Skip to Content

Atezolizumab

Class: Antineoplastic Agents
Chemical Name: Immunoglobulin G1-κ, anti-[Homo sapiens CD274 (programmed death ligand 1, PDL1, PD-L1, B7 homolog 1, B7H1)], humanized monoclonal antibody
Molecular Formula: C6446H9902N1706O1998S42
CAS Number: 1380723-44-3
Brands: Tecentriq

Introduction

Antineoplastic agent; humanized anti-programmed-death ligand-1 (anti-PD-L1) monoclonal antibody.1 2 4 10

Uses for Atezolizumab

Urothelial Carcinoma

Treatment of locally advanced or metastatic urothelial carcinoma that has progressed during or following platinum-containing therapy for advanced disease or within 12 months of platinum-containing therapy in the neoadjuvant or adjuvant setting.1 2

Accelerated approval based on objective response rate and duration of response.1 2 Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.1

Non-small Cell Lung Cancer (NSCLC)

Treatment of metastatic NSCLC that has progressed during or following platinum-based chemotherapy.1 11 12 Patients with epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)-positive tumors also should have documented disease progression during or following an FDA-labeled anti-EGFR or anti-ALK therapy prior to initiating therapy with atezolizumab.1

Atezolizumab Dosage and Administration

General

Restricted Distribution

  • Obtain atezolizumab through a limited network of specialty distributors.3 5

  • Contact manufacturer at 800-551-22313 or consult the Tecentriq website () for specific availability information.5

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.1 Do not administer by rapid IV injection (e.g., IV push or bolus).1

Atezolizumab injection concentrate must be diluted prior to administration.1 Immediate administration recommended.1 (See Storage under Stability.)

Do not infuse simultaneously through the same IV line with other drugs.1

Use of low-protein-binding 0.2- to 0.22-mcm inline filter is optional.1

Dilution

Undiluted solution should be colorless to slightly yellow.1 Do not use if it is cloudy or discolored or if particulate matter is present.1

Do not shake vial.1

Withdraw 20 mL of atezolizumab injection concentrate (containing 60 mg/mL) and dilute in a PVC, polyethylene, or polyolefin infusion bag containing 250 mL of 0.9% sodium chloride.1 Do not use any other diluent.1 Mix the diluted solution by gentle inversion; do not shake.1 Discard any partially used vial.1

Rate of Administration

Initial dose: Administer over 60 minutes.1

Subsequent doses: Administer over 30 minutes (if first infusion well tolerated).1

Dosage

Adults

Urothelial Carcinoma
IV

1.2 g every 3 weeks.1 Continue therapy until disease progression or unacceptable toxicity occurs.1

NSCLC
IV

1.2 g every 3 weeks.1 Continue therapy until disease progression or unacceptable toxicity occurs.1

Therapy Interruption for Toxicity
Immune-mediated Pneumonitis
IV

If grade 2 immune-mediated pneumonitis occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated Pneumonitis under Cautions.)

If grade 3 or 4 immune-mediated pneumonitis occurs, discontinue drug.1

Immune-mediated Hepatic Effects
IV

For grade 2 immune-mediated hepatitis, serum ALT or AST elevations >3 times but ≤5 times the ULN, or total bilirubin concentrations >1.5 times but ≤3 times the ULN, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated Hepatic Effects under Cautions.)

For grade 3 or 4 immune-mediated hepatitis, ALT or AST elevations >5 times the ULN, or total bilirubin concentrations >3 times the ULN, discontinue drug.1

Immune-mediated GI Effects
IV

If grade 2 or 3 immune-mediated colitis or diarrhea occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated GI Effects under Cautions.)

If grade 4 immune-mediated colitis or diarrhea occurs, discontinue drug.1

Immune-mediated Endocrine Effects
IV

If symptomatic immune-mediated hypophysitis, adrenal insufficiency, hypothyroidism, or hyperthyroidism occurs or if grade 3 or 4 immune-mediated hyperglycemia occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated Endocrine Effects under Cautions.)

If grade 4 immune-mediated hypophysitis occurs, discontinue drug.1

Other Immune-mediated Adverse Effects
IV

If grade 2 immune-mediated ocular inflammatory toxicity, grade 2 or 3 immune-mediated pancreatitis, or grade 3 or 4 elevations in amylase or lipase concentrations (>2 times the ULN) occur, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Other Immune-mediated Effects under Cautions.)

If myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, meningoencephalitis, grade 3 or 4 immune-mediated ocular inflammatory toxicity, grade 4 immune-mediated pancreatitis, or recurrent immune-mediated pancreatitis of any severity occurs, discontinue drug.1

Infusion-related Reactions
IV

If grade 2 infusion-related reactions occur, interrupt infusion until reaction resolves to grade 0 or 1.1 (See Infusion-related Effects under Cautions.)

If grade 3 or 4 infusion-related reactions occur, discontinue drug.1

Infectious Complications
IV

If grade 3 or 4 infection occurs, interrupt therapy.1 (See Infectious Complications under Cautions.)

Dermatologic Effects
IV

If grade 3 rash occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1

If grade 4 rash occurs, discontinue drug.1

Special Populations

Hepatic Impairment

Mild hepatic impairment: No dosage adjustment required.1 (See Special Populations under Pharmacokinetics.)

Moderate or severe hepatic impairment: No dosage recommendations at this time.1

Renal Impairment

Mild, moderate, or severe renal impairment: No dosage adjustment required.1 (See Special Populations under Pharmacokinetics.)

Geriatric Patients

No special dosage recommendations at this time.1 (See Geriatric Use under Cautions.)

Cautions for Atezolizumab

Contraindications

  • No known contraindications.1

Warnings/Precautions

Immune-mediated Pneumonitis

Immune-mediated pneumonitis or interstitial lung disease, sometimes fatal, reported.1 2

Monitor patients for manifestations of pneumonitis.1

If immune-mediated pneumonitis occurs, temporarily withhold or discontinue atezolizumab.1 (See Immune-mediated Pneumonitis under Dosage and Administration.) If grade 2 or greater pneumonitis occurs, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.1

Immune-mediated Hepatic Effects

Immune-mediated hepatitis, sometimes fatal, and liver function test abnormalities reported.1 2 11

Monitor patients for signs and symptoms of hepatitis.1 Evaluate liver function tests (i.e., ALT, AST, total bilirubin) prior to initiation of and periodically during therapy.1

If immune-mediated hepatitis or liver function test abnormalities occur, temporarily withhold or discontinue atezolizumab.1 (See Immune-mediated Hepatic Effects under Dosage and Administration.) If grade 2 or greater serum ALT or AST elevations occur, with or without concurrent elevations of total bilirubin concentrations, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.1

Immune-mediated GI Effects

Immune-mediated colitis or diarrhea, sometimes fatal, reported.1

Monitor patients for signs and symptoms of colitis or diarrhea.1

If grade 2 colitis or diarrhea occurs, temporarily withhold atezolizumab; if symptoms recur or persist for >5 days, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) and gradually taper corticosteroid dosage over ≥1 month once symptoms improve to grade 0 or 1.1

If grade 3 colitis or diarrhea occurs, temporarily withhold atezolizumab and initiate IV corticosteroid therapy (1–2 mg/kg of methylprednisolone daily); once symptoms have improved, convert to an oral corticosteroid and then taper dosage over ≥1 month once symptoms improve to grade 0 or 1.1 If toxicity resolves to grade 0 or 1 within 12 weeks and corticosteroid dosage has been reduced to ≤10 mg of prednisone daily (or equivalent), resume atezolizumab.1

If grade 4 immune-mediated colitis or diarrhea occurs, permanently discontinue drug.1

Immune-mediated Endocrine Effects

Immune-mediated endocrinopathies, such as thyroid dysfunction (i.e., hypothyroidism, hyperthyroidism), adrenal insufficiency, hypophysitis, and diabetes mellitus (including ketoacidosis), reported.1

Thyroid Dysfunction

Evaluate thyroid function prior to initiation of and periodically during therapy.1 Patients with asymptomatic abnormalities in thyroid function tests may receive atezolizumab.1

If symptomatic immune-mediated hypothyroidism occurs, temporarily withhold atezolizumab and initiate thyroid hormone replacement therapy as clinically indicated.1 Once symptoms are controlled and thyroid function test results improve to grade 0 or 1, resume atezolizumab.1 If isolated immune-mediated hypothyroidism occurs, initiate thyroid hormone replacement therapy without systemic corticosteroid therapy.1

