BE/H/0181/002
SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
Clean versions
(02.02.2016)
1
SUMMARY OF PRODUCT CHARACTERISTICS
(02.02.2016)
2 1. NAME OF THE MEDICINAL PRODUCT
[national name of the medicinal product to be included; e.g. in Belgium (RMS): Mucoangin Menthe 20 mg pâtes à sucer]
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
One pastille contains 20 mg of ambroxol hydrochloride.
Excipient(s) with known effect: Each pastille contains 0.92 g sorbitol For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Pastille
Light brown, round pastilles with odour/taste of peppermint
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Pain relief in acute sore throat.
4.2 Posology and method of administration
Posology Adults and children over 12 years of age: up to 6 pastilles to be sucked per day, with a maximum of 1 pastille per dose.
Paediatric population
Method of administration Oromucosal use.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Patients with fructose intolerance should not receive
3 4.4 Special warnings and precautions for use
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 ambroxol hydrochloride. If symptoms or signs of a progressive skin rash (sometimes associated with blisters or mucosal lesions) are present, ambroxol hydrochloride treatment should be discontinued immediately and medical advice should be sought.
Dyspnoea may be observed in the context of an underlying disease e.g. swollen throat. Local allergic reactions (see section 4.8: angioneurotic oedema) may also cause dyspnoea. The local anaesthetic properties of ambroxol may contribute to an altered perception in the pharyngeal space (see section 4.8: oral and pharyngeal hypoaesthesia).
In the presence of impaired renal function or severe hepatopathy,
This product contains 5.5 g of sorbitol per maximum recommended daily dose (0.92 g per pastille). Patients with the rare hereditary condition of fructose intolerance should not take this medicine.
Paediatric population
4.5 Interaction with other medicinal products and other forms of interaction
No clinically relevant unfavourable interaction with other medications has been reported.
4.6 Fertility, pregnancy and lactation
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
Breast-feeding: Ambroxol hydrochloride is excreted in breast milk. Although unfavourable effects on breastfed infants would not be expected,
Fertility: Nonclinical studies do not indicate direct or indirect harmful effects with respect to fertility.
4 4.7 Effects on ability to drive and use machines
There is no evidence from postmarketing data for an effect on ability to drive and use machines. Studies on the effects on the ability to drive and use machines have not been performed.
4.8 Undesirable effects
Frequency estimation based on a database of clinical trials: very common (≥ 1/10) common (≥ 1/100 and < 1/10) uncommon (≥ 1/1,000 and < 1/100) rare (≥ 1/10,000 and < 1/1,000) very rare (< 1/10,000) not known (frequency cannot be estimated from the available data). This adverse reaction has been observed in post-marketing experience. With 95 % certainty, the frequency category is not greater than uncommon (3/1226), 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 1226 patients
Immune system disorders
Rare: hypersensitivity reactions Not known: anaphylactic reactions including anaphylactic shock, angioedema and pruritus
Skin and subcutaneous tissue disorders
Rare: rash, urticaria Not known: severe cutaneous adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis and acute generalized exanthematous pustulosis)
As generally observed for allergies, the severity of allergic reactions may increase if the patient is again exposed to the same substance (see section 4.3.).
Nervous system disorders
Common: dysgeusia (e.g. changed taste)
Gastrointestinal disorders and Respiratory, mediastinal and thoracic disorders
Common: oral and pharyngeal hypoaesthesia (see section 4.4), nausea Uncommon: diarrhoea, upper abdominal pain, dyspepsia, dry mouth Rare: dry throat Not known: vomiting
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 [the national reporting system listed in Appendix V*].
5 4.9 Overdose
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
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Throat preparations (Anaesthetics, local) ATC code: R02AD05
A local anaesthetic effect of ambroxol hydrochloride has been observed in the rabbit eye model and is likely to result from sodium channel blocking properties: ambroxol hydrochloride blocks hyperpolarised cloned neuronal voltage-gated sodium channels in vitro; binding was reversible and concentration-dependent.
This property is in accordance with the ancillary observations of a pain relief when using inhaled ambroxol hydrochloride in other diseases of the upper respiratory tract.
Clinical studies confirmed the pain relieving effects of Ambroxol lozenges (containing 20 mg ambroxol hydrochloride/lozenge) in patients with sore throat due to an acute viral pharyngitis. Except one, clinical trials have shown a rapid onset of action which can be experienced within 20 minutes at the latest. The effect will last for at least three hours.
