SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

orange 2 mg / 0.6 mg / 1.2 mg lozenges honey & lemon 2 mg / 0.6 mg / 1.2 mg lozenges

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each lozenge contains: hydrochloride 2.00 mg Amylmetacresol 0.60 mg 2,4-Dichlorobenzyl alcohol 1.20 mg

Excipients with known effect: Each lozenge contains: Sucrose 1,495.33 mg Liquid glucose 1,016.82 mg Cochineal red (E124) 0.0125 mg in orange-flavoured lozenges Sunset yellow (E110) 0.080 mg in orange-flavoured lozenges 0.010 mg in honey-lemon-flavoured lozenges For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Lozenge. orange lozenges are orange, biconvex, cylindrical, 19 mm diameter, orange- flavoured lozenges. honey & lemon lozenges are yellow, biconvex, cylindrical, 19 mm diameter, honey and lemon-flavoured lozenges.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Symptomatic treatment of painful conditions of the mouth and throat, such as , sore throat and after a tonsillectomy in adults and adolescents over 12 years of age.

4.2 Posology and method of administration

Posology Adults and adolescents over 12 years of age: 1 lozenge every 2 – 3 hours, and when necessary, up to a maximum of 8 lozenges in a 24- hour period.

Paediatric population The medicine is contraindicated in children under 12 years of age.

Elderly Adjustment of the dose is not required.

Renal and/or hepatic impairment There are no data available for use of in patients with hepatic or renal impairment.

Method of administration For oromucosal use. Slowly dissolve the lozenge in the mouth, do not dissolve it in the sac of the cheek. Do not take this medicine before meals or drinking. If there is no improvement after 3 to 4 days, the patient is advised to consult a physician (see section 4.4).

The prolonged use of this medicine for more than 5 days is not recommended (see section 4.4).

4.3 Contraindications

− Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. − The product is contraindicated in children below 12 years of age, given the risk of rapid resorption of the anaesthetic and laryngospasm reflex.

4.4 Special warnings and precautions for use

Follow the indicated dosage: When taken in large amounts or repeatedly, this medicine may impact the nervous system as it passes through the bloodstream, possibly causing convulsions or affecting the heart. The prolonged use of this medicine for more than 5 days is not recommended, as it may alter the natural microbial balance of the oral cavity.

If symptoms persist for more than 3 to 4 days, get worse or if other symptoms appear, such as high fever, headache, nausea or vomiting, and skin rash, the clinical condition should be evaluated for bacterial (angina, tonsillitis).

It should be administered with caution in acutely ill or frail elderly patients, as they are more sensitive to adverse reactions of this medicinal product. This medicine should not be used in the area of mouth and throat if there are greater acute wounds. may cause numbness of the tongue and may increase the danger of biting trauma. Therefore, care should be taken in eating and drinking hot foods. The patient should be aware that the production of topical anaesthesia may impair swallowing and thus enhance the danger of aspiration. For this reason, food should not be ingested directly following use of local anaesthetic preparations in the mouth or throat area. Asthmatic patients must use this medicinal product under a medical supervision. Patients allergic to amide-type local anaesthetic drugs should be aware of cross-sensitivity to other agents of the amide type such as lidocaine (see section 4.5).

contains terpenes found in levomenthol. Excessive doses of terpenes have been associated with neurological complications such as convulsions in children. contains 1,495.33 mg sucrose per lozenge. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. contains 1,016.82 mg glucose per lozenge. Patients with rare glucose- galactose malabsorption should not take this medicine. contains sunset yellow and cochineal red colorants, which may cause allergic reactions.

4.5 Interaction with other me dicinal products and other forms of interaction

does not interact with (except antibiotics metabolised through the cytochrome P450 isoenzymes CYP1A2 and CYP3A4 such as erythromycin), making concomitant use possible.

4.6 Fertility, pregnancy and lactation

Pregnancy The safety of in pregnancy has not been established. A large amount of data on the local use of lidocaine during pregnancy indicates no increased risk of congenital malformations. Lidocaine crosses the placenta; however, there is very little absorption as a result of the low dose. Animal studies do not indicate reproductive toxicity (see section 5.3). There are no data on the use of active substances amylmetacresol and 2,4-dichlorobenzyl alcohol during pregnancy. In the absence of documented experience, the use of is not recommended during pregnancy.

Breast-feeding The safety of during breast-feeding has not been established. Lidocaine is excreted in small amounts in breast milk. Because of the low dose, no effect of lidocaine on the infant is anticipated. There are no data on the excretion of amylmetacresol and 2,4- dichlorobenzyl alcohol in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue therapy with taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility There are no data on the effect of lidocaine, amylmetacresol and 2,4-dichlorobenzyl alcohol on fertility.

