PUREGON SOLUTION FOR INJECTION 300 IU/0.36 ML [SIN12185P]

Product Info

PUREGON SOLUTION FOR INJECTION 300 IU/0.36 ML

[SIN12185P]

4.1 Therapeutic indications
In the female
Puregon is indicated for the treatment of female infertility in the following clinical situations:

• Anovulation (including polycystic ovarian syndrome, PCOS) in women who have been unresponsive to treatment with clomifene citrate.

• Controlled ovarian hyperstimulation to induce the development of multiple follicles in medically assisted reproduction programs [e.g., in vitro fertilization/embryo transfer (IVF/ET), gamete intra-fallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)].

In the male

• Deficient spermatogenesis due to hypogonadotrophic hypogonadism.

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
When using the pen injector, it should be realized that the pen is a precision device that 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.

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 estradiol levels may also be useful.

In comparative clinical studies with Puregon and urinary FSH it was shown that Puregon is more effective than urinary FSH in terms of a lower total dose and a shorter treatment period needed to achieve pre-ovulatory conditions. Therefore, it is considered appropriate to give a lower dosage of Puregon than generally used for urinary FSH, not only in order to optimize follicular development but also to reduce the risk of unwanted ovarian hyperstimulation.

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 international units 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 estradiol levels indicate an adequate pharmacodynamic response. A daily increase of estradiol 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 estradiol levels of 300–900 picograms/mL (1000–3000 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 estradiol levels increase too rapidly, i.e. more than a daily doubling for estradiol 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 international units 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 international units 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 estradiol levels may be useful. When ultrasound assessment indicates the presence of at least three follicles of 16–20 mm, and there is evidence of a good estradiol response (plasma levels of about 300–400 picogram/mL (1000–1300 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 international units/week, preferably divided in 3 dosages of 150 international units, 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.

There is no relevant indication for use of Puregon in children.

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 injector, injection of Puregon can be carried out by the patient or partner, provided that proper instructions are given by the physician. Self administration of Puregon should only performed by patients who are well-motivated, adequately trained and with access to expert advice.

4.3 Contraindications
For males and females

• Hypersensitivity to the active substance or any of the excipients.

• Tumors of the ovary, breast, uterus, testis, pituitary or hypothalamus.

• Primary gonadal failure.

Additionally for females

• Pregnancy or lactation.

• Undiagnosed vaginal bleeding.

• Ovarian cysts or enlarged ovaries, not related to polycystic ovarian syndrome (PCOS).

• Malformations of the reproductive organs incompatible with pregnancy.

• Fibroid tumors of the uterus incompatible with pregnancy.