Rituximab
Rituximab
Generic Name
Rituximab
Mechanism
- CD20 binding → B‑cell apoptosis via complement‑dependent cytotoxicity (CDC) or antibody‑dependent cellular cytotoxicity (ADCC)
- B‑cell depletion lowers autoantibody production, cytokine release, and antigen presentation (critical in B‑cell–mediated diseases)
Pharmacokinetics
| Parameter | Detail |
| Route | IV infusion |
| Absorption | Not applicable (directly in circulation) |
| Distribution | Large volume (∼3 L), extracellular fluid and interstitial space; limited CNS penetration <1% of plasma concentration |
| Metabolism | Catabolized by proteolytic enzymes (lysosomal proteases) into peptides & amino acids |
| Elimination | Linear elimination; half‑life 9–12 days in normal patients; 30–50 % depletion of CD20 + cells typically after 3–4 cycles |
| Drug‑Drug Interactions | No significant CYP interactions; potential increased infusion‑reaction risk with concurrent high‑dose steroids or antiprotozoals |
Indications
- B‑cell non‑Hodgkin lymphoma (NHL) (e.g., follicular, diffuse large B‑cell) in combination with chemo
- Chronic lymphocytic leukemia (CLL) (in combination therapy)
- Rheumatoid arthritis (RA) (≥‐5 mg methotrexate)
- Granulomatosis with polyangiitis (GPA) & Microscopic polyangiitis (ANCA‑associated vasculitis)
- Idiopathic membranous nephropathy (in selected patients)
- Hodgkin lymphoma (limited use)
- Autoimmune hemolytic anemia (AHA), dermatomyositis, or systemic lupus erythematosus (off‑label)
Contraindications
- Known hypersensitivity to rituximab, murine proteins, or any excipients (e.g., polysorbate 80)
- Active, untreated infection (including tuberculosis)
- Severe hepatic impairment – avoid or use with heightened caution
- Inflammatory bowel disease flares – rituximab may precipitate colitis
- Pregnancy – category C; avoid if possible; high‑risk during lactation
- Infusion‐reaction risk – pre‑medication required; monitor patients with a history of severe reactions
- Post‑infusion ALC < 1 × 10⁹/L – increases risk of viral reactivation (e.g., hepatitis B, CMV)
Dosing
| Indication | Dose | Schedule | Notes |
| NHL | 375 mg/m² IV over 90‑120 min (day 1) | 4 weekly cycles (Days 1, 8, 15, 22) | Premedication: prednisone 100 mg, diphenhydramine 50 mg, acetaminophen 650 mg |
| CLL | 375 mg/m² IV (day 1) | 4 cycles (weekly) | Add fludarabine + cyclophosphamide if indicated |
| RA | 1000 mg IV (day 1 & 15) | 2 infusions 2 weeks apart, then every 6 months | Initiate with methotrexate (≥ 5 mg) |
| GPA/MPA | 375 mg/m² IV | 4 weekly cycles (Days 1, 8, 15, 22) | Add cyclophosphamide or azathioprine |
| Idiopathic membranous nephropathy | 375 mg/m² IV | 4 weekly cycles | 1–2‑year course; assess remission after 6 mo |
• Infusion times may be lengthened (up to 12 h) if reactions occur.
• For patients > 20 kg, a weight‑based 10 mg/mL solution may be used.
Adverse Effects
Common (≥ 10 %):
• Infusion reactions (fever, chills, hypotension, bronchospasm)
• Headache, fatigue, arthralgia
• Mild rash, pruritus
Serious (≤ 2 %–3 %):
• Severe infusion reactions (anaphylaxis, severe hypotension)
• Progressive multifocal leukoencephalopathy (PML) in immune‑suppressed patients
• Hepatitis B reactivation (> 10 % in seropositive pts)
• Neutropenia, thrombocytopenia, anemia (especially after repeated cycles)
• Lymphopenia → opportunistic infections (CMV, varicella zoster, fungal)
• Cardiovascular events (rare)
Monitoring
| Parameter | Timing | Rationale |
| Baseline CBC & BMP | Pre‑infusion | Identify cytopenias, renal & hepatic function |
| Severe infection screening (HBV, HCV, HSV, VZV, TB) | Baseline + before cycle 4 (if indicated) | Prevent viral reactivation |
| Liver function tests (AST, ALT, ALP, bilirubin) | Every 2–3 cycles | Detect hepatotoxicity |
| Infectious work‑up (especially CMV PCR) | At signs of infection | Early detection in immunosuppressed pts |
| Neurological exam | At each visit and if symptomatic | PML surveillance |
| Observation during infusion | Full infusion + 1 h post‑infusion | Manage infusion reactions promptly |
| Immunoglobulin levels | Every 6–12 mo in patients with hypogammaglobulinemia | Guide IVIG replacement if needed |
Clinical Pearls
- Red‑flag for infusion reaction: A patient who develops a temperature > 38.5 °C, systolic BP < 90 mmHg, or bronchospasm before completing a 3‑hour infusion should have the infusion stopped, treated with antihistamine, antipyretic, and possibly epinephrine.
- “Dose‑leveling” infusion: For patients with a history of reaction, start at 1/3 the weight‑based dose over 12 h, then gradually titrate to 1 × dose over the next 2–3 h.
- HBV prophylaxis: All HBsAg‑positive or anti‑HBc‐positive patients should receive antiviral prophylaxis (lamivudine, entecavir, or tenofovir) for 6 months after the last rituximab dose.
- Serum IgG monitoring: If IgG < 400 mg/dL with recurrent infections, consider intravenous immunoglobulin (IVIG) replacement.
- Elderly patients: Pre‑medication is essential; their risk of infusion reactions and infections is elevated, and they may have sub‑optimal immune reconstitution.
- Cross‑reactivity: Chimeric rituximab can trigger anti‑human/mouse antibodies; be vigilant for serum sickness later in therapy.
- Storage: Reconstituted rituximab is stable at 2–8 °C for 24 h; avoid repeated freeze‑thaw cycles.
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• *Sources:*
• Korean and American consensus guidelines (2023) on lymphoma and RA
• FDA drug labeling (latest revision)
• UpToDate® review, “Rituximab: Pharmacology & Clinical Use” (2024)
*Note:* Treat each patient individually; always cross‑check contraindications and monitor for infections when using rituximab.*