Dosing & Uses
Dosage Forms & Strengths
injection, solution concentrate
- 250mg/10mL (25mg/mL) single-dose vial
Breast Cancer
Indicated in combination with chemotherapy for metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer in patients who have received ≥2 anti-HER2 regimens, at least 1 of which was for metastatic disease
15 mg/kg IV q3weeks
Continue until disease progression or unacceptable toxicity
Refer to prescribing information for each therapeutic agent administered in combination therapy for dosing information
Dosage Modifications
Left ventricular dysfunction
-
Withhold dosing for ≥4 weeks
- ≥16% absolute decrease in left ventricular ejection fraction (LVEF) from pretreatment levels
- LVEF below institutional limits of normal (or 50% if no limits are available) and ≥10% absolute decrease in LVEF from pretreatment values
- May resume if, within 8 weeks, LVEF returns to normal limits and absolute decrease from base line ≤15%
-
Permanently discontinue
- LVEF decline persists for >8 weeks, or
- Dosing interrupted on >3 occasions for LVEF decline
Infusion-related reactions
- Mild or moderate: Decrease infusion rate
- Dyspnea or clinically significant hypotension: Interrupt infusion
- Severe or life-threatening IRRs: Permanently discontinue
Renal impairment
- Mild-to-moderate (CrCl 30-89 mL/min): No dose adjustment needed
- Severe (CrCl 15-29 mL/min), end-stage renal disease with or without hemodialysis) Unknown
Hepatic impairment
- Mild (total bilirubin [TB]
ULN, or TB 1-1.5 ULN and any AST): No dose adjustment needed - Moderate-to-severe (TB >1.5 ULN and any AST): Unknown
Dosing Considerations
Assess LVEF before initiating and regularly during treatment
Verify pregnancy status before initiating in females of reproductive potential
Safety and efficacy not established
There was a higher incidence of Grade ≥3 adverse reactions observed in patients aged ≥65 years (56%) compared with younger patients (47%), including those associated with potential cardiotoxicity (35% vs 18%)
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (0)
Minor (0)
Adverse Effects
>10%
All Grades
- Increased creatinine (68%)
- Fatigue/asthenia (57%)
- Decreased hemoglobin (52%)
- Decreased leukocytes (40%)
- Decreased neutrophils (34%)
- Nausea (33%)
- Increased activated partial thromboplastin time (aPTT) (32%)
- Increased ALT (32%)
- Decreased lymphocytes (31%)
- Increased lipase (30%)
- Diarrhea (25%)
- Increased INR (24%)
- Increased AST (23%)
- Vomiting (21%)
- Increased alkaline phosphatase (21%)
- Pyrexia (19%)
- Constipation (19%)
- Headache (19%)
- Alopecia (18%)
- Abdominal pain (17%)
- Peripheral neuropathy (16%)
- Cough (14%)
- Decreased appetite (14%)
- Arthralgia/myalgia (14%)
- Palmoplantar erythrodysesthesia (13%)
- Dyspnea (13%)
- Infusion-related reaction (13%)
- Extremity pain (11%)
1-10%
All Grades
- Dizziness (10%)
- Stomatitis (10%)
- Decreased weight (6%)
- Dysgeusia (6%)
- Rash (6%)
- Insomnia (6%)
- Hypertension (5%)
- Syncope (1.5%)
Grade 3 or 4
- Decreased neutrophils (9%)
- Fatigue (7%)
- Increased lipase (6%)
- Decreased leukocytes (5%)
- Decreased lymphocytes (4.4%)
- Increased aPTT (3.4%)
- Decreased hemoglobin (3.2%)
- Diarrhea (2.3%)
- Increased ALT (2%)
- Increased AST (2%)
- Abdominal pain (1.5%)
- Infusion-related reaction (1.5%)
- Increased INR (1.2%)
- Nausea (1.1%)
- Peripheral neuropathy (1.1%)
- Dyspnea (1.1%)
<1%
Grade 3 or 4
- Vomiting (0.8%)
- Constipation (0.8%)
- Extremity pain (0.8%)
- Pyrexia (0.4%)
- Cough (0.4%)
- Decreased appetite (0.4%)
- Arthralgia/myalgia (0.4%)
- Increased creatinine (0.4%)
Warnings
Black Box Warnings
Left ventricular dysfunction
- May lead to reductions in LVEF
- Evaluate cardiac function before and during treatment
- Discontinue treatment for confirmed clinically significant decrease in left ventricular function
Embryofetal toxicity
- Exposure during pregnancy can cause embryofetal harm
- Advise patients of risk and use for effective contraception
Contraindications
None
Cautions
May cause fetal harm when administered to pregnant females
Left ventricular dysfunction
- Left ventricular dysfunction may occur
- Not studied in patients with pretreatment LVEF <50%, history of myocardial infarction or unstable angina within 6 months, or congestive heart failure NYHA class II-IV
- Conduct thorough cardiac assessment (eg, history, physical examination, determination of LVEF by ECG or multiple gated acquisition (MUGA) scan
- Measure baseline LVEF within 4 weeks before initiation; then every 3 months during and upon completion
- Repeat LVEF at 4-week intervals if therapy withheld for significant left ventricular dysfunction
Infusion-related reactions
- Infusion-related reactions (IRRs) reported
- Symptoms may include fever, chills, arthralgia, cough, dizziness, fatigue, nausea, vomiting, headache, diaphoresis, tachycardia, hypotension, pruritus, rash, urticaria, and dyspnea
