What is the most potent antitussive for a dry, non‑productive cough in an adult, including recommended dosing and safety considerations?

Strongest Cough Medicine for Dry, Non-Productive Cough in Adults

For maximum cough suppression, dextromethorphan at 60 mg is the strongest and safest non-opioid antitussive, with efficacy equal to codeine but a far superior safety profile; if opioids become necessary for refractory cases, morphine 5-10 mg slow-release twice daily provides the most potent suppression but should be reserved only after all other options fail. 1, 2

First-Line Approach: Non-Opioid Antitussives

Dextromethorphan (Preferred Agent)

• Dextromethorphan 60 mg provides maximum cough reflex suppression and represents the most potent non-opioid option available 1, 2
• Standard dosing is 10-15 mg three to four times daily, with a maximum of 120 mg per day 1
• Most over-the-counter preparations contain subtherapeutic doses—ensure adequate dosing at 60 mg for optimal effect 1, 2
• Meta-analysis confirms suppression of acute cough, with a dose-response relationship demonstrating maximum efficacy at 60 mg 1, 2
• When using higher doses, verify that combination products do not contain excessive paracetamol or other ingredients 1

Alternative Non-Opioid Options

• Menthol by inhalation suppresses the cough reflex acutely but provides only short-lived relief 1, 2
• First-generation sedating antihistamines (e.g., diphenhydramine, chlorpheniramine) suppress cough through sedative properties and are particularly useful for nocturnal cough 1, 2
• Simple home remedies such as honey and lemon represent the simplest, cheapest initial approach with reasonable patient-reported benefit 1, 3

Second-Line: Opioid Antitussives (When Non-Opioids Fail)

Preferred Opioid Options

• Codeine 30-60 mg four times daily is commonly used but offers no efficacy advantage over dextromethorphan while carrying a significantly greater adverse effect profile including constipation, sedation, and respiratory depression risk 1, 2
• Pholcodine, hydrocodone (5 mg twice daily), or dihydrocodeine (10 mg three times daily) are preferred over codeine due to better side effect profiles 1, 2
• Hydrocodone extended-release formulations allow twice-daily dosing with steady-state plasma concentrations, reducing CNS side effects and improving compliance 2

Most Potent Option: Morphine (Reserved for Refractory Cases)

• Morphine 5-10 mg slow-release twice daily provides the strongest cough suppression for intractable cases 1
• Initial trial with immediate-release morphine 5 mg; if effective, transition to 5-10 mg slow-release formulation 1
• Should be reserved only for severe chronic cough unresponsive to all other measures, or in palliative care settings 1, 4, 5
• Patients typically develop tolerance to constipation and drowsiness with continued use 5

Third-Line: Peripherally Acting Antitussives (For Opioid-Resistant Cough)

• Levodropropizine 75 mg three times daily is probably equally effective to dihydrocodeine 1, 2
• Moguisteine 100-200 mg three times daily or levocloperastine 20 mg three times daily are alternatives 1
• Sodium cromoglycate (inhaled) 10 mg four times daily can be considered for refractory cases 1, 2

Fourth-Line: Local Anesthetics (For Highly Refractory Cases)

• Nebulized lidocaine 5 mL of 0.2% three times daily or nebulized bupivacaine 5 mL of 0.25% three times daily 1
• Benzonatate 100-200 mg four times daily (peripherally acting local anesthetic) 1
• Critical safety consideration: Local anesthetics increase aspiration risk—assess swallowing function before use and avoid food/drink for at least 1 hour after administration 1
• First dose should be given as an inpatient due to risk of reflex bronchospasm 1

Treatment Algorithm

1. Start with dextromethorphan 60 mg (not subtherapeutic OTC doses) 1, 2
2. Add menthol inhalation for acute breakthrough relief if needed 1, 2
3. Use sedating antihistamines specifically for nocturnal cough disrupting sleep 1, 2
4. If no improvement after 3-5 days, escalate to opioid derivatives: prefer pholcodine, hydrocodone, or dihydrocodeine over codeine 1, 2
5. For opioid-resistant cough, trial peripherally acting antitussives (levodropropizine, moguisteine, or cromoglycate) 1, 2
6. For highly refractory cases, consider local anesthetics (nebulized lidocaine/bupivacaine or benzonatate) with appropriate safety precautions 1
7. Reserve morphine slow-release only for severe intractable cough unresponsive to all other measures 1, 5

Critical Safety Considerations and Pitfalls

• Codeine and other opioids have significant adverse effects including constipation, sedation, confusion (especially in elderly), respiratory depression, and addiction potential 1, 2
• Hydrocodone is contraindicated in patients under 18 years due to respiratory depression and fatal overdose risk 2
• Screen for substance use disorders and monitor for polypharmacy before prescribing opioids; risk of overdose increases with concomitant benzodiazepines or CNS depressants 2
• Avoid cough suppression in productive cough where clearance serves a physiological function 1, 3
• If short-course treatment (3-5 days) produces no improvement, discontinue and try alternative approaches rather than continuing ineffective therapy 1, 2
• Avoid decongestant-containing products in patients with hypertension, heart disease, glaucoma, or benign prostatic hypertrophy 6

When to Refer or Investigate Further

• Hemoptysis, progressive breathlessness, or voice changes require immediate specialist referral 1, 6
• Cough persisting beyond 3 weeks warrants discontinuation of symptomatic treatment and diagnostic workup rather than continued suppression 6, 3
• Tachycardia, tachypnea, fever, or abnormal chest findings suggest pneumonia and require evaluation before antitussive use 6