Version May 2024
Note: Premedicate with an antihistamine and acetaminophen prior to the first 4 infusions; consider premedication for subsequent infusions based on clinical judgment and the presence and/or severity of infusion-related reactions with previous infusions.
Gestational trophoblastic neoplasia, chemotherapy-resistant (off-label use; based on limited data): IV: 10 mg/kg once every 2 weeks, continue for 3 cycles after human chorionic gonadotropin (hCG) is normal (Ref).
Merkel cell carcinoma, metastatic: IV: 800 mg once every 2 weeks until disease progression or unacceptable toxicity.
Off-label dosing: 10 mg/kg once every 2 weeks until disease progression or unacceptable toxicity (Ref).
Renal cell carcinoma, advanced, first-line combination therapy: Note: Avelumab in combination with axitinib may be used regardless of risk stratification; although may be considered for first-line treatment, other immunotherapy combinations are preferred since this combination has not demonstrated an overall survival benefit in randomized trials (Ref).
IV: 800 mg once every 2 weeks (in combination with axitinib) until disease progression or unacceptable toxicity.
Off-label dosing: 10 mg/kg once every 2 weeks (in combination with axitinib) until disease progression or unacceptable toxicity (Ref).
Urothelial carcinoma, locally advanced or metastatic (first-line maintenance therapy or for therapy of progressive disease): IV: 800 mg once every 2 weeks until disease progression or unacceptable toxicity.
Off-label dosing: 10 mg/kg once every 2 weeks until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically meaningful differences were observed in a population pharmacokinetic analysis in patients with CrCl 15 to 89 mL/minute.
Kidney toxicity during treatment :
Immune-mediated nephritis with kidney dysfunction: If avelumab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to ≤ grade 1, then follow with a corticosteroid taper.
Grade 2 or grade 3 serum creatinine elevation: Withhold avelumab; resume avelumab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper. Permanently discontinue avelumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 week of corticosteroid initiation.
Grade 4 serum creatinine elevation: Permanently discontinue avelumab.
Hepatic impairment prior to treatment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically meaningful differences were observed in a population pharmacokinetic analysis in patients with mild (bilirubin ≤ ULN and AST > ULN or bilirubin between 1 to 1.5 times ULN) or moderate (bilirubin between 1.5 to 3 times ULN) impairment. Limited data is available in patients with severe (bilirubin >3 times ULN) impairment.
Hepatotoxicity during treatment:
If avelumab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to ≤ grade 1, then follow with a corticosteroid taper. Permanently discontinue avelumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 week of corticosteroid initiation.
Merkel cell carcinoma and urothelial carcinoma:
Immune-mediated hepatitis without tumor involvement of the liver:
AST or ALT >3 up to 8 times ULN or total bilirubin >1.5 up to 3 times ULN: Withhold avelumab treatment. Resume avelumab treatment with complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper.
AST or ALT >8 times ULN or total bilirubin >3 times ULN: Discontinue avelumab permanently.
Immune-mediated hepatitis with tumor involvement of the liver: Note: If AST and ALT are ≤ ULN at baseline, follow recommendations for hepatitis without tumor involvement of the liver.
If baseline AST or ALT >1 up to 3 times ULN and increases to >5 up to 10 times ULN or baseline AST or ALT >3 up to 5 times ULN and increases to >8 up to 10 times ULN: Withhold avelumab treatment. Resume avelumab treatment with complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper.
AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN: Discontinue avelumab permanently.
Renal cell carcinoma (in combination with axitinib):
AST or ALT ≥3 to <10 times ULN without concurrent total bilirubin ≥2 times ULN: Withhold avelumab (and axitinib) until recovery to grade 0 or 1 and consider corticosteroid therapy. After recovery, consider rechallenge with a single drug (either avelumab or axitinib) or sequential rechallenge with both avelumab and axitinib; axitinib may require a dose reduction (refer to axitinib monograph).
AST or ALT ≥10 times ULN or >3 times ULN with concurrent total bilirubin ≥2 times ULN: Discontinue avelumab (and axitinib) permanently; may require systemic corticosteroids.
