ACTION AND MECHANISM

- Mucolytic, expectorant. Ambroxol is N-desmethyl-bromhexine, the active metabolite of bromhexine. Its administration leads to a decrease in the viscosity of bronchial secretions and an increase in their volume, while also promoting their expulsion.

Its mechanism of action is unknown, but it could be related to the increase in the synthesis of sialomucins by activation of sialyl-transferase, thereby restoring the normal glycoprotein composition of bronchial mucus secretion, and normalizing the viscoelasticity of bronchial mucus.

It could also stimulate the mucous glands of the bronchial epithelium, increase lysozyme levels, which would produce the breakdown of mucopolysaccharides, and stimulate mucociliary activity.

SPECIAL WARNINGS

- The use of mucolytics and expectorants in children under 2 years of age is contraindicated due to the risk of bronchial obstruction.

- In case of the appearance of skin rashes on skin or mucous membranes, ambroxol will be discontinued and the possibility of conditions such as toxic epidermal necrolysis or Stevens-Johnson syndrome will be evaluated.

PATIENT ADVICE

- Drink plenty of water during treatment.

- Do not use antitussives while using ambroxol.

- Consult your doctor and/or pharmacist if symptoms worsen or do not improve within 5 days, or if fever, headache or sore throat develops.

- Inform your doctor and/or pharmacist if skin rashes appear during treatment, sometimes associated with blisters or lesions on the mucous membranes.

CONTRAINDICATIONS

- Hypersensitivity to ambroxol, bromhexine or any other component of the medication.

- Children < 2 years. Risk of bronchial obstruction.

ADVANCED AGE

No specific problems have been described in the elderly that would require a dosage adjustment.

EFFECTS ON DRIVING

It does not appear likely that ambroxol could negatively affect the ability to drive.

PREGNANCY

Animal safety : Ambroxol did not produce teratogenic or embryotoxic effects at doses of 3,000 mg/kg/24 h (rat) or 200 mg/kg/24 h (rabbit). Cases of decreased fetal body weight and reduced number of live offspring were reported at maternally toxic doses.

Safety in humans : Clinical use has not revealed adverse effects on pregnancy or postnatal development when administered from week 28 of gestation onward. Adequate and well-controlled studies in humans are not available. Its administration is only acceptable if there are no safer therapeutic alternatives and the benefits outweigh the potential risks.

Effects on fertility : Ambroxol did not produce adverse effects on the fertility of male or female animals at a dose of 500 mg/kg/24 h. No specific studies have been conducted in humans.

PHARMACOKINETICS

- Absorption: It is rapidly and completely absorbed after oral administration, reaching a Cmax of 88.8 ng/ml within 1-2.5 h (30 mg orally, immediate release) or 6.5 h (extended-release formulations). After oral administration, it undergoes a first-pass effect, with 30% of the dose being eliminated. Its bioavailability is 79%.

Effect of food : has no clinically significant effect on the pharmacokinetics of ambroxol.

INDICATIONS

- Reduction of [BRONCHIAL HYPERVISCOSITY] in [COMMON COLD] and [FLU].

LACTATION

Animal safety: no data available.

Safety in humans: Ambroxol is excreted in breast milk. The consequences for the infant are unknown. Its use during breastfeeding is not recommended.

CHILDREN

The use of mucolytics in children under 2 years of age has been associated with the development of bronchial obstruction, resulting from increased production and thinning of bronchial secretions and insufficient bronchial drainage. Therefore, the use of mucolytics in these children is contraindicated.

In older children, the pharmaceutical form and dose should be adapted to the child's age ( see Dosage ).

GUIDELINES FOR PROPER ADMINISTRATION

It is recommended to drink a glass of water after each dose. Drink plenty of water during treatment.

POSOLOGY

- Adults, oral: 30 mg/8 h.

- Children and adolescents under 18 years of age, oral:

* Adolescents > 12 years: 30 mg/8 h.

* Children 6-12 years: 15 mg/8 h.

* Children 2-5 years: 7.5 mg/8 h.

* Children < 2 years: contraindicated.

- Elderly, oral: no dosage adjustment required.

Administration with food : it is recommended to administer without food.

Treatment duration : consult your doctor if symptoms do not improve after 5 days.

DOSAGE IN HEPATIC INSUFFICIENCY

It may be necessary to reduce the dose or increase the interval between doses.

DOSAGE IN RENAL INSUFFICIENCY

It may be necessary to reduce the dose or increase the interval between doses.

PRECAUTIONS

- Patients with severe [RENAL INSUFFICIENCY] (CLcr < 30 ml/min) or severe [HEPATIC INSUFFICIENCY] (Child-Pugh class C), due to the risk of accumulation.

- Gastric damage. Administration of mucolytics has been associated with disruption of the gastric protective barrier and gastric damage. Consider their use in patients with a history of gastritis or peptic ulcer.

- Skin reactions. The administration of ambroxol has been associated with the occurrence of severe and potentially life-threatening skin reactions, such as toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (STEVENS-JOHNSON SYNDROME). If skin or mucous membrane lesions appear or worsen, ambroxol should be discontinued and the patient should be evaluated.

PRECAUTIONS RELATING TO EXCIPIENTS

This medicine contains sorbitol. Patients with hereditary fructose intolerance should not take this medicine.

ADVERSE REACTIONS

Adverse reactions are described according to each frequency interval, being considered very common (>10%), common (1-10%), uncommon (0.1-1%), rare (0.01-0.1%), very rare (<0.01%) or of unknown frequency (cannot be estimated from the available data).

- Digestive: frequent [NAUSEA], [DYSGEUSIA], oral [HYPOESTHESIA]; infrequent [VOMITING], [DIARRHEA], [DYSPEPSIA], [ABDOMINAL PAIN], [DRY MOUTH]; rare dry throat.

- Dermatological: rare [SKIN ERUPTIONS], [URTICARIA]; frequency unknown [ERYTHEMA MULTIFORME], [STEVENS-JOHNSON SYNDROME], [TOXIC EPIDERMAL NECROLYSIS], acute generalized exanthematous pustulosis.

- Allergic: rare [HYPERSENSITIVITY REACTIONS]; frequency unknown [ANAPHYLAXIS], [ANGIOEDEMA], [PRURITUS].

ADVERSE REACTIONS RELATED TO EXCIPIENTS

- Because it contains methyl parahydroxybenzoate, it may cause [PARABEN ALLERGY], possibly delayed.

OVERDOSE

Symptoms : No serious reactions to ambroxol poisoning have been reported. As a rule, doses of 15 mg/kg/24 h (IV) or 25 mg/kg/24 h (PO) were well tolerated. Symptoms of overdose included nervousness and diarrhea. In cases of significant overdose, sialorrhea, nausea and vomiting, and hypotension have been reported.

Measures to be taken :

- Antidote: there is no specific antidote.

- General elimination measures: Induced emesis or gastric lavage are not indicated, except in cases of very severe poisoning. Forced diuresis or dialysis do not appear to be effective measures for treating overdose due to its high plasma protein binding.

- Patient care: keep the airways clear of secretions by laying the patient down and performing bronchial aspiration.

- Treatment: symptomatic treatment.