at each clinic visit, review proper storage, preparation, administration, disposal, and clean-up of accidental spillage with the patient or caregiver; direct patients and caregivers to read the Instruction for Use at each mercaptopurine refill.
The oral suspension comes with a press-in bottle adapter and 2 oral dispensing syringes (1-mL and 5-mL syringe); instruct patients and caregivers on which syringe to use and how to administer the specific dose.
Shake well for at least 30 seconds.
Wash the syringe with warm, soapy, water and rinse well; move the plunger up and down under water several times to make sure the inside of the syringe is clean. The syringe should be completely dry before re-use; store in a hygienic place.
If a dose is missed, skip that dose and take the next dose at the next scheduled time.
Use the suspension within 8 weeks of opening; discard any remaining drug after 8 weeks.

pancreatitis / Delayed / 0-3.3
tumor lysis syndrome (TLS) / Delayed / Incidence not known
hepatic encephalopathy / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
spontaneous fetal abortion / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
skin cancer / Delayed / Incidence not known
lymphoma / Delayed / Incidence not known
pulmonary fibrosis / Delayed / Incidence not known

jaundice / Delayed / 0-40.0
oral ulceration / Delayed / 0-5.0
hyperuricemia / Delayed / 0-5.0
elevated hepatic enzymes / Delayed / 0-5.0
hyperbilirubinemia / Delayed / 0-5.0
thrombocytopenia / Delayed / 20.0
neutropenia / Delayed / 20.0
anemia / Delayed / 20.0
lymphopenia / Delayed / 20.0
bleeding / Early / Incidence not known
cholestasis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
hepatomegaly / Delayed / Incidence not known
ascites / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known

nausea / Early / 5.0-20.0
anorexia / Delayed / 5.0-20.0
vomiting / Early / 5.0-20.0
diarrhea / Early / 5.0-20.0
rash / Early / 5.0-20.0
malaise / Early / 5.0-20.0
infection / Delayed / 0-5.0
skin hyperpigmentation / Delayed / 0-5.0
urticaria / Rapid / 0-5.0
fever / Early / 0-1.0
alopecia / Delayed / Incidence not known
oligospermia / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known

Purinethol, PURIXAN

Rx

Thiopurine antimetabolite
Indicated for ALL as part of a combination chemotherapy regimen; common off-label use in gastroenterology for Crohn's disease and ulcerative colitis
Patients with TPMT or NUDT15 deficiency may be at a higher risk for developing toxicity, especially severe myelosuppression

1.5 to 2.5 mg/kg orally daily in combination with other agents; start mercaptopurine therapy after a complete hematologic remission is achieved. Single-agent mercaptopurine therapy is rarely used as remission maintenance of ALL. Mercaptopurine oral suspension may be dosed as 1.5 to 2.5 mg/kg daily or 50 to 75 mg/m2 daily in combination with multi-agent chemotherapy. Adjust the mercaptopurine dose to maintain desirable blood counts; a dose reduction is necessary in patients who develop severe hematologic toxicity.

Use is not established; however, 50 or 70 mg/m2/day PO as part of a combination chemotherapy regimen has been studied. Three cycles of consolidation followed by 6 cycles of maintenance therapy did not improve 5-year overall survival (OS) (58.4% vs. 52.4%) or disease-free survival (DFS) (30.4% vs. 35.8%) rates compared with 4 cycles of consolidation in 598 acute myelogenous leukemia (AML) patients (age range, 15 to 64 years) who achieved a complete remission following standard induction therapy in a large, randomized study. In the maintenance therapy regimen used in this study, the mercaptopurine dosage was 70 mg/m2/day orally on days 1 to 7 given in cycles 1, 4, and 5 in combination with other chemotherapy agents. In another study, 18 months of maintenance therapy with mercaptopurine 50 mg/m2/day orally and cytarabine resulted in a significantly worse 5-year OS rate compared with no maintenance therapy (58% vs. 81%; p = 0.04) in AML patients less than 20 years of age who had received induction therapy and 2 cycles of consolidation therapy; additionally, the 5-year DFS rate was not significantly different in the 2 treatment arms (50% vs. 60%, respectively).

