Slideshows Images Quizzes

Copyright © 2018 by RxList Inc. RxList does not provide medical advice, diagnosis or treatment. See additional information.

Bavencio

Last reviewed on RxList: 7/13/2020
Bavencio Side Effects Center

What Is Bavencio?

Bavencio (avelumab) injection is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC).

What Are Side Effects of Bavencio?

Common side effects of Bavencio include:

Dosage for Bavencio

Administer a dose of 10 mg/kg Bavencio as an intravenous infusion over 60 minutes every 2 weeks. Premedicate with acetaminophen and an antihistamine for the first 4 infusions and subsequently as needed.

What Drugs, Substances, or Supplements Interact with Bavencio?

Bavencio may interact with other drugs. Tell your doctor all medications and supplements you use.

Bavencio During Pregnancy and Breastfeeding

Bavencio is not recommended for use during pregnancy; it may harm a fetus. Women are advised to use effective contraception during treatment with Bavencio and for at least one month after the last dose. It is unknown if Bavencio passes into breast milk. Because of the potential for adverse effects on nursing infants, breastfeeding is not recommended while using Bavencio and for at least one month after the last dose.

Additional Information

Our Bavencio (avelumab) Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Skin Cancer Symptoms, Types, Images See Slideshow
Bavencio Professional Information

SIDE EFFECTS

The following adverse reactions are described elsewhere in the label:

  • Immune-mediated pneumonitis [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity and immune-mediated hepatitis [see WARNINGS AND PRECAUTIONS]
  • Immune-mediated colitis [see WARNINGS AND PRECAUTIONS]
  • Immune-mediated endocrinopathies [see WARNINGS AND PRECAUTIONS]
  • Immune-mediated nephritis and renal dysfunction [see WARNINGS AND PRECAUTIONS]
  • Other immune-mediated adverse reactions [see WARNINGS AND PRECAUTIONS]
  • Infusion-related reactions [see WARNINGS AND PRECAUTIONS]
  • Major adverse cardiovascular events [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described in the WARNINGS AND PRECAUTIONS section reflect exposure to BAVENCIO 10 mg/kg intravenously every 2 weeks as a single agent in 1738 patients enrolled in the JAVELIN Merkel 200 and JAVELIN Solid Tumor trials and to BAVENCIO 10 mg/kg intravenously every 2 weeks in combination with axitinib 5 mg orally twice daily in 489 patients enrolled in the JAVELIN Renal 100 and JAVELIN Renal 101 trials. In the BAVENCIO monotherapy population, 24% of patients were exposed for ≥ 6 months and 7% were exposed for ≥ 12 months. The population characteristics of BAVENCIO in combination with axitinib are shown below. When BAVENCIO was used in combination with axitinib, 70% of patients were exposed for ≥ 6 months and 31% were exposed for ≥ 12 months. The following criteria were used to classify an adverse reaction as immune-mediated: onset within 90 days after last dose of BAVENCIO, no spontaneous resolution within 7 days of onset, treatment with corticosteroids or other immunosuppressant or hormone replacement therapy, biopsy consistent with immune-mediated reaction, and no other clear etiology.

Metastatic Merkel Cell Carcinoma

The data described below reflect exposure to BAVENCIO 10 mg/kg intravenously every 2 weeks in 88 patients with metastatic MCC enrolled in the JAVELIN Merkel 200 trial. Patients with any of the following were excluded: autoimmune disease; medical conditions requiring systemic immunosuppression; prior organ or allogeneic stem cell transplantation; prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies; central nervous system (CNS) metastases; infection with HIV, hepatitis B, or hepatitis C; or ECOG performance score ≥2.

The median duration of exposure to BAVENCIO was 4 months (range: 2 weeks to 21 months). Forty percent of patients received BAVENCIO for more than 6 months and 14% were treated for more than one year [see Clinical Studies]. The study population characteristics were: median age of 73 years (range: 33 to 88), 74% male, 92% White, ECOG performance score of 0 (56%) or 1 (44%), and 65% of patients had one prior anti-cancer therapy for metastatic MCC and 35% had two or more prior therapies.

