Ambrolex

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMBROLEKS (AMBROLEKS)

Composition:

Active substance: ambroxol hydrochloride;

1 ml of solution contains 7.5 mg of ambroxol hydrochloride;

Excipients: sodium chloride, citric acid monohydrate (E 330), disodium phosphate dodecahydrate (E 339), water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: colorless or yellowish transparent liquid.

Pharmacotherapeutic group. Medicinal products used for cough and colds. Mucolytic agents. ATC code R05C B06.

Pharmacological properties.

Pharmacodynamics.

Preclinical studies have shown that ambroxol hydrochloride, the active ingredient of Ambrolex, increases secretion in the respiratory tract. It also enhances pulmonary surfactant secretion and stimulates ciliary epithelium activity. These effects lead to improved mucus clearance and expectoration (mucociliary clearance). Improvement of mucociliary clearance has been demonstrated in clinical pharmacological studies. Activation of fluid secretion and enhanced mucociliary clearance facilitate mucus elimination and alleviate cough.

In vitro studies have demonstrated that ambroxol hydrochloride reduces the levels of cytokines as well as the number of circulating and tissue-bound mononuclear and polymorphonuclear cells.

Antioxidant effects of ambroxol have also been observed in numerous preclinical studies.

Following administration of ambroxol hydrochloride, concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin) increase in bronchopulmonary secretions and sputum.

Pharmacokinetics.

Ambroxol hydrochloride is approximately 90% bound to plasma proteins in adults and 60–70% in newborns. The drug crosses the placental barrier and reaches fetal lungs. A high volume of distribution (410 L) indicates greater tissue accumulation than in plasma, with lung tissue concentrations exceeding plasma levels by a factor of ≥ 17.

Metabolism and elimination. Ambroxol hydrochloride is mainly metabolized in the liver via glucuronidation and, to a lesser extent, via degradation to dibromanthranilic acid (which accounts for approximately 10% of the dose); other minor metabolites are also formed. Studies with human liver microsomes have shown that the enzyme CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromanthranilic acid. Within 3 days after intravenous administration, 4.6% of the dose is excreted unchanged, while 35.6% of the dose is excreted in conjugated form in urine.

The plasma half-life of ambroxol hydrochloride is approximately 10 hours.

In newborns, following repeated intravenous administration, the elimination half-life is approximately doubled, indicating reduced clearance.

In severe hepatic impairment, ambroxol clearance is reduced by 20–40%. In severe renal impairment, accumulation of ambroxol metabolites, specifically dibromanthranilic acid and glucuronides, may occur.

Ambroxol crosses the blood-brain and placental barriers and is excreted into breast milk.

Clinical characteristics.

Indications.

For enhancing pulmonary surfactant production in preterm infants and newborns with respiratory distress syndrome.

Contraindications.

Known hypersensitivity to ambroxol hydrochloride or to any of the excipients of the medicinal product.

Special precautions.

There have been only a few reports of severe skin reactions: Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), associated with the use of expectorants such as ambroxol hydrochloride. In most cases, these reactions could be explained by the severity of the underlying disease in patients or by concomitant use of other medicinal products. Therefore, if new skin or mucosal lesions appear, immediate medical attention must be sought and treatment with ambroxol hydrochloride should be discontinued.

Since ambroxol may enhance mucus secretion, Ambrolex, solution for injection, should be used with caution in patients with impaired bronchial motility and increased mucus secretion (e.g., in rare conditions such as primary ciliary dyskinesia).

Ambrolex, solution for injection, should be administered with caution in patients with impaired renal function or severe hepatic impairment (i.e., the dosing interval should be prolonged or the dose reduced).

Accumulation of metabolites formed in the liver is expected in patients with severe renal insufficiency.

Interaction with other medicinal products and other forms of interaction.

To date, no clinically significant interactions of this medicinal product with other medicinal products have been established.

Concomitant use of Ambrolex, solution for injection, with antitussive agents may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such combination should only be used after careful assessment by a physician of the benefit-risk ratio.

Concomitant administration with antibiotics (amoxicillin, doxycycline, cefuroxime, erythromycin) leads to increased concentrations of these antibiotics in lung tissue.

