Levodropropizine A Valuable Peripheral Anti-tussive for Dry Cough in Primary Care Settings: Latest Indian Clinicians' Review
India: Levodropropizine, a nonopioid peripheral antitussive, may be a valuable agent for providing symptomatic relief in nonproductive, dry cough in Indian primary care settings by reducing cough severity and frequency, while offering a superior safety profile and comparable efficacy to central antitussives.
The recently published review in the Journal of the Association of Physicians of India, July 2025 issue comprehensively studied the efficacy and safety of levodropropizine across diverse age groups and various etiologies of dry cough.
Cough is the second most common presenting symptom in Indian clinical practice, with dry cough having a significant burden. Although a symptom, it can be distressing and significantly impact quality of life (QoL). For symptomatic relief of dry cough, traditional centrally acting antitussives are commonly used, but they are associated with safety and tolerability concerns such as addiction, dependence, respiratory depression, sedation, and CNS suppression. Levodropropizine, a non-opioid peripherally acting antitussive acts on C-fibers present on vagal afferents in the larynx, suprapharyngeal area, and tracheobronchial tree (i.e. in the afferent arm of the cough reflex arc). Hence, it demonstrates high efficacy but with a better safety profile compared to central antitussives like codeine and dextromethorphan.
Comparative Studies vs Other Antitussives:
Across diverse studies, levodropropizine demonstrated:
- Comparable or superior efficacy in reducing cough frequency, severity, and nocturnal awakenings, with faster onset of relief.
- Normal hypercapnia response confirming its peripheral action and lack of central respiratory depression.
- Better patient-reported outcomes, including earlier cough resolution and improved physical quality of life.
- Minimal impact on psychomotor function, especially at recommended doses (60 mg)
- Better safety profile with lower incidence of somnolence and adverse events.
Catena and Daffonchio studied the efficacy and safety of levodropropizine in adults with dry cough and noted that:-
- Both levodropropizine and dextromethorphan reduced number of coughing spells and cough intensity similarly, but levodropropizine achieved cough intensity reduction earlier (day 2) compared to dextromethorphan (day 3) [efficacy parameters]
- Levodropropizine group had better reduction in nocturnal awakenings (↓92%) than dextromethorphan (↓72%) at day 5. [efficacy parameter]
- Levodropropizine group had significantly lesser proportion of patients experiencing somnolence (4.6%) compared to dextromethorphan (10.4%). [safety parameter]
Non-Comparative & Placebo-Controlled Studies:
Studies have consistently highlighted the therapeutic value of levodropropizine in managing cough across various patient groups. Levodropropizine demonstrated:
- Significant and faster resolution of both daytime and nocturnal cough symptoms
- Effectiveness in pediatric patients, with clinical improvement seen in up to 98.5% of children with URTI-associated cough.
- Favorable safety profile demonstrated by Levodropropizine with no impact on mouth occlusion pressure (P0.1), tidal volume, respiratory rate, minute ventilation, mean inspiratory flow, or end tidal CO₂.
- Reduction in allergen- and irritant-induced bronchoconstriction by partially inhibiting histamine and neuropeptide release.
- Significant improvement in nocturnal sleep quality.
Meta-analysis Evidence:
A meta-analysis of seven clinical studies involving 1,178 adult and pediatric patients demonstrated superior antitussive efficacy of levodropropizine. Additionally, another meta-analysis of four randomized controlled trials (RCTs) with 780 pediatric patients showed that levodropropizine significantly improved cough frequency, severity, and nocturnal awakenings compared to control treatments.
Guideline recommendations for Levodropropizine:
| Scientific Authority | Recommended Considerations |
| 2022 Indian Association of Paediatrics (IAP) | Levodropropizine at 1–2 mg/kg once or twice daily for presumed viral cough. |
| 2021 Italian Society of Pediatric Allergy and Immunology (SIAIP) | Levodropropizine recommended as a suitable option for acute cough in children and adolescents |
| 2020 Indian Environmental Medical Association (EMA) | Levodropropizine for dry cough due to URTI, acute/chronic bronchitis, cough variant asthma, pulmonary tuberculosis, interstitial lung disease (ILD), and primary or metastatic lung cancer. |
| 2017 CHEST | Levodropropizine for symptomatic treatment of opioid-resistant cough. |
Evidence from clinical studies, meta-analyses, and guidelines highlights levodropropizine’s efficacy in reducing cough frequency, severity, and nocturnal symptoms. It has demonstrated efficacy in various etiologies of non-productive cough. Also a favorable safety profile with minimal central effects and good tolerability across pediatric, adult and geriatric age groups has been demonstrated across various studies. Levodropropizine, as a peripheral antitussive, may serve as a useful option for the symptomatic treatment of patients with nonproductive cough.
Reference: Nayar S, Vora A, Tiwaskar M, et al. Levodropropizine: Comprehensive Review of the Peripheral Antitussive. J Assoc Physicians India 2025;73(7):e35-e44.
