PUREGON Solution for injection Ref.[9735] Active ingredients: Follitropin beta

Treatment with Puregon should be initiated under the supervision of a physician experienced in the treatment of fertility problems.

The first injection with Puregon should be performed under direct medical supervision.

Posology

Dosage in the female

There are great inter- and intra-individual variations in the response of the ovaries to exogenous gonadotrophins. This makes it impossible to set a uniform dosage scheme. The dosage should, therefore, be adjusted individually depending on the ovarian response. This requires ultrasound assessment of follicular development. The concurrent determination of serum oestradiol levels may also be useful.

Based on the results of comparative clinical studies, it is considered appropriate to give a lower total dosage of Puregon over a shorter treatment period than generally used for urinary FSH, not only in order to optimise follicular development but also to reduce the risk of unwanted ovarian hyperstimulation (see section 5.1).

Clinical experience with Puregon is based on up to three treatment cycles in both indications. Overall experience with IVF indicates that in general the treatment success rate remains stable during the first four attempts and gradually declines thereafter.

Anovulation

A sequential treatment scheme is recommended starting with daily administration of 50 IU Puregon. The starting dose is maintained for at least seven days. If there is no ovarian response, the daily dose is then gradually increased until follicle growth and/or plasma oestradiol levels indicate an adequate pharmacodynamic response. A daily increase of oestradiol levels of 40-100% is considered to be optimal. The daily dose is then maintained until pre-ovulatory conditions are reached. Pre-ovulatory conditions are reached when there is ultrasonographic evidence of a dominant follicle of at least 18 mm in diameter and/or when plasma oestradiol levels of 300-900 picograms/mL (1,000-3,000 pmol/L) are attained. Usually, 7 to 14 days of treatment is sufficient to reach this state. The administration of Puregon is then discontinued and ovulation can be induced by administering human chorionic gonadotrophin (hCG).

If the number of responding follicles is too high or oestradiol levels increase too rapidly, i.e. more than a daily doubling for oestradiol for two or three consecutive days, the daily dose should be decreased.

Since follicles of over 14 mm may lead to pregnancies, multiple pre-ovulatory follicles exceeding 14 mm carry the risk of multiple gestations. In that case hCG should be withheld and pregnancy should be avoided in order to prevent multiple gestations.

Controlled ovarian hyperstimulation in medically assisted reproduction programs

Various stimulation protocols are applied. A starting dose of 100-225 IU is recommended for at least the first four days. Thereafter, the dose may be adjusted individually, based upon ovarian response. In clinical studies it was shown that maintenance dosages ranging from 75-375 IU for six to twelve days are sufficient, although longer treatment may be necessary.

Puregon can be given either alone, or, to prevent premature luteinisation, in combination with a GnRH agonist or antagonist. When using a GnRH agonist, a higher total treatment dose of Puregon may be required to achieve an adequate follicular response.

Ovarian response is monitored by ultrasound assessment. The concurrent determination of serum oestradiol levels may also be useful. When ultrasound assessment indicates the presence of at least three follicles of 16-20 mm, and there is evidence of a good oestradiol response (plasma levels of about 300-400 picograms/mL (1,000-1,300 pmol/L) for each follicle with a diameter greater than 18 mm), the final phase of maturation of the follicles is induced by administration of hCG. Oocyte retrieval is performed 34-35 hours later.

Dosage in the male

Puregon should be given at a dosage of 450 IU/week, preferably divided in 3 dosages of 150 IU, concomitantly with hCG. Treatment with Puregon and hCG should be continued for at least 3 to 4 months before any improvement in spermatogenesis can be expected. To assess the response, semen analysis is recommended 4 to 6 months after the beginning of treatment. If a patient has not responded after this period, the combination therapy may be continued; current clinical experience indicates that treatment for up to 18 months or longer may be necessary to achieve spermatogenesis.

Paediatric population

There is no relevant use of Puregon in the paediatric population for the approved indication.

Method of administration

To prevent painful injections and minimise leakage from the injection site Puregon should be slowly administered intramuscularly or subcutaneously. The subcutaneous injection site should be alternated to prevent lipoatrophy. Any unused solution should be discarded. Subcutaneous injection of Puregon may be carried out by patient or partner, provided that proper instructions are given by the physician. Self-administration of Puregon should only be performed by patients who are well-motivated, adequately trained and with access to expert advice.

No data on acute toxicity of Puregon in humans is available, but the acute toxicity of Puregon and of urinary gonadotrophin preparations in animal studies has been shown to be very low. Too high a dosage of FSH may lead to hyperstimulation of the ovaries (see section 4.4).

Shelf-life: 3 years.

The contents of a vial should be used immediately after piercing of the rubber stopper

Store in a refrigerator (2°C–8°C).

Do not freeze.

Keep the vial(s) in the outer carton.

For patient convenience, Puregon may be stored at or below 25ºC by the patient for a single period of not more than 3 months.

For storage conditions after first opening of the medicinal product, see section 6.3.

0.5 mL of solution in 3 mL vial (type I glass) with stopper (chlorobutyl rubber).

Pack of 1, 5 or 10 vials.

Not all pack sizes may be marketed.

Do not use if the solution contains particles or if the solution is not clear.

The contents of a vial should be used immediately after piercing of the rubber stopper.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.