Version July 2025
Dosage guidance:
Dosage form information: Atezolizumab/hyaluronidase is for SUBQ administration only. Do not substitute atezolizumab (IV) for atezolizumab/hyaluronidase (SUBQ). Use caution during product selection, preparation, and administration. Patients receiving atezolizumab (IV) may transition to atezolizumab/hyaluronidase (SUBQ) or vice versa (at the appropriate/recommended doses for each product) at the next scheduled dose.
Alveolar soft part sarcoma, unresectable or metastatic: SUBQ: Atezolizumab 1,875 mg/hyaluronidase 30,000 units once every 3 weeks, as a single agent; continue until disease progression or unacceptable toxicity.
Hepatocellular carcinoma, unresectable or metastatic: SUBQ: Atezolizumab 1,875 mg/hyaluronidase 30,000 units once every 3 weeks, in combination with bevacizumab; continue until disease progression or unacceptable toxicity. If bevacizumab is discontinued due to unacceptable toxicity, may continue atezolizumab/hyaluronidase, as a single agent, until disease progression or unacceptable toxicity.
Melanoma, unresectable or metastatic, BRAF V600 mutation positive: Note: Prior to initiating atezolizumab/hyaluronidase, administer a 28-day cycle of cobimetinib and vemurafenib.
SUBQ: Atezolizumab 1,875 mg/hyaluronidase 30,000 units once every 3 weeks, in combination with cobimetinib and vemurafenib; continue until disease progression or unacceptable toxicity.
Non–small cell lung cancer, stage II to IIIA, with PD-L1 expression (≥1%), adjuvant treatment:
SUBQ: Atezolizumab 1,875 mg/hyaluronidase 30,000 units once every 3 weeks, as a single agent; after up to 4 cycles of adjuvant platinum-based chemotherapy; continue atezolizumab/hyaluronidase for up to 1 year (16 cycles), unless disease recurrence or unacceptable toxicity occurs.
Non–small cell lung cancer (NSCLC), metastatic:
Single-agent atezolizumab/hyaluronidase:
NSCLC, with PD-L1 expression (PD-L1 stained ≥50% of tumor cells [TC ≥50%] or PD-L1 stained tumor-infiltrating immune cells covering ≥10% [IC ≥10%]), first-line treatment: SUBQ: Atezolizumab 1,875 mg/hyaluronidase 30,000 units once every 3 weeks; continue until disease progression or unacceptable toxicity.
NSCLC, previously treated: SUBQ: Atezolizumab 1,875 mg/hyaluronidase 30,000 units once every 3 weeks; continue until disease progression or unacceptable toxicity (Ref).
Combination therapy:
Nonsquamous NSCLC, first-line treatment:
SUBQ: Atezolizumab 1,875 mg/hyaluronidase 30,000 units once every 3 weeks, in combination with bevacizumab, carboplatin, and paclitaxel for up to 4 to 6 cycles (ABCP regimen), followed by atezolizumab/hyaluronidase and bevacizumab maintenance therapy every 3 weeks until disease progression or unacceptable toxicity.
SUBQ: Atezolizumab 1,875 mg/hyaluronidase 30,000 units once every 3 weeks, in combination with paclitaxel (protein bound) and carboplatin for 4 or 6 cycles, followed by atezolizumab/hyaluronidase maintenance, as a single agent, until disease progression or unacceptable toxicity.
Small cell lung cancer, extensive stage (first-line treatment): SUBQ: Atezolizumab 1,875 mg/hyaluronidase 30,000 units once every 3 weeks, in combination with carboplatin and etoposide for 4 cycles, followed by atezolizumab/hyaluronidase maintenance, as a single agent, 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.
Altered kidney function prior to treatment:
eGFR 30 to 89 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in atezolizumab pharmacokinetics were observed with mild or moderate altered kidney function.
eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (effect of severe kidney impairment is unknown).
Acute kidney toxicity during treatment:
Immune-mediated nephritis with kidney dysfunction:
Grade 2 or grade 3 serum creatinine elevation: Withhold atezolizumab/hyaluronidase treatment and initiate systemic corticosteroid therapy (prednisone 1 to 2 mg/kg/day [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions; resume atezolizumab/hyaluronidase treatment with complete or partial resolution of nephritis (to grade 0 or 1 serum creatinine elevation) after corticosteroid taper. Permanently discontinue atezolizumab/hyaluronidase if no complete or partial resolution within 12 weeks of corticosteroid initiation, 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/hyaluronidase. 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.
