Treating Acute Cough With Ambroxol Hydrochloride: What the Evidence Shows

Cough is a protective reflex that helps clear accumulated mucus and foreign material from the airways. It is also one of the most common symptoms that prompts parents to seek medical attention from a pediatrician or family physician. Cough can interfere with a child's daily activities, school performance, and sleep, as well as disturb the sleep of other family members. Proper assessment of the type of cough, identification of its underlying cause, and appropriate treatment are therefore essential.

Cough and Mucus Hypersecretion

Acute cough is most commonly caused by upper and lower respiratory tract infections [1].

Following respiratory tract infections, cough receptors become sensitized, particularly in children. As a result, coughing may persist long after the infection itself has resolved [1].

A two-year prospective cohort study found that the pathogens most commonly associated with prolonged cough were rhinovirus (32%), Bordetella pertussis (17%), and respiratory syncytial virus (11%) [2].

Prospective studies have shown that acute cough lasts:

• up to 10 days in 50% of young children,
• up to 25 days in 90%,
• and 3–4 weeks in approximately 10% [1].

Cough itself is an important airway-clearing mechanism and generally does not require treatment, particularly suppression. Over-the-counter medications—including decongestants, antihistamines, and cough suppressants—do not treat the underlying cause of cough and may produce undesirable adverse effects [1].

Management of acute cough associated with respiratory tract infection is usually symptomatic and includes adequate fluid intake, nasal hygiene, and, when appropriate, inhalation of isotonic saline or 2–3% sodium chloride solution.

Inhalations containing additional substances such as eucalyptus or other herbal extracts may irritate inflamed airways and worsen coughing, particularly in individuals with allergic conditions.

Because cough receptors are abundant in the upper respiratory tract, cough is frequently associated not only with lower respiratory tract infections but also with otitis media, adenoiditis, sinusitis, and other upper airway disorders [3].

Repeated coughing further stimulates cough receptors and promotes mucus hypersecretion. The resulting mucus becomes thick and viscous. Accumulated secretions provide an excellent environment for microbial growth, facilitating the spread of infection and making treatment more difficult.

Children often have difficulty clearing retained secretions because they are less effective at expectorating mucus. During illness, they also tend to drink less and be less physically active. In these situations, medications that reduce mucus viscosity and facilitate expectoration may be beneficial.

Ambroxol Preparations

One of the most widely used and extensively studied medications in clinical practice is ambroxol hydrochloride. Its effectiveness in treating respiratory tract diseases in both adults and children has been well documented [4].

Ambroxol is the active metabolite of bromhexine, itself a semisynthetic derivative of vasicine, an expectorant compound obtained from medicinal plants that have been used therapeutically since ancient times. Bromhexine was introduced for the treatment of respiratory diseases in 1965. Ambroxol, developed later, demonstrated superior efficacy and more favorable pharmacokinetic properties [5].

One of ambroxol's most important pharmacological actions is stimulation of pulmonary surfactant production. This contributes to its secretomotor and secretolytic effects by improving mucociliary clearance and facilitating mucus expectoration during productive cough.

Experimental evidence also suggests that ambroxol may inhibit certain factors required for viral replication, stimulate phagocytosis, and enhance the penetration of antibiotics into lung tissue [6].

Stimulation of Surfactant Production: Secretomotor Action

Pulmonary surfactant represents an important first-line mechanical defense against bacterial and viral infections.

Adequate hydration of the airway surface is essential for effective ciliary movement and normal mucociliary clearance. When mucus becomes excessively thick or sticky, bacteria are more likely to become trapped, produce virulence factors, and trigger infection-related inflammation.

Surfactant reduces mucus adhesion to the respiratory epithelium and facilitates mucus clearance [5].

In vitro studies have shown that ambroxol directly stimulates surfactant production by acting on type II alveolar pneumocytes and Clara (club) cells within the small airways.

Preclinical studies have demonstrated that ambroxol increases serous bronchial secretions, thereby reducing mucus viscosity and promoting its clearance from the respiratory tract [5].

Studies using respiratory and renal cell cultures have also demonstrated that ambroxol hydrochloride inhibits bacterial adhesion. Significant reductions in adhesion were observed for several important pathogens, including Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus [7].

By stimulating surfactant production, ambroxol improves ciliary function, enhances mucociliary clearance, and reduces pathogen adhesion within the respiratory tract [5].

Enhancement of Antibiotic Penetration Into Lung Tissue

Increased surfactant production also promotes activation of macrophages and enhances phagocytosis through surfactant proteins, particularly SP-A.

Ambroxol hydrochloride is rapidly and almost completely absorbed after oral administration. Drug concentrations in lung tissue are approximately 15–20 times higher than those measured in the bloodstream [5].

Ambroxol may be safely administered together with antibiotics. However, caution is recommended when combining it with other mucolytic agents, particularly acetylcysteine.

In vitro studies have shown that acetylcysteine may reduce the activity of several antibiotics, including tetracyclines, aminoglycosides, and penicillins. Therefore, these medications should not be taken simultaneously, and an interval of at least two hours should separate their administration. This recommendation does not apply to cefixime or loracarbef [8,9].

Conversely, studies have demonstrated that ambroxol hydrochloride enhances the activity of amoxicillin, cefuroxime, doxycycline, and erythromycin by increasing their penetration into bronchial secretions [10].

Tolerability

Ambroxol has been used in clinical practice since 1973.

Its safety profile is supported by more than 100 clinical studies involving over 15,000 patients.

Importantly, ambroxol hydrochloride can also be used in patients with asthma. The medication inhibits phosphodiesterase IV—an enzyme involved in asthma pathogenesis—and suppresses histamine release from mast cells, thereby reducing bronchial hyperresponsiveness and bronchospasm [11].

By contrast, other mucolytics, such as acetylcysteine, are contraindicated during severe asthma exacerbations because they have been reported to provoke bronchial obstruction [9].

Recent comprehensive safety evaluations have confirmed that ambroxol possesses a favorable safety profile and is well tolerated in both adults and children.

Summary

• When treating cough in children, it is advisable to minimize the number of active ingredients prescribed and avoid unnecessary combination products whenever possible.
• Children's airways naturally produce more mucus than those of adults, making productive cough more common. Additional stimulation of mucus production should be avoided when the cough is already productive, as this may prolong symptoms.
• Owing to its convenient formulations (tablets, syrup, and orally disintegrating tablets), rapid gastrointestinal absorption, and favorable pharmacological properties, ambroxol may be a valuable treatment option for respiratory diseases accompanied by productive cough.
• Public education regarding the natural course of viral upper respiratory tract infections and the limitations of unreliable online information about childhood cough treatment may also help reduce inappropriate medication use.

Prepared by Dr. Valdonė Misevičienė and Dovilė Lukoševičiūtė-Zikė

Reprinted from Pharmacist's Practice

Literature references are available from the editorial office.

LT/Fla/2015/02