will be liberated after the administration of hCG.
Clinical efficacy and safety in women
In clinical trials, patients with severe FSH and LH deficiency were defined by an endogenous serum LH level < 1.2 IU/L as measured in a central laboratory. However, it should be taken into account that there are variations between LH measurements performed in different laboratories.
In clinical studies comparing r-hFSH (follitropin alfa) and urinary FSH in ART (see table 3 below) and in ovulation induction, follitropin alfa was more potent than urinary FSH in terms of a lower total dose and a shorter treatment period needed to trigger follicular maturation.
In ART, follitropin alfa at a lower total dose and shorter treatment period than urinary FSH, resulted in a higher number of oocytes retrieved when compared to urinary FSH.
Table 3: Results of study GF 8407 (randomised parallel group study comparing efficacy and safety of follitropin alfa with urinary FSH in ART)
follitropin alfa
(n = 130)
urinary FSH
(n = 116)
Number of oocytes retrieved
11.0 ± 5.9
8.8 ± 4.8
Days of FSH stimulation required
11.7 ± 1.9
14.5 ± 3.3
Total dose of FSH required (number of FSH 75 IU ampoules)
27.6 ± 10.2
40.7 ± 13.6
Need to increase the dose (%)
56.2
85.3
Differences between the 2 groups were statistically significant (p < 0.05) for all criteria listed.
Clinical efficacy and safety in men
In men deficient in FSH, follitropin alfa administered concomitantly with hCG for at least 4 months induces spermatogenesis.
5.2 Pharmacokinetic properties
Following intravenous administration, follitropin alfa is distributed to the extracellular fluid space with an initial half-life of around 2 hours and eliminated from the body with a terminal half-life of about one day. The steady state volume of distribution and total clearance are 10 L and 0.6 L/h, respectively. One-eighth of the follitropin alfa dose is excreted in the urine.
Following subcutaneous administration, the absolute bioavailability is about 70 %. Following repeated administration, follitropin alfa accumulates 3-fold achieving a steady-state within 3-4 days. In women whose endogenous gonadotropin secretion is suppressed, follitropin alfa has nevertheless been shown to effectively stimulate follicular development and steroidogenesis, despite unmeasurable LH levels.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity and genotoxicity additional to that already stated in other sections of this SmPC.
Impaired fertility has been reported in rats exposed to pharmacological doses of follitropin alfa (≥ 40 IU/kg/day) for extended periods, through reduced fecundity.
Given in high doses (≥ 5 IU/kg/day) follitropin alfa caused a decrease in the number of viable foetuses without being a teratogen and dystocia similar to that observed with urinary Menopausal Gonadotropin (hMG). However, since Ovaleap is not indicated in pregnancy, these data are of limited clinical relevance.
6. Pharmaceutical particulars
6.1 List of excipients
Sodium dihydrogen phosphate dihydrate
Sodium hydroxide (2 M) (for pH adjustment)
Mannitol
Methionine
Polysorbate 20
Benzyl alcohol
Benzalkonium chloride
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other m |