If symptomatic immune-mediated hyperthyroidism occurs, temporarily withhold atezolizumab and initiate appropriate medical therapy as clinically indicated.1 Once symptoms are controlled and thyroid function test results improve to grade 0 or 1, resume atezolizumab.1

Adrenal Insufficiency

If symptomatic immune-mediated adrenal insufficiency occurs, temporarily withhold atezolizumab and initiate IV corticosteroid therapy (1–2 mg/kg of methylprednisolone daily) followed by an oral corticosteroid (1–2 mg/kg of prednisone daily [or equivalent]) once symptoms have improved; taper corticosteroid dosage over ≥1 month once toxicity improves to grade 0 or 1.1 If the toxicity resolves to grade 0 or 1 within 12 weeks, the corticosteroid dosage has been reduced to ≤10 mg of prednisone daily (or equivalent), and the patient is stable on replacement therapy, if needed, resume atezolizumab.1

Hypophysitis

Monitor for signs and symptoms of hypophysitis.1

If immune-mediated hypophysitis occurs, temporarily withhold or discontinue atezolizumab.1 (See Immune-mediated Endocrine Effects under Dosage and Administration.) Initiate systemic corticosteroid therapy and hormone replacement as clinically indicated.1

Diabetes Mellitus

If immune-mediated type 1 diabetes mellitus occurs, initiate insulin therapy.1 If grade 3 or greater hyperglycemia (fasting blood glucose concentration >250 mg/dL) occurs, temporarily withhold atezolizumab.1 Once blood glucose concentrations have stabilized on insulin therapy, resume atezolizumab.1

Other Immune-mediated Effects

Immune-mediated myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, meningoencephalitis, ocular inflammatory toxicity, and pancreatitis (including elevations in serum amylase and lipase concentrations) reported rarely.1

Meningitis or Encephalitis

Monitor patients for manifestations of meningitis or encephalitis.1

If immune-mediated meningitis or encephalitis occurs, permanently discontinue atezolizumab and initiate IV corticosteroid therapy (1–2 mg/kg of methylprednisolone daily [or equivalent]) followed by an oral corticosteroid (60 mg of prednisone daily [or equivalent]) once symptoms improve; taper corticosteroid dosage over ≥1 month once symptoms improve to grade 0 or 1.1

Peripheral Neuropathy

Monitor patients for symptoms of motor or sensory neuropathy.1

If immune-mediated myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome occurs, permanently discontinue atezolizumab and institute medical intervention as clinically appropriate.1 Consider systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]).1

Pancreatitis

Monitor patients for signs and symptoms of acute pancreatitis.1

If grade 3 or greater elevations in serum amylase or lipase concentrations (>2 times the ULN) or grade 2 or 3 pancreatitis occurs, temporarily withhold atezolizumab and initiate IV corticosteroid therapy (1–2 mg/kg of methylprednisolone daily [or equivalent]) followed by an oral corticosteroid (1–2 mg/kg of prednisone daily [or equivalent]) once symptoms improve.1 If serum amylase and lipase concentrations resolve to grade 0 or 1 within 12 weeks, symptoms of pancreatitis resolve, and the corticosteroid dosage has been reduced to ≤10 mg of prednisone daily (or equivalent), resume atezolizumab therapy.1

If grade 4 immune-mediated pancreatitis or recurrent immune-mediated pancreatitis of any severity occurs, permanently discontinue atezolizumab.1

Infectious Complications

Serious, sometimes fatal, infections (e.g., sepsis, herpes encephalitis, mycobacterial infection resulting in retroperitoneal hemorrhage) reported.1

Monitor patients for signs and symptoms of infection and initiate appropriate anti-infective treatment as clinically indicated.1 If infection occurs, temporary interruption of atezolizumab may be necessary.1 (See Infectious Complications under Dosage and Administration.)

Infusion-related Effects

Severe infusion-related reactions reported.1

If mild or moderate infusion-related reactions occur, interrupt infusion or reduce infusion rate.1 (See Infusion-related Reactions under Dosage and Administration.)

