Version May 2024
Note: Per the manufacturer's labeling, atezolizumab may be dosed at 840 mg IV once every 2 weeks or 1,200 mg IV once every 3 weeks or 1,680 mg IV once every 4 weeks. Indication, combination, and/or trial-specific dosing is listed below; refer to protocols for further information.
Alveolar soft part sarcoma, unresectable or metastatic: IV: 1,200 mg once every 3 weeks (as a single agent); continue until disease progression or unacceptable toxicity (Ref).
Hepatocellular carcinoma, unresectable or metastatic: IV: 1,200 mg once every 3 weeks (in combination with bevacizumab); continue until disease progression or unacceptable toxicity; may continue beyond disease progression if clinical benefit demonstrated (Ref). If bevacizumab is discontinued due to unacceptable toxicity, may continue atezolizumab monotherapy (at any of the approved doses/intervals) until disease progression or unacceptable toxicity.
Melanoma, unresectable or metastatic (BRAF V600 mutation-positive): IV: 840 mg once every 2 weeks (in combination with cobimetinib and vemurafenib); continue until disease progression or unacceptable toxicity; prior to initiating atezolizumab, patients should receive a 28-day treatment cycle of cobimetinib and vemurafenib (Ref). Refer to protocol for further information.
Non–small cell lung cancer, adjuvant treatment: IV: 1,200 mg once every 3 weeks (as a single agent; after up to 4 cycles of adjuvant platinum-based chemotherapy) (Ref); continue atezolizumab for up to 1 year, unless disease recurrence or unacceptable toxicity occurs. Note: Select patients for atezolizumab therapy based on the programmed death-ligand 1 (PD-L1) expression on tumor cells.
Non–small cell lung cancer (NSCLC), metastatic:
Single-agent atezolizumab:
First-line treatment NSCLC: IV: 1,200 mg once every 3 weeks (Ref); continue until disease progression or unacceptable toxicity. Note: Select patients for atezolizumab therapy based on the PD-L1 expression on tumor cells or on tumor-infiltrating immune cells.
Previously treated NSCLC: IV: 1,200 mg once every 3 weeks; continue until disease progression or unacceptable toxicity (Ref).
Combination therapy:
First-line treatment, nonsquamous NSCLC:
IV: 1,200 mg on day 1 every 3 weeks (in combination with bevacizumab, paclitaxel, and carboplatin) for 4 to 6 cycles, followed by atezolizumab 1,200 mg on day 1 (followed by bevacizumab) every 3 weeks until disease progression or unacceptable toxicity (Ref); if bevacizumab is discontinued after the 4 to 6 cycles of combination chemotherapy, atezolizumab may be continued as a single agent (at any of the approved doses/intervals) until disease progression or unacceptable toxicity.
IV: 1,200 mg on day 1 every 3 weeks (in combination with paclitaxel [protein bound] and carboplatin) for 4 to 6 cycles (Ref); after the 4 to 6 cycles of induction combination chemotherapy, atezolizumab may be continued as a single agent (at any of the approved doses/intervals) until disease progression or unacceptable toxicity.
Small cell lung cancer (extensive stage), first-line treatment: IV: 1,200 mg once every 3 weeks (in combination with carboplatin and etoposide for 4 cycles) (Ref), followed by maintenance therapy of single-agent atezolizumab (at any of the approved doses/intervals) until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney impairment prior to treatment initiation:
eGFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; however, eGFR 30 to 89 mL/minute/1.73 m2 had no clinically significant effect on the systemic exposure of atezolizumab.
eGFR <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
Kidney toxicity during treatment:
Immune-mediated nephritis with kidney dysfunction: If atezolizumab 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 or lower, then follow with a corticosteroid taper.
Grade 2 or grade 3 serum creatinine elevation: Withhold atezolizumab; resume atezolizumab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper. Permanently discontinue atezolizumab 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 serum creatinine elevation: Permanently discontinue atezolizumab.
Hepatic impairment prior to treatment:
Mild (bilirubin ≤ ULN and AST > ULN or bilirubin >1 to 1.5 times ULN and any AST) or moderate (bilirubin >1.5 to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, mild or moderate impairment had no clinically significant effect on the systemic exposure of atezolizumab.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Hepatotoxicity during treatment:
If atezolizumab 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 or lower, then follow with a corticosteroid taper. Permanently discontinue atezolizumab 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.
