Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized cake powder for reconstitution
- 4.5 mg/single-dose vial
Acute Myeloid Leukemia
Newly Diagnosed CD33-positive AML
- Indicated for newly diagnosed CD33-positive AML in adults
- Combination Regimen
- Induction cycle: 3 mg/m² IV (up to one 4.5-mg vial) on Days 1, 4, and 7 in combination with daunorubicin and cytarabine
- For patients requiring a second induction cycle, do not administer gemtuzumab during second induction cycle
- Consolidation: 3 mg/m² IV on Day 1 (up to one 4.5-mg vial) in combination with daunorubicin and cytarabine
- Monotherapy
- Treatment course consists of 1 cycle of induction and up to 8 cycles of continuation therapy
- Induction: 6 mg/m² IV on Day 1, and 3 mg/m² on Day 8
- Continuation therapy: 2 mg/m² IV on Day 1 q4weeks
Relapsed or Refractory CD33-positive AML
- Indicated for relapsed/refractory CD33-positive AML in adults and children aged ≥2 years
- 3 mg/m² on Days 1, 4, and 7 for 1 cycle
Premedication
- Premediate 1 hr before with acetaminophen and diphenhydramine, then 30 min before with methylprednisolone
- Acetaminophen 650 mg PO AND
- Diphenhydramine 50 mg PO/IV AND
- Methylprednisolone 1 mg/kg IV or an equivalent dose of an alternative corticosteroid
- Additional doses of acetaminophen and diphenhydramine may be administered q4hr after the initial pretreatment dose
- Repeat with the same dose of methylprednisolone or an equivalent corticosteroid for any sign of an infusion reaction (eg, fever, chills, hypotension, or dyspnea) during the infusion or within 4 hr afterwards
Dosing Modifications
Veno-occlusive disease (VOD): Discontinue treatment
Renal impairment
- Mild-moderate (CrCl: 30-89 mL/min): No dosage adjustment necessary
- Severe (CrCl: 15-29 mL/min): Safety and efficacy unknown
Hepatic impairment
- Mild (total bilirubin <1.5X ULN): No dosage adjustment necessary
- Moderate (total bilirubin >1.5-3.0X ULN) or severe (total bilirubin >3X ULN): Unknown
Total bilirubin >2X ULN, or AST and/or ALT >2.5X ULN
- Hold treatment until total bilirubin to ≤2X ULN and AST/ALT to ≤2.5X ULN prior to each dose
- Omit scheduled dose if delayed >2 days between sequential infusions
Infusion-related reactions
- Interrupt infusion and institute appropriate medical management
- Administer acetaminophen, diphenhydramine, and/or methylprednisolone, if needed
- Provide supportive care measures as needed
- Consider resuming the infusion at less than or half the rate at which the reaction occurred once symptoms resolve
- Repeat the procedure above in the event of recurrence of symptoms
- Permanently discontinue gemtuzumab if a severe infusion reaction occurs or for any life-threatening infusion reaction
Other severe/life-threatening nonhematologic toxicities
- Hold treatment until reaction severity is no more than mild
- Omit scheduled dose if delayed more than 2 days between sequential infusions
Combination therapy only
- Persistent thrombocytopenia
- If platelet count does not recover to greater than 100 Gi/L ≤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 cycle
- Persistent neutropenia
- If neutrophil count does not recover to greater than 0.5 Gi/L ≤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 cycle
Dosing Considerations
Use appropriate measures to prevent tumor lysis syndrome
Patients with hyperleukocytosis (leukocyte count ≥30 Gi/L): Cytoreduction is recommended prior to gemtuzumab administration
Monitor blood cell counts frequently through resolution of cytopenias
Monitor blood cell counts and chemistries <3X/week through recovery from treatment-related toxicities
Dosage Forms & Strengths
injection, lyophilized cake powder for reconstitution
- 4.5-mg/single-dose vial
Acute Myeloid Leukemia (AML)
Indicated for relapsed/refractory CD33-positive AML in adults and children aged ≥2 years
<2 years: Safety and efficacy not established
≥2 years: 3 mg/m² IV on Days 1, 4, and 7 for 1 cycle
Premedication