Altered liver function prior to treatment:
Mild (bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in atezolizumab pharmacokinetics were observed.
Severe impairment (total bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (effect of severe hepatic impairment is unknown).
Acute hepatotoxicity during treatment:
Immune-mediated hepatitis in patients 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/hyaluronidase treatment and initiate systemic corticosteroid therapy (prednisone 1 to 2 mg/kg/day [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions; resume atezolizumab/hyaluronidase treatment with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper. Permanently discontinue atezolizumab/hyaluronidase if no complete or partial resolution within 12 weeks of corticosteroid initiation, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
AST or ALT >8 times ULN or total bilirubin >3 times ULN: Permanently discontinue atezolizumab/hyaluronidase. 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.
Immune-mediated hepatitis in patients 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 is >1 up to 3 times ULN and increases to >5 up to 10 times ULN or baseline AST or ALT is >3 up to 5 times ULN and increases to >8 up to 10 times ULN: Withhold atezolizumab/hyaluronidase treatment and initiate systemic corticosteroid therapy (prednisone 1 to 2 mg/kg/day [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions; resume atezolizumab/hyaluronidase treatment with complete or partial resolution of hepatitis (to grade 0 or 1) after corticosteroid taper. Permanently discontinue atezolizumab/hyaluronidase if no complete or partial resolution within 12 weeks of corticosteroid initiation, or if unable to reduce prednisone to ≤10 mg/day (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: Permanently discontinue atezolizumab/hyaluronidase. 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.
Alternative recommendations (all patients):
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/day 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).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m 2: The dosing in the approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).
Note: No dose reduction for atezolizumab/hyaluronidase is recommended. Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
Immune-mediated adverse reactions (general information): Withhold atezolizumab/hyaluronidase for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue atezolizumab/hyaluronidase 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/hyaluronidase 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 immune checkpoint inhibitor therapy for most grade 2 toxicities and resume when symptoms and/or laboratory 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 immune checkpoint inhibitor therapy.
|
Adverse reaction |
Severity |
Atezolizumab/Hyaluronidase dosage modification |
|---|---|---|
|
a AIHA = autoimmune hemolytic anemia; CK = creatine kinase; NSAIDs = nonsteroidal anti-inflammatory drugs; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; DRESS = drug rash with eosinophilia and systemic symptoms. | ||
|
b ASCO (Schneider 2021). | ||
|
c Refer to prednisone monograph for tapering recommendations when used for immune-mediated adverse effects associated with immune checkpoint inhibitor therapy. | ||
|
d Myocarditis may also be a clinical manifestation of myositis and should be managed accordingly; patients with possible myositis should also be assessed for signs of myocarditis. | ||
|
Immune-mediated adverse reactions | ||
|
Cardiovascular toxicity: myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, and vasculitisb |
Grade 1 |
Obtain cardiology consultation for work-up and guideline-based intervention.b Withhold atezolizumab/hyaluronidase for grade 1 elevated troponin; recheck in 6 hours. May resume therapy once normalized if not related to atezolizumab/hyaluronidase.b |
|
Grade 2, 3, or 4 |
Permanently discontinue atezolizumab/hyaluronidase. | |
|
Dermatologic toxicity |
Mild or moderate nonexfoliative rash (grade 1 or 2) |
May be managed with topical emollients and/or topical corticosteroids; may add an oral antihistamine for grade 2 rash.b |
|
Exfoliative dermatologic conditions: suspected SJS, TEN, or DRESSa |
Refer to a specialist for further diagnosis and management. Withhold atezolizumab/hyaluronidase. | |
|
Exfoliative dermatologic conditions: confirmed SJS or TEN regardless of severity |
Permanently discontinue atezolizumab/hyaluronidase. | |
|
Endocrinopathies |
Grade 3 or 4 |
Withhold atezolizumab/hyaluronidase until clinically stable or permanently discontinue depending on severity. |
|
Adrenal insufficiency, ≥ grade 2 |
