THIOGUANINE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and hepatotoxicity.

Breastfeeding	Contraindicated. No human data on M/P ratio; thioguanine and its metabolites are excreted in breast milk in rats. Potential for neonatal myelosuppression and immunosuppression. Discontinue breastfeeding or avoid thioguanine.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

Hypersensitivity to thioguanine or any component of the formulation; documented TPMT deficiency (relative). Concurrent use with live vaccines. Severe hepatic impairment (relative).

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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