As a mucolytic in the management of viscid mucoid secretions associated with bronchitis, bronchiectasis, sinusitis.

Oral.

Adults and children over 12 years:

Recommended total daily dose	Recommended maximum daily dose
10 ml (8 mg) three times daily	15 ml (12 mg) four times daily

The recommended maximum daily dose which may be needed at the commencement of treatment should not be exceeded.

Children over 5 to ≤ 12 years:	Recommended total daily dose 5 ml (4 mg) four times daily.
Children 2 to ≤ 5 years:	Recommended total daily dose 5 ml (4 mg) twice daily.

Solvex can be taken with or without food (see section 5.2).

Additional information on specific populations

Solvex is suitable for diabetes patients.

Solvex is contraindicated in patients known to be hypersensitive to bromhexine or other components of the formulation. In case of conditions that may be incompatible with an excipient of the product (please refer to “Special warnings and precautions”) the use of this product is contraindicated

Bromhexine should be used with caution in patients with a history of, or existing, peptic ulceration.

There have been reports of severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN) and acute generalised exanthematous pustulosis (AGEP) associated with the administration of bromhexine hydrochloride. If symptoms or signs of a progressive skin rash (sometimes associated with blisters or mucosal lesions) are present, bromhexine hydrochloride treatment should be discontinued immediately and medical advice should be sought.

Solvex contains propylene glycol, benzoic acid, aspartame and liquid sorbitol

Solvex  contains propylene glycol

• If your child is less than 5 years old, talk to your doctor or pharmacist before giving them this medicine, in particular if they use other medicines that contain propylene glycol or alcohol.
• If you are pregnant or breast‑feeding, do not take this medicine unless recommended by your doctor. Your doctor may carry out extra checks while you are taking this medicine.
• If you suffer from a liver or kidney disease, do not take this medicine unless recommended by your doctor. Your doctor may carry out extra checks while you are taking this medicine.

Solvex  contains benzoic acid

• Benzoic acid may increase jaundice (yellowing of the skin and eyes) in newborn babies (up to 4 weeks old).

Solvex  contains aspartame

• Neither non-clinical nor clinical data are available to assess aspartame use in infants below 12 weeks of age.

Solvex  contains liquid sorbitol

• Sorbitol may cause gastrointestinal discomfort and mild laxative effect.

No clinically relevant unfavourable interactions with other medications, such as ampicillin, amoxicillin, oxytetracycline or erythromycin, have been reported (see section 5.1).

Interaction studies with oral anticoagulants or digoxin were not performed.

 

Pregnancy

There are limited data from the use of bromhexine in pregnant women.

Pre-clinical 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 bromhexine hydrochloride during pregnancy.

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 breast milk. A risk to the breastfed infant cannot be excluded.

Solvex should not be used during breast-feeding.

Fertility

No studies on the effect on human fertility have been conducted with bromhexine hydrochloride.

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 bromhexine hydrochloride.

The following side effects have been reported based on clinical trials involving 3,992 patients

Frequencies

Very common ≥1/10

Common ≥ 1/100 < 1/10

Uncommon ≥ 1/1,000 < 1/100

Rare ≥ 1/10,000 < 1/1,000

Very rare < 1/10,000

Not known cannot be estimated from the available data

Immune system disorders
Hypersensitivity reactions	Rare
Anaphylactic reactions including anaphylactic shock*, angioedema* and pruritus*	Not known
Respiratory, thoracic and mediastinal disorders
Bronchospasm*	Not known
Gastro-intestinal disorders
Abdominal pain upper	Uncommon
Nausea	Uncommon
Vomiting	Uncommon
Diarrhoea	Uncommon
Skin and subcutaneous tissue disorders
Rash	Rare
Urticaria*	Rare
Severe cutaneous adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis and acute generalized exanthematous pustulosis)	Not known

*This adverse reaction has been observed in post-marketing experience. With 95 % certainty, the frequency category is not greater than rare (3/3,992), but might be lower. A precise frequency estimation is not possible as the adverse drug reaction did not occur in a clinical trial database of 3,992 patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

• Saudi Arabia

The National Pharmacovigilance and Drug Safety Centre (NPC)

Fax: + (966-11) 2057662

Toll free: 800-249-0000

Phone No.: + (966-11) 2038222, Exts: 2317-2356-2353-2354-2334-2340.

e-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc

• Other GCC States:

Please contact the relevant competent authority

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 bromhexine hydrochloride at recommended doses and may need symptomatic treatment.

Pharmacotherapeutic group: Expectorants, excl. combinations with cough suppressants

ATC-Code: R05CB02

Bromhexine is a 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.

Drug/ drug interactions in Pharmacodynamics and Pharmacokinetics

Following the administration of bromhexine antibiotic concentrations (amoxycillin, erythromycin, oxytetracycline) in the sputum and bronchopulmonary secretions are increased. Bromhexine pharmacokinetics are not relevantly affected by co-administration of ampicillin or oxytetracycline.

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 bromhexine hydrochloride tablets and solution, respectively. The first pass metabolism amounts to about 75-80%. Concomitant food leads to an increase of bromhexine plasma concentrations.

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 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 or oxytetracyclin. There is insufficient pharmacokinetic data to evaluate a possible drug-drug interaction between bromhexine and erythromycin.

Elimination

Bromhexine is a high extraction ratio drug after IV administration in the range of the hepatic blood flow, 843-1073 mL/min resulting in high inter- and intraindividual 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.

Special populations

There are no data for bromhexine pharmacokinetics in the elderly or in patients with renal or liver insufficiency.

No details on schedule.

- Propylene glycol

- Benzoic acid

- Aspartame

- Glycerin

- Liquid sorbitol

- Tutti frutti liquid flavor

- Citric acid

- Purified water

Not applicable.

Unopened: 36 months. Discard this medicine immediately after finishing the prescribed dose.

Store below 30°C.

Store in the original package.

Plastic bottle sealed with white child resistant cap with plug.

Pack size: 1 bottle (100 ml).

No special requirements.