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 atezolizumab treatment. Resume atezolizumab 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 atezolizumab 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 atezolizumab treatment. Resume atezolizumab treatment with complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper.
If AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN: Discontinue atezolizumab permanently.
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 atezolizumab is recommended. Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
Immune-mediated adverse reactions (general information): Withhold atezolizumab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue atezolizumab 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 atezolizumab 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 or lower, 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 check point 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 |
Atezolizumab dosage modification |
|---|---|---|
|
a ASCO (Schneider 2021). | ||
|
b CK = creatinine kinase; DRESS = drug rash with eosinophilia and systemic symptoms; NSAIDs = nonsteroidal anti-inflammatory drugs; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis. | ||
|
c 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, pericarditis, arrhythmias, impaired ventricular function with heart failure, and vasculitisa |
Grade 1 |
Obtain cardiology consultation for work-up and guideline-based interventiona. Withhold atezolizumab for grade 1 elevated troponin; recheck in 6 hours. May resume therapy once normalized if not related to atezolizumaba. |
|
Grade 2, 3, or 4 |
Permanently discontinue atezolizumab. | |
|
Dermatologic toxicity |
Mild or moderate nonexfoliative rash |
May be managed with topical emollients and/or topical corticosteroids. |
|
Exfoliative dermatologic conditions: Suspected SJS, TEN, or DRESSb |
Withhold atezolizumab. | |
|
Confirmed SJS, TEN, or DRESS |
Permanently discontinue atezolizumab. | |
|
Endocrinopathies |
Grade 3 or 4 |
Withhold atezolizumab 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. Long-term insulin therapy may be required. | |
|
Hypophysitis |
Withhold or discontinue atezolizumab (depending on severity). Initiate hormone replacement therapy as clinically indicated. | |
|
Hyperthyroidism |
Administer medical management as clinically indicated. | |
|
Hypothyroidism |
Initiate thyroid hormone replacement therapy as clinically indicated. | |
|
GI toxicity: Colitis |
Grade 2 or 3 |
Withhold atezolizumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperc. Permanently discontinue atezolizumab 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 atezolizumab. | |
|
Neurologic toxicities |
Grade 2 |
Withhold atezolizumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperc. Permanently discontinue atezolizumab 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 atezolizumab. | |
|
Neuromuscular/skeletal: Myositis |
Grade 1 |
Continue treatment. May consider acetaminophen or NSAIDsb for analgesia (if no contraindications); consider withholding statins. If CKb is elevated and patient has muscle weakness, consider oral corticosteroids (prednisone 0.5 mg/kg/day).a |
|
Grade 2 |
Temporarily withhold treatment. Administer NSAIDs as needed. Refer to rheumatologist or neurologist for work-up. If CK is elevated ≥3 times, initiate corticosteroids (prednisone at 0.5 to 1 mg/kg/day [or equivalent]). May resume atezolizumab upon symptom control, if CK is normal, and if prednisone dose is <10 mg/day. If other objective findings of severe muscle involvement or extensive involvement (very elevated enzymes, abnormal electromyography, abnormal muscle MRI or biopsy) may require permanent discontinuation.a | |
|
Grade 3 or 4 |
Withhold treatment. Initiate corticosteroids (prednisone 1 mg/kg/day [or equivalent]); if severely compromised, initiate IV methylprednisolone 1 to 2 mg/kg or higher dose bolus. Refer to rheumatologist or neurologist for work-up. Consider hospitalization for severe weakness. Consider plasmapheresis in patients with acute or severe disease or IV immunoglobulin therapy. If symptoms and CK levels do not improve or worsen after 2 weeks or if symptoms and CK levels do not resolve completely after 4 weeks, consider other immunosuppressant therapy (eg, methotrexate, azathioprine, mycophenolate mofetil). Consider permanent atezolizumab discontinuation.a | |
|
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 atezolizumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperc. Permanently discontinue atezolizumab 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 atezolizumab. | |
|
Other adverse reactions | ||
|
Infusion reactions |
Grade 1 or 2 |
Interrupt or slow the rate of atezolizumab infusion. Consider premedications with subsequent doses. |
|
Grade 3 or 4 |
Permanently discontinue atezolizumab. | |
Refer to adult dosing.
