Crinone 8% Progesterone Vaginal Gel

Active Ingredient

Vaginal gel

Treatment of infertility due to inadequate luteal phase.

For use during in-vitro fertilisation, where infertility is mainly due to tubal, idiopathic or endometriosis linked sterility associated with normal ovulatory cycles.

Posology

Intravaginal application

Treatment of infertility due to inadequate luteal phase

One application (1.125g 8% gel) every day, starting after documented ovulation or arbitrarily on the 18^th– 21^st day of the cycle.

Use during in-vitro fertilisation

Daily application of Crinone 8% gel should be continued for 30 days if there is laboratory evidence of pregnancy.

Children: Not applicable

The Elderly: Not applicable

Method of Administration

Crinone is applied directly from the specially designed sealed applicator into the vagina. The applicator should be removed from the sealed wrapper. The twist-off cap should not be removed at this time.

1. The applicator should be gripped firmly by the thick end. It should be shaken down like a thermometer to ensure that the contents are at the thin end.

2. The tab should be twisted off and discarded.

3. The applicator may be inserted while patient is in a sitting position or when lying on her back with the knees bent. The thin end of applicator should be gently inserted well into the vagina.

4. The thick end of the applicator should be pressed firmly to deposit gel. The applicator should be removed and discarded in a waste container.

1. Known hypersensitivity to progesterone or any of the excipients

2. Undiagnosed vaginal bleeding

3. Known or suspected progesterone-sensitive malignant tumours

4. Porphyria

Cautious use in severe hepatic insufficiency.

In cases of breakthrough bleeding, as in all cases of irregular vaginal bleeding, non-functional causes should be considered. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures should be undertaken.

Crinone is not indicated in threatened abortion. Treatment should be discontinued in the event of a missed abortion.

Although risk of thromboembolism has been associated with estrogens, a link with progestins remains questionable. Therefore, in women with generally recognised risk factors for thrombo-embolic events, such as personal or family history, treatment with Crinone may further increase the risk. In these women, the benefits of Crinone administration need to be weighed against the risks. It should be noted however, that pregnancy itself carries an increased risk of thrombo-embolic events.

Avoid concurrent use with other intravaginal preparations. See section 4.5.

The excipient sorbic acid may cause local skin reactions (e.g. contact dermatitis) or vaginal irritation.

Crinone is not recommended for use concurrently with other vaginal preparations.

Although there is evidence of interaction between oral progestogens and CYP3A4 inducers, resulting in a decrease of serum progestogen levels, no significant consequences on progesterone levels is expected from concurrent administration of CRINONE^® vaginal gel with CYP3A inducers

In case of corpus luteum deficiency, Crinone can be used during the first month of pregnancy.

Do not use during lactation.

Drivers and users of machines are warned that risk of somnolence may occur.

Common (>1/100 – 1/10)

Headache, Somnolence, Breast Tenderness, Vaginal irritation, Itching or Burning

Post Marketing Reports

In addition, intermenstrual bleeding (spotting), hypersensitivity reactions usually manifesting as skin rash, and other mild application site reactions have been reported post-marketing.

Rare events of urticaria and pruritis were noted.

Not applicable

The pharmacological particulars of the product are those of the naturally occurring progesterone with induction of a full secretory endometrium.

The progesterone vaginal gel is based on a polycarbophil delivery system which attaches to the vaginal mucosa and provides a prolonged release of progesterone for at least three days.

In rabbits, Crinone was an eye irritant categorised class IV (minimal effects clearing in less than 24 hours), but not a dermal irritant.

A moderate vaginal irritation was found in rabbits after application of 2.0 ml/day of 8% gel for 5 days.

Glycerin, Light Paraffin, Hydrogenated Palm Oil Glyceride, Carbopol 974P, Sorbic acid, Polycarbophil, Sodium hydroxide, Purified water.

No incompatibilities were found with the usual contraceptive devices.

36 months

Store below 25°C

A single use, one piece, white polyethylene applicator with a twist-off top, designed for intravaginal application.

Each applicator contains 1.45g of gel and delivers 1.125g of gel. Each one is wrapped up and sealed in a paper/aluminium/polyethylene foil overwrap.

The applicators are packed in cardboard boxes containing 6 or 15 units of Crinone 8% progesterone vaginal gel.

No special requirements

Serono Ltd

Bedfont Cross

Stanwell Road

Feltham

Middlesex TW14 8NX

United Kingdom

Tel: 020 8818 7200

PL 03400/0081

Date of first authorisation: 26^th January 2000

Date of last renewal: 26^th June 2004

4^th January 2011