- Premediate 1 hr before with acetaminophen and diphenhydramine, then 30 min before with methylprednisolone
- Acetaminophen 15 mg/kg (not to exceed 650 mg/dose) PO AND
- Diphenhydramine 1 mg/kg (not to exceed 50 mg/dose) PO/IV AND
- Methylprednisolone 1 mg/kg PO/IV
- Additional doses of acetaminophen and diphenhydramine may be administered q4hr after the initial pretreatment dose
- Repeat with the same dose of methylprednisolone or an equivalent corticosteroid for any sign of an infusion reaction (eg, fever, chills, hypotension, or dyspnea) during the infusion or within 4 hr afterwards
Dosing Modifications
Veno-occlusive disease (VOD): Discontinue treatment
Renal impairment
- Mild-moderate (CrCl: 30-89 mL/min): No dosage adjustment necessary
- Severe (CrCl: 15-29 mL/min): Safety and efficacy unknown
Hepatic impairment
- Mild (total bilirubin <1.5x ULN): No dosage adjustment necessary
- Moderate (total bilirubin >1.5-3.0X ULN) or severe (total bilirubin >3x ULN): Unknown
Total bilirubin >2X ULN, or AST and/or ALT >2.5X ULN
- Hold treatment until total bilirubin improves to ≤2X ULN and AST/ALT to ≤2.5X ULN prior to each dose
- Omit scheduled dose if delayed >2 days between sequential infusions
Infusion-related reactions
- Interrupt infusion and institute appropriate medical management
- Administer acetaminophen, diphenhydramine, and/or methylprednisolone, if needed
- Provide supportive care measures as needed
- Consider resuming the infusion at less than or half the rate at which the reaction occurred once symptoms resolve
- Repeat the procedure above in the event of recurrence of symptoms
- Permanently discontinue gemtuzumab if a severe infusion reaction occurs or for any life-threatening infusion reaction
Other severe/life-threatening nonhematologic toxicities
- Hold treatment until reaction severity is no more than mild
- Omit scheduled dose if delayed more than 2 days between sequential infusions
Dosing Considerations
Use appropriate measures to prevent tumor lysis syndrome
Patients with hyperleukocytosis (leukocyte count ≥30 Gi/L): Cytoreduction is recommended prior to gemtuzumab administration
Monitor blood cell counts frequently through resolution of cytopenias
Monitor blood cell counts and chemistries <3X/week through recovery from treatment-related toxicities
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10% (Newly diagnosed plus Daunorubicin and Cytarabine)
Hypophosphatemia, grade 3 or higher (64%)
Hypokalemia, grade 3 or higher (57%)
Infection, grade 3 or higher (47-55%)
Hyponatremia, grade 3 or higher (44%)
Prolonged thrombocytopenia (19-35%)
Hemorrhage, grade 3 or higher (5-18%)
AST increased, grade 3 or higher (14%)
Alkaline phosphatase increased, grade 3 or higher (13%)
>10% (Monotherapy for Relapsed)
Fever, all grades (79%)
Infection, all grades (42%)
Increased AST, all grades (40%)
Bleeding, all grades (23%)
Nausea and vomiting, all grades (21%)
Constipation, all grades (21%)
Mucositis, all grades (21%)
Headache, all grades (19%)
Increased ALT, all grades (16%)
Rash, all grades (16%)
Sepsis, grade 3 (32%)
Fever, grade 3 (16%)
Rash, grade 3 (11%)
1-10% (Newly diagnosed plus Daunorubicin and Cytarabine)
ALT increased, grade 3 or higher (10%)
Blood bilirubin increased, grade 3 or higher (8%)
Prolonged neutropenia (2-3%)
Veno-occlusive disease, grade 3 or higher (2%)
1-10% (Monotherapy for Relapsed)
Hyperbilirubinemia (7%)
Pneumonia, grade 3 (7%)
Bleeding, grade 3 (7%)
Mucositis, grade 3 (4%)
Pain, grade 3 (4%)
Diarrhea, grade 3 (2%)
Headaches, grade 3 (2%)
Tachycardia, grade 3 (2%)
Lung edema, grade 3 (2%)
Warnings
Black Box Warnings
Hepatotoxicity, including severe or fatal veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), has been reported in association with the use of gemtuzumab
In clinical trials, the risk of VOD was higher in adults who received higher gemtuzumab doses as monotherapy, in patients with moderate/severe hepatic impairment prior to treatment, in patients treated with gemtuzumab after HSCT, and in patients who underwent hematopoietic stem cell transplantation (HSCT), after treatment with gemtuzumab
