Actions and spectrum: 

• Antibody-Dependent Cellular Cytotoxicity (ADCC): obinutuzumab binds to CD20 on B-cells, triggering the immune system to attack and destroy these cells. It recruits immune cells, such as natural killer cells, which can recognize the bound antibody and destroy the B-cells. 
• Complement-Dependent Cytotoxicity (CDC): obinutuzumab activates the complement system. This activation leads to the destruction of CD20-positive B-cells. 

The spectrum of obinutuzumab’s action includes targeting CD20-positive B-cells, which are typically found in various types of B-cell malignancies, including: 

• Non-Hodgkin lymphomas: obinutuzumab is used in combination with chemotherapy for the treatment of certain types of non-Hodgkin lymphomas, such as follicular lymphoma and diffuse large B-cell lymphoma. 
• Chronic lymphocytic leukemia (CLL): obinutuzumab is used in combination with chemotherapy or as a monotherapy for the treatment of CLL, a type of cancer affecting the B-cells. 

DRUG INTERACTION

Frequency defined 

1-10% 

Cough (10%) 

Tumor lysis syndrome (2%) 

Pyrexia (10%) 

Leukopenia (7%)  

>10% 

Neutropenia (33%) 

Hyperkalemia (31%) 

increased Creatinine (28%) 

increased AST/SGPT (25%) 

increased Alkaline phosphatase (16%) 

Hypokalemia (13%) 

Infusion reactions (69%) 

Hypocalcemia (32%) 

Hyponatremia (29%) 

increased AST/SGOT (28%) 

Hypoalbuminemia (16%) 

Thrombocytopenia (15%) 

Anemia (12%)  

Post marketing Reports 

Diarrhea 

Insomnia 

Serum sickness 

Hypophosphatemia 

Headache 

Pruritus 

Chronic lymphocytic leukemia 

Black Box Warning: 

There were no black box warnings specifically associated with obinutuzumab 

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: obinutuzumab is contraindicated in individuals with a known hypersensitivity or severe allergic reaction to obinutuzumab or any of its components. Hypersensitivity reactions may include symptoms such as itching, rash, shortness of breath, or swelling of face, lips, or tongue. 
• Severe Active Infections: obinutuzumab should not be administered in patients with severe active infections. Treatment should be postponed until the infection is adequately controlled. 

Caution: 

• Infusion Reactions: obinutuzumab can cause infusion-related reactions, which may include fever, chills, rigors, low blood pressure, and allergic reactions. Close monitoring should be performed during infusion, and appropriate premedications may be given to help mitigate these reactions. 
• Infections: obinutuzumab may increase the risk of developing infections, including bacterial, viral, or fungal infections. Patients to be monitored for signs of infection, and appropriate treatment should be initiated promptly if an infection occurs. 
• Hepatitis B Reactivation: chronic hepatitis B patients should be closely monitored for reactivation of the virus during obinutuzumab treatment. Precautions and antiviral therapy may be necessary to prevent hepatitis B reactivation. 
• Immunization: Live vaccines should not be administered during or after treatment with obinutuzumab due to the potential for reduced vaccine efficacy and increased risk of infection. The timing of immunization should be coordinated with the healthcare professional. 
• Pregnancy and Lactation: obinutuzumab may cause harm to the fetus, and its use during pregnancy is not recommended. Adequate contraception should be used during treatment and for a certain period after the last dose. It is not known whether obinutuzumab is excreted in human milk, so breastfeeding should be discontinued during treatment and for a certain period thereafter.

Comorbidities: 

• Cardiovascular Disease: Patients with B-cell malignancies, such as lymphomas and CLL, may have an increased risk of coronary artery disease, hypertension, and heart failure. 
• Renal Impairment: Chronic kidney disease and renal impairment can be comorbidities in patients with B-cell malignancies. 
• Hepatic Dysfunction: Liver dysfunction, including hepatitis or liver cirrhosis, can be present in patients with B-cell malignancies. It is important to consider liver function when administering obinutuzumab. 
• Immunodeficiency: B-cell malignancies and their treatments can lead to immunodeficiency, making patients more susceptible to infections and other complications. 
• Autoimmune Disorders: Some patients with B-cell malignancies may have comorbid autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus, or autoimmune thyroid disease. 

