BEMFOLA

What it is

Bemfola is follitropin alfa (rch) solution for injection cartridge in a pre-filled pen. Follitropin alfa (rch) is produced by a Chinese Hamster Ovary cell line transfected with the human FSH subunit genes by recombinant DNA technology. It is supplied as a solution for injection in a cartridge pre-assembled in a pen.

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 spermatogenesis in gonadotrophin-deficient men in whom hCG alone is ineffective, used with concomitant human chorionic gonadotrophin (hCG) therapy.

Dosing overview

Treatment with Bemfola should be initiated under the supervision of a physician experienced in the treatment of fertility disorders. Bemfola should be administered subcutaneously. For women with anovulatory infertility, a commonly used regimen commences at 75–150 IU daily and is increased by 37.5 IU up to 75 IU at 7- or 14-day intervals if necessary, to obtain an adequate but not excessive response. For women undergoing assisted reproductive technologies, a commonly used regimen involves the administration of 150 IU to 225 IU daily, commencing on days 2 or 3 of the cycle, continued until adequate follicular development has been achieved, with the dose adjusted according to the patient's response, usually not higher than 450 IU daily. For men with hypogonadotrophic hypogonadism, Bemfola should be given concomitantly with hCG at the dosage of 150 IU three times a week, and this regimen should be continued for a minimum of 4 months.

Key safety warnings

Bemfola is a potent gonadotrophic substance capable of causing mild to severe adverse reactions, and should only be used by physicians who are thoroughly familiar with infertility problems and their management. Safe and effective use of Bemfola in women calls for monitoring of ovarian response with ultrasound, alone or preferably in combination with measurement of serum oestradiol levels, on a regular basis. Mild to moderate uncomplicated ovarian enlargement, which may be accompanied by abdominal distension and/or abdominal pain, occurs in approximately 20% of those treated with follitropin and hCG, and generally regresses without treatment within two or three weeks. Patients undergoing superovulation are at an increased risk of developing Ovarian Hyperstimulation Syndrome (OHSS), a condition comprising marked ovarian enlargement, high serum sex steroids and an increase in vascular permeability which can result in an 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. Patients should be followed for at least two weeks after follitropin or hCG administration, and if there are any symptoms or signs of OHSS, the patient must be evaluated, investigated, and monitored. 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 women with recent or ongoing thromboembolic disease or women with generally recognised risk factors for thromboembolic events, treatment with gonadotrophins may further increase the risk for aggravation or occurrence of such events, and the benefits of gonadotrophin administration need to be weighed against the risks. In patients undergoing induction of ovulation, the incidence of multiple pregnancy is increased compared with natural conception, and 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

Bemfola is contraindicated in cases of prior hypersensitivity to follitropin alfa, or to any excipients of Bemfola, and in cases of tumours of the hypothalamus or pituitary gland. In women, it is contraindicated in pregnancy and lactation, ovarian enlargement or ovarian cyst of unknown aetiology, gynaecological haemorrhages of unknown aetiology, and ovarian, uterine or breast carcinoma. It is also contraindicated in women with primary ovarian failure as indicated by high levels of FSH, malformations of sexual organs incompatible with pregnancy, and fibroid tumours of the uterus incompatible with pregnancy. In men, it is contraindicated where elevated gonadotrophin levels indicate primary testicular failure and in infertility disorders other than hypogonadotrophic hypogonadism.

PBS listing

Bemfola is listed on the PBS in five strengths: 75 IU in 0.125 mL pre-filled pen at A$102.62 ex-manufacturer price with streamlined and restricted restrictions; 150 IU in 0.25 mL pre-filled pen at A$205.25 with streamlined and restricted restrictions; 225 IU in 0.375 mL pre-filled pen at A$307.87 with streamlined and restricted restrictions; 300 IU in 0.5 mL pre-filled pen at A$410.50 with streamlined restriction; and 450 IU in 0.75 mL pre-filled pen at A$615.74 with streamlined restriction.

Regulatory history

Bemfola was first listed on the ARTG on 27 November 2015 in five strengths (75 IU, 150 IU, 225 IU, 300 IU and 450 IU). The TGA approved Bemfola, concluding that the administrative, product usage, chemical, pharmaceutical, and microbiological data were satisfactory and supported registration. In March 2018, the PBAC recommended changes to the listing for assisted reproductive technology, anovulatory infertility, and infertility due to hypogonadotrophic hypogonadism, with addition of administrative advice to encourage prescribing of biosimilar brands.