1 retard capsule contains 75 mg trans-4-[(2-amino-3,5-dibromo-benzyl)amino] cyclohexanol hydrochloride( = ambroxol hydrochloride).
Oblong hard gelatin capsules consisting of red opaque capand an orange opaque body; the cap is printed with "MUC 01" in white, the body is printed with the BI Company symbol.
Capsule contents: round, yellowish white-pallets with a smooth, shiny surface, mixed with a small quantity of powder.
Dimensions: Capsule size: 2.
Diameter of capsule cap: 6.0-6.4mm.
Length of capsule: 17.4-18.4mm.
Excipients**/Inactive Ingredients: Crospovidone collidon CL, carnauba wax, stearyl alcohol, magnesium stearate.
Pharmacology: Preclinically, ambroxol hydrochloride, the active ingredient of MUCOSOLVAN, has been shown to increase respiratory tract secretion. It enhances pulmonary surfactant production and stimulates ciliary activity. These actions result in improved mucus flow and transport (mucociliary clearance). Improvement of mucociliary clearance has been shown in clinical pharmacologic studies. Enhancement of fluid secretion and mucociliary clearance facilitates expectoration and eases cough.
In patients suffering from COPD, long-term treatment (6 months) with Mucosolvan (Mucosolvan Retard Capsule 75 mg) resulted in a significant reduction of exacerbations that became evident after 2 months of treatment. Patients in the Mucosolvan treatment group lost significantly fewer days through illness and had fewer days when they needed antibiotic therapy. Treatment with Mucosolvan Retard also induced a statistically significant improvement of symptoms (difficulty of expectoration, cough, dyspnea, auscultatory signs) compared with placebo.
Following the administration of ambroxol antibiotic concentrations (amoxicilline, cefuroxime, erythromycin) in bronchopulmonary secretions and in the sputum are increased.
Antiviral properties in in vitro studies and in animal models: In in vitro studies in human tracheal epithelial cells a reduction of rhinovirus (RV14) replication has been observed. In a mouse airway model, a reduction of Influenza A virus replication was observed with ambroxol pretreatment.
Pharmacokinetics: Absorption: Absorption of all immediate release oral forms of ambroxol hydrochloride is rapid and complete, with dose linearity in the therapeutic range. Maximum plasma levels are reached within 1 to 2.5 hours following oral administration of the immediate-release formulation and after a median of 6.5 hours of the slow release formulation. The absolute bioavailablility after a 30 mg tablet was found to be 79%. The slow release capsule showed a relative availability of 95% (dose-normalized) in comparison to a daily dose of 60 mg (30 mg twice daily) administered as immediate-release tablet.
Distribution: In the therapeutic range plasma protein binding was found to be approximately 90%. Distribution of ambroxol hydrochloride from blood to tissue is rapid and pronounced, with the highest concentration of the active substance found in the lungs. The volume of distribution following oral administration was estimated to be 552L.
Metabolism and elimination: About 30% of an orally administered dose is eliminated via first pass metabolism.
Studies in human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol. Ambroxol hydrochloride is metabolized primarily in the liver by glucuronidation and some cleavage to dibromanthranilic acid (approximately 10% of dose) aside from some minor metabolites.
Ambroxol hydrochloride is eliminated with a terminal elimination half-life of approximately 10 hours. Total clearance is in the range of 660 ml/min, with renal clearance accounting for approximately 8% of the total clearance. It has been estimated that the amount of dose excreted in urine after 5 days represents about 83% of total dose (radioactivity).
Pharmacokinetics in special populations: In patients with hepatic dysfunction elimination of ambroxol hydrochloride is reduced, resulting in approximately 1.3 to 2-fold higher plasma levels.
Due to the high therapeutic range of ambroxol hydrochloride, dose adjustments are not necessary.
Others: Age and gender were not found to affect the pharmacokinetics of ambroxol hydrochloride to a clinically relevant extent and thus there is no necessity for adjustment of dosage regimens.
Food was not found to influence the bioavailability of ambroxol hydrochloride.
Secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport.
Adult: 1 retard capsule once daily.
The capsules should not be opened or chewed, but swallowed whole with ample liquid. The "carrier pellets" which are occasionally present in the stools have released the active substance during their passage through the digestive system and are therefore without significance.
In acute respiratory indications, medical advice should be sought if symptoms do not improve or worsen in the course of therapy.
Mucosolvan can be taken with or without food.
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 MUCOSOLVAN at recommended doses and may need symptomatic treatment.
MUCOSOLVAN should not be used in patients known to be hypersensitive to ambroxol hydrochloride or other components of the formulation.
In case of rare hereditary conditions that may be incompatible with an excipient of the product (please refer to Precautions) the use of the product is contraindicated.
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. Mostly these 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 may first experience non-specific influenza-like prodromes 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 ambroxol discontinued as a precaution.
In the presence of impaired renal function MUCOSOLVAN may be used only after consulting a physician.
Effects on ability to drive and use machines: There is no evidence from postmarketing data for an effect on the ability to drive and use machines. Studies on the effects on the ability to drive and use machines have not been performed.
Pregnancy: Ambroxol hydrochloride crosses the placental barrier. Nonclinical studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Extensive clinical experience after the 28th week of pregnancy has shown no evidence of harmful effects on the foetus. Nonetheless, the usual precautions regarding the use of drugs during pregnancy should be observed. Especially during the first trimester, the use of MUCOSOLVAN is not recommended.
Lactation: Ambroxol hydrochloride is excreted in breast milk. Although unfavourable effects on breastfed infants would not be expected, MUCOSOLVAN is not recommended for use in nursing mothers.
Fertility: Nonclinical studies do not indicate direct or indirect harmful effects with respect to fertility.
Gastro-intestinal Disorders: Dyspepsia, nausea, vomiting, diarrhoea and abdominal pain.
Immune System Disorders, Skin and Subcutaneous Tissue Disorders: Anaphylactic reactions including anaphylactic shock, angioedema, rash, urticaria, pruritus, and other hypersensitivity.
No clinically relevant unfavourable interaction with other medications have been reported.
R05CB06 - ambroxol ; Belongs to the class of mucolytics. Used in the treatment of wet cough.
Cap (oblong, red opaque cap and orange opaque body, printed with "MUC 01" in white, printed with BI company symbol in the body) 75 mg x 10's, 50's.