Version October 2024
The FDA is alerting health care providers of the rare risk of intrahepatic cholestasis of pregnancy (ICP) associated with the use of thiopurines (azathioprine, mercaptopurine, and thioguanine). Thiopurines have a known risk of hepatotoxicity and are currently labeled for risk of fetal harm with use during pregnancy. Pregnant patients should stop using thiopurines if they develop ICP. Reported cases of ICP occurred among pregnant patients using azathioprine or mercaptopurine for inflammatory bowel disease (eg, Crohn disease, ulcerative colitis) or systemic lupus erythematosus.
The FDA is requiring updates to the prescribing information to include the following: postmarketing cases of ICP have been reported in women treated with thiopurines during pregnancy; ICP symptoms and elevated bile acid levels improved following azathioprine discontinuation; and pregnant individuals should discontinue use of thiopurines if they develop ICP.
Further information may be found at https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-pregnancy-problems-associated-thiopurines
Dosage guidance:
Safety: Consider testing for thiopurine S-methyltransferase (TPMT) deficiency and nudix hydrolase 15 (nucleotide diphosphatase [NUDT15]) deficiency; patients with TPMT or NUDT15 deficiency are at increased risk for severe toxicity at conventional thioguanine doses and generally require dose reduction (CPIC [Relling 2019]). Initiate adequate hydration and prophylactic antihyperuricemics (eg, allopurinol) to prevent tumor lysis syndrome.
Acute lymphoblastic leukemia (off-label use):
CALGB 8811 and 9111 regimens (late intensification treatment phase): Oral: 60 mg/m2 once daily on days 29 to 42 (in combination with doxorubicin, vincristine, dexamethasone, cyclophosphamide, and cytarabine) (Larson 1995; Larson 1998).
CALGB 10403 regimen (delayed intensification [course IV]): Oral: 60 mg/m2 once daily on days 29 to 42 (in combination with cyclophosphamide, cytarabine, dexamethasone, doxorubicin, methotrexate [intrathecal], pegaspargase, and vincristine) (Stock 2019).
MRC UKALLXII/ECOG 2993 regimen (consolidation [cycle 3]): Note: Consolidation cycle 3 to begin 4 weeks following consolidation cycle 2. Oral: 60 mg/m2 once daily on days 29 to 42 (in combination with cyclophosphamide, daunorubicin, and cytarabine) (Rowe 2005).
Acute myeloid leukemia: Oral: 2 mg/kg once daily for 4 weeks; if no clinical improvement after 4 weeks and ANC and platelet counts are not depressed, may increase dose to 3 mg/kg once daily with careful monitoring.
Dosage adjustment for TPMT and/or NUDT15 deficiency:
Clinical Pharmacogenetics Implementation Consortium guidelines; refer to guidelines for further information:
Normal TPMT or NUDT15 activity (wild type): No initial dosage adjustment necessary. Allow 2 weeks after each dosage adjustment to reach steady state. For patients receiving combination therapy, dosage adjustments (of all agents) should be made without any emphasis on thioguanine compared to other agents (CPIC [Relling 2019]).
TPMT intermediate or possible intermediate metabolizer or NUDT15 intermediate or possible intermediate metabolizer : Initiate thioguanine with the dose reduced to 50% to 80% of the usual dose and adjust based on the degree of myelosuppression and condition being treated. Allow 2 to 4 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the thioguanine dose over other agents (depending on concomitant therapy). If the starting dose is already below the normal recommended dose, dose reduction may not be recommended (CPIC [Relling 2019]).
TPMT poor metabolizer: Initiate thioguanine with drastically reduced doses (reduce the daily dose by 10-fold and reduce the frequency from once daily to 3 times per week). Adjust dose based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the thioguanine dose over other agents (depending on concomitant therapy) (CPIC [Relling 2019]).
NUDT15 poor metabolizer: Initiate thioguanine with the dose reduced to 25% of the usual dose and adjust dose based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state. For patients receiving combination therapy who experience severe myelosuppression, the focus should be on reducing the thioguanine dose over other agents (depending on concomitant therapy) (CPIC [Relling 2019]).
TPMT and/or NUDT15 indeterminate phenotypes: If TPMT indeterminate, consider evaluating TPMT erythrocyte activity to assess phenotype. If NUDT15 indeterminate, monitor closely for toxicity if thioguanine is required (CPIC [Relling 2019]).
