Treosulfan

GRAFAPEX is an alkylating drug indicated for: Use in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients 1 year of age and older with acute myeloid leukemia (AML). Use in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation in adult and pediatric patients 1 year of age and older with myelodysplastic syndrome (MDS).

Treosulfan is an alkylating agent. DNA alkylation is thought to be responsible for the cytotoxic activities of treosulfan. Treosulfan showed hematopoietic stem cell depleting activity as well as immunosuppressive and antitumor activity in mouse models of leukemia.

Recommended dosage: 10 g/m² body surface area (BSA) per day as a two hour intravenous infusion, given on three consecutive days (day -4, -3, -2) in conjunction with fludarabine before hematopoietic stem cell infusion (day 0). See Full Prescribing Information for instructions on preparation and administration.

GRAFAPEX is contraindicated in patients with hypersensitivity to any component of the drug product. Hypersensitivity to any component of the drug product.

Boxed warning (myelosuppression grafapex): causes severe and prolonged myelosuppression at the recommended dosage. Hematopoietic stem cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression. Monitor hematologic laboratory parameters. WARNING: MYELOSUPPRESSION GRAFAPEX causes severe and prolonged myelosuppression. Seizures: Monitor signs of neurological adverse reactions and consider clonazepam prophylaxis for patients at higher risk. Skin disorders: Keep skin clean and dry on days of GRAFAPEX infusion and change occlusive dressings after infusion. Change diapers frequently during the 12 hours after each infusion of GRAFAPEX. Injection Site Reactions and Tissue Necrosis: May cause local tissue necrosis and injection site reactions, including erythema, pain, and swelling, in case of extravasation.

The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression Seizures Skin Disorders Injection Site Reactions and Tissue Necrosis Secondary Malignancies The most common adverse reactions (≥20%) are musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting. Selected Grade 3 or 4 nonhematological laboratory abnormalities are increased GGT, increased bilirubin, increased ALT, increased AST, and increased creatinine.

Certain CYP2C19 and CYP3A4 Substrates: Monitor for adverse reactions of these substrates where minimal concentration changes may lead to serious or life-threatening toxicities.

Store at 20°C to 25°C (68°F to 77°F). (Excursions permitted between 15°C and 30°C) GRAFAPEX is a hazardous drug.