Availability of Promethazine with Codeine for Cough
Yes, promethazine with codeine is still available in the United States, but it should not be your first-line choice for cough suppression given the superior efficacy of other agents and significant safety concerns.
Current Status and Regulatory Context
Promethazine-codeine combination products remain FDA-approved and commercially available as prescription medications in the U.S. However, the evidence does not support this specific combination as optimal therapy for cough management.
Why This Combination Is Suboptimal
Codeine's Limited Efficacy
- Codeine is outperformed by other antitussives. Dextromethorphan has been demonstrated to be more effective than codeine in controlling cough, including in patients with lung cancer 1.
- The American College of Chest Physicians recommends pholcodine or hydrocodone over codeine when an opioid is indicated for cough, specifically due to codeine's greater side effect burden 2.
- Hydrocodone is preferred over codeine in the treatment hierarchy for opioid-responsive cough, with documented efficacy in reducing cough frequency 2.
Promethazine's Problematic Profile
- Promethazine is a first-generation antihistamine with significant sedative effects and anticholinergic side effects 3.
- The combination adds sedation without clear evidence that promethazine enhances codeine's antitussive effect beyond what codeine alone provides 3.
- Antiemetics like promethazine can prolong QT intervals, creating cardiovascular risks 1.
Better Alternatives for Cough Management
For Non-Opioid Approaches
- Dextromethorphan is superior to codeine without adding opioid burden and should be tried first for symptomatic cough suppression 1, 2.
- Benzonatate (a peripherally-acting antitussive) has been shown to control cough effectively in patients with lung cancer when opioids were ineffective 1.
When Opioids Are Necessary
- Hydrocodone (typically 5 mg twice daily) is the preferred opioid for cough suppression, available in liquid formulations for flexible dosing 2, 4.
- Low-dose morphine (2.5-5 mg oral) can be used for refractory dyspnea and cough, particularly in palliative care settings 1, 5.
Clinical Algorithm for Cough Suppression
First-line: Over-the-counter dextromethorphan for symptomatic relief 1.
Second-line: If dextromethorphan fails and cough is severe, prescribe hydrocodone 5 mg twice daily rather than codeine-containing products 2, 4.
Third-line: For opioid-resistant cough, consider benzonatate or peripherally-acting agents like levodropropizine (though not available in the U.S.) 1, 6.
Reserve for refractory cases: Low-dose morphine (5-10 mg slow-release twice daily) for intractable cough, particularly in cancer or palliative care patients 5, 6.
Critical Safety Considerations
- All opioid antitussives carry risks of respiratory depression, particularly in opioid-naive patients or those with underlying pulmonary disease 2.
- Graduated dosing with caution is essential due to risks of respiratory depression and hypoventilation 1.
- The evidence quality for all antitussives remains surprisingly low, with most recommendations based on clinical experience rather than robust randomized trials 2, 7.
The Bottom Line
While promethazine with codeine remains available, prescribe hydrocodone alone or dextromethorphan instead for superior efficacy and better safety profiles. The promethazine component adds sedation and cardiovascular risks without clear antitussive benefit beyond what codeine provides, and codeine itself is inferior to other available options 1, 2.