Initiate symptomatic treatment, including hormone replacement, as clinically indicated. Withhold or permanently discontinue atezolizumab/hyaluronidase depending on severity. | |
|
Diabetes, type 1 |
Initiate insulin as clinically indicated. Withhold or permanently discontinue atezolizumab/hyaluronidase depending on severity. | |
|
Hypophysitis |
Initiate corticosteroid and/or hormone replacement therapy as clinically indicated. Withhold or permanently discontinue atezolizumab/hyaluronidase depending on severity. | |
|
Hyperthyroidism, symptomatic |
Initiate medical management as clinically indicated. Withhold or permanently discontinue atezolizumab/hyaluronidase depending on severity. | |
|
Hypothyroidism, symptomatic |
Initiate thyroid hormone replacement therapy as clinically indicated. Withhold or permanently discontinue atezolizumab/hyaluronidase depending on severity. | |
|
GI toxicity: colitis |
Grade 2 or 3 |
Withhold atezolizumab/hyaluronidase and initiate corticosteroid therapy; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper.c Permanently discontinue atezolizumab/hyaluronidase if no complete or partial resolution within 12 weeks of corticosteroid initiation, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 4 |
Permanently discontinue atezolizumab/hyaluronidase. | |
|
Neurologic toxicity |
Grade 2 |
Withhold atezolizumab/hyaluronidase and initiate corticosteroid therapy; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper.c Permanently discontinue atezolizumab/hyaluronidase if no complete or partial resolution within 12 weeks of corticosteroid initiation, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grades 3 or 4 |
Permanently discontinue atezolizumab/hyaluronidase. | |
|
Neuromuscular/Skeletal toxicity: myositisd |
Grade 1 |
Continue atezolizumab/hyaluronidase treatment. May consider acetaminophen or NSAIDs for analgesia (if no contraindications); consider withholding statins. If CK is elevated and patient has muscle weakness, consider oral corticosteroids (prednisone 0.5 mg/kg/day).b |
|
Grade 2 |
Temporarily withhold atezolizumab/hyaluronidase. Administer NSAIDs as needed. Refer to rheumatologist or neurologist for work-up. If CK is elevated ≥3 times ULN, 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.b | |
|
Grade 3 or 4 |
Withhold atezolizumab/hyaluronidase. 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/hyaluronidase discontinuation.b | |
|
Ocular toxicity: Vogt-Koyanagi-Harada–like syndrome |
May require systemic corticosteroids to reduce the risk of permanent vision loss. | |
|
Pulmonary toxicity: pneumonitis |
Grade 2 |
Withhold atezolizumab/hyaluronidase and initiate corticosteroid therapy; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroids taper.c Permanently discontinue atezolizumab/hyaluronidase if no complete or partial resolution within 12 weeks of corticosteroid initiation, 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/hyaluronidase. | |
|
Other adverse reactions | ||
|
Infusion-related reactions |
Grade 1 or 2 |
Pause injection or reduce the rate of injection. Consider premedication with an antipyretic and antihistamine for subsequent doses. |
|
Grade 3 or 4 |
Permanently discontinue atezolizumab/hyaluronidase. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see individual agents.
>10%:
Endocrine & metabolic: Decreased serum albumin (34%), decreased serum calcium (22%), decreased serum sodium (46%), increased serum calcium (20%), increased serum potassium (21%)
Gastrointestinal: Decreased appetite (11%)
Hematologic & oncologic: Decreased hemoglobin (67%; grades 3/4: 6%), increased INR (20%; grades 3/4: 2%), lymphocytopenia (37%; grades 3/4: 9%)
Hepatic: Increased serum alanine aminotransferase (28%), increased serum alkaline phosphatase (33%), increased serum aspartate aminotransferase (28%)
Immunologic: Antibody development (20%; neutralizing: 54%)
Nervous system: Fatigue (19%)
Neuromuscular & skeletal: Musculoskeletal pain (15%)
Renal: Increased serum creatinine (19%)
Respiratory: Cough (13%), dyspnea (12%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (>1%)
Endocrine & metabolic: Hyperthyroidism (2%), hypothyroidism (10%)
Hepatic: Hepatitis (1%)
Local: Injection-site reaction (5%)
Respiratory: Pleural effusion (>1%), pneumonia (>1%), pneumonitis (2%)
Miscellaneous: Fever (1%)
<1%:
Dermatologic: Toxic epidermal necrolysis
Endocrine & metabolic: Adrenocortical insufficiency, hypophysitis, thyroiditis
Frequency not defined: Respiratory: Viral respiratory tract infection
Known hypersensitivity to hyaluronidase, or any component of the formulation.
Canadian labeling: Known hypersensitivity to atezolizumab, hyaluronidase, or any component of the formulation.