Pregnancy consideration: N/A 

Lactation: N/A  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence when combined with risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence when combined with risk when combined with adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care when combined with potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence when combined with 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 the risks over benefits. Hence these categories when combined with drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology: 

• Antibody-Dependent Cellular Cytotoxicity (ADCC): obinutuzumab binds to CD20 on B-cells, leading to the activation of immune effector cells, such as NK cells and macrophages. These immune cells then recognize and destroy the CD20-expressing B-cells through ADCC. 
• Complement-Dependent Cytotoxicity (CDC): obinutuzumab can activate the complement system, leading to the formation of the membrane attack complex that lyses CD20-expressing B-cells. 
• Induction of Apoptosis: obinutuzumab can directly induce programmed cell death, or apoptosis, in CD20-expressing B-cells. 
• Antibody-Dependent Cellular Phagocytosis (ADCP): obinutuzumab facilitates the phagocytosis of CD20-expressing B-cells by macrophages. 

Pharmacodynamics: 

• B-Cell Depletion: obinutuzumab binds to CD20 on B-cells, resulting in the depletion of both normal and malignant B-cells. This depletion occurs through various mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), induction of apoptosis, and antibody-dependent cellular phagocytosis (ADCP). By targeting CD20-positive B-cells, obinutuzumab helps reduce the B-cell population, which is important in the treatment of B-cell malignancies. 
• Immune Activation: obinutuzumab activates the immune system by engaging immune effector cells, such as natural killer (NK) cells and macrophages, through its Fc region. This immune activation enhances the clearance of CD20-expressing B-cells and contributes to the therapeutic effects of obinutuzumab. 
• Modulation of B-Cell Signalling: obinutuzumab binding to CD20 on B-cells can disrupt B-cell receptor (BCR) signalling pathways. This modulation can interfere with the survival and proliferation of B-cells and impair their ability to support tumor growth and progression.

Pharmacokinetics: 

Absorption 

obinutuzumab is administered intravenously, which allows for rapid and complete absorption into the bloodstream. As an intravenous infusion, the drug directly enters systemic circulation. 

Distribution 

obinutuzumab has a large volume of distribution, indicating extensive distribution throughout the body. It distributes into the extravascular space, including lymphoid tissues where B-cells are present. 

Metabolism 

Monoclonal antibodies like obinutuzumab are not typically metabolized in the same way as small-molecule drugs. They undergo catabolism into smaller peptides and amino acids via normal protein degradation pathways. obinutuzumab is primarily eliminated from the body without undergoing significant metabolism. 

Elimination and excretion 

obinutuzumab is eliminated through proteolytic degradation and clearance mechanisms within the body. The exact route and rate of excretion are not well-defined, but it is expected to be eliminated through various routes, including renal filtration and hepatic clearance. 

Administration: 

• Pre-Medication: Prior to the infusion, patients may receive pre-medication to reduce the risk of infusion-related reactions. This may include antihistamines, corticosteroids, and antipyretics. 
• Dilution: obinutuzumab is typically supplied as a concentrate that needs to be diluted before administration. The appropriate dilution should be prepared using aseptic techniques and according to the instructions provided by the manufacturer. 
• Infusion Rate: The initial infusion rate is typically started at a slow rate, and it is gradually increased over time if tolerated well. The healthcare provider will determine the appropriate infusion rate based on the patient’s tolerance and the specific treatment regimen. 
• Monitoring: During the infusion, patients are closely monitored for any signs of infusion-related reactions, such as fever, chills, rash, shortness of breath, or changes in blood pressure. Vital signs and other relevant parameters are monitored throughout the infusion. 
• Duration and Frequency: obinutuzumab treatment depend on the specific indication and treatment plan. It is usually administered in cycles, with each cycle consisting of several infusions given at specified intervals.

Patient information leaflet 

Generic Name: obinutuzumab 

Pronounced: (oh-bi-NOO-tuh-zoo-mab)  

Why do we use obinutuzumab? 

• Chronic Lymphocytic Leukemia (CLL): obinutuzumab, in combination with other chemotherapy agents, is approved for the treatment of previously untreated CLL. It is used in combination with chlorambucil or bendamustine to improve progression-free survival and overall survival in patients with CLL. 
• Follicular Lymphoma: obinutuzumab, in combination with chemotherapy (such as cyclophosphamide, doxorubicin, vincristine, and prednisone), is indicated for the treatment of previously untreated advanced-stage follicular lymphoma. 
• Diffuse Large B-Cell Lymphoma (DLBCL): obinutuzumab, in combination with chemotherapy (such as cyclophosphamide, doxorubicin, vincristine, and prednisone), is used for the treatment of previously untreated DLBCL in adult patients. 
• Previously Treated CLL: obinutuzumab, in combination with other agents, is also used for the treatment of CLL that has relapsed or did not respond to prior therapy.