DiffCof Chesty Cough Syrup

Each 5 mL contains Bromhexine hydrochloride 4 mg.
Excipients/Inactive Ingredients: Methyl hydroxybenzoate, Sorbitol Solution 70% (crystallising), Glycerol, Citric acid anhydrous, Polysorbate 20, Flavour Forestberry, L-Menthol, Hydroxyethylcellulose, Purified Water.

Pharmacology: Pharmacodynamics: Mechanism of Action: Bromhexine is synthetic derivative of the herbal active ingredient vasicine.
Preclinically, it has been shown to increase the proportion of serous bronchial secretion. Bromhexine enhances mucus transport by reducing mucus viscosity and by activating the ciliated epithelium (mucociliary clearance).
In clinical studies, Bromhexine showed a secretolytic and secretomotor effect in the bronchial tract area, which facilitates expectoration and eases cough.
Following the administration of bromhexine, the antibiotic concentrations of amoxycillin, erythromycin and oxytetracycline in the sputum and bronchopulmonary secretions are increased.
Pharmacokinetics: Absorption: Bromhexine is rapidly and completely absorbed from the gastrointestinal tract.
After oral administration solid and liquid formulations show similar bioavailability.
The absolute bioavailability of bromhexine hydrochloride was about 22.2 ± 8.5% and 26.8 ± 13.1% for tablets and solution, respectively. The first-pass metabolism amounts to about 75-80%. Concomitant food intake tended to increase bromhexine plasma concentrations probably due to partial inhibition of the first-pass effect.
Distribution: After intravenous administration bromhexine was rapidly and widely distributed throughout the body with a mean volume of distribution (V_ss) of up to 1209 ± 206 L (19 L/kg). The distribution into lung tissue (bronchial and parenchymal) was investigated after oral administration of 32 mg and 64 mg bromhexine. Lung-tissue concentrations two hours post dose 1.5-4.5 times higher in bronchiolo-bronchial tissues and between 2.4-5.9 times higher in pulmonary parenchyma compared to plasma concentrations.
Unchanged bromhexine is bound to plasma proteins by 95% (non-restrictive binding).
Metabolism: Bromhexine is extensively metabolised to a variety of hydroxylated metabolites and to dibromoanthranilic acid. All metabolites and bromhexine itself are conjugated most probably in form of N-glucuronides and O-glucuronides. There are no substantial hints for a change of the metabolic pattern by a sulphonamide, oxytetracycline or erythromycin. Thus relevant interactions with CYP 450 2C9 or 3A4 substrates are unlikely.
Elimination: Bromhexine is a high extraction ratio drug after i.v. administration in the range of the hepatic blood flow, 843-1073 mL/min resulting in high inter- and intra-individual variability (CV >30%). After administration of radiolabelled bromhexine about 97.4 ± 1.9% of the dose were recovered as radioactivity in urine, with less than 1% as parent compound. Bromhexine plasma concentrations showed a multiexponential decline. After administration of single oral doses between 8 and 32 mg, the terminal elimination half-life ranged between 6.6 and 31.4 hours. The relevant half-life to predict the multiple dose pharmacokinetics is about 1 hour, thus no accumulation was seen after multiple dosing (accumulation factor 1.1).
Linearity/Non-Linearity: Bromhexine shows dose proportional pharmacokinetics in the range of 8-32 mg following oral administration.
Kinetics in Special Populations: There are no data for bromhexine pharmacokinetics in the elderly or in patients with renal or liver insufficiency. Extensive clinical experience did not give rise to relevant safety concerns in these populations.

For secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport.

Recommended Dose: Adults and children over 12 years: 10 mL (2 teaspsoonfuls) 3 times daily.
Children over 6 to ≤12 years: 5 mL (1 teaspoonful) 3 times daily.
Children 2 to ≤6 years: 2.5 mL (½ teaspoonful) 3 times daily.
Children under 2 years: 1.25 mL (¼ teaspoonful) 3 times daily.
Using the measuring cup provided or a suitable measuring device to measure the doses correctly.
Recommended total daily dose: Children under 2 years: up to 4 mg/day.
Children 2 years to ≤6 years: 8 mg/day.
Children over 6 years to ≤12 years: 12 mg/day.
Adults and children over 12 years: 24 mg/day.
Recommended maximum daily dose: The maximum daily dose, which may be necessary at commencement of treatment, should not exceed twice the recommended daily dose in adults and children.
Duration of treatment: In acute respiratory indications, medical advice should be sought if symptoms do not improve after 4-5 days or worsen during course of therapy.
Additional information on specific populations: DiffCof Chesty Cough Syrup is sugar-free and therefore suitable for diabetes patients and small children.
Mode of Administration: For oral use.
DiffCof Chesty Cough Syrup can be taken with or without food.

Overdose and Treatment: No specific overdose symptoms have been reported in human to date. Based on accidental overdose and/or medication error reports, the observed symptoms are consistent with the known undesirable effects of Bromhexine at recommended doses and may need symptomatic treatment.

DiffCof Chesty Cough Syrup is contraindicated in patients known to be hypersensitive to bromhexine or other components of the formulations.
In case of hereditary conditions that may be incompatible with an excipient of the product, the use of the product is contraindicated.

Patients being treated with DiffCof Chesty Cough Syrup should be notified of an expected increase in the flow of secretions.
There have been very rare reports of severe skin lesions such as Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (TEN) in temporal association with the administration of mucolytic substances such as bromhexine. Mostly, these could be explained by the severity of the patient's underlying disease and/or concomitant medication. In addition, during the early phase of a Stevens-Johnson syndrome or TEN a patient may first experience non-specific influenza-like prodromes like e.g. fever, aching body, rhinitis, cough and sore throat. Misled by these non-specific influenza-like prodromes it is possible that a symptomatic treatment is started with a cough and cold medication. Therefore, if new skin or mucosal lesions occur, medical advice should be sought immediately and treatment with bromhexine should be discontinued as a precaution.
DiffCof Chesty Cough Syrup contains sorbitol, which may have a laxative effect or can cause diarrhoea in some people.
Effects on the ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed with DiffCof Chesty Cough Syrup.

Use In Pregnancy: There are limited data from the use of bromhexine in pregnant women.
Preclinical studies do not indicate direct and indirect harmful effects with respect to reproductive toxicity.
As a precautionary measure, it is preferable to avoid the use of DiffCof Chesty Cough Syrup during pregnancy.
Use In Lactation: It is unknown whether bromhexine/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in pre-clinical studies have shown excretion of bromhexine/metabolites in the breast milk. A risk to the breastfed infant cannot be excluded. Therefore, DiffCof Chesty Cough Syrup should not be used in breastfeeding mothers.

Immune system disorder: Hypersensitivity, anaphylactic reaction including anaphylactic shock.
Respiratory, thoracic and mediastinal disorders: Bronchospasm.
Gastro-intestinal disorders: Nausea, vomiting, diarrhoea, upper abdominal pain.
Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus, angioedema.

No clinically relevant unfavourable interactions with other medicines have been reported.

Store below 30°C.

Cough & Cold Preparations

R05CB02 - bromhexine ; Belongs to the class of mucolytics. Used in the treatment of wet cough.

NDD