Concerns related to adverse effects:
• Adverse reactions (immune mediated): PD-1/PD-L1 blockers (including atezolizumab/hyaluronidase) 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/hyaluronidase initiation); reactions may also occur after atezolizumab/hyaluronidase discontinuation. Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of atezolizumab/hyaluronidase. If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection). Medically manage immune-mediated adverse reactions with corticosteroids and/or supportive care promptly and refer for specialty consultation as appropriate.
• Cardiovascular toxicity: Myocarditis, including fatal cases, 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 (Ref). Myocarditis may be a manifestation of myositis. Pericarditis and vasculitis have also been reported.
• Dermatologic toxicity: Atezolizumab/hyaluronidase may cause immune-mediated rash or dermatitis, including grade 3 and fatal events. Exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms has occurred with anti-PD-1/PD-L1 monoclonal antibodies, including atezolizumab/hyaluronidase.
• Endocrinopathies: Atezolizumab/hyaluronidase is associated with immune-mediated endocrinopathies, including adrenal insufficiency, hypophysitis, thyroid disorders (eg, hyperthyroidism, hypothyroidism, thyroiditis), and type 1 diabetes mellitus (including diabetic ketoacidosis).
- Adrenal insufficiency: Adrenal insufficiency (primary or secondary) may occur. Grade 2 and 3 events have been reported (rare). Systemic corticosteroids were administered for adrenal insufficiency in one-half of cases; some patients remained on corticosteroid therapy.
- Diabetes mellitus: Type 1 diabetes mellitus has occurred with atezolizumab/hyaluronidase, including grade 3 events and diabetic ketoacidosis. Insulin therapy may be required.
- Hypophysitis: Atezolizumab/hyaluronidase has been associated with immune-mediated hypophysitis (including grade 2 reactions), which may present with acute mass effect symptoms, including headache, photophobia, or visual field cuts. Hypophysitis may lead to hypopituitarism.
- Thyroid disorders: Immune-mediated thyroid disorders have occurred with atezolizumab/hyaluronidase (as a single agent) and intravenous atezolizumab (as a single agent or in combination with other anticancer therapies). 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 anti-thyroid treatment. In cases where atezolizumab was withheld due to hyperthyroidism, some patients reinitiated therapy following symptom improvement; recurrence occurred following reinitiation 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 and resolved in 50% of patients.
• GI adverse effects: Immune-mediated colitis (including grade 3 events) has occurred with atezolizumab/hyaluronidase. Colitis may present with diarrhea, abdominal pain, and/or lower GI bleeding. 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: Atezolizumab/hyaluronidase may cause immune-mediated hepatitis, including fatal cases. Immune-mediated hepatitis has occurred with atezolizumab/hyaluronidase (as a single agent) and intravenous atezolizumab (as a single agent and when used in combination with other anticancer agents). Systemic corticosteroids were used to manage immune-mediated hepatitis in one-half to two-thirds of cases, with resolution in most patients. Of the patients that therapy was withheld for hepatitis, a majority reinitiated therapy after symptom improvement with recurrence of hepatitis in some of these patients.
• Infusion-related reactions: Atezolizumab/hyaluronidase may cause severe or life-threatening infusion reactions, including grade 3 reactions.
• Kidney toxicity: Immune-mediated nephritis with kidney dysfunction has occurred with atezolizumab/hyaluronidase. Immune-mediated nephritis with kidney dysfunction has also occurred (rarely) with intravenous 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: Optic neuritis, iritis, uveitis, keratitis, retinopathy, 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: Atezolizumab/hyaluronidase may cause immune-mediated pneumonitis, including fatal cases. Immune-mediated pneumonitis has been reported in patients receiving atezolizumab/hyaluronidase (as a single agent) and with atezolizumab (as a single agent or in combination with cobimetinib and vemurafenib). Pneumonitis occurred more frequently in patients with a history of prior thoracic radiation. Pneumonitis was managed with systemic corticosteroids in approximately one-half of patients and resolved in most cases. In cases where atezolizumab/hyaluronidase or atezolizumab was withheld for pneumonitis, atezolizumab/hyaluronidase or atezolizumab was reinitiated after symptom improvement; recurrence occurred following reinitiation in one-half of patients.
