U.S. Brand Names

• Tabloid®

Medication Safety Issues

International issues:

• Lanvis® [Canada and multiple international markets] may be confused with Lantus® brand name for insulin glargine [U.S., Canada, and multiple international markets]

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

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

Generic Available

No

Pharmacologic Categories

• Antineoplastic Agent, Antimetabolite (Purine Antagonist)

Related Terms

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

Available Products

Image	Description
	Brand Name Tabloid® Strength 40 mg Labeler Glaxo Wellcome Class Rx Route oral NDC 001730880

Restrictions on Use

The I.V. formulation is not available in U.S.

Indications

Treatment of acute myelogenous (nonlymphocytic) leukemia (AML)

Hypersensitivity to thioguanine or any component of the formulation; pregnancy

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal.

Concerns related to adverse effects:

• Bone marrow suppression: Myelosuppression is a common dose-related toxicity (may be delayed); patients with genetic deficiency of thiopurine methyltransferase (TPMT) or who are receiving drugs which inhibit this enzyme (mesalazine, olsalazine, sulfasalazine) may be highly sensitive to myelosuppressive effects.
• Hepatotoxicity: Not recommended for long-term continuous therapy due to potential for hepatotoxicity (hepatic veno-occlusive disease); discontinue in patients with evidence of hepatotoxicity.
• Secondary malignancies: Thioguanine is potentially carcinogenic.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment recommended.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.

Special populations:

• Pregnancy: Thioguanine is potentially teratogenic.

Other warnings/precautions:

• Resistance: Caution with history of previous therapy resistance with either thioguanine or mercaptopurine (there is usually complete cross resistance between these two).

>10%: Hematologic: Myelosuppressive:

• WBC: Moderate
• Platelets: Moderate
• Onset: 7-10 days
• Nadir: 14 days
• Recovery: 21 days

1% to 10%:

• Dermatologic: Skin rash
• Endocrine & metabolic: Hyperuricemia
• Gastrointestinal: Mild nausea or vomiting, anorexia, stomatitis, diarrhea
• Neuromuscular & skeletal: Unsteady gait

<1%: Ascites, esophageal varices, hepatic necrosis, hepatitis, jaundice, LFTs increased, neurotoxicity, photosensitivity, portal hypertension, splenomegaly, thrombocytopenia, veno-occlusive hepatic disease

Drug Interactions

5-ASA Derivatives: May decrease the metabolism of Thiopurine Analogs. Risk C: Monitor therapy

BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination

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

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification

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. Risk D: Consider therapy modification

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

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

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy

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

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy

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

Ethanol/Nutrition/Herb Interactions

Food: Enhanced absorption if administered between meals.

Dosing: Adults

Total daily dose can be given at one time.

Antineoplastic: Oral: Refer to individual protocols: 2-3 mg/kg/day calculated to nearest 20 mg or 75-200 mg/m²/day in 1-2 divided doses for 5-7 days or until remission is attained

Dosing: Elderly

Refer to adult dosing.

Dosing: Pediatric

Total daily dose can be given at one time.

Antineoplastic: Oral (refer to individual protocols):

• Infants and Children <3 years: Combination drug therapy for acute nonlymphocytic leukemia: 3.3 mg/kg/day in divided doses twice daily for 4 days
• Children >3 years: Refer to adult dosing.

Dosing: Renal Impairment

Reduce dose.

Dosing: Hepatic Impairment

Reduce dose.

Dosage Forms

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

Tablet [scored]:

• Tabloid®: 40 mg

Pregnancy Risk Factor

D

Lactation

Excretion in breast milk unknown

Mechanism of Action

Purine analog that is incorporated into DNA and RNA resulting in the blockage of synthesis and metabolism of purine nucleotides

Pharmacodynamics/Kinetics

Absorption: 30% (highly variable)

Distribution: Crosses placenta

Metabolism: Hepatic; rapidly and extensively via TPMT to 2-amino-6-methylthioguanine (active) and inactive compounds

Half-life elimination: Terminal: 11 hours

Time to peak, serum: Within 8 hours

Excretion: Urine

Monitoring Parameters

CBC with differential and platelet count; liver function tests (weekly when beginning therapy then monthly, more frequently in patients with liver disease or concurrent hepatotoxic drugs); hemoglobin, hematocrit, serum uric acid; some laboratories offer testing for TPMT deficiency

Hepatotoxicity may present with signs of portal hypertension (splenomegaly, esophageal varices, thrombocytopenia) or veno-occlusive disease (fluid retention, ascites, hepatomegaly with tenderness, or hyperbilirubinemia)

Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed. Maintain adequate hydration unless instructed to restrict fluid intake. May cause nausea and vomiting, diarrhea, or loss of appetite (small, frequent meals may help/request medication); weakness or lethargy (use caution when driving or engaging in tasks requiring alertness until response to drug is known); mouth sores (use good oral care); or headache (request medication). You will be susceptible to infection (avoid crowds and exposure to infection). Report signs or symptoms of infection (eg, fever, chills, sore throat, burning urination, fatigue); bleeding (eg, tarry stools, easy bruising); vision changes; unresolved mouth sores, nausea, or vomiting; CNS changes (hallucinations); or respiratory difficulty. Pregnancy/breast-feeding precautions: Do not get pregnant. Consult prescriber for appropriate contraceptive measures. The drug may cause permanent sterility and may cause birth defects. Consult prescriber if breast-feeding.

Storage

Store tablet at room temperature.

• Broxson EH, Dole M, Wong R, et al, “Portal Hypertension Develops in a Subset of Children With Standard Risk Acute Lymphoblastic Leukemia Treated With Oral 6-Thioguanine During Maintenance Therapy,” Pediatr Blood Cancer, 2005, 44(3):226-31
• Elgemeie GH, "Thioguanine, Mercaptopurine: Their Analogs and Nucleosides as Antimetabolites," Curr Pharm Des, 2003, 9(31):2627-42. [PMID:14529546]
• Estlin EJ, “Continuing Therapy for Childhood Acute Lymphoblastic Leukaemia: Clinical and Cellular Pharmacology of Methotrexate, 6-Mercaptopurine and 6-Thioguanine,” Cancer Treat Rev, 2001, 27(6):351-63. [PMID:11908928]