BAVENCIO was permanently discontinued for adverse reactions in six (7%) patients; adverse reactions resulting in permanent discontinuation were ileus, Grade 3 transaminitis, Grade 3 creatine kinase elevation, tubulointerstitial nephritis, and Grade 3 pericardial effusion. BAVENCIO was temporarily discontinued in 21 (24%) patients for adverse events, excluding temporary dose interruption for infusion-related reactions where infusion was restarted the same day. The most common adverse reaction requiring dose interruption was anemia. Serious adverse reactions that occurred in more than one patient were acute kidney injury, anemia, abdominal pain, ileus, asthenia, and cellulitis. The most common adverse reactions (≥ 20%) were fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema.

Table 2 and Table 3 summarize the incidence of adverse reactions and laboratory abnormalities, respectively, that occurred in patients receiving BAVENCIO.

Table 2: Adverse Reactions in ≥ 10% of Patients Receiving BAVENCIO in the JAVELIN Merkel 200 Trial

Adverse Reactions BAVENCIO
(N=88)
All Grades
%
Grade 3-4
%
General Disorders
  Fatiguea 50 2
  Infusion-related reactionb 22 0
  Peripheral edemac 20 0
Musculoskeletal and Connective Tissue Disorders
  Musculoskeletal paind 32 2
  Arthralgia 16 1
Gastrointestinal Disorders
  Diarrhea 23 0
  Nausea 22 0
  Constipation 17 1
  Abdominal paine 16 2
  Vomiting 13 0
Skin and Subcutaneous Tissue Disorders
  Rashf 22 0
  Pruritusg 10 0
Metabolism and Nutrition Disorders
  Decreased appetite 20 2
  Decreased weight 15 0
Respiratory, Thoracic and Mediastinal Disorders
  Cough 18 0
  Dyspneah 11 1
Nervous System Disorders
  Dizziness 14 0
  Headache 10 0
Vascular Disorders
  Hypertension 13 6
a Fatigue is a composite termthat includes fatigue and asthenia
b Infusion-related reaction is a composite term that includes drug hypersensitivity, hypersensitivity, chills, pyrexia, back pain, and hypotension
c Peripheral edemais a compositetermthat includesperipheral edema and peripheral swelling
d Musculoskeletal pain is a composite termthat includes back pain, myalgia, neck pain, pain in extremity
e Abdominal pain is a composite term that includes abdominal pain and abdominal pain upper
f Rash is a compositetermthat includes rash maculo-papular,erythema,and dermatitis bullous
g Pruritus is a composite termthat includespruritus andpruritus generalized
h Dyspnea is a compositeterm that includes dyspnea anddyspneaexertional

Table 3: Selected Treatment-Emergent* Laboratory Abnormalities in Patients Receiving BAVENCIOin the JAVELIN Merkel200Trial

Laboratory Tests Any Grade
(N=88)
%
Grade 3-4
(N=88)
%
Chemistry
  Increased aspartate aminotransferase (AST) 34 1
  Increased alanine aminotransferase (ALT) 20 5
  Increased lipase 14 4
  Increased amylase 8 1
  Increased bilirubin 6 1
  Hyperglycemia** - 7
Hematology
  Anemia 35 9
  Lymphopenia 49 19
  Thrombocytopenia 27 1
  Neutropenia 6 1
* Treatment emergent consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality
** Hyperglycemia limited to Grade ≥ 3 eventssincefasting measurementswere not obtainedroutinely

Locally Advanced Or Metastatic Urothelial Carcinoma

Table 4 describes adverse reactions reported in 242 patients with locally advanced or metastatic UC receiving BAVENCIO at 10 mg/kg every 2 weeks in the UC cohorts of the JAVELIN Solid Tumor trial. Patients received pre-medication with an anti-histamine and acetaminophen prior to each infusion. The median duration of exposure to BAVENCIO was 12 weeks (range: 2 weeks to 92 weeks) [see Clinical Studies].

Fourteen patients (6%)whowere treated with BAVENCIOexperienced either pneumonitis, respiratory failure, sepsis/urosepsis, cerebrovascular accident, or gastrointestinal adverse events, which led to death.

BAVENCIO was permanently discontinued for Grade 1-4 adverse reactions in 30 (12%) patients. The adverse reaction that resulted in permanent discontinuation in > 1% of patients was fatigue. BAVENCIO was temporarily discontinued in 29% of patients for adverse reactions, excluding temporary dose interruption for infusion-related reactions where infusion was restarted the same day. The adverse reactions that resulted in temporary discontinuation in > 1% of patients were diarrhea, fatigue, dyspnea, urinary tract infection, and rash.

