Characteristics of the medicinal product
GONAL-f is available as a solution for injection in pre-filled pens or as a powder and solvent for solution for injection. GONAL-f contains the active substance follitropin alfa.
Therapeutic indications
Treatment with GONAL-f is indicated in the following cases:
• Women with anovulation (ie where ovulation is absent) who do not respond to treatment with clomiphene citrate (another medicine that stimulates ovulation).
• Women subjected to assisted reproduction techniques (such as in vitro fertilization). GONAL-f is given to stimulate the ovary to produce more than one egg at a time.
• Women with severe impairment of luteinizing hormone (LH) and follicle stimulating hormone (FSH). GONAL-f is given in combination with an LH preparation to stimulate ovulation in the ovary.
GONAL-f can also be used in combination with human chorionic gonadotropin (hCG) to induce sperm production in men suffering from hypogonadotrophic hypogonadism (a rare disease characterized by hormone deficiency).
The medicine can only be obtained with a prescription.
Method of use
Treatment with GONAL-f should be performed by a doctor experienced in treating fertility problems. GONAL-f should be administered subcutaneously (under the skin). If the powder is used, it must be mixed with the solvent supplied immediately before use; if necessary, more than one product container can be dissolved in a solvent ampoule. Subcutaneous injection of GONAL-f can be performed by the patient or partner, provided they are properly trained. The dosage and frequency of administration of GONAL-f depend on the use (see above) and the patient's response to treatment. For a complete description of the doses, see the package leaflet.
Mechanisms of action
The active substance in GONAL-f, follitropin alfa, is a copy of the natural hormone FHS (follicle stimulating hormone). In the body, FSH regulates reproductive function: in women it stimulates ovulation and in men the production of sperm by the testicles. In the past, FSH used as a medicine was extracted from urine. The follitropin alfa contained in the medicinal product GONAL-f is produced by a method known as "recombinant DNA technology": that is, it is obtained from a cell in which a gene (DNA) has been introduced which makes it capable of producing human FSH.
Studies carried out
The efficacy of GONAL-f was studied in an assisted reproduction procedure in 470 patients and in 222 women who were unable to ovulate. In these studies, GONAL-f was compared to human FSH extracted from urine. GONAL-f has also been studied in 38 women with severe LH / FSH insufficiency and in 19 men with hypogonadotropic hypogonadism. Given the rarity of these diseases, the two studies were not controlled (GONAL-f was not compared to any other treatment).
Benefits found following the studies
In assisted reproduction procedures, GONAL-f was as effective as the comparator for stimulating the ovary. In women with anovulation, GONAL-f induced ovulation in 84% of women compared with 91% of patients treated with the comparator. GONAL-f has also been shown to be effective in stimulating follicular development in women with severe LF / FSH insufficiency. In the study conducted on GONAL-f men induced sperm production: 63% of patients achieved sperm counts above 1.5 million / ml.
In studies conducted on women with severe LH / FSH insufficiency and on men with hypogonadotrophic hypogonadism the number of patients was small but acceptable, given the rarity of these conditions.
Associated risks
The most frequent side effects (seen in more than 1 patient in 10) are ovarian cysts, local reactions at the injection site (pain, redness, hematoma, swelling and / or irritation) and headache. For the full list of all side effects reported with GONAL-f, see the Package Leaflet. It may happen that the ovary responds to excessive treatment (ovarian hyperstimulation syndrome), especially if hCG has been used; both the doctor and the patients must be aware of this possibility.
GONAL-f must not be used in people who may be hypersensitive (allergic) to follitropin alfa, FSH or any of the excipients, or to patients with tumors of the pituitary gland, hypothalamus, breast, uterus or 'ovary. It must also not be used in subjects where it is not possible to obtain an effective response (such as in patients with ovarian or primary testicular failure). In women it is contraindicated in the presence of ovarian enlargement or cysts not due to polycystic ovary syndrome or gynecological bleeding. For the complete list of limitations, see the package leaflet.
Grounds for approval
The Committee for Medicinal Products for Human Use (CHMP) decided that the benefits of GONAL-f outweigh the risks in women with anovulation, in women who have to ovulate before undergoing fertility therapy, with luteinizing hormone for stimulation of follicular development in women with severe LH and FSH insufficiency, and in men with hypogonadotropic hypogonadism. The CHMP therefore recommended that it be given marketing authorization for GONAL-f.
Further information
On 20 October 1995 the European Commission granted a marketing authorization valid throughout the European Union for GONAL-f to Serono Europe Limited. The marketing authorization was renewed on 20 October 2000 and 20 October 2005. For the full version of the evaluation (EPAR) click here.
Last update of this summary: April 2006
