GONAL-F

What it is

GONAL-F contains the active ingredient follitropin alfa (rch), which is recombinant human follicle stimulating hormone. This is produced by a Chinese Hamster Ovary cell line transfected with the human FSH subunit genes by recombinant DNA technology. GONAL-F is a clear, colourless solution for injection for subcutaneous injection pre-assembled in a disposable pen. GONAL-F is available as solution for injection, containing follitropin alfa 75 IU/0.125 mL, 150 IU/0.25 mL, 225 IU/0.375 mL, 300 IU/0.5 mL or 450 IU/0.75 mL in pre-filled pens.

Approved indications —

Treatment of anovulatory infertility in women who have been unresponsive to clomiphene citrate or where clomiphene citrate is contraindicated. — Controlled ovarian hyperstimulation in women undergoing assisted reproductive technologies. — Stimulation of follicular development in women with severe LH and FSH deficiency, in association with a luteinising hormone (LH) preparation. — Stimulation of spermatogenesis in gonadotrophin-deficient men in whom human chorionic gonadotrophin (hCG) alone is ineffective, with concomitant hCG therapy.

Dosing overview

Treatment should be initiated under the supervision of a physician experienced in the treatment of fertility disorders, and GONAL-F should be administered subcutaneously.

Key safety warnings

Mild to moderate uncomplicated ovarian enlargement occurs in approximately 20% of those treated with follitropin and hCG, and generally regresses without treatment within two or three weeks. In the presence of marked ovarian enlargement, treatment should be discontinued. Ovarian Hyperstimulation Syndrome (OHSS) is a condition that can manifest with increasing degrees of severity, comprising marked ovarian enlargement, high serum sex steroids and an increase in vascular permeability which can result in accumulation of fluid in the peritoneal, pleural and, rarely, in the pericardial cavities. OHSS can become a serious complication of human gonadotrophin therapy and sometimes leads to fatal complications if not adequately treated. Independent risk factors for developing OHSS include young age, lean body mass, polycystic ovarian syndrome, higher doses of exogenous gonadotrophins, high absolute or rapidly rising serum oestradiol levels and previous episodes of OHSS. Careful monitoring of ovarian response with ultrasound alone or preferably in combination with measurement of oestradiol levels is recommended prior to and during stimulation therapy, especially in patients with PCOS. Thromboembolic events, including thrombophlebitis, pulmonary embolism, stroke and arterial occlusion, have been reported following gonadotrophin therapy. In rare cases, thromboembolic events have resulted in death. In patients undergoing induction of ovulation, the incidence of multiple pregnancy is increased compared with natural conception. Multiple pregnancies, especially higher order, carry an increased risk of adverse maternal and perinatal outcomes. The patient should be advised of the potential risk of multiple births before starting treatment.

Contraindications

GONAL-F is contraindicated in cases of prior hypersensitivity to follitropin alfa, or to any excipients, and in tumours of the hypothalamus or pituitary gland. In women, FSH therapy is contraindicated where pregnancy and lactation exist, ovarian enlargement or ovarian cyst of unknown aetiology, gynaecological haemorrhages of unknown aetiology, or ovarian, uterine or breast carcinoma. FSH is contraindicated when an effective response cannot be obtained, such as in primary ovarian failure as indicated by high levels of FSH, malformations of sexual organs incompatible with pregnancy, or fibroid tumours of the uterus incompatible with pregnancy. In men, FSH is contraindicated with elevated gonadotrophin levels that indicate primary testicular failure or infertility disorders other than hypogonadotrophic hypogonadism.

PBS listing

GONAL-F is listed on the PBS in three strengths: 300 IU in 0.5 mL multi-dose cartridge, 450 IU in 0.75 mL multi-dose cartridge, and 900 IU in 1.5 mL multi-dose cartridge. All strengths have streamlined or restricted restrictions, with ex-manufacturer prices of A$86.42, A$129.63, and A$327.48 respectively.

Regulatory history

GONAL-F follitropin alfa was first registered on the ARTG on 20 March 2002 as a 1050 IU multidose powder for injection vial with diluent pre-filled syringe. Pre-filled pen formulations were registered from December 2003 onwards, including 300 IU/0.48 mL, 450 IU/0.72 mL, and 900 IU/1.44 mL cartridges. In March 2016, the PBAC recommended listing of follitropin alfa (Bemfola) as a biosimilar of follitropin alfa (Gonal-f) on a cost-minimisation basis for treatment of assisted reproduction, anovulatory infertility, and hypogonadotrophic hypogonadism.