It is recommended that you also refer to http://www.medicines.ie as the Summary of Product Characteristics may have been updated since this copy was printed.

Bayer Limited

Bayer Limited

Summary of Product Characteristics last updated on medicines.ie: 9/4/2015

Canesten Combi Pessary and Cream

1. NAME OF THE MEDICINAL PRODUCT

Canesten Combi Pessary & Cream.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

The pessary contains clotrimazole 500 mg

Each gram of cream contains 20mg clotrimazole (equivalent to 2% w/w).

Excipients: Cetostearyl alcohol 100mg/g

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Pessary and vaginal cream.

White, convex pessary marked "Bayer" on one side and "MU" on the other side.

A white oil-in-water type cream.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

The pessary is recommended for the treatment of candidal vaginitis.

The cream is recommended for the treatment of candidal vulvitis. It should be used as an adjunct to treatment of candidal vaginitis.

The cream can also be used for treatment of the sexual partner's penis to prevent re-infection.

4.2 Posology and method of administration

The pessary should be inserted intravaginally, as high as possible, using the applicator provided.

Adults and children of 12 years of age and older:

Insert one pessary, preferably at night, before going to bed.

If symptoms persist for more than 7 days the patient may have a medical condition that requires treatment by a doctor.

The treatment can be repeated if necessary, however, recurrent infections may indicate an underlying medical cause. Patient should seek medical advice if symptoms return within 2 months.

Canesten pessaries need moisture in the vagina in order to dissolve completely, otherwise undissolved pieces of the pessary might crumble out of the vagina. Pieces of undissolved pessary may be noticed by women who experience vaginal dryness. To help prevent this it is important that the pessary is inserted as high as possible into the vagina at bedtime.

To insert the pessary:

1. Pull out plunger until it stops. Place the pessary into the applicator.

2. Carefully insert the applicator containing the pessary as deeply as is comfortable into the vagina. This is best done with the patient lying on her back with the knees bent up.

3. Push plunger until it stops, thereby depositing the pessary into the vagina . Withdraw the applicator and dispose of it hygienically

Treatment during the menstrual period should be avoided due to the risk of the pessary being washed out by the menstrual flow. The treatment should be finished before the onset of menstruation.

The cream should be applied two or three times daily to the vulva and surrounding area and rubbed in gently.

If the cream is being used for treatment of the sexual partner's penis it should be applied two or three times daily for up to two weeks.

Do not use tampons, intravaginal douches, spermicides or other vaginal products while using this product.

Avoidance of vaginal intercourse in case of vaginal infection is recommended while using this product because your partner could become infected.

Children under 12 years of age:

As this product is administered with an applicator, paediatric use is not recommended.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Medical advice should be sought if this is the first time the patient has experienced symptoms of candidal vaginitis.

Before using Canesten Combi Pessary & Cream, medical advice must be sought if any of the following are applicable:

- More than two infections of candidal vaginitis in the last 6 months.

- Previous history of a sexually transmitted disease or exposure to partner with a sexually transmitted disease.

- Pregnancy or suspected pregnancy.

- Aged under 12 or over 60 years.

- Known hypersensitivity to imidazoles or other vaginal antifungal products.

Canesten Combi Pessary & Cream should not be used if the patient has any of the following symptoms whereupon medical advice should be sought:

- Irregular vaginal bleeding.

- Abnormal vaginal bleeding (vaginal haemorrhage) or a blood-stained discharge.

- Vulval or vaginal ulcers, blisters or sores.

- Lower abdominal pain or dysuria.

- Any adverse events such as redness, irritation or swelling associated with the treatment.

- Fever (temperature of 38°C or above) or chills.

- Nausea or vomiting.

- Diarrhoea.

- Foul smelling vaginal discharge.

- Back pain.

- Associated shoulder pain.

Avoid contact with eyes and do not swallow.

This product contains cetostearyl alcohol, which may cause local skin reactions (e.g. contact dermatitis).

All possibly infected areas should be treated at the same time.

4.5 Interaction with other medicinal products and other forms of interaction

Laboratory tests have suggested that, when used together, this product may cause damage to latex contraceptives. Consequently the effectiveness of such contraceptives may be reduced. Patients should be advised to use alternative precautions for at least five days after using this product.

Concomitant medication with vaginal clotrimazole and oral tacrolimus (FK-506; immunosuppressant) might lead to increased tacrolimus plasma levels and similarly with sirolimus. Patients should thus be thoroughly monitored for symptoms of tacromilus or sirolimus overdosage, if necessary by determination of the respective plasma levels.

4.6 Fertility, pregnancy and lactation

Fertility:

No human studies of the effects of clotrimazole on fertility have been performed, however, animal studies have not demonstrated any effects of the drug on fertility.

