Bavencio (Avelumab Injection) – updated on RxList

Bavencio (Avelumab Injection) – updated on RxList

<h1>Bavencio (Avelumab Injection) – updated on RxList</h1>

Bavencio (Avelumab Injection) – updated on RxList

Included as part of the PRECAUTIONS section. PRECAUTIONS Immune-Mediated Pneumonitis
BAVENCIO can cause immune-mediated pneumonitis, including fatal cases [see ADVERSE REACTIONS ]. Monitor patients for signs and symptoms of pneumonitis and evaluate patients with suspected pneumonitis with radiographic imaging. Administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent, followed by a corticosteroid taper) for Grade 2 or greater pneumonitis. Withhold BAVENCIO for moderate (Grade 2) pneumonitis, and permanently discontinue for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis [see DOSAGE AND ADMINISTRATION ].
Pneumonitis occurred in 1.2% (21/1738) of patients receiving BAVENCIO including one (0.1%) patient with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3 pneumonitis. Immune-mediated pneumonitis led to permanent discontinuation of BAVENCIO in 0.3% (6/1738) of patients. Among the 21 patients with immune-mediated pneumonitis, the median time to onset was 2.5 months (range: 3 days to 11 months) and the median duration of pneumonitis was 7 weeks (range: 4 days to 4+ months). All 21 patients were treated with systemic corticosteroids; 17 (81%) of the 21 patients received high-dose corticosteroids for a median of 8 days (range: 1 day to 2.3 months). Resolution of pneumonitis occurred in 12 (57%) of the 21 patients at the time of data cut-off. Immune-Mediated Hepatitis
BAVENCIO can cause immune-mediated hepatitis including fatal cases [see ADVERSE REACTIONS ]. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent, followed by a corticosteroid taper) for Grade 2 or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) immune-mediated hepatitis [see DOSAGE AND ADMINISTRATION ].
Immune-mediated hepatitis occurred in 0.9% (16/1738) of patients receiving BAVENCIO including two (0.1%) patients with Grade 5 and 11 (0.6 %) patients with Grade 3 immune-mediated hepatitis. Immunemediated hepatitis led to permanent discontinuation of BAVENCIO in 0.5% (9/1738) of patients. Among the 16 patients with immune-mediated hepatitis, the median time to onset was 3.2 months (range: 1 week to 15 months), and the median duration of hepatitis was 2.5 months (range: 1 day to 7.4+ months). All 16 patients were treated with corticosteroids; 15 (94%) of the 16 patients received high-dose corticosteroids for a median of 14 days (range: 1 day to 2.5 months). Resolution of hepatitis occurred in nine (56%) of the 16 patients at the time of data cut-off. Immune-Mediated Colitis
BAVENCIO can cause immune-mediated colitis [see ADVERSE REACTIONS ]. Monitor patients for signs and symptoms of colitis. Administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a corticosteroid taper) for Grade 2 or greater colitis. Withhold BAVENCIO for moderate or severe (Grade 2 or 3) colitis until resolution. Permanently discontinue BAVENCIO for life-threatening (Grade 4) or for recurrent (Grade 3) colitis upon re-initiation of BAVENCIO [see DOSAGE AND ADMINISTRATION ].
Immune-mediated colitis occurred in 1.5% (26/1738) of patients receiving BAVENCIO including seven (0.4%) patients with Grade 3 colitis. Immune-mediated colitis led to permanent discontinuation of BAVENCIO in 0.5% (9/1738) of patients. Among the 26 patients with immune-mediated colitis, the median time to onset was 2.1 months (range: 2 days to 11 months) and the median duration of colitis was 6 weeks (range: 1 day to 14+ months). All 26 patients were treated with corticosteroids; 15 (58%) of the 26 patients received high-dose corticosteroids for a median of 19 days (range: 1 day to 2.3 months). Resolution of colitis occurred in 18 (70%) of the patients at the time of data cut-off. Immune-Mediated Endocrinopathies
BAVENCIO can cause immune-mediated endocrinopathies [see ADVERSE REACTIONS ]. Adrenal Insufficiency
Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment. Administer corticosteroids as appropriate for adrenal insufficiency. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency [see DOSAGE AND ADMINISTRATION ].
Adrenal insufficiency occurred in 0.5% (8/1738) of patients receiving BAVENCIO including one patient (0.1%) with Grade 3 adrenal insufficiency. Immune-mediated adrenal insufficiency led to permanent discontinuation of BAVENCIO in 0.1% (2/1738) of patients. Among the 8 patients with immune-mediated adrenal insufficiency, the median time to onset was 2.5 months (range: 1 day to 8 months). All eight patients were treated with corticosteroids; four (50%) of the eight patients received high-dose corticosteroids for a median of 1 day (range: 1 day to 24 days). Thyroid Disorders (Hypothyroidism/Hyperthyroidism)
BAVENCIO can cause immune-mediated thyroid disorders. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with hormonereplacement therapy. Initiate medical management for control of hyperthyroidism. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders [see DOSAGE AND ADMINISTRATION ].
