THIOGUANINE
Clinical safety rating: avoid
Contraindicated (not allowed)
Thioguanine is a purine analog that incorporates into DNA and RNA, inhibiting purine nucleotide synthesis and cell replication. It acts as an antimetabolite, specifically targeting S-phase of the cell cycle.
| Metabolism | Thioguanine is metabolized by thiopurine S-methyltransferase (TPMT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) to active thioguanine nucleotides. |
| Excretion | Primarily renal; 40% excreted unchanged in urine within 24 hours; minor biliary/fecal elimination (<10%). |
| Half-life | Terminal half-life approximately 11 hours (range 5-16 hours) in adults; extends to 20-30 hours in renal impairment. |
| Protein binding | 30% bound to albumin. |
| Volume of Distribution | 0.5-0.8 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral: approximately 30% (variable, 14-46%) due to incomplete absorption and first-pass metabolism. |
| Onset of Action | Oral: 7-14 days for antileukemic effect (bone marrow remission). |
| Duration of Action | Myelosuppressive effects persist for 1-3 weeks after cessation; clinical remission duration variable. |
| Molecular Weight | 167.19 |
2 mg/kg orally once daily for 4 weeks, then 2 mg/kg orally every other day; or 2-3 mg/kg/day orally for 5 days per cycle.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended; use caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation of metabolites. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use or use with extreme caution. |
| Pediatric use | 2-3 mg/kg/day orally divided every 12 hours; maximum daily dose 200 mg. Alternatively, 75-100 mg/m²/day orally for 5 days. |
| Geriatric use | Start at lower end of dosing range (2 mg/kg/day) due to increased risk of myelosuppression and renal clearance decline. |
| 1st trimester | Avoid; teratogenic potential similar to other thiopurines. Use only if clearly needed and no alternative. |
| 2nd trimester | Use only if maternal benefit outweighs possible risks; fetal growth restriction and hematologic effects reported. |
| 3rd trimester | Risk of neonatal myelosuppression and immunosuppression; consider withholding 2-3 weeks before delivery if possible. |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and hepatotoxicity.
| Placental transfer | Crosses placenta; fetal concentrations may be similar to maternal. Associated with intrauterine growth restriction and fetal bone marrow suppression. |
| Breastfeeding | Excreted into breast milk in small amounts; potential for severe myelosuppression in nursing infants. Due to risk, breastfeeding is not recommended during therapy. |
■ FDA Black Box Warning
Thioguanine can cause severe myelosuppression, leading to life-threatening infections and bleeding. It is also associated with hepatotoxicity, including veno-occlusive liver disease. The drug should be used under the supervision of a physician experienced in cancer chemotherapy.
| Common Effects | Myelosuppression |
| Serious Effects |
Hypersensitivity to thioguanine or any componentSevere hepatic impairmentPrior severe myelosuppression from thiopurines
| Precautions | Hepatotoxicity, including hepatic veno-occlusive disease, myelosuppression, increased risk of secondary malignancies (e.g., acute myeloid leukemia), teratogenicity, and photosensitivity. Monitor liver function tests and complete blood counts regularly. TPMT deficiency increases risk of toxicity. |
| Food/Dietary |
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| Lactation Rating | L4 (Hazardous) |
| Teratogenic Risk | Pregnancy Category D. First trimester: Increased risk of fetal malformations including cleft palate, craniofacial anomalies, and skeletal defects. Second and third trimesters: Risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Avoid use in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor complete blood count with differential and platelets weekly for mother. Monitor liver function tests and uric acid levels. Fetal monitoring: Serial ultrasound for growth restriction and fetal anomalies; consider fetal echocardiogram. |
| Fertility Effects | May cause oligospermia or azoospermia in males and amenorrhea or ovarian failure in females. Reversible upon discontinuation. Advise fertility counseling prior to treatment. |
| No specific food interactions documented. Maintain adequate hydration to prevent hyperuricemia. Avoid grapefruit juice as it may affect metabolism, though not well-established. |
| Clinical Pearls | Thioguanine is a purine analog used in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). It is activated by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Myelosuppression is dose-limiting; monitor CBC weekly. Hepatotoxicity, including veno-occlusive disease, is a risk, especially with doses >2.5 mg/kg/day. Reduce dose in renal impairment. Thioguanine is metabolized by thiopurine S-methyltransferase (TPMT); measure TPMT activity prior to initiation to avoid severe toxicity. Do not use with allopurinol without dose adjustment as allopurinol inhibits xanthine oxidase, reducing thioguanine metabolism. |
| Patient Advice | Take thioguanine exactly as prescribed, typically once daily. · Avoid alcoholic beverages due to risk of liver damage. · Report any signs of infection (fever, sore throat), unexplained bruising/bleeding, or jaundice immediately. · Use effective contraception during treatment and for at least 6 months after for females, 3 months for males. · Do not take allopurinol, febuxostat, or other xanthine oxidase inhibitors without consulting your doctor. · Your blood counts and liver function will be monitored regularly. |