Can rituximab (Rituxan) be co‑administered with the inhaled triple therapy Trelegy (fluticasone furoate + umeclidinium + vilanterol) without dose adjustments, and what safety considerations should be noted?

Rituxan and Trelegy Interaction

Rituximab (Rituxan) can be safely co-administered with Trelegy (fluticasone furoate/umeclidinium/vilanterol) without dose adjustments, as there are no known pharmacokinetic or pharmacodynamic interactions between these medications.

Mechanism and Rationale

The two medications act through completely separate pathways with no overlapping mechanisms:

• Rituximab is a monoclonal antibody that targets CD20-positive B lymphocytes systemically, used primarily for autoimmune conditions and hematologic malignancies 1
• Trelegy is an inhaled triple therapy containing a corticosteroid (fluticasone furoate), a long-acting muscarinic antagonist (umeclidinium), and a long-acting beta-agonist (vilanterol) that acts locally in the airways 2, 3

The systemic absorption of Trelegy components is minimal, with pharmacokinetic studies showing that all three components are adequately described by two-compartment models with first-order absorption and no clinically relevant drug interactions 4, 5.

Safety Considerations

Infection Risk with Combined Therapy

The primary safety concern when using these medications together relates to additive immunosuppression:

• Rituximab causes B-cell depletion that can persist for months, increasing infection risk 1
• The inhaled corticosteroid component of Trelegy (fluticasone furoate) may increase pneumonia risk in COPD patients 6
• Monitor closely for respiratory infections, particularly pneumonia, when using both medications concurrently

Specific Monitoring Recommendations

For patients on both medications:

• Watch for signs of respiratory infection (increased dyspnea, sputum purulence, fever) 6
• Monitor for oral candidiasis, hoarseness, and upper respiratory tract infections related to inhaled corticosteroid use 6
• Ensure proper inhaler technique to minimize systemic corticosteroid absorption 6
• Consider pneumococcal and annual influenza vaccination to reduce infection risk 6

Corticosteroid Considerations

While Trelegy contains an inhaled corticosteroid, the systemic exposure is minimal compared to oral corticosteroids 4, 5. However:

• If the patient requires systemic corticosteroids for COPD exacerbations (prednisone 30-40 mg daily for 5 days), this can be safely administered alongside both Rituxan and Trelegy 6
• The inhaled corticosteroid in Trelegy does not require adjustment when rituximab is initiated or ongoing 4

Common Pitfalls to Avoid

• Do not discontinue Trelegy when starting rituximab, as COPD maintenance therapy should be continued without interruption 6
• Do not increase the inhaled corticosteroid dose in Trelegy as a response to rituximab therapy; these medications serve different purposes 6
• Do not delay treatment of COPD exacerbations due to concerns about rituximab; standard exacerbation management with bronchodilators, systemic corticosteroids, and antibiotics (when indicated) should proceed as usual 6

Clinical Bottom Line

No dose adjustments are needed for either medication when used concurrently. The main clinical consideration is heightened vigilance for respiratory infections, particularly pneumonia, given the combined immunosuppressive effects. Maintain standard COPD management protocols and ensure patients understand the importance of reporting early signs of infection 1, 6, 3.