GONAL-F 450 IU/0.75 ML (33 MCG/0.75 ML) SOLUTION FOR INJECTION IN A PRE-FILLED PEN [SIN13022P]

Product Info

GONAL-F 450 IU/0.75 ML (33 MCG/0.75 ML) SOLUTION FOR INJECTION IN A PRE-FILLED PEN

[SIN13022P]

Indication

4.1 Therapeutic indications
In adult women

• Anovulation (including polycystic ovarian syndrome) in women who have been unresponsive to treatment with clomiphene citrate.

• Stimulation of multifollicular development in women undergoing superovulation for assisted reproductive technologies (ART) such as in vitro fertilisation (IVF), gamete intra-fallopian transfer and zygote intra-fallopian transfer.

In adult men

• GONAL-f is indicated for the stimulation of spermatogenesis in men who have hypogonadotrophic hypogonadism (congenital or acquired) with concomitant human chorionic gonadotropin (hCG) therapy.

Dosing

4.2 Posology and method of administration
Treatment with GONAL-f should be initiated under the supervision of a physician experienced in the treatment of fertility disorders.

Patients must be provided with the correct number of pens for their treatment course and educated to use the proper injection techniques.

Posology
Clinical assessment of GONAL-f indicates that its daily doses, regimens of administration, and treatment monitoring procedures should be individualised to optimise follicular development and to minimise the risk of unwanted ovarian hyperstimulation. It is advised to adhere to the recommended starting doses indicated below.

Bioequivalence has been demonstrated between equivalent doses of the monodose presentation and the multidose presentation of GONAL-f.

Women with anovulation (including polycystic ovarian syndrome)
GONAL-f may be given as a course of daily injections. In menstruating women treatment should commence within the first 7 days of the menstrual cycle.

In the registration trials, a commonly used regimen commenced at 75 to 150 international units FSH daily and was increased preferably by 37.5 or 75 international units at 7- or preferably 14- day intervals if necessary, to obtain an adequate, but not excessive, response.

In clinical practice, the starting dose is typically individualised based on the patient’s clinical characteristics, such as markers of ovarian reserve, age, body mass index, and, if applicable, previous ovarian response to ovarian stimulation.

Starting dose

The starting dose can be adjusted in a stepwise manner (a) lower than 75 international units per day if an excessive ovarian response in terms of number of follicles is anticipated based on the patient’s clinical profile (age, body mass index, ovarian reserve); or (b) higher than 75 up to a maximum of 150 international units per day may be considered if a low ovarian response is anticipated.

The patient’s response should be closely monitored by measuring follicle size and number by ultrasound and/or estrogen secretion.

Dose adjustments

If a patient fails to respond adequately (either low or excessive ovarian response), continuation of that treatment cycle should be evaluated and managed according to the physician’s standard of care. In cases of low response, the daily dose should not exceed 225 international units FSH.

If an excessive ovarian response is obtained according to the physician’s assessment, treatment should be stopped and hCG withheld (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Treatment should recommence in the next cycle at a dose lower than that of the previous cycle.

Final follicular maturation

When an optimal ovarian response is obtained, a single injection of 250 micrograms recombinant human choriogonadotropin alfa (r-hCG) or 5 000 international units, up to 10 000 international units hCG should be administered 24 to 48 hours after the last GONAL-f injection. The patient is recommended to have coitus on the day of, and the day following, hCG administration. Alternatively intrauterine insemination may be performed.

Women undergoing ovarian stimulation for multiple follicular development prior to in vitro fertilisation or other assisted reproductive technologies.
In the registration trials, a commonly used regimen for superovulation involved the administration of 150 to 225 international units of GONAL-f daily, commencing on days 2 or 3 of the cycle.

In clinical practice, the starting dose is typically individualised based on the patient’s clinical characteristics, such as markers of ovarian reserve, age, body mass index, and, if applicable, previous ovarian response to ovarian stimulation.

Starting dose

If a low ovarian response is anticipated, the starting dose may be adjusted in a stepwise manner to not higher than 450 international units daily. Conversely, if an excessive ovarian response is expected, the starting dose may be decreased below 150 international units.

The patient’s response should continue to be closely monitored by measuring follicle size and number by ultrasound and/or estrogen secretion until adequate follicular development has been achieved.

GONAL-f can be given either alone, or, to prevent premature luteinisation, in combination with a gonadotropin-releasing hormone (GnRH) agonist or antagonist.

Dose adjustments

If a patient fails to respond adequately (either low or excessive ovarian response), continuation of that treatment cycle should be evaluated and managed according to the physician’s standard of care. In cases of low response, the daily dose should not exceed 450 international units FSH.

Final follicular maturation

When an optimal ovarian response is obtained, a single injection of 250 micrograms r-hCG or 5 000 international units up to 10 000 international units hCG is administered 24 to 48 hours after the last GONAL-f injection to induce final follicular maturation.

Men with hypogonadotrophic hypogonadism

GONAL-f should be given at a dose of 150 international units three times a week, concomitantly with hCG, for a minimum of 4 months. If after this period, the patient has not responded, the combination treatment may be continued; current clinical experience indicates that treatment for at least 18 months may be necessary to achieve spermatogenesis.

Special population

Elderly population
There is no relevant use of GONAL-f in the elderly population. Safety and efficacy of GONAL-f in elderly patients have not been established.

Renal or hepatic impairment
Safety, efficacy and pharmacokinetics of GONAL-f in patients with renal or hepatic impairment have not been established.

Paediatric population
There is no relevant use of GONAL-f in the paediatric population.

Method of administration
GONAL-f is intended for subcutaneous administration. The first injection of GONAL--f should be performed under direct medical supervision. Self-administration of GONAL-f should only be performed by patients who are well motivated, adequately trained and have access to expert advice.

As GONAL-f pre-filled pen with multidose cartridge is intended for several injections, clear instructions should be provided to the patients to avoid misuse of the multidose presentation.

For instructions on the administration with the pre-filled pen, see section 6.5 and the “Instructions for Use” – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Contraindications

4.3 Contraindications

• hypersensitivity to the active substance follitropin alfa, FSH or to any of the excipients

• tumours of the hypothalamus or pituitary gland

• ovarian enlargement or ovarian cyst unrelated to polycystic ovarian disease and of unknown origin

• gynaecological haemorrhages of unknown origin

• ovarian, uterine or mammary carcinoma

GONAL-f must not be used when an effective response cannot be obtained, such as:

• primary ovarian failure

• malformations of sexual organs incompatible with pregnancy

• fibroid tumours of the uterus incompatible with pregnancy

• primary testicular insufficiency