Acute Myeloid Leukemia: GRAFAPEX is an alkylating drug indicated in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation in adult and pediatric patients >1 year old with acute myeloid leukemia.
Myelodysplastic Syndrome: GRAFAPEX is an alkylating drug indicated in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation in adult and pediatric patients >1 year old with myelodysplastic syndrome.
This product includes the following Boxed Warning:
WARNING: MYELOSUPPRESSION
Myelosuppression: Profound myelosuppression with pancytopenia is the desired therapeutic effect of a GRAFAPEX-based preparative regimen, occurring in all patients. Do not begin the preparative regimen if the stem cell donor is not available. Monitor blood cell counts at least daily until hematopoietic recovery. Provide standard supportive care for infections, anemia, and thrombocytopenia until there is adequate hematopoietic recovery.
Seizures: Monitor patients for signs of neurological adverse reactions, including seizure. Clonazepam prophylaxis may be considered for patients at higher risk for seizures, including infants.
Skin Disorders: An increase in skin disorders (eg, rash, dermatitis) was observed when patients received sodium bicarbonate–containing hydration in the course of treosulfan infusion. Keep skin clean and dry on days of GRAFAPEX infusion. Diaper dermatitis may occur because of excretion of treosulfan in the urine. Change diapers frequently during the 12 hours after each infusion of GRAFAPEX. Dermatitis may occur under occlusive dressings; change occlusive dressings after each infusion of GRAFAPEX.
Injection Site Reactions and Tissue Necrosis: Treosulfan may cause local tissue necrosis and injection site reactions, including erythema, pain, and swelling, in cases of extravasation. Assure venous access patency prior to starting GRAFAPEX infusion, and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of GRAFAPEX. If extravasation occurs, stop the infusion immediately and manage medically as required. Do not administer by intramuscular or subcutaneous routes.
Secondary Malignancies: There is an increased risk of a secondary malignancy with the use of GRAFAPEX. Treosulfan is carcinogenic and genotoxic.
The risk of secondary malignancy is increased in patients with Fanconi anemia and other DNA breakage disorders. The safety of GRAFAPEX has not been established for patients with these disorders.
Increased Early Morbidity and Mortality at Dosages Higher Than Recommended: A higher incidence of early fatal and/or serious adverse reactions has been observed in patients receiving treosulfan at dosages of 14 g/m2 (1.4 times the recommended dose). Avoid exceeding the recommended GRAFAPEX dosage of 10 g/m2 daily for three consecutive days.
Embryo-Fetal Toxicity: GRAFAPEX can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception.
The most common adverse reactions (≥20%) in patients treated with GRAFAPEX were musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting. Select Grade 3 or 4 nonhematological laboratory abnormalities were increased GGT, increased bilirubin, increased ALT, increased AST, and increased creatinine.
Effect of GRAFAPEX on Other Drugs (Certain CYP2C19 and CYP3A Substrates): Concomitant use of GRAFAPEX is predicted to increase the exposure of CYP2C19 and CYP3A4 substrates based on a mechanistic understanding of treosulfan metabolism, which may increase the risk of adverse reactions.
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