Grade 1-4 serious adverse reactions were reported in 41% of patients. The most frequent serious adverse reactions reported in ≥ 2% of patients were urinary tract infection/urosepsis, abdominal pain, musculoskeletal pain, creatinine increased/renal failure, dehydration, hematuria/urinary tract hemorrhage, intestinal obstruction/small intestine obstruction, and pyrexia.

The most common Grade 3 and 4 adverse reactions (≥ 3%) were anemia, fatigue, hyponatremia, hypertension urinary tract infection, and musculoskeletal pain.

The most common adverse reactions (≥ 20%) were fatigue, infusion-related reaction, musculoskeletal pain, nausea, decreased appetite, and urinary tract infection.

Eleven (4.5%) patients received an oral prednisone dose equivalent to ≥ 40 mg daily for an immune-mediated adverse reaction [see WARNINGS AND PRECAUTIONS].

Table 4 summarizes the adverse reactions that occurred in at least 10% of patients with locally advanced or metastatic UC receiving BAVENCIO while Table 5 summarizes selected Grade 3-4 laboratory abnormalities that occurred in ≥ 1% of patients treated with BAVENCIO.

Table 4: All Grade Adverse Reactions in ≥ 10% of Patients with Locally Advanced or Metastatic UC in the JAVELIN Solid Tumor Trial

Adverse Reactions BAVENCIO
(N=242)
All Grades
(%)
Grade 3-4
(%)
Any 98 59
Gastrointestinal Disorders
  Nausea 24 1
  Abdominal paina 19 2
  Diarrhea 18 2
  Constipation 18 1
  Vomiting/Retching 14 1
General Disorders and Administration Site Conditions
  Fatigueb 41 7
  Infusion-related reactionc 30 0.4
  Peripheral edemad 17 0.4
  Pyrexia/Temperature increased 16 1
Infections
  Urinary tract infectione 21 5
Investigations
  Weight decreased 19 0
Metabolism and Nutrition Disorders
  Decreased appetite/Hypophagia 21 2
Musculoskeletal and Connective Tissue Disorders
  Musculoskeletal painf 25 3
Renal Disorders
  Creatinine increased/Renal failureg 16 3
Respiratory, Thoracic and Mediastinal Disorders
  Dyspnea/Exertional dyspnea 17 2
  Cough/Productive cough 14 0
Skin and Subcutaneous Tissue Disorders
  Rashh 15 0.4
  Pruritus/Generalized pruritus 10 0.4
Vascular Disorders
  Hypertension/Hypertensive crisis 10 5
a Includes abdominal discomfort, abdominal pain upperandlower, and gastrointestinal pain
b Includes asthenia and malaise
c Infusion-related reaction is a composite term thatincludes chills, pyrexia, back pain, flushing, dyspnea, and hypotension
d Includes edema, generalized edema, and peripheral swelling
e Includes urosepsis, cystitis, kidney infection, pyuria,and urinary tract infection due to fungus, bacterial, and enterococcus
f Includesback pain, myalgia, neck pain,and painin extremity
g Includes acute kidney injury and glomerular filtration rate decreased
h Includes dermatitis acneiform, eczema, erythema, erythema multiforme, erythematous, macular, maculopapular, papular, and pruritic rash

Table 5: Selected Laboratory Abnormalities* (Grade 3-4) in ≥ 1% of Patients with Locally Advanced or Metastatic UC Receiving BAVENCIO in the JAVELIN Solid Tumor Trial

Laboratory Tests Grade 3-4
(N=242)**
%
Chemistry  
  Hyponatremia 16
  GGT increased 12
  Hyperglycemia 9
  Increased alkaline phosphatase 7
  Increased lipase 6
  Hyperkalemia 3
  Increased aspartate aminotransferase (AST)*** 3
  Increased creatinine 2
  Increased amylase 2
  Increased bilirubin 1
Hematology  
  Lymphopenia 11
  Anemia 6
*Including Grade 3 and 4 lab abnormalities worsening from and unchangedsince baseline.
** The number of patients withon studyavailablelaboratories varies between188 and 235.
***Increased alanine aminotransferase(ALT)was reported in 0.9% (Grade 3-4)of platinum-pretreated patients with locally advanced or metastatic UC.

Advanced Renal Cell Carcinoma

The safety of BAVENCIO was evaluated in JAVELIN Renal 101. Patients with autoimmune disease other than type I diabetes mellitus, vitiligo, psoriasis, or thyroid disorders not requiring immunosuppressive treatment were excluded. Patients received BAVENCIO 10 mg/kg every 2 weeks administered in combination with axitinib 5 mg twice daily (N=434) or sunitinib 50 mg once daily for 4 weeks followed by 2 weeks off (N=439).

