Rituximab.pptx

cd 20 monoclonal antibody

1. Rituximab Presenter : Dr Ankita

2. Mechanism of Action Rituximab is an anti CD20 chimeric antibody . CD20 is surface transmembrane protein marker expressed on B cells during differentiation from the pre-B cell until the plasma cell stage. CD20 believed to function as a calcium channel and play a role in the maturation and activation of B cells. Once rituximab is bound to CD20 positive cells, cell death is induced by various mechanisms including : A ntibody-dependent cell-mediated cytotoxicity (ADCC) Complement-mediated-cytotoxicity(CDC) A ntibody-dependent phagocytosis (ADP) Direct effects of binding of rituximab to CD20.

3. Indication Rituximab is an anti-CD20 monoclonal antibody that was first approved by the FDA in 1997 CD20 positive B-cell Non-Hodgkin’s Lymphoma (NHL) Chronic Lymphocytic Leukemia (CLL). Rheumatoid Arthritis Microscopic Polyangiitis (MP) and Granulomatosis with Polyangiitis (GPA). Pemphigus Vulgaris (PV) : Approved in 2018 for use in combination with glucocorticoids for adult patients with moderate to severe disease

4. Administration Rituximab and its biosimilars are approved for use by intravenous infusion. S hould not be administered as IV bolus or push.  Patients should be given acetaminophen and antihistamine before each infusion. Rituximab should be diluted in an infusion bag of either 0.9% sodium chloride, 5% dextrose in water, or USP. No other drugs should be mixed with it Rituximab-hyaluronidase human is approved for subcutaneous use. It should be administered in the subcutaneous abdominal tissue over five to seven minutes Hyaluronidase causes a reversible increase in permeability of subcutaneous tissue by causing depolymerization of hyaluronan, which leads to an increase in the absorption rate of rituximab

5. Adverse Effects Infusion reactions   -  M ost common and most serious adverse effects. Allergic or anaphylactic reactions were seen in 80 to 90% of patients. Seen within 30 to 120 minutes . Infusion reactions can include fever, chills, skin rash, urticaria, angioedema, hypotension, ARDS, ventricular fibrillation, shock, anaphylaxis, and death.

6. Infections -  Serious bacterial, viral, and fungal infections can occur. New or reactivated viral infections can include JC virus infection, herpes simplex, CMV, varicella-zoster, West Nile Virus, and hepatitis B and C. Due to the risk of reactivation, live vaccines are contraindicated during treatment with rituximab. They should be given at least four weeks before starting rituximab. PCP is an opportunistic fungal infection whose prophylaxis is recommended in patients receiving fludarabine/cyclophosphamide/rituximab combination in CLL

7. Hematologic -  Lymphopenia is the most commonly seen hematologic adverse effect. Others include leukopenia, neutropenia, thrombocytopenia, and anemia. Dermatologic/mucocutaneous reactions -  Include pruritis, alopecia, skin rash, and life-threatening reactions like toxic epidermal necrolysis, paraneoplastic pemphigus, and Stevens-Johnson syndrome. Renal -  Tumor lysis syndrome can present with hypocalcemia , hyperphosphatemia, hyperkalemia , hyperuricemia, and acute renal failure within 24 hours of the first infusion. Aggressive hydration and uric acid lowering therapy should be given to high-risk patients. . Respiratory -  These include cough, upper respiratory tract infections, rhinitis, epistaxis, bronchospasm, dyspnea , pulmonary toxicity, ILD. There have been reports of rare cases of hypersensitivity pneumonitis, status asthmaticus, diffuse alveolar hemorrhage , and bronchiolitis obliterans

8. Cardiovascular -  Tachycardia, supraventricular arrhythmias, non-ischemic cardiomyopathy, peripheral edema, chest pain, hypertension GI -  Diarrhea, nausea, and vomiting can be seen. Symptoms of abdominal pain should be thoroughly investigated as there have been reports of bowel obstruction and perforation. Neuropsychiatric -  Dizziness, headache, anxiety, depression, and insomnia can occur. Pregnancy -  A limited amount crosses the placental barrier during the first trimester but crossing increases in the second and third trimester. Administration of rituximab during the third trimester can lead to immunosuppression in the neonate. Levels of rituximab in fetal circulation are similar to maternal levels near term

9. Gonadal effect Repeated administration of rituximab to the arthritic DBA/1 J mice suppressed disease severity and decreased testicular disruptions. Rituximab treatment also diminished gonadal oxidative stress, through decreasing reactive oxygen species generation and restoring the reduced glutathione level in arthritic DBA/1 J mice. In conclusion, rituximab safe therapeutic agent and can mitigate gonadal disruptions  Al- Hamamah MA, Alotaibi MR, Ahmad SF, Nadeem A, Attia MSM, Ansari MA, Bakheet SA, Alanazi MM, Attia SM. Treatment with the anti-CD20 monoclonal antibody rituximab mitigates gonadal disruptions in the collagen-induced arthritis in male DBA/1 J mouse model

10. Contraindications Some absolute and relative contraindications of the drug include Severe, active infection Hypersensitivity to any of the components of the formulation Severe heart failure Uncontrolled cardiac disease Pregnancy