Assess ALT, AST, total bilirubin, and alkaline phosphatase prior to each gemtuzumab dose
Monitor frequently for signs/symptoms of VOD (eg, elevations in ALT, AST, total bilirubin, hepatomegaly, rapid weight gain, ascites) after treatment; monitoring only total bilirubin may not identify all patients at risk of VOD
Patients who develop abnormal liver tests: More frequent monitoring of liver tests and clinical signs/symptoms of hepatotoxicity is recommended
Patients who proceed to HSCT: Monitor liver tests frequently during the post-HSCT period, as appropriate
Manage signs or symptoms of hepatic toxicity by dose interruption or discontinuation
In patients who experience VOD, discontinue treatment and treat according to standard medical practice
Contraindications
Hypersensitivity to the active substance in gemtuzumab or any of its components or to any of the excipients
Cautions
Hepatotoxicity, including severe or fatal VOD also known as SOS, has been reported; see Black Box Warnings
For patients being treated with gemtuzumab in combination with daunorubicin and cytarabine for newly diagnosed de novo AML, when cytogenetics testing results become available consider whether the potential benefit of continuing treatment outweighs the risks for the individual patient
Animal data report gemtuzumab may cause embryo-fetal harm when administered to pregnant women; see Pregnancy
Infusion-related reactions
- Life-threatening or fatal infusion related-reactions can occur during or within 24 hr following gemtuzumab infusion
- Premedicate prior to gemtuzumab infusion
- Monitor vital signs frequently during infusion
- Interrupt infusion immediately for patients who are suspected of infusion-related reaction, especially dyspnea, bronchospasm, or hypotension
- Monitor patients during and for ≥1 hr after infusion completed or until signs/symptoms completely resolve
- Discontinue gemtuzumab use in patients who develop signs or symptoms of anaphylaxis (eg, severe respiratory symptoms or clinically significant hypotension)
Hemorrhage
- Risk of fatal or life-threatening hemorrhage owing to prolonged thrombocytopenia
- Proportion of patients with persistent thrombocytopenia increased with progressive treatment phases and was higher in patients treated with combination therapy plus gemtuzumab than with chemotherapy alone
- Assess blood cell counts prior to each gemtuzumab dose; monitor frequently after treatment until resolution of cytopenias
- Monitor patients for signs/symptoms of bleeding during treatment; manage severe bleeding, hemorrhage, or persistent thrombocytopenia by treatment interruption or discontinuation and provide appropriate medical care
QT interval prolongation
- QT interval prolongation has been observed in patients treated with other drugs containing calicheamicin
- Obtain ECG and electrolytes before initiating drug and during treatment as needed in patients with history of or predisposition for QTc prolongation, who are taking drugs known to prolong QT interval, or with electrolyte disturbances
Pregnancy
Pregnancy
Based on animal data, gemtuzumab can cause embryo-fetal harm when administered to a pregnant woman
No available data on gemtuzumab use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage
In rat embryo-fetal development studies, gemtuzumab ozogamicin caused embryofetal toxicity at maternal systemic exposures that ≥0.4 times the exposure in patients at the maximum recommended dose, based on AUC
For patients who are pregnant, or become pregnant during treatment, advise the patient of the potential risk to a fetus
Verify the pregnancy status of females of reproductive potential prior to initiating treatment
Gemtuzumab may impair fertility in male or females of reproductive potential
Contraception
- Advise females of reproductive potential to avoid becoming pregnant while receiving gemtuzumab
- Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after last dose
- Advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after last dose
Lactation
No data on the presence of gemtuzumab ozogamicin or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production
Owing to potential for adverse reactions in breastfed infants, women should not breastfeed during treatment and for at least 1 month after the final dose
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
CD33-directed antibody-drug conjugate (ADC); the antibody portion (hP67.6) recognizes human CD33 antigen and the small molecule, N-acetyl gamma calicheamicin, is a cytotoxic agent that is covalently attached to the antibody via a linker
Nonclinical data suggest that the anticancer activity results from ADC binding to CD33-expressing tumor cells, followed by internalization of the ADC-CD33 complex, and intracellular release of N-acetyl gamma calicheamicin dimethyl hydrazide via hydrolytic cleavage of the linker
Activation of N-acetyl gamma calicheamicin dimethyl hydrazide induces double-strand DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death
Absorption
Peak plasma concentration: 3 mg/mL (first dose); 3.6 mg/mL (second dose)
Distribution
Protein bound: 97% (N-acetyl gamma calicheamicin dimethyl hydrazide)
Vd: ~21.4 L (hP67.6 antibody)
Metabolism
N-acetyl gamma calicheamicin dimethyl hydrazide is extensively metabolized, primarily via nonenzymatic reduction of the disulfide moiety
Elimination
Half-life (hP67.6 antibody): 62 hr (first dose); 90 hr (second dose)
Clearance (hP67.6 antibody): 0.35 L/hr (first dose); 0.15 L/hr (second dose)
Administration
IV Compatibilities
0.9% NaCl
IV Preparation
Cytotoxic drug; follow applicable special handling and disposal procedures
Reconstitution
- Calculate dose in mg and determine number of vials required
- Before reconstitution, allow vials to reach ambient temperature for ~5 minutes
- Reconstitute each vial with 5 mL sterile water for injection to obtain a concentration of 1 mg/mL (each vial delivers 4.5 mL [4.5 mg])
- Do not shake; gently swirl vial to aid dissolution
- Inspect reconstituted solution for particulates and discoloration
- Reconstituted solution may contain small white to off-white, opaque-to-translucent, and amorphous to fiber like particles
- Contains no bacteriostatic preservatives
- Use solution immediately to further dilute or refrigerate (see Storage)
Further dilution required
- Calculate the required volume of the reconstituted solution needed to obtain the appropriate dose according to patient body surface area
- Withdraw this amount from the vial(s) using a syringe; discard unused reconstituted solution
- Remove a volume of 0.9% NaCl from the prefilled bag equal to the volume of product (mL) calculated above
- Add the reconstituted solution to infusion container with 0.9% NaCl to make a total volume of 50 mL or 100 mL, depending on dose
- Do not shake; gently invert infusion container to mix diluted solution
- See storage information listed below if not used immediately
IV Administration
Must use an in-line 0.2 micron polyethersulfone (PES) filter for infusion
Protect IV bag from light using a light-blocking cover during infusion; the infusion line does not need to be protected from light
Infuse diluted solution IV over 2 hr
Do not mix or coadminister gemtuzumab with other medicinal products
Storage
Protect from light
Do not freeze
Unopened vials
- Refrigerate at 2-8°C (36-46°F) store in the original carton
Reconstituted solution
- May refrigerate at 2-8°C (36-46°F) for up to 1 hr
Diluted solution
- May store at room temperature 15-25°C (59-77°F) for up to 6 hr; the 6-hr timeframe includes the 2-hr infusion time and 1 hr, if needed, to allow the refrigerated diluted solution to equilibrate to room temperature
- May be refrigerated at 2-8°C (36-46°F) for up to 12 hr, which includes up to 1 hr in the vial following reconstitution
Images
Patient Handout
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
