Generic
Treosulfan
1 brands available in the market
At a glance
Treosulfan is indicated in combination with fludarabine as part of conditioning treatment prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult patients with AML or MDS at increased risk, and in pediatric patients older than 1 year with AML or MDS.
Description
Treosulfan is a prodrug of a bifunctional alkylating agent with cytotoxic activity to hematopoietic stem cells. It converts to mono-epoxide and di-epoxybutane, which alkylate and cross-link DNA, causing stem cell depleting, immune-suppressive, and antineoplastic effects.
Indications
- Acute myeloid leukemia (AML)
- Myelodysplastic syndrome (MDS)
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
Alkylating Agent
Pharmacology
Treosulfan is a prodrug of a bifunctional alkylating agent. It spontaneously converts to mono-epoxide and di-epoxybutane in a pH-dependent manner. These epoxides alkylate and cross-link DNA and other biological molecules, causing stem cell depleting, immune-suppressive, and antineoplastic effects.
Mechanism of action
Alkylates and cross-links DNA, causing stem cell depletion and antineoplastic effects.
Dosage
Adult Dose (IV):
- Treosulfan: 10 g/m² BSA daily as 2-hour IV infusion on 3 consecutive days (day -4, -3, -2) before stem cell infusion (day 0); total dose 30 g/m²
- Fludarabine: 30 mg/m² BSA daily as 0.5-hour IV infusion on 5 consecutive days (day -6, -5, -4, -3, -2); total dose 150 mg/m²
- Administer treosulfan before fludarabine on days -4, -3, -2 (FT 10 regimen)
Pediatric Dose (>1 year): Same regimen applies
Administration
- Administered by a healthcare professional as IV infusion
- Use safe technique for IV application
- If extravasation suspected, implement general safety measures
Missed dose
If you miss a dose, consult your doctor.
Side effects
Common Side Effects:
- Profound myelosuppression/pancytopenia (desired therapeutic effect)
- Nausea
- Stomatitis
- Vomiting
- Diarrhea
- Increased bilirubin
- Fatigue
- Infections
- Febrile neutropenia
- Hepatotoxicity
- Alopecia
Precautions & warnings
- Profound myelosuppression is expected; blood counts recover after HSCT
- Contraindicated in active non-controlled infectious disease
- Contraindicated in severe cardiac, lung, liver, or renal impairment
- Contraindicated in Fanconi anemia and other DNA breakage repair disorders
- Do not administer live vaccines
Contraindications
- Active non-controlled infectious disease
- Severe concomitant cardiac, lung, liver, and renal impairment
- Fanconi anemia and other DNA breakage repair disorders
- Pregnancy
- Administration of live vaccine
Drug interactions
- CYP3A4 or CYP2C19 substrates (midazolam, omeprazole): weak interaction (AUC ratio ≥1.25)
- P-gp substrates (digoxin): negligible interaction
- Narrow therapeutic index drugs that are CYP3A4 or CYP2C19 substrates should not be given during treosulfan treatment
Food interactions
Food interactions are not significant.
Use in pregnancy
Use in Pregnancy: Contraindicated; do not use during pregnancy.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Unknown if excreted in human milk; discontinue breastfeeding during treatment.
Pediatric use
Not authorized for children less than 1 year; not fully investigated in pediatric population
Geriatric use
Not fully investigated in patients over 65 years
Renal / hepatic impairment
Renal Impairment: Mild or moderate: no dose adjustment necessary; severe: contraindicated
Hepatic Impairment: Mild or moderate: no dose adjustment necessary; severe: contraindicated
Overdose effects
Symptoms: Profound myelosuppression.
Treatment: Supportive care.
Storage conditions
Store unopened vials at 15-30°C. Treosulfan dissolved in 0.45% or 0.9% Sodium Chloride Injection or 5% Glucose Injection or Water for Injection is stable for 3 days at 15-30°C. Do not store under refrigeration (2-8°C).