Levodropropizine – a non-codeine antitussive with minimal side effects, contraindications, and drug interactions

Indications and Mechanism of Action

Levodropropizine is the levorotatory isomer of dropropizine. It is indicated for bronchopulmonary conditions accompanied by irritating dry cough from the age of 2 years and is also used before bronchoscopic examination.

As a non-codeine-type antitussive, it exhibits mainly a peripheral antitussive effect in the trachea and bronchi. It does not suppress respiratory functions or mucociliary clearance and, through its antiallergic effect, it suppresses bronchospasm. Compared to centrally acting antitussives, it achieves comparable efficacy with a significantly lower incidence of side effects, particularly drowsiness and nocturnal awakening.

Contraindications of Levodropropizine vs. Codeine

Contraindications of levodropropizine include, besides hypersensitivity to the active substance or excipients, only bronchial hypersecretion, reduced mucociliary clearance (Kartagener's syndrome, ciliary dyskinesia), significantly reduced liver function, and further pregnancy and breastfeeding.

On the other hand, codeine antitussives, which act on the cough center in the brainstem, can be addictive, cause constipation, suppress the respiratory center, and affect the ability to drive motor vehicles. Contraindications of codeine include age under 12 years generally or under 18 years in case of post-tonsillectomy/adenoidectomy, CYP2D6 ultrarapid metabolizer phenotype, first and third trimester of pregnancy, breastfeeding, respiratory depression, impaired expectoration, acute asthma attack, diarrhea in intoxications and pseudomembranous colitis, paralytic ileus, head injury, increased intracranial pressure, and severe liver failure.

Drug Interactions

The advantage of levodropropizine is the minimal number of drug interactions. Clinical studies have not proven any interaction with drugs used in the treatment of bronchopulmonary diseases, such as β₂-agonists, methylxanthines, corticosteroids, antibiotics, mucoregulators, and antihistamines.

The SPC of Levopront notes that although no interactions with benzodiazepines were observed during clinical trials, levodropropizine must be used with caution for possible enhancement of the sedative effect. A French clinical study comparing EEG recordings under normal conditions, after administration of benzodiazepines, and after the administration of benzodiazepines and levodropropizine, did not demonstrate a synergistic effect of the drugs. A slight shift to lower wave frequency after administration of benzodiazepines did not change with concurrent administration of levodropropizine.

Practice Warnings

Studies on the efficacy of levodropropizine in children under 2 years of age have not been conducted sufficiently, and therefore the drug should be administered to this patient group only with caution. Caution is also needed in patients with severe renal impairment (creatinine clearance <35 ml/min) and in older patients who generally have altered sensitivity to various drugs. Levodropropizine is best taken between meals, as there is no data available on the effect of food on its absorption.

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Sources:
1. Fojtů H. Cough – Differential Diagnosis and Therapy. Remedia 2013; 23 (3): 180–185.
2. SPC Levopront. Available at: www.sukl.cz/modules/medication/download.php?file=SPC170522.pdf&type=spc&as=levopront-spc
3. SPC Codein Slovakofarma. Available at: www.sukl.cz/modules/medication/download.php?file=SPC142314.pdf&type=spc&as=codein-slovakofarma-spc  
4. Arrigo A., Bejor M., Beungarbe D., Cosentina R. Interaction between diazepam and levodropropizine evaluated by quantification of EEG. Riv Eur Sci Med Pharmacol 1989; 11 (1): 51–54.