In vitro, ambroxol hydrochloride seems to exert an anti-inflammatory effect. Cytokine release from blood mononuclear and polymorphonuclear cells but also from tissue-bound mononuclear and polymorphonuclear cells was found to be significantly reduced by ambroxol hydrochloride in vitro. In clinical trials, Ambroxol lozenges (containing 20 mg ambroxol hydrochloride/lozenge) have been shown to reduce redness in sore throat significantly.
5.2 Pharmacokinetic properties
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 immeditae-release formulation and after a median of 6.5 hours for the slow release formulation. The absolute bioavailability 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.
Due to the additional absorption via the oral mucosa, administration of lozenge results approximately 25% (90% confidence interval = 116-134%) increase in total exposure compared to syrup formulation. The increased exposure does not negatively affect ambroxol hydrochloride pharmacodynamics in the proposed indication.
Distribution: 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 552 L. In the therapeutic range, plasma protein binding was found to be approximately 90%.
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Biotransformation and elimination: About 30% of an orally administered dose is eliminated via first pass metabolism.
Ambroxol hydrochloride is primarily metabolized in the liver by glucuronidation and some cleavage to dibromanthranilic acid (approximately 10% of dose) aside from some minor metabolites. Studies in human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromanthranilic acid. Within 3 days of oral administration, approximately 6% of the dose is found in free form, while approximately 26 % of the dose is recovered in a conjugated form in the urine. 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 83% of the total clearance.
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.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Acacia Sorbitol liquid (non-crystallising) Karion 83 (Sorbitol 83) Saccharin sodium Peppermint oil Eucalyptus oil Parrafin light liquid
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
7 6.4 Special precautions for storage
Store in the original package, keep the blister in the outer carton.
6.5 Nature and contents of container
PVC / PVDC / Aluminium blister Pack sizes: 6, 10, 12, 18, 20, 24, 30, 36, 40, 42, 48, 50 pastilles / package. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7. MARKETING AUTHORISATION HOLDER
<[To be completed nationally]>
{Name and address} <{tel}> <{fax}> <{e-mail}>
8. MARKETING AUTHORISATION NUMBER(S)
<[To be completed nationally]>
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10. DATE OF REVISION OF THE TEXT
<{MM/YYYY}> <{DD/MM/YYYY}> <{DD month YYYY}>
<[To be completed nationally]>
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LABELLING
(02.02.2016)
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PARTICULARS TO APPEAR ON THE OUTER PACKAGING
Outer packaging: folding box
1. NAME OF THE MEDICINAL PRODUCT
Ambroxol hydrochloride
2. STATEMENT OF ACTIVE SUBSTANCE(S)
One pastille contains 20 mg ambroxol hydrochloride.
3. LIST OF EXCIPIENTS
Acacia, sorbitol liquid (non-crystallising), Karion 83 (Sorbitol 83), saccharin sodium, peppermint oil, eucalyptus oil, paraffin light liquid. For further information, please refer to the package leaflet. sugar free
4. PHARMACEUTICAL FORM AND CONTENTS
6 pastilles 10 pastilles 12 pastilles 18 pastilles 20 pastilles 24 pastilles 30 pastilles 36 pastilles 40 pastilles 42 pastilles 48 pastilles 50 pastilles
5. METHOD AND ROUTE(S) OF ADMINISTRATION
Pastille to be sucked (oromucosal use). Read the package leaflet before use.
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN
Keep out of the sight and reach of children.
7. OTHER SPECIAL WARNING(S), IF NECESSARY
Not applicable.
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8. EXPIRY DATE
[national used abbreviation for expiry date] e.g. EN: EXP
9. SPECIAL STORAGE CONDITIONS
Store in the original package, keep the blister in the outer carton.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
Not applicable.
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
{Name and Address} <{tel}> <{fax}> <{e-mail}>
12. MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
13. BATCH NUMBER
[national used abbreviation for batch number] e.g. EN: BN
14. GENERAL CLASSIFICATION FOR SUPPLY
[To be completed nationally]
15. INSTRUCTIONS ON USE
Pain relief of acute sore throat. Adults and children over 12 years: one pastille to be sucked (up to 6 pastilles per day). The duration of effect will last for at least 3 hours. Read the package leaflet before use.
