amivantamab (Rx)

Brand and Other Names:Rybrevant, amivantamab-vmjw
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Dosing & Uses

AdultPediatric

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

<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
  • Subsequent weeks (after Week 4): 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
  • Subsequent weeks (after Week 4): 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

Safety and efficacy not established

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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%)
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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
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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.

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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

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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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Images

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Patient Handout

A Patient Handout is not currently available for this monograph.
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Formulary

FormularyPatient Discounts

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.
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  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.