(For additional information see "Atezolizumab: Pediatric drug information")
Alveolar soft part sarcoma, unresectable or metastatic: Children ≥2 years and Adolescents: IV: 15 mg/kg/dose every 3 weeks; maximum dose: 1,200 mg/dose; continue until disease progression or unacceptable toxicity.
Dosing adjustment for toxicity:
Children ≥2 years and Adolescents: IV: No dose reduction for atezolizumab is recommended. Other concomitant combination therapy medications may also require treatment interruption, dosage reduction, and/or discontinuation.
Immune-mediated adverse reactions (general information): Withhold atezolizumab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue atezolizumab 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 in adults (or equivalent) within 12 weeks of initiating corticosteroids. If atezolizumab 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 or lower, 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: Based on experience in adult patients, 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 |
Atezolizumab Dosage Modification |
|---|---|---|
|
a DRESS = drug rash with eosinophilia and systemic symptoms; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis. | ||
|
Immune-mediated adverse reactions | ||
|
Cardiovascular toxicity: Myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, and vasculitis |
Grade 2, 3, or 4 |
Permanently discontinue atezolizumab. |
|
Dermatologic toxicity |
Mild or moderate nonexfoliative rash |
May be managed with topical emollients and/or topical corticosteroids. |
|
Exfoliative dermatologic conditions: Suspected SJS, TEN, or DRESSa |
Withhold atezolizumab. | |
|
Confirmed SJS, TEN, or DRESS |
Permanently discontinue atezolizumab. | |
|
Endocrinopathies |
Grade 3 or 4 |
Withhold atezolizumab 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; DKA |
Initiate insulin as clinically indicated. Long-term insulin therapy may be required. | |
|
Hypophysitis |
Initiate hormone replacement therapy as clinically indicated. | |
|
Hyperthyroidism |
Administer medical management as clinically indicated. | |
|
Hypothyroidism |
Initiate thyroid hormone replacement therapy as clinically indicated. | |
|
GI toxicity: Colitis |
Grade 2 or 3 |
Withhold atezolizumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper. Permanently discontinue atezolizumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day in adults (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 4 |
Permanently discontinue atezolizumab. | |
|
Neurologic toxicities |
Grade 2 |
Withhold atezolizumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper. Permanently discontinue atezolizumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day in adults (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 3 or 4 |
Permanently discontinue atezolizumab. | |
|
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 atezolizumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper. Permanently discontinue atezolizumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day in adults (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 3 or 4 |
Permanently discontinue atezolizumab. | |
|
Other adverse reactions | ||
|
Infusion reactions |
Grade 1 or 2 |
Interrupt or slow the rate of atezolizumab infusion. Consider premedications with subsequent doses. |
|
Grade 3 or 4 |
Permanently discontinue atezolizumab. | |
Children ≥2 years and Adolescents: IV:
Baseline kidney impairment:
eGFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; however, eGFR 30 to 89 mL/minute/1.73 m2 had no clinically significant effect on the systemic exposure of atezolizumab.
eGFR <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
Kidney toxicity during treatment:
Immune-mediated nephritis with kidney dysfunction: If atezolizumab 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 or lower, then initiate corticosteroid taper and continue to taper over at least 1 month.
Grade 2 or grade 3 serum creatinine elevation: Withhold atezolizumab; resume atezolizumab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper. Permanently discontinue atezolizumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day in adults (or equivalent) within 12 weeks of corticosteroid initiation.
Grade 4 serum creatinine elevation: Permanently discontinue atezolizumab.
Children ≥2 years and Adolescents: IV:
Baseline hepatic impairment:
Mild impairment (bilirubin ≤ ULN and AST > ULN or bilirubin >1 to 1.5 times ULN and any AST) or moderate impairment (bilirubin >1.5 to 3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling; however, mild or moderate impairment had no clinically significant effect on the systemic exposure of atezolizumab.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Hepatotoxicity during treatment:
If atezolizumab 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 or lower, then initiate corticosteroid taper and continue to taper over at least 1 month.
