Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 350mg/7mL (50mg/mL) single-dose vial
Non–Small Cell Lung Cancer
Indicated for locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations in adults whose disease has progressed on or after platinum-based chemotherapy
Dose based on baseline body weight
Administer premedication (ie, diphenhydramine, acetaminophen, dexamethasone or methylprednisolone) before each infusion
<80 kg
- Week 1, Day 1: 350 mg IV x 1 dose
- Week 1, Day 2: 700 mg IV x 1 dose
- Weeks 2-4: 1050 mg IV weekly
- Week 5 and thereafter: 1050 mg IV q2Weeks
- Continue until disease progression or unacceptable toxicity
≥80 kg
- Week 1, Day 1: 350 mg IV x 1 dose
- Week 1, Day 2: 1050 mg IV x 1 dose
- Weeks 2-4: 1400 mg IV weekly
- Week 5 and thereafter: 1400 mg IV q2Weeks
- Continue until disease progression or unacceptable toxicity
Dosage Modifications
Dose reductions for adverse reactions
-
<80 kg
- First dose reduction: 700 mg
- Second dose reduction: 350 mg
-
≥80 kg
- First dose reduction: 1050 mg
- Second dose reduction: 700 mg
- Unable to tolerate second dose reduction: Discontinue treatment
Infusion-related reactions (IRRs)
All grades
- Interrupt infusion if suspected or confirmed and administer supportive care medications; monitor until symptoms resolve
- Resume infusion at 50% of the infusion rate at which the reaction occurred; may increase rate in 30 minutes if no additional symptoms occur
- Include corticosteroids with premedication for subsequent dose
Permanently discontinue
- Recurrent Grade 3
- Grade 4
Interstitial lung disease (ILD)/pneumonitis
- Suspected ILD/pneumonitis: Withhold
- Confirmed ILD/pneumonitis: Permanently discontinue
Dermatologic adverse reactions
- Includes dermatitis acneiform, pruritus, dry skin
-
Grade 2
- Initiate supportive care management
- Reassess after 2 weeks; consider dose reduction if rash does not improve
-
Grade 3
- Withhold; initiate supportive care management
- Upon recovery to Grade ≤2, resume at reduced dose
-
Permanently discontinue
- Grade 2 with no improvement within 2 weeks, permanently discontinue
- Grade 4
- Severe bullous blistering or exfoliating skin conditions (eg, toxic epidermal necrolysis [TEN])
Other adverse reactions
-
Grade 3
- Withhold until recovery to Grade ≤1 or baseline
- Resume at same dose if recovery occurs ≤1 week
- Resume at reduced dose if recovery occurs >1 to ≤4 weeks
-
Grade 4
- Withhold until recovery to Grade ≤1 or baseline
- Resume at reduced dose if recovery occurs ≤4 weeks
-
Permanently discontinue
- Unable to recover within 4 weeks
- Recurrent Grade 4 reactions
Renal impairment
- Mild-to-moderate (CrCl >29 to 276 mL/min): No dosage adjustment necessary
- Severe (CrCl 15-29 mL/min): Not studied
Hepatic impairment
- Mild-to-moderate (total bilirubin [TB] ≤1.5x ULN and any AST): No dosage adjustment necessary
- Severe (TB >1.5x to 3x ULN and any AST): Not studied
Dosing Considerations
Verify pregnancy status of females of reproductive potential before initiating therapy
Patient selection
- Select patients based on presence of EGFR exon 20 insertion mutations
- Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics
Safety and efficacy not established
Adverse Effects
>10%
All grades
- Rash (84%)
- Decrease albumin (79%)
- Infusion-related reaction (64%)
- Increased glucose (56%)
- Increased alkaline phosphatase (53%)
- Paronychia (50%)
- Musculoskeletal pain (47%)
- Increased creatinine (46%)
- Increased ALT (38%)
- Dyspnea (37%)
- Nausea (36%)
- Decreased lymphocytes (36%)
- Decreased phosphate (33%)
- Increased AST (33%)
- Decreased magnesium (27%)
- Increased gamma-glutamyl transferase (GGT) (27%)
- Decreased sodium (27%)
- Decreased potassium (26%)
- Stomatitis (26%)
- Fatigue (33%)
- Edema (27%)
- Cough (25%)
- Constipation (23%)
- Vomiting (22%)
- Hemorrhage (19%)
- Pruritus (18%)
- Diarrhea (16%)
- Decreased appetite (15%)
- Dry skin (14%)
- Peripheral neuropathy (13%)
- Pyrexia (13%)
- Dizziness (12%)
- Abdominal pain (11%)
1-10%
All grades
- Pneumonia (10%)
- Headache (10%)
Grade 3 or 4
- Decreased albumin (8%)
- Decreased phosphate (8%)
- Decreased lymphocytes (8%)
- Decreased potassium (6%)
- Increased alkaline phosphatase (4.8%)
- Increased glucose (4%)
- Increased GGT (4%)
- Decreased sodium (4%)
- Rash (3.9%)
- Diarrhea (3.1%)
- Paronychia (3.1%)
- Infusion related reaction (3.1%)
- Dyspnea (2.3%)
- Fatigue (2.3%)
- Increased ALT (1.6%)
<1%
Grade 3 or 4
- Abdominal pain (0.8%)
- Dizziness (0.8%)
- Headache (0.8%)
- Stomatitis (0.8%)
- Edema (0.8%)
- Pneumonia (0.8%)
Warnings
Contraindications
None
Cautions
ILD/pneumonitis reported; monitor for new or worsening symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever)
May cause ocular toxicity (eg, keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, uveitis); promptly refer patients with eye symptoms to an ophthalmologist
Based on mechanism of action and findings from animal models, fetal harm may occur when administered to pregnant females
IRRs
- IRRs occurred
- Signs and symptoms of IRRs include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting
- Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse as recommended
- Monitor any signs and symptoms of infusion reactions during infusion in a setting where cardiopulmonary resuscitation medication and equipment are available
Dermatologic adverse reactions
- TEN, rash (including dermatitis acneiform), pruritus, and dry skin reported
- Instruct patient to limit sun exposure during and for 2 months after treatment
- Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen
- For dry skin, recommend alcohol-free emollient cream
- If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics
- For Grade 3 reactions, add oral steroids and consider dermatologist consultation
- Promptly refer to a dermatologist if patients do not improve within 2 weeks or present with severe rash or atypical appearance or distribution
Pregnancy & Lactation
Pregnancy
Based on mechanism of actions and findings in animal models, fetal harm may occur when administered to pregnant females
No data are available on use in pregnant females or animal data to assess drug risk in pregnancy
Verify pregnancy status of females of reproductive potential before initiating therapy
Animal data
- No animal studies conducted
- Disruption or depletion of EGFR in animal models resulted in impairment of embryofetal development (eg, effects on placental, lung, cardiac, skin, neural development)
- Absence of EGFR or MET signaling has resulted in embryolethality, malformations, and postnatal death in animals
- Human IgG1 is known to cross the placenta; therefore, amivantamab has potential to be transmitted from mother to developing fetus
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 3 months after final dose
Lactation
There are no data on drug presence in human milk or on milk production, or its effects on breastfed children
Advise females not to breastfeed during treatment and for 3 months after 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
Bispecific antibody that binds to the extracellular domains of EGFR and MET
Absorption
Steady-state reached at the 9th infusion
Accumulation ratio (steady-state): 2.4
Distribution
Vd: 5.13 L
Increases in body weight increased volume of distribution
Elimination
Clearance: 360 mL/day; increases in body weight increased clearance
Half-life: 11.3 days
Administration
IV Incompatibilities
Do not infuse concomitantly in the same IV line with other agents
IV Compatibilities
D5W
0.9% NaCl
IV Preparation
Visually inspect vials for particulate matter and discoloration before administration; solution is colorless to pale yellow; discard if discoloration or visible particles are present
Determine dose required and vials needed based on patient’s baseline weight
Withdraw and then discard a volume from either a D5W or 0.9% NaCl 250-mL infusion bag equal to drug volume to be added (ie, discard 7 mL diluent from infusion bag for each vial)
Only use infusion bags made of polyvinylchloride (PVC), polypropylene (PP), polyethylene (PE), or polyolefin blend
Withdraw 7 mL from each vial and inject into infusion bag; final volume in infusion bag should be 250 mL
Discard any unused portion left in vial
Gently invert the bag to mix the solution; do not shake
Premedication
Administer before each infusion as recommended
Before all infusions
- Administer both antihistamine and antipyretic IV 15-30 min or PO 30-60 min before infusion
- Diphenhydramine (25-50 mg) or equivalent IV/PO
- Acetaminophen (650-1000 mg) IV/PO
Week 1, Days 1 and 2 doses only and subsequent infusions, if necessary
- Dexamethasone (10 mg IV) or methylprednisolone (40 mg IV) or equivalent
- Administer IV 45-60 min before infusion
IV Administration
IV infusion only
Infuse diluted solution using an infusion set fitted with a flow regulator and with an in-line, sterile, nonpyrogenic, low protein–binding polyethersulfone filter (pore size 0.2 micrometer) primed with diluent only
Administration sets must be made of either polyurethane, polybutadiene, PVC, PP, or PE
Weeks 1-2: Administer via peripheral line; for initial infusion, prepare as close to administration time as possible to allow for extended infusion time in the event of an infusion-related reaction
Subsequent weeks: Administer via central line
IV infusion rates
-
<80 kg
- Week 1, Days 1 and 2: Start at 50 mL/hr; may increase to 75 mL/hr after 2 hr if no IRRs occur
- Week 2: Infuse at 85 mL/hr
- Subsequent weeks (after Week 2): Infuse at 125 mL/hr
-
≥80 kg
- Week 1, Day 1: Start at 50 mL/hr; may increase to 75 mL/hr after 2 hr if no IRRs occur
- Week 1, Day 2: Start at 35 mL/hr; may increase to 50 mL/hr after 2 hr if no IRRs occur
- Week 2: Infuse at 65 mL/hr
- Week 3: 85 mL/hr
- Subsequent weeks (after Week 3): Infuse at 125 mL/hr
Storage
Unopened vials
- Refrigerate at 2-8C (36-46ºF) in original carton to protect from light
- Do not freeze
Diluted solutions
- Store at room temperature 15-25ºC (59-77ºF) for up to 10 hr (including infusion time)
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Formulary
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