If grade 3 or 4 infusion-related reactions occur, permanently discontinue atezolizumab.1

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.1 May disrupt maternal immune tolerance to the fetus and increase risk of fetal loss (abortion, stillbirth); also may increase risk of immune-mediated disorders.1

Avoid pregnancy during therapy.1 Women of childbearing potential should use an effective contraceptive method while receiving atezolizumab and for ≥5 months after the drug is discontinued.1 If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.1

Immunogenicity

Potential for immunogenicity.1 Development of binding antibodies to atezolizumab reported.1 Effects on safety, efficacy, or pharmacokinetics of the drug not observed.1

Impairment of Fertility

May impair female fertility.1

Specific Populations

Pregnancy

May cause fetal harm.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether atezolizumab is distributed into milk.1 Discontinue nursing during therapy and for ≥5 months after drug discontinuance.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

No overall differences in safety and efficacy in geriatric patients (≥65 years of age) compared with younger adults.1

Hepatic Impairment

Systemic exposure and clearance not affected by mild hepatic impairment.1 4 Data lacking in patients with moderate or severe hepatic impairment.1 4 (See Special Populations under Pharmacokinetics.)

Renal Impairment

Clearance not affected by mild or moderate renal impairment.1 4 Limited data available in patients with severe renal impairment.1 4 (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Advanced or metastatic urothelial carcinoma: Fatigue,1 2 loss of appetite,1 2 nausea,1 2 urinary tract infection,1 constipation,1 pyrexia,1 diarrhea,1 peripheral edema,1 abdominal pain,1 vomiting,1 dyspnea,1 back/neck pain,1 rash,1 arthralgia,1 cough,1 hematuria,1 pruritus,1 2 lymphopenia,1 hyponatremia,1 anemia,1 hyperglycemia.1

Metastatic NSCLC: Loss of appetite,1 11 dyspnea,1 11 cough,1 pneumonia,1 11 pyrexia,1 11 arthralgia,1 11 musculoskeletal (e.g., back) pain,1 11 insomnia,1 11 hypoalbuminemia,1 hyponatremia,1 elevated alkaline phosphatase concentrations,1 elevated ALT/AST concentrations,1 elevated Scr,1 hypokalemia,1 hypercalcemia,1 elevated total bilirubin concentrations.1

Interactions for Atezolizumab

No formal drug interaction studies to date.1

Atezolizumab Pharmacokinetics

Absorption

Bioavailability

Steady-state concentrations achieved within 6–9 weeks.1 4 10

Systemic exposure is dose proportional over the dose range of 1–20 mg/kg, including fixed dosage of 1.2 g every 3 weeks; systemic accumulation is 1.9-fold when administered every 3 weeks.1 4 10

Distribution

Extent

Not known whether atezolizumab is distributed into milk.1

Elimination

Half-life

27 days.1 4 10

Special Populations

Mild hepatic impairment (total bilirubin concentration not exceeding the ULN with AST concentration exceeding the ULN, or total bilirubin concentration between 1–1.5 times the ULN with any AST concentration) does not affect clearance and systemic exposure.1 4 Effect of moderate or severe hepatic impairment on atezolizumab pharmacokinetics not established.1 4

Mild or moderate renal impairment (estimated GFR 30–89 mL/minute per 1.73 m2) does not affect clearance.1 4 Limited data available for severe renal impairment.1 4

Age (range of 21–89 years), body weight, gender, presence of anti-atezolizumab antibodies, serum albumin concentration, tumor burden, geographic region, and race do not have meaningful effects on systemic exposure of atezolizumab.1 4

Stability

Storage

Parenteral

Injection

2–8°C.1 Do not freeze; protect from light.1

Diluted solution: Room temperature for ≤6 hours from time of preparation (including infusion time) or 2–8°C for ≤24 hours.1 Do not freeze.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility1

Compatible

Sodium chloride 0.9%

Actions

  • An IgG1 kappa immunoglobulin that is selective for PD-L1.1 2 4

  • Overexpression of PD-1 ligands on surface of tumor cells results in activation of PD-1 and B7.1 and suppression of cytotoxic T-cell activity, T-cell proliferation, and cytokine production.1 8 9 10

  • Blocks interaction between PD-L1 and the receptors PD-1 and B7.1, resulting in activation of antitumor immune response without inducing antibody-dependent cell-mediated cytotoxicity (ADCC).1 10

