Presentation and Status in Health Basket
300 IU / 0.5 ml
450 IU / 0.75 ml
900 IU / 1.5 ml
The dose recommendations given for GONAL-f are those in use for urinary FSH. Clinical assessment of GONAL-f indicates that its daily doses, regimens of administration, and treatment monitoring procedures should not be different from those currently used for urinary FSH-containing medicinal products. It is advised to adhere to the recommended starting doses indicated below.
Comparative clinical studies have shown that on average patients require a lower cumulative dose and shorter treatment duration with GONAL-f compared with urinary FSH. Therefore, it is considered appropriate to give a lower total dose of GONAL-f than generally used for urinary FSH, not only in order to optimise follicular development but also to minimise the risk of unwanted ovarian hyperstimulation.
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.
A commonly used regimen commences at 75-150 IU FSH daily and is increased preferably by 37.5 or 75 IU at 7 or preferably 14 day intervals if necessary, to obtain an adequate, but not excessive, response. Treatment should be tailored to the individual patient’s response as assessed by measuring follicle size by ultrasound and/or oestrogen secretion. The maximal daily dose is usually not higher than 225 IU FSH. If a patient fails to respond adequately after 4 weeks of treatment, that cycle should be abandoned and the patient should undergo further evaluation after which she may recommence treatment at a higher starting dose than in the abandoned cycle.
When an optimal response is obtained, a single injection of 250 micrograms recombinant human choriogonadotropin alfa (r-hCG) or 5,000 IU up to 10,000 IU hCG should be administered 24-48 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 (IUI) may be performed.
If an excessive response is obtained, treatment should be stopped and hCG withheld.
Treatment should recommence in the next cycle at a dose lower than that of the previous cycle.
Women undergoing ovarian stimulation for multiple follicular development prior to in vitro fertilisation or other assisted reproductive technologies: A commonly used regimen for superovulation involves the administration of 150-225 IU of GONAL-f daily, commencing on days 2 or 3 of the cycle. Treatment is continued until adequate follicular development has been achieved (as assessed by monitoring of serum oestrogen concentrations and/or ultrasound examination), with the dose adjusted according to the patient’s response, to usually not higher than 450 IU daily. In general adequate follicular development is achieved on average by the tenth day of treatment (range 5 to 20 days).
A single injection of 250 micrograms r-hCG or 5,000 IU up to 10,000 IU hCG is administered 24-48 hours after the last GONAL-f injection to induce final follicular maturation.
Down-regulation with a gonadotropin-releasing hormone (GnRH) agonist or antagonist is now commonly used in order to suppress the endogenous LH surge and to control tonic levels of LH. In a commonly used protocol, GONAL-f is started approximately 2 weeks after the start of agonist treatment, both being continued until adequate follicular development is achieved. For example, following two weeks of treatment with an agonist, 150-225 IU GONAL-f are administered for the first 7 days. The dose is then adjusted according to the ovarian response.
Overall experience with IVF indicates that in general the treatment success rate remains stable during the first four attempts and gradually declines thereafter.
Women with anovulation resulting from severe LH and FSH deficiency: In LH and FSH deficient women (hypogonadotrophic hypogonadism), the objective of GONAL-f therapy in association with lutropin alfa is to develop a single mature Graafian follicle from which the oocyte will be liberated after the administration of human chorionic gonadotrophin (hCG). GONAL-f should be given as a course of daily injections simultaneously with lutropin alfa. Since these patients are amenorrhoeic and have low endogenous oestrogen secretion, treatment can commence at any time.
A recommended regimen commences at 75 IU of lutropin alfa daily with 75-150 IU FSH. Treatment should be tailored to the individual patient’s response as assessed by measuring follicle size by ultrasound and oestrogen response.
If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7-14 day intervals and preferably by 37.5-75 IU increments. It may be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.
When an optimal response is obtained, a single injection of 250 micrograms r-hCG or 5,000 IU up to 10,000 IU hCG should be administered 24-48 hours after the last GONAL-f and lutropin alfa injections. The patient is recommended to have coitus on the day of, and on the day following, hCG administration.
Alternatively, intrauterine insemination (IUI) may be performed.
Luteal phase support may be considered since lack of substances with luteotrophic activity (LH/hCG) after ovulation may lead to premature failure of the corpus luteum.
If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment should recommence in the next cycle at a dose of FSH lower than that of the previous cycle.
Men with hypogonadotrophic hypogonadism: GONAL-f should be given at a dosage of 150 IU 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.
See prescribing information for full details.
In adult women:
• Anovulation (including polycystic ovarian syndrome) in women who have been unresponsive to treatment with clomiphene citrate.
• Stimulation of multifollicular development in patients undergoing superovulation for assisted reproductive technologies (ART) such as in vitro fertilization (IVF), gamete intra-fallopian transfer (GIFT) and zygote intra-fallopian transfer (ZIFT).
• GONAL-f in association with a luteinising hormone (LH) preparation is recommended for the stimulation of follicular development in women with severe LH and FSH deficiency. In clinical trials these patients were defined by an endogenous serum LH level < 1.2 IU/L.
In adult men:
• GONAL-f is indicated for the stimulation of spermatogenesis in men who have congenital or acquired hypogonadotrophic hypogonadism with concomitant human Chorionic Gonadotrophin (hCG) therapy.
• hypersensitivity to the active substance or to any of the excipients
• tumours of the hypothalamus or pituitary gland
• ovarian enlargement or ovarian cyst not due to polycystic ovarian syndrome
• gynaecological haemorrhages of unknown aetiology
• 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
Should be used only by physicians familiar with infertility problems and management.
Therapy requires the availability of appropriate monitoring facilities. Regular monitoring of ovarian response with ultrasound, alone or preferably in combination with measurement of serum estradiol levels.
The lowest effective dose in relation to the treatment objective should be used in both men and women.
Patients with porphyria or a family history of porphyria should be closely monitored during treatment with GONAL-f.
Before starting treatment, the couple’s infertility should be assessed as appropriate and putative contraindications for pregnancy evaluated. In particular, patients should be evaluated for hypothyroidism, adrenocortical deficiency, hyperprolactinemia and appropriate specific treatment given.
See prescribing information for full details.
The most commonly reported adverse reactions are headache, ovarian cysts and local injection site reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection).
Mild or moderate ovarian hyperstimulation syndrome (OHSS) has been commonly reported and should be considered as an intrinsic risk of the stimulation procedure. Severe OHSS is uncommon.
Thromboembolism may occur very rarely.
See prescribing information for full details.
Concomitant use of GONAL-f with other medicinal products used to stimulate ovulation (e.g. hCG, clomiphene citrate) may potentiate the follicular response, whereas concurrent use of a GnRH agonist or antagonist to induce pituitary desensitisation may increase the dose of GONAL-f needed to elicit an adequate
ovarian response. No other clinically significant medicinal products interaction has been reported during GONAL-f therapy.
Pregnancy and Lactation
Pregnancy: There is no indication for use of GONAL-f during pregnancy. Data on a limited number of exposed pregnancies (less than 300 pregnancy outcomes) indicate no malformative or feto/neonatal toxicity of follitropin alfa.
No teratogenic effect has been observed in animal studies. In case of exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of GONAL-f.
Breast-feeding: GONAL-f is not indicated during breast-feeding.
The effects of an overdose of GONAL-f are unknown, nevertheless, there is a possibility that OHSS may occur.