What is the recommended first-generation antihistamine-decongestant combination, such as Drixoral (Dexbrompheniramine maleate plus pseudoephedrine sulfate), for the treatment of upper airway cough syndrome?

First-Generation Antihistamine-Decongestant Combinations for Upper Airway Cough Syndrome

The combination of dexbrompheniramine maleate (6 mg twice daily) plus sustained-release pseudoephedrine sulfate (120 mg twice daily) is the recommended first-generation antihistamine-decongestant combination for treating upper airway cough syndrome. 1

Mechanism and Efficacy

First-generation antihistamine-decongestant combinations are effective primarily due to:

• Anticholinergic properties of first-generation antihistamines, not their antihistaminic effects 1
• Vasoconstriction from the decongestant component that reduces secretory response 1

These combinations have been shown to be consistently efficacious in:

• Randomized, double-blind, placebo-controlled studies of acute cough
• Prospective descriptive studies of chronic cough 1

Specific Recommended Combinations

Two specific combinations have demonstrated efficacy in clinical studies:

1. Dexbrompheniramine maleate (6 mg BID) + sustained-release pseudoephedrine sulfate (120 mg BID) 1, 2
2. Azatadine maleate (1 mg BID) + sustained-release pseudoephedrine sulfate (120 mg BID) 1

Important Clinical Considerations

Newer vs. Older Generation Antihistamines

• Newer generation (non-sedating) antihistamines are ineffective for treating cough associated with upper airway cough syndrome 1
• Studies with terfenadine (with or without pseudoephedrine) and loratadine showed ineffectiveness in treating acute cough 1

Treatment Duration and Response

• Improvement typically occurs within days to 2 weeks of starting therapy 1, 2
• A minimum treatment duration of 3 weeks is recommended for optimal effect 2
• If cough persists despite 4 weeks of appropriate treatment, further investigation is warranted 2

Side Effect Management

• Common side effects include dry mouth, transient dizziness, and sedation 1
• To minimize sedation, consider starting with once-daily dosing at bedtime before advancing to twice-daily 1, 2
• Monitor for insomnia, urinary difficulties (especially in older men), jitteriness, tachycardia, hypertension, and increased intraocular pressure 1

Special Populations and Cautions

Use with Caution In:

• Patients with glaucoma
• Men with prostatic hypertrophy
• Patients with hypertension 1, 2

Alternative Options

• For patients who cannot tolerate first-generation A/D combinations, ipratropium bromide nasal spray may be effective, though evidence is limited 1
• For allergic rhinitis specifically, nasal corticosteroids may be more appropriate 1, 2

Diagnostic Approach

• Upper airway cough syndrome is a clinical diagnosis with no pathognomonic findings 1
• Response to treatment with first-generation A/D combinations is both diagnostic and therapeutic 1, 2
• If no response to empiric A/D therapy after appropriate trial, sinus imaging should be considered 1

First-generation antihistamine-decongestant combinations, particularly dexbrompheniramine with pseudoephedrine, remain the cornerstone of treatment for upper airway cough syndrome due to their proven efficacy and the anticholinergic properties that specifically address the underlying mechanism of cough.