SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Gynoxin 2% vaginal cream

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Gynoxin contains 20 mg of the active ingredient fenticonazole nitrate in 1 g of cream.

For excipients, see 6.1

3.    PHARMACEUTICAL FORM

Vaginal cream

White homogenous cream

4.    CLINICAL PARTICULARS

4.1.    Therapeutic indications

Treatment of vulvovaginal candidiasis.

4.2 Posology and method of administration

Route of Administration:

Intravaginal

Adults:

One applicator full (about 5 g) is administered into the vagina by a re-usable applicator (morning and evening for three days).

Gynoxin is not greasy, does not soil and can easily be removed with water. Children:

The use of Gynoxin in children is not recommended.

4.3. Contraindications

Ascertained hypersensitive to the product and to other imidazole derivatives.

4.4. Special warnings and precautions for use

The product should not be used in conjunction with barrier contraceptives.

In the event of a hypersensitivity reaction or development of resistant organisms, treatment should be discontinued and the physician consulted.

4.5 Interaction with other medicinal products and other forms of interaction

Not investigated. Since systemic absorption of fenticonazole after application is low, interactions with other drugs are unlikely.

4.6. Pregnancy and lactation

Oral administration of fenticonazole in rats has been reported to produce prolonged gestation and embryotoxic effects after doses above 40mg/kg/day. Fenticonazole does not interfere with the function of male and female gonads and does not modify the first phases of reproduction.

Fenticonazole has shown no teratogenic effects in rats and rabbits. Fenticonazole or its metabolites cross the placental barrier in pregnant rats and rabbits after vaginal application and are excreted in milk of lactating rats.

Since there is no experience of use during pregnancy or lactation, Gynoxin should not be used unless the physician considers it essential to the welfare of the patient.

Pregnant women should not use an applicator without medical instruction.

4.7. Effects on ability to drive and use machines

None.

4.8. Undesirable effects

After intravaginal administration slight transient burning, which usually disappears rapidly, may occasionally occur.

Prolonged topical application may cause sensitisation reactions.

Overdose

Because of the low systemic absorption after vaginal application, overdosage is unlikely. In case of a suspected accidental oral ingestion emesis should be induced or gastric lavage may be attempted. Irrespective of success in inducing emesis the patient should be made to drink water or lemonade with active charcoal and a laxative. Symptomatic therapy may be administered if indicated.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties

ATC code: G01A F12

Fenticonazole is a broad-spectrum antimycotic agent.

•    In vitro: high fungistatic and fungicidal activity against Candida albicans

•    In vivo: healing of vaginal mycoses due to Candida within 5 days in mice.

5.2. Pharmacokinetic properties

Pharmacokinetic studies in humans have shown that systemic absorption of fenticonazole nitrate after vaginal administration is minimal.

5.3. Preclinical safety data

LD50 mice: oral>3000mg/kg; i.p 1276mg/kg (M), 1265mg/kg (F)

LD50 rats: oral>3000mg/kg; s.c.>750mg/kg; i.p. 440mg/kg (M), 309mg/kg (F)

Chronic toxicity: following oral administration of 40-80-160mg/kg/day for 6 months in rats and dogs, fenticonazole was well tolerated, although some evidence of light and moderate general toxicity occurred (increase in liver weight at 160mg/kg without histopathological alterations in rats, and a transient increase in serum SGPT at 80 and 160mg/kg, together with an increase in liver weight in dogs).

Fenticonazole does not interfere with the function of male and female gonads, and does not modify the first phases of reproduction. Studies in reproductive toxicology revealed, as for other imidazole derivatives, an embryolethal effect at high dosages (>20mg/kg). Fenticonazole has shown no teratogenic effects in rats and rabbits and has revealed no mutagenic potential in six mutagenicity tests.

Satisfactory results were obtained in tolerability tests performed in guinea pigs, rabbits as well as in mini-pigs, the skin of which is similar to that of humans, as far as morphology, functionality and sensitivity to irritating agents are concerned.

Fenticonazole has shown no evidence of sensitisation, phototoxicity and photoallergy.

Pharmacokinetic studies have revealed no transcutaneous absorption either in man or in animals and a very low vaginal absorption.

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients

Propylene glycol Wool fat, hydrogenated Almond oil

Polyglycolic ester of fatty acids Cetyl alcohol Glyceryl monostearate Sodium edetate Purified water

6.2. Incompatibilities

None.

6.3. Shelf life

3 years

6.4. Special precautions for storage

Do not store above 30°C. Store in the original container.

6.5    Nature and contents of container

Epoxy-lined blind-end aluminium tubes with a low density polyethylene screw cap, plus polyethylene applicator. Pack size: 1 x 30 g.

6.6    Special precautions for disposal

None.

7.    MARKETING AUTHORISATION HOLDER

Recordati Industria Chimica e Farmaceutica SpA Via Matteo Civitali 1-20148 Milano

Italy

8.    MARKETING AUTHORISATION NUMBER(S)

PL 04595/0006

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

27/10/2004

10 DATE OF REVISION OF THE TEXT

30/09/2010