Dose is not established; doses of 50 to 200 mg/day PO or 1.5 mg/kg/day PO divided into 2 doses has been studied with no improvement in survival. Mercaptopurine 50 to 200 mg resulted in no hematologic complete responses (CR) in 30 patients with chronic myelogenous leukemia in blast crisis compared with 6 CR (20%) in 30 matched control patients who received treatment with IV chemotherapy in a small study. The median overall survival (OS) times were not significantly different between the 2 treatment arms (4.7 vs. 3.8 months, respectively). In a nonrandomized study in 47 patients with Philadelphia chromosome-positive, chronic phase chronic granulocytic leukemia, mercaptopurine (1.5 mg/kg daily orally in 2 divided doses) plus hydroxyurea (1.5 mg/kg daily orally in 2 divided doses) given until disease progression resulted in a median chronic phase duration of 41 months and a median OS time of 45 months. However, these efficacy parameters were not significantly different for combination therapy compared with hydroxyurea alone in another nonrandomized study in 45 patients.

50 mg PO once daily, initially. Increase the dose to 1.5 mg/kg/day after 2 weeks as tolerated. Guidelines state that mercaptopurine may be used in treatment of active Crohn's disease. Mercaptopurine alone is not more effective than placebo to induce remission; however, it is effective for maintenance of remission in patients with Crohn's disease. Once remission is induced with corticosteroids, a thiopurine should be considered for use for steroid-sparing. Patients who are steroid dependent should be started on thiopurines with or without anti-TNF therapy. Mercaptopurine. typically at reduced doses, can also be used as adjunctive therapy for reducing immunogenicity against biologic therapy.

25 mg PO once daily, initially. Increase the dose to 0.75 mg/kg/day after 2 weeks as tolerated. Guidelines state that mercaptopurine may be used in treatment of active Crohn's disease. Mercaptopurine alone is not more effective than placebo to induce remission; however, it is effective for maintenance of remission in patients with Crohn's disease. Once remission is induced with corticosteroids, a thiopurine should be considered for use for steroid-sparing. Patients who are steroid dependent should be started on thiopurines with or without anti-TNF therapy. Mercaptopurine. typically at reduced doses, can also be used as adjunctive therapy for reducing immunogenicity against biologic therapy.

1 to 1.5 mg/kg/day PO is the usual initial and maximal target dose range recommended for maintenance of steroid-free remission in children at risk for poor disease outcome. Thiopurines alone are not recommended as induction therapy. Consider thiopurine methyltransferase (TPMT) genotyping or enzymatic activity testing prior to initiating therapy, as doses need to be adjusted based on metabolizer status.

50 mg PO once daily, initially. Increase dose to 1.5 mg/kg/day after 2 weeks if white blood cell count is 4 x 109 or more and has not decreased by more than 50% from baseline and liver function tests and amylase are not rising. Consider thiopurine methyltransferase (TPMT) genetic or enzyme activity testing before initiating therapy; dosage adjustments may be necessary. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Guidelines recommend thiopurines for maintenance of remission for persons with moderate to severely active ulcerative colitis after steroid induction. Guidelines do not recommend thiopurine monotherapy for induction of remission.

1 to 1.5 mg/kg/dose PO once daily. Consider thiopurine methyltransferase (TPMT) genetic or enzyme activity testing before initiating therapy; dosage adjustments may be necessary. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Thiopurines monotherapy is not recommended as induction therapy. Thiopurines may be somewhat more effective than 5-ASA products for maintaining remission in ulcerative colitis; however, considering their safety profile, generally reserve thiopurines for second-line therapy after 5-ASA has failed.

†Indicates off-label use

Initiate mercaptopurine therapy at the lowest recommended starting dosage in patients with hepatic impairment. Adjust subsequent mercaptopurine doses based on efficacy and toxicity.

Initiate mercaptopurine therapy at the lowest recommended starting dosage in patients with renal impairment. Adjust subsequent mercaptopurine doses based on efficacy and toxicity. Use the lowest recommended starting dosage or increase the dosing interval to 36 to 48 hours in patients with renal impairment (creatinine clearance less than 50 mL/min).