Additional recommendations:
Grade 2 immune-mediated hepatitis: Withhold immune checkpoint inhibitor (ICI); if no improvement within 3 to 5 days after ICI is withheld, consider initiation of corticosteroids (prednisone 0.5 to 1 mg/kg/day or equivalent) (Ref).
Grade 3 or 4 immune-mediated hepatitis: Withhold ICI; initiate corticosteroids (methylprednisolone 1 to 2 mg/kg or equivalent) (Ref). Based on data from a retrospective cohort study in patients with grade 3 or 4 immune-mediated hepatitis, initial treatment with methylprednisolone 1 mg/kg/day demonstrated similar time to ALT normalization (compared with higher methylprednisolone doses), while reducing the potential for corticosteroid-related complications (Ref).
Note: No dose reduction for avelumab is recommended. Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
Immune-mediated adverse reactions (general information): Withhold avelumab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue avelumab for life-threatening (grade 4) immune-mediated adverse reactions, recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or inability to reduce corticosteroid dose to prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating corticosteroids. If avelumab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) until improvement to ≤ grade 1; upon improvement to ≤ grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with systemic corticosteroid therapy. Systemic corticosteroids may not be necessary for certain adverse reactions. Hormone replacement therapy may be required for endocrinopathies (if clinically indicated). See table for additional dosage modification guidance.
Additional management recommendations: Consider withholding checkpoint inhibitor therapy for most grade 2 toxicities and resume when symptoms and/or lab values resolve to ≤ grade 1; systemic corticosteroids (initial dose of 0.5 to 1 mg/kg/day prednisone [or equivalent]) may be administered if indicated for grade 2 toxicities (Ref). Refer to guideline for further information regarding management of immune-mediated adverse reactions associated with checkpoint inhibitor therapy.
|
Adverse reaction |
Severity |
Avelumab dosage modification |
|---|---|---|
|
a Refer to Prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with checkpoint inhibitor therapy. | ||
|
Immune-mediated adverse reactions | ||
|
Cardiovascular toxicity: Myocarditis |
Grade 2, 3, or 4 |
Permanently discontinue avelumab. |
|
Dermatologic toxicity |
Mild or moderate nonexfoliative rash |
May be managed with topical emollients and/or topical corticosteroids. |
|
Suspected Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS) |
Withhold avelumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid tapera. Permanently discontinue avelumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. | |
|
Confirmed SJS, TEN, or DRESS |
Permanently discontinue avelumab. | |
|
Endocrinopathies |
Grade 3 or 4 |
Withhold avelumab until clinically stable or permanently discontinue (depending on severity). |
|
Adrenal insufficiency, ≥ grade 2 |
Initiate symptomatic management (including hormone replacement as clinically indicated). | |
|
Diabetes, type 1 |
Initiate insulin as clinically indicated. | |
|
Hypophysitis |
Withhold or discontinue avelumab (depending on severity). Initiate hormone replacement therapy as clinically indicated. | |
|
Hyperthyroidism |
Initiate medical management as clinically indicated. | |
|
Hypothyroidism |
Initiate thyroid hormone replacement therapy as clinically indicated. | |
|
GI toxicity: Colitis |
Grade 2 or 3 |
Withhold avelumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid tapera. Permanently discontinue avelumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 4 |
Permanently discontinue avelumab. | |
|
Neurologic toxicities |
Grade 2 |
Withhold avelumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid tapera. Permanently discontinue avelumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 week of corticosteroid initiation. |
|
Grade 3 or 4 |
Permanently discontinue avelumab. | |
|
Ocular disorders: Vogt-Koyanagi-Harada-like syndrome |
May require systemic corticosteroids to reduce the risk of permanent vision loss. | |
|
Pulmonary toxicity: Pneumonitis |
Grade 2 |
Withhold avelumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid tapera. Permanently discontinue avelumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 3 or 4 |
Permanently discontinue avelumab. | |
|
Other adverse reactions | ||
|
Infusion reactions |
Grade 1 or 2 |
Interrupt or slow the rate of avelumab infusion. |
|
Grade 3 or 4 |
Permanently discontinue avelumab. | |
|
Combination therapy with axitinib (cardiovascular events) |
Grade 3 or 4 |
Discontinue avelumab and axitinib. |
Refer to adult dosing.
