Thioguanine
Thioguanine (6-TG) is a **purine antimetabolite** antineoplastic agent used primarily as an adjunctive treatment for acute lymphocytic or granulocytic leukemia in dogs and cats. **Clinical Pearls:** * It is a **cell-cycle phase-specific** drug, acting primarily in the **S-phase** (DNA synthesis). * While it shares extensive cross-resistance with mercaptopurine, its metabolism is distinct (it does not rely on xanthine oxidase for degradation), which alters its interaction profile compared to azathioprine or mercaptopurine. * It has a very narrow therapeutic index and requires rigorous monitoring of hematologic parameters. * Cats are particularly sensitive to its myelosuppressive effects.
Mecanismo: Thioguanine acts as a false purine base. * **Intracellular Activation:** It is converted by the enzyme **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)** → **thioguanine monophosphate (TGMP)**. * **DNA/RNA Incorporation:** TGMP is further phosphorylated into di- and tri-nucleotides, which are then incorporated into **DNA and RNA**. * **Cytotoxicity:** The insertion of these fraudulent nucleotides disrupts normal nucleic acid synthesis and function, leading to DNA strand breaks and **apoptosis**. * It also causes feedback inhibition of *de novo* purine synthesis, further starving the cancer cells of essential nucleotides.
Dosificación por especie
- Acute lymphocytic and granulocytic leukemia · 25 mg/m2 PO once daily (q24 hours) for 1-5 days, then every 30 days thereafter as necessary · PO · q24h initially, then q30d · 1-5 days initially, then ongoing · Cats are particularly susceptible to hematologic effects.
- Acute lymphocytic and granulocytic leukemia · 40 mg/m2 PO once daily (q24 hours) for 4-5 days, then every 3rd day thereafter · PO · q24h initially, then q72h · 4-5 days initially, then ongoing · Consultation with a veterinary oncologist is strongly recommended.
- Acute myelogenous leukemias (Protocol 1 & 2) · 50 mg/m2 PO q24-48h · PO · q24-48h · Ongoing · Used as part of a protocol with Cytarabine (100 mg/m2 SC daily for 2-6 days) +/- Doxorubicin (10 mg/m2 IV once a week).
Las dosis son una referencia clínica para médicos veterinarios. Confirme siempre con la información vigente del producto y el paciente individual.
Vías de administración
Contraindicaciones
- Hypersensitivity to thioguanine
- Pregnancy (Category D - teratogenic and mutagenic)
Efectos adversos
- Nausea
- Anorexia
- Vomiting
- Diarrhea
- Bone marrow suppression (leukopenia, thrombocytopenia, anemia)
- Hepatotoxicity
- Pancreatitis
- Gastrointestinal ulceration (including oral ulcers)
- Dermatologic reactions
Interacciones farmacológicas
- Hepatotoxic drugs (e.g., halothane, ketoconazole, valproic acid, phenobarbital, primidone) · Increased risk of hepatotoxicity; use concurrently with caution.
- Immunosuppressive drugs (e.g., azathioprine, cyclophosphamide, corticosteroids) · Increased risk of severe infection due to additive immunosuppression.
- Myelosuppressive drugs (e.g., chloramphenicol, flucytosine, amphotericin B, colchicine) · Additive bone marrow depression; extreme caution required.
- Live vaccines · Increased risk of vaccine-induced infection or decreased vaccine efficacy; use with caution or avoid.
Monitoreo
- Hemograms (including platelets) initially every 1-2 weeks, then every 1-2 months on maintenance. (Dose reduction of 25% recommended if WBC drops to 5,000-7,000 cells/mm3; discontinue if < 5,000 cells/mm3 until resolved)
- Liver function tests
- Serum amylase (if pancreatitis is suspected)
- Clinical efficacy (remission status)
Sobredosis
Toxicity from overdosage can manifest as **acute** (severe gastrointestinal effects like nausea, vomiting, diarrhea) or **delayed** (profound bone marrow depression, hepatotoxicity, severe gastroenteritis). **Treatment:** * If ingestion was recent, use standard protocols to empty the GI tract (emesis/gastric lavage followed by activated charcoal), keeping in mind the risks of handling cytotoxic emesis. * Provide aggressive supportive care (IV fluids, broad-spectrum antibiotics if neutropenic, blood products if severely anemic or thrombocytopenic).
La referencia de fármacos de VetSheet está destinada a médicos veterinarios como apoyo a la decisión clínica; no sustituye el juicio profesional ni la información vigente del fabricante.