Thioguanine is an oral cell cycle-phase specific antineoplastic agent used chiefly in the treatment of acute lymphoblastic leukemia. It is an antimetabolite chemotherapy agent related to guanine. Thioguanine is structurally and functionally similar to another antimetabolite, mercaptopurine. The two agents have similar indications, adverse effects, and cross-resistance. Thioguanine is only FDA-approved for remission induction and remission consolidation therapy for acute myeloid leukemia. However, it is not recommend for use during maintenance therapy or other long-term continuous treatments due to the high risk of liver toxicity (see Adverse Reactions). Thioguanine was approved by the FDA in 1966.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
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
-Minimal/Low
-Administer prn antiemetics as necessary.
Route-Specific Administration
Oral Administration
-Thioguanine is administered orally. For patients who are unable to swallow tablets, a suspension form may be prepared.
Extemporaneous Compounding-Oral
Extemporaneous suspension:
-To make a solution containing 40 mg/mL of thioguanine, crush the appropriate number of tablets and suspending with a volume of Cologel equal to one-third the final desired volume. Then, bring the suspension to the final volume using a 2:1 mixture of simple syrup and wild cherry syrup. The final suspension is stable for at least 84 days if stored in an amber glass bottle at room temperature.
Myelosuppression (pancytopenia), manifested as thrombocytopenia, leukopenia, neutropenia, and anemia, is the major dose-limiting adverse reaction of thioguanine therapy. Thioguanine-induced bone marrow suppression may be delayed. Patients with an inherited deficiency of the enzyme thiopurine methyltransferase are at an increased risk for developing myelosuppression. Life-threatening infection and bleeding have been reported secondary to thioguanine-induced myelosuppression. Monitor complete blood counts with differential frequently during thioguanine therapy. Withhold thioguanine if an abnormally large decrease in blood counts occur. Dosage adjustments may be necessary to prevent life-threatening cytopenias.
Due to a high risk of hepatotoxicity associated with vascular endothelial damage, chronic, continuous thioguanine therapy is not recommended. Hepatotoxicity has been observed in a high proportion of pediatric patients (particularly in boys) receiving thioguanine as part of maintenance therapy for acute lymphoblastic leukemia and other conditions. Liver toxicity typically presents as the clinical syndrome of hepatic sinusoidal obstruction syndrome (SOS), previously termed hepatic veno-occlusive disease (VOD) (hyperbilirubinemia, tender hepatomegaly, weight gain due to fluid retention, and ascites) or signs of portal hypertension (splenomegaly, thrombocytopenia, and esophageal varices). Histopathologic features associated with thioguanine-induced hepatotoxicity include hepatoportal sclerosis, nodular regenerative hyperplasia, peliosis hepatis, and periportal fibrosis. Elevated hepatic enzymes, alkaline phosphatase, and gamma glutamyl transferase concentrations have also been reported in association with thioguanine hepatic toxicity but do not always occur. Jaundice has been reported in 2 adult males and in 4 children with acute myelogenous leukemia and in an adult male with acute lymphocytic leukemia who developed hepatic SOS. Centrilobular hepatic necrosis has been reported in a few patients; however, some of these patients also received high doses of thioguanine, other chemotherapy agents, or oral contraceptives, or had chronic alcohol abuse. Carefully monitor patients for early indications of portal hypertension such as thrombocytopenia out of proportion with neutropenia and splenomegaly. Weekly monitoring of serum transaminases, alkaline phosphatase, and bilirubin is recommended when initiating thioguanine. Monthly monitoring may suffice thereafter, but more frequent monitoring may be advisable for patients with pre-existing liver disease or for patients taking concomitant hepatotoxic drugs. All patients who developed SOS were also receiving other chemotherapy agents. Until the hepatic dysfunction etiology is ascertained, withholding of thioguanine is recommended if evidence of toxic hepatitis or biliary stasis (biliary obstruction) is present. Discontinue thioguanine in patients with jaundice or other evidence of hepatotoxicity or deterioration of liver function tests during thioguanine receipt; reversal of signs and symptoms may occur.
Gastrointestinal (GI) adverse events such as nausea, vomiting, anorexia, and stomatitis have been reported with thioguanine use. Bowel necrosis and GI perforation have been reported in patients who received multiple-drug regimens including thioguanine..
Hyperuricemia may occur with thioguanine use due to rapid cell lysis. This adverse event may be minimized by administering increased hydration, urine alkalinization, and a xanthine oxidase inhibitor (e.g., allopurinol).