(For additional information see "Avelumab: Pediatric drug information")
Note: Prior to first 4 infusions, premedicate with an antihistamine and acetaminophen; for subsequent infusions, consider premedication based on clinical judgment and a history of and/or severity of infusion-related reactions with previous infusions.
Merkel cell carcinoma, metastatic: Children ≥12 years and Adolescents: IV: 800 mg once every 2 weeks until disease progression or unacceptable toxicity; fixed dose of 800 mg based on pharmacokinetic/dynamic data (primarily adult patients) which showed no meaningful difference in exposure between 800 mg/dose and 10 mg/kg/dose; avelumab abbreviated approval and additional adult trial data report a weight-directed dose of 10 mg/kg/dose once every 2 weeks; specific pediatric data is scant (Ref)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Children ≥12 years and Adolescents:
Endocrinopathies:
Adrenal insufficiency, grade 3 or 4: Withhold treatment; administer corticosteroids as appropriate. Resume avelumab treatment with complete or partial resolution to grade 0 or 1 after corticosteroid taper.
Hyperglycemia, grade 3 or 4: Withhold treatment and administer insulin or other anti-hyperglycemic treatment as necessary. Resume avelumab with complete or partial solution to grade 0 or 1 and metabolic control has been achieved.
Hyperthyroidism or hypothyroidism, grade 3 or 4: Withhold treatment. Initiate medical management for hyperthyroidism; manage hypothyroidism with hormone replacement therapy. Resume avelumab with complete or partial resolution to grade 0 or 1.
Other endocrinopathies, grade 3 or 4: Withhold treatment; administer corticosteroids as appropriate. Resume avelumab treatment with complete or partial resolution to grade 0 or 1 after corticosteroid taper.
Gastrointestinal toxicity:
Diarrhea or colitis, grade 2 or 3: Withhold treatment. Administer high-dose systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper. Resume avelumab treatment with complete or partial resolution to grade 0 or 1 after corticosteroid taper.
Diarrhea or colitis, grade 4 or recurrent grade 3: Discontinue permanently. Administer high-dose systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper.
Infusion-related reaction:
Grade 1 or 2: Interrupt or slow the rate of infusion.
Grade 3 or 4: Permanently discontinue.
Pulmonary toxicities:
Pneumonitis, grade 2: Withhold treatment. Administer high-dose systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper. May resume avelumab treatment with complete or partial resolution to grade 0 or 1 after corticosteroid taper.
Pneumonitis, grade 3 or 4, or recurrent grade 2: Discontinue permanently. Administer high-dose systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper.
Other immune-mediated toxicities (eg, arthritis, bullous dermatitis, demyelination, encephalitis, erythema multiforme, exfoliative dermatitis, Guillain-Barré syndrome, hemolytic anemia, histiocytic necrotizing lymphadenitis, hypophysitis, hypopituitarism, iritis, myasthenia gravis, myocarditis, myositis, pancreatitis, pemphigoid, psoriasis, rhabdomyolysis, Stevens Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN), uveitis, vasculitis):
Immune-mediated toxicities, moderate or severe clinical signs/symptoms (not described previously): Withhold treatment and evaluate. Administer high-dose systemic corticosteroids, and if appropriate, initiate hormone replacement therapy. When toxicity improves to grade 1 or less, initiate a corticosteroid taper. Resume avelumab treatment with complete or partial response to grade 0 or 1 after corticosteroid taper.
Life-threatening reactions (excluding endocrinopathies), recurrent severe immune-mediated reactions, or persistent grade 2 or 3 immune-mediated reactions lasting 12 weeks or longer, or requirement for ≥10 mg/day prednisone in adults (or equivalent) for >12 weeks: Discontinue permanently. If appropriate, administer high-dose systemic corticosteroids followed by a corticosteroid taper.