• Other immune-mediated toxicities: Other clinically relevant immune-mediated disorders have been observed rarely with atezolizumab (or other anti-PD-L1/PD-1 monoclonal antibodies) and may affect any organ system (may be fatal), including meningitis, encephalitis, and myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, autoimmune neuropathy, and nerve paresis, hypoparathyroidism, hemophagocytic lymphohistiocytosis, sarcoidosis, aplastic anemia, autoimmune hemolytic anemia, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (corneal graft) rejection, myositis/polymyositis, and rhabdomyolysis (and associated sequelae including kidney failure, arthritis, and polymyalgia rheumatic).
Disease-related concerns:
• Hematopoietic cell transplant: Fatal and other serious complications may occur in patients who received allogeneic hematopoietic cell transplant (HCT) 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 anti–PD-L1/PD-1 monoclonal antibody therapy and HCT. 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 allogeneic HCT.
• 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 (Ref).
Dosage form specific issues:
• Do not interchange: Atezolizumab/hyaluronidase (for SUBQ administration) and atezolizumab (for IV administration) have different dosing and are NOT interchangeable on a mg-per-mg basis.
Other warnings/precautions:
• Appropriate use: For first-line treatment of metastatic non–small cell lung cancer (NSCLC) (as a single agent), select patients for atezolizumab/hyaluronidase 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/hyaluronidase therapy based on the PD-L1 expression on tumor cells. For treatment of locally advanced or metastatic triple-negative breast cancer, select patients for atezolizumab/hyaluronidase therapy based on the PD-L1 expression on tumor-infiltrating immune 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.
Tecentriq Hybreza: FDA approved September 2024; anticipated availability currently unknown.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous [preservative free]:
Tecentriq Hybreza: 1875-30000 MG-UT/15ML (15 mL)
No
Solution (Tecentriq Hybreza Subcutaneous)
1875-30000MG-UT/15ML (per mL): $900.14
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, Subcutaneous:
Tecentriq SC: 1875 mg/15 mL (15 mL)
Note: Check label to ensure appropriate product is administered; atezolizumab/hyaluronidase (SUBQ) and atezolizumab (IV) are different products and are NOT interchangeable on a mg-per-mg basis. The volume of the SUBQ dose of atezolizumab/hyaluronidase is 15 mL.
SUBQ: For SUBQ administration only. If stored in the refrigerator, allow syringe to reach room temperature prior to administration. Administer SUBQ into the thigh over ~7 minutes; do NOT administer residual hold-up volume in the tubing. Use of a SUBQ infusion set (eg, winged/butterfly) is recommended. Alternate the injection site between the left and right thigh. Administer new injections on healthy skin at least 1 inch (2.5 cm) from the previous site; do not administer into areas where the skin is red, bruised, tender, or hard. Do not administer other SUBQ medications at the same sites as atezolizumab/hyaluronidase.
Administration sequence (for combination therapy):
Hepatocellular carcinoma, unresectable or metastatic: When administered in combination with bevacizumab on the same day, administer atezolizumab/hyaluronidase prior to bevacizumab.
Nonsquamous non–small cell lung cancer, metastatic, combination with bevacizumab, carboplatin, and paclitaxel (ABCP regimen): When administered in combination with chemotherapy and bevacizumab on the same day, administer atezolizumab/hyaluronidase first, followed by bevacizumab, followed by paclitaxel, and then followed by carboplatin.
Nonsquamous non–small cell lung cancer, metastatic, combination with carboplatin, and paclitaxel (protein bound): When administered in combination with chemotherapy on the same day, administer atezolizumab/hyaluronidase first, followed by paclitaxel (protein bound), and then followed by carboplatin.
Small cell lung cancer, extensive stage, in combination with carboplatin and etoposide: When administered in combination with chemotherapy on the same day, administer atezolizumab/hyaluronidase first, followed by carboplatin, and then followed by etoposide.
Alveolar soft part sarcoma, unresectable or metastatic: Treatment (as a single agent) of unresectable or metastatic alveolar soft part sarcoma in adults.
Hepatocellular carcinoma, unresectable or metastatic: Treatment (in combination with bevacizumab) of unresectable or metastatic hepatocellular carcinoma in adults who have not received prior systemic therapy.
Melanoma, unresectable or metastatic, BRAF V600 mutation-positive: Treatment (in combination with cobimetinib and vemurafenib) of BRAF V600 mutation-positive (as determined by an approved test) unresectable or metastatic melanoma 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 (as a single agent) of metastatic NSCLC in adults whose tumors have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells [TC] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥10% of the tumor area), as determined by an approved test, and with no 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 (as a 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 NSCLC therapy for EGFR or ALK genomic tumor mutations prior to receiving atezolizumab/hyaluronidase).