Immune-mediated thyroid disorders occurred in 6% (98/1738) of patients receiving BAVENCIO including 3 (0.2%) Grade 3 immune-mediated thyroid disorders. Immune-mediated thyroid disorders led to discontinuation of BAVENCIO in 0.1% (2/1738) of patients. Hypothyroidism occurred in 90 (5%) patients; hyperthyroidism in seven (0.4%) patients; and thyroiditis in four (0.2%) patients treated with BAVENCIO. Among the 98 patients with immune-mediated thyroid disorders, the median time to onset was 2.8 months (range: 2 weeks to 13 months) and the median duration was not estimable (range: 6 days to more than 26 months). Immune-mediated thyroid disorders resolved in seven (7%) of the 98 patients. Type 1 Diabetes Mellitus
BAVENCIO can cause type 1 diabetes mellitus, including diabetic ketoacidosis . Monitor patients for hyperglycemia or other signs and symptoms of diabetes . Withhold BAVENCIO and administer antihyperglycemics or insulin in patients with severe or life-threatening (Grade ≥ 3) hyperglycemia. Resume treatment with BAVENCIO when metabolic control is achieved on insulin replacement or antihyperglycemics [see DOSAGE AND ADMINISTRATION ].
Type 1 diabetes mellitus without an alternative etiology occurred in 0.1% (2/1738) of patients including two cases of Grade 3 hyperglycemia that led to permanent discontinuation of BAVENCIO. Immune-Mediated Nephritis And Renal Dysfunction
BAVENCIO can cause immune-mediated nephritis [see ADVERSE REACTIONS ]. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a corticosteroid taper) for Grade 2 or greater nephritis. Withhold BAVENCIO for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to ≤ Grade 1. Permanently discontinue BAVENCIO for life-threatening (Grade 4) nephritis [see DOSAGE AND ADMINISTRATION ].
Immune-mediated nephritis occurred in 0.1% (1/1738) of patients receiving BAVENCIO; BAVENCIO was permanently discontinued in this patient. Other Immune-Mediated Adverse Reactions
BAVENCIO can result in severe and fatal immune-mediated adverse reactions [see ADVERSE REACTIONS ]. These immune-mediated reactions may involve any organ system. Most immune-mediated reactions initially manifest during treatment with BAVENCIO; however, immune-mediated adverse reactions can occur after discontinuation of BAVENCIO.
For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an immune-mediated adverse reaction and to exclude other causes. Depending upon the severity of the adverse reaction, withhold or permanently discontinue BAVENCIO, administer high dose corticosteroids, and if appropriate, initiate hormone replacement therapy. Upon improvement to Grade 1 or less, initiate corticosteroid taper. Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction [see DOSAGE AND ADMINISTRATION ].
The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% of 1738 patients treated with BAVENCIO for each of the following adverse reactions: immune-mediated myocarditis including fatal cases, immune-mediated myositis , psoriasis , arthritis , exfoliative dermatitis , erythema multiforme , pemphigoid, hypopituitarism, uveitis , Guillain-Barré syndrome, and systemic inflammatory response. The following clinically significant, immune-mediated adverse reactions have been reported with other products in this class: 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 . Infusion-Related Reactions
BAVENCIO can cause severe or life-threatening infusion-related reactions [see ADVERSE REACTIONS ]. Premedicate with antihistamine and acetaminophen prior to the first 4 infusions. Monitor patients for signs and symptoms of infusion-related reactions including pyrexia, chills, flushing, hypotension , dyspnea , wheezing , back pain , abdominal pain, and urticaria . Interrupt or slow the rate of infusion for mild or moderate infusion-related reactions. Stop the infusion and permanently discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS ].
Infusion-related reactions occurred in 25% (439/1738) of patients treated with BAVENCIO including three (0.2%) Grade 4 and nine (0.5%) Grade 3 infusion-related reactions. Ninety-three percent (1615/1738) of patients received premedication with antihistamine and acetaminophen. Eleven (92%) of the 12 patients with Grade ≥ 3 reactions were treated with intravenous corticosteroids. Fourteen percent of patients (252/1738) had infusion-related reactions that occurred after the BAVENCIO infusion was completed. Embryo-Fetal Toxicity
Based on its mechanism of action, BAVENCIO can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. If this drug is used during pregnancy, or if the patient becomes pregnant while taking BAVENCIO, inform the patient of the potential risk to a fetus. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least one month after the last dose of BAVENCIO [see Use In Specific Populations ]. Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Immune-Mediated Adverse Reactions
