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# Tabovoihep (Thioguanine)
## Overview
Thioguanine is a purine antimetabolite that interferes with nucleic acid synthesis.
## Primary Indications
* Treatment of acute myeloid leukemia (AML).
* Treatment of acute lymphoblastic leukemia (ALL).
## Adult Dosing
* **Induction and consolidation:** Typically 200 mg/m² orally once daily.
* **Maintenance:** Typically 40 mg/m² orally once daily.
* Dosing is highly individualized and depends on the specific regimen, patient response, and toxicity. Protocols vary significantly.
## Pediatric Dosing
* Dosing is highly individualized and depends on the specific regimen, patient response, and toxicity. Protocols vary significantly.
* A common starting dose is 75 mg/m² orally once daily.
## Dose Adjustments
* **Myelosuppression:** Dose reductions are often necessary in the event of significant neutropenia, thrombocytopenia, or anemia. Specific guidelines for dose reduction should be followed per institutional protocol.
* **Hepatic dysfunction:** Use with caution. Monitor liver function closely. Some protocols suggest dose reduction or discontinuation.
* **Renal dysfunction:** Data is limited. Dose reduction may be necessary.
## Contraindications
* Hypersensitivity to thioguanine or its components.
* In general, avoid in patients with severe bone marrow hypoplasia.
## Adverse Effects
* **Hematologic:** Myelosuppression (leukopenia, thrombocytopenia, anemia) is dose-limiting and common.
* **Hepatotoxicity:** Veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a serious and potentially fatal adverse effect, particularly in patients receiving bone marrow transplantation. Elevations in AST, ALT, bilirubin, and alkaline phosphatase can occur.
* **Gastrointestinal:** Nausea, vomiting, stomatitis, diarrhea.
* **Other:** Hyperuricemia, rash, hair loss (less common than with other antimetabolites).
## Key Drug Interactions
* **Allopurinol/Febuxostat:** Increased risk of hyperuricemia and potential for thioguanine toxicity due to inhibition of xanthine oxidase, which metabolizes thioguanine. Concomitant use is generally avoided or requires significant dose reduction of thioguanine.
* **Immunosuppressants:** Increased risk of infection and lymphoproliferative disorders.
* **Warfarin:** Thioguanine may decrease the effect of warfarin. Monitor INR closely.
## Monitoring
* **Complete blood counts (CBC) with differential and platelet count:** Frequently (e.g., daily to weekly) during induction and consolidation, then as clinically indicated.
* **Liver function tests (LFTs):** Including AST, ALT, bilirubin, and alkaline phosphatase. Monitor regularly, especially in patients at risk for VOD.
* **Renal function tests:** BUN and creatinine.
* **Uric acid levels:** Especially during induction therapy.
## Clinical Pearls
* Thioguanine is a prodrug that is converted intracellularly to active metabolites.
* The metabolism of thioguanine is influenced by the enzyme thiopurine S-methyltransferase (TPMT). Genetic variations in TPMT can lead to altered metabolism and increased risk of toxicity. TPMT testing may be considered, especially with difficult-to-manage toxicity.
* VOD is a significant concern, particularly in bone marrow transplant recipients. Risk factors include high-dose chemotherapy and a history of liver disease.
* Patients should be advised to avoid high-purine foods if hyperuricemia is a concern.
**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for complete details and to ensure patient safety. Dosing and management should be individualized based on patient-specific factors and institutional protocols.
