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Thioguanine

Medically reviewed by Drugs.com. Last updated on May 23, 2020.

Pronunciation

(thye oh GWAH neen)

Index Terms

  • 2-Amino-6-Mercaptopurine
  • 6-TG (error-prone abbreviation)
  • 6-Thioguanine (error-prone abbreviation)
  • TG
  • Tioguanine

Dosage Forms

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

Tablet, Oral:

Tabloid: 40 mg [scored]

Brand Names: U.S.

  • Tabloid

Pharmacologic Category

  • Antineoplastic Agent, Antimetabolite
  • Antineoplastic Agent, Antimetabolite (Purine Analog)

Pharmacology

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

Excretion

Urine, primarily as metabolites

Time to Peak

Serum: Within 8 hours; predominantly metabolite(s)

Half-Life Elimination

Terminal: 5 to 9 hours

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.

Off Label Uses

Acute lymphoblastic leukemia

Data from two studies supports the use of thioguanine as a component of combination therapy in late intensification phase in acute lymphoblastic leukemia (ALL) treatment in adults [Larson 1995], [Larson 1998].

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

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).

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.

Acute lymphoblastic leukemia (off-label use): Oral: Late intensification treatment phase: 60 mg/m2 once daily on days 29 to 42 (in combination with doxorubicin, vincristine, dexamethasone, cyclophosphamide and cytarabine) (Larson 1995; Larson 1998)

Dosage adjustment for TPMT and/or NUDT15 deficiency:

Clinical Pharmacogenetics Implementation Consortium guidelines (Relling 2019):

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).

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: Pediatric

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.

Extemporaneously Prepared

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 fifteen 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 30 mL. Label "shake well." Stable for 63 days at room temperature.

Methylcellulose and simple syrup: Crush fifteen 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 30 mL. Label "shake well." Stable for 63 days at room temperature.

Aliabadi HM, Romanick M, Somayaji V, Mahdipoor P, Lavasanifar A. Stability of compounded thioguanine oral suspensions [published correction appears in Am J Health Syst Pharm. 2011;68(14):1278.]. Am J Health Syst Pharm. 2011;68(10):900-908.21546641

Administration

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

Storage

Store at 15°C to 25°C (59°F to 77°F). Protect from moisture.

Drug Interactions

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. 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. Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

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

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

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

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

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

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

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

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

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Inebilizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. 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. 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. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. 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. Consider therapy modification

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Talimogene Laherparepvec: Immunosuppressants may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk for disseminated herpetic infection may be increased. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Management: Concomitant use of upadacitinib with potent immunosuppressants is not recommended. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated less than 2 weeks before starting or during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

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

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); monitor for infection (due to leukopenia) or bleeding (due to thrombocytopenia); withhold treatment with abnormally significant drop in blood counts. 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. Monitor liver function carefully for liver toxicity and discontinue in patients with evidence of hepatotoxicity, hepatic SOS (eg, hyperbilirubinemia, hepatomegaly [tender], and weight gain due to ascites and fluid retention) or portal hypertension (eg, splenomegaly, thrombocytopenia, esophageal varices). 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. Long-term/maintenance treatment with thioguanine is not recommended. 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; institute adequate hydration and prophylactic allopurinol.

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. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for thiopurine dosing based on TPMT and NUDT15 genotypes (Relling 2019) recommends reduced initial doses for TPMT and NUDT15 intermediate (and possible intermediate) metabolizers (with dosage adjustments based on myelosuppression). For TPMT and NUDT15 poor metabolizers, the CPIC guideline recommends drastically reduced doses. 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:

• Appropriate use: Not recommended for maintenance therapy or long term continuous treatment due to toxicities.

• Cross resistance: Cross resistance with mercaptopurine generally occurs.

• Vaccines: Avoid vaccination with live vaccines during treatment.

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. Monitor adherence.

Reproductive Considerations

Females of reproductive potential should avoid becoming pregnant during treatment.

Pregnancy Risk Factor

D

Pregnancy Considerations

Adverse effects have been observed in animal reproduction studies. May cause fetal harm if administered during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat a type of leukemia.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Lack of appetite

• Mouth sores

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding

• Severe loss of strength and energy

• Abdominal swelling

• Excessive weight gain

• Tumor lysis syndrome like fast heartbeat or abnormal heartbeat; any passing out; unable to pass urine; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.