Inform patients of the risk of immune-mediated adverse reactions requiring corticosteroids or hormone replacement therapy, including, but not limited to: Pneumonitis: Advise patients to contact their healthcare provider immediately for new or worsening cough, chest pain, or shortness of breath [see WARNINGS AND PRECAUTIONS ]. Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice , severe nausea or vomiting, pain on the right side of abdomen, lethargy , or easy bruising or bleeding [see WARNINGS AND PRECAUTIONS ]. Colitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain [see WARNINGS AND PRECAUTIONS ]. Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of adrenal insufficiency, hypothyroidism, hyperthyroidism, and diabetes mellitus [see WARNINGS AND PRECAUTIONS ]. Nephritis and Renal Dysfunction: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis including decreased urine output, blood in urine, swelling in ankles, loss of appetite, and any other symptoms of renal dysfunction [see WARNINGS AND PRECAUTIONS ]. Infusion-Related Reactions
Advise patients to contact their healthcare provider immediately for signs or symptoms of potential infusion-related reactions [see WARNINGS AND PRECAUTIONS ]. Embryo-Fetal Toxicity
Advise females of reproductive potential that BAVENCIO can cause fetal harm. Instruct females of reproductive potential to use highly effective contraception during and for at least one month after the last dose of BAVENCIO [see WARNINGS AND PRECAUTIONS and Use In Specific Populations ]. Lactation
Advise nursing mothers not to breastfeed while taking BAVENCIO and for at least one month after the final dose [see Use In Specific Populations ]. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility
No studies have been conducted to assess the potential of avelumab for genotoxicity or carcinogenicity.
Fertility studies have not been conducted with avelumab; however, an assessment of male and female reproductive organs was included in 3-month repeat-dose toxicity study in Cynomolgus monkeys. Weekly administration of avelumab did not result in any notable effects in the male and female reproductive organs. Use In Specific Populations Pregnancy Risk Summary
Based on its mechanism of action, BAVENCIO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of BAVENCIO in pregnant women [see CLINICAL PHARMACOLOGY ]. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death [see Data ]. Human IgG1 immunoglobulins (IgG1) are known to cross the placenta. Therefore, BAVENCIO has the potential to be transmitted from the mother to the developing fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data
Animal Data
Animal reproduction studies have not been conducted with BAVENCIO to evaluate its effect on reproduction and fetal development. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. In murine models of pregnancy, blockade of PD-L1 signaling has been shown to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering BAVENCIO during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-1/PD-L1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to BAVENCIO may increase the risk of developing immune-related disorders or altering the normal immune response . Lactation Risk Summary
There is no information regarding the presence of avelumab in human milk, the effects on the breastfed infant, or the effects on milk production. Since many drugs including antibodies are excreted in human milk, advise a lactating woman not to breastfeed during treatment and for at least one month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants. Females And Males Of Reproductive Potential Contraception
Based on its mechanism of action, BAVENCIO can cause fetal harm when administered to a pregnant woman [see Use In Specific Populations ]. Advise females of reproductive potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. Pediatric Use
The safety and effectiveness of BAVENCIO have been established in pediatric patients aged 12 years and older for metastatic MCC. Use of BAVENCIO in this age group is supported by evidence from adequate and well-controlled studies of BAVENCIO in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the steady state exposure of avelumab, that drug exposure is generally similar between adults and pediatric patients age 12 years and older for monoclonal antibodies, and that the course of MCC is sufficiently similar in adult and pediatric patients to allow extrapolation of data in adults to pediatric patients. The recommended dose in pediatric patients 12 years of age or greater is the same as that in adults [see DOSAGE AND ADMINISTRATION , CLINICAL PHARMACOLOGY , and Clinical Studies ].
Safety and effectiveness of BAVENCIO have not been established in pediatric patients less than 12 years of age. Geriatric Use Metastatic Merkel Cell Carcinoma
Clinical studies of BAVENCIO in MCC did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Locally Advanced Or Metastatic Urothelial Carcinoma
Of the 226 patients with locally advanced or metastatic UC treated with BAVENCIO, 68% were 65 years or over and 29% were 75 years or over. Among patients 65 years or over who were followed for at least 13 weeks, 14% (22/153) responded to BAVENCIO and 58% (89/153) developed a Grade 3-4 adverse reaction. No overall differences in safety or efficacy were reported between elderly patients and younger patients. Overdosage & Contraindications
No information on BAVENCIO overdosage is available. CONTRAINDICATIONS

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