Follitropin Alfa

Follitropin Alfa is a recombinant human follicle-stimulating hormone (r-hFSH) indicated for use in reproductive medicine. Its approved and clinically accepted uses include:

Approved Indications:

• Female infertility due to anovulation: Including women with polycystic ovary syndrome (PCOS) who do not ovulate naturally.
• Assisted reproductive technologies (ART): Stimulation of follicular development in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).
• Hypogonadotropic hypogonadism in women: To induce ovulation and follicular development in patients with low or absent endogenous gonadotropins.
• Male infertility: Treatment of male hypogonadotropic hypogonadism to stimulate spermatogenesis in combination with human chorionic gonadotropin (hCG).

Off-label / Clinically Accepted Uses:

• Mild ovarian stimulation protocols in women undergoing ART.
• Adjunct therapy in controlled ovarian hyperstimulation cycles for donor egg programs.

Adults (Females):

• Ovulation induction in anovulatory women: Start 75–150 IU daily subcutaneously, adjusted based on ovarian response. Treatment continues until adequate follicular development is achieved.
• ART (IVF/ICSI) stimulation: Typical starting dose 150–225 IU daily subcutaneously, adjusted according to patient response; treatment duration usually 8–12 days.

Adults (Males):

• Hypogonadotropic hypogonadism: 75–150 IU subcutaneously 3 times per week in combination with hCG; duration 3–12 months until adequate spermatogenesis occurs.

Special Populations:

• Elderly: Not typically indicated in postmenopausal women.
• Renal or hepatic impairment: No dose adjustment required; use with clinical monitoring.

Administration Route:

• Subcutaneous injection (preferred) or intramuscular injection.
• Daily administration at the same time of day is recommended.

Follitropin Alfa is a recombinant form of human follicle-stimulating hormone (FSH), a glycoprotein hormone. It binds specifically to FSH receptors on ovarian granulosa cells in females and Sertoli cells in males. In women, receptor activation stimulates follicular growth, estrogen production, and maturation of oocytes. In men, it promotes Sertoli cell function and spermatogenesis. The hormone mimics the action of endogenous FSH, enhancing gamete development and supporting fertility.

• Absorption: Rapid subcutaneous absorption; peak serum concentrations in 12–24 hours post-injection.
• Bioavailability: Approximately 70–80% following subcutaneous administration.
• Distribution: Limited tissue distribution; primarily acts on gonadal target tissues.
• Metabolism: Cleared mainly by the kidneys; protein catabolism results in small peptide fragments.
• Half-life: 24–36 hours after subcutaneous injection.
• Excretion: Renal elimination of metabolites.

• Pregnancy: Not indicated for use in pregnancy; should be discontinued once pregnancy is confirmed. The drug is classified as Pregnancy Category X due to lack of necessity and potential risk during gestation.
• Lactation: Limited data; caution is advised. Minimal transfer into breast milk is expected, but use during breastfeeding is not recommended unless clinically justified.

• Primary Class: Gonadotropin
• Subclass: Recombinant human FSH (r-hFSH)

• Hypersensitivity to follitropin alfa or any component of the formulation.
• Primary ovarian failure or ovarian cysts not due to polycystic ovary syndrome.
• Uncontrolled thyroid or adrenal dysfunction.
• Tumors of the pituitary or hypothalamus.
• Pregnancy or active lactation (unless clinically indicated).

• Ovarian Hyperstimulation Syndrome (OHSS): High-risk patients include women with PCOS or previous OHSS episodes; monitor follicular development closely.
• Multiple pregnancy: Increased risk; adjust dosing to minimize multiple follicle development.
• Fluid retention and thromboembolic events: Rare but possible; monitor patients with cardiovascular risk factors.
• Injection-site reactions: Monitor for local inflammation or pain.
• Early discontinuation: Discontinue if excessive ovarian response or OHSS occurs.

Common:

• Headache, fatigue, mild injection-site reactions, abdominal discomfort.
• Breast tenderness, bloating, mood swings.

Serious / Rare:

• Ovarian Hyperstimulation Syndrome (OHSS): abdominal pain, rapid weight gain, ascites, dyspnea.
• Multiple gestations.
• Thromboembolic events (rare).

Timing & Severity:

• Most adverse effects occur during the stimulation phase; severity is dose-dependent.

• Gonadotropins and estrogen/progestin therapy: May alter ovarian response; adjust dosage carefully.
• Drugs affecting CYP450 metabolism: Minimal interactions, as follitropin alfa is a protein hormone not metabolized via CYP pathways.
• Alcohol: No significant interaction reported.
• Concurrent hCG therapy: Necessary for final oocyte maturation; dose and timing critical.

• Current ART guidelines recommend individualized dosing based on patient age, ovarian reserve, and AMH levels.
• Safety monitoring now emphasizes early detection of OHSS and minimization of multiple gestations.
• Recombinant FSH is preferred over urinary FSH for more predictable dosing and purity.
• Use in men continues to be limited to hypogonadotropic hypogonadism.

• Store refrigerated at 2°C to 8°C; do not freeze.
• Protect from light and heat.
• Keep vials in original packaging until use.
• Reconstituted solution should be used immediately; if needed, store for up to 24 hours at 2°C–8°C.
• Avoid vigorous shaking; gentle inversion recommended to dissolve powder.