4.7 Effects on ability to drive and use machines

This medicinal product has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

No systemic reactions have been reported up to now and generally only occur after a long- term treatment. During the period of use, the following adverse reactions have been reported for the combination of active substances in this medicinal product: Immune system disorders Rare (≥ 1/10,000 to ≤1/1,000): Hypersensitivity reactions (burning, itching), angioedema, stinging of the throat and unpleasant taste.

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.

4.9 Overdose

Symptoms Given the low concentrations of active ingredients overdosage is virtually impossible. Overdosage may occur in the event of abnormal use (much higher dosage, mucosal lesions). This manifests itself initially by unusual numbness of the upper respiratory and digestive tracts. Systemic reactions may occur due to the absorption of lidocaine. The most serious effects of lidocaine intoxication are expressed in the central nervous system (insomnia,

restlessness, excitement and respiratory depression) and the cardiovascular system (hypotension, cardiac dysrhythmia, cardiac arrest); methemoglobinemia may also occur.

Treatment Treatment is symptomatic and supportive; medical observation is desirable. Methemoglobinaemia can be treated by immediate intravenous injection of methylene blue (1 – 4 mg/kg).

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties

Pharmacotherapeutic group: Throat preparations, . ATC code: R02AA03.

Through its active substances, this medicinal product combines properties of local , bactericide, fungicide and local analgesic. This medicinal product contains: − 2,4-Dichlorobenzyl alcohol and amylmetacresol, two antiseptics which act against pathogenic bacterial flora of the oropharyngeal cavity. They belong to the chemical group of alcohols and , respectively. − Lidocaine, which belongs to the group of local amide anaesthetics and induces rapid relief from pain.

5.2 Pharmacokinetic properties

Absorption and distribution Lidocaine is absorbed relatively quickly after topical application to the mucous membranes. Based on a study with a lozenge containing 8 mg of lidocaine and assuming linear PK, peak plasma levels obtained after the administration of 2 mg lidocaine lozenges would be around 11 ng/mL, which is far below the levels associated with higher incidence of systemic adverse reactions. Although lidocaine is absorbed in the , only 35% of the oral dose reaches systemic circulation unchanged through a first-pass effect (hepatic portal circulation).

Biotransformation and elimination Lidocaine is largely metabolised in the liver, whereby any alteration in hepatic function or hepatic blood flow can have a significant effect on and dosage requirements. Hepatic metabolism is fast and close to 90% of an administered dose, it is dealkylated to form monoethylglycinexylidide (MEGX) and glycinexylidide (GX). Less than 10% of lidocaine is excreted unchanged by the kidneys. The metabolites are also excreted in the urine.

There are no relevant data on the pharmacokinetics of either 2,4-dichlorobenzyl alcohol or amylmetacresol.

5.3 Preclinical safety data

Single-dose toxicity LD50 of lidocaine has not been established. Doses provoking adverse reactions in cardiovascular system (arrhythmia, myocardial depression and cardiovascular shock) and CNS (seizures) are much higher than those contained in this medicinal product.

LD50 of 2,4-dichlorobenzyl alcohol is 3 g/kg body weight in rats and 2.3 g/kg body weight in mice after oral administration, 1.7 g/kg body weight after subcutaneous administration. LD50 of amylmetacresol is 15 g/kg body weight in rats after oral administration.

Repeated-dose toxicity No repeated-dose toxicity studies of lidocaine are available. Effects of 2,4-dichlorobenzyl alcohol in repeated-dose toxicity studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. No repeated-dose toxicity studies of amylmetacresol are available.

Carcinogenicity There are no carcinogenicity studies involving lidocaine, but metabolite 2,6-xylidine has some the carcinogenic potential observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. No carcinogenicity studies are available for 2,4-dichlorobenzyl alcohol and amylmetacresol.

Genotoxicity Nor lidocaine neither its metabolite 2,6-xylidine show any mutagenic effects. No indication of genotoxic potential was observed in in vitro and in vivo genotoxicity studies performed with 2,4-dichlorobenzyl alcohol and amylmetacresol.

Reproductive and developmental toxicity No effect of lidocaine on the fertility and reproductive development of offspring, or on organogenesis, embryonic or foetal development, birth or nursing, except at very high doses, has been demonstrated. An embryonic toxicity study in rabbits showed no teratogenic effect of 2,4-dichlorobenzyl alcohol and amylmetacresol.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Orange lozenges Levomenthol, Sodium saccharin (E954), Sucrose, Liquid glucose, Sunset yellow (E110), Cochineal red (E124), Citric acid monohydrate (E330), Orange flavour.

