Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN, Haarlem, The Netherlands
Pharmacotherapeutic group: sex hormones and modulators of the genital system, gonadotrophins
ATC code: G03GA06
Puregon contains a recombinant FSH. This is produced by recombinant DNA technology, using a Chinese hamster ovary cell line transfected with the human FSH subunit genes. The primary amino acid sequence is identical to that of natural human FSH. Small differences in the carbohydrate chain structure are known to exist.
FSH is indispensable in normal follicular growth and maturation, and gonadal steroid production. In the female the level of FSH is critical for the onset and duration of follicular development, and consequently for the timing and number of follicles reaching maturity. Puregon can thus be used to stimulate follicular development and steroid production in selected cases of disturbed gonadal function. Furthermore Puregon can be used to promote multiple follicular development in medically assisted reproduction programs [e.g. in vitro fertilisation/embryo transfer (IVF/ET), gamete intrafallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)]. Treatment with Puregon is generally followed by administration of hCG to induce the final phase of follicle maturation, resumption of meiosis and rupture of the follicle.
In clinical studies comparing recFSH (follitropin beta) and urinary FSH for controlled ovarian stimulation in women participating in an Assisted Reproduction Technology (ART) program and for ovulation induction (see tables 1 and 2 below), Puregon was more potent than urinary FSH in terms of a lower total dose and a shorter treatment period needed to trigger follicular maturation.
For controlled ovarian stimulation, Puregon resulted in a higher number of oocytes retrieved at a lower total dose and with a shorter treatment period, when compared to urinary FSH.
Table 1. Results of study 37,608 (randomized, group comparative clinical study comparing safety and efficacy of Puregon with urinary FSH in controlled ovarian stimulation):
| Puregon (n=546) | u-FSH (n=361) | |
|---|---|---|
| Mean no. of oocytes retrieved | 10.84* | 8.95 |
| Mean total dose (no. of 75 IU ampoules) | 28.5* | 31.8 |
| Mean duration of FSH stimulation (days) | 10.7* | 11.3 |
* Differences between the 2 groups were statistically significant (p<0.05).
For ovulation induction, Puregon resulted in a lower median total dose and shorter median duration of treatment when compared to urinary FSH.
Table 2. Results of study 37,609 (randomized, group comparative clinical study comparing safety and efficacy of Puregon with urinary FSH in ovulation induction):
| Puregon (n=105) | u-FSH (n=66) | ||
|---|---|---|---|
| Mean no. of follicles | ≥12 mm | 3.6* | 2.6 |
| ≥15 mm | 2.0 | 1.7 | |
| ≥18 mm | 1.1 | 0.9 | |
| Median total dose (IU))a | 750* | 1.035 | |
| Median duration of treatment (days)a | 10.0* | 13.0 | |
* Differences between the 2 groups were statistically significant (p<0.05).
a Restricted to women with ovulation induced (Puregon, n=76; u-FSH, n=42).
After intramuscular or subcutaneous administration of Puregon, maximum concentrations of FSH are reached within about 12 hours. After intramuscular administration of Puregon, the maximum FSH concentrations are higher and reached earlier in men as compared to women. Due to the sustained release from the injection site and the elimination half-life of about 40 hours (ranging from 12 to 70 hours), FSH levels remain increased for 24-48 hours. Due to the relatively long elimination half-life, repeated administration of the same dose will lead to plasma concentrations of FSH that are approximately 1.5-2.5 times higher than after single-dose administration. This increase enables therapeutic FSH concentrations to be reached. There are no significant pharmacokinetic differences between intramuscular and subcutaneous administration of Puregon. Both have an absolute bioavailability of approximately 77%.
Recombinant FSH is biochemically very similar to urinary human FSH and is distributed, metabolised, and excreted in the same way.
Single-dose administration of Puregon to rats induced no toxicologically significant effects. In repeated-dose studies in rats (two weeks) and dogs (13 weeks) up to 100-fold the maximal human dose, Puregon induced no toxicologically significant effects. Puregon showed no mutagenic potential in the Ames test and in the in vitro chromosome aberration test with human lymphocytes.
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