Thioguanine, 6-TG should not be used in patients whose disease has demonstrated prior thioguanine, 6-TG resistance.
Thioguanine should be used cautiously in patients who have had previous myelosuppressive therapy such as chemotherapy or radiation therapy. Severe bone marrow suppression, including neutropenia and/or thrombocytopenia, is a relative contraindication to thioguanine depending upon the disease; however, myelosuppression is unavoidable during the management of acute leukemia. Patients with aggressive leukemia or lymphoma may require treatment with thioguanine despite severe bone marrow suppression. Therefore, this drug should be used only by clinicians experienced in the use of cancer therapy. Frequent monitoring of the patient's hematologic status including hemoglobin, hematocrit, total white blood cell count and white cell differential, and platelet count, should be performed frequently during thioguanine therapy. Dosage adjustments of thioguanine should take into consideration the absolute changes in blood counts and the rapidity with which the changes are occurring. Increased susceptibility to infection, especially opportunistic viral or fungal infection, may result from thioguanine-induced immunosuppression and myelosuppression; life-threatening infections and bleeding have been observed. Patients with an active infection should be treated prior to receiving thioguanine, the dose should be reduced or discontinued in patients who develop such infections. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.
Individuals with homozygous thiopurine methyltransferase deficiency (TPMT deficiency) are unusually sensitive to the myelosuppressive effects of thioguanine and prone to developing rapid bone marrow suppression following initiation of treatment. Laboratory tests are available, genotypic and phenotypic, to determine TPMT status. Substantial thioguanine dosage reductions may be required in homozygous-TPMT deficient patients to avoid the development of life-threatening bone marrow suppression in these patients. Although heterozygous patients with intermediate TPMT activity may have increased thioguanine toxicity, this is variable, and the majority of patients tolerate normal doses of thioguanine. If a patient has clinical or laboratory evidence of severe toxicity, particularly myelosuppression, TPMT testing should be considered. Concurrent administration of drugs that inhibit TPMT such as olsalazine, mesalazine, or sulfasalazine may exacerbate this issue (see Drug Interactions).
Thioguanine is not recommended for maintenance or other long-term continuous treatment due to the high risk of hepatotoxicity associated with vascular endothelial damage (see Adverse Reactions). This liver toxicity has been noted in a high proportion of children receiving thioguanine as part of maintenance therapy for acute lymphocytic leukemia and other conditions associated with continuous use of thioguanine. Liver toxicity is particularly prevalent in males. Thioguanine therapy should be discontinued in patients with evidence of liver toxicity (e.g., jaundice, ascites, biliary obstruction, biliary stasis/cholestasis) as reversal of toxic effects has been noted with the discontinuation of therapy. Patients should be closely monitored; it is advisable to monitor LFTs at weekly intervals when first beginning therapy and monthly thereafter. Early indications of hepatic toxicity are signs associated with portal hypertension such as thrombocytopenia out of proportion with neutropenia and splenomegaly. Patients with preexisting hepatic disease or receiving other drugs with hepatotoxic potential may be at increased risk of liver toxicity and it may be advisable to perform more frequent laboratory and clinical monitoring in these patients.
Myelosuppressive effects of thioguanine can increase the risk of infection or bleeding; therefore, dental work should be delayed until blood counts have returned to normal. Patients, especially those with dental disease, should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.
Intramuscular injections should not be administered to patients with a platelet count < 50,000/mm3 who are receiving thioguanine. IM injections may cause bleeding, bruising, or hematomas due to thioguanine-induced thrombocytopenia.
Hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and decreased urine output may be indicative of thioguanine-induced tumor lysis syndrome (TLS). Appropriate measures (e.g. aggressive hydration and allopurinol) must be taken to prevent severe electrolyte imbalances and renal toxicity during and following chemotherapy administration in patients with large chemosensitive tumors.
Thioguanine is categorized as FDA pregnancy risk category D. Thioguanine is a known teratogen and mutagen in animals and its use should be avoided during pregnancy. There are no adequate and well-controlled studies in pregnant women. Females of childbearing age should be advised to avoid becoming pregnant while taking thioguanine. If this drug is used during pregnancy or if the patient becomes pregnant while taking thioguanine, the patient should be apprised of the potential toxicity to the fetus.