16. INFORMATION IN BRAILLE
[To be completed nationally]
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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
Blister: PVC / PVDC / Aluminium blister
1. NAME OF THE MEDICINAL PRODUCT
Ambroxol hydrochloride
2. NAME OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
3. EXPIRY DATE
[national used abbreviation for expiry date] e.g. EN: EXP
4. BATCH NUMBER
[national used abbreviation for batch number] e.g. EN: BN
5. OTHER
Not applicable.
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PACKAGE LEAFLET
(02.02.2016)
13 Package leaflet: Information for the user
[national name of the medicinal product in Belgium (RMS): Mucoangin Menthe 20 mg pâtes à sucer]
Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
Always take this medicine exactly as described in this leaflet or as your doctor or pharmacist has told you. - Keep this leaflet. You may need to read it again. - Ask your pharmacist if you need more information or advice. - If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. - You must talk to a doctor if you do not feel better or if you feel worse after 3 days.
What is in this leaflet: 1. What
1. What
2. What you need to know before you take
Do not take
Warnings and precautions Talk to your doctor or pharmacist before taking
14 -
Children If you are under 12 years of age you should not use
Other medicines and
Pregnancy, breast-feeding and fertility If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Ambroxol passes into the body of the unborn child. You should not take
Driving and using machines
If you have been told by your doctor that you have an intolerance to some types of sugar, contact your doctor before taking this medicinal product.
3. How to take
Always take this medicine exactly as described in this leaflet or as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.
The recommended dose is: For adults and children over 12 years of age, 1 pastille should be sucked when you need pain relief. You should not take more than 6 pastilles per day.
You should not use
Clinical data have shown a rapid onset of action (within 20 minutes at the latest). The effect will last for at least 3 hours.
If you take more
15 If you have any further questions on the use of this product, ask your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If one of following side effects occur, stop taking
The severity of allergic reactions may increase if you take the product again, or if you take another product with the same substance (see section 2, Before you take
Further side effects that may occur:
Common: may affect up to 1 in 10 people - feeling sick (nausea) - numbness of mouth, tongue and throat (oral and pharyngeal hypoaesthesia) - taste disturbance (dysgeusia)
Uncommon: may affect up to 1 in 100 people - diarrhoea - indigestion (dyspepsia) - tummy pain (upper abdominal pain) - dry mouth
Rare: may affect up to 1 in 1,000 people - hypersensitivity reactions - rash, urticaria - dry throat
Not known: frequency cannot be estimated from the available data (a precise frequency estimation is not possible, as the side effects did not occur in a set of clinical trial of 1226 patients. The frequency category is probably not greater than uncommon, but might be lower) - anaphylactic reactions including anaphylactic shock, angioedema (rapidly developing swelling of the skin, subcutaneous, mucosa or submucosal tissues) and pruritus - severe cutaneous adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis and acute generalised exanthematous pustulosis) - vomiting
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via [the national reporting system listed in Appendix V*]. By reporting side effects you can help provide more information on the safety of this medicine.
16 5. How to store
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and the blister foil. The expiry date (EXP {local abbreviation to be included}) refers to the last day of that month.
Store in the original package, keep the blister in the outer carton.
Do not throw away any medicine via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longeruse. These measures will help protect the environment.
6. Contents of the pack and other information
What
The active substance is ambroxol hydrochloride. One pastille contains 20 mg ambroxol hydrochloride.
The other ingredients are - acacia - sorbitol liquid (non-crystallising) - Karion 83 (Sorbitol 83) - saccharin sodium - peppermint oil - eucalyptus oil - paraffin light liquid
What
This medicinal product is presented as light brown, round pastilles with odour/taste of peppermint. The pastilles are available in plastic/aluminium blister packs.
Pack sizes: 6, 10, 12, 18, 20, 24, 30, 36, 40, 42, 48 and 50 pastilles.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
The marketing authorization holder for
[To be completed nationally]
The manufacturer of
Boehringer Ingelheim Pharma GmbH & Co.KG Binger Strasse 173 55216 Ingelheim Germany
17 This medicinal product is authorised in the Member States of the EEA under the following names:
- Belgium: Mucoangin® Menthe - Luxembourg: Mucoangin® Menthe
This leaflet was last revised in <{MM/YYYY}><{month YYYY}>.
[To be completed nationally]
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