As an auxiliary for the liquefaction of the mucus secretions of the respiratory tracts, in case of acute and chronic bronchoalveolar disorders (bronchitis, emphysema, tracheobronchitis, chronic asthmatic bronchitis).

It is also indicated for the prevention of respiratory complications after retention of secretions following major surgical operations on the thorax - upper abdomen and after prolonged bed rest.

It must be administered concomitantly with the proper antibiotic during acute bronchitis exacerbations.

Adults: 1 Tablet 3 times daily.

The therapeutic effect may be enhanced by administrating 2 Tablets 2 times daily.

Mucum tablets should preferably be swallowed whole, followed by an appropriate amount of liquid (e.g. water, tea or fruit juice). The tablets should be taken after meals.

The use of the drug may lead to an increase in the volume of fluid bronchial secretions and if not removed by coughing an intubation of the patient might be preferable for the airway to remain open.

Mucum tablets conatins lactose. This medicine should not be administered in patients with rare hereditary galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

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 ambroxol hydrochloride. Most of these cases 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 symptoms such as fever, aching body, rhinitis, cough and sore throat. Misled by these non-specific influenza-like symptoms, it is possible that 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 ambroxol hydrochloride discontinued as a precaution.

In the presence of impaired renal function or severe hepatopathy, Mucum must only be used after consulting a physician.  As for all medications metabolized by the liver, followed by renal elimination, accumulation of metabolites of ambroxol, generated in the liver, can be expected in the presence of severe renal insufficiency.

-      Ambroxol is not recommended for co-administration with: Cough-suppressing medicines (antitussive agents): No medicines that suppress the coughing reflex (so called antitussive medicines) should be used concomitantly with Mucum. The coughing reflex is important for expectoration of liquefied mucus and its removal from the lungs.

-      This medicine can be used simultaneously with antibiotics such as amoxicillin, cefuroxime, erythromycin and doxycycline, antibiotics penetration into lung tissues and their efficacy increase.

Pregnancy

During animal studies, there was no indication of direct or indirect harm with respect to pregnancy, embryo fetal development, parturition, or postnatal development.

There are no adequate data on the use of ambroxol during human pregnancy and there is no evidence of fetal harm.

Breast-feeding

Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during breastfeeding.

Administer to lactating women only if the potential benefit outweighs the potential risk to the infant.

Mucum either does not affect, or has only negligible impact on ability to drive vehicles and operate machines.

-   Dermatologic effects

Contact dermatitis, rash, pruritus, urticaria, exanthema, itching, pruritic erythema and vesicular eruptions about the nose, upper lips, and cheeks, and pharyngeal soreness and spasm have been reported with therapeutic use.

-   Gastrointestinal Effects

Dry mouth, diarrhea, excessive salivation, constipation, nausea and vomiting, xerostomia and sialorrhea have all been reported with therapeutic use.

-   Neurologic Effects

Fatigue was infrequently reported in patients receiving ambroxol therapy.

-   Renal Effects

Dysuria occurred infrequently with ambroxol therapy.

-   Respiratory Effects

Rhinorrhea reported in patients with ambroxol therapy.

-   Other

Fatigue was reported in 1 of 63 patients receiving ambroxol 60 to 120 milligrams/day for bronchitis

To report any side effect(s):

The National Pharmacovigilance and Drug Safety Centre (NPC)

Fax: +966-11-205-7662

Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.

Toll free phone: 8002490000

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

Website: www.sfda.gov.sa/npc

Until now, there were no specific signs of overdose in humans. On the basis of reports of accidental overdose and / or errors in the treatment of the observed symptoms consistent with the known side effects of Ambroxol at recommended doses and may need symptomatic treatment.

Pharmacotherapeutic group: mucolytic agents.

ATC code: R05CB06.

Mucum is a mucolytic agent used in respiratory tract diseases.

Ambroxol is an active N-desmethyl metabolite of the mucolytic bromhexine. Although its mechanism of action has not been fully defined, it may increase the quantity and decrease the viscosity of tracheobronchial secretions. It may also act as an expectorant, increasing mucociliary transport via stimulation of ciliary motility.

Ambroxol may stimulate the synthesis and secretion of pulmonary surfactant; the drug has been referred to as a "surfactant activator”.

