Ezolvin contains a medicine called bromhexine. This belongs to a group of medicines called mucolytic agents.

Ezolvin helps in breathing more easily when having breathing problems such as bronchitis or sinusitis. It works by making the mucus thinner so that patients can get rid of it more easily.

§ The usual dose is as follows, to be taken orally:

-    Adults and children over 12 years: 1 tablet three times a day (can be increased to 2 tablets three times a day for the first 7 days).

-    Children over 6 years: 1 tablet 3 times a day.

-    Children 6 - 11 years: Ezolvin should only be used on the medical advice by a doctor, pharmacist or nurse practitioner.

§ Not to be used in children under 6 years.

§ The recommended dose should not be exceeded.

Ezolvin should be used with caution in the following cases:

§ Patients with stomach ulcer.

§ Skin lesions such as severe blistering or peeling of the skin, mouth, eyes and genitals (refer to section 4.  Possible Side Effects) after having flu-like symptoms e.g. fever, aching body, blocked or runny nose, cough and sore throat, Ezolvin should be discontinued straight away.

Ezolvin can affect the way the following medicines work or they can affect the way Ezolvin works:

Antibiotics such as ampicillin, amoxicillin, erythromycin or oxytetracycline.

Ezolvin should not be taken in case of pregnancy or breast-feeding.

Pregnancy

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 Ezolvin during pregnancy.

Lactation

-    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.

-    Ezolvin should not be used during breast-feeding.

Fertility

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

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 Ezolvin.

If any of the following serious side effects were noticed, Ezolvin should be stopped and urgent medical treatment is needed:

§ Serious allergic reactions that may cause swelling of face or throat, wheezing or sudden difficulties in breathing.

§ Skin lesions such as severe blistering or peeling of the skin, mouth, eyes and genitals.

Other side effects

Other side effects:

Uncommon (affects less than 1 in 100 people)

§ Feeling sick (nausea) or being sick (vomiting)

§ Pain in the upper part of your abdomen

§ Diarrhoea

Rare (affects less than 1 in 1000 people)

§ Allergic reactions, skin rash

The following side effects can also happen but the frequency of these is not known

§ Tightness of chest

§ Nettle rash (urticaria) or itching

In addition, an expected increase in the flow of the mucus secretion will result from taking Ezolvin.

To report any side effect(s):

·   Saudi Arabia:

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 Ezolvin at recommended doses and may need symptomatic treatment.

ATC Code: R05CB0.

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.

Following the administration of bromhexine antibiotic concentrations (amoxycillin, erythromycin, oxytetracycline) in the sputum and bronchopulmonary secretions are increased.

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 Ezolvin 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 i.v. 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).

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.

Bromhexine pharmacokinetics are not relevantly affected by co-administration of ampicillin or oxytetracycline.

Interaction studies with oral anticoagulants or digoxin were not performed.

No details on schedule.

None reported.

§ Keep in a safe place, out of the reach and sight of children.

§ Store below 30º C.

Ezolvin Tablets are available in blister of PVC-film (the upper part) & aluminium foil (the lower part.

No special requirements.