Albuterol; Budesonide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Allopurinol: (Major) The concomitant use of mercaptopurine and allopurinol may result in increased mercaptopurine toxicity (e.g., bone marrow suppression, nausea, and vomiting). If these drugs are used together, reduce the mercaptopurine dose to one-third to one-quarter of the usual dose to avoid severe toxicity. Allopurinol inhibits xanathine oxidase; mercaptopurine is inactivated via the xanathine oxidase enzyme.
Alpha interferons: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Azathioprine: (Contraindicated) Mercaptopurine, 6-MP is an active metabolite of azathioprine. Concurrent usage is, in essence, a duplication of pharmacologic therapy and may lead to overdosage. Co-therapy of azathioprine and 6-MP should be avoided to reduce the risk of a serious potential for drug-induced side effects and toxicity; case reports of severe immunosuppression and bone marrow suppression have occurred, and some of these cases have resulted in hospitalization, sepsis, and even patient mortality.
Azelastine; Fluticasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Balsalazide: (Moderate) Increased myelosuppression may occur if mercaptopurine is coadministered with balsalazide. If concomitant use is necessary, use the lowest possible doses of each drug and closely monitor the patient for bone marrow suppression. 5-Aminosalicylates, such as balsalazide, have been shown to inhibit the thiopurine methyltransferase (TPMT) enzyme in vitro. Mercaptopurine is inactivated via the TPMT enzyme.
Basiliximab: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents may result in additive effects. A dosage reduction of the purine analog may be indicated when used in combination with other myelosuppressive chemotherapy.
Beclomethasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Betamethasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Budesonide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Budesonide; Formoterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciclesonide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Corticosteroids: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Cortisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Cyclosporine: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as immunosuppressives may result in additive effects. A dosage reduction of the antineoplastic may be indicated when used in combination with other myelosuppressive chemotherapy.
Deflazacort: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Dexamethasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Doxorubicin Liposomal: (Moderate) Use mercaptopurine and doxorubicin together with caution; doxorubicin may potentiate mercaptopurine-induced hepatotoxicity. If these drugs are used together, monitor patients for signs and symptoms of hepatic dysfunction. Additionally, a mercaptopurine dosage reduction may be required when it is used in combination with other myelosuppressive agents such as doxorubicin. Hepatic dysfunction (i.e., hyperbilirubinemia, elevated AST and alkaline phosphatase levels) occurred in all 11 patients with refractory leukemia who received mercaptopurine (500 mg/m2 IV daily for 5 days) and doxorubicin (50 mg/m2 IV) repeated every 2 to 3 weeks; some patients also received vincristine and prednisone. Hepatotoxicity was observed in 19 of 20 patients who received mercaptopurine and doxorubicin as induction therapy for resistant leukemia in another report.
Doxorubicin: (Moderate) Use mercaptopurine and doxorubicin together with caution; doxorubicin may potentiate mercaptopurine-induced hepatotoxicity. If these drugs are used together, monitor patients for signs and symptoms of hepatic dysfunction. Additionally, a mercaptopurine dosage reduction may be required when it is used in combination with other myelosuppressive agents such as doxorubicin. Hepatic dysfunction (i.e., hyperbilirubinemia, elevated AST and alkaline phosphatase levels) occurred in all 11 patients with refractory leukemia who received mercaptopurine (500 mg/m2 IV daily for 5 days) and doxorubicin (50 mg/m2 IV) repeated every 2 to 3 weeks; some patients also received vincristine and prednisone. Hepatotoxicity was observed in 19 of 20 patients who received mercaptopurine and doxorubicin as induction therapy for resistant leukemia in another report.
Febuxostat: (Contraindicated) The use of febuxostat with mercaptopurine is contraindicated. Febuxostat inhibits xanthine oxidase (XO) and is expected to greatly increase the concentrations of drugs metabolized substantially by this enzyme, such as mercaptopurine. Inhibition of XO by febuxostat may cause increased plasma concentrations of mercaptopurine, 6-MP, leading to serious toxicity. Drug interaction studies of febuxostat with mercaptopurine have not been conducted.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Fludrocortisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Flunisolide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone; Salmeterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone; Vilanterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Formoterol; Mometasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Hydrocortisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Infliximab: (Moderate) Post-marketing fatal cases of hepatosplenic T-cell lymphoma have been reported, mostly in adolescent and young adult males with inflammatory bowel disease such as Crohn's disease or ulcerative colitis; almost all cases have occurred in patients who had received a TNF blocker such as infliximab concomitantly with either mercaptopurine, 6-MP or azathioprine at or before diagnosis. It is unknown whether the occurrence of hepatosplenic T-cell lymphoma is related to a TNF blocker or to a TNF blocker in combination with these other immunosuppressants. Use with caution.
Interferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Interferon Alfa-n3: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Intranasal Influenza Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Lesinurad; Allopurinol: (Major) The concomitant use of mercaptopurine and allopurinol may result in increased mercaptopurine toxicity (e.g., bone marrow suppression, nausea, and vomiting). If these drugs are used together, reduce the mercaptopurine dose to one-third to one-quarter of the usual dose to avoid severe toxicity. Allopurinol inhibits xanathine oxidase; mercaptopurine is inactivated via the xanathine oxidase enzyme.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Mesalamine, 5-ASA: (Moderate) Increased bone marrow suppression may occur if mercaptopurine is coadministered with mesalamine. If concomitant use is necessary, use the lowest possible doses of each drug and closely monitor the patient for myelosuppression. 5-Aminosalicylates, such as mesalamine, have been shown to inhibit the thiopurine methyltransferase (TPMT) enzyme in vitro. Mercaptopurine is inactivated via the TPMT enzyme.
Methylprednisolone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Mometasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Natalizumab: (Major) The concomitant use of natalizumab and immunosuppressives may further increase the risk of infections, including progressive multifocal leukoencephalopathy (PML), over the risk observed with use of natalizumab alone. Prior treatment with an immunosuppressant is also a risk factor for PML. Natalizumab for Crohn's disease should not be used in combination with immunosuppressants such as 6-mercaptopurine. Ordinarily, patients with mulitple sclerosis who are receiving chronic immunosuppressant therapy should not be treated with natalizumab, for similar reasons.
Olopatadine; Mometasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Olsalazine: (Moderate) Increased bone marrow suppression may occur if mercaptopurine is coadministered with olsalazine. If concomitant use is necessary, use the lowest possible doses of each drug and closely monitor the patient for myelosuppression. 5-Aminosalicylates, such as olsalazine, have been shown to inhibit the thiopurine methyltransferase (TPMT) enzyme in vitro. Mercaptopurine is inactivated via the TPMT enzyme.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Peginterferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Peginterferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with mercaptopurine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Platelet Inhibitors: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Porfimer: (Major) Avoid coadministration of porfimer with mercaptopurine due to the risk of increased photosensitivity. All patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like mercaptopurine may increase the risk of a photosensitivity reaction.
Prednisolone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Prednisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Pretomanid: (Major) Avoid coadministration of pretomanid with mercaptopurine, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and mercaptopurine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ropeginterferon alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Rotavirus Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Increased bone marrow suppression may occur if mercaptopurine is coadministered with trimethoprim sulfamethoxazole. If concomitant use is necessary, monitor complete blood counts and adjust the dose of mercaptopurine if severe neutropenia or thrombocytopenia occur.
Sulfasalazine: (Moderate) Increased bone marrow suppression may occur if mercaptopurine is coadministered with sulfasalazine. If concomitant use is necessary, use the lowest possible doses of each drug and closely monitor the patient for myelosuppression. 5-Aminosalicylates, such as sulfasalazine, have been shown to inhibit the thiopurine methyltransferase (TPMT) enzyme in vitro. Mercaptopurine is inactivated via the TPMT enzyme.
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Tofacitinib: (Major) Concomitant use of tofacitinib in combination with potent immunosuppressants such as mercaptopurine is not recommended. A risk of added immunosuppression exists when tofacitinib is coadministered with potent immunosuppressives. Combined use of multiple-dose tofacitinib with potent immunosuppressives has not been studied in patients with rheumatoid arthritis.
Triamcinolone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Typhoid Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Upadacitinib: (Major) The use of upadacitinib in combination with potent immunosuppressants such as mercaptopurine is not recommended. A risk of added immunosuppression exists when upadacitinib is coadministered with potent immunosuppressives. Combined use of multiple-dose upadacitinib with potent immunosuppressives has not been studied in patients with rheumatoid arthritis.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with mercaptopurine is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like mercaptopurine may increase the risk of a photosensitivity reaction.
Warfarin: (Major) The concomitant use of mercaptopurine and warfarin may decrease the anticoagulant effectiveness of warfarin. If concurrent use is required, monitor prothrombin time or INR and adjust the warfarin dose to maintain the desired level of anticoagulation.
Yellow Fever Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.