Manufacturer's labeling:
Heterozygous deficiency (intermediate activity): Reduce the dose based on tolerability; most patients with heterozygous deficiency of TPMT or NUDT15 tolerate recommended doses, although some require dosage reduction. Patients who are heterozygous for both TPMT and NUDT15 may require more substantial dose reductions (manufacturer’s labeling).
Homozygous deficiency (low or deficient activity): Reduce the thioguanine dose to 10% of the usual dose or lower for homozygous deficiency in either TPMT or NUDT15 (manufacturer’s labeling).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
Hepatic impairment prior to treatment: There are no dosage adjustments provided in the manufacturer’s labeling.
Acute hepatotoxicity during treatment: Discontinue thioguanine for deterioration in transaminases, alkaline phosphatase or bilirubin, toxic hepatitis, biliary stasis, clinical jaundice, evidence of hepatotoxicity, hepatic sinusoidal obstruction syndrome (veno-occlusive disease) (eg, hyperbilirubinemia, hepatomegaly [tender], and weight gain due to ascites and fluid retention), or evidence of portal hypertension (eg, splenomegaly, thrombocytopenia, esophageal varices).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).
Hematologic toxicity: Withhold treatment for abnormally significant drop in blood counts.
Refer to adult dosing. Start at the low end of the dosing range.
(For additional information see "Thioguanine: Pediatric drug information")
Note: Consider testing for thiopurine S-methyltransferase (TPMT) deficiency and nudix hydrolase 15 (nucleotide diphosphatase [NUDT15]) deficiency; patients with TPMT or NUDT15 deficiency are at increased risk for severe toxicity at conventional thioguanine doses and generally require dose reduction (see Dosage adjustment for TPMT and/or NUDT15 deficiency below) (Relling 2011). Refer to individual protocols for dosing, and frequency; dosing presented as mg/m2 and mg/kg; use extra precaution.
Acute lymphoblastic leukemia (ALL): Limited data available: Delayed intensification treatment phase: Children ≥1 year and Adolescents: Oral: 60 mg/m2/dose once daily for 14 days (Lange 2002; Nachman 1998)
Acute myeloid leukemia (AML):
DCTER regimen: Limited data available (Lange 1998): Induction:
Infants and Children <3 years: Oral: 3.3 mg/kg/day divided once or twice daily for 4 days in combination with cytarabine and daunorubicin
Children ≥3 years and Adolescents: Oral: 100 mg/m2/day divided once or twice daily for 4 days in combination with cytarabine and daunorubicin
Manufacturer's labeling: Infants, Children, and Adolescents: Oral: 2 mg/kg once daily for 4 weeks; if no clinical improvement after 4 weeks and ANC and platelet counts are not depressed, may increase dose to 3 mg/kg once daily with careful monitoring
Acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) with Down syndrome: Limited data available: DCTER regimen: Induction:
Infants and Children <3 years: Oral: 3.3 mg/kg/day divided once or twice daily for 4 days in combination with cytarabine and daunorubicin (Gamis 2003; Lange 1998; Sorrell 2012; Woods 1990)
Children ≥3 years and Adolescents: Oral: 100 mg/m2/day divided once or twice daily for 4 days in combination with cytarabine and daunorubicin (Sorrell 2012)
CNS Tumors, low-grade gliomas: Limited data available (Ater 2012): TPCV regimen: Children <10 years: Oral: 30 mg/m2 every 6 hours x 11 doses (from hours 0 to 66) in a 42-day cycle for a total of 8 cycles (in combination with procarbazine, lomustine, and vincristine)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment in TPMT and/or NUDT15 deficiency: Limited data available (Relling 2011; Relling 2013): Infants, Children, and Adolescents:
Heterozygous deficiency (intermediate activity): Reduce the dose based on tolerability; according to the manufacturer, most patients with heterozygous deficiency of TPMT or NUDT15 tolerate recommended doses, although some require dosage reduction. Patients who are heterozygous for both TPMT and NUDT15 may require more substantial dose reductions.
Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for reduced TPMT activity (Relling 2011; Relling 2013): Initiate thioguanine with the dose reduced by 30% to 50% of the usual dose and adjust based on the degree of myelosuppression and condition being treated. Allow 2 to 4 weeks after each dosage adjustment to reach steady state. For patients receiving combination therapy who experience severe myelosuppression, the focus should be on reducing the thioguanine dose over other agents (depending on concomitant therapy).
Homozygous deficiency (low or deficient activity): Reduce the thioguanine dose to 10% of the usual dose or lower for homozygous deficiency in either TPMT or NUDT15.
