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Thioguanine: Drug information

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

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

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 2019). Initiate adequate hydration and prophylactic antihyperuricemics (eg, allopurinol) to prevent tumor lysis syndrome.

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (off-label use): 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).

Acute myeloid leukemia

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 (Relling 2019); 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.

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.

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).

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).

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.

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.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Adult

Hepatic impairment prior to treatment: There are no dosage adjustments provided in the manufacturer’s labeling.

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).

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).

Dosing: Adjustment for Toxicity: Adult

Hematologic toxicity: Withhold treatment for abnormally significant drop in blood counts.

Dosing: Older Adult

Refer to adult dosing. Start at the low end of the dosing range.

Dosing: Pediatric

(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

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

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/myelodysplastic syndrome with Down syndrome

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

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.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; some suggest that no adjustment required in pediatric patients (Aronoff 2007).

Dosing: Hepatic Impairment: Pediatric

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.

Adverse Reactions

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

Contraindications

Prior resistance to thioguanine (or mercaptopurine)

Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to thioguanine or any component of the formulation

Warnings/Precautions

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]) (see "Warnings/Precautions: TPMT or NUDT15 deficiency") 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; formerly 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 (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 (Relling 2019).

Other warnings/precautions:

• Cross resistance: Cross resistance with mercaptopurine generally occurs.

• Vaccines: Avoid vaccination with live vaccines during treatment.

Warnings: Additional Pediatric Considerations

Liver toxicity is particularly prevalent in children (up to 25%) receiving maintenance therapy for acute lymphoblastic leukemia and in males.

Dosage Forms: US

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

Tablet, Oral:

Tabloid: 40 mg [scored]

Generic Equivalent Available: US

No

Pricing: US

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.

Dosage Forms: Canada

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

Tablet, Oral:

Lanvis: 40 mg

Administration: Adult

Oral: Administer orally; total daily dose can be administered at one time.

Administration: Pediatric

Oral: Total daily dose may be administered at one time.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

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

Use: Labeled Indications

Acute 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.

Use: Off-Label: Adult

Acute lymphoblastic leukemia

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

Thioguanine may be confused with thiotepa

High alert medication:

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

Other safety concerns:

6-thioguanine and 6-TG are error-prone abbreviations (associated with sixfold overdoses of thioguanine)

International issues:

Lanvis [Canada and multiple international markets] may be confused with Lantus brand name for insulin glargine [US, Canada, and multiple international markets]

Metabolism/Transport Effects

None known.

Drug Interactions

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Reproductive Considerations

Patients should avoid becoming pregnant during treatment.

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to thioguanine may cause fetal harm.

Thioguanine crosses the placenta (NTP 2013; Pavlidis 2014).

Pregnancy outcomes following use of thioguanine for cancer chemotherapy have been described (NTP 2013).

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).

Breastfeeding Considerations

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.

Monitoring Parameters

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 (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 (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.

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

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

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

  • (AE) United Arab Emirates: Lanvis;
  • (AR) Argentina: Lanvis;
  • (AT) Austria: Thioguanin;
  • (AU) Australia: Lanvis;
  • (BE) Belgium: Lanvis;
  • (BG) Bulgaria: Lanvis;
  • (BR) Brazil: Lanvis;
  • (CH) Switzerland: Lanvis;
  • (CL) Chile: Lanvis;
  • (CN) China: Thioguanine;
  • (CO) Colombia: Lanvis;
  • (CZ) Czech Republic: Lanvis;
  • (DE) Germany: Thioguanin aspen | Thioguanin gsk | Thioguanine;
  • (DO) Dominican Republic: Lanvis;
  • (EE) Estonia: Lanvis;
  • (ES) Spain: Lanvis | Tioguanina;
  • (FI) Finland: Lanvis;
  • (FR) France: Lanvis;
  • (GB) United Kingdom: Lanvis;
  • (GR) Greece: Lanvis;
  • (HK) Hong Kong: Lanvis;
  • (HU) Hungary: Lanvis;
  • (IE) Ireland: Lanvis;
  • (IL) Israel: Lanvis;
  • (IN) India: 6 TG;
  • (IT) Italy: Thioguanine;
  • (JO) Jordan: Lanvis;
  • (KR) Korea, Republic of: Lanvis | Thioguanine | Union thioguanine;
  • (LT) Lithuania: Lanvis;
  • (LV) Latvia: Lanvis | Tioguanina aspen;
  • (MY) Malaysia: Lanvis;
  • (NL) Netherlands: Aces tg | Lanvis | Thiosix;
  • (NO) Norway: Lanvis | Tioguanina farma mondo | Tioguanine farma mondo;
  • (NZ) New Zealand: Lanvis | Thioguanine;
  • (PE) Peru: Tioguanina;
  • (PK) Pakistan: Thioguanine;
  • (PL) Poland: Lanvis;
  • (PR) Puerto Rico: Tabloid | Thioguanine;
  • (PT) Portugal: Lanvis;
  • (RU) Russian Federation: Lanvis;
  • (SA) Saudi Arabia: Lanvis;
  • (SE) Sweden: Lanvis;
  • (SG) Singapore: Lanvis;
  • (SI) Slovenia: Lanvis;
  • (SK) Slovakia: Lanvis;
  • (TH) Thailand: Lanvis;
  • (TR) Turkey: Lanvis;
  • (TW) Taiwan: Lanvis;
  • (UA) Ukraine: Lanvis;
  • (UY) Uruguay: Tabloid;
  • (ZA) South Africa: Lanvis
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