It is unknown whether thioguanine is distributed into breast milk. The potential for serious adverse effects on the infant indicate that breast-feeding should be discontinued during thioguanine therapy. According to the manufacturer, a decision should be made whether to discontinue breast-feeding or discontinue the drug, taking onto account the importance of the drug to the mother.
Vaccination during chemotherapy (such as thioguanine) or radiation therapy should be avoided because the antibody response is suboptimal. When chemotherapy is being planned, vaccination should precede the initiation of chemotherapy by >= 2 weeks. The administration of live vaccines to immunocompromised patients should be avoided. Those undergoing chemotherapy should not be exposed to others who have recently received the oral poliovirus vaccine (OPV). Measles-mumps-rubella (MMR) vaccination is not contraindicated for the close contacts, including health care professionals, of immunocompromised patients. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination. When exposed to a vaccine-preventable disease such as measles, severely immunocompromised children should be considered susceptible regardless of their vaccination history.
For use in combination remission induction and remission consolidation therapy for acute myelogenous leukemia (AML):
NOTE: Thioguanine is not recommended for use during maintenance or similar long-term continuous treatments due to the high risk for liver toxicity.
Oral dosage:
Adults and Children: 100 mg/m2 orally every 12 hours for 5 to 10 days, usually in combination with cytarabine. Alternatively as a single agent, thioguanine 2 to 2.5 mg/kg/day orally, which can be increased to 3 mg/kg/day in the absence of serious toxicity. Doses should be rounded to the nearest 20 mg. The response to thioguanine is higher in younger patients and in previously untreated patients. Use of thioguanine alone is seldom justified for initial remission induction of acute myelogenous leukemia (AML) as the use of combination therapy including thioguanine results in more frequent remissions and longer duration of remission than single-agent thioguanine therapy. Of 163 pediatric patients with previously untreated AML, 59% (96 patients) obtained a complete remission with a multiple-drug regimen including thioguanine, prednisone, cytarabine, cyclophosphamide, and vincristine. Remission was maintained with daily thioguanine, 4-day pulses of cytarabine and cyclophosphamide, and vincristine every 28 days. The median duration of remission was 11.5 months. In another study, 53% of previously untreated adult patients with AML achieved remission following the use of combination thioguanine and cytarabine. The median duration of remission of 8.8 was reported with a multi-drug maintenance regimen that included thioguanine.
For the treatment of acute lymphocytic leukemia (ALL)*:
NOTE: Thioguanine is not recommended for use during maintenance or similar long-term continuous treatments due to the high risk for liver toxicity.
Oral dosage:
Adults and Children: The usual dosage, when used in combination chemotherapy for induction of remission in patients with acute leukemia, ranges from 75 to 200 mg/m2 orally per day, given in 1 or 2 divided doses for 5 to 7 days of the treatment course, or until remission is attained. Typical maintenance dosage is 2 to 3 mg/kg/day, or 100 mg/m2/day orally. The dose should be rounded to the nearest 20 mg.
For the treatment of psoriasis*:
Oral dosage:
Adults: Various dosage regimens have been evaluated. The American Academy of Dermatology suggests initiating at 80 mg orally twice weekly increasing by 20 mg every 2 to 4 weeks up to 160 mg orally 3 times per week. In an open-label study, 81 patients were administered various dosage regimens of 6-thioguanine for a period of 1 to 220 months (median 16 months). A total of 49% of patients were effectively controlled for a median of 33 months. Discontinuation of therapy occurred in 51% of patients and was attributed to initial failure of therapy (5%), side effects (36%), or relapse of psoriasis (10%). The most frequently reported adverse effect was myelosuppression (47%), which led to discontinuation of therapy in 21% of subjects. Elevated hepatic enzymes were reported in 25% of evaluated subjects. Another study evaluated the efficacy of pulse-dosing of 6-thioguanine in patients with recalcitrant psoriasis. Patients were given between 120 mg orally twice weekly up to 160 mg 3 times per week. Marked improvement (i.e., 75% or more clearing) of psoriasis was reported in 10 of 14 patients. The authors reported that compared to previous studies using daily dosing of 6-thioguanine, the incidence of bone marrow suppression appeared to be greatly reduced using pulse-dosing.
Maximum Dosage Limits:
The suggested maximum tolerated dose (MTD) for thioguanine is dependent on the disease state, performance status, and other chemotherapy agents or radiation therapy given in combination.
-Adults
As a single agent, 3mg/kg/day PO.
-Elderly
As a single agent, 3mg/kg/day PO.
