GONAL-F
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GONAL-F (GONAL-F).
GONAL-F (follitropin alfa) is a recombinant human follicle-stimulating hormone (FSH) that binds to FSH receptors on ovarian granulosa cells and testicular Sertoli cells, stimulating follicular development and estrogen production in females and spermatogenesis in males.
| Metabolism | Metabolized via hepatic and renal pathways; exact enzymes not fully characterized. Clearance involves proteolytic degradation and renal excretion. |
| Excretion | Primarily renal (hepatic metabolism and biliary excretion are minor routes). Approximately 80% of the dose is excreted in urine, with less than 20% in feces. |
| Half-life | Terminal elimination half-life is approximately 24 hours (range 16–32 hours) following subcutaneous administration. This supports once-daily dosing. |
| Protein binding | Approximately 70–80% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.3–0.6 L/kg, indicating distribution primarily into extracellular fluid. |
| Bioavailability | Subcutaneous: approximately 70% (range 60–80%) relative to intravenous administration. |
| Onset of Action | Subcutaneous: After a single dose, serum estradiol levels begin to rise within 5–7 days, reflecting follicular recruitment and development. |
| Duration of Action | The pharmacodynamic effect (follicular stimulation) persists for up to 7–10 days after a single dose, consistent with once-daily or alternate-day dosing in controlled ovarian stimulation. |
Subcutaneous injection: 75-300 IU once daily for follicular stimulation; individualized based on response.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustments provided; use with caution in severe renal impairment (GFR <30 mL/min). |
| Liver impairment | No specific Child-Pugh based modifications; caution in severe hepatic impairment. |
| Pediatric use | Not indicated for use in children; no established pediatric dosing. |
| Geriatric use | Not indicated for use in elderly patients; no specific dosing recommendations. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GONAL-F (GONAL-F).
| Breastfeeding | It is not known whether follitropin alfa is excreted in human breast milk. Due to its protein nature and high molecular weight (approximately 30 kDa), transfer into milk is likely limited. However, because GONAL-F is typically used in fertility treatments and not during breastfeeding, no specific M/P ratio is available. Caution is advised if use is considered during lactation. |
| Teratogenic Risk | GONAL-F (follitropin alfa) is not indicated for use during pregnancy and has no direct fetal risk as it is administered for ovulation induction prior to conception. However, if inadvertent administration occurs during pregnancy, there is a potential risk of luteal phase defect and multiple gestation. Human data on fetal effects are limited; animal studies show no evidence of teratogenicity at clinically relevant doses. No consistent pattern of malformations has been reported. |
■ FDA Black Box Warning
GONAL-F should only be used by physicians experienced in fertility treatment. Ovarian hyperstimulation syndrome (OHSS) is a serious, potentially fatal complication. Patients should be monitored for signs of OHSS. GONAL-F may increase the risk of multiple gestation and pregnancy loss.
| Common Effects | Injection site allergic reaction Headache Acne Swelling of breast in male Abdominal pain Gastrointestinal discomfort Ovarian cysts Rash |
| Serious Effects |
["Hypersensitivity to follitropin alfa or any excipient","High levels of FSH indicating primary ovarian failure","Uncontrolled thyroid or adrenal dysfunction","Sex hormone-dependent tumors (e.g., ovarian, breast, uterine, pituitary)","Pregnancy and lactation","Ovarian cyst or enlargement of unknown origin"]
| Precautions | ["Ovarian hyperstimulation syndrome (OHSS): can progress to severe form with respiratory distress, oliguria, and thromboembolism","Ovarian torsion","Multiple pregnancy","Ectopic pregnancy","Pulmonary embolism","Ovarian neoplasia (rare)","Hypersensitivity reactions including anaphylaxis"] |
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| Fetal Monitoring | During treatment with GONAL-F, monitoring includes: serum estradiol levels and transvaginal ultrasound to assess follicular growth and prevent ovarian hyperstimulation syndrome (OHSS); assessment for multiple pregnancies; monitoring for ovarian enlargement, ascites, and thromboembolic events. During pregnancy after GONAL-F use, standard prenatal monitoring is recommended. |
| Fertility Effects | GONAL-F is used for ovulation induction and controlled ovarian hyperstimulation in assisted reproductive technologies. It increases the number of developing follicles, thereby enhancing fertility in women with anovulation or undergoing IVF. Overuse can lead to multiple follicle development and multiple gestation. There is no evidence of negative impact on future fertility. |