AGI-BROMHEXINE®16

Composition: Each hard capsule contains:
Bromhexine hydrochloride . . . . . . . . . . . . .16 mg
Presentation:
Cardboard box containing 03 blisters of 10 hard capsules.
Cardboard box containing 10 blisters of 10 hard capsules.
Indications:
For the treatment of bronchial secretion disorders, particularly in acute bronchitis, acute exacerbation of chronic bronchitis.
Bromhexine is often used as an adjunct to antibiotics, in severe respiratory infections.

Category:

Additional information

Dosage and administration

Dosage:
Adults and children over 10 years old: 1 capsule once, 3 times a day or there is a physician’s instruction.
The duration of treatment should not last longer than 8 – 10 days without physician’s advice.
Administration:
The capsule should be swallowed whole with a glass of water, preferably after meals.

Contraindications

Patients with a known hypersensitivity to bromhexine or to any of the excipients of this medicine.

Warnings and precautions for use

– Bromhexine use should be avoided in combination with antitussives, drugs that reduce bronchial secretions because they may cause a risk of stagnant phlegm in the respiratory tract.
– Due to its mucolytic activity, bromhexine may disrupt the gastric mucosal barrier; therefore, bromhexine should be used with caution in patients with a history of peptic ulceration.
– Bromhexine should be used with caution in patients with a history of asthma since bromhexine may induce bronchial spasm in some hypersensitive people.
– Clearance of bromhexine or its metabolites may be reduced in patients with severe hepatic or renal impairment; therefore, bromhexine should be used with caution in these patients and they should be closely monitored.
– Bromhexine should be used with caution in children or elderly or asthenic patients who are unable to expectorate effectively resulting in excess mucus build-up.

Recommendation for pregnancy and breastfeeding

Pregnancy: There are no adequate and controlled studies on bromhexine use in pregnant women, therefore, bromhexine is not recommended for pregnant women.
Lactation: It is not known whether bromhexine is excreted in human milk; therefore, bromhexine is not recommended for breast-feeding women. If bromhexine use is required, discontinue breastfeeding.

Effects on ability to drive and use machines

There have been no studies on the effects of bromhexine on ability to drive and use machines.

Interactions, incompatibilities of medicine

– Bromhexine should not be used in combination with mucolytics (including drugs that reduce bronchial secretions) such as atropine-like drugs (or anticholinergics) because they reduce the effect of bromhexine.
– Bromhexine should not be used in combination with antitussives.
– Bromhexine in combination with antibiotics (amoxicillin, cefuroxime, erythromycin, doxycycline) increases antibiotic concentration in pulmonary tissues and bronchi.

Undesirable effects (ADRs)

Uncommon, 1/1000 <ADR <1/100
– Gastro-intestinal: Epigastric pain, nausea, vomiting, diarrhea.
– Nervous system: Headache, dizziness, sweating.
– Skin: Rash, urticaria.
– Respiratory: Risk of stagnation of bronchial secretions in patients unable to cough up sputum.
Rare, ADR <1/1000
– Gastrointestinal: Dry mouth.
– Hepatic: Increased transaminase AST, ALT.
Management of ADRs
ADRs are usually mild and resolve during treatment (except bronchospasm when bromhexine is given to people with asthma).

Overdose and management

Overdose:
Bromhexine overdose data have not been reported until now.
Management:
If overdose occurs, symptomatic and supportive treatment should be applied.

Pharmacodynamic properties

– Bromhexine is an expectorant/mucolytic agent. It activates sialomucin synthesis and disrupts the structure of acid mucopolysaccharide fibres in mucoid sputum and produces a less viscous mucus, which is easier to expectorate and is coughed up effectively.
– Bromhexine in combination with antibiotics (amoxicillin, cefuroxime, erythromycin, doxycycline) increases antibiotic concentration in pulmonary tissues and bronchi. Thus, bromhexine can act as an adjunct to the treatment of respiratory infections, increasing the effect of antibiotics.
– Clinical effect is generally observed 2 – 3 days after oral administration.
– Bromhexine was given at doses of 16mg once, three times a day for the treatment of dry eye syndrome accompanied by abnormal mucus production (Sjögren's syndrome), but the results were unstable and unclear, thus, this effects is rarely applied.

Pharmacokinetic properties

– Bromhexine is rapidly absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism in the liver, so its bioavailability is only 20%. Food increases the bioavailability of bromhexine hydrochloride. Peak plasma concentrations are reached ½ hour to 1 hour after oral administration.
– Bromhexine is widely distributed to body tissues. Over 95% of dose is bound to plasma proteins.
– Bromhexine is mainly metabolized in the liver. Ambrosol is an active metabolite.
– The terminal elimination half-life of bromhexine is from 13 to 40 hours depending on the individual.
– Bromhexine crosses the blood-brain barrier and small amounts cross the placenta.
– Approximately 85 – 90% of the dose is excreted in the urine, mainly as glucuronic acid and sulfuric acid conjugated metabolites, and a small amount is excreted as unchanged drug. Less than 4% bromhexine is excreted in faeces.

Storage conditions, shelf-life, quality specification of the medicine

Storage conditions: Protect from humidity and light, below 30 degrees C.
Shelf – life: 36 months from the manufacture date.
Quality specification: In house specification.