CPIC guidelines for reduced TPMT activity (Relling 2011; Relling 2013): Initiate thioguanine with drastically reduced doses (reduce the daily dose by 10-fold and reduce the frequency from once daily to 3 times per week). Adjust doses based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state. For patients receiving combination therapy who experience severe myelosuppression, the focus should be on reducing the thioguanine dose over other agents (depending on concomitant therapy). When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy.
Homozygous wild type (normal activity): CPIC guidelines for reduced TPMT activity (Relling 2011; Relling 2013): No initial dosage adjustment necessary. Allow 2 weeks after each dosage adjustment to reach steady state. For patients receiving combination therapy, dosage adjustments (of all agents) should be made without any emphasis on thioguanine compared to other agents.
There are no dosage adjustments provided in the manufacturer’s labeling; some suggest that no adjustment required in pediatric patients (Aronoff 2007).
There are no dosage adjustments provided in the manufacturer’s labeling for patients with baseline hepatic impairment. For hepatotoxicity during treatment (eg, deterioration in transaminases, alkaline phosphatase or bilirubin, toxic hepatitis, biliary stasis, clinical jaundice, evidence of hepatic sinusoidal obstruction syndrome (veno-occlusive disease), or evidence of portal hypertension: Discontinue treatment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Esophageal varices, portal hypertension
Endocrine & metabolic: Fluid retention, hyperuricemia (common), increased gamma-glutamyl transferase, weight gain
Gastrointestinal: Anorexia, intestinal necrosis, intestinal perforation, nausea, stomatitis, vomiting
Hematologic & oncologic: Anemia (may be delayed), bone marrow depression, granulocytopenia, hemorrhage, leukopenia (common; may be delayed), pancytopenia, splenomegaly, thrombocytopenia (common; may be delayed)
Hepatic: Ascites, hepatic disease (hepatoportal sclerosis), hepatic focal nodular hyperplasia (regenerative), hepatic necrosis (centrilobular), hepatic sinusoidal obstruction syndrome, hepatomegaly (tender), hepatotoxicity, hyperbilirubinemia, increased liver enzymes, increased serum alkaline phosphatase, jaundice, peliosis hepatitis, periportal fibrosis
Infection: Infection
Neuromuscular & skeletal: Bone hypoplasia
Prior resistance to thioguanine (or mercaptopurine).
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to thioguanine or any component of the formulation.
Concerns related to adverse effects:
• Bone marrow suppression: Myelosuppression (anemia, leukopenia, and/or thrombocytopenia) is a common dose-related toxicity (may be delayed). Patients with genetic enzyme deficiency of thiopurine methyltransferase (TPMT) or nudix hydrolase 15 (nucleotide diphosphatase [NUDT15]) or who are receiving drugs which inhibit this enzyme (mesalazine, olsalazine, sulfasalazine) may be highly sensitive to myelosuppressive effects and may require substantial dose reductions.
• Hepatotoxicity: Long-term continuous therapy or maintenance treatment is associated with a high risk for hepatotoxicity, hepatic sinusoidal obstruction syndrome (SOS; also called veno-occlusive disease [VOD]), or portal hypertension. Hepatotoxicity with or without transaminase elevations may occur. Pathologic findings of hepatotoxicity include hepatoportal sclerosis, idiopathic noncirrhotic portal hypertension (including nodular regenerative hyperplasia), peliosis hepatitis, and periportal fibrosis. Hepatotoxicity may be more prevalent in male patients. Advise patients to avoid alcohol; may increase the risk for hepatotoxicity.
• Photosensitivity: Thioguanine may cause photosensitivity; sunscreen and protective clothing are recommended.
• Secondary malignancies: Thioguanine is potentially carcinogenic.
• Tumor lysis syndrome: Hyperuricemia occurs commonly with treatment.
Disease-related concerns:
• TPMT or NUDT15 deficiency: Patients with reduced TPMT or NUDT15 activity have a higher risk of severe myelosuppression with usual doses of thiopurines (eg, thioguanine, azathioprine, mercaptopurine) and may require substantial thiopurine dose reductions. Individuals who are TPMT homozygous or compound heterozygous deficient may be at risk for myelosuppression (CPIC [Relling 2019]). TPMT genotyping or phenotyping and NUDT15 genotyping may assist in identifying patients at risk for developing toxicity. Consider testing for NUDT15 and TPMT deficiency in patients who experience severe bone marrow toxicities or repeated myelosuppressive episodes. Accurate phenotyping (red blood cell TPMT activity) results are not possible in patients who have received recent blood transfusions. Genetic TPMT deficiency is the primary cause of thiopurine intolerance in Europeans and Africans; NUDT15 risk alleles are associated with a majority of thiopurine intolerance in Asians and are also common in Hispanics (CPIC [Relling 2019]).