Children ≥12 years and Adolescents:
Renal impairment prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically meaningful differences were observed in a population pharmacokinetic analysis in patients with CrCl 15 to 89 mL/minute.
Renal toxicity during treatment (nephritis and renal dysfunction):
Serum creatinine >1.5 to 6 times ULN: Withhold treatment. Administer high-dose systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent, followed by a taper). Resume avelumab treatment with complete or partial resolution to grade 0 or 1 after corticosteroid taper.
Serum creatinine >6 times ULN: Discontinue permanently. Administer high-dose systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper.
Children ≥12 years and Adolescents:
Hepatic impairment prior to treatment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically meaningful differences were observed in a population pharmacokinetic analysis in patients with mild (bilirubin ≤ ULN and AST > ULN or bilirubin between 1 to 1.5 times ULN) or moderate (bilirubin between 1.5 to 3 times ULN) impairment. Limited data is available in patients with severe (bilirubin >3 times ULN) impairment.
Hepatotoxicity during treatment (hepatitis):
AST or ALT >3 to 5 times ULN or total bilirubin >1.5 to 3 times ULN: Withhold treatment. Administer high-dose systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent, followed by a taper). Resume avelumab treatment with complete or partial resolution to grade 0 or 1 after corticosteroid taper.
AST or ALT >5 times ULN or total bilirubin >3 times ULN: Discontinue permanently. Administer high-dose systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Edema (17%), hypertension (11%)
Dermatologic: Pruritus (16%), skin rash (25%)
Endocrine & metabolic: Weight loss (16%)
Gastrointestinal: Abdominal pain (16%), constipation (22%), decreased appetite (18%), diarrhea (21%; grades 3/4: 1%), increased serum lipase (21%), nausea (23%), vomiting (12%; grades 3/4: 1%)
Genitourinary: Urinary tract infection (≥20%; including urinary tract infection with sepsis)
Hematologic & oncologic: Decreased hemoglobin (40%; grades 3/4: 6%), decreased platelet count (23%; grades 3/4: 2%), lymphocytopenia (51%; grades 3/4: 16%)
Hepatic: Increased serum alanine aminotransferase (22%), increased serum aspartate aminotransferase (31%)
Hypersensitivity: Infusion-related reaction (26%; serious infusion-related reaction: ≥2%)
Immunologic: Antibody development (8% to 18%)
Nervous system: Fatigue (47%; including asthenia)
Neuromuscular & skeletal: Arthralgia (13%), musculoskeletal pain (29%)
Respiratory: Cough (22%), dyspnea (15%)
1% to 10%:
Dermatologic: Dermatological reaction (6%)
Endocrine & metabolic: Dehydration (≥2%), hyponatremia (≥2%), hypothyroidism (5%)
Gastrointestinal: Colitis (2%), intestinal obstruction (≥2%)
Genitourinary: Hematuria (≥2%), urinary tract hemorrhage (≥2%)
Hepatic: Hepatitis (1%)
Infection: Sepsis (≥2%)
Nervous system: Dizziness (<10%), headache (<10%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (<10%)
Renal: Acute kidney injury (≥2%), increased serum creatinine (≥2%), interstitial nephritis (<10%), kidney failure (≥2%)
Respiratory: Pneumonitis (1%)
Miscellaneous: Fever (≥2%)
<1%:
Cardiovascular: Myocarditis, pericarditis, vasculitis
Endocrine & metabolic: Adrenocortical insufficiency, hyperthyroidism, hypoparathyroidism, pituitary insufficiency, thyroiditis, type 1 diabetes mellitus
Gastrointestinal: Duodenitis, gastritis, increased serum amylase, pancreatitis
Hematologic & oncologic: Aplastic anemia, hemolytic anemia, hemophagocytic lymphohistiocytosis, immune thrombocytopenia, lymphadenitis (histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis])
Immunologic: Organ transplant rejection (solid), sarcoidosis
Infection: Systemic inflammatory response syndrome
Nervous system: Demyelinating disease, encephalitis, Guillain-Barré syndrome, meningitis, myasthenia (myasthenic syndrome), myasthenia gravis (including exacerbation of myasthenia gravis), neuropathy (autoimmune), paresis (nerve)
