Follitropin alfa Other names: FSH Follicle-stimulating hormone

In women, the most important effect resulting from parenteral administration of FSH is the development of mature Graafian follicles. In women with anovulation, the object of follitropin alfa therapy is to develop a single mature Graafian follicle from which the ovum will be liberated after the administration of hCG. In men deficient in FSH, follitropin alfa administered concomitantly with hCG for at least 4 months induces spermatogenesis.

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.

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 follitropin alfa is not indicated in pregnancy, these data are of limited clinical relevance.