Mucolytic treatment of acute and chronic bronchopulmonary diseases associated with impaired formation and transport of mucus.

Ambolar^® should be taken exactly as doctor or health care provider instructions. The doctor determines the quantity to be taken and the timing.

Unless otherwise prescribed by doctor, the recommended dose are as follows:

For adults and adolescents over 12 years of age, the therapeutic effect may be enhanced by increasing the dosage to 120 mg ambroxol hydrochloride per day.

Route and method of administration and duration of treatment

Ambolar^® syrup is for oral use.

Ambolar^® syrup can be taken with or without food.

You should contact a doctor if your symptoms worsen or do not improve after 4-5 days.

Special care must be taken with Ambolar^® syrup in the following circumstances:

There is a small risk of allergy and skin reactions with ambroxol and used as expectorants to clear mucus in the airways. In a very small number of cases, there have been reports of severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) occurring in temporal association with the use of expectorants such as ambroxol hydrochloride. Most of these cases were attributable to the underlying disease and/or to other medication being taken concomitantly. In addition, during the early phase of Stevens-Johnson syndrome or TEN, patients may initially experience non-specific influenza-like symptoms such as fever, joint pain, rhinitis, cough and sore throat. Because of these non-specific influenza-like initial symptoms, symptomatic treatment with cough and cold medications, which is inappropriate, may be started. If new skin or mucosal lesions appear, therefore, medical advice should be sought immediately and the use of ambroxol hydrochloride discontinued.

Patients with impaired kidney or liver function

If you have impaired kidney function or severe liver disease, you must not take Ambolar® syrup except on medical advice. With ambroxol, as with any medicine which is broken down in the liver and then eliminated via the kidneys, accumulation of the breakdown products which are formed in the liver can be expected to occur in patients with severely impaired kidney function.

In some rare bronchial diseases which are associated with excessive accumulation of secretions (such as primary ciliary dyskinesia), Ambolar^® syrup should only be used under medical supervision because of the risk that secretions may accumulate.

Use in children

Ambolar^® syrup must not be used in children under 2 years of age except on medical advice.

Ambolar^® contains sorbitol, Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Information to patients

• There is a small risk of allergy and skin reactions with ambroxol and bromhexine used as expectorants to clear mucus in the airways.
• If you experience allergic or skin reactions such as skin swellings or rash, stop treatment immediately and contact your doctor.
• If you are taking ambroxol or bromhexine and have any questions or concerns speak to your doctor of pharmacist.

Information to healthcare professionals

• Anaphylactic reactions and severe cutaneous adverse reactions (SCARs), including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis and acute generalised exanthematous pustulosis, have been reported in patients receiving ambroxol.
• As ambroxol is a metabolite of bromhexine, the risk of anaphylactic and severe cutaneous reactions is considered to apply also to bromhexine.
• The risk of anaphylactic reactions and SCARs with ambroxol or bromhexine is low. Frequencies of these side effects are unknown.
• Advise your patients that they should stop treatment immediately if symptoms of progressive skin rash occur.

Simultaneous use of Ambroxol syrup and cough suppressants may lead to the development of a dangerous accumulation of secretions owing to reduction of the cough reflex and should be undertaken only after careful risk-benefit assessment.

Pregnancy

Ambroxol passes through the placenta to the unborn child. You should not take this medicine while you are pregnant, especially during the first 3 months,

Breast-feeding

Ambroxol has been shown to pass into breast milk in animal studies. Use while breast-feeding is not recommended.

There is no evidence for an effect on ability to drive and use machines.

No relevant studies have been performed.

Ambroxol syrup is generally well tolerated.

The following categories are normally used when reporting the frequencies of side effects:

Very common: More than 1 in 10 patients

Common: Between 1 in 10 and 1 in 100 patients

Uncommon: Between 1 in 100 and 1 in 1000 patients

Rare: Between 1 in 1000 and 1 in 10,000 patients

Very rare: Fewer than 1 in 1/10,000

Not known: Frequency cannot be estimated from the available data.

Side effects:

Immune system disorders / Skin and subcutaneous tissue disorders

Rare: Skin rash, urticaria (nettle rash)

Not known: Swelling of the skin and mucus membranes, itching, anaphylactic reactions* (severe allergic reactions) and severe cutaneous adverse reactions (SCARs)*, including shock, erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis and acute generalised exanthematous pustulosis and other hypersensitivity reactions.