In the BAVENCIO plus axitinib arm, 70% were exposed to BAVENCIO for ≥ 6 months and 29% were exposed for ≥ 1 year in JAVELIN Renal 101 [see Clinical Studies].

The median age of patients treated with BAVENCIO in combination with axitinib was 62 years (range: 29 to 83), 38% of patients were 65 years or older, 71% were male, 75% were White, and the ECOG performance score was 0 (64%) or 1 (36%).

Fatal adverse reactions occurred in 1.8% of patients receiving BAVENCIO in combination with axitinib. These included sudden cardiac death (1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing pancreatitis (0.2%).

Serious adverse reactions occurred in 35% of patients receiving BAVENCIO in combination with axitinib. Serious adverse reactions in ≥ 1% of patients included diarrhea (2.5%), dyspnea (1.8%), hepatotoxicity (1.8%), venous thromboembolic disease (1.6%), acute kidney injury (1.4%), and pneumonia (1.2%).

Permanent discontinuation due to an adverse reaction of either BAVENCIO or axitinib occurred in 22% of patients: 19% BAVENCIO only, 13% axitinib only, and 8% both drugs. The most common adverse reactions (> 1%) resulting in permanent discontinuation of BAVENCIO or the combination were hepatotoxicity (6%) and infusion-related reaction (1.8%).

Dose interruptions or reductions due to an adverse reaction, excluding temporary interruptions of BAVENCIO infusions due to infusion-related reactions, occurred in 76% of patients receiving BAVENCIO in combination with axitinib. This includes interruption of BAVENCIO in 50% of patients. Axitinib was interrupted in 66% and dose reduced in 19% of patients. The most common adverse reaction (> 10%) resulting in interruption of BAVENCIO was diarrhea (10%) and the most common adverse reactions resulting in either interruption or dose reduction of axitinib were diarrhea (19%), hypertension (18%), palmar-plantar erythrodysesthesia (18%), and hepatotoxicity (10%).

The most common adverse reactions (≥ 20%) in patients receiving BAVENCIO in combination with axitinib were diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain, and headache.

Forty-eight (11%) of patients treated with BAVENCIO in combination with axitinib received an oral prednisone dose equivalent to ≥ 40 mg daily for an immune-mediated adverse reaction [see WARNINGS AND PRECAUTIONS].

Table 6 summarizes adverse reactions that occurred in ≥ 20% of BAVENCIO in combination with axitinib-treated patients.

Table 6: Adverse Reactions (≥ 20%)of Patients Receiving BAVENCIO in Combination with Axitinib (JAVELIN Renal 101 Trial)1

Adverse Reactions BAVENCIO plus
Axitinib
(N=434)
Sunitinib
(N=439)
All Grades
%
Grade 3-4
%
All Grades
%
Grade 3-4
%
Gastrointestinal Disorders
  Diarrhea2 62 8 48 2.7
  Nausea 34 1.4 39 1.6
  Mucositis3 34 2.8 35 2.1
  Hepatotoxicity4 24 9 18 3.6
  Abdominal pain5 22 1.4 19 2.1
General Disorders and Administration Site Conditions
  Fatigue6 53 6 54 6
Vascular Disorders
  Hypertension7 50 26 36 17
Musculoskeletal and Connective Tissue Disorders
  Musculoskeletal pain8 40 3.2 33 2.7
Skin and Subcutaneous Tissue Disorders
  Palmar-plantar erythrodysesthesia 33 6 34 4
  Rash9 25 0.9 16 0.5
Respiratory, Thoracic and Mediastinal Disorders
  Dysphonia 31 0.5 3.2 0
  Dyspnea10 23 3.0 16 1.8
  Cough 23 0.2 19 0
Metabolism and Nutrition Disorders
  Decreased appetite 26 2.1 29 0.9
Endocrine Disorders
  Hypothyroidism 25 0.2 14 0.2
Nervous System Disorders
  Headache 21 0.2 16 0.2
Toxicity was graded per NationalCancer Institute Common Terminology Criteria for Adverse Events. Version4.03 (NCI CTCAE v4).
1 The trial was not designed to demonstrate a statistically significant differencein the incidence of adverse reactions between BAVENCIO in combination with axitinibandsunitinib.
2 Diarrhea is a composite term thatincludesdiarrhea,autoimmune colitis,and colitis
3 Mucositis is a composite term that includes mucosal inflammation and stomatitis
4 Hepatotoxicity is a composite term that includes ALT increased, ASTincreased, autoimmune hepatitis, bilirubin conjugated, bilirubin conjugated increased, blood bilirubin increased, drug-induced liver injury, hepatic enzyme increased, hepatic function abnormal, hepatitis, hepatitis fulminant, hepatocellular injury, hepatotoxicity, hyperbilirubinemia, immune-mediated hepatitis, liver function test increased, liver disorder, liver injury, and transaminases increased
5 Abdominal pain is a composite term that includesabdominal pain,flank pain,abdominal pain upper, and abdominal pain lower
6 Fatigue is a composite termthat includesfatigue and asthenia
7 Hypertension is a composite term that includeshypertension andhypertensive crisis
8 Musculoskeletalpain is a compositeterm that includesmusculoskeletal pain,musculoskeletal chest pain,myalgia, back pain,bone pain,musculoskeletal discomfort,neck pain,spinal pain,andpain in extremity
9 Rash is a composite term that includes rash,rash generalized,rash macular,rash maculo-papular,rash pruritic,rash erythematous,rash papular, andrash pustular
10 Dyspnea is a composite term thatincludesdyspnea,dyspnea exertional and dyspnea at rest

