BISOLVON(r) CHESTY FORTE Bromhexine hydrochloride tablets Bromhexine hydrochloride oral solution
BISOLVON CHESTY FORTE tablets are round, white bevel-edged tablets. One side is scored and impressed with '51B' on both sides of the score. The other side is impressed with the company logo. Each tablet contains 8 mg bromhexine hydrochloride. BISOLVON CHESTY FORTE oral solution is a clear to almost clear and colourless to almost colourless solution with an aroma of chocolate and cherry. Each 5 ml contains 8 mg bromhexine hydrochloride.
Bromhexine hydrochloride is a mucolytic. It has been shown to enhance the transport of mucus by reducing its viscosity and by activating the ciliated epithelium (mucociliary clearance). Preclinical studies show that there is an increase in the amount of thin watery bronchial secretion. Clinical studies show that bromhexine has 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.
Absorption Following oral administration, bromhexine shows dose linear pharmacokinetics in the dose range of 8-32 mg. It is rapidly and completely absorbed from the gastrointestinal tract. The bioavailability after oral administration is substantially reduced by an extensive first-pass effect in the range of 70- 80%. The absolute bioavailability of bromhexine hydrochloride is about 22.2 +- 8.5 % up to 26.8 +- 13.1 % for BISOLVON CHESTY FORTE tablets and oral solution, respectively. Concomitant food intake leads to an increase of bromhexine plasma concentrations. Distribution After intravenous administrations bromhexine was rapidly and widely distributed throughout the body with a mean volume of distribution (Vss) 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 and 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 almost completely metabolised to a variety of hydroxylated metabolites and to dibromanthranilic 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 (CL after intravenous administration is ~ 843-1073 mL/min) resulting in high inter- and intra-individual variability. Bromhexine is almost completely metabolised to a variety of hydroxylated metabolites and to dibromanthranilic acid. Ambroxol is a metabolite of bromhexine. After administration of radiolabelled bromhexine, about 97.4 +- 1.9 % of the dose was recovered in the urine, with less than 1% as the parent compound. Unchanged bromhexine is 95% bound to plasma proteins. Bromhexine plasma concentrations showed a multi- exponential decline. After administration of single oral doses between 8 and 32 mg, the terminal elimination half-life of bromhexine ranged between 6.6 and 31.4 hours. The relevant half-life to predict the multiple dose pharmacokinetics is about 1 hour. No accumulation was observed after multiple dosing. General Bromhexine shows dose proportional pharmacokinetics in the range of 8-32 mg following oral administration. 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. Also, interaction studies with oral anticoagulants or digoxin were not performed. Bromhexine pharmacokinetics are not relevantly affected by co-administration of ampicillin or oxytetracycline. There was also no relevant interaction between bromhexine and erythromycin according to a historical comparison. The lack of any relevant interaction reports during the long term marketing of the drug suggests no substantial interaction potential with these drugs.
For use as a mucolytic to break down mucus and help clear the chest in conditions accompanied by excessive mucus secretions, such as in the common cold, influenza, infections of the respiratory tract or in other conditions where excess mucus is produced.
Do not use in children under 6 years of age. Use in children aged 6 to 11 years only on the advice of a doctor, pharmacist or nurse practitioner Tablets: Adults: One tablet (8 mg) three times a day. May be increased to two tablets (16 mg) three times a day for the first seven days. Children 6 - 11 years: 1 tablet three times a day. Oral solution: Adults: 5 ml (8 mg) three times a day. May be increased to 10 ml (16 mg) three times a day for the first seven days. Children 6-11 years: 5 ml (8 mg) three times a day. The oral liquid is alcohol-free and sugar-free and therefore suitable for diabetics. When infection is present, specific treatment with antibiotics could be indicated in addition to BISOLVON CHESTY FORTE therapy. In acute respiratory indications, medical advice should be sought if symptoms do not improve or worsen during the course of therapy.
BISOLVON CHESTY FORTE should not be used in patients known to be hypersensitive to bromhexine or any other component of the formulation. Do not use BISOLVON CHESTY FORTE tablets or oral solution in children under 6 years of age. In case of rare hereditary conditions that may be incompatible with an excipient of the product (refer to Warnings and Precautions), the use of the product is contraindicated.
BISOLVON CHESTY FORTE should be used with caution in patients with severe liver disease and severe renal failure (refer Pharmacokinetics). Use with caution in patients with gastric ulceration. Patients should be advised to expect an increase in the flow of mucus secretions. BISOLVON CHESTY FORTE tablets contain 444 mg of lactose per maximum recommended daily dose. Patients with rare hereditary galactose intolerance e.g. galactosaemia should not take this product. BISOLVON CHESTY FORTE oral solution contains at least 7.5 g of maltitol and up to 1.2 g of sorbitol per maximum recommended daily dose of 30 ml. Products containing maltitol and sorbitol may have a laxative effect or cause diarrhoea in some people. This is more likely if several products containing maltitol, sorbitol or related substances are consumed simultaneously. Patients with rare hereditary fructose intolerance should not take these products. There have been very few reports of severe skin lesions such as Stevens Johnson Syndrome and toxic epidermal necrolysis (TEN) in temporal association with the administration of expectorants such as bromhexine. Mostly, these could be explained by 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 prodomes like e.g. fever, aching body, rhinitis, cough and sore throat. Misled by these non-specific influenza-like prodomes 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.
There are limited data from the use of bromhexine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of BISOLVON CHESTY FORTE during pregnancy.
It is unknown whether bromhexine/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of bromhexine/metabolites in breast milk. A risk to the breastfed infant cannot be excluded. BISOLVON CHESTY FORTE should not be used during breast-feeding.
No studies on the effect on human fertility have been conducted with BISOLVON CHESTY FORTE. Based on available pre-clinical experience there are no indications for possible effects of the use of bromhexine on fertility
No studies on the effect on the ability to drive and use machines have been performed with BISOLVON CHESTY FORTE.
Immune system disorder, Skin and subcutaneous tissue disorders and Respiratory, mediastinal and thoracic disorders: Anaphylactic reaction including anaphylactic shock, angioedema, bronchospasm, rash, urticaria, pruritus, and other hypersensitivity.
Gastro-intestinal disorders:
Nausea, vomiting, diarrhoea and abdominal pain upper.
No clinically relevant unfavourable interactions with other medicines have been reported (refer to Actions for the effects of bromhexine on antibiotic concentrations).
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 side effects of BISOLVON CHESTY FORTE at recommended doses and may need symptomatic treatment. Advice can be obtained from the Poisons Information Centre (telephone 0800 764 766).
BISOLVON CHESTY FORTE tablets should be stored in a safe place out of the reach of children, below 25degC. BISOLVON CHESTY FORTE oral solution should be stored in a safe place out of the reach of children, below 30degC.
Pharmacy Medicine.
BISOLVON CHESTY FORTE tablets are available in blister packs of 50. Each tablet contains 8 mg bromhexine hydrochloride. BISOLVON CHESTY FORTE oral liquid is available in bottles of 200 mL. Each 5 mL contains 8 mg bromhexine hydrochloride.
Bisolvon(r) is a registered trademark.
Tablets: lactose, maize starch, magnesium stearate. Oral solution: Maltitol solution, sucralose, benzoic acid, menthol, chocolate flavour 96534-33, cherry flavour 96323-33 and purified water.
Boehringer Ingelheim (N.Z.) Limited PO Box 76-216 Manukau City Auckland NEW ZEALAND Telephone: (09) 274-8664 Facsimile: (09) 271-0629
3 August 2012 CCDS 0052-06 6.1.2012