Advice to Patients

  • Importance of advising patients to read the manufacturer's medication guide.1

  • Risk of immune-mediated pneumonitis.1 Importance of informing clinician immediately if new or worsening cough, chest pain, or shortness of breath occurs.1

  • Risk of immune-mediated hepatitis.1 Importance of informing clinician immediately if signs and symptoms of liver damage (e.g., jaundice, severe nausea or vomiting, abdominal pain [particularly in right upper quadrant], lethargy, easy bruising or bleeding, lack of appetite, dark urine, drowsiness) occur.1

  • Risk of immune-mediated colitis.1 Importance of informing clinician immediately if diarrhea, severe abdominal pain, or changes in stool occur.1

  • Risk of immune-mediated endocrine effects.1 Importance of informing clinician immediately if manifestations of hypophysitis, hyperthyroidism, hypothyroidism, adrenal insufficiency, or diabetes mellitus (including ketoacidosis) occur.1

  • Risk of immune-mediated meningoencephalitis, myasthenic syndrome/myasthenia gravis, and Guillain-Barré syndrome.1 Importance of informing clinician immediately if manifestations of these conditions occur.1

  • Risk of immune-mediated ocular inflammatory toxicity.1 Importance of informing clinician immediately if signs and symptoms of ocular inflammatory toxicity (e.g., ocular pain, redness, blurred or double vision) occur.1

  • Risk of immune-mediated pancreatitis.1 Importance of informing clinician immediately if manifestations of pancreatitis occur.1

  • Risk of infections.1 Importance of informing clinician if fever, flu-like symptoms, cough, or painful or frequent urination occurs.1

  • Risk of infusion-related reactions.1 Importance of informing clinician if signs and symptoms of such reactions, including dizziness, chills, fever, breathing difficulty (i.e., shortness of breath, wheezing), pruritus, flushing, feeling of faintness, back or neck pain, or angioedema, occur.1

  • Risk of rash.1 Importance of informing clinician if rash occurs.1

  • Risk of fetal harm.1 Necessity of advising women of childbearing potential that they should use an effective method of contraception while receiving atezolizumab and for ≥5 months after discontinuance of therapy.1 Importance of women informing clinicians if they are or plan to become pregnant.1 If pregnancy occurs, advise pregnant women of potential risk to the fetus.1

  • Importance of advising women to avoid breast-feeding while receiving atezolizumab and for ≥5 months after discontinuance of therapy.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of atezolizumab is restricted.3 5 (See Restricted Distribution under Dosage and Administration.)

Atezolizumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Concentrate, for injection, for IV infusion

60 mg/mL (1.2 g)

Tecentriq

Genentech

AHFS DI Essentials. © Copyright 2017, Selected Revisions January 26, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Genentech. Tecentriq (atezolizumab) injection for intravenous infusion prescribing information. South San Francisco, CA; 2016 Oct.

2. Rosenberg JE, Hoffman-Censits J, Powles T et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016; 387:1909-20. [PubMed 26952546]

3. Genentech. Genentech Tecentriq distribution quick reference guide. From Genentech for Healthcare Professionals website. Accessed 2016 Sep 13.

4. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761034Orig1s000: Clinical pharmacology and biopharmaceutics review(s). From FDA website.

5. Genentech. Tecentriq distribution. 2016 Sept. From Genentech for Healthcare Professionals website. Accessed 2016 Sep 13.

6. Robert C, Ribas A, Wolchok JD et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014; 384:1109-17. [PubMed 25034862]

7. Hamid O, Robert C, Daud A et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013; 369:134-44. [PubMed 23724846]

8. Poole RM. Pembrolizumab: first global approval. Drugs. 2014; 74:1973-81. [PubMed 25331768]

9. Gentzler R, Hall R, Kunk PR et al. Beyond melanoma: inhibiting the PD-1/PD-L1 pathway in solid tumors. Immunotherapy. 2016; 8:583-600. [PubMed 27140411]

10. Markham A. Atezolizumab: First Global Approval. Drugs. 2016; 76:1227-32. [PubMed 27412122]

11. Fehrenbacher L, Spira A, Ballinger M et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016; 387:1837-46. [PubMed 26970723]

12. Anon. ESMO 2016 press release: significant survival gains with atezolizumab vs docetaxel for non-small-cell lung cancer. 2016 Oct 9. From European Society for Medical Oncology website.

Hide