DiffCof Dual Action Chesty Cough Syrup

Each 5 mL contains Bromhexine hydrochloride 4 mg, Guaifenesin 100 mg.
Excipients/Inactive Ingredients: Disodium edetate, Sorbitol Solution 70% (crystallising), Hydroxyethyl cellulose, Sucralose, Saccharin sodium, Citric acid anhydrous, Sodium benzoate, Strawberry flavour, 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.
Guaifenesin is an expectorant which is thought to act by irritating the gastric mucosa and subsequently stimulating respiratory tract secretions. This increase in fluid increases the volume and decreases the viscosity of bronchial secretions.
Following the administration of bromhexine, the antibiotic concentrations of amoxycillin, erythromycin and oxytetracycline in the sputum and bronchopulmonary secretions are increased.
No information on guaifenesin.
Pharmacokinetics: Absorption: Bromhexine shows dose proportional pharmacokinetics. It 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 leads to an increase bromhexine plasma concentrations.
Guaifenesin is well absorbed from the gastrointestinal tract.
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).
No available information on Guaifenesin.
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.
Guaifenesin is metabolised and it is rapidly hydrolyzed (60% within 7 hours).
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).
Guaifenesin has a plasma half-life of approximately 1 hour and then excreted in the urine, with beta-(2-methoxyphenoxy)-lactic acid as its major urinary metabolite.
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 and expectorant 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 teaspoonfuls) 3 times daily.
Children 6 - 12 years: 5 mL (1 teaspoonful) 3 times daily.
Children 2 - 6 years: 2.5 mL (½ teaspoonful) 3 times daily.
Children under 2 years: Not recommended.
Using measuring cup provided or suitable measuring device to measure the doses correctly.
Duration of treatment: In acute respiratory indications, medical advice should be sought if symptoms do not improve rapidly or worsen during course of therapy.
Additional information on specific populations: DiffCof Dual Action Chesty Cough Syrup is sugar-free and therefore suitable for diabetics and small children.
Mode of Administration: For oral use.

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

DiffCof Dual Action Chesty Cough Syrup must not be used in patients known to be hypersensitive to bromhexine, guaifenesin or other components of the formulations.
Guaifenesin is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals.
In case of rare hereditary conditions that may be incompatible with an excipient of the product the use of the product is contraindicated.

Patients being treated with DiffCof Dual Action Chesty Cough Syrup should be notified of an expected increase in the flow of secretions.
In acute respiratory indications, medical advice should be sought if symptoms do not improve rapidly or worsen during course of therapy.
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 can 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.
This product contains 7,500 mg of 70% Sorbitol Solution per maximum recommended daily dose for adult. Patients with the rare hereditary condition of fructose intolerance should not take this medicine. This product contains sorbitol, which may have a laxative effect or can cause diarrhoea in some people.
Urinary calculi have been reported in patients consuming large quantities of the products containing guaifenesin. Small quantities of ephedrine were also present in the stones of one of several patients who had ingested preparations containing a combination of guaifenesin and ephedrine.
Risk in Specific Populations: When using preparations containing guaifenesin, caution should be exercised in the presence of severe renal or severe hepatic impairment as there have been no specific studies of guaifenesin in subjects with renal or hepatic impairment.
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 Dual Action Chesty Cough Syrup.

Use In Pregnancy: Bromhexine crosses the placental barrier. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development. Clinical experience to date has shown no evidence of harmful effects on the foetus during pregnancy. Nonetheless, the usual precautions regarding the use of drugs during pregnancy should be observed. Especially during the first trimester, the use of bromhexine is not recommended.
There is no data on the use of guaifenesin in pregnant women. The effects, if any, on the developing fetus are unknown.
Use In Lactation: The risk on an infant when use of guaifenesin during breastfeeding is inconclusive. Guaifenesin is excreted in breast milk in small quantities. Bromhexine is expected to enter breast milk. Unfavourable effects on breastfed infants would not be expected. DiffCof Dual Action Chesty Cough Syrup is not recommended for use in nursing mothers.

Immune system disorder, skin and subcutaneous tissue disorders and respiratory, thoracic and mediastinal disorders: Bromhexine: anaphylactic reaction including anaphylactic shock, angioedema, bronchospasm, rash, urticaria, pruritus and other hypersensitivity reactions.
Guaifenesin: rash, including urticaria.
Gastro-intestinal disorders: Bromhexine: nausea, vomiting, diarrhoea, upper abdominal pain.
Guaifenesin: gastrointestinal discomfort, nausea and vomiting have occasionally been reported, particularly in very large doses.
Nervous system disorders: Bromhexine: no available information.
Guaifenesin: dizziness and headache has been reported. Abuse of medications containing guaifenesin may produce urolithiasis.

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

Store below 30°C.

Cough & Cold Preparations

R05CB10 - combinations ; Belongs to the class of mucolytics. Used in the treatment of wet cough.

NDD