Table 2: Results of study 37609 (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*
 1035
 
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).

5.2 Pharmacokinetic properties
 Absorption

After subcutaneous administration of Puregon, maximum concentration of FSH is reached within about 12 hours. 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. The absolute bioavailability of subcutaneously administered Puregon is approximately 77%.

Distribution, biotransformation and elimination

Recombinant FSH is biochemically very similar to urinary human FSH and is distributed, metabolised, and excreted in the same way.

5.3 Preclinical safety data
 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.

6. Pharmaceutical particulars
  
6.1 List of excipients
 Puregon 300 IU/0.36 ml, Puregon 600IU/0.72 ml and Puregon 900IU/1.08 ml solution for injection contains:

Sucrose

Sodium citrate

L-methionine

Polysorbate 20

Benzyl alcohol

Water for injections.

The pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.

6.2 Incompatibilities
 In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life
 3 years.

Once the rubber inlay of a cartridge is pierced by a needle, the product may be stored for a maximum of 28 days.

6.4 Special precautions for storage
 Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

Keep the cartridge in the outer carton.

For patient convenience, Puregon may be stored at or below 25 °C 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.

6.5 Nature and contents of container
 Puregon 300 IU/0.36 ml solution for injection

0.36 ml of solution in 1.5 ml cartridge (type I glass) with a grey rubber piston and an aluminium crimp-cap with a rubber inlay.

Pack of 1 cartridge and 6 needles to be u