SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Canesten Combi Soft Gel Pessary & External Cream 500mg / 2% w/w vaginal capsule & cream

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Canesten Soft Gel Pessary contains Clotrimazole 500mg.

Canesten External Cream contains Clotrimazole 2% w/w.

Excipient with known effect:

Cream: cetostearyl alcohol

For full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Vaginal capsule, soft

Yellow teardrop-shaped soft capsule

Cream White cream

4    CLINICAL PARTICULARS

4.1 Therapeutic indications

Canesten 500mg Soft Gel Pessary is indicated for the treatment of candidal vaginitis

The cream is indicated for the treatment of candidal vulvitis. It should be used as an adjunct to treatment of candidal vaginitis. It can also be used for treatment of the sexual partner’s penis to prevent re-infection.

4.2 Posology and method of administration

Adults: One 500mg soft gel pessary should be inserted at night. Using the applicator provided, the soft gel pessary should be inserted as high as possible into the vagina. This is best achieved when lying back with legs bent up. A second treatment may be carried out if necessary.

Generally:

Treatment during the menstrual period should not be performed due to the risk of the soft gel pessary being washed out by the menstrual flow. The treatment should be finished before the onset of menstruation.

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

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

Treatment with the cream should be continued until symptoms of the infection disappear. However, if after concomitant treatment of the vaginitis, the symptoms do not improve within seven days, the patient should consult a physician.

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.

Vaginal intercourse should be avoided in case of vaginal infection and while using this product because the partner could become infected.

Children:

Not recommended for children under 16 as the product is used with an applicator.

4.3 Contraindications

Hypersensitivity to clotrimazole or any other excipients listed in section 6.1.

4.4 Special warnings and precautions for use

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

Patients should be advised to consult their physician if the symptoms have not been relieved within one week of using Canesten 500mg Soft Gel Pessary. Canesten 500mg Soft Gel Pessary can be used again if the candidal infection returns after 7 days. However, if the candidal infection recurs more than twice within six months, patients should be advised to consult their physician.

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 closely monitored for signs and symptoms of tacrolimus 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 is a limited amount of data from the use of clotrimazole in pregnant women. Animal studies with clotrimazole have shown reproductive toxicity at high oral doses (see section 5.3). At the low systemic exposures of clotrimazole following vaginal treatment, harmful effects with respect to reproductive toxicity are not predicted.

Clotrimazole can be used during pregnancy, but only under the supervision of a physician or midwife

During pregnancy the soft gel pessary should be inserted without using an applicator.

Lactation:

Available pharmacodynamic/toxicological data in animals have shown excretion of clotrimazole/metabolites in milk after intravenous administration (see section 5.3). A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from clotrimazole therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

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

As the listed undesirable effects are based on spontaneous reports, assigning accurate frequency of occurence for each is not possible

Immune system disorders:

allergic reaction (syncope, hypotension, dyspnea, urticaria, pruritus)

Canesten Soft Gel Pessary Reproductive system and breast disorders:

genital peeling, pruritus, rash, oedema, erythema, discomfort, burning, irritation, pelvic pain, vaginal haemorrhage.

Gastrointestinal disorders: abdominal pain

Canesten Cream

Skin and subcutaneous tissue disorders: blisters, discomfort/pain, oedema, erythema, irritation, peeling/exfoliation, pruritus, rash, stinging/burning

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

No risk of acute intoxication is seen as it is unlikely to occur following a single vaginal or dermal application of an overdose (application over a large area under conditions favourable to absorption) or inadvertent oral ingestion. There is no specific antidote.

However, 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). Gastric lavage should be carried out only if the airway can be protected adequately.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Gynaecological antiinfectives and antiseptics -imidazole derivatives

ATC Code: G01A F02

Mechanism of Action

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

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 pg/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 vaginalis) and gramnegative 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 pg/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%) is absorbed. Due to the rapid hepatic metabolism of absorbed clotrimazole into pharmacologically inactive metabolites the resulting peak plasma concentrations of clotrimazole after vaginal application 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 ^g/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 studies of repeated dose toxicity, genotoxicity and carcinogenicity.

Clotrimazole was not teratogenic in reproductive toxicity studies in mice, rats and rabbits. In rats high oral doses were associated with maternal toxicity, embryotoxicity, reduced fetal weights and decreased pup survival.

In rats clotrimazole and/or its metabolites were secreted into milk at levels higher than in plasma by a factor of 10 to 20 at 4 hrs after administration, followed by a decline to a factor of 0.4 by 24 hrs.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

The soft gel pessary contains:

White soft paraffin Liquid paraffin Gelatin Glycerol Water

Titanium dioxide (E171) Quinoline yellow (E104) Sunset yellow (E110) Lecithin

Medium-chain triglycerides.

The cream contains:

Sorbitan stearate Poly sorb ate 60 Cetyl palmitate Cetostearyl alcohol Octyldodecanol Benzyl alcohol Purified Water

Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This product should be stored in the original carton in a dry place in order to protect it from moisture.

Do not store above 30°C.

6.5 Nature and contents of container

Each soft gel pessary is packed into a blister consisting of formed clear triplex laminate film PVC/PVdC/PVC (Total PVC 250pm; PVdC 120g/m2) sealed with 20 pm hard tempered aluminium lidding foil ) and is supplied with an applicator

The cream is filled into Aluminium tubes (10g) with internal lacquer coating, latex stopper and HDPE screw top.

6.6 Special precautions for disposal

No special requirements

MARKETING AUTHORISATION HOLDER

Bayer plc Bayer House Strawberry Hill Newbury, Berkshire RG14 1JA United Kingdom

Trading as Bayer plc, Consumer Care Division.

8    MARKETING AUTHORISATION NUMBER(S)

PL 00010/0636

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

05/09/2011

10    DATE OF REVISION OF THE TEXT

23/06/2016