Usual Adult Dose for Acute Myeloid Leukemia

Newly diagnosed CD33-positive acute myeloid leukemia (AML):
COMBINATION REGIMEN (therapy consists of 1 induction cycle and 2 consolidation cycles in combination with chemotherapy):

• Induction: 3 mg/m2 (maximum 4.5 mg/dose) IV over 2 hours on Days 1, 4, and 7 in combination with daunorubicin and cytarabine (for patients who require a second induction cycle, gemtuzumab is NOT given during the second induction cycle)
• Consolidation (2 cycles): 3 mg/m2 (maximum 4.5 mg/dose) IV over 2 hours on Day 1 in combination with daunorubicin and cytarabine

• Induction: 6 mg/m2 IV over 2 hours on Day 1 and 3 mg/m2 IV on Day 8
• Continuation: 2 mg/m2 IV over 2 hours on Day 1 every 4 weeks

• Treatment in the relapsed or refractory setting consists of a single course of gemtuzumab.

• Premedicate with acetaminophen 650 mg orally and diphenhydramine 50 mg orally or IV one hour prior to infusion, and methylprednisolone (or equivalent) 1 mg/kg orally or IV within 30 minutes prior to infusion. Repeat the same dose of methylprednisolone (or equivalent) for any sign of an infusion reaction (e.g., fever, chills, hypotension, dyspnea) during the infusion or within 4 hours of the infusion.
• Monitor vital signs during infusion and for 4 hours following infusion.
• For patients with hyperleukocytosis (leukocyte count greater than or equal to 30 Gi/L), cytoreduction is recommended prior to administration of this drug.

• For newly diagnosed CD33-positive acute myeloid leukemia (AML)
• For relapsed or refractory CD33-positive AML

Usual Pediatric Dose for Acute Myeloid Leukemia

Newly Diagnosed De Novo CD33-positive AML (Combination Regimen):
ONE MONTH AND OLDER:

• Body surface area (BSA) less than 0.6 m2: 0.1 mg/kg IV over 2 hours
• BSA 0.6 m2 or greater: 0.3 mg/m2 IV over 2 hours

• For Induction 1, gemtuzumab is given once in combination with standard chemotherapy; no gemtuzumab is given in the second induction cycle.

• No gemtuzumab is given in the first or third intensification cycles; for Intensification 2, gemtuzumab is given once in combination with standard chemotherapy; consider the risks and potential benefits before giving gemtuzumab during Intensification 2.

• Treatment in the relapsed or refractory setting consists of a single course of gemtuzumab.

• Premedicate children 1 month and older with acetaminophen 15 mg/kg (maximum of 650 mg) orally and diphenhydramine 1 mg/kg (maximum of 50 mg) orally or IV within 1 hour of infusion, and methylprednisolone 1 mg/kg orally or IV within 30 minutes of infusion. Additional doses of acetaminophen and diphenhydramine may be administered every 4 hours if needed. Repeat with the same dose of methylprednisolone (or equivalent) for an infusion reaction (e.g., fever, chills, hypotension, dyspnea) during the infusion or within 4 hours of the infusion.
• Monitor vital signs during infusion and for 4 hours following infusion.
• For patients with hyperleukocytosis (leukocyte count greater than or equal to 30 Gi/L), cytoreduction is recommended prior to administration of this drug.

• For the treatment of newly diagnosed CD33-positive acute myeloid leukemia in pediatric patients 1 month and older
• For relapsed or refractory CD33-positive acute myeloid leukemia (AML) in pediatric patients 2 years and older

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

MONOTHERAPY OR COMBINATION THERAPY:

• Total bilirubin greater than 2 times upper limit of normal (ULN) or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 2.5 x ULN: Delay therapy with gemtuzumab until recovery of total bilirubin to less than or equal to 2 x ULN and AST and ALT to less than or equal to 2.5 x ULN prior to each dose; omit scheduled dose if delayed more than 2 days between sequential infusions.
• Veno-occlusive disease (VOD): Discontinue gemtuzumab.

Dose Adjustments

FOR PATIENTS RECEIVING GEMTUZUMAB IN COMBINATION THERAPY:
PERSISTENT THROMBOCYTOPENIA:

• ADULTS: If platelet count does not recover to greater than or equal to 100 Gi/L within 14 days following the planned start date of the consolidation cycle (14 days after hematologic recovery following previous cycle), discontinue gemtuzumab (do not administer gemtuzumab in the consolidation cycles).
• PEDIATRICS: Patients should have a platelet count of 75 Gi/L before the next cycle (induction or intensification).

• ADULTS: If neutrophil count does not recover to greater than 0.5 Gi/L within 14 days following the planned start date of the consolidation cycle (14 days after hematologic recovery following previous cycle), discontinue gemtuzumab (do not administer gemtuzumab in the consolidation cycles).
• PEDIATRICS: Patients should have a neutrophil count of 1 Gi/L before the next cycle (induction or intensification).

• Manage hepatic toxicity by dose interruption or discontinuation of therapy.
• In patients who experience VOD, discontinue therapy and treat according to standard medical practice.

• Interrupt the infusion and manage medically.
• Administer acetaminophen, diphenhydramine and/or methylprednisolone, if needed. Provide supportive care as needed.
• For mild, moderate, or severe infusion related reactions, once symptoms resolve, consider resuming the infusion at no more than one-half the rate at which the reaction occurred.
• Repeat the procedure in the event of recurrence of symptoms.
• Permanently discontinue therapy upon occurrence of a severe infusion reaction or for any life-threatening infusion reaction.

• Delay therapy until recovery to a severity of no more than mild.
• Omit scheduled dose if delayed more than 2 days between sequential infusions.

Precautions

US BOXED WARNINGS:
HEPATOTOXICITY:

• Hepatotoxicity (including severe or fatal hepatic veno-occlusive disease [VOD]), also known as sinusoidal obstruction syndrome (SOS), has been reported with the use of this drug both as a single agent and as part of a combination chemotherapy regimen. Monitor frequently for VOD.

• Safety and efficacy have not been established in patients younger than 1 month for newly diagnosed CD-33-positive acute myeloid leukemia
• Safety and efficacy have not been established in patients younger than 2 years for relapsed or refractory CD33-positive acute myeloid leukemia.

Dialysis

Data not available

Other Comments

Administration advice:

• Use an in-line 0.2-micron polyethersulfone (PES) filter for infusion.
• Protect the IV bag from light using a light-blocking cover during the infusion. The infusion line does not need to be protected from light.
• Infuse the diluted solution over 2 hours.

• Refrigerate vials (2C to 8C) and store in the original carton to protect from light. Do not freeze.
• This drug is cytotoxic; follow special handling and disposal procedures.

• Prior to reconstitution, allow vials to reach ambient temperature for approximately 5 minutes.
• Reconstitute vials per the manufacturer product information.
• Gently swirl vials to aid dissolution; do not shake.
• Inspect the reconstituted solution for particulates and discoloration. The reconstituted solution may contain small white to off-white, opaque to translucent, and amorphous to fiber-like particles.
• The product contains no bacteriostatic preservatives.
• Use reconstituted solution immediately or after being refrigerated at 2C to 8C for up to 1 hour.

• Do not mix this drug with, or administer as an infusion with, other medicinal products.