In an otherwise healthy adult with an acute dry cough due to a viral upper‑respiratory infection, which antitussive—dextromethorphan, butamirate citrate, or levodropropizine—is preferred as first‑line therapy, including appropriate dosing and contraindications?

Dextromethorphan vs Butamirate Citrate vs Levodropropizine for Acute Viral Dry Cough

Dextromethorphan is the recommended first-line antitussive for acute dry cough in otherwise healthy adults, dosed at 30–60 mg every 6–8 hours (maximum 120 mg/day), with the caveat that standard over-the-counter doses (10–15 mg) are subtherapeutic and unlikely to provide meaningful relief. 1

Evidence-Based Treatment Algorithm

Step 1: Non-Pharmacological First-Line Approach

• Honey and lemon mixtures should be offered initially, as they may be as effective as pharmacological treatments for benign viral cough and avoid medication side effects. 1, 2
• Voluntary cough suppression through central modulation may suffice to reduce cough frequency in some patients. 1, 2

Step 2: Pharmacological Therapy When Non-Pharmacological Measures Fail

Preferred Agent: Dextromethorphan

• Dextromethorphan 30–60 mg per dose (every 6–8 hours, maximum 120 mg/day) is the first-line pharmacological antitussive due to its superior safety profile compared to opioid alternatives. 1
• Maximum cough reflex suppression occurs at 60 mg, which is substantially higher than typical over-the-counter formulations. 1, 2
• A critical prescribing pitfall is using subtherapeutic doses below 30 mg, which fail to provide adequate cough suppression. 1
• Caution: Many combination products contain acetaminophen or other ingredients; verify total daily acetaminophen does not exceed 4 grams to avoid hepatotoxicity. 1

Alternative Agents: Butamirate and Levodropropizine

• Butamirate citrate is a centrally-acting antitussive with additional bronchodilator and anti-inflammatory effects, achieving therapeutic plasma concentrations within 5–10 minutes of administration. 3
• Levodropropizine is a peripherally-acting antitussive that demonstrated statistically significant superiority over central antitussives (including dextromethorphan, codeine, and cloperastine) in a meta-analysis of 1,178 patients, reducing cough frequency, severity, and nocturnal awakenings (p = 0.0015). 4
• Levodropropizine has an optimal safety profile and is particularly useful when central antitussives are contraindicated or have failed. 4, 5

However, neither butamirate nor levodropropizine is mentioned in major North American guidelines (ACCP, British Thoracic Society), whereas dextromethorphan has explicit guideline support. 6, 1, 2

Step 3: Adjunctive Therapy for Nocturnal Cough

• First-generation sedating antihistamines (e.g., diphenhydramine 25–50 mg at bedtime) can suppress cough while promoting sleep when nocturnal cough is particularly disruptive. 1, 2
• Menthol inhalation (crystals or proprietary capsules) provides acute but short-lived cough suppression for breakthrough symptoms. 1, 2

Dosing Summary

Agent	Dose	Frequency	Maximum Daily Dose
Dextromethorphan	30–60 mg	Every 6–8 hours	120 mg
Butamirate citrate	Per product labeling	Varies by formulation	Per product labeling
Levodropropizine	Per product labeling	Varies by formulation	Per product labeling

Contraindications and Safety Considerations

Dextromethorphan

• Do not use in patients requiring pneumonia assessment (tachycardia, tachypnea, fever, abnormal chest examination). 2
• Avoid in patients taking monoamine oxidase inhibitors (MAOIs) due to risk of serotonin syndrome.
• Limited efficacy (less than 20% cough suppression) in acute upper respiratory infections, though this reflects inadequate dosing in most studies. 1, 7

Agents to Avoid

• Codeine-containing products should not be prescribed; they provide no greater efficacy than dextromethorphan but carry significantly higher risks of drowsiness, nausea, constipation, and physical dependence. 1, 2
• Promethazine has no established efficacy for cough suppression and is associated with serious adverse effects including hypotension, respiratory depression, and extrapyramidal reactions. 1
• Guaifenesin (an expectorant) is inappropriate for dry cough and has Grade D evidence (good evidence of no benefit) from the American College of Chest Physicians. 2

When to Escalate or Refer

• Cough persisting beyond 3 weeks requires full diagnostic workup rather than continued antitussive therapy. 1
• Red flags requiring immediate evaluation: hemoptysis, significant breathlessness, fever with purulent sputum, tachypnea, or suspected foreign body aspiration. 2
• For postinfectious cough (persisting 3–8 weeks after acute infection), consider inhaled ipratropium before central antitussives; if severe paroxysms occur, a short course of prednisone 30–40 mg daily may be indicated. 1, 2

Comparative Evidence Strength

The British Thoracic Society and American College of Chest Physicians explicitly recommend dextromethorphan as the preferred antitussive, providing the strongest guideline-level support. 1, 2 While levodropropizine showed superior efficacy in meta-analysis 4, this represents research-level evidence without guideline endorsement in major North American or European respiratory society guidelines. Butamirate has theoretical advantages (bronchodilation, rapid onset) 3 but lacks comparative trials against appropriately-dosed dextromethorphan (60 mg).

In clinical practice, dextromethorphan at adequate doses (30–60 mg) remains the evidence-based first choice, with levodropropizine serving as a reasonable alternative when dextromethorphan fails or is contraindicated. 1, 4