avelumab (Rx)

Brand and Other Names:Bavencio
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 20mg/mL (200mg/10mL single-dose vial)

Merkel Cell Carcinoma

Indicated in adults with metastatic Merkel cell carcinoma (MCC)

800 mg IV q2Weeks

Continue until disease progression or unacceptable toxicity

Also see Administration

Urothelial Carcinoma

Indicated for locally advanced or metastatic urothelial carcinoma (UC) in patients who have disease progression during or following platinum-containing chemotherapy or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

800 mg IV q2Weeks

Continue until disease progression or unacceptable toxicity

Also see Administration

Dosage Modifications

Interrupt or slow infusion rate: Grade 1 or 2 infusion-related reaction

Withhold for any of the following (may resume when recover to Grade 0-1)

  • Grade 2 pneumonitis
  • Grade 2 or 3 diarrhea or colitis
  • Grade 3 or 4 endocrinopathies (including but not limited to hypothyroidism, hyperthyroidism, adrenal insufficiency, or hyperglycemia)
  • Serum creatinine >1.5 and up to 6x ULN
  • AST or ALT >3 and up to 5x ULN or total bilirubin >1.5 and up to 3x ULN
  • Moderate or severe clinical signs or symptoms of an immune-mediated adverse reaction (including but not limited to myocarditis, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, bullous dermatitis, Stevens Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN), pancreatitis, rhabdomyolysis, myasthenia gravis, histiocytic necrotizing lymphadenitis, demyelination, vasculitis, hemolytic anemia, hypophysitis, iritis, and encephalitis)

Permanently discontinue for any of the following

  • Any life-threatening adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy)
  • Grade 3 or 4 pneumonitis or recurrent Grade 2 pneumonitis
  • Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis
  • Serum creatinine >6x ULN
  • AST or ALT >5x ULN or total bilirubin >3x ULN
  • Grade 3 or 4 infusion-related reactions
  • Inability to reduce corticosteroid dose to ≥10 mg/day of prednisone or equivalent within 12 weeks
  • Persistent Grade 2 or 3 adverse reactions that do not recover to Grade 0-1 within 12 weeks after last dose
  • Recurrent severe immune-mediated adverse reaction

Dosing Considerations

MCC and UC: Approved under accelerated approval based on tumor response and duration of response; continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials

Orphan Designations

Treatment of gastric cancer (GC) including cancer of the gastroesophageal junction (GEJ)

Sponsor

  • EMD Serono Research & Development Institute, Inc. 45A Middlesex Turnpike Billerica, Massachusetts 01821 USA

Dosage Forms & Strengths

injectable solution

  • 20mg/mL (200mg/10mL single-dose vial)

Merkel Cell Carcinoma

Indicated for metastatic Merkel cell carcinoma (MCC) in adults and pediatric patients aged ≥12 yr

<12 years: Safety and efficacy not established

≥12 years: 800 mg IV q2Weeks

Continue until disease progression or unacceptable toxicity

Also see Administration

Dosage Modifications

Interrupt or slow infusion rate: Grade 1 or 2 infusion-related reaction

Withhold for any of the following (may resume when recover to Grade 0-1)

  • Grade 2 pneumonitis
  • Grade 2 or 3 diarrhea or colitis
  • Grade 3 or 4 endocrinopathies (including but not limited to hypothyroidism, hyperthyroidism, adrenal insufficiency, or hyperglycemia)
  • Serum creatinine >1.5 and up to 6x ULN
  • AST or ALT >3 and up to 5x ULN or total bilirubin >1.5 and up to 3x ULN
  • Moderate or severe clinical signs or symptoms of an immune-mediated adverse reaction (including but not limited to myocarditis, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, bullous dermatitis, Stevens Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN), pancreatitis, rhabdomyolysis, myasthenia gravis, histiocytic necrotizing lymphadenitis, demyelination, vasculitis, hemolytic anemia, hypophysitis, iritis, and encephalitis)

Permanently discontinue for any of the following

  • Any life-threatening adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy)
  • Grade 3 or 4 pneumonitis or recurrent Grade 2 pneumonitis
  • Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis
  • Serum creatinine >6x ULN
  • AST or ALT >5x ULN or total bilirubin >3x ULN
  • Grade 3 or 4 infusion-related reactions
  • Inability to reduce corticosteroid dose to ≥10 mg/day of prednisone or equivalent within 12 weeks
  • Persistent Grade 2 or 3 adverse reactions that do not recover to Grade 0-1 within 12 weeks after last dose
  • Recurrent severe immune-mediated adverse reaction

Dosing Considerations

MCC: Approved under accelerated approval based on tumor response and duration of response; continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials

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Adverse Effects

Adverse effects include all grades unless otherwise stated

>10%

Fatigue (50%)

Musculoskeletal pain (32%)

Diarrhea (23%)

Nausea (22%)

Infusion-related reaction (22%)

Rash (22%)

Peripheral edema (20%)

Decreased appetite (20%)

Cough (18%)

Constipation (17%)

Abdominal pain (16%)

Arthralgia (16%)