- Monitor for IRRs during administration and as clinically indicated after completing infusion
- Have medications and emergency equipment available to immediately to treat IRRs
Drug interaction overview
-
Anthracyclines
- Avoid anthracycline-based therapy for up to 4 months after discontinuing margetuximab
- Patients treated with anthracyclines <4 months after discontinuing therapy may be at increased risk of cardiac dysfunction
- Interaction has not been studied with margetuximab
- Clinical data from other HER2-directed antibodies warrant consideration
- If use is unavoidable, closely monitor cardiac function
Pregnancy & Lactation
Pregnancy
Based on findings in animals and mechanism of action, fetal harm may occur when administered to pregnant females
No data available on use in pregnant females to inform of the drug-associated risks
In postmarketing reports, use of a HER2- directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death
Verify pregnancy status of females of reproductive potential before initiation
Animal data
- IV administration to pregnant cynomolgus monkeys once every 3 weeks, starting at gestational day 20 until delivery, resulted in oligohydramnios and delayed infant kidney development
- Animal exposures were ≥3x the human exposures at the recommended dose, based on peak plasma levels
- Advise patients of potential risks to a fetus
Fetal/neonatal adverse reactions
- Monitor treated females during pregnancy or within 4 months before conception for oligohydramnios
- If oligohydramnios occurs, perform fetal testing appropriate for gestational age and consistent with community standards of care
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 4 months following final dose
Lactation
No information available on drug presence in human milk, effects on breastfed child, or effects on milk production
Published data suggest human IgG is present in human milk but does not enter neonatal or infant circulation in substantial amounts
Consider drug washout period of 4 months when weighing the risks versus benefits
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
Human epidermal growth factor receptor 2 (HER2)/neu receptor antagonist; chimeric Fc-engineered IgG1 kappa monoclonal antibody that targets HER2-expressing tumors
Binds to extracellular domain of HER2 protein; upon binding to HER2-expressing tumor cells, the drug inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain, and mediates antibody-dependent cellular cytotoxicity
Absorption
Peak plasma concentration (steady-state): 466 mcg/mL
AUC (steady-state): 4120 mcg⋅day/mL
Steady-steady is reached at 2 months
No clinically significant differences were observed when infusion time was reduced from 120 to 30 minutes
Distribution
Vd (steady-state): 5.47 L
Metabolism
Expected to be metabolized into small peptides by catabolic pathways
Elimination
Half-life: 19.2 days
Clearance: 0.22 L/days
4 months after discontinuation, concentrations decrease to ~3% of steady-state trough serum concentration
Administration
IV Incompatibilities
D5W
IV Compatibilities
0.9% NaCl
IV Preparation
Inspect visually for particulate matter and discoloration; solution is clear to slightly opalescent, colorless to pale yellow or pale brown; some visible, translucent, inherent proteinaceous particles may be present
Swirl the vial(s) gently; do not shake vial(s)
Calculate required volume (rounded to nearest 0.1 mL)
Transfer calculated dose into 100- to 250-mL 0.9% NaCl IV bag (ie, polyvinyl chloride, polyolefins [polyethylene, polypropylene], polyamide or polyolefins only, or copolymer of olefins) may be used
Final concentration of diluted soltuion: 0.5-7.2 mg/mL
Gently invert IV bag to mix diluted solution; do NOT shake
Discard any unused portion left in vial(s)
Do not mix with other drugs
IV Administration
Administer through IV line containing sterile, nonpyrogenic, low-protein-binding polyethersulfone 0.2-micron in-line or add-on filter
Do NOT give IV push or bolus
On days when administered with chemotherapy, administer margetuximab immediately after chemotherapy completion
Do not coadminister other drugs through same infusion line
Infusion rate
- Initial dose: Administer over 2 hr
- Subsequent doses: Administer over at least 30 minutes
Missed dose
- Administer scheduled dose as soon as possible
- Adjust schedule to maintain 3-week interval between doses
Storage
Does not contain a preservative
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
- Do not freeze
- Do not shake
Diluted IV solution
- Room temperature: Up to 4 hr
- Refrigerated: 2-8ºC (36-46ºF) up to 24 hr
- If refrigerated, allow the diluted solution to come to room temperature prior to administration
- Do not freeze
Images
Formulary
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