Dosing & Uses
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
Urothelial Carcinoma
Indicated for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy
Also, indicated for locally advanced or metastatic UC in patients who have disease progression during or following platinum-containing chemotherapy or have 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
Renal Cell Carcinoma
Indicated in combination with axitinib for first-line treatment in patients with advanced renal cell carcinoma (RCC)
Avelumab 800 mg IV q2Weeks in combination with
Axitinib 5 mg PO BID
Continue until disease progression or unacceptable toxicity
When axitinib is used in combination with avelumab, consider dose escalation of axitinib above the initial 5-mg dose at ≥2-week intervals
Refer also to prescribing information for axitinib dosing information
Dosage Modifications
No dose reductions are recommended
Pneumonitis
- Grade 2: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 3 or 4: Permanently discontinue
Colitis
- Grade 2 or 3: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 4: Permanently discontinue
Hepatitis with no tumor involvement of the liver
- AST or ALT increases to >3 and ≤8x ULN or total bilirubin increases to >1.5 and <3x ULN: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- AST or ALT increases to >8x ULN or total bilirubin increases to >3x ULN: Permanently discontinue
Hepatitis with tumor involvement of the liver
- If AST and ALT ≤ULN at baseline, withhold or permanently discontinue treatment based on recommendations for hepatitis where there is no tumor involvement of the liver
-
Withhold therapy
- Baseline AST or ALT >1 and ≤3x ULN and increases to >5 and ≤10x ULN
- Baseline AST or ALT >3 and ≤5x ULN and increases to >8 and ≤10x ULN
- Resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
-
Permanently discontinue
- AST or ALT increases to >10x ULN or total bilirubin increases to >3x ULN
Endocrinopathies
- Grade 3 or 4: Withhold until clinically stable or permanently discontinue depending on severity
Nephritis with renal dysfunction
- Grade 2 or 3 increased blood creatinine: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 4 increased blood creatinine: Permanently discontinue
Exfoliative dermatologic conditions
- Suspected Steven Johnson Syndrome (SJS), toxic epidermal necrosis (TEN), or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS): Withhold therapy
- Confirmed SJS, TEN, or DRESS: Permanently discontinue
Myocarditis
- Grade 2, 3, or 4: Permanently discontinue
Neurologic toxicities
- Grade 2: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 3 or 4: Permanently discontinue
Infusion-related reactions
- Grade 1 or 2: Interrupt or slow infusion rate
- Grade 3 or 4: Permanently discontinue
RCC treated with avelumab in combination with axitinib
-
ALT/AST ≥3x to <5x ULN or total bilirubin ≥1.5x to <3x ULN
- Withhold both avelumab and axitinib until these reactions recover to grade ≤1
- If persistent (>5 days), consider corticosteroid therapy (initial dose of 0.5-1 mg/kg/day) prednisone or equivalent followed by a taper
- Consider rechallenge with a single drug or sequential rechallenge with both drugs after recovery
- If rechallenging axitinib, reduce dose per axitinib full prescribing information
-
ALT/AST ≥5x ULN or >3x ULN with concurrent total bilirubin ≥2x ULN or total bilirubin ≥3x ULN
- Permanently discontinue both avelumab and axitinib
- Consider corticosteroid therapy
Dosage Forms & Strengths
injectable solution
- 20mg/mL (10mL)
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 treatment (resume when recovery to grade ≤1 after corticosteroid taper)
- 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 >3x 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
- 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 immune-mediated adverse reactions lasting ≥12 weeks
- Recurrent severe immune-mediated adverse reaction
Adverse Effects
Adverse effects include all grades unless otherwise stated
>10%
Fatigue (41-50%)
Lymphopenia (49%)
Anemia (35%)
Increased AST (34%)
Infusion-related reaction (22-30%)
Thrombocytopenia (27%)
Musculoskeletal pain (25%)
Diarrhea (18-23%)
Nausea (22-24%)
Rash (15-22%)
Urinary tract infection (21%)
Decreased appetite (20-21%)
Peripheral edema (17-20%)
Increased ALT (20%)
Lymphopenia, grade 3-4 (19%)
Abdominal pain (16-19%)
Decreased weight (15-19%)
Increased creatinine/renal failure (16%)
Pyrexia/increased temperature (16%)
Increased lipase (14%)
Cough (14-18%)
Constipation (17-18%)
Dyspnea (11-17%)
Hyponatremia (16%)
Arthralgia (16%)
Dizziness (14%)
Vomiting/retching (13-14%)