Honey & lemon lozenges Peppermint oil Quinoline yellow (E104), Sodium saccharin (E954), Tartaric acid (E334), Sucrose, Liquid glucose, Sunset yellow (E110), Lemon essence, Honey flavour.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

27 months.

6.4 Special precautions for storage

Do not store above 30 ºC.

6.5 Nature and contents of container

PVC-PVDC/Aluminium blisters

24 lozenges.

6.6 Special precautions for disposal and other handling

Any unused medicinal product and all material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

[To be completed nationally]

8. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION

[To be completed nationally]

10. DATE OF REVISION OF THE TEXT

[To be completed nationally]

LABELLING

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

Carton box

1. NAME OF THE MEDICINAL PRODUCT

2 mg / 0.6 mg / 1.2 mg orange lozenges honey & lemon 2 mg / 0.6 mg / 1.2 mg lozenges

Lidocaine hydrochloride / amylmetacresol / 2,4-dichlorobenzyl alcohol

2. STATEMENT OF ACTIVE SUBSTANCES

Each lozenge contains 2 mg lidocaine hydrochloride, 0.6 mg amylmetacresol and 1.2 mg 2,4-dichlorobenzyl alcohol.

3. LIST OF EXCIPIENTS

Orange lozenges also contain sucrose, liquid glucose, sunset yellow (E110), cochineal red (E124). Honey & lemon lozenges also contain sucrose, liquid glucose, sunset yellow (E110). See the leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Lozenge 24 lozenges

5. METHOD AND ROUTE OF ADMINISTRATION

Oromucosal use.

Read the package leaflet before use.

6. THAT PRODUCT MUST BE STORED OUT OF THE REACH AND SIGHT OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 30 ºC.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

[To be completed nationally]

12. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

[To be completed nationally]

15. INSTRUCTIONS ON USE

Symptomatic treatment of painful conditions of the mouth and throat, such as: − Pharyngitis. − Sore throat. − After tonsils removal. For adults and adolescents over 12 years of age. Dosage: 1 lozenge every 2 – 3 hours, up to a maximum of 8 lozenges per day. See package leaflet for further information.

16. INFORMATION IN BRAILLE

orange honey & lemon

17. UNIQUE IDENTIFIER – 2D BARCODE Not applicable.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

Not applicable.

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister

1. NAME OF THE MEDICINAL PRODUCT

2 mg / 0.6 mg / 1.2 mg orange lozenges honey & lemon 2 mg / 0.6 mg / 1.2 mg lozenges

Lidocaine hydrochloride / amylmetacresol / 2,4-dichlorobenzyl alcohol

2. NAME OF THE MARKETING AUTHORISATION HOLDER

[To be completed nationally]

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

Package leaflet: Information for the user

2 mg/0.6 mg/1.2 mg orange lozenges honey & lemon 2 mg/0.6 mg/1.2 mg lozenges Lidocaine hydrochloride / amylmetacresol / 2,4-dichlorobenzyl alcohol

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 to 4 days.

What is in this leaflet 1. What is and what it is used for 2. What you need to know before you take 3. How to take 4. Possible side effects 5. How to store 6. Contents of the pack and other information

1. What is and what it is used for

contains amylmetacresol and 2,4-dichlorobenzyl alcohol – both antiseptics, and lidocaine hydrochloride – a local anaesthetic which relieves the pain. is indicated for symptomatic treatment of painful conditions of the mouth and throat, such as pharyngitis, sore throat and after tonsils removal in adults and adolescents over 12 years of age.

You must talk to a doctor if you do not feel better or if you feel worse after 3 to 4 days.

2. What you need to know before you take

Do not take if you are − allergic to lidocaine hydrochloride or other amide-type local anaesthetic drugs; amylmetacresol; 2,4-dichlorobenzyl alcohol or any of the other ingredients of this medicine (listed in section 6). − a child under 12 years of age.

Warnings and precautions You should consult the use of this medicine with your doctor if − the sore throat is accompanied by fever, headache, nausea, vomiting or skin rash. − your symptoms do not improve or worse within 3 to 4 days of treatment. − you suffer from bronchial asthma. − you have greater acute wounds in the area of mouth and throat ( should not be used then).

