Summary of Product Characteristics, Labelling and Package Leaflet

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SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Batrafen S 10 mg/g Shampoo

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One-gram shampoo contains 10 mg ciclopirox.

Excipient with known effect: - Benzoic acid and sodium benzoate 1.678 mg/mL (see section 4.4).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Shampoo Almost colourless to yellowish, translucent solution.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Batrafen S 10 mg/g Shampoo is indicated for the treatment of seborrheic dermatitis of the scalp.

4.2 Posology and method of administration

Posology For cutaneous use. For the initial treatment of the symptoms of seborrheic dermatitis Batrafen S 10 mg/g Shampoo is applied on the scalp once or twice a week, depending on severity, for four weeks. For subsequent prophylaxis of symptoms, the treatment may be continued for a further 12 weeks.

The use of Batrafen S 10 mg/g Shampoo is limited to a maximum of 16-weeks of continuous use.

Paediatric population The safety and efficacy of Batrafen S 10 mg/g Shampoo in children have not been established. No data are available.

Method of administration The contents of one sealing cup (about 5 mL) Batrafen S 10 mg/g Shampoo are applied to the wet hair and scalp and worked to a lather. This is then thoroughly massaged on the scalp. If the hair has more than shoulder length, up to two capfuls (about 10 mL) are used. Batrafen S 10 mg/g Shampoo is left to take effect for 3 minutes and is then rinsed off with water.

4.3 Contraindications

Hypersensitivity to ciclopirox, ciclopirox-olamine, or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

When using Batrafen S 10 mg/g Shampoo, patients should be advised to avoid contact with eyes. If accidental contact occurs, rinse eyes with copious amounts of water.

This medicine contains 0.525 mg sodium benzoate and 1.08 mg benzoic acid per 1 g of shampoo which is equivalent to a total 1.678 mg/ mL (corresponding to 0.548 mg/mL sodium benzoate and 1.13 mg/mL benzoic acid). Benzoic acid/Benzoate salt may cause local irritation. Benzoic acid/Benzoate salt may increase jaundice in new-born babies (up to 4 weeks old). In case of irritation or sensitisation after prolonged use of the product, the therapy should be stopped and another appropriate treatment initiated. Colour changes of hair have been observed, mostly in patients with damaged hair by chemical agents (i.e. caused by hair colouration) or grey or white hair.

4.5 Interactions with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6 Fertility, pregnancy and lactation

Pregnancy For ciclopirox, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development and parturition. However, there are no sufficient data concerning possible long term effects on postnatal development (see section 5.3). Caution should be exercised when prescribing to pregnant women.

Breast-feeding The excretion of ciclopirox in human milk is unknown. Therefore, breast-feeding women should not use Batrafen S 10 mg/g Shampoo.

Fertility No studies on the effect of ciclopirox on human fertility have been conducted. Reduced fertility index was found in rats at a dosage of 5 mg/kg following the oral administration (see section 5.3).

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Skin and Subcutaneous Disorders Uncommon (>1/1000 to <1/100): skin reactions at the application site such as irritation and eczema, subjective discomfort such as burning and itching and hair disorders, like mild hair loss or discoloration, matted and dull hair, mild dry hair.

Immune System Disorders Rare (> 1/10,000 to <1/1000): allergic contact dermatitis may occur.

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

No case of overdose has been reported. However too frequent use of Batrafen S 10 mg/g Shampoo should not be expected to lead to any major systemic effects. In case of accidental ingestion, adequate treatment should be initiated.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: antifungal agents, ATC code: D01A E14 (other antifungals for topical use).

Mechanism of action The mode of action is very complex by targeting a variety of metabolic processes in the fungal cell. Unlike most antifungal agents, ciclopirox does not affect sterol biosynthesis. The basis of the main mechanism in fungal cells is the high affinity of ciclopirox for trivalent metal cations such as Fe3+. The trapping of this essential enzymatic co-factor causes an inhibitory effect on enzymes such as cytochromes, which are involved in mitochondrial electron transport processes in the course of energy production. In addition, the activity of catalase and peroxidase, which are responsible for the intracellular degradation of toxic peroxides is strongly reduced in the presence of the drug. As a consequence, ciclopirox impairs the fungal metabolism by affecting transport mechanisms, which are located in the fungus cell membrane. This particular mode of action of ciclopirox suggests that there is a low risk for the development of resistance and minimises the risk of cross-resistance with other antimycotic agents such as azoles and allylamines.