Neuromuscular & skeletal: Arthritis, myelitis, myositis, polymyalgia rheumatica, polymyositis, rhabdomyolysis
Renal: Nephritis
Frequency not defined: Respiratory: Nasopharyngitis, pulmonary infection
Postmarketing:
Dermatologic: Pemphigoid (SITC [Brahmer 2021]), Stevens-Johnson syndrome (SITC [Brahmer 2021]), toxic epidermal necrolysis (SITC [Brahmer 2021])
Endocrine & metabolic: Hypophysitis (SITC [Brahmer 2021])
Gastrointestinal: Cholangitis (SITC [Brahmer 2021]), cholecystitis (SITC [Brahmer 2021]), esophagitis (SITC [Brahmer 2021]), xerostomia (SITC [Brahmer 2021])
Hematologic & oncologic: Pure red cell aplasia (SITC [Brahmer 2021])
Hepatic: Hepatotoxicity (Chalasani 2021)
Immunologic: Sjögren disease (SITC [Brahmer 2021])
Neuromuscular & skeletal: Myalgia (SITC [Brahmer 2021])
Ophthalmic: Dry eye syndrome (SITC [Brahmer 2021]), uveitis (SITC [Brahmer 2021])
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to avelumab or any component of the formulation.
Concerns related to adverse effects:
• Adverse reactions (immune mediated): PD-1/PD-L1 blockers (including avelumab) remove immune response inhibition, thus potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Severe and fatal immune-mediated adverse reactions may occur in any organ system or tissue. Reactions generally occur during treatment (may occur at any time after avelumab initiation); reactions may also occur after avelumab discontinuation. Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of avelumab. If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection). Medically manage immune-mediated adverse reactions promptly and refer for specialty consultation as appropriate.
• Cardiovascular events: Myocarditis, pericarditis, and vasculitis have been observed with avelumab monotherapy. Avelumab/axitinib combination therapy (for advanced renal cell carcinoma) may cause severe and fatal cardiovascular events. Major adverse cardiovascular events occurred in a small percentage of patients who received avelumab/axitinib combination therapy; death due to cardiac events (including grade 3 or 4 myocardial infarction and heart failure) was reported (rare). The median time to onset of major cardiac event was 4.2 months (range: 2 days to 24.5 months). Optimize management of cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia). Discontinue avelumab and axitinib for grade 3 or 4 cardiovascular events.
• Dermatologic toxicity: Avelumab may cause immune-mediated rash or dermatitis. Immune-mediated dermatologic adverse reactions (including grade 2 and 3 events) occurred with avelumab. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis has occurred with other anti-PD-L1/PD-1 monoclonal antibodies. Mild to moderate nonbullous/exfoliative rashes may be managed with topical emollients and/or topical corticosteroids. Immune-mediated dermatologic reactions were treated with systemic corticosteroids in one-fourth of patients, and dermatologic adverse reactions resolved in almost half of patients. Some patients reinitiated avelumab after therapy interruption; dermatologic adverse reactions did not recur in these patients.
• Endocrinopathies: Avelumab is associated with immune-mediated endocrinopathies.
- Adrenal insufficiency: Adrenal insufficiency (primary or secondary) may occur. Grade 2 and 3 events have been reported (rare). Initiate symptomatic treatment, including hormone replacement, as clinically necessary for ≥ grade 2 adrenal insufficiency. Systemic corticosteroids were administered for adrenal insufficiency; resolution occurred in some patients. Avelumab therapy was withheld in some patients, and was not reinitiated. Withhold avelumab for adrenal insufficiency, depending on the severity.
- Diabetes mellitus: Type 1 diabetes mellitus has occurred (which may present with diabetic ketoacidosis), including grade 3 events. Insulin or other anti-hyperglycemic therapy may be required. Depending on the severity, withhold avelumab. Systemic corticosteroids were not administered for the management of diabetes mellitus; diabetes did not resolve in any patient (ongoing insulin treatment was necessary).