Small cell lung cancer, extensive stage: First-line treatment (in combination with carboplatin and etoposide) of extensive-stage small cell lung cancer in adults.
Atezolizumab/hyaluronidase may be confused with alemtuzumab, atezolizumab (IV formulation), avelumab, daratumumab/hyaluronidase, durvalumab, nivolumab, pembrolizumab, pertuzumab/trastuzumab/hyaluronidase, rituximab/hyaluronidase, trastuzumab/hyaluronidase.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral, and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Atezolizumab/hyaluronidase is for SUBQ administration only. Do not substitute atezolizumab (IV) for atezolizumab/hyaluronidase (SUBQ). Use caution during product selection, preparation, and administration.
Refer to individual components.
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetaminophen: May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Alpha-/Beta-Agonists: Hyaluronidase may increase vasoconstricting effects of Alpha-/Beta-Agonists. Management: Do not use hyaluronidase to enhance the dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Risk D: Consider Therapy Modification
Antibiotics: May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Antihistamines: May decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
Corticosteroids (Systemic): May decrease therapeutic effects of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider Therapy Modification
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Estrogen Derivatives: May decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Ketoconazole (Systemic): Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may increase hepatotoxic effects of Ketoconazole (Systemic). Risk C: Monitor
Local Anesthetics: Hyaluronidase may increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Opioid Agonists: Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may decrease therapeutic effects of Opioid Agonists. Opioid Agonists may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Phenylephrine (Systemic): Hyaluronidase may increase vasoconstricting effects of Phenylephrine (Systemic). Management: Do not use hyaluronidase to enhance the dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Risk D: Consider Therapy Modification
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Salicylates: May decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
Vitamin K Antagonists: Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
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 5 months after the last atezolizumab/hyaluronidase dose.
Animal reproduction studies have not been conducted. Atezolizumab is an Fc-engineered humanized nonglycosylated monoclonal antibody (IgG1). Human IgG crosses the placenta. Based on the mechanism of action of atezolizumab, in utero exposure may cause fetal harm.
Refer to individual monographs for additional information.
It is not known if atezolizumab is present in breast milk.
Atezolizumab is an Fc-engineered humanized nonglycosylated monoclonal antibody (IgG1). Human IgG is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 5 months after the last atezolizumab/hyaluronidase dose.
Refer to individual monographs for additional information.
PD-L1 expression status (based on PD-L1 expression on tumor cells or on tumor-infiltrating immune cells for single-agent, first-line treatment of metastatic non–small cell lung cancer [NSCLC]; based on the PD-L1 expression on tumor cells for single-agent adjuvant treatment of stage II to IIIA NSCLC. BRAF V600 mutation status (in patients with unresectable or metastatic melanoma).
Monitor LFTs (AST, ALT, and total bilirubin; at baseline and periodically during treatment), serum creatinine (at baseline and periodically during treatment), thyroid function (at baseline and periodically during treatment), monitor serum glucose (for hyperglycemia). Evaluate pregnancy status (prior to treatment initiation in patients who could become pregnant). Evaluate for the presence of varices prior to treatment in patients with hepatocellular carcinoma. 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), endocrinopathies (adrenal insufficiency, diabetes, hypophysitis, thyroid disorders), hepatitis, cardiovascular toxicity (myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, and vasculitis), meningitis or encephalitis, myositis, pancreatitis, pneumonitis (dyspnea, hypoxia), dermatologic toxicity, fatigue, weakness, hypotension, mental status changes, visual disturbances, and ocular toxicity. 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 (Ref) 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 (Ref):
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 (Ref). 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) (Ref). 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 (Ref).
Hyaluronidase increases permeability of the SUBQ tissue by depolymerizing hyaluronan, allowing for increased dispersion and absorption of coadministered drugs when administered SUBQ. At the recommended dose, hyaluronidase acts locally and the effects are reversible, and permeability of the SUBQ tissue is restored within 24 to 48 hours.
Distribution: Vdss: SUBQ: 6.9 L.
Bioavailability: SUBQ: 72%.
Half-life elimination: SUBQ: 27 days.
Time to peak: SUBQ: 4.5 days (range: 2.2 to 9 days).
Excretion: SUBQ: Clearance: 0.2 L/day.
