Which prescription cough syrups contain codeine (e.g., Robitussin AC (guaifenesin and codeine phosphate), Cheratussin AC (guaifenesin and codeine phosphate), Phenergan (promethazine) with codeine, Mucinex DM (guaifenesin and dextromethorphan) with codeine)?

Codeine-Containing Cough Medicines

The most common prescription cough medicines containing codeine are guaifenesin with codeine phosphate (e.g., Robitussin AC, Cheratussin AC) and promethazine with codeine, though these should NOT be first-line choices due to their inferior safety profile compared to dextromethorphan-based alternatives. 1, 2, 3

Available Codeine-Containing Formulations

FDA-Approved Products

• Guaifenesin with codeine phosphate is the standard formulation, containing 10 mg codeine phosphate per 5 mL teaspoon combined with 100 mg guaifenesin as an expectorant 4
• Promethazine with codeine combines the antihistamine promethazine with codeine, though promethazine has no established efficacy for cough suppression and is primarily used for nausea and sedation 2

Common Brand Names

• Robitussin AC (guaifenesin and codeine phosphate) 4
• Cheratussin AC (guaifenesin and codeine phosphate) 4
• Phenergan with codeine (promethazine and codeine) 2

Critical Clinical Guidance: Why Codeine Should NOT Be First-Line

Superior Alternative Exists

• Dextromethorphan is the preferred antitussive agent with a superior safety profile compared to codeine, providing equivalent efficacy without the significant adverse effects 1, 2, 3
• The British Thoracic Society explicitly states that codeine and pholcodine have no greater efficacy than dextromethorphan but carry a much greater adverse side effect profile 1, 2

Codeine's Significant Drawbacks

• Adverse effects include: drowsiness, nausea, constipation, and risk of physical dependence 1, 2, 5
• Codeine is a prodrug requiring CYP2D6 metabolism to morphine for its opioid effects, leading to variable efficacy and opioid-related complications 6
• Drug abusers often use codeine-containing cough syrups as morphine/heroin substitutes 7

When Codeine Might Be Considered

Limited Clinical Scenarios

• Only after dextromethorphan and other measures have failed for severe postinfectious cough 1, 2
• In advanced cancer patients with refractory cough where opioid-based antitussives may be necessary 3, 8
• When the sedative and analgesic properties are specifically needed alongside cough suppression 6, 5

Appropriate Dosing When Used

• Standard dosing contains 10 mg codeine phosphate per 5 mL 4
• Multiple therapeutic doses over 2 days (8 doses of 4.5 mg each) can produce positive morphine screens in urine for 12-30 hours after the last dose 7

Recommended Treatment Algorithm

First-Line Approach

• Start with honey and lemon mixtures as the simplest, cheapest, and often effective treatment 1, 2, 3
• Consider voluntary cough suppression through central modulation 1, 2

Second-Line Pharmacological Treatment

• Dextromethorphan 30-60 mg is the preferred antitussive, with maximum cough suppression at 60 mg 1, 2, 3
• For nocturnal cough, first-generation sedating antihistamines may be appropriate 1, 2

Third-Line Options (Before Codeine)

• Inhaled ipratropium for postinfectious cough 1, 2
• Short-course prednisone 30-40 mg daily for severe paroxysms 1, 2

Last Resort Only

• Codeine-containing preparations should only be considered when all other measures fail 1, 2

Common Pitfalls to Avoid

• Do not prescribe codeine as first-line treatment when dextromethorphan provides equivalent efficacy with better safety 1, 2, 3
• Do not use promethazine with codeine expecting enhanced cough suppression, as promethazine has no established antitussive efficacy 2
• Avoid codeine for productive cough where clearance of secretions is beneficial 3
• Be aware of abuse potential and that codeine-containing syrups are frequently misused 7