- Hypophysitis: Avelumab has been associated with immune-mediated hypophysitis, which may present with acute mass effect symptoms, including headache, photophobia, or visual field defects. Hypophysitis may lead to hypopituitarism. Initiate hormone replacement as clinically indicated and, depending on the severity, withhold or permanently discontinue avelumab. Immune-mediated pituitary disorders occurred rarely in patients receiving avelumab, and did not require avelumab interruption or systemic corticosteroids.
- Thyroid disorders: Immune-mediated thyroid disorders have occurred. Depending on severity, immune-mediated thyroid disorders may require treatment interruption or permanent discontinuation. Administer medical management for hyperthyroidism as appropriate. Systemic corticosteroids were required in over one-fourth of patients with hyperthyroidism. Resolution occurred in the majority of patients with hyperthyroidism. In cases where avelumab was withheld due to hyperthyroidism, some patients reinitiated therapy following symptom improvement; hyperthyroidism did not recur in those patients. Hypothyroidism has occurred, including grade 2 and 3 cases. Hypothyroidism may follow hyperthyroidism. Manage hypothyroidism with hormone replacement therapy. Systemic corticosteroids were required in some patients; hypothyroidism resolved in a small percentage of patients. Avelumab was not reinitiated in cases where it was withheld due to hypothyroidism. Thyroiditis may present with or without endocrinopathy. Thyroiditis occurred rarely, and did not result in permanent discontinuation or therapy interruption of avelumab. Patients did not require systemic corticosteroids, but thyroiditis did not resolve in any patient.
• GI adverse effects: Immune-mediated colitis has occurred, including grades 2 and 3 events. Diarrhea is the primary colitis symptom. Colitis has led to avelumab treatment interruption or discontinuation. Systemic corticosteroids were administered for immune-mediated colitis; more than two-thirds of patients with colitis experienced resolution. In cases where avelumab was withheld for colitis, some patients reinitiated treatment after symptom improvement; 40% had colitis recurrence. Cytomegalovirus infection or reactivation has been observed in patients with corticosteroid-refractory immune-mediated colitis. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.
• Hepatotoxicity: Immune-mediated hepatitis has occurred with avelumab monotherapy, including fatal cases. Hepatitis has led to avelumab treatment interruption or discontinuation. Systemic corticosteroids were used to manage immune-mediated hepatitis; resolution occurred in over half of patients. In cases where avelumab was withheld for hepatitis, some patients reinitiated treatment after symptom improvement with some patients experiencing recurrence of hepatitis. Avelumab in combination with axitinib (for advanced renal cell carcinoma) may cause hepatotoxicity with higher than expected frequencies of grade 3 and 4 ALT and AST elevations (compared to avelumab monotherapy). Most patients receiving combination therapy with grades 2 to 4 ALT elevations experienced resolution to grade 0 or 1. Among patients who were rechallenged with avelumab or axitinib either as monotherapy or with both, recurrence of ALT ≥3 times ULN occurred in some patients receiving axitinib monotherapy or combination therapy; the majority of patients subsequently recovered to grade 0 or 1. Immune-mediated hepatitis was reported in some patients receiving combination therapy, including grade 3 or 4 events. Most of these patients required systemic corticosteroids (rarely, a nonsteroidal immunosuppressant was necessary). Immune-mediated hepatitis resolution occurred in most patients receiving combination therapy.
• Infusion-related reactions: Infusion-related reactions (including severe and life-threatening cases) have occurred. Prior to the initial four infusions, premedicate with an antihistamine and acetaminophen. Signs/symptoms of a reaction included pyrexia, chills, wheezing, flushing, hypotension, dyspnea, back pain, abdominal pain, and urticaria. Some infusion-related reactions occurred after completion of the infusion. Interrupt or slow the rate of infusion for mild or moderate infusion-related reactions. Stop infusion and permanently discontinue avelumab for severe (grade 3) or life-threatening (grade 4) infusion-related reactions.
