Rituximab

# Rituximab ## Overview - **Classification**: Monoclonal antibody (mAb), Anti-CD20 - **Mechanism**: Binds specifically to the CD20 antigen on pre-B and mature B-lymphocytes, leading to cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis. ## Primary Indications 1. **Non-Hodgkin's Lymphoma (NHL)** - CD20-positive, relapsed/refractory, previously untreated, or diffuse large B-cell lymphoma (DLBCL). 2. **Chronic Lymphocytic Leukemia (CLL)** - CD20-positive, in combination with fludarabine and cyclophosphamide. 3. **Rheumatoid Arthritis (RA)** - Moderate to severe, active, in combination with methotrexate, inadequate response to TNF antagonists. 4. **Granulomatosis with Polyangiitis (GPA) & Microscopic Polyangiitis (MPA)** - In combination with glucocorticoids, for induction and maintenance. 5. **Pemphigus Vulgaris (PV)** - Moderate to severe, in combination with glucocorticoids. ## Adult Dosing ### Standard Dosing **Non-Hodgkin's Lymphoma (NHL)** - **Dose**: **375 mg/m² IV** - **Frequency**: Once weekly - **Route**: Intravenous infusion - **Duration**: 4-8 doses, or with chemotherapy regimens (e.g., R-CHOP) **Chronic Lymphocytic Leukemia (CLL)** - **Dose**: **375 mg/m² IV** on Day 1 of cycle 1, then **500 mg/m² IV** on Day 1 of subsequent cycles. - **Frequency**: Every 28 days (with fludarabine/cyclophosphamide) - **Route**: Intravenous infusion - **Duration**: Up to 6 cycles **Rheumatoid Arthritis (RA)** - **Dose**: **1000 mg IV** - **Frequency**: On Day 1 and Day 15 (two infusions per treatment course) - **Route**: Intravenous infusion - **Duration**: Repeat course every 24 weeks or based on clinical evaluation. **Granulomatosis with Polyangiitis (GPA) & Microscopic Polyangiitis (MPA)** - **Induction**: **375 mg/m² IV** - **Frequency**: Once weekly for 4 doses - **Route**: Intravenous infusion - **Maintenance**: **500 mg IV** - **Frequency**: Every 6 months, starting 6 months after the last induction dose, for at least 2 years. **Pemphigus Vulgaris (PV)** - **Dose**: **1000 mg IV** - **Frequency**: On Day 1 and Day 15 (first course). Subsequent courses: **500 mg IV** at Month 12, Month 18, and then every 6 months. - **Route**: Intravenous infusion ### Dose Adjustments - **Renal Impairment**: No specific dose adjustment required. - **Hepatic Impairment**: No specific dose adjustment required. - **Elderly Patients**: No specific dose adjustment required based on age alone. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: Not recommended for routine use. - **Special Notes**: Safety and efficacy not established. ### Infants (1-12 months) - **Dose**: Not recommended for routine use. - **Special Notes**: Safety and efficacy not established. ### Children (2-12 years) **Granulomatosis with Polyangiitis (GPA) & Microscopic Polyangiitis (MPA)** - **Dose**: **375 mg/m² IV** - **Frequency**: Once weekly for 4 doses (induction) - **Maximum**: Refer to adult maximum single dose (no specific pediatric maximum defined, but based on BSA). - **Special Notes**: Premedicate with antihistamine, acetaminophen, and corticosteroid. ### Adolescents (13-18 years) **Granulomatosis with Polyangiitis (GPA) & Microscopic Polyangiitis (MPA)** - **Dose**: **375 mg/m² IV** (induction); **500 mg IV** (maintenance) - **Frequency**: Weekly x 4 (induction); every 6 months (maintenance) - **Maximum**: Adult dosing applies. - **Special Notes**: Dosing follows adult recommendations for GPA/MPA and other indications (e.g., NHL) based on BSA or fixed dose. ## Safety Information ### Contraindications - **Absolute**: Known severe hypersensitivity to rituximab or murine proteins. - **Absolute**: Active, severe infections. ### Common Adverse Effects - **Very Common (>10%)**: Infusion-related reactions (fever, chills, nausea, rash, pruritus), infections (bacterial, viral), headache. - **Common (1-10%)**: Nausea, vomiting, diarrhea, cough, neutropenia, peripheral edema, asthenia. - **Serious but Rare**: Progressive multifocal leukoencephalopathy (PML), Hepatitis B reactivation (fatal cases reported), severe mucocutaneous reactions (SJS, TEN), tumor lysis syndrome, cytokine release syndrome, cardiac arrest. ### Key Drug Interactions - **Live Vaccines**: Avoid concurrent administration; risk of vaccine-induced infection or reduced efficacy. - **Other Immunosuppressants**: May increase risk of severe infections. Monitor closely. - **Antihypertensives**: Consider temporarily withholding on infusion days due to risk of infusion-related hypotension. ## Monitoring & Follow-up - **Before Treatment**: - Complete Blood Count (CBC) with differential. - Hepatitis B Virus (HBV) screening (HBsAg and anti-HBc). - Quantitative immunoglobulins (IgG, IgA, IgM). - **During Treatment**: - Monitor for signs/symptoms of infusion-related reactions (especially during first infusion). - Monitor for signs of infection (fever, chills, sore throat). - CBC with differential regularly. - Monitor for neurological symptoms (PML). - **Clinical Signs**: Watch for fever, shortness of breath, chills, rash, severe headache, confusion, weakness, vision changes. ## Clinical Pearls - 💡 **Premedicate**: Always premedicate with an antihistamine, acetaminophen, and a corticosteroid (e.g., methylprednisolone) 30-60 minutes prior to each infusion to reduce infusion-related reactions. - 💡 **Hep B Reactivation**: Screen all patients for HBV. If positive (HBsAg+ or anti-HBc+), consider antiviral prophylaxis or consult with an infectious disease specialist. - 💡 **PML Risk**: Counsel patients on symptoms of PML (new or worsening neurological symptoms). Discontinue rituximab immediately if PML is suspected. - 💡 **Infusion Rate**: Start infusion slowly and gradually increase rate if well-tolerated. Slow or interrupt for infusion reactions. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.