Antineoplastic Agent, Monoclonal Antibody

Treatment of acute myeloid leukemia (CD33 positive) in first relapse in patients who are greater than or equal to 60 years of age and who are not considered candidates for cytotoxic chemotherapy.

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May cause fetal harm when administered to a pregnant woman. Women of childbearing potential should avoid becoming pregnant while receiving treatment. If used in pregnancy, or if patient becomes pregnant during treatment, the patients should be apprised of potential hazard to the fetus. Excretion in breast milk unknown, breast feeding is not recommended.

Known hypersensitivity to gemtuzumab ozogamicin or any component of the formulation including anti-CD33 antibody; hypersensitivity to calicheamicin derivatives

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Safety and efficacy in patients with poor performance status and organ dysfunction have not been established. Postinfusion reactions, which may include fever, chills, hypotension, or dyspnea, may occur during the first 24 hours after administration. Severe myelosuppression occurs in all patients at recommended dosages. Use caution in patients with renal impairment (no clinical experience) and hepatic impairment (no clinical experience in patients with bilirubin >2 mg/dL). Tumor lysis syndrome may occur as a consequence of leukemia treatment - adequate hydration and prophylactic allopurinol must be instituted prior to use.

Percentages established in adults >60 years of age.

Cardiovascular: Peripheral edema (21%), hypertension (20%), hypotension (16%)

Central nervous system: Chills (66%), fever (80%), headache (26%), pain (25%), dizziness (11%), insomnia (18%)

Dermatologic: Rash (23%), petechiae (21%), ecchymosis (15%)

Endocrine and metabolic: Hypokalemia (30%), hypokalemia

Gastrointestinal: Nausea (64%), vomiting (55%), diarrhea (38%), anorexia (31%), abdominal pain (29%), constipation (28%), stomatitis/mucositis (25%), abdominal distention (11%), dyspepsia (11%)

Hematologic: Neutropenia (98%; median recovery 40.5 days), thrombocytopenia (99%; median recovery 39 days); anemia (47%), bleeding (15%), lymphopenia

Hepatic: Hyperbilirubinemia (23%) increased LDH (18%), increased transaminases (9% to 17%)

Local: Local reaction (25%)

Neuromuscular & skeletal: Weakness (45%), back pain (18%)

Respiratory: Dyspnea (36%), epistaxis (29%; severe 3%), cough (19%), pharyngitis (14%)

Miscellaneous: Infection (28%), sepsis (24%), neutropenic fever (20%)

1% to 10%:

Cardiovascular: Tachycardia (10%)

Central nervous system: Depression (10%), cerebral hemorrhage (2%), intracranial hemorrhage (2%)

Endocrine and metabolic: Hypomagnesemia (4%), hyperglycemia (2%)

Genitourinary: Hematuria (10%; severe 1%), vaginal hemorrhage (7%)

Hematologic: Hemorrhage (8%), disseminated intravascular coagulation (DIC) (2%)

Hepatic: Elevated PT

Respiratory: Rhinitis (10%), hypoxia (6%), pneumonia (10%), rhinitis (10%)

Neuromuscular & skeletal: Arthralgia (10%)

<1% (limited to significant and/or life threatening): Hepatic failure, jaundice, hepatosplenomegaly, veno-occlusive disease

Symptoms are unknown. General supportive measures should be instituted. Gemtuzumab ozogamicin is not dialyzable.

No formal drug interaction studies have been conducted.

Storage: Light sensitive; protect from light. Store vials under refrigeration 2°C to 8°C or 36°F to 46°F). Reconstituted vials may be stored under refrigeration for up to 8 hours.

Reconstitution: Prepare in biologic safety hood with the fluorescent light turned off. Allow to warm to room temperature prior to reconstitution. Reconstitute vial with 5 mL sterile water for injection, USP. Final concentration in vial is 1 mg/mL. Dilute desired dose in 100 mL of 0.9% sodium chloride injection. The resulting I.V. bag should be placed in a UV protectant bag and infused immediately.

Compatibility: No information (infuse via separate line)

Antibody to CD33 antigen, which is expressed on leukemic blasts in 80% of patients with acute myeloid leukemia (AML), as well as normal myeloid cells. Binding results in internalization of the antibody-antigen complex. Following internalization, the calicheamicin derivative is released inside the myeloid cell. The calicheamicin derivative binds to DNA resulting in double strand breaks and cell death. Pluripotent stem cells and nonhematopoietic cells are not affected.

Half-life:

Unconjugated calicheamicin: 100 hours (no change noted in repeat dosing)

I.V.: Adults greater than or equal to 60 years: 9 mg/m², infused over 2 hours. The patient should receive diphenhydramine 50 mg and acetaminophen 650-1000 mg orally 1 hour prior to administration of each dose. Acetaminophen dosage should be repeated as needed every 4 hours for two additional doses. A full treatment course is a total of two doses administered with 14 days between doses. Full hematologic recovery is not necessary for administration of the second dose. There has been only limited experience with repeat courses of gemtuzumab ozogamicin.

Dosage adjustment in hepatic impairment: No recommendation (not studied)

Administer as infusion only, over at least 2 hours. Do not administer I.V. push (bolus). Infuse through a separate line equipped with a low protein-binding 1.2 micron terminal filter. May be infused peripherally or through a central line. Premedication with acetaminophen and diphenhydramine should be administered prior to each infusion.

Monitor vital signs during the infusion and for 4 hours following the infusion. Monitor for signs/symptoms of post-infusion reaction. Monitor electrolytes, LFTs, CBC with differential, and platelet counts frequently.

None known

This medication can only be administered I.V. During therapy do not use ethanol, aspirin-containing products, antiplatelet medications (ticlopidine, clopidogrel, or dipyridamole), OTC medications, or supplements/herbal products without consulting healthcare provider. It is important to maintain adequate nutrition and hydration. You may experience nausea and vomiting (small frequent meals, frequent mouth care, sucking lozenges or chewing gum may help). Frequent mouth care and use of a soft toothbrush or cotton swabs may reduce mouth sores. You will be susceptible to infection (avoid crowds and exposure to infection). Report fever, chills, unusual bruising or bleeding, signs of infection, dizziness, lightheadedness, difficulty breathing, or yellowing of the eyes or skin to healthcare provider. Keep all appointments and get required blood work done.

Monitor vital signs during infusion and for 4 hours afterward. May be administered in an outpatient setting. Cover with UV protective bag during infusion. Premedicate with acetaminophen and diphenhydramine.

Powder for injection: 5 mg