Systemic Therapy Program
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Date



Disease Group



Cancer Type

Document Type

Drug Monographs
Treatment Regimens
Scientific Name:
THIOGUANINE
Brand Name(s):
6TG, Lanvis®

Drug Monograph

Pharmacology

Mechanism of Action

6-Thioguanine (6-TG) is converted intracellularly to nucleotides which are incorporated into DNA and RNA. Incorporation into DNA is thought to be the primary cytotoxic mechanism.

Pharmacokinetics

Oral Absorption:
variable and incomplete, 14-46% bioavailability
Distribution:
not completely elucidated, crosses the placenta; excretion in breast-milk unknown
cross blood brain barrier? trace
Vd, PPB: no information
Metabolism:
predominantly in liver and other tissues by guanase to 6-thioinosine, then by thiopurine methyltransferase (TPMT) to 2-amino-6-methylthiopurine
metabolite(s):
 active- 2-amino-6-methylmercaptopurine   inactive- yes (6-thioinosine)
Excretion:
via hepatic metabolism
urine; hemodialysis unlikely to decrease toxicity
Urine: 24-46% within 24 hours
t½a 15 minutes t½ b  2.8-4 hours
Cl: no information

Side Effects

IMMEDIATE ONSET (hours to days)
• nausea and vomiting (uncommon, rare in children)
• increased uric acid levels (hyperuricemia)

EARLY ONSET (days to weeks)
• low WBC, RBC, platelets (myelosuppression, nadir 7-14 days, recovery 14-21 days)
• mouth sores (stomatitis, mild, rare)
• diarrhea
• anorexia
• rash (rare)
• liver problems (elevated liver function tests, veno-occlusive disease, jaundice)

DELAYED/LATE ONSET (weeks to years)
• birth defects (congenital anomalies)
• loss of vibration sensitivity (rare)
• unsteady gait (rare)

Therapeutics

Approved Indications

• Acute lymphocytic leukemia       
• Acute myelogenous leukemia
• Chronic myelogenous leukemia

Routes

Oral

Dosing

• calculate doses to nearest 20 mg

Induction
:
• daily: 2-3 mg/kg po, as a single dose, on an empty stomach
• 75-200 mg/m²/day po x 5-7 days/course or until remission

Maintenance:
• daily: 2-3 mg/kg po

Pediatric:
• calculate doses to nearest 10 mg
Induction:
• daily: 2-3 mg/kg po until adequate decrease in WBC count
• 75-200 mg/m²/day po x 5-7 days

Maintenance:
• 2 mg/kg/day po
• q8w: 300 mg/m²/day po x 4 days

Consolidation:
• 75 mg/m²/day po x 2-8 weeks

Dose Adjustment Criteria

Renal failure:
Consider dose reduction if renal function is reduced (eg. reduced creatinine clearance/serum creatinine)
 (Suggested action)

Antiemetic Risk

LOW RISK (Less than 10% of patients)
• No routine antiemetic pre-chemotherapy or post-chemotherapy

Contraindications

• Known hypersensitivity to thioguanine • Pregnancy and breast feeding

Monitoring

Clinical Monitoring

RECOMMENDED CRITERIA
• Complete blood count including differential, platelets and hemoglobin (CBC) before each cycle of treatment

SUGGESTED CRITERIA
• Baseline & periodic liver function tests [serum alkaline phosphatase, GGT, ALT, AST & Bilirubin levels (serum proteins may be added if indicated)]
• Baseline renal function tests (if failure suspected) [serum creatinine, electrolytes & BUN]

Significant Interactions

• 5-ASA derivatives: may decrease the metabolism of Thioguanine • CloZAPine: may increase the toxicity of Clozapine (specifically, agranulocytosis). Avoid combination. • Echinacea: may decrease the therapeutic effect of Thioguanine • Leflunomide: may increase toxicity of Leflunomide (specifically, the risk of hematologic toxicity). Consider not using a leflunomide loading dose in patients receiving Thioguanine. Monitor patient for bone marrow suppression at least monthly if using these drugs concurrently. • Tacrolimus (topical): may increase the toxicity of Thioguanine (avoid combination) • Vaccines (inactivated, live): may increase toxicity and decrease therapeutic effect of vaccines (avoid combination)

Product Information

Commercial Product Description

Greenish-yellow tablets with 40mg Thioguanine.

Handling Risk Level

Pregnancy DKNOWN HAZARDOUS DRUG
FDA Pregnancy Risk Factor D

  • This drug must be handled using precuations outlined in CCNS Policies for Occupational Safety and Administering Cancer Chemotherapy

Note

HANDLING RISK LEVEL:

HAZARD RISK LEVEL 2
FDA Pregnancy Risk Factor D
• This drug must be handled using precautions outlined in CCNS Policies for Preparing Cancer Chemotherapy and Administering Cancer Chemotherapy and the CCNS Standard for Oral Systemic Therapy for Cancer
• Go to "Additional Information" tab (above) for links to CCNS Policies

Availability & Funding

Administrative Information (Nova Scotia)

• CCNS Provincial Formulary Status- Basic Level for ordering on preprinted Physician • Go to "Additional Information" tab (above) for links to Provincial Formulary of Cancer Drugs • Pharmacare Formulary Status- Formulary • NOTE: It is recommended to limit ordering of this medication to standard preprinted order forms, for patient safety.