Pharmacodynamic effects Ciclopirox is a broad-spectrum N-hydroxypyridone antifungal agent with fungicidal action against pathogenic dermatophytes, moulds and yeasts including Pityrosporum ovale which is regarded as principal cause of seborrheic dermatitis. Preclinical studies a steep dose-response curve indicating not only fungistatic but also fungicidal activity, a favourable pH-optimum, a long duration of action, a low influence of protein on the inhibiting concentrations, a good penetration into the deeper layers of the epidermis, and an additional antibacterial activity against Gram-positive as well as against Gram-negative aerobic bacteria. The influence of Batrafen S 10 mg/g Shampoo on the viability of Pityrosporum ovale was studied in a model of excised back skin of pigs indicating that the shampoo is active even after short periods of treatment. Penetration experiments into the stratum corneum of excised pig skin showed that a short contact time of Batrafen S 10 mg/g Shampoo is sufficient to achieve active drug concentrations even in deeper layers of the stratum corneum. In vivo experiments confirmed the efficacy of ciclopirox using experimental dermatophytosis in guinea pigs. Ciclopirox demonstrated a clear dose-response efficacy against infections with Microsporum canis and Trichophyton mentagrophytes. A quick onset of action was observed. Ciclopirox has anti-inflammatory properties. In vitro studies have shown that ciclopirox inhibits the production of cyclooxygenase and 5-lipoxygenase inflammatory mediators. Ciclopirox shows also in vivo anti-inflammatory effects in animals, which were confirmed in UV-erythema in human volunteers. The inflammation-inhibiting activity can promote healing in certain fungal skin infections, such seborrheic dermatitis.

Clinical efficacy and safety A total of 1189 patients with seborrheic dermatitis were treated over a 4-week period in three vehicle- controlled double-blind studies using four disease’s signs and symptoms (status, scaling, inflammation, itching) as efficacy variables which were combined to two derived main response criteria: “effectively treated” and “cleared”. After using the shampoo, 17.2% (application once a week) and 21.3% (application twice a week) of the patients became completely cleared. Cleared or effectively treated were 44.2% (application once a week), and 52.5% (application twice a week).

As an extension of the above results for the acute treatment of the disease, a clinical study has shown that a maintenance treatment once a week led to a re-occurrence of the disease in only 16% of the patients compared to 36% if a shampoo without active substance was used. A total of 737 subjects were randomised in a double-blind study comparing the efficacy of a twice weekly application of the shampoo containing ciclopirox 1% to another with ketoconazole 2% using analogous response criteria. After the 4-week treatment period, about 74% of the patients responded in the ciclopirox group and 78.7% in the ketoconazole group respectively. The similar response to both treatments gave in the statistical test for non-inferiority a p-value of 0.047 for the ITT population and p=0.061 for the VC population. When account is taken of the greater number of more severe cases at baseline in the 1-% ciclopirox group, the p-values for non-inferiority were 0.014 (VC) and 0.021 (ITT).

5.2 Pharmacokinetic properties

In three clinical trials of the 1% shampoo formulation, ciclopirox serum and urine concentrations were measured in patients with seborrheic dermatitis of the scalp. In the first study, patients were treated twice weekly for 4 weeks. In the second study, patients were treated under exaggerated use conditions, i.e. the patients washed their hair with Batrafen S 10 mg/g Shampoo every day for 29 days, increasing the contact time from 3 min to 6 min after 15 days. In one Phase III trial, ciclopirox serum and urine levels were measured after 4 weeks of once- or twice- weekly treatment and again after an additional 12 weeks of prophylactic treatment used once a week or once every 2 weeks. After four weeks of treatment, serum levels were detected in 21 of 293 patients, with maximum serum levels ranging between 13.2 and 39.0 g/L. After another 12 weeks of prophylactic treatment, ciclopirox levels were detected in 2 of 94 patients (max. 14.4 g/L). In chronic oral toxicity studies, the no-toxic-effect levels of ciclopirox and its main metabolites were 2210 – 2790 µg/L in rats and 1500 – 3500 µg/L in dogs, indicating high safety margins. When urinary output of ciclopirox was measured, excretion peaks were produced within the first 4 hours of administration which fell off rapidly thereafter. Since the kidney eliminates more than 98 % of absorbed ciclopirox, urinary excretion is a reliable measure of the amount of drug absorbed during shampooing. In these studies, the median urinary excretion of ciclopirox ranged between 0.42 and 1.36% of the administered dose.

