How to manage nasal congestion in a patient taking Keytruda (pembrolizumab)?

Managing Nasal Congestion in Patients on Pembrolizumab (Keytruda)

Start with intranasal corticosteroids as first-line therapy, as they are the most effective treatment for nasal congestion regardless of etiology, including drug-induced rhinitis from systemic medications like pembrolizumab. 1, 2

Understanding the Problem

• Drug-induced rhinitis from oral/systemic medications has a distinct pathophysiology and does not resolve by simply stopping the causative agent when the medication is medically necessary 2
• Pembrolizumab-related nasal congestion should be managed symptomatically while continuing cancer therapy, as the immunotherapy benefit far outweighs this side effect

First-Line Treatment: Intranasal Corticosteroids

Intranasal corticosteroids are superior to all other medication classes for nasal congestion and should be your initial choice. 1, 2, 3

• These agents effectively treat nonallergic rhinitis (including drug-induced forms) with minimal systemic side effects at recommended doses 1, 2
• Onset of action typically occurs within 12 hours, though full benefit may take several days to weeks 1, 2
• Examples include fluticasone, mometasone, or budesonide nasal sprays 3

Practical Administration Tips

• Direct patients to spray away from the nasal septum to minimize local irritation and bleeding 2
• Periodically examine the nasal septum to ensure no mucosal erosions develop 2
• Use the lowest effective dose 2

Second-Line and Combination Options

If intranasal corticosteroids alone provide insufficient relief after 2-4 weeks:

• Add intranasal antihistamines (azelastine or olopatadine) for enhanced efficacy with rapid onset of action (15-30 minutes) 1, 2
• The combination of intranasal antihistamine plus intranasal corticosteroid is more effective than either alone, particularly for nonallergic rhinitis 1, 2

Oral Decongestants: Use With Caution

• Pseudoephedrine may provide temporary relief of congestion 1, 4
• However, use extreme caution in cancer patients who may have: 2
  • Hypertension (common with immunotherapy)
  • Cardiac arrhythmias
  • Cerebrovascular disease
  • Other CNS-active medications
• Monitor blood pressure if used, as pseudoephedrine can increase systolic BP by approximately 1 mmHg and heart rate by 2-3 beats/min 2

Critical Pitfalls to Avoid

Never use topical nasal decongestants (oxymetazoline, xylometazoline) for more than 3-5 days maximum. 2, 4

• These cause rhinitis medicamentosa with rebound congestion, nasal hyperreactivity, and mucosal damage 2
• This is especially problematic in patients requiring long-term pembrolizumab therapy

Do not rely on oral antihistamines alone. 2, 4

• Nonsedating oral antihistamines are ineffective for nonallergic/drug-induced rhinitis 2
• They have only modest decongestant action even in allergic rhinitis 1, 4

When to Reassess or Refer

• If nasal congestion persists despite 2-4 weeks of appropriate intranasal corticosteroid therapy, evaluate for other causes beyond the pembrolizumab effect 2
• Consider referral to an allergist/immunologist if symptoms significantly impair quality of life, sleep, or daily functioning despite treatment 2
• Monitor for complications such as sinusitis or sleep disturbance that would warrant more aggressive intervention 2, 5

Treatment Algorithm Summary

1. Start: Intranasal corticosteroid (e.g., fluticasone 2 sprays each nostril daily) 1, 2, 3
2. If inadequate response after 2 weeks: Add intranasal antihistamine (azelastine) 1, 2
3. If still inadequate: Consider short-term oral decongestant (pseudoephedrine) if no contraindications 1, 2
4. If persistent after 4 weeks: Reassess for alternative causes and consider specialist referral 2