Immune-mediated hepatitis without tumor involvement of the liver:
AST or ALT >3 up to 8 times ULN or total bilirubin >1.5 to 3 times ULN: Withhold atezolizumab treatment. Resume atezolizumab treatment with complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper. Permanently discontinue atezolizumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day in adults (or equivalent) within 12 weeks of corticosteroid initiation.
AST or ALT >8 times ULN or total bilirubin >3 times ULN: Discontinue atezolizumab 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 to 3 times ULN and increases to >5 to 10 times ULN or baseline AST or ALT >3 to 5 times ULN and increases to >8 to 10 times ULN: Withhold atezolizumab treatment. Resume atezolizumab treatment with complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper. Permanently discontinue atezolizumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day in adults (or equivalent) within 12 weeks of corticosteroid initiation.
If AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN: Discontinue atezolizumab permanently.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults administered monotherapy atezolizumab for non-small cell lung cancer (NSCLC), unless otherwise noted.
>10%:
Dermatologic: Skin rash (12% to 17%)
Endocrine & metabolic: Hyperkalemia (24% to 29%), hypoalbuminemia (48%), hypocalcemia (24%), hypomagnesemia (26%), hyponatremia (42% to 44%), hypophosphatemia (23% to 27%), hypothyroidism (14% to 17%)
Gastrointestinal: Constipation (12% to 18%), decreased appetite (15% to 23%), diarrhea (11% to 16%; grades 3/4: <1%), nausea (14% to 18%; grades 3/4: <1%)
Hematologic & oncologic: Anemia (67% to 69%; grades 3/4: 2% to 3%), lymphocytopenia (47% to 49%; grades 3/4: 9% to 14%)
Hepatic: Increased serum alanine aminotransferase (27% to 38%), increased serum alkaline phosphatase (39% to 46%), increased serum aspartate aminotransferase (31% to 36%)
Immunologic: Antibody development (13% to 36%; incidence may be reported from studies with concomitant chemotherapies and various indications)
Nervous system: Asthenia (≤44%), fatigue (≤44%), peripheral neuropathy (12%; grades 3/4: <1%)
Neuromuscular & skeletal: Arthralgia (11% to 12%), musculoskeletal pain (≤20%), myalgia (≤20%)
Renal: Increased serum creatinine (23% to 31%)
Respiratory: Cough (12% to 26%), dyspnea (14% to 22%)
Miscellaneous: Fever (14% to 18%)
1% to 10%:
Dermatologic: Pruritus (10%)
Endocrine & metabolic: Adrenocortical insufficiency (1%), hyperthyroidism (6%), thyroiditis (1%)
Gastrointestinal: Colitis (1%)
Hepatic: Hepatitis (2%)
Hypersensitivity: Infusion-related reaction (including severe infusion-related reactions: 1%)
Respiratory: Pneumonia (serious: 2% to 3%), pneumonitis (2% to 4%)
<1%:
Cardiovascular: Myocarditis, pericarditis, vasculitis
Dermatologic: Dermatological reaction (including dermatitis)
Endocrine & metabolic: Hypoparathyroidism, hypophysitis, type 1 diabetes mellitus
Gastrointestinal: Duodenitis, gastritis, increased serum amylase, increased serum lipase, 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-Barre syndrome, meningitis, myasthenia (myasthenic syndrome), myasthenia gravis (including exacerbation of myasthenia gravis), neuropathy (autoimmune), paresis (nerve)
Neuromuscular & skeletal: Myelitis, myositis, polymyositis, rhabdomyolysis
Ophthalmic: Iritis, uveitis
Renal: Nephritis
Frequency not defined:
Cardiovascular: Pulmonary embolism
Infection: Infection, sepsis
Nervous system: Headache
Neuromuscular & skeletal: Back pain
Respiratory: Chronic obstructive pulmonary disease, pleural effusion, respiratory tract infection
Postmarketing (any indication):
Gastrointestinal: Cholangitis (SITC [Brahmer 2021]), cholecystitis (SITC [Brahmer 2021]), esophagitis (SITC [Brahmer 2021]), xerostomia (SITC [Brahmer 2021])
Hematologic & oncologic: Neutropenia (SITC [Brahmer 2021]), pure red cell aplasia (SITC [Brahmer 2021])
Hepatic: Hepatotoxicity (Chalasani 2021)
Immunologic: Sjögren disease (SITC [Brahmer 2021])
Ophthalmic: Dry eye syndrome (SITC [Brahmer 2021])
Renal: Acute kidney injury (SITC [Brahmer 2021])
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to atezolizumab or any component of the formulation.