Decreased weight (15%)

Dizziness (14%)

Vomiting (13%)

Hypertension (13%)

Dyspnea (11%)

1-10%

Pruritus (10%)

Headache (10%)

Thyroid disorders (6%)

Hypertension, Grade 3 or 4 (6%)

Decreased appetite, Grade 3 or 4 (2%)

Abdominal pain, Grade 3 or 4 (2%)

Musculoskeletal pain, Grade 3 or 4 (2%)

Fatigue, Grade 3 or 4 (2%)

Colitis (1.5%)

Pneumonitis (1.2%)

Constipation, Grade 3 or 4 (1%)

Arthralgia, Grade 3 or 4 (1%)

<1%

Hepatitis

Adrenal insufficiency

Type 1 diabetes mellitus

Nephritis

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Warnings

Contraindications

None

Cautions

Infusion-related reactions, including severe and life-threatening reactions, reported; monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever

Embryo-fetal toxicity is possible based on its mechanism of action (see Pregnancy)

Also see Dosage Modifications

Immune-mediated adverse reactions

  • Immune-mediated pneumonitis, including fatal cases; monitor for signs and symptoms of pneumonitis and evaluate patients with suspected pneumonitis with radiographic imaging Immune-mediated hepatitis, including fatal cases, reported; monitor LFTs before initiating and periodically during treatment
  • Monitor for symptoms of immune-mediated colitis
  • Immune-mediated adrenal insufficiency should be treated with corticosteroids as appropriate for the adrenal insufficiency
  • Immune-mediated endocrinopathies (eg, hypothyroidism, hyperthyroidism) reported; monitor thyroid function before initiating drug and during treatment; treat hypothyroidism with hormone-replacement therapy; initiate medical management for control of hyperthyroidism
  • Immune-mediated nephritis and renal dysfunction reported; monitor for elevated serum creatinine before treatment and periodically during treatment
  • Type 1 diabetes mellitus, including diabetic ketoacidosis, reported; monitor for hyperglycemia or other signs and symptoms of diabetes; may resume avelumab when metabolic control is achieved with insulin or antihyperglycemics
  • For Grade ≥2 immune-mediated adverse reactions, administer corticosteroids (initial dose of 1-2 mg/kg/day prednisone or equivalent, followed by taper) for Grade ≥2 nephritis until resolution
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Pregnancy

Pregnancy

Based on its mechanism of action, fetal harm may occur when administered to a pregnant woman

Animal studies demonstrated that PD-1/PD-L1 pathway inhibition can lead to increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death

Human IgG1 immunoglobulins (IgG1) are known to cross the placenta; therefore, transmission may potentially occur between the mother to the developing fetus

Advise patient of the potential risk to a fetus

Contraception

  • Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose

Lactation

Unknown if distributed in human breast milk

Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose owing to the potential for serious adverse reactions in breastfed infants

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.

more...
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Pharmacology

Mechanism of Action

Anti-PD-L1 IgG1 monoclonal antibody

PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells and can contribute to the inhibition of the antitumor immune response in the tumor microenvironment

Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen-presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation, and cytokine production

Avelumab binds PD-L1 and blocks interaction between PD-L1 and its receptors PD-1 and B7.1; therefore, inhibiting PD-L1, resulting in restoration of immune responses, including antitumor immune responses

Absorption

Steady-state: ~4-6 weeks (2-3 cycles)

Distribution

Vd: 4.72 L

Elimination

Half-life: 6.1 days

Primary elimination mechanism is proteolytic degradation

Total systemic clearance: 0.59 L/day

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Administration

IV Compatibilities

0.45% NaCl

0.9% NaCl

IV Preparation

Visually inspect vial for particulate matter and discoloration; should appear as a clear, colorless to slightly yellow solution

Discard vial if solution is cloudy, discolored, or contains particulate matter

Withdraw required dosage volume and inject it into a 250-mL infusion bag containing either 0.9% or 0.45% NaCl

Gently invert bag to mix diluted solution and avoid foaming or excessive shearing

Inspect admixture solution to ensure it is clear, colorless, and free of visible particles

Discard any partially used or empty vials

IV Administration

Infuse IV over 60 minutes through an IV line containing a sterile, nonpyrogenic, low protein-binding inline filter (pore size of 0.2 micron)

Do not coadminister other drugs through the same IV line

Premedication

  • Premedicate with an antihistamine and acetaminophen before the first 4 infusions
  • Premedication for subsequent doses should be based on clinical judgment and presence/severity of prior infusion reactions

Storage

Unopened vials

  • Store refrigerated at 36-46°F (2-8°C) in original package to protect from light
  • Do not freeze or shake vials
  • Vial stopper is not made with natural rubber latex

Diluted solution

  • Room temperature (up to 77°F [25°C]): Store for no more than 4 hr from the time of dilution, OR
  • Refrigerated (36-46°F [2-8°C]): Store for no more than 24 hr from the time of dilution; if refrigerated, allow the diluted solution to come to room temperature before administering
  • Do not freeze or shake diluted solution
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Images

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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.
  • 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.

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.