• Nephrotoxicity: Immune-mediated nephritis with kidney dysfunction has occurred (rarely), and led to permanent discontinuation of avelumab in 1 patient. Grade 2 and 3 events were observed. Nephritis was treated with systemic corticosteroids, and resolved in half of the patients who experienced it.
• Ocular toxicity: Immune-mediated uveitis, iritis, and other ocular inflammatory toxicities may occur with avelumab. Some cases can be associated with retinal detachment. Differing grades of visual impairment (including blindness) may occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.
• Pulmonary toxicity: Immune-mediated pneumonitis has been observed, including grade 2 to 4 and fatal cases. Pneumonitis was managed with systemic corticosteroids, and resolved in approximately half of the affected patients. In cases where avelumab was withheld for pneumonitis, all reinitiated avelumab after symptom improvement with no recurrence. Pneumonitis incidence is higher in patients who have received prior thoracic radiation.
• Other immune-mediated toxicities: Other clinically relevant immune-mediated disorders have been observed rarely with avelumab use (or with other anti-PD-L1/PD-1 monoclonal antibodies) and may affect any organ system (may be fatal), including meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy, myositis/polymyositis, rhabdomyolysis (and associated sequelae including kidney failure), arthritis, polymyalgia rheumatic, hypoparathyroidism, hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, and solid organ transplant rejection.
Disease-related concerns:
• Hematopoietic cell transplant: Fatal and other serious complications may occur in patients who received allogeneic hematopoietic cell transplant (HSCT) before or after treatment with an anti-PD-L1/PD-1 monoclonal antibody. Transplant-related complications may include hyperacute graft-versus-host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease (also known as sinusoidal obstruction syndrome) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (with no identified infectious etiology). These complications may occur despite intervening therapy between avelumab and HSCT. Manage early signs/symptoms of transplant-related complications promptly. Assess the risks/benefits of treatment with an anti-PD-L1/PD-1 monoclonal antibody prior to or after an allogenic HSCT.
• Myasthenia gravis: Checkpoint inhibitors may worsen or precipitate new myasthenia gravis (MG), especially within the first 16 weeks of treatment; use with caution. Patients with well-controlled MG may be considered for checkpoint inhibitor therapy if MG treatment is maintained (or reinitiated in patients whose MG is in remission), combination therapy (eg, anti–CTLA-4 with anti–PD-a/PD-L1 monoclonal antibodies) is avoided, and respiratory and bulbar function are closely followed. In patients who develop overt MG during checkpoint inhibitor therapy, early aggressive treatment with plasma exchange or IVIG in combination with high-dose corticosteroids may be required (AAN [Narayanaswami 2021]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Bavencio: 200 mg/10 mL (10 mL)
No
Solution (Bavencio Intravenous)
200 mg/10 mL (per mL): $225.56
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Bavencio: 200 mg/10 mL (10 mL)
IV: Infuse over 60 minutes through a 0.2 micron sterile, nonpyrogenic, low-protein binding inline filter. Do not infuse other medications through the same infusion line.
IV: Infuse over 60 minutes through a 0.2 micron sterile, nonpyrogenic, low-protein binding inline filter. Do not infuse other medications through the same infusion line.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761049s015lbl.pdf#page=36, must be dispensed with this medication.
Merkel cell carcinoma, metastatic: Treatment of metastatic Merkel cell carcinoma in adults and children ≥12 years of age.
Renal cell carcinoma, advanced: First-line treatment of advanced renal cell carcinoma (in combination with axitinib).
Urothelial carcinoma, locally advanced or metastatic:
First-line maintenance treatment of locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.
Treatment of locally advanced or metastatic urothelial carcinoma in previously treated 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.
Gestational trophoblastic neoplasia, chemotherapy-resistant
Avelumab may be confused with atezolizumab, durvalumab, emapalumab, nivolumab.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetaminophen: May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Antibiotics: May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Axitinib: May enhance the cardiotoxic effect of Avelumab. Axitinib may enhance the hepatotoxic effect of Avelumab. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modification
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Ketoconazole (Systemic): Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may enhance the hepatotoxic effect of Ketoconazole (Systemic). Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Patients who could become pregnant should use effective contraception during therapy and for at least 1 month after the last avelumab dose.
