GONAL-f PEN is supplied in Australia by:

Merck Serono Australia Pty Ltd. 3-4/25 Frenchs Forest Road East. Frenchs Forest NSW 2086

For enquiries call: 1800 633 463

GONAL-f® 300 IU/0.5 ml (22 micrograms/0.5 ml), 450 IU/0.75 ml (33 micrograms /0.75 ml), 900 IU/1.5 ml (66 micrograms/1.5 ml) solution for injection in a pre-filled pen.

Qualitative composition: Pre-filled pens containing follitropin alfa, recombinant human follicle stimulating hormone (r-hFSH) produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology.

Indications:

(1) Anovulation (including polycystic ovarian syndrome, PCOS) in adult women who have been unresponsive to treatment with clomiphene citrate.

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

(3) In association with a luteinising hormone (LH) preparation for stimulation of follicular development in adult women with severe LH and FSH deficiency. In clinical trials these patients were defined by an endogenous serum LH level < 1.2 IU/L.

(4) Stimulation of spermatogenesis in adult men who have congenital or acquired hypogonadotrophic hypogonadism with concomitant human Chorionic Gonadotropin (hCG) therapy.

Dosage and administration:

Initiate under the supervision of a physician experienced in the treatment of fertility disorders. For subcutaneous injection.

Women with anovulation (including PCOS): Daily injections, starting by Day 7 of the cycle. Treatment should be tailored to the patient’s response. Treatment typically 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 required. Maximum daily dose is usually not higher than 225 IU FSH. If a patient fails to respond after 4 weeks of treatment; that cycle should be abandoned and treatment recommended at a higher starting dose. When an optimal response is obtained, a single injection of 250 micrograms r-hCG or 5,000 IU 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 day following, hCG administration. Alternatively intrauterine insemination (IUI) may be performed. If the response is excessive, treatment should be stopped and the hCG withheld (see precautions).

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 day 2 or 3 of the cycle. Continue treatment until adequate follicular development has been achieved. Maximum daily dose is usually not higher than 450 IU daily. 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 commonly used in order to suppress the endogenous LH surge and to control tonic levels of LH. GONAL-f® is started approximately 2 weeks after the start of agonist treatment, both being continued until adequate follicular development is achieved.

Women with anovulation resulting from severe LH and FSH deficiency: Treatment should be tailored according to response. Treatment may commence at 75 IU of lutropin alfa daily with 75 IU-150 IU FSH. If appropriate, the FSH dose should be adapted after 7-14 day intervals and by 37.5 IU-75 IU increments for up to 5 weeks. When an optimal response is obtained, a single injection of 250 micrograms rhCG or administer 5,000 IU to 10,000 IU hCG 24-48 hours after the last lutropin alfa and GONAL-f® injections.The patient is recommended to have coitus on the day of, and on the day following, Hcg administration. Alternatively, IUI may be performed. If the response is excessive, treatment should be stopped and the hCG withheld.

Men with hypogonadotrophic hypogonadism: 150 IU GONAL-f® should be given 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.

Contraindications:

Hypersensitivity to active substance or to any of the excipients, tumours of the hypothalamus or pituitary gland.

In women, ovarian enlargement or cyst not due to polycystic ovarian syndrome, gynaecological haemorrhages of unknown aetiology, ovarian, uterine or mammary carcinoma or when an effective response cannot be obtained such as primary ovarian failure, malformations of sexual organs or fibroid tumours of the uterus incompatible with pregnancy.

In men, primary testicular insufficiency.

Precautions:

Treatment with GONAL-f® should be initiated under the supervision of a physician experienced in the treatment of infertility problems. Self-administration should only be performed by patients adequately trained and with access to expert advice.

The first injection should be performed under direct medical supervision.

Patients with porphyria or a family history of porphyria should be closely monitored during treatment with GONAL-f®.

Assess couple’s infertility and putative contraindications for pregnancy before starting treatment.

Monitor for ovarian enlargement or hyperstimulation. Excessive ovarian response to gonadotropin treatment can give rise to ovarian hyperstimulation syndrome (OHSS) with varying degrees of severity.

Risk factors for OHSS include PCOS, as well as high or rapidly rising serum oestradiol levels.

To minimise the risk of OHSS, adherence to recommended doses and administration schedule is important.

Monitoring with ultrasound scans as well as oestradiol measurements are also recommended.

There is evidence that hCG can trigger OHSS and that the syndrome may be more severe and more protracted if pregnancy occurs.

If OHSS occurs, withhold hCG and advise the patient to avoid coitus or use barrier methods of contraception for at least 4 days.

Very rarely, severe OHSS may be complicated by ovarian torsion, pulmonary embolism, ischaemic stroke and myocardial infarction.

Patients should be advised of the potential risk of multiple births before starting treatment.

Ectopic pregnancy is more common following ART and may occur in patients with prior tubal disease.

Pregnancy loss is higher than in the normal population.

Prevalence of congenital malformations may be slightly higher than after spontaneous conceptions.

In women with recent or ongoing thromboembolic disease or those with generally recognised risk factors for thromboembolic events, treatment with gonadotropins increases the risk.

There have been reports of ovarian and other reproductive system neoplasms, both benign and malignant, in women who have undergone multiple treatment regimens for infertility treatment. It is not yet established whether or not treatment with gonadotropins increases the risk of these tumours in infertile women.

GONAL-f® should not be used during breastfeeding.

In men, semen analysis is recommended 4–6 months after the beginning of the treatment in assessing the response. GONAL-f® should not be used in men when an effective response cannot be obtained. Interactions: 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.

Undesirable effects

+ Treatment in women:

Very common: Headache, ovarian cysts, injection site reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection).

Common: abdominal pain, abdominal distension, abdominal discomfort, nausea, vomiting, diarrhoea; mild or moderate OHSS (including associated symptomatology).

Uncommon: Severe OHSS (including associated symptomatology).

Rare: Complication of severe OHSS.

Very rare: Mild to severe hypersensitivity reactions including anaphylactic reactions and shock, thromboembolism (usually associated with severe OHSS), exacerbation or aggravation of asthma.

+ Treatment in men:

Very common: Injection site reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection), weight gain.

Common: Acne, gynaecomastia, varicocele.

Very rare: Mild to severe hypersensitivity reactions including anaphylactic reactions and shock, exacerbation or aggravation of asthma.