Atezolizumab

Action and Spectrum

Programmed cell death-ligand 1 (PD-L1) is found on various immune and tumor-infiltrating cells, where it binds to PD-1 and B7.1 receptors to suppress cytotoxic T-cell activity. This interaction impairs T-cell movement, growth, and the release of cytotoxic agents, thereby reducing the immune system’s ability to destroy tumor cells. 

Atezolizumab, a humanized monoclonal antibody, blocks PD-L1 from engaging with PD-1 and B7.1. By doing so, it restores T-cell function and enhances the immune response against cancer. Clinical trials have demonstrated its early and broad antitumor activity across multiple cancer types. 

Drug Interaction

Adverse Reaction

Adverse drug reactions:  

Frequency defined  

>10%  

Rash  

pruritus    

Nausea  

constipation  

diarrhea  

abdominal pain  

vomiting  

Urinary tract infection  

Immune related colitis  

Decreased appetite    

Back/neck pain  

Arthralgia  

Fatigue  

pyrexia  

peripheral edema  

Dyspnea  

cough  

<10%  

Dyspnea  

Pneumonia  

Hematuria  

Confusional state  

Increased creatinine  

Hyponatremia  

hyperglycemia  

Hypoalbuminemia  

Immune related pneumonitis  

immune related hepatitis  

Sepsis  

Acute kidney injury  

liver enzyme increase  

increased ALT  

increased AST  

Anemia  

lymphopenia  

increased alkaline phosphatase  

Dehydration  

intestinal obstruction  

Venous thromboembolism  

Frequency not defined  

Immune-related thyroid disorders  

Infusion related reactions  

Immune related endocrinopathies  

Ocular inflammatory toxicity

Black Box Warning

None currently assigned by the FDA.

Contraindication / Caution

Contraindications 

None 

Cautions 

Pneumonitis: Higher risk in patients with prior thoracic radiation; monitor respiratory symptoms. 

Hepatitis: Immune-mediated; monitor liver function; fatal cases reported. 

Colitis/Diarrhea: Monitor for GI symptoms suggestive of immune-mediated colitis. 

Infusion Reactions: Severe or life-threatening reactions may occur; monitor during and after infusion. 

Infections: Risk of severe infections including sepsis and encephalitis; monitor for signs of infection. 

Hematologic/Immune Effects: Rare but serious conditions like hemolytic anemia, HLH, sarcoidosis, and transplant rejection may occur. 

Ocular Toxicity: Includes uveitis and possible vision loss; evaluate for Vogt-Koyanagi-Harada-like syndrome if eye symptoms co-occur with other immune effects. 

Drug Substitution Warning: Do not substitute paclitaxel protein-bound with standard paclitaxel outside clinical trials in TNBC treatment. 

Pregnancy / Lactation

Pregnancy warnings:    

• AU TGA pregnancy category: D 
• US FDA pregnancy category: Not assigned 

Breastfeeding warnings: 

• The release of the drug into the human breastmilk is unknown  
• The release of the drug into the animal milk is unknown 
• Therefore, the use of the drug is not recommended 

Pregnancy Categories:      

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first trimester or the later trimester      
• Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women      
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a result in humans must take care of potential risks in pregnant women      
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits      
• Category X: Drugs listed in this category outweigh risks over benefits Hence these categories of drugs need to be avoided by pregnant women      
• Category N: There is no data available for the drug under this category   

Pharmacology

Atezolizumab is a humanized monoclonal antibody (IgG1 isotype) that specifically targets programmed death-ligand 1 (PD-L1), a transmembrane protein expressed on tumor cells and tumor-infiltrating immune cells. PD-L1 binds to PD-1 and B7.1 (CD80) receptors on T cells, leading to the suppression of T-cell activation, proliferation, and cytotoxic function—allowing cancer cells to evade immune detection. 

By blocking PD-L1 from binding to both PD-1 and B7.1, atezolizumab restores T-cell activity, enabling the immune system to recognize and destroy cancer cells. It does not bind PD-1 directly, offering selective inhibition of the immune checkpoint pathway. 

It is indicated in various cancers, including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), urothelial carcinoma, and hepatocellular carcinoma, among others 

Pharmacokinetics 

Absorption
Atezolizumab shows systemic accumulation over 2–3 cycles of repeated dosing. 

• Peak plasma concentration increases by ~1.91-fold. 

• Minimum plasma concentration increases by ~1.46-fold. 

• Area Under the Curve (AUC) increases by ~2.75-fold. 

• Steady-state is typically achieved within 6–9 weeks. 

Distribution 

Volume of distribution (Vd) is approximately 6.9 liters, indicating limited distribution outside the vascular space. 

Metabolism 

As a monoclonal antibody, atezolizumab is expected to be degraded into small peptides and amino acids via non-specific catabolism, not metabolized by cytochrome P450 enzymes. 

Elimination/Excretion 

Terminal half-life: ~27 days 

Clearance: ~0.2 L/days 

Pharmacodynamics 

Atezolizumab is a humanized IgG1 monoclonal antibody that selectively binds to PD-L1 (programmed death-ligand 1). By blocking PD-L1’s interaction with PD-1 and B7.1 receptors, it restores T-cell activity and enhances the immune response against tumor cells. This reactivation of cytotoxic T lymphocytes leads to tumor cell recognition and destruction. Atezolizumab does not deplete T cells (due to lack of ADCC or CDC activity), preserving immune cell populations while enabling anti-tumor immunity. The response is typically dose-dependent, with immune-related adverse events correlating to increased immune activation. 

Adminstartion

Administer as an infusion only; never as an IV bolus or push. 

Use an IV line with or without a sterile, low-protein-binding, nonpyrogenic in-line filter (0.2–0.22 micron). 

First infusion over 60 minutes; if tolerated, subsequent infusions can be given over 30 minutes. 

Patient Information Leaflet

Generic name: Atezolizumab

Pronunciation: ah-tez-oh-LIZ-ue-mab 

Atezolizumab is an immunotherapy drug responsible for helping the immune system fight cancer. The structure of atezolizumab is a protein that blocks (PDL1 or programmed death-ligand).

It helps increase the life expectancy of cancerous patients.

It is used to treat urinary tract cancer/urothelial carcinoma, non-small cell lung cancer, liver cancer, and skin melanoma.

Side effects may arise due to atezolizumab, including intestinal problems like diarrhea, abdominal pain, dysentery, etc.

The liver problems that may occur are yellowing of skin/eyes, nausea, vomiting, and dark urine.

Other side effects may include hair loss, polyurea, loss of appetite, blurred vision, and anemia.

You should not take the medication if you are pregnant, lactating, or planning to conceive.