Hypertension (13%)
Increased GGT (12%)
1-10%
Pruritus (10%)
Headache (10%)
Hypertension (10%)
Anemia, grade 3-4 (9%)
Increased amylase (8%)
Hyperglycemia, grade 3-4 (7%)
Increased bilirubin (6%)
Neutropenia, grade 3-4 (6%)
Thyroid disorders (6%)
Hypertension, grade 3 or 4 (5-6%)
Increased ALT, grade 3-4 (5%)
Urinary tract infection, grade 3-4 (5%)
Increased lipase, grade 3-4 (4%)
Musculoskeletal pain, grade 3-4 (3%)
Increased creatinine/renal failure, grade 3 or 4 (3%)
Dyspnea, grade 3 or 4 (2%)
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%)
Dyspnea, grade 3 or 4 (2%)
Colitis (1.5%)
Pneumonitis (1.2%)
Constipation, grade 3 or 4 (1%)
Arthralgia, grade 3 or 4 (1%)
Increased AST, grade 3-4 (1%)
Increased amylase, grade 3-4 (1%)
Increased bilirubin, grade 3-4 (1%)
Thrombocytopenia, grade 3-4 (1%)
Neutropenia, grade 3-4 (1%)
Pyrexia/increased temperature, grade 3-4 (1%)
<1%
Hepatitis
Adrenal insufficiency
Type 1 diabetes mellitus
Nephritis
Postmarketing Reports
Pancreatitis
Myocarditis
Myositis
Congestive heart failure
Myocardial infarction
Warnings
Contraindications
None
Cautions
Embryofetal toxicity is possible based on its mechanism of action (see Pregnancy)
The patient should contact healthcare provider when experiencing lung symptoms, including cough shortness of breath, chest pain, gastrointestinal symptoms, including diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky, or have blood or mucus, or severe stomach-area (abdomen) pain or tenderness, and hepatic symptoms, including yellowing of the skin or the whites of eyes, dark urine (tea colored, severe nausea or vomiting bleeding, or bruising more easily than normal, pain on the right side of your stomach-area (abdomen)
Infusion reactions
- Infusion-related reactions, including severe and life-threatening reactions, reported
- Monitor for signs and symptoms of infusion-related reactions (eg, rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, fever)
- Premedicate with an antihistamine and acetaminophen
Hepatotoxicity
- In combination with axitinib can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 ALT and AST elevation
- Consider more frequent monitoring of liver enzymes as compared to when drugs are used as monotherapy
- Withhold combination therapy for moderate (Grade 2) hepatotoxicity and permanently discontinue for severe or life-threatening (Grade 3 or 4) hepatotoxicity
- Administer corticosteroids as needed
Cardiovascular effects
- In combination with axitinib, can cause severe and fatal cardiovascular events
- Consider baseline and periodic evaluations of left ventricular ejection fraction; monitor for signs and symptoms of cardiovascular events
- Optimize management of cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia)
- Discontinue avelumab and axitinib for Grade 3-4 cardiovascular events
- 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
- In combination with axitinib, can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 ALT and AST elevation; consider more frequent monitoring of liver enzymes
- Monitor for symptoms of immune-mediated colitis; administer systemic corticosteroids for grade 2 or higher colitis
- Immune-mediated adrenal insufficiency should be treated with corticosteroids as appropriate for the adrenal insufficiency; monitor for signs/symptoms of adrenal insufficiency during and after treatment
- 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
Complications of allogeneic HSCT
- Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody
- Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause)
- These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT
- Follow patients closely for evidence of transplant-related complications and intervene promptly; consider benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT
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 from 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.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 the interaction between PD-L1 and its receptors PD-1 and B7.1, thereby inhibiting PD-L1 and 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
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
- Based clinical judgment, premedicate for subsequent doses and presence/severity of prior infusion reactions
Storage
Unopened vials
- Store refrigerated at 36-46ºF (2-8ºC) 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
Images
BRAND | FORM. | UNIT PRICE | PILL IMAGE |
---|---|---|---|
Bavencio intravenous - | 20 mg/mL vial | ![]() |
Copyright © 2010 First DataBank, Inc.
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.