Dosing and uses of 6TG, 6Thioguanine (thioguanine)
Adult dosage forms and strengths
tablet
- 40mg
Acute Nonlymphocytic Leukemia
2 mg/kg/day PO
Cautiously increase to 3 mg/kg/day if no response after 4 weeks
May be used in multi-drug thearpy, including prednisone, cytarabine, cyclophosphamide, vincristine
Monitor: CBC, LFTs
Take on empty stomach to reduce risk of nausea and vomiting
Pediatric dosage forms and strengths
tablet
- 40mg
Acute Nonlymphocytic Leukemia
2 mg/kg/day PO
Cautiously increase to 3 mg/kg/day if no response after 4 weeks
May be used in multi-drug thearpy, including prednisone, cytarabine, cyclophosphamide, vincristine
Monitor: CBC, LFTs
Take on empty stomach to reduce risk of nausea and vomiting
6TG, 6Thioguanine (thioguanine) adverse (side) effects
Frequency not defined
Anorexia
Stomatitis
Vomiting
Nausea
Myelosuppression
Hyperuricemia
Nephrotoxicity
Hepatotoxicity
Warnings
Contraindications
Hypersensitivity; prior resistance to 6-TG or mercaptopurine
Not effective for CLL, lymphomas, multiple myeloma, solid tumors
Cautions
Not for long-term use (risk of hepatotoxicity)
Myelosuppression may occur
Monitor for infections (leukopenia)
Monitor for bleeding (thrombocytopenia)
Secondary malignancies may occur
Tumor lysis syndrome may occur
Although active in CML, busulfan is preferred
Avoid pregnancy
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of 6TG, 6Thioguanine (thioguanine)
Mechanism of action
Purine analog that is incorporated into DNA and RNA and inhibits purine ribonucleotide synthesis
Pharmacokinetics
Half-Life: 15 min (initial phase); 5-9 hr (terminal phase)
Absorption: 30%
Time to peak: 8hr (serum)
Metabolism: Liver
Metabolites: 2-amino-6-methylthiopurine, inorganic sulfate, thiouric acid
Excretion: Urine
Dialyzable: No
Pharmacogenomics
Converted via thiopurine S-methyltransferase (TPMT) to 2-amino-6-methylthioguanine (MTG, active metabolite) and inactive metabolites
Complete TPMT deficiency is rare in the general population (0.3%); increased myelosuppression when used with TPMT deficiency
Alleles associated with decreased TPMT enzymatic activity are TPMT*2, TPMT*3A, and TPMT*3C
Companies providing genetic testing
- The following companies currently offer testing for TPMT variants
- Prometheus Labs (https://www.prometheuslabs.com/)
- Arup Laboratories (https://www.aruplab.com/)