-Adolescents
As a single agent, 3mg/kg/day PO.
-Children
As a single agent, 3mg/kg/day PO.
Patients with Hepatic Impairment Dosing
No specific dosage adjustment recommendations are available. It may be advisable to perform more frequent LFTs in patients with pre-existing liver disease due to the hepatotoxic effects of thioguanine.
Patients with Renal Impairment Dosing
No dosage adjustment is needed.
Intermittent hemodialysis
Because of the rapid metabolism of thioguanine to active intracellular derivatives, hemodialysis would not be expected to be useful in decreasing plasma concentrations of the drug.
*non-FDA-approved indication
5-Aminosalicylates: (Moderate) Use these drugs together with caution; concomitant use may result in reduced metabolism of thioguanine via TPMT and an increased risk for thioguanine-induced toxicity. Monitor patients for signs and symptoms of hematologic and hepatic toxicity. There is in vitro evidence that 5-aminosalicylate derivatives inhibit thiopurine methyltransferase (TPMT), the enzyme that metabolizes thioguanine. Increased thioguanine concentrations can lead to an increased risk for severe thioguanine-induced myelosuppression. In cases of bone marrow suppression, a dose reduction of thioguanine may be necessary.
Abciximab: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Acetaminophen; Ibuprofen: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
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.
Amlodipine; Celecoxib: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Anagrelide: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Aspirin, ASA; Dipyridamole: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
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) Use these drugs together with caution; concomitant use may result in reduced metabolism of thioguanine via TPMT and an increased risk for thioguanine-induced toxicity. Monitor patients for signs and symptoms of hematologic and hepatic toxicity. There is in vitro evidence that 5-aminosalicylate derivatives inhibit thiopurine methyltransferase (TPMT), the enzyme that metabolizes thioguanine. Increased thioguanine concentrations can lead to an increased risk for severe thioguanine-induced myelosuppression. In cases of bone marrow suppression, a dose reduction of thioguanine may be necessary.
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.
Bupivacaine; Meloxicam: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Busulfan: (Moderate) Use thioguanine and busulfan together with caution; adverse effects such as hepatotoxicity, myelosuppresion, and immunosuppression may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of liver dysfunction, bleeding, and infection. Portal hypertension and esophageal varices associated with abnormal liver function tests occurred in 12 patients with chronic myelogenous leukemia (therapy duration, 6 to 45 months) who received continuous busulfan and thioguanine therapy in a comparative study (n = 330); no hepatotoxicity was observed in patients who received single-agent busulfan. Liver biopsies in 4 of these patients revealed nodular regenerative hyperplasia.
Celecoxib: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib; Tramadol: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Chikungunya 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.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
Cilostazol: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Clopidogrel: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
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.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
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.
Diclofenac: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diflunisal: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diphenhydramine; Ibuprofen: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Dipyridamole: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Eptifibatide: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Etodolac: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Fenoprofen: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
Flurbiprofen: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
Ibuprofen: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Famotidine: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Indomethacin: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
Ketoprofen: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketorolac: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
Meclofenamate Sodium: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Mefenamic Acid: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Meloxicam: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Mesalamine, 5-ASA: (Moderate) Use these drugs together with caution; concomitant use may result in reduced metabolism of thioguanine via TPMT and an increased risk for thioguanine-induced toxicity. Monitor patients for signs and symptoms of hematologic and hepatic toxicity. There is in vitro evidence that 5-aminosalicylate derivatives inhibit thiopurine methyltransferase (TPMT), the enzyme that metabolizes thioguanine. Increased thioguanine concentrations can lead to an increased risk for severe thioguanine-induced myelosuppression. In cases of bone marrow suppression, a dose reduction of thioguanine may be necessary.
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.
Nabumetone: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Esomeprazole: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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) Use these drugs together with caution; concomitant use may result in reduced metabolism of thioguanine via TPMT and an increased risk for thioguanine-induced toxicity. Monitor patients for signs and symptoms of hematologic and hepatic toxicity. There is in vitro evidence that 5-aminosalicylate derivatives inhibit thiopurine methyltransferase (TPMT), the enzyme that metabolizes thioguanine. Increased thioguanine concentrations can lead to an increased risk for severe thioguanine-induced myelosuppression. In cases of bone marrow suppression, a dose reduction of thioguanine may be necessary.
Oxaprozin: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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 thioguanine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Piroxicam: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
Prasugrel: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
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 thioguanine, 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 thioguanine. 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.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (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.
