Gonal-F75

Gonal-F is a recombinant human follicle-stimulating hormone (FSH) used in the management of infertility. Its uses are classified by strength of evidence below.

Established / FDA-approved indications

• Ovulation induction: Gonal-F is indicated for induction of ovulation and pregnancy in oligo-anovulatory infertile women in whom the cause of infertility is functional and not due to primary ovarian failure.
• Controlled ovarian stimulation for Assisted Reproductive Technology (ART): Gonal-F is indicated for development of multiple follicles in ovulatory infertile women participating in an ART program (e.g. in-vitro fertilisation, IVF).
• Male hypogonadotropic hypogonadism: Gonal-F, in combination with human chorionic gonadotropin (hCG), is indicated for the induction of spermatogenesis in men with primary or secondary hypogonadotropic hypogonadism in whom the cause is not primary testicular failure.

Adjunct / combination-therapy uses

• In ART cycles, Gonal-F is typically used together with a GnRH agonist or GnRH antagonist to prevent a premature LH surge, and with hCG or an LH-activity agent to trigger final oocyte maturation.
• In male hypogonadotropic hypogonadism, Gonal-F is used only after pretreatment with hCG alone has failed to achieve adequate response, and is always combined with continued hCG therapy.

Gonal-F is not indicated for use during pregnancy and is not a treatment for male or female infertility caused by primary gonadal failure.

Each formulation of Follitropin Alfa contains recombinant human follicle-stimulating hormone (r-hFSH) produced by recombinant DNA technology in a mammalian (Chinese Hamster Ovary) cell line. It is available as a lyophilised powder for reconstitution or as a pre-filled solution in a multi-dose injection pen, typically expressed in International Units (IU) of FSH activity per vial or cartridge (e.g. 75 IU, 300 IU, 450 IU, 900 IU strengths), along with standard excipients (e.g. sucrose, methionine, polysorbate 20, and a phosphate buffer) and, for the powder form, a bacteriostatic water diluent.

Gonal-F is a purified preparation of recombinant follicle-stimulating hormone (FSH), a gonadotropin that plays a central role in reproductive physiology. Unlike urinary-derived gonadotropins, Gonal-F is manufactured using recombinant DNA technology, giving it a highly consistent and predictable FSH content with negligible luteinising hormone (LH) activity. It is used under specialist supervision to stimulate ovarian follicular development in women undergoing fertility treatment and to stimulate spermatogenesis in men with certain forms of hypogonadism.

Gonal-F belongs to the therapeutic class of gonadotropins, specifically recombinant follicle-stimulating hormone (FSH) preparations used as fertility agents / ovulation-stimulating drugs.

Mechanism of action: Follitropin Alfa is biologically and structurally similar to endogenous pituitary FSH. It binds to FSH receptors on the surface of ovarian granulosa cells (in women) and Sertoli cells (in men), stimulating growth and maturation of ovarian follicles and, in men, supporting spermatogenesis when combined with hCG.

Pharmacokinetics: After subcutaneous injection, Follitropin Alfa is absorbed with a bioavailability of approximately 70%. Peak serum concentrations occur roughly 12-24 hours after dosing. It has a terminal half-life of about 24-30 hours after subcutaneous administration, supporting once-daily dosing, and is eliminated primarily via renal and hepatic pathways.

Gonal-F is given by subcutaneous injection, usually self-administered by the patient (or a caregiver) after appropriate training, typically in the abdomen or thigh, with injection sites rotated to reduce local irritation. Pre-filled pen presentations allow dose selection in small increments; powder formulations must be reconstituted (see Reconstitution) immediately before use and any unused reconstituted solution handled per the product's specific in-use storage instructions. Used needles and pen devices must be disposed of safely in a sharps container. Missed or mistimed doses should be discussed promptly with the treating physician, as timing is critical to cycle monitoring.

Formal drug-interaction studies with Gonal-F have not been conducted, but the following clinically relevant interactions are recognised:

• Clomiphene citrate: Concomitant use may enhance the follicular response to Gonal-F; this combination is used intentionally in some protocols under specialist supervision.
• GnRH agonists/antagonists: Co-administration (to prevent premature LH surge in ART cycles) may increase the ovarian dose of Gonal-F required to achieve an adequate follicular response.
• Other gonadotropin preparations (e.g. hCG, hMG): Used deliberately in combination as part of stimulation protocols; concurrent use of unrelated hormonal fertility agents outside a supervised protocol is not recommended.

Patients should inform their physician of all medicines, supplements, and hormonal products being used before starting Gonal-F.

The most common adverse effects reported with Gonal-F differ by sex and treatment context.

In women

• Headache, nausea, abdominal or pelvic pain, bloating
• Ovarian cyst formation, injection-site reactions (pain, redness, bruising)
• Ovarian hyperstimulation syndrome (OHSS) - see Precautions and Warnings for details
• Intermenstrual bleeding, breast tenderness

In men

• Acne, injection-site pain, fatigue
• Gynecomastia (breast enlargement), seborrhea

Serious but less common effects include thromboembolic events and ovarian torsion; patients should seek urgent medical attention for severe abdominal pain, breathlessness, leg swelling, or rapid weight gain.