In preclinical investigations, ambroxol hydrochloride has shown to increase the proportion of serous bronchial secretion. It promotes the formation and outward transfer of surface-active material in the alveolar and bronchial region of the foetal and adult lungs. These actions have resulted in improved flow and transport of mucus (mucociliary clearance). Improving mucus clearance has been shown in clinical pharmacological studies. Increasing secretion and clearance of mucus facilitates expectoration and relieves cough.

A local anaesthetic effect of ambroxol hydrochloride has been observed in the rabbit eye model, which may be explained by the sodium channel blocking properties.

It has been shown in vitro that ambroxol hydrochloride blocks sodium channels, the binding is reversible and dependent on the concentration of the substance.

The release of cytokines in the blood stream and the mononuclear and polymorphonuclear cells which are riveted in tissues have shown a significant decrease in vitro because of ambroxol hydrochloride. 

In clinical studies of patients with sore throat, pain and redness in the pharynx decreased significantly. 

After administration of ambroxol, concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin) in bronchopulmonary secretions and sputum are increased.

Absorption

Pharmacokinetic studies showed rapid absorption of orally administered immediate release forms of ambroxol hydrochloride, with linearity in the therapeutic dose range. The maximum plasma levels arrive within 1 to 2.5 hours for oral immediate-release forms.

Distribution

The protein binding at therapeutic levels in plasma is approximately 90 %.  The distribution of ambroxol after oral, I.V. and I.M. administration, from the blood to the tissues is rapid and peak drug concentrations are observed in the lungs. The volume of distribution after oral administration was estimated to be 552 L. 

Metabolism and elimination 

Approximately 30 % of an oral dose is eliminated via the phenomenon of the first passage.

Studies in human liver microsomes showed that coenzyme CYP3A4 is responsible for the metabolism of ambroxol hydrochloride in dibromoanthranilic acid. The ambroxol hydrochloride metabolized primarily by the liver and converted via glucuronidation todibromoanthranilic acid acid (about 10 % of dose) and some minor metabolites. Within three days after oral administration, approximately 6 % of the dose is detoxified in free form, while about 26 % of the dose is in conjugated form in urine.

Plasma half-life is approximately 10 hours. The total clearance is about 660 ml/min, and renal clearance accounts for about 8 % of total clearance. 

Pharmacokinetics in special populations 

In patients with hepatic impairment the elimination of ambroxol hydrochloride is reduced, resulting in 1.3 to 2 times higher plasma levels. Because of the large therapeutic range of ambroxol hydrochloride, dose adjustments are not considered necessary.

Other 

Age and gender did not affect the pharmacokinetics of ambroxol hydrochloride in clinical level and therefore dose adjustment is not required.

Food was not found to affect the bioavailability of ambroxol hydrochloride.

Ambroxol hydrochloride has a low acute toxicity index.

Repeated oral dose of 150 mg/kg/day in mice (4 weeks), of 50 mg/kg/day in rat (52 and 78 weeks) , of 40 mg/kg/day in rabbits (26 weeks) and a dose of 10 mg/kg/day in dogs

(52 weeks) showed no discernible toxicity in any organ.

In intravenous toxicity studies four weeks with ambroxol hydrochloride administered in rats at 4, 16 and 64 mg/kg/day and in dogs at 45, 90 and 120 mg/kg/day (infusion 3 hours/day) showed no severe local or systemic toxicity including histopathology.  All adverse reactions were reversible. 

Dosing ambroxol hydrochloride orally when tested at doses of up to 3000 mg/kg/day in rats, and 200 mg/kg/day in rabbits showed no embryotoxic or teratogennic actions. The fertility in male and female rats was not affected at doses up to 500 mg/kg/day. 

The NOAEL in a perinatal and postnatal study and development was 50 mg/kg/day. At 500 mg/kg/day, ambroxol hydrochloride was slightly toxic for dogs, as shown by a retarded body-weight development.

Genotoxicity studies both in vitro (Ames test and chromosome aberration test) and in vivo (mouse micronucleus test) showed no mutagenic potential of ambroxol hydrochloride.  

Ambroxol hydrochloride did not show any tumorigenic potential in carcinogenicity studies in mice (50, 200 and 800 mg/kg/day) and rats (65, 250 and 1000 mg/kg/day) when treated with a dietary admixture for 105 and 116 weeks, respectively.

None known

Store below 30°C

2 x 10’s tablets in blister strips, packed in a printed carton along with a leaflet

No special requirements.