Pregnancy:

There are limited amount of data from the use of clotrimazole in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of clotrimazole during the first trimester of pregnancy.

During pregnancy the treatment should be carried out with clotrimazole vaginal tablets, since these can be inserted without using an applicator.

Lactation:

Available pharmacodynamic/toxicological data in animals have shown excretion of clotrimazole/metabolites in milk (see section 5.3). Breast-feeding should be discontinued during treatment with clotrimazole.

4.7 Effects on ability to drive and use machines

The medication has no or negligible influence on the ability to drive or use machinery.

4.8 Undesirable effects

The following adverse reactions have been identified during post-approval use of Clotrimazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.

Immune system disorders

Allergic reaction (ME) with symptoms such as dyspnea (PT), hypotension (PT), syncope (PT), and urticaria (ME)

Reproductive system and breast disorders

Vulvovaginal discomfort (PT), edema (PT), burning (PT), genital peeling, irritation, pruritus (ME), pelvic pain (PT), rash (ME), vaginal haemorrhage (PT), erythema (PT).

Gastrointestinal disorders

Abdominal pain (ME)

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9 Overdose

In the event of accidental oral ingestion, routine measures such as gastric lavage should be performed only if clinical symptoms of overdose become apparent (e.g. dizziness, nausea or vomiting)

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Gynaecological antiifectives and antiseptics – imidazole derivates.

ATC Code: G01AF02

Mechanism of Action

Clotrimazole acts against fungi by inhibiting ergosterol synthesis. Inhibition of ergosterol synthesis leads to structural and functional impairment of the cytoplasmic membrane.

Pharmacodynamic Effects

Clotrimazole has a broad antimycotic spectrum of action in vitro and in vivo, which includes dermatophytes, yeasts, moulds, etc.

Under appropriate test conditions, the MIC values for these types of fungi are in the region of less than 0.062 –8.0 μg/ml substrate. The mode of action of clotrimazole is fungistatic or fungicidal depending on the concentration of clotrimazole at the site of infection. In vitro activity is limited to proliferating fungal elements; fungal spores are only slightly sensitive.

In addition to its antimycotic action, clotrimazole also acts on gram-positive microorganisms (streptococci/staphylococci /Gardnerella vagiinalis) and gram-negative microorganisms (Bacteroides). It has no effect on lactobacilli.

In vitro, clotrimazole inhibits the multiplication of Corynebacteria and gram-positive cocci – with the exception of enterococci – in concentrations of 0.5 – 10 μg/ml substrate.

Primarily resistant variants of sensitive fungal species are very rare; the development of secondary resistance by sensitive fungi has so far only been observed in very isolated cases under therapeutic conditions.

5.2 Pharmacokinetic properties

Pharmacokinetic investigations after vaginal application have shown that only a small amount of clotrimazole (3 – 10% of the dose) is absorbed. Due to the rapid hepatic metabolism of absorbed clotrimazole into pharmacologically inactive metabolites the resulting peak plasma concentrations of clotrimazole after vaginal applications of a 500mg dose were less than 10 ng/ml, reflecting that clotrimazole applied intravaginally does not lead to measurable systemic effects or side effects.

Pharmacokinetic investigations after dermal application have shown that clotrimazole is practically not absorbed from the intact or inflamed skin into the human blood circulation. The resulting peak serum concentrations of clotrimazole were below the detection limit of 0.001 μg/ml, reflecting that clotrimazole applied topically does not lead to measurable systemic effects or side effects.

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 and development.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Pessary:

Lactose Monohydrate

Cellulose, Microcrystalline

Lactic Acid

Maize Starch

Crospovidone

Calcium Lactate Pentahydrate

Magnesium Stearate

Silica, Colloidal Anhydrous

Hypromellose

Cream:

Sorbitan stearate

Polysorbate 60

Cetyl palmitate

Cetostearyl alcohol

Octyldodecanol

Benzyl alcohol

Purified water

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Each pessary is packed into a blister consisting of 25µm PA / 45µm Soft Aluminium / 60µm PVC and 20µm Hard Aluminium / 7 g/m2 heat seal lacquer. The cream is supplied in aluminium tubes (10g) with internal lacquer coating, latex stopper and HDPE screw cap.

Both components are enclosed in a cardboard carton with a disposable applicator and patient information leaflet.

6.6 Special precautions for disposal and other handling

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

7. MARKETING AUTHORISATION HOLDER

Bayer Ltd

The Atrium

Blackthorn Road

Dublin 18

8. MARKETING AUTHORISATION NUMBER(S)

PA 1410/039/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of First Authorisation: 24th August 2001

Date of Last Renewal: 24th August 2006

10. DATE OF REVISION OF THE TEXT

March 2015

It is recommended that you also refer to http://www.medicines.ie as the Summary of Product Characteristics may have been updated since this copy was printed.