*The risk is low

Nervous system disorders:

Common: Taste disturbances.

Gastrointestinal disorders:

Common: Nausea, feeling of numbness in the mouth.

Uncommon: Vomiting, diarrhea, indigestion, abdominal pain, dry mouth.

Rare: Dry throat

Very rare: Constipation, increased salivation

Respiratory, thoracic and mediastinal disorders

Common: Feeling of numbness in the throat 

Very rare: Increased nasal discharge

Not known: Shortness of breath (as symptom of a hypersensitivity reaction)

Renal and urinary disorders:

Very rare: Difficulty in urinating

General disorders and administration site conditions

Uncommon:  Fever, mucous membrane reactions

Action to be taken in the event of side effects

At the first signs of a hypersensitivity reaction, stop taking Ambolar^® syrup. If you experience allergic or skin reactions such as skin swellings or rash, stop treatment immediately and contact your doctor.

To report any side effects in Saudi Arabia:

o     National Pharmacovigilance and Drug Safety Centre (NPC)

-     Fax: + 966 112057662

-     Call NPC at + 966 112038222, Exts: 2317-2356-2353-2354-2334-2340

-     Toll free phone: 8002490000

-     E-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc

not included 

Pharmacotherapeutic group: Mucolytics, ATC code: R05CB06

Ambroxol, a metabolite of bromhexin, is a mucoactive drug with several properties including secretolytic and secretomotoric actions that restore the physiological clearance mechanisms of the respiratory tract which play an important role in the body’s defence mechanisms and resulting in more productive cough. The pharmacological effect is exerted on mucus quality, ciliary function and the production of alveolar surfactant.

Mucus quality: ambroxol stimulates the activity of serous glandular cells, clears granules of mucus that have already formed, normalizes secretion viscosity and finally regularizes the activity of the tubuloacinar glands in the respiratory tract.

Ciliary function: ambroxol increases both the number of microvilli in the vibratile epithelium and the frequency of ciliary movements, with a resulting increase in the speed of transport of secretion produced, and finally normalizes respiratory tone, improving expectoration.

Increase in surfactant production: ambroxol stimulates synthesis and release of surfactant by type II pneumocytes in alveolae and in small airways in foetal, as well as in adult lungs, thus ensuring the stability of the lung tissue, allowing correct bronchiolar and alveolar clearance and finally facilitating respiratory mechanics and encouraging gaseous exchanges. Those effects were observed in vitro as well in vivo in different animal species.

 In several pre-clinical experiments antioxidative effects of ambroxol were noted. Up to date no clinical relevance ofthis observation was confirmed.

After ambroxol administration concentrations of antibiotics amoxicilline, cefuroxime, erythromycine and doxycycline were higher in sputum and bronchial secretion, however, without clinical significance.

The bioavailability of ambroxol has been evaluated in humans after the oral administration of the drug in healthy volunteers.

Ambroxol is almost completely absorbed after oral administration. Tmax is 1-3 hours.

It is extensively bound to plasma proteins (90%). Half-time of ambroxol in plasma is 7-12 hours. Sum of half-life of ambroxol and its metabolites in plasma is about 22 hours.

Ambroxol crosses in the amniotic fluid and placenta, and is secreted in breast milk.

Ambroxol is metabolized in the liver. Bioavailability of absorbed ambroxol is lowered by a third due to the first pass metabolism in the liver.

About 90% of ambroxol and its metabolites are eliminated through the kidneys. Less than 10% of ambroxol is eliminated unchanged by the kidneys.

Due to high protein binding and big distribution volume, as well as slow re-release from the tissues in blood dialysis or forced diuresis will be ineffective in elimination of ambroxol.

In patients with severe hepatic impairment clearance of ambroxol lowers 20 – 40%.

In patients with severe renal impairment accumulation of ambroxol metabolites is to be expected.

Non-clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction.

Citric acid, glycerin, sorbitol 70%, hydroxyethyl cellulose, sodium benzoate, propylene glycol, acesulfame potassium, strawberry flavor, cherry flavor, menthol and purified water.

None known.

Do not store above 30˚C.

Discard unused content three months after first opening

Ambolar^® is available in a carton containing one amber glass bottle (filled with 100 ml of the syrup) as well as an insert.

No special requirements