5.3 Preclinical safety data

Non-clinical data reveal no evidence of toxicity up to a daily oral dose of 10 mg/kg based on conventional studies of repeated dose toxicity, and no evidence of genotoxicity and carcinogenicity. A reduced fertility index was found with 5 mg/kg by weightciclopirox in rats. No embryo-/fetotoxicity or teratogenicity was observed in rats and rabbits. There was no evidence of peri/postnatal toxicity, however possible long-term effects on offspring have not been investigated.

In a cutaneous tolerance study in rabbits, Batrafen S 10 mg/g Shampoo showed no irritant effect. In a mucosal tolerance study in rabbits, undiluted Batrafen S 10 mg/g Shampoo produced ocular irritation. To date, no studies have investigated irritation after repeated local administration, or evaluated sensitisation.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium dodecyl- di(oxyethylene) sulphate , 27 % solution1) Disodium dodecyl- poly(oxyethylene)-3-2-sulphosuccinate, 33 % solution2) Macrogol lauryl ether Sodium chloride Purified water

1) consisting of: sodium dodecyl- di(oxyethylene) sulphate; purified water; benzoic acid (E210)

2) consisting of: disodium dodecyl poly(oxyethylene)-3-2-sulphosuccinate; sodium benzoate (E211); purified water

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years. After first opening the bottle, the shampoo may be used for up to 8 weeks.

6.4 Special precautions for storage

Do not store above 30°C.

6.5 Nature and contents of container

This medicinal product is supplied in low density polyethylene (LDPE) bottles with polypropylene (PP) hinged closure in 60 mL bottle, box of 1 or 2 Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements. Any unused medicinal product or waste material should be disposed of in accordance with local 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

<[To be completed nationally]>

10. DATE OF REVISION OF THE TEXT

<{MM/YYYY}> <{DD/MM/YYYY}> <{DD month YYYY}>

<[To be completed nationally]>

LABELLING

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

Outer cardboard box

1. NAME OF THE MEDICINAL PRODUCT

Batrafen S 10 mg/g shampoo

Ciclopirox

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 g shampoo contains 10 mg ciclopirox

3. LIST OF EXCIPIENTS sodium dodecyl- di(oxyethylene) sulphate; benzoic acid (E210); disodium dodecyl- poly(oxyethylene)-3-2-sulphosuccinate; sodium benzoate (E211), macrogol lauryl ether; sodium chloride; purified water.

Read the package leaflet before use.

4. PHARMACEUTICAL FORM AND CONTENTS

60 mL shampoo 2 x 60 mL shampoo

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For cutaneous use (scalp) Read the package leaflet before use.

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

Keep out of the reach and sight of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

Read the package leaflet before use.

8. EXPIRY DATE

EXP After the bottle has once been opened, the shampoo can be used for 8 weeks.

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.

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

{Name and Address} <{tel}> <{fax}> <{e-mail}>

12. MARKETING AUTHORISATION NUMBER(S)

To be completed nationally

13. BATCH NUMBER

Lot:

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Batrafen S 10 mg/g

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: SN: NN: MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 11

Sticker of the bottle

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Batrafen S 10 mg/g shampoo Ciclopirox

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP {MM/YYYY}

4. BATCH NUMBER<, DONATION AND PRODUCT CODES>

Lot {number}

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

1 g

6. OTHER

PACKAGE LEAFLET

PACKAGE LEAFLET: INFORMATION FOR THE USER

Batrafen S 10 mg/g Shampoo Ciclopirox

Read all of this leaflet carefully before you start using this medicine. • Keep this leaflet. You may need to read it again. • If you have any further questions, ask your doctor or pharmacist. • This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. • If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

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

1. What Batrafen Shampoo is and what it is used for

What Batrafen Shampoo is The name of your medicine is Batrafen S 10 mg/g Shampoo (called “Batrafen Shampoo” in this leaflet). Batrafen Shampoo contains an active substance called “ciclopirox”, an antifungal agent (which kills moulds and yeasts).

What Batrafen Shampoo is used for Batrafen Shampoo is used to treat a disorder of the scalp called “seborrheic dermatitis”. This is when the skin on the scalp becomes inflamed, causing flaking, burning and itching.

How Batrafen Shampoo works Batrafen Shampoo works by killing moulds and yeasts on the upper layers of the skin. These moulds and yeasts are one of the main causes of seborrheic dermatitis.

2. What you need to know before you use Batrafen Shampoo

Do not use Batrafen Shampoo: • if you are allergic (hypersensitive) to the active substance ciclopirox, ciclopirox olamine, or any of the other ingredients of Batrafen Shampoo (listed in section 6). If you are not sure, talk to your doctor or pharmacist before using Batrafen Shampoo.