Concerns related to adverse effects:
• Adverse reactions (immune mediated): PD-1/PD-L1 blockers (including atezolizumab) 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 atezolizumab initiation); reactions may also occur after atezolizumab discontinuation. Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of atezolizumab. 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 toxicity: Myocarditis has been reported with atezolizumab (case reports); may be related to the mechanism of action and/or may be immune-mediated. May require treatment interruption, discontinuation, systemic corticosteroids, and/or other immunosuppressive therapy (ASCO [Schneider 2021]; Perez 2017). Pericarditis and vasculitis have also been reported.
• Dermatologic toxicity: Atezolizumab may cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis has occurred with anti-PD-1/PD-L1 monoclonal antibodies. Immune-mediated dermatologic adverse reactions (including grade 2 and 3 events) occurred with atezolizumab monotherapy. Immune-mediated dermatologic reactions were treated with systemic corticosteroids in some patients, and reactions resolved in the majority of cases, although atezolizumab was not reinitiated following treatment interruption.
• Endocrinopathies: Atezolizumab is associated with immune-mediated endocrinopathies.
– Adrenal insufficiency: Adrenal insufficiency (primary or secondary) may occur. Grade 2 and 3 events have been reported (rare). Systemic corticosteroids were usually administered for adrenal insufficiency; some patients remained on corticosteroid therapy.
– Diabetes mellitus: Type 1 diabetes mellitus has occurred (which may present with diabetic ketoacidosis), including grade 3 events. Insulin therapy may be required.
– Hypophysitis: Atezolizumab 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. Systemic corticosteroids were required in 50% of patients with hypophysitis; hypophysitis did not resolve in some cases.
– Thyroid disorders: Immune-mediated thyroid disorders have occurred. Depending on severity, immune-mediated thyroid disorders may require treatment interruption or permanent discontinuation. Antithyroid medication was administered in some patients with hyperthyroidism, and most patients remained on antithyroid treatment. In cases where atezolizumab was withheld due to hyperthyroidism, some patients reinitiated therapy following symptom improvement; hyperthyroidism recurred in some patients. Hypothyroidism has occurred, including grade 2, 3, and 4 cases. Hypothyroidism may follow hyperthyroidism. Hormone replacement therapy was required in the majority of patients with hypothyroidism and was continued in most cases. Thyroiditis may present with or without endocrinopathy. Thyroiditis occurred rarely. Hormone replacement therapy was required in 75% of patients; systemic corticosteroids were administered in some patients. Thyroiditis resolved in 50% of patients.
• GI adverse effects: Immune-mediated colitis (including grade 2 and 3 cases) has occurred with atezolizumab when administered as a single agent and may present with diarrhea, abdominal pain, and lower GI bleeding. Colitis has led to atezolizumab treatment interruption or discontinuation. Systemic corticosteroids were administered for immune-mediated colitis in 50% of patients; ~75% of patients with colitis experienced resolution. In cases where atezolizumab was withheld for colitis, some patients reinitiated treatment after symptom improvement; 25% had colitis recurrence. Cytomegalovirus infection or reactivation has been observed in patients with corticosteroid-refractory immune-mediated colitis. Consider initiating or repeating infectious workup in patients with corticosteroid-refractory immune-mediated colitis to exclude alternative causes. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.
• Hepatotoxicity: Immune-mediated hepatitis has occurred with atezolizumab when administered as a single agent and in combination with other anticancer agents, including grade 2 to 4 and fatal cases. Hepatitis has led to atezolizumab treatment interruption or discontinuation. Systemic corticosteroids were used to manage immune-mediated hepatitis in some cases; resolution occurred in ~50% to 90% of patients. In cases where atezolizumab was withheld for hepatitis, some patients reinitiated treatment after symptom improvement with recurrence of hepatitis in some cases.
