2. Local reactions at the site of injection include induration and pain.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, website www.mhra.gov.uk/yellowcard.
4.9 Overdose
 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).
5. Pharmacological properties
  
5.1 Pharmacodynamic properties
 Pharmacotherapeutic group: sex hormones and modulators of the genital system, gonadotrophins; ATC code: G03G A06.

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.

Mechanism of Action

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 intra-fallopian 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.

Clinical Efficacy and Safety

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 37608 (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 sh