Immunoglobulins are known to cross the placenta and fetal exposure to avelumab is expected. Based on the mechanism of action, avelumab may cause fetal harm. Immune-mediated fetal rejection causing increased abortion or stillbirth was observed in animal reproduction studies.
It is not known if avelumab is present in breast milk.
According to the manufacturer, due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for at least 1 month after the last avelumab dose.
Liver (AST, ALT, and total bilirubin), kidney (creatinine), and thyroid function tests (at baseline, periodically during treatment, and as clinically indicated); blood glucose (for hyperglycemia). Monitor closely for signs/symptoms of immune-mediated adverse reactions, including diarrhea/colitis (consider initiating or repeating infectious work-up in patients with corticosteroid-refractory immune-mediated colitis to exclude alternative causes), thyroid disorders, pneumonitis, adrenal insufficiency, dermatologic toxicity, diabetes mellitus, hepatitis, ocular disorders, and other immune-mediated adverse reactions. Monitor for signs/symptoms of infusion-related reactions. If received/receiving hematopoietic cell transplant, monitor closely for early signs/symptoms of transplant-related complications.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Avelumab/axitinib combination therapy: Consider monitoring liver enzymes more frequently when avelumab is used in combination with axitinib Also consider baseline and periodic left ventricular ejection fraction evaluations and monitor for signs/symptoms of cardiovascular events.
Gestational trophoblastic neoplasia (off-label use): Assess human chorionic gonadotropin (hCG) weekly (You 2020).
Additional suggested monitoring (ASCO [Schneider 2021]): Prior to therapy: CBC with differential, serum chemistries, creatine kinase, comprehensive clinical assessment including performance status, weight, BMI, heart rate, BP, and oxygen saturation; consider chest x-ray, electrocardiogram, and CT scan; assess history of autoimmune conditions, organ-specific disease, endocrinopathies, neuropathy, and infectious disease; assess bowel habits, respiratory symptoms, skin (for rash), arthralgias, and neurologic symptoms. During therapy: Assess BP, weight, heart rate, and oxygen saturation; assess for infections, screen for hyperglycemia/diabetes (polyuria, polydipsia, weight loss); eye exam (including intraocular pressure after 6 weeks), CBC with differential, serum chemistries, and creatine kinase; monitor bone mineral density (with long-term therapy).
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Obtain baseline ECG, natriuretic peptides, and troponins in all patients; obtain a baseline echocardiogram in high-risk patients; consider serial ECGs and cardiac troponins prior to doses 2, 3, and 4, and if normal, reduce to every 3 doses until completion of therapy; cardiovascular risk assessment every 6 to 12 months in high-risk patients who require long-term (>12 months therapy, consider cardiovascular risk assessment every 6 to 12 months in all patients requiring long-term therapy) (ESC [Lyon 2022]). Refer to a cardiologist when clinically indicated.
Avelumab is a fully human monoclonal antibody that binds to programmed death ligand 1 (PD-L1) to selectively prevent the interaction between the programmed cell death-1 (PD-1) and B7.1 receptors, while still allowing interaction between PD-L2 and PD-1 (Kaufman 2016). PD-L1 is an immune check point protein expressed on tumor cells and tumor infiltrating cells and down regulates anti-tumor t-cell function by binding to PD-1 and B7.1; blocking PD-1 and B7.1 interactions restores antitumor t-cell function (Fehrenbacher 2016; Rosenberg 2016).
Distribution: Vdss: 4.72 L (10 mg/kg dose)
Half-life elimination: 6.1 days
Excretion: Total systemic clearance was 0.59 L/day in patients receiving a 10 mg/kg dose.
Clearance: In patients with advanced renal cell carcinoma, avelumab clearance was 15% higher in those who tested positive for treatment-emergent anti-drug antibodies (ADA) compared to those who tested negative for treatment-emergent ADA.
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