Special precautions for use.

If intravenous administration is performed too rapidly, headache, increased fatigue, exhaustion, and a feeling of heaviness in the legs may rarely occur.

Since ambroxol may enhance mucus secretion, Ambrolex, injection solution, should be used with caution in patients with impaired bronchial motility and increased mucus secretion (e.g., in rare conditions such as primary ciliary dyskinesia).

Ambrolex should be used with caution in patients with renal function impairment or severe liver disease. When ambroxol, like any active substance metabolized in the liver and subsequently excreted by the kidneys, is administered, accumulation of metabolites formed in the liver may occur in patients with severe renal insufficiency.

Very rarely, severe skin reactions such as Stevens-Johnson syndrome or Lyell's syndrome (toxic epidermal necrolysis, TEN) have been reported, sometimes occurring during ambroxol treatment. Most of these cases were associated with the underlying disease or concomitant use of other medicinal products. If any changes in the skin or mucous membranes occur, ambroxol should be discontinued immediately and medical advice should be sought without delay.

Ambrolex, injection solution, contains less than 1 mmol (23 mg) of sodium per ampoule.

Use during pregnancy or breastfeeding.

Use in premature infants and newborns.

Ability to affect reaction speed when driving or operating machinery.

Use in premature infants and newborns.

Method of administration and dosage.

An effective total daily dose of 30 mg of ambroxol hydrochloride per 1 kg of body weight has been demonstrated.

The dose should be administered in 4 divided doses by slow intravenous infusion; each individual dose is recommended to be given by intravenous infusion using an infusion pump over at least 5 minutes.

The contents of 1–6 ampoules should be diluted in 250–500 ml of physiological saline or Ringer's solution immediately before use. The resulting infusion solution should be used within 6 hours after preparation.

Duration of treatment: 5 days.

Instructions for handling the ampoule.

1. Detach 1 ampoule from the block and shake it by holding the neck (Fig. 1).
2. Squeeze the ampoule with your hand (ensuring no leakage of the solution) and twist off the top (Fig. 2).
3. Immediately connect a syringe to the ampoule through the opening formed (Fig. 3).
4. Invert the ampoule and slowly draw the contents into the syringe (Fig. 4).
5. Attach the needle to the syringe.

Fig. 1   Fig. 2   Fig. 3   Fig. 4

Children.

Use in premature infants and newborns as indicated.

Overdose.

Currently, there are no reports of specific symptoms of overdose. Symptoms observed following accidental overdose or medical error are similar to known adverse reactions occurring with recommended doses and may require symptomatic treatment.

Side effects.

The following classification was used to assess the frequency of adverse reactions:

Immune system/skin and subcutaneous tissue disorders:

Uncommon − erythema;

Unknown − anaphylactic reactions (including shock), angioneurotic edema, skin rashes, urticaria, pruritus, and other hypersensitivity reactions, severe skin reactions: Stevens-Johnson syndrome and Lyell's syndrome.

Gastrointestinal disorders:

Uncommon − dry mouth, constipation, salivation, dryness in the throat;

Unknown − nausea, vomiting, diarrhea, dyspepsia, abdominal pain.

Respiratory, thoracic and mediastinal disorders:

Uncommon − rhinorrhea, dyspnea (as a symptom of hypersensitivity reaction).

Renal and urinary disorders:

Uncommon − urinary disorders.

General disorders and administration site conditions:

Uncommon − increased body temperature and chills, reactions at mucous membranes.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as patients' legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life.

2.5 years.

Unused contents of the ampoule should be discarded and must not be stored for future use.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Incompatibilities.

Ambrolex must not be mixed with any medicinal products other than those specified in the section "Administration and dosage."

Do not mix with other solutions, as this may lead to mixtures with a pH above 6.3, and possible precipitation of ambroxol hydrochloride in the form of free base due to increased pH.

Packaging.

2 ml in an ampoule; 5 ampoules in a cardboard pack.

Prescription status.

Prescription only.

Manufacturer.

LLC "PHARMASELL"

Manufacturer's address and location of its business activity.

3, Prorizna Street, Kvitneve, Brovary District, Kyiv Region, 07408, Ukraine