What are the precautions for Treosulfan-Grafapex?

Treosulfan-Grafapex in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome ( MDS), warnings and precautions such as bone marrow suppression, epileptic seizures, skin diseases, injection site reactions and tissue necrosis, secondary malignant tumors, embryo-fetal toxicity have emerged. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Myelosuppression: Severe myelosuppression caused by pancytopenia is an expected therapeutic effect of trioxofan-based preparation regimen and occurs in all patients. After adult patients received allogeneic hematopoietic stem cell transplantation, the median time for neutrophil count to be >0.5Gi/L was 18 days, and triosulfan combined with fludarabine was used as a preparatory regimen. If you don't have a stem cell donor, don't start planning. Monitor blood cell counts daily until hematopoiesis is restored. Provide standard supportive care for infection, anemia, and thrombocytopenia until hematopoiesis is fully restored.

2. Epileptic seizures: There are reports of patients experiencing epileptic seizures after receiving Trioxovan treatment. Monitor patients for signs of neurological adverse reactions. For patients at increased risk of seizures, including infants, prophylaxis with clonazepam may be considered.

3. Dermatology: An increase in skin disorders (e.g., rash, dermatitis) was observed when patients received sodium bicarbonate-containing hydration during infusion of trioxovan, possibly due to accelerated pH-dependent formation of alkylated epoxides. Keep skin clean and dry duringtriosuvan infusion. Diaper dermatitis may be caused by excretion of trisulfentrazone in the urine. Change diapers frequently within 12 hours of each infusion of Trioxovan. Dermatitis may occur under occlusive dressings; change the occlusive dressing after each injection of Trioxovan.

4. Injection site reaction and tissue necrosis: If extravasation occurs, trioxovan may cause local tissue necrosis and injection site reaction, including erythema, pain and swelling. Before initiating an infusion of trioxovan, ensure that the intravenous access is patent and monitor the intravenous infusion site for redness, pain, infection, and necrosis during and after use. If extravasation occurs, the infusion should be stopped immediately and drug treatment should be initiated as required. Do not administer by intramuscular or subcutaneous route.

5. Secondary malignant tumors: The use of Trioxovan will increase the risk of secondary malignant tumors. Trioxofan is carcinogenic and genotoxic. Patients with anemia and other DNA-breaking diseases are at increased risk of secondary malignancies. The safety and effectiveness of trioxofan in patients with these conditions have not been established.

6. When the dose is higher than the recommended dose, early morbidity and mortality are increased.

7. Embryo-Fetal Toxicity: Based on its mechanism of action, trioxovan may cause harm to the fetus when administered to pregnant women because it is genotoxic and affects dividing cells. Inform pregnant women of potential risks to the fetus. Advise females of childbearing potential to use effective contraception during treatment with trioxovan and for 6 months after the last dose. Advise men who are partners of a female of reproductive potential to use effective contraception during treatment with trioxovan and for 3 months after the last dose.

Reference materials:https://www.drugs.com/grafapex.html