GONAL-F
Clinical safety rating
cautionComprehensive clinical and safety monograph for GONAL-F (GONAL-F).
Comprehensive clinical and safety monograph for GONAL-F (GONAL-F).
Induction of ovulation in anovulatory women with polycystic ovary syndrome (PCOS)Controlled ovarian stimulation for assisted reproductive technologies (ART) such as in vitro fertilization (IVF)Induction of spermatogenesis in men with hypogonadotropic hypogonadism
Injection site allergic reaction Headache Acne Swelling of breast in male Abdominal pain Gastrointestinal discomfort Ovarian cysts Rash
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. |
| Molecular Weight | 17000 |
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 | Contraindicated. Risk of fetal harm based on animal studies and potential for teratogenic effects. |
| 2nd trimester | Contraindicated. Cases of fetal abnormalities reported; use only if clearly needed for maternal condition. |
| 3rd trimester | Limited data; avoid unless maternal benefit outweighs risk. Potential for hormonal effects on fetus. |
Clinical note
Comprehensive clinical and safety monograph for GONAL-F (GONAL-F).
| Placental transfer | Follitropin alfa is a large glycoprotein (MW ~17 kDa); placental transfer is expected to be limited but has been demonstrated in animal studies at high doses. |
| Breastfeeding | Excretion into human milk unknown; due to protein nature and low oral bioavailability, risk to infant is likely minimal. However, use with caution. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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 excipientsPregnancyOvarian, uterine, or breast cancerActive thyroid or adrenal dysfunctionHigh FSH levels indicating primary ovarian failureSex hormone-dependent tumorsUncontrolled thyroid or adrenal disorders
| 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 |
| Food/Dietary | No specific food interactions. Maintain adequate hydration to reduce OHSS risk. |
| Clinical Pearls | GONAL-F (follitropin alfa) is a recombinant FSH used for ovulation induction and controlled ovarian stimulation. Monitor estradiol levels and follicle growth via ultrasound to adjust dosing and reduce OHSS risk. Use the lowest effective dose. Do not administer if ovarian cyst or enlargement is present. LH supplementation may be needed in hypogonadotropic hypogonadism. |
| Patient Advice | Inject subcutaneously as directed; rotate injection sites to avoid lipodystrophy. · Report severe pelvic pain, nausea, weight gain, or shortness of breath immediately (OHSS symptoms). · Missed doses can affect cycle; do not double dose without consulting healthcare provider. · Store vials in refrigerator (2-8°C) before mixing; after mixing, use immediately or store refrigerated for up to 28 days. · Avoid pregnancy tests until instructed; false positives may occur from hCG trigger. |
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