Posology : מינונים

4.2 Posology and method of administration
Treatment with Puregon should be initiated under the supervision of a physician experienced in the treatment of fertility problems.

The first injection of 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.
When using the pen-injector, it should be realised that the pen is a precision device which accurately delivers the dose to which it is set. It was shown that on average an 18% higher amount of FSH is given with the pen compared with a conventional syringe. This may be of particular relevance when switching between the pen- injector and a conventional syringe within one treatment cycle. Especially when switching from a syringe to the pen, small dose adjustments may be needed to prevent too high a dose being given.

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 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
Puregon solution for injection in cartridges has been developed for use in the Puregon Pen and should be administered subcutaneously. The injection site should be alternated to prevent lipoatrophy.
Using the pen, injection of Puregon can be carried out by the patient or partner, provided that proper instructions are given by the physician. Before using the pen, the instructions for use must be read carefully.