Version July 2025
Dosage guidance:
Dosing: In pediatric patients, dosing presented as mg/m2 and mg/kg; use extra precaution. Refer to individual protocols for dosing and frequency.
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 (see Dosage adjustment for TPMT and/or NUDT15 deficiency below) (Ref).
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 in combination with asparaginase, cyclophosphamide, cytarabine, dexamethasone, doxorubicin, methotrexate intrathecal, vincristine (Ref)
Acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) with Down syndrome: Limited data available:
AAML0431, AAML1531 protocol: Induction:
Infants ≥3 months and Children <36 months: Oral: 1.65 mg/kg/dose twice daily for 4 days in combination with cytarabine and daunorubicin; refer to specific protocol for number and sequence of induction cycles (Ref).
Children ≥36 months and <4 years: Oral: 50 mg/m2/dose twice daily for 4 days in combination with cytarabine and daunorubicin; refer to specific protocol for number and sequence of induction cycles (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment in TPMT and/or NUDT15 deficiency: Limited data available:
Infants, Children, and Adolescents:
Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines (Ref), updated March 2024:
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.
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. 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).
TPMT intermediate or possible intermediate metabolizer and NUDT15 intermediate or possible intermediate metabolizer: Initiate thioguanine with the dose reduced to 20% 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).
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. 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.
NUDT15 poor metabolizer: Initiate thioguanine with the dose reduced to 25% of the usual dose and adjust 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.
Manufacturer's labeling:
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.
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.
Children and Adolescents: Oral: There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; some suggest that no adjustment required in pediatric patients (Ref).
Children and Adolescents: Oral:
Baseline liver impairment: There are no dosage adjustments provided in the manufacturer's labeling for patients with baseline hepatic impairment.
Hepatotoxicity during treatment: Discontinue treatment for deterioration in transaminases, alkaline phosphatase or bilirubin, toxic hepatitis, biliary stasis, clinical jaundice, evidence of hepatotoxicity, evidence of 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).
(For additional information see "Thioguanine: Drug information")
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 (Ref). 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) (Ref).
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) (Ref).
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) (Ref).
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 (CPIC) guidelines (Ref):
|
TPMT/NUDT15 phenotype |
Thioguanine starting dose |
Thioguanine dose adjustment |
|---|---|---|
|
a Relling 2019. | ||
|
b CPIC Guideline for Thiopurine and TPMT and NUDT15 March 2024 update; CPIC guidelines (including updates) are located at https://cpicpgx.org/guidelines/guideline-for-thiopurines-and-tpmt/. | ||
|
TPMT normal metabolizer OR NUDT15 normal metabolizer |
Follow instructions for the specific determinate phenotype: Utilize the more stringent determinate phenotype for dosage modification (eg, if TPMT normal metabolizer and NUDT15 poor metabolizer, follow instructions for NUDT15 poor metabolizer). | |
|
TPMT normal metabolizer AND NUDT15 normal metabolizer |
No initial dosage adjustment necessary.a |
Adjust dose based on the condition being treated. Allow 2 weeks to reach steady state after each dose adjustment. For patients receiving combination therapy, dosage adjustments (of all agents) should be made without any emphasis on thioguanine compared to other agents.a |
|
TPMT intermediate metabolizer or possible intermediate metabolizer OR NUDT15 intermediate metabolizer or possible intermediate metabolizer |
Normal starting dose ≥40 to 60 mg/m2/day: Initiate thioguanine with a reduced starting dose (50% to 80% of the normal dose).a Note: Follow instructions for the specific determinate phenotype: Utilize the more stringent determinate phenotype for dosage modification (eg, if TPMT intermediate metabolizer and NUDT15 poor metabolizer, follow instructions for NUDT15 poor metabolizer). |
Adjust dose based on the degree of myelosuppression and the condition being treated. Allow 2 to 4 weeks to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing the thioguanine dose over other agents (depending on concomitant therapy).a |
|
TPMT intermediate metabolizer or possible intermediate metabolizer AND NUDT15 intermediate metabolizer or possible intermediate metabolizer |
Normal starting dose ≥40 to 60 mg/m2/day: Initiate thioguanine with a reduced starting dose (20% to 50% of the normal dose).b |
Adjust dose based on the degree of myelosuppression and the condition being treated. Allow at least 2 to 4 weeks to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing the thioguanine dose over other agents (depending on concomitant therapy).b |
|
TPMT poor metabolizer |
Nonmalignant conditions: Consider alternative (non-thiopurine) immunosuppressant therapy.a Malignant conditions: Initiate thioguanine with a drastically reduced dose (reduce daily dose by 10-fold and reduce the frequency from once daily to 3 times a week).a |
Adjust doses of azathioprine based on the degree of myelosuppression and the condition being treated. Allow 4 to 6 weeks to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing the thioguanine dose over other agents (depending on concomitant therapy).a |