Pregnancy: Gonal-F is contraindicated once pregnancy is confirmed; it has no indication for use during an established pregnancy and should be discontinued as soon as pregnancy is diagnosed. Use only under specialist supervision as part of a fertility treatment cycle, since ART pregnancies carry a somewhat increased risk of multiple gestation and, potentially, congenital malformations related to underlying parental infertility factors and multiple pregnancy rather than the drug itself; consult a physician for individualised risk assessment.

Lactation: Women are generally advised not to breastfeed during treatment with Gonal-F, as the physiological increase in prolactin associated with breastfeeding may interfere with the ovarian response to treatment. Discuss feeding plans with the treating physician if fertility treatment is being considered while breastfeeding.

Ovarian Hyperstimulation Syndrome (OHSS): Gonal-F can cause OHSS, a potentially life-threatening condition marked by a rapid increase in vascular permeability, leading to fluid accumulation in the abdomen/chest, electrolyte disturbance, and thromboembolism. Close monitoring with serial ultrasound and serum estradiol measurements during stimulation is required, and treatment should be withheld or adjusted if excessive ovarian response is detected.

Multiple pregnancy: Both ovulation induction and ART cycles with Gonal-F carry a substantially increased risk of multiple gestation (twins or more), which carries added maternal and perinatal risk; careful dose titration and cycle monitoring aim to reduce this risk.

Thromboembolism: Serious venous and arterial thromboembolic events, including pulmonary embolism and stroke, have been reported in association with gonadotropin therapy, particularly in the presence of OHSS or other risk factors.

Ovarian torsion: Enlarged ovaries following Gonal-F treatment may predispose to ovarian torsion, a surgical emergency.

Specialist monitoring required: Gonal-F should be used only by physicians experienced in fertility treatment, with access to ultrasound and hormonal (estradiol) monitoring facilities throughout the treatment cycle.

Pulmonary and allergic reactions: Rare hypersensitivity reactions can occur; discontinue and seek medical care if signs of a severe allergic reaction develop.

Overdosage with Gonal-F is primarily associated with an increased risk of ovarian hyperstimulation syndrome (OHSS) and multiple gestation in women. There is no specific antidote. If overdose is suspected, seek immediate medical attention or contact emergency services / a poison control centre; the patient should be monitored closely by the treating fertility specialist, with supportive care (fluid/electrolyte management, monitoring for OHSS) provided as clinically indicated.

Store Gonal-F under refrigeration at 2°C to 8°C (36°F to 46°F); some presentations may alternatively be stored at room temperature (up to 25°C) for a limited, product-specific period - check the specific product's package insert. Do not freeze. Keep the vial, cartridge, or pen in the outer carton to protect from light. After reconstitution (powder formulations), use within the timeframe stated on the product labeling (commonly up to 28 days when refrigerated) and discard any unused solution thereafter. Keep out of reach of children.

Renal/hepatic impairment: Gonal-F has not been formally studied in patients with renal or hepatic impairment; use with caution and under specialist supervision if such impairment is present.

Elderly: Gonal-F is used exclusively in patients of reproductive age (women undergoing ovarian stimulation, men with hypogonadotropic hypogonadism) and has no established use in elderly populations.

Pediatric use: Safety and effectiveness of Gonal-F in pediatric patients have not been established; it is not indicated for use in children.

Duration varies by indication. For ovulation induction, a treatment course of up to 14 days is typical, extendable in adjusted increments; if there is no adequate ovarian response after approximately 4-5 weeks, that cycle is usually abandoned and reassessed. For ART/IVF controlled ovarian stimulation, treatment usually lasts 8-12 days until follicles reach the target size for triggering final maturation. For male hypogonadotropic hypogonadism, therapy is prolonged, generally continued for a minimum of 3-4 months (and sometimes up to 18 months) to assess spermatogenic response, following an initial 3-6 month course of hCG pretreatment.

Powder formulations of Gonal-F must be reconstituted immediately before use with the accompanying diluent (typically bacteriostatic water for injection). Gently swirl (do not shake) the vial until the powder is fully dissolved into a clear, colourless solution; discard the solution if it is discoloured or contains particulate matter. Use the reconstituted solution promptly, or store as directed on the product labeling (commonly refrigerated, for use within 28 days) if multiple doses are to be drawn from one vial. Pre-filled pen/cartridge presentations of Gonal-F do not require reconstitution and are ready to use after priming per the device instructions.

Follitropin Alfa is classified under: Gonadotropins; Recombinant human follicle-stimulating hormone (r-hFSH); Fertility / ovulation-stimulating agents; Hormones and related agents used in assisted reproduction.

Follitropin Alfa acts as an exogenous source of follicle-stimulating hormone (FSH). It binds specifically to FSH receptors on ovarian granulosa cells, promoting recruitment, growth, and maturation of ovarian follicles and stimulating estradiol production. In men, it binds FSH receptors on testicular Sertoli cells, supporting spermatogenesis when used together with hCG (which provides LH-like activity to support testosterone production by Leydig cells). Because it is produced by recombinant DNA technology, Follitropin Alfa has minimal LH activity and a highly consistent, batch-to-batch reproducible FSH potency.

X

Gonal-F is not indicated for use in pediatric patients. Safety and efficacy in children and adolescents have not been established, and the drug's approved indications (ovulation induction, ART cycle stimulation, male hypogonadotropic hypogonadism) apply only to adults of reproductive age under specialist fertility care.