Susceptible persons may experience strange feeling in the mouth due to the local anaesthetic effect. The anaesthetics contained in this medicine may cause aspiration (coughing during meals or a choking sensation) while eating. Do not take food directly following the use of this medicine. This medicine may cause numbness of the tongue and may increase the danger of biting trauma. Therefore, care should be taken in eating and drinking hot foods. Prolonged use of this medicine (more than 5 days) is not recommended, as it may alter the natural microbial balance of the throat. Follow the indicated dosage: if taken in large quantities or over time this medicine may affect the heart or nervous system, and may cause convulsions. Elderly persons or persons in a weakened condition are more sensitive to possible adverse reactions and should consult their doctor before taking this medicine.

Children and adolescents This medicine should not be used in children under 12 years of age.

Other medicines and Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. There is no interaction between and antibiotics (excluding erythromycin); concomitant use is therefore possible.

with food, drink and alcohol Do not take this medicine before meals or before drinking.

Pregnancy and breast-feeding 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.

Pregnancy The use of this medicine is not recommended during pregnancy.

Breast-feeding Given that there is no concrete data on the use of this drug during breast-feeding; caution is recommended during this period. If you are breast-feeding, ask your doctor for advice before you start taking this medicine.

Driving and using machines This medicinal product has no or negligible influence on the ability to drive and use machines.

contains sucrose, glucose, sunset yellow and cochineal red colorants If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product. Sunset yellow and cochineal red colorants may cause allergic reactions.

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 doses are the following: Adults and adolescents over 12 years (including elderly) Dissolve one lozenge slowly in the mouth every 2 to 3 hours, up to a maximum of 8 lozenges over 24 hours. Do not dissolve the lozenge in the sac of the cheek.

Use in children and adolescents The medicine should not be used in children under 12 years of age.

Do not use this medicine for more than 5 days. If you are not completely free of the symptoms after that time, consult your doctor.

If you take more than you should Do not exceed the recommended dosing.

To date, no cases of overdose have been reported. Symptoms that may occur in case of misuse or overdose: Excessive anaesthesia of upper digestive and respiratory tract, insomnia, restlessness, excitement, respiratory depression, low blood pressure, irregular heartbeat. Methemoglobinaemia may also occur. If you take too much , immediately consult your doctor or pharmacist. Take this leaflet with you as it will ensure that the appropriate treatment is given as soon as possible. Treatment should be symptomatic and supportive and under medical observation. Methemoglobinaemia can be treated by immediate intravenous injection of methylene blue (1 – 4 mg/kg).

If you forget to take Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. − Adverse effects occur rarely (may affect up to 1 in 1,000 people) and usually only after long term treatment (see actions to be taken if using excessive amounts). − Unlike many local analgesics, lidocaine does few if any hypersensitivity reactions. These reactions are in the form of erythema, a burning sensation or tingling in the mouth or throat or swelling of the mouth or throat. − The sense of taste can be affected.

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.

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 after ‘EXP’. The expiry date refers to the last day of that month. Do not store above 30 ºC. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What contains The active substances are: Lidocaine hydrochloride 2.00 mg Amylmetacresol 0.60 mg 2,4-Dichlorobenzyl alcohol 1.20 mg

The other ingredients are: Orange lozenges: Levomenthol, sodium saccharin (E954), sucrose, liquid glucose, sunset yellow (E110), cochineal red (E124), citric acid monohydrate (E330), orange flavour. Honey & lemon lozenges: Peppermint oil, partly dementholised, quinoline yellow (E104), sodium saccharin (E954), tartaric acid (E334), sucrose, liquid glucose, sunset yellow (E110), lemon essence, honey flavour.

What looks like and contents of the pack orange lozenges are orange, biconvex, cylindrical, 19 mm diameter, orange- flavoured lozenges. honey & lemon lozenges are yellow, biconvex, cylindrical, 19 mm diameter, honey and lemon-flavoured lozenges. PVC-PVDC/Aluminium blisters. 24 lozenges.

Marketing authorisation holder and Manufacturer [To be completed nationally]

This medicinal product is authorised in the Member States of the EEA under the following names:

Czech Republic RYKY med a citron RYKY pomeranč Slovak Republic RYKY med a citrón RYKY pomaranč Bulgaria СЕПТАЗУЛЕН ПЛЮС МЕД И ЛИМОН СЕПТАЗУЛЕН ПЛЮС ПОРТОКАЛ Romania SEPTAZULEN PLUS MIERE ȘI LĂMÂIE SEPTAZULEN PLUS PORTOCALĂ

This leaflet was last revised in {MM/YYYY} [To be completed nationally]