GONAL-F RFF
Clinical safety rating
cautionComprehensive clinical and safety monograph for GONAL-F RFF (GONAL-F RFF).
Comprehensive clinical and safety monograph for GONAL-F RFF (GONAL-F RFF).
Induction of ovulation in anovulatory womenControlled ovarian hyperstimulation for assisted reproductive technologiesSpermatogenesis induction in hypogonadotropic hypogonadism (with hCG)
Recombinant human follicle-stimulating hormone (FSH) that binds to FSH receptors on ovarian granulosa cells and testicular Sertoli cells, stimulating follicular growth and maturation and spermatogenesis.
| Metabolism | Primarily hepatic via proteolytic degradation and renal clearance |
| Excretion | Renal excretion: approximately 70% of the dose is eliminated in urine as intact hormone and metabolites; fecal excretion is negligible (<5%). |
| Half-life | Terminal elimination half-life: approximately 24-30 hours (range 24-36 h) following subcutaneous administration; supports once-daily dosing regimen. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Volume of distribution: 6-10 L/kg, indicating extensive distribution into extracellular fluid and tissues (e.g., ovaries). |
| Bioavailability | Subcutaneous: approximately 70-80% (relative to intravenous administration); intramuscular: 100% (absolute bioavailability for Gonal-f RFF not explicitly reported, but similar to follitropin alfa). |
| Onset of Action | Subcutaneous: follicular growth (increase in estradiol levels) detectable within 24-48 hours; maximal response occurs after 5-7 days of daily dosing. |
| Duration of Action | Subcutaneous: effects on follicular development persist for up to 7-10 days after discontinuation; daily dosing required to maintain steady-state concentrations. |
| Molecular Weight | 34000 |
Subcutaneous injection, initially 75-150 IU once daily for 5-7 days for ovulation induction. For controlled ovarian hyperstimulation, 75-300 IU once daily starting day 2 or 3 of cycle. Dose adjusted based on response.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment provided by manufacturer. GFR <30 mL/min: use with caution due to limited data. |
| Liver impairment | No specific dose adjustment provided by manufacturer. Child-Pugh Class C: use with caution; no established guidelines. |
| Pediatric use | Not indicated for use in pediatric patients. Safety and efficacy not established. |
| Geriatric use | Not indicated for use in geriatric patients. Safety and efficacy not established. |
| 1st trimester | Follitropin alfa is contraindicated in pregnancy. Not indicated for use during pregnancy; has no established role in treatment of infertility during first trimester. |
| 2nd trimester | Contraindicated in pregnancy. No data in second trimester; fetal exposure unlikely as drug is used only for ovulation induction. |
| 3rd trimester | Contraindicated in pregnancy. No data in third trimester. |
Clinical note
Comprehensive clinical and safety monograph for GONAL-F RFF (GONAL-F RFF).
| Placental transfer | Follitropin alfa is a large glycoprotein (~34 kDa) and is not expected to cross the placenta to a significant extent. However, no formal studies have been conducted. |
| Breastfeeding | It is not known whether follitropin alfa is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GONAL-F RFF is administered to a nursing woman. However, the drug is not indicated for use during breastfeeding and is unlikely to reach significant levels due to its protein nature. |
| Lactation Rating | L3 (Moderately Safe) - No controlled studies in breastfeeding women; potential for infant risk exists. |
| Teratogenic Risk | Fetal risk cannot be ruled out. Category X: contraindicated in pregnancy due to risk of multiple gestation and ectopic pregnancy; no systematic evidence of teratogenicity but animal studies show post-implantation loss and fetal abnormalities at high doses. |
| Fetal Monitoring | Monitor ovarian response via ultrasound and serum estradiol levels; assess for ovarian hyperstimulation syndrome (OHSS); monitor progesterone levels for luteal support. |
| Fertility Effects | Induces ovulation and follicular development; risk of multiple gestation; may cause ovarian hyperstimulation syndrome; utilized in assisted reproductive technology. |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancyHigh levels of FSH indicating primary gonadal failureUncontrolled thyroid or adrenal dysfunctionPresence of hormone-dependent tumors (e.g., ovarian, breast, uterine)Ovarian cysts or enlargement of unknown originHypersensitivity to follitropin alfa or any excipients
| Precautions | Ovarian hyperstimulation syndrome (OHSS), Ovarian torsion, Multiple pregnancy, Pulmonary embolism and thromboembolic events, Ovarian enlargement, Ectopic pregnancy, Congenital malformations (risk similar to general population) |
| Food/Dietary | No significant food interactions. Maintain a balanced diet; avoid excessive alcohol intake as it may impair fertility. Caffeine in moderation (≤200 mg/day) is generally acceptable, but discuss with your healthcare provider. |
| Clinical Pearls | GONAL-F RFF (follitropin alfa) is a recombinant follicle-stimulating hormone (FSH) used for ovulation induction and controlled ovarian hyperstimulation. Administer subcutaneously; rotate injection sites to prevent lipodystrophy. Adjust dose based on ovarian response monitoring (ultrasound and estradiol levels). Risk of ovarian hyperstimulation syndrome (OHSS) requires vigilance; withhold hCG if estradiol >3000 pg/mL or >20 follicles ≥14 mm. Use with GnRH agonist or antagonist to prevent premature LH surge. Prefilled syringe ensures accurate dosing; do not mix with other drugs. Store refrigerated, but may be stored at room temperature (≤25°C) for up to 28 days. |
| Patient Advice | Inject exactly as prescribed, preferably at the same time daily. · Rotate injection sites (abdomen, thigh) to avoid lumps or pain. · Do not skip doses; contact your doctor if you miss a dose. · Report symptoms of OHSS: severe pelvic pain, bloating, nausea, rapid weight gain, or decreased urination. · Avoid pregnancy tests until instructed, as the medication may cause false results. · Store unopened vials in the refrigerator. Once opened, use within 28 days if kept at room temperature. |
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