Promethazine is NOT Recommended for Chronic Cough Management
Promethazine has no established role in treating chronic cough and should be avoided, particularly in patients with COPD, as recent evidence demonstrates significantly increased risk of severe exacerbations and death. 1
Critical Safety Concerns
In patients with severe COPD, promethazine treatment is associated with a 42% increased risk of severe exacerbations and death (HR 1.42, CI 1.27-1.58) compared to melatonin, with risk increasing to 115% (HR 2.15) in patients using ≥400 tablets/year. 1
This excess mortality and morbidity risk persists regardless of comorbid asthma status. 1
Promethazine is a sedating antihistamine used primarily as an anxiolytic/hypnotic agent, not as an antitussive, and has no evidence base for cough suppression. 1
Evidence-Based Approach to Chronic Cough
Initial Management Algorithm
The American College of Chest Physicians and Thorax guidelines recommend a systematic algorithmic approach addressing the most common etiologies before considering any cough suppressants. 2
The five most common causes to address first are: 3
- Asthma (39% of cases) 4
- Upper airway cough syndrome (UACS) from rhinosinus conditions 2
- Gastroesophageal reflux disease (GERD) 2
- Nonasthmatic eosinophilic bronchitis 2
- COPD (11% of cases) 4
For GERD-Related Cough Specifically
If GERD is suspected with typical symptoms (heartburn, regurgitation), the American College of Chest Physicians recommends: 2, 5
- Diet modification and weight loss in overweight/obese patients 2, 5
- Head of bed elevation and avoiding meals within 3 hours of bedtime 2, 5
- PPIs (omeprazole 20 mg or lansoprazole 30 mg once daily), H2-receptor antagonists, or alginates sufficient to control GI symptoms 2, 5
Critical caveat: In patients WITHOUT heartburn or regurgitation, PPIs alone are NOT recommended as they are unlikely to resolve cough (Grade 1C). 2, 5
For Upper Airway Cough Syndrome
In patients with prominent upper airway symptoms, topical corticosteroids are recommended as first-line therapy. 2
- There is disparity in reported efficacy of antihistamines for UACS-related cough. 2
For Asthma-Related Cough
No currently available tests can reliably exclude corticosteroid-responsive cough. 2
- A 2-week oral steroid trial is recommended; if no response occurs, eosinophilic airway inflammation is unlikely. 2
Essential Exclusions
Stop ACE inhibitors immediately in any patient with troublesome chronic cough, as this is one of the most common reversible causes. 2
Encourage smoking cessation, as smoking is one of the commonest causes of persistent cough and appears dose-related. 2
When Specific Therapy Fails: Refractory Cough
Only after 4-6 weeks of empiric treatment for the most likely diagnoses should symptomatic antitussives be considered. 3
Evidence-Based Symptomatic Antitussives
For refractory chronic cough, low-dose morphine is the preferred symptomatic treatment. 2, 3
Alternative options with weaker evidence include: 2, 3
Traditional over-the-counter antitussives like dextromethorphan and codeine have efficacy often no better than placebo, particularly in COPD-related cough. 6
Common Pitfalls to Avoid
Never suppress cough when clearance is important (pneumonia, bronchiectasis). 2
Do not use promethazine or other sedating antihistamines as antitussives, especially in COPD patients. 1
Failure to consider GORD as a cause is a common reason for treatment failure, but remember that reflux-associated cough may occur without GI symptoms. 2
An algorithmic approach resolves chronic cough in 82-100% of cases when properly applied. 2, 4