• Infusion-related reactions: Severe or life-threatening infusion reactions have been reported with atezolizumab. The frequency and severity of infusion reactions was similar whether atezolizumab was administered as a single agent or in combination with other anticancer agents and was similar across the various approved dose/frequency ranges.
• Nephrotoxicity: Immune-mediated nephritis with renal dysfunction has occurred (rarely) with atezolizumab when used as monotherapy or in combination with other anticancer agents. Nephritis has led to atezolizumab treatment interruption or discontinuation. Nephritis was treated with systemic corticosteroids in a majority of patients and resolved in cases where corticosteroids were utilized. In cases where atezolizumab was withheld for nephritis, recurrence did not occur upon treatment reinitiation after symptom improvement.
• Ocular toxicity: Uveitis, iritis, and other ocular inflammatory adverse events have been reported. Some cases may be associated with retinal detachment. Visual impairment of varying grades (including blindness) may occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome.
• Pulmonary toxicity: Immune-mediated pneumonitis, including grades 2 to 4 and fatal cases, has been reported in patients receiving atezolizumab (as a single agent and in combination with other anticancer agents). Pneumonitis was managed with systemic corticosteroids in over half of cases and resolved in the majority of affected patients. In cases where atezolizumab was withheld for pneumonitis, atezolizumab was reinitiated in some patients after symptom improvement; pneumonitis recurred in some cases. Pneumonitis occurred more frequently in patients with a history of prior thoracic radiation.
• Other immune-mediated toxicities: Other clinically relevant immune-mediated disorders have been observed rarely with atezolizumab use (or 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 renal 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 stem cell transplant: Fatal and other serious complications may occur in patients who received allogeneic hematopoietic stem 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 atezolizumab and HSCT. Mange 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]).
Other warnings/precautions:
• Appropriate use: For first-line treatment of metastatic NSCLC (as a single agent), select patients for atezolizumab therapy based on the PD-L1 expression on tumor cells or on tumor-infiltrating immune cells; for adjuvant treatment of stage II to IIIA NSCLC (as a single agent), select patients for atezolizumab therapy based on the PD-L1 expression on tumor cells. For unresectable or metastatic melanoma, select patients for atezolizumab therapy based on the presence of a BRAF V600 mutation. Information on approved tests is available at http://www.fda.gov/companiondiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Tecentriq: 840 mg/14 mL (14 mL); 1200 mg/20 mL (20 mL)
No
Solution (Tecentriq Intravenous)
840 mg/14 mL (per mL): $636.36
1200 mg/20 mL (per mL): $636.35
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Tecentriq: 840 mg/14 mL (14 mL); 1200 mg/20 mL (20 mL)
IV: Infuse the initial dose over 60 minutes, if tolerated, may infuse subsequent doses over 30 minutes. May be infused with or without a 0.2- to 0.22-micron sterile, non-pyrogenic, low-protein binding in-line filter. Do not administer as an IV push or bolus. Do not administer other medications at the same time through the same IV line.
Monitor for infusion reactions. Interrupt or slow the infusion for grade 1 or 2 infusion-related reactions (and consider premedications with subsequent infusions); permanently discontinue for grade 3 or 4 infusion-related reactions.
When administering in combination with other chemotherapy agents and/or bevacizumab on the same day, administer atezolizumab prior to chemotherapy and/or bevacizumab.
Parenteral: IV: May be infused with or without a 0.2- to 0.22-micron sterile, non-pyrogenic, low-protein binding in-line filter. Do not administer as an IV push or bolus. Do not administer other medications at the same time through the same IV line. Monitor for infusion reactions. Interrupt or slow the infusion for grade 1 or 2 infusion-related reactions (and consider premedications with subsequent infusions); permanently discontinue for grade 3 or 4 infusion-related reactions.
Initial dose: Infuse dose over 60 minutes. Monitor for infusion reactions.
Subsequent doses: If initial dose tolerated without infusion reaction, may infuse dose over 30 minutes.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Tecentriq: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761034s049s051lbl.pdf#page=62
Alveolar soft part sarcoma, unresectable or metastatic: Treatment of unresectable or metastatic alveolar soft part sarcoma in adult and pediatric patients ≥2 years of age.