|
NUDT15 poor metabolizer |
Nonmalignant conditions: Consider alternative (non-thiopurine) immunosuppressant therapy.a Malignant conditions: Initiate thioguanine with a reduced starting dose (25% of the normal dose).a |
Adjust doses of thioguanine based on the degree of myelosuppression and the condition being treated. Allow 4 to 6 weeks to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing the thioguanine dose over other agents (depending on concomitant therapy).a |
|
TPMT indeterminate AND NUDT15 indeterminate |
Consider evaluating TPMT erythrocyte activity to assess phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.b | |
|
TPMT indeterminate OR NUDT15 indeterminate |
Follow instructions above for the specific determinate phenotype. If TPMT indeterminate, consider evaluating TPMT erythrocyte activity to assess phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.b | |
Manufacturer's labeling:
Heterozygous deficiency (intermediate activity): Reduce the dose based on tolerability; most patients with heterozygous deficiency of TPMT or NUDT15 tolerate recommended doses, although some require dosage reduction. Patients who are heterozygous for both TPMT and NUDT15 may require more substantial dose reductions.
Homozygous deficiency (low or deficient activity): Reduce the thioguanine dose to 10% of the usual dose or lower for homozygous deficiency in either TPMT or NUDT15.
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).
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): $648.76
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
20 mg/mL (ASHP Standard Concentration) (ASHP 2017)
A 20 mg/mL oral suspension may be prepared in a vertical flow hood with tablets and Ora-Plus and Ora-Sweet or methylcellulose 1% and simple syrup (Aliabadi 2011).
Ora-Plus and Ora-Sweet: Crush five 40 mg thioguanine tablets in a mortar and reduce to a fine powder. Add 5 mL of Ora-Plus in incremental proportions and mix to a uniform paste. Transfer to a graduated amber glass bottle, rinse mortar with Ora-Sweet and add sufficient quantity to make 10 mL. Label "shake well." Stable for 63 days at room temperature.
Methylcellulose and simple syrup: Crush five 40 mg thioguanine tablets in a mortar and reduce to a fine powder. Add 3.33 mL of methylcellulose 1% in incremental proportions and mix to a uniform paste. Transfer to a graduated amber glass bottle, rinse mortar with simple syrup and add sufficient quantity to make 10 mL. Label "shake well." Stable for 63 days at room temperature.
Oral: Administer at the same time(s) each day. Total daily dose may be administered at one time; refer to specific protocol for timing of doses.
Tablets: Tablets are scored; doses can be rounded to half tablet.
Oral: Administer orally; total daily dose can be administered at one time.
Hazardous agent (NIOSH 2024 [table 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 2023; NIOSH 2024; USP-NF 2020).
Store at 15°C to 25°C (59°F to 77°F). Protect from moisture.
Remission induction and remission consolidation treatment of acute nonlymphocytic leukemia (ANLL, AML) [FDA approved in pediatrics (age not specified) and adults]; has also been used for treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia or myelodysplastic syndrome in individuals with Down syndrome
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.
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
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Thiopurine Analogs. 5-Aminosalicylic Acid Derivatives may increase active metabolite exposure of Thiopurine Analogs. Specifically, exposure to the active 6-thioguanine nucleotides (6-TGN) may be increased. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Anti-TNF Agents: May increase adverse/toxic effects of Thiopurine Analogs. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Agents that Undergo Intracellular Phosphorylation may decrease therapeutic effects of Cladribine. Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. 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 (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects 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 decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects 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 increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 increase immunosuppressive effects 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 decrease therapeutic effects 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 increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects 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 decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects 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 decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of 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 increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects 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 increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects 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
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
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).
CBC with differential and platelet count (frequently with therapy), liver function tests (serum transaminases, alkaline phosphatase, bilirubin [weekly at initiation of therapy, then periodically; more frequent monitoring if hepatic impairment or concurrent hepatotoxic agents]), serum uric acid; evaluate thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (nucleotide diphosphatase [NUDT15]) genotyping to identify TPMT and NUDT15 status; signs/symptoms for liver-related adverse effects including: 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. Monitor adherence.
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