Sulfasalazine: (Moderate) Use these drugs together with caution; concomitant use may result in reduced metabolism of thioguanine via TPMT and an increased risk for thioguanine-induced toxicity. Monitor patients for signs and symptoms of hematologic and hepatic toxicity. There is in vitro evidence that 5-aminosalicylate derivatives inhibit thiopurine methyltransferase (TPMT), the enzyme that metabolizes thioguanine. Increased thioguanine concentrations can lead to an increased risk for severe thioguanine-induced myelosuppression. In cases of bone marrow suppression, a dose reduction of thioguanine may be necessary.
Sulindac: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Sumatriptan; Naproxen: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ticagrelor: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Tirofiban: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Tolmetin: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
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.
Vorapaxar: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
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.
Thioguanine functions as an antimetabolite, substituting for the purine base guanine in RNA and DNA. Similar to other antimetabolites, thioguanine is most active in the S-phase of the cell cycle. Thioguanine must be phosphorylated to its active form by hypoxanthine-guanine phosphoribosyltransferase (HGPRT), competing with endogenous ribotides hypoxanthine and guanine, and is converted to 6-thioguanylic acid (TGMP). This nucleotide reaches high intracellular concentrations at therapeutic doses. TGMP interferes with the synthesis of guanine nucleotides at several points. It inhibits de novo purine synthesis by pseudo-feedback inhibition of glutamine-5-phosphoribosyl 1-pyrophosphate amidotransferase, the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis. TGMP also inhibits the conversion of inosinic acid (IMP) to xanthylic acid (XMP) by competition for the enzyme IMP dehydrogenase. Thioguanylic acid is further converted to di- and tri-phosphates, thioguanosine diphosphate (TGDP), and thioguanosine triphosphate (TGTP) and their 2'-deoxyribosyl analogs by the same enzymes that metabolize guanine nucleotides. Although not the only mechanism of action, it is thought that the incorporation of these bases into RNA and DNA contributes to the cytotoxicity of thioguanine. Other mechanisms of cytotoxicity include feedback inhibition of de novo purine synthesis and inhibition of purine nucleotide interconversion. Overall, the net effect of thioguanine is a sequential blockade of synthesis and utilization of purine nucleotides.
In some tumors, resistance to thioguanine correlates with the loss of HGPRT activity and the resulting inability to convert thioguanine to thioguanylic acid. Other mechanisms of resistance include increased catabolism of TGMP by non-specific phosphatase. Complete cross-resistance with mercaptopurine is common.
Pharmacokinetics:
Thioguanine is administered orally. Thioguanine does not reach appreciable levels in the CNS. Thioguanine is metabolized via intracellular anabolic and catabolic pathways for purines. The active intracellular metabolites have significantly longer half-life than the parent compound. The catabolism of thioguanine and its metabolites is complex. In humans, thioguanine undergoes extensive methylation. The product of methylation, 2-amino-6-methylthiopurine (MTG), is substantially less active and toxic than thioguanine; its formation is unaffected by the presence of allopurinol. Only trace amounts of thioguanine are recovered in the urine. However MTG appears very early in the urine, increases over 6-8 hours after drug administration, and continues to be excreted in the urine after 12-22 hours. The sulfate thioguanine metabolite appears somewhat later than MTG but is the principle metabolite excreted after 8 hours. Thiouric acid and other thioguanine metabolites have also been found in the urine in small amounts.
-Route-Specific Pharmacokinetics
Oral Route
The absorption of thioguanine is incomplete and variable, with about 30% (range: 14-46%) of the administered dose absorbed. Following administration of radiolabeled thioguanine, peak plasma radioactivity was reached at about 8 hours and then slowly declined. The parent drug was virtually undetectable for most of the measurements. Following administration thioguanine is rapidly incorporated into the DNA and RNA of cells. The amount of thioguanine incorporated into nucleic acids is more than 100-times higher after 5 daily doses than after a single dose. With a 5-day schedule, half to almost all of the guanine in residual DNA was replaced by thioguanine.
-Special Populations
Hepatic Impairment
There are no pharmacokinetic data of thioguanine available for patients with hepatic impairment.
Renal Impairment
There are no pharmacokinetic data available for patients renal impairment. Because of the rapid metabolism of thioguanine to active intracellular derivatives, hemodialysis would not be expected to be useful in decreasing plasma concentrations of the drug.