Mercaptopurine/Purinethol Oral Tab: 50mg
PURIXAN Oral Susp: 1mL, 20mg

2.5 mg/kg or 75 mg/m2 PO daily.

2.5 mg/kg or 75 mg/m2 PO daily.

2.5 mg/kg or 75 mg/m2 PO daily.

2.5 mg/kg or 75 mg/m2 PO daily.

2.5 mg/kg or 75 mg/m2 PO daily.

Mercaptopurine (6-MP) is activated via hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) to form 6-thioguanine nucleotides (6-TGN) and thioinosinic acid (TIMP). Additionally, 6-methylthioinosinate (MTIMP) is formed by the methylation of TIMP. 6-TGN is incorporated into nucleic acids in place of purine bases resulting in cell-cycle arrest and cell death. TIMP 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 via adenylosuccinate. 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. Some mercaptopurine is converted to nucleotide derivatives of 6-thioguanine (6-TG) by the sequential actions of IMP dehydrogenase and XMP aminase, converting TIMP to thioguanylic acid.

Mercaptopurine is administered orally. It has a Vd exceeding that of total body water (0.9 L/kg) and has minimal cerebrospinal fluid penetration. The plasma protein binding averaged 19% following an investigational IV formulation of mercaptopurine at doses exceeding 5 to 10 mg/kg. The median elimination half-life of mercaptopurine oral suspension is 1.3 hours (range, 0.9 to 5.4 hours). The elimination half-life of mercaptopurine oral suspension is approximately 2 hours. Mercaptopurine is metabolized via 2 major pathways: thiol methylation and oxidation. Thiol methylation is catalyzed by the polymorphic enzyme thiopurine S-methyltransferase (TPMT) to an inactive metabolite, methyl-mercaptopurine. TPMT activity is highly variable in patients due to a genetic polymorphism in the TPMT gene. During oxidation, mercaptopurine is catalyzed via xanthine oxidase to another inactive metabolite, 6-thiouric acid. Following the oral administration of radiolabeled mercaptopurine in 1 subject, 46% of the dose was excreted in the urine as parent drug and metabolites within the first 24 hours.

Oral mercaptopurine has demonstrated incomplete and variable absorption in clinical studies; approximately 50% of the dose is absorbed. Following a single oral dose of mercaptopurine 50 mg in healthy adults under fasted conditions, the mean AUC(0 to inf) value was 129 ng X hour/mL and the mean Cmax was 69 ng/mL. The median Cmax and AUC(0 to inf) values were 93 ng/mL (range, 40 to 204 ng/mL) and 136 ng X hour/mL (range, 77 to 268 ng X hour/mL), respectively, following a single 50 mg dose of mercaptopurine oral suspension in adults under fasting conditions. The Tmax was 0.75 hours (range, 0.33 to 2.5 hours).
Effects of food: Administering mercaptopurine with food results in decreased drug exposure.

Mercaptopurine may cause fetal harm when administered during pregnancy; intrauterine fetal death has been reported. Females of reproductive potential should avoid becoming pregnant while receiving mercaptopurine. If this drug is used during pregnancy, the patient should be apprised of the potential hazard to the fetus. Women receiving mercaptopurine in the first trimester have an increased incidence of fetal loss; the risk of malformation in offspring surviving the first trimester is not known. In a report of 28 women who received mercaptopurine after the first trimester, 3 patients died undelivered, 1 patient experienced intrauterine fetal death, and 1 patient aborted; there were no cases of macroscopically abnormal fetuses.