Warnings and precautions Talk to your doctor or pharmacist before using Batrafen Shampoo. If you accidentally get some Batrafen Shampoo in your eyes, rinse them with plenty of water. If you accidentally swallow some Batrafen Shampoo, talk to a doctor or pharmacist straight away.

You may have changes in hair colour, especially if your hair is damaged by chemical agents, like hair colouration, or is grey or white in colour.

Other medicines and Batrafen Shampoo Tell your doctor or pharmacist if you are using or have recently used any other medicines. This includes medicines obtained without a prescription.

Pregnancy and 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 using this medicine.

It is not known if ciclopirox passes into breastmilk, therefore if you are breast-feeding, you are advised not to use Batrafen Shampoo.

There have been no studies on the effect of ciclopirox on human fertility conducted; however, reduced fertility has been seen in rats after oral administration.

Batrafen Shampoo contains, benzoic acid and sodium benzoate

3. How to use Batrafen Shampoo

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Using this medicine • Use Batrafen Shampoo on the skin of your scalp only. • Wet your hair and scalp and apply Batrafen Shampoo. • Lather and massage the shampoo well into your scalp. • Leave the shampoo lather on your scalp for about 3 minutes. • Then rinse out with water.

How much to use Use the cap from the Batrafen Shampoo bottle to measure your dose. The usual amount to use is one capful (about 5 mL) of Batrafen Shampoo. Up to two capfuls (about 10 mL) may be used for hair longer than shoulder-length.

How often to use this medicine • First, use the shampoo once or twice a week - depending on how bad your symptoms are. Do this for 4 weeks to get rid of your symptoms. • You can then keep using the shampoo once or twice a week for up to 12 weeks. This will help stop the symptoms from coming back. Do not use Batrafen Shampoo for more than 16 weeks in a row.

Use in children Batrafen Shampoo has not been tested in children.

If you use more Batrafen Shampoo than you should If you use more Batrafen Shampoo than you should it is unlikely you will get any side effects. There is no information on what happens with overdose of medicines containing ciclopirox.

If you stop using Batrafen Shampoo Do not stop using Batrafen Shampoo without talking to your doctor. This is because if you stop using the medicine too early, it may reduce the effectiveness of the treatment.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may happen with this medicine:

Uncommon (affects less than 1 in 100 people) • Skin reactions on the scalp - this includes skin irritation or eczema (inflamed skin, with itching, rash and often blisters that weep and become crusted) or discomfort like burning or itching. • Hair problems - such as slight hair loss, discoloured, matted, dull or slightly dry hair.

Rare (affects less than 1 in 1,000 people) • Skin rash where the shampoo comes into contact with your skin (allergic contact dermatitis).

Stop using Batrafen Shampoo and talk to your doctor if you get skin or scalp reactions such as irritation or sensitisation (allergic reactions) after prolonged use of the medicine. Your doctor may want to start you on a different treatment.

Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. 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 Batrafen Shampoo

Keep this medicine out of the reach and sight of children.

Do not use this medicine after the expiry date which is stated on the outer cardboard and the bottle after EXP. The expiry date refers to the last day of that month.

Do not store above 30°C.

After the bottle has first been opened, Batrafen Shampoo can be used for up to 8 weeks.

Do not use throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer required. These measures will help protect the environment.

6. Content of the pack and other information

What Batrafen Shampoo contains The active substance is ciclopirox, 1 gram of shampoo contains 10 milligrams (mg) of ciclopirox.

The other ingredients are: Sodium dodecyl- di(oxyethylene) sulphate , 27 % solution1) Disodium dodecyl- poly(oxyethylene)-3-2-sulphosuccinate, 33 % solution2) Macrogol lauryl ether Sodium chloride Purified water 1) consisting of: sodium dodecyl- di(oxyethylene) sulphate; purified water; benzoic acid (E210) 2) consisting of: disodium dodecyl poly(oxyethylene)-3-2-sulphosuccinate; sodium benzoate (E211); purified water

What Batrafen Shampoo looks like and contents of the pack The shampoo is almost colourless to yellowish. Batrafen Shampoo is supplied in plastic bottles with hinged closure in packs of: 1 bottle containing 60 mL 2 bottles containing 120 mL (2x60 mL)

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder [To be completed nationally] {Name and address}

Manufacturer: Sanofi-Aventis Deutschland GmbH D-65926 Frankfurt am Main Germany

This medicinal product is authorised in the Member States of the EEA under the following names: France: Mycoster 10mg/g shampoing Germany: Batrafen S 10mg/g Shampoo Italy: CareDS

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