Other warnings/precautions:
• Cross resistance: Cross resistance with mercaptopurine generally occurs.
• Vaccines: Avoid vaccination with live vaccines during treatment.
Liver toxicity is particularly prevalent in children (up to 25%) receiving maintenance therapy for acute lymphoblastic leukemia and in males.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tabloid: 40 mg [scored]
No
Tablets (Tabloid Oral)
40 mg (per each): $623.80
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Lanvis: 40 mg
Oral: Administer orally; total daily dose can be administered at one time.
Oral: Total daily dose may be administered at one time.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Acute myeloid leukemia: Treatment (remission induction and consolidation) of acute myeloid (nonlymphocytic) leukemia (AML).
Limitations of use: The use of thioguanine for AML maintenance therapy or other similar long-term continuous treatments is not recommended due to the high risk of hepatotoxicity.
Acute lymphoblastic leukemia
Thioguanine may be confused with thiotepa
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
6-thioguanine and 6-TG are error-prone abbreviations (associated with sixfold overdoses of thioguanine)
Lanvis [Canada and multiple international markets] may be confused with Lantus brand name for insulin glargine [US, Canada, and multiple international markets]
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Thiopurine Analogs. 5-Aminosalicylic Acid Derivatives may increase serum concentrations of the active metabolite(s) of Thiopurine Analogs. Specifically, exposure to the active 6-thioguanine nucleotides (6-TGN) may be increased. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Antithyroid Agents: Myelosuppressive Agents may enhance the neutropenic effect of Antithyroid Agents. Risk C: Monitor therapy
Anti-TNF Agents: May enhance the adverse/toxic effect of Thiopurine Analogs. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Linezolid: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Patients should avoid becoming pregnant during treatment.
Thioguanine crosses the placenta (NTP 2013; Pavlidis 2014).
Outcome data following maternal use of thioguanine for cancer chemotherapy (NTP 2013) and inflammatory bowel disease during pregnancy are available (Crouwel 2023).
Intrahepatic cholestasis of pregnancy (ICP) has been associated with thiopurine use. Patients with symptoms of ICP and elevated bile acid levels should discontinue treatment. Symptoms improve after the thiopurine is discontinued (FDA 2024).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy; the guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]). When treatment is needed for acute myeloid leukemia during pregnancy, agents other than thioguanine are preferred (Ali 2015; ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).
Thioguanine is present in breast milk (Pavlidis 2014).
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue thioguanine or to discontinue breastfeeding during treatment, taking into account the importance of treatment to the breastfeeding patient.
CBC with differential and platelet count (frequently); LFTs (weekly when beginning therapy then monthly, more frequently in patients with liver disease or concurrent hepatotoxic drugs); serum uric acid.
TPMT genotyping or phenotyping: Consider testing for TPMT deficiency, particularly in patients with abnormally low CBC unresponsive to dose reduction. TPMT genotyping or phenotyping may assist in identifying patients at risk for developing toxicity (CPIC [Relling 2019]).
NUDT15 genotyping: Consider genotyping for NUDT15 deficiency in patients who experience severe bone marrow toxicities or repeated myelosuppressive episodes. NUDT15 genotyping may assist in identifying patients at risk for developing toxicity (CPIC [Relling 2019]).
Monitor for signs/symptoms of hepatotoxicity, portal hypertension (splenomegaly, esophageal varices, thrombocytopenia), or sinusoidal obstruction syndrome (veno-occlusive disease; fluid retention, ascites, hepatomegaly with tenderness, or hyperbilirubinemia); monitor for tumor lysis syndrome, infection, or bleeding. Monitor for secondary malignancies. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Thioguanine is a purine analog of guanine that is incorporated into DNA and RNA resulting in the blockage of synthesis and metabolism of purine nucleotides.
Absorption: ~30% (range: 14% to 46%; highly variable)
Distribution: Does not reach therapeutic concentrations in the CSF
Metabolism: Hepatic; rapidly and extensively via thiopurine methyltransferase (TPMT) to 2-amino-6-methylthioguanine (MTG; active) and inactive compounds
Half-life elimination: Terminal: 5 to 9 hours
Time to peak, serum: Within 8 hours; predominantly metabolite(s)
Excretion: Urine, primarily as metabolites
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