Hepatocellular carcinoma, unresectable or metastatic: Treatment of unresectable or metastatic hepatocellular carcinoma (in combination with bevacizumab) in adults who have not received prior systemic therapy.
Melanoma, unresectable or metastatic: Treatment of BRAF V600 mutation-positive unresectable or metastatic melanoma (in combination with cobimetinib and vemurafenib) in adults.
Non–small cell lung cancer:
Adjuvant treatment (as a single agent) following resection and platinum-based chemotherapy in adults with stage II to IIIA non–small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥1% of tumor cells, as determined by an approved test.
First-line treatment (single agent) of metastatic NSCLC in adults whose tumors have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells [TC ≥50%] or PD-L1 stained tumor-infiltrating IC covering ≥10%), as determined by an approved test, with no epidermal growth factor receptor (EGFR) or ALK genomic tumor aberrations.
First-line treatment (in combination with bevacizumab, paclitaxel, and carboplatin) of metastatic nonsquamous NSCLC in adults with no EGFR or ALK genomic tumor aberrations.
First-line treatment (in combination with paclitaxel [protein bound] and carboplatin) of metastatic nonsquamous NSCLC in adults with no EGFR or ALK genomic tumor aberrations.
Treatment (single agent) of metastatic NSCLC in adults with disease progression during or following platinum-containing chemotherapy (patients with EGFR or ALK genomic aberrations should have disease progression on approved therapy for EGFR or ALK genomic tumor mutations prior to receiving atezolizumab).
Small cell lung cancer, extensive stage: First-line treatment of extensive-stage small cell lung cancer in adults (in combination with carboplatin and etoposide).
Atezolizumab may be confused with alemtuzumab, avelumab, durvalumab, nivolumab, pembrolizumab.
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
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
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
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
Verify pregnancy status prior to treatment initiation in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for at least 5 months after the last atezolizumab dose.
Based on the mechanism of action, atezolizumab is expected to cause fetal harm if used during pregnancy.
It is not known if atezolizumab is present in breast milk; however, IgG immunoglobulins are found in milk.
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 5 months after the last atezolizumab dose.
PD-L1 expression status (in patients with non–small cell lung cancer [NSCLC] [first-line, single-agent therapy for metastatic NSCLC or for adjuvant treatment]); BRAF V600 mutation status (in patients with unresectable or metastatic melanoma). Monitor LFTs (AST, ALT, and bilirubin; at baseline and periodically during treatment), serum creatinine (at baseline and periodically during treatment), thyroid function (prior to and periodically during treatment), monitor serum glucose (for hyperglycemia). Evaluate pregnancy status (prior to treatment initiation in patients who could become pregnant). Monitor closely for signs/symptoms of immune-mediated adverse reactions, including diarrhea/colitis (consider initiating or repeating infectious workup in patients with corticosteroid-refractory immune-mediated colitis to exclude alternative causes), diarrhea, endocrinopathies (adrenal insufficiency, diabetes, hypophysitis, thyroid disorders), hepatitis, cardiovascular toxicity (myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, and vasculitis), myositis, pneumonitis, dermatologic toxicity, and ocular toxicity. Monitor for signs/symptoms of infusion-related reactions. If received/receiving hematopoietic stem 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.
Additional suggested monitoring (ASCO [Schneider 2021): Prior to therapy: CBC with differential, serum chemistries, creatine kinase, comprehensive clinical assessment including performance status, weight, body mass index, heart rate, BP, and oxygen saturation; consider chest x-ray, ECG, 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.
Atezolizumab is a humanized monoclonal antibody immune checkpoint inhibitor 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 (also known as CD80) receptors, while still allowing interaction between PD-L2 and PD-1. PD-L1 is an immune checkpoint 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).
Immune checkpoint inhibition combined with the mitogen-activated protein kinase (MAPK) pathway increase antigen presentation and T-cell infiltration/activation to suppress tumor growth and improve tumor immunogenicity (when compared to targeted therapy alone).
Distribution: Vdss: 6.9 L
Half-life, elimination: 27 days
Excretion: Clearance: 0.2 L/day
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