What are the alternatives to codeine (opioid) cough syrup?

Alternatives to Codeine Cough Syrup

Dextromethorphan is the preferred first-line alternative to codeine for cough suppression, as it has equal or superior efficacy with a significantly better safety profile and lacks the adverse effects associated with opioid antitussives. 1

Primary Non-Opioid Alternatives

Dextromethorphan (First Choice)

• Dextromethorphan has no greater efficacy disadvantage compared to codeine but has a much lower adverse side effect profile 1
• The effective dose is 60 mg for maximum cough reflex suppression, which is higher than typical over-the-counter formulations that contain subtherapeutic doses 1
• Meta-analysis demonstrates suppression of acute cough 1
• Objective assessment shows dextromethorphan lowers cough intensity to a greater degree than codeine (p < 0.0008) and is preferred by the majority of patients (p < 0.001) 2
• It is non-narcotic, safe even in overdose, and non-sedating 2
• Caution: When recommending higher doses (60 mg), ensure combined preparations don't contain excessive amounts of other ingredients like paracetamol 1

Benzonatate

• FDA-approved for symptomatic relief of cough 3
• Peripherally acting antitussive that has been extensively studied in acute and chronic cough settings with high efficacy and safety profiles 4
• Specifically studied in cancer and advanced cancer cough with demonstrated effectiveness 4

Simple Demulcents and Home Remedies

• Honey and lemon is the simplest and cheapest initial approach for acute viral cough 1
• Glycerol-based cough syrups show evidence of cough reduction 1
• Over-the-counter preparations include various demulcent syrups, though they may be less effective for profound cough, particularly when containing subtherapeutic levels of active ingredients 1, 5

Additional Non-Opioid Options

Menthol

• Suppresses the cough reflex acutely when inhaled 1
• Can be prescribed as menthol crystals or proprietary capsules 1
• Effect is short-lived 1

Sedating Antihistamines

• First-generation antihistamines (e.g., chlorpheniramine) suppress cough but cause drowsiness 1
• Particularly suitable for nocturnal cough when sedation is beneficial 1
• Often used in combination with other antitussives 6

Alternative Opioid Options (If Opioid Needed)

If non-opioid alternatives fail and an opioid is necessary:

Preferred Opioid Alternatives to Codeine

• Pholcodine, hydrocodone (where available), or dihydrocodeine are preferred over codeine due to better side effect profiles 1
• Codeine is specifically noted as less preferred despite being the most researched drug in this field, due to its greater side effect profile compared to other opioids 1
• Morphine should be reserved for cases where cough is not suppressed by other opioid derivatives or other means 1

Peripherally Acting Antitussives

Levodropropizine

• Probably equally effective to dihydrocodeine or moguisteine 1
• May provide earlier cough reduction than dextromethorphan 1
• Specifically studied in advanced cancer cough with demonstrated effectiveness and safety 4

Other Peripherally Acting Options

• Moguisteine has been studied with some evidence of efficacy 1, 7
• Sodium cromoglycate can be considered for refractory cases 5

Clinical Algorithm

1. Start with dextromethorphan 60 mg (ensuring adequate dosing, not subtherapeutic OTC formulations) 1
2. Consider benzonatate as an alternative peripherally acting option 3, 4
3. Add menthol for acute, short-term relief if needed 1
4. Use sedating antihistamines specifically for nocturnal cough 1
5. Reserve opioids (preferably pholcodine, hydrocodone, or dihydrocodeine—NOT codeine) only when non-opioid options fail 1

Important Caveats

• Opiate antitussives including codeine have a significant adverse side effect profile and are not recommended as first-line therapy 1
• Most over-the-counter dextromethorphan preparations contain subtherapeutic doses; the effective dose is 60 mg 1
• Simple voluntary cough suppression and demulcents may work through central modulation of the cough reflex 1
• For patients with aspiration concerns, local anesthetics (nebulized lidocaine) can be considered but require careful risk-benefit assessment as they can increase aspiration risk 5