What prescription antitussive is appropriate for an adult with a persistent non‑productive cough that has not responded to over‑the‑counter therapy after excluding serious underlying disease?

Prescription Antitussive for Persistent Non-Productive Cough

For an adult with persistent non-productive cough unresponsive to over-the-counter therapy, prescribe dextromethorphan 30–60 mg every 6–8 hours (maximum 120 mg daily) as the first-line prescription antitussive, or benzonatate 100–200 mg three times daily as an alternative when opioid-related agents are contraindicated. 1, 2, 3

First-Line Prescription Option: Dextromethorphan

Dextromethorphan is the preferred prescription antitussive because it has superior efficacy at prescription doses and a better safety profile than codeine-based alternatives. 1, 2

Optimal Dosing Strategy

• Standard over-the-counter doses (10–15 mg) are subtherapeutic and explain why patients fail OTC therapy. 1, 2
• Maximum cough suppression occurs at 60 mg per dose, with a dose-response relationship demonstrating inadequate relief below 30 mg. 1, 2
• Prescribe 30–60 mg every 6–8 hours, not to exceed 120 mg daily, for effective cough control. 1, 2
• A bedtime dose of 30 mg can suppress nocturnal cough and improve sleep quality. 1

Critical Safety Precautions

• Verify the formulation contains dextromethorphan alone without acetaminophen, antihistamines, or other additives that increase toxicity risk at higher doses. 1, 2
• Avoid dextromethorphan-quinidine combinations (e.g., Nuedexta) in elderly or dementia patients due to fall risk and drug interactions. 4
• Do not use with three or more CNS-active medications (antidepressants, antipsychotics, benzodiazepines, antiepileptics, opioids) due to increased fall risk. 1

Alternative Prescription Option: Benzonatate

Benzonatate 100–200 mg three times daily is FDA-approved for symptomatic cough relief and offers a non-opioid mechanism with a different adverse-effect profile. 3

• Use benzonatate when dextromethorphan is contraindicated or when patients have concerns about opioid-related agents. 1
• Benzonatate acts peripherally by anesthetizing stretch receptors in the respiratory tract, unlike centrally acting dextromethorphan. 3

Agents to Avoid

Codeine and Codeine-Containing Products

Codeine-based antitussives are explicitly not recommended because they provide no greater efficacy than dextromethorphan but carry significantly higher adverse-effect burdens. 1, 2

• Codeine causes drowsiness, nausea, constipation, respiratory depression, and physical dependence without additional therapeutic benefit. 1, 2
• The British Thoracic Society explicitly recommends against codeine for cough management. 2

Promethazine

Promethazine has no established efficacy for cough suppression and is associated with serious adverse effects including hypotension, respiratory depression, neuroleptic malignant syndrome, and extrapyramidal reactions. 1, 4

Guaifenesin (Expectorants)

Guaifenesin is not indicated for dry cough because it functions as an expectorant, not a suppressant, and has Grade D evidence (good evidence of no benefit) for cough in chronic bronchitis. 1

Adjunctive Non-Pharmacological Measures

Before or alongside prescription therapy, recommend:

• Honey and lemon mixtures provide patient-reported benefit through central cough-reflex modulation. 1, 2
• Menthol inhalation (crystals or proprietary capsules) offers acute, short-lived cough suppression for breakthrough symptoms. 1, 2
• Voluntary cough-suppression techniques may reduce cough frequency through behavioral modification. 1, 2

When to Add First-Generation Antihistamines

For nocturnal cough disrupting sleep, add a first-generation sedating antihistamine (e.g., diphenhydramine 25–50 mg at bedtime) to dextromethorphan. 1, 2

• Avoid antihistamines in elderly or dementia patients due to anticholinergic burden causing delirium, cognitive slowing, and falls. 4
• Do not use promethazine for this purpose due to lack of efficacy and serious adverse effects. 1, 4

Treatment Duration and Reassessment

• Limit dextromethorphan to short-term use (typically ≤3 weeks) for symptomatic relief. 1, 2
• If cough persists beyond 3 weeks despite adequate dosing, discontinue antitussive therapy and pursue full diagnostic workup for alternative causes rather than continuing suppression. 1, 2
• Persistent cough requires evaluation for asthma, eosinophilic bronchitis, gastroesophageal reflux disease, upper airway cough syndrome, or medication-induced cough (ACE inhibitors). 1, 5

Special Populations

Chronic Kidney Disease

No dose adjustment of dextromethorphan is required because it undergoes hepatic CYP2D6 metabolism, not renal excretion. 1

COPD and Chronic Bronchitis

Dextromethorphan is safe and recommended for short-term cough relief in COPD patients with dry, non-productive cough. 1

• Do not suppress productive cough where secretion clearance is beneficial. 1, 2
• In acute COPD exacerbations with increased sputum volume/purulence, prioritize bronchodilators, antibiotics, and corticosteroids over antitussives. 1

Postinfectious Cough

For cough persisting after acute respiratory infection but <8 weeks:

• Trial inhaled ipratropium bromide first before central antitussives. 1, 2
• If ipratropium fails and quality of life is impaired, add dextromethorphan 30–60 mg. 1, 2
• For severe paroxysms, consider prednisone 30–40 mg daily for a short course (5–10 days) after ruling out other causes. 1, 2

Common Prescribing Pitfalls

• Prescribing subtherapeutic doses (<30 mg) that fail to provide adequate cough suppression. 1, 2
• Using combination products with acetaminophen or antihistamines at higher dextromethorphan doses, risking hepatotoxicity or anticholinergic toxicity. 1, 2, 4
• Continuing antitussive therapy beyond 3 weeks without diagnostic reassessment. 1, 2
• Suppressing productive cough in pneumonia, bronchiectasis, or acute exacerbations where clearance is protective. 1, 2

Red Flags Requiring Immediate Evaluation

Do not prescribe antitussives if the patient has:

• Hemoptysis, tachypnea, tachycardia, fever, or abnormal chest examination suggesting pneumonia or serious lung pathology. 1
• Increasing breathlessness indicating possible asthma exacerbation or anaphylaxis. 1
• Suspected foreign body aspiration. 1