Other clinically important adverse reactions that occurred in less than 20% of patients in JAVELIN Renal 101 included arthralgia, weight decreased, and chills.

Patients received pre-medication with an anti-histamine and acetaminophen prior to each infusion. Infusion-related reactions occurred in 12% (Grade 3: 1.6%; no Grade 4) of patients treated with BAVENCIO in combination with axitinib.

Table 7 summarizes selected laboratory abnormalities that occurred in ≥ 20% of BAVENCIO in combination with axitinib-treated patients.

Table 7: Selected Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% of Patients Receiving BAVENCIO in Combination with Axitinib (JAVELIN Renal 101 Trial)1

Laboratory Abnormality BAVENCIO plus Axitinib2 Sunitinib2
Any Grade
%
Grade 3-4
%
Any Grade
%
Grade 3-4
%
Chemistry
  Blood triglycerides increased 71 13 48 5
  Blood creatinine increased 62 2.3 68 1.4
  Blood cholesterol increased 57 1.9 22 0.7
  Alanine aminotransferase increased (ALT) 50 9 46 3.2
  Aspartate aminotransferase increased (AST) 47 7 57 3.2
  Blood sodium decreased 38 9 37 10
  Lipase increased 37 14 25 7
  Blood potassium increased 35 3.0 28 3.9
  Blood bilirubin increased 21 1.4 23 1.4
Hematology
  Platelet count decreased 27 0.7 80 15
  Hemoglobin decreased 21 2.1 65 8
1 The trial was not designed to demonstrate a statistically significant differencein the incidence of laboratory abnormalities between BAVENCIO in combination with axitinib and sunitinib.
2 Each test incidence is based on the number of patients who had bothbaseline and at least one on-study laboratory measurement available: BAVENCIOin combination with axitinib group(range: 413 to 428 patients) and sunitinib group (range:405 to 433 patients).

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to avelumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Of the 1738 patients treated with BAVENCIO 10 mg/kg as an intravenous infusion every 2 weeks, 1558 were evaluable for treatment-emergent anti-drug antibodies (ADA) and 64 (4.1%) tested positive. The development of treatment-emergent ADA against avelumab did not appear to alter the pharmacokinetic profile or risk of infusion-related reactions.

Of the 480 patients treated with BAVENCIO 10 mg/kg as an intravenous infusion every 2 weeks in combination with axitinib 5 mg twice daily, 453 were evaluable for treatment-emergent anti-drug antibodies (ADA) and 66 (15%) tested positive. A new ADA method with improved sensitivity was used in the RCC population. Patients who tested positive for treatment-emergent ADA had decreased systemic BAVENCIO exposure [see CLINICAL PHARMACOLOGY]. The development of treatment-emergent ADA against avelumab did not appear to alter the risk of infusion-related reactions.

Read the entire FDA prescribing information for Bavencio (Avelumab Injection)

Related Resources for Bavencio

© Bavencio Patient Information is supplied by Cerner Multum, Inc. and Bavencio Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Health Solutions From Our Sponsors

CONTINUE SCROLLING FOR RELATED SLIDESHOW