BLACK BOX WARNING
- fatal infusion reactions
- severe mucocutaneous reactions
- PML (progressive multifocal leukoencephalopathy)
- hepatitis B reactivation
rituximab
Brand: Rituxan, MabThera
⚠ BBW ISMP High Alert Prototype Drug
Drug Class: anti-CD20 monoclonal antibody
Drug Family: antineoplastic
Subclass: chimeric murine-human IgG1 anti-CD20 monoclonal antibody
Organ Systems: hematology-oncologyimmunology
Mechanism of Action
Binds CD20 (a B cell-specific surface antigen) on normal and malignant B cells; depletes B cells via complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and direct induction of apoptosis; spares plasma cells and B cell precursors (lack CD20).
CD20 antigen on B lymphocytes
Indications
- non-Hodgkin lymphoma (CD20+)
- chronic lymphocytic leukemia (CLL)
- rheumatoid arthritis (with methotrexate, after anti-TNF failure)
- granulomatosis with polyangiitis/microscopic polyangiitis (ANCA vasculitis)
- pemphigus vulgaris
Contraindications
- rituximab hypersensitivity
- active, severe infections
- live vaccine administration within 4 weeks
Adverse Effects
Common
- infusion-related reactions (fever, chills, nausea — very common with first infusion)
- fatigue
- rash
Serious
- fatal infusion reactions (severe bronchospasm, hypoxia, hypotension)
- progressive multifocal leukoencephalopathy (PML — JC virus reactivation)
- hepatitis B reactivation
- severe mucocutaneous reactions (TEN, SJS, pemphigus)
- late-onset neutropenia
- prolonged hypogammaglobulinemia
Pharmacokinetics (ADME)
| Absorption | IV only |
| Distribution | binds to CD20+ B cells throughout the body; CSF levels negligible |
| Metabolism | proteolytic catabolism |
| Excretion | no urinary or biliary excretion of the molecule; catabolized in target cells and reticuloendothelial system |
| Half-life | 22 days (highly variable with B cell depletion) |
| Onset | days (B cell depletion immediate); clinical response weeks |
| Peak | end of infusion |
| Duration | every 3 weeks (oncology) or every 6 months (rheumatology) |
| Protein Binding | not applicable (IgG1) |
| Vd | low (3–4 L) |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| immunosuppressants | additive immunosuppression; increased infection risk | moderate |
| live vaccines | B cell depletion impairs vaccine response; live vaccines contraindicated during and for ≥12 months after therapy | major |
Nursing Considerations
- Pre-medicate with acetaminophen and diphenhydramine (and methylprednisolone for some protocols) before each infusion to reduce infusion reactions.
- Start infusion at 50 mg/hr and increase every 30 minutes as tolerated up to 400 mg/hr; never administer as rapid infusion or bolus — resuscitation equipment must be available.
- Screen for hepatitis B surface antigen and hepatitis B core antibody before initiating; HBV-seropositive patients require antiviral prophylaxis (entecavir preferred) throughout and for 12 months after therapy.
- Monitor for PML signs and symptoms (new neurological symptoms, cognitive changes, vision changes); alert any neurological changes to the prescriber immediately.
Clinical Pearls
- Rituximab transformed the treatment of CD20+ B cell malignancies: adding rituximab to CHOP chemotherapy (R-CHOP) for diffuse large B cell lymphoma improved 5-year overall survival by 10–15% — one of the largest single improvements in lymphoma outcomes.
- PML from JC virus reactivation is a devastating but rare complication of rituximab — most patients with rituximab-associated PML have severely compromised immune systems from concurrent immunosuppression or underlying lymphoma.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.