FOLLISTIM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FOLLISTIM (FOLLISTIM).
Follistim (follitropin beta) is a recombinant follicle-stimulating hormone (FSH) that binds to FSH receptors on ovarian granulosa cells and testicular Sertoli cells, stimulating follicular development and steroidogenesis.
| Metabolism | Follitropin beta is metabolized primarily in the liver and kidneys via proteolytic degradation; no specific cytochrome P450 involvement. |
| Excretion | Primarily renal; approximately 70% of the dose is excreted unchanged in urine. A minor fraction (less than 5%) appears in feces via biliary elimination. The remainder is metabolized via hepatic pathways to inactive metabolites. |
| Half-life | The terminal elimination half-life ranges from 16 to 24 hours (mean ~19 hours) following subcutaneous administration. In patients with renal impairment, half-life may be prolonged, necessitating dose adjustment. |
| Protein binding | Approximately 45-50% bound, primarily to albumin and to a lesser extent to alpha-2-macroglobulin. |
| Volume of Distribution | Volume of distribution is approximately 0.3 L/kg (range 0.2-0.4 L/kg), consistent with distribution largely into extracellular fluid. |
| Bioavailability | Subcutaneous: Approximately 77% (compared to intravenous administration). Intramuscular: approximately 75%. Not available for other routes. |
| Onset of Action | Subcutaneous: Serum estradiol levels increase within 6-8 hours after a single dose. Follicular growth stimulation is detectable by ultrasound within 3-5 days of daily administration. |
| Duration of Action | After a single subcutaneous dose, follicular stimulation persists for approximately 24-36 hours. With daily dosing, continuous ovarian stimulation is maintained; the effect subsides within 2-3 days after last administration. |
Subcutaneous: 75-300 IU once daily for 7-21 days, adjusted based on response. Intramuscular: 75-150 IU once daily for 7-21 days.
| Dosage form | INJECTABLE |
| Renal impairment | No specific guidelines; use caution in severe impairment (eGFR <30 mL/min/1.73m²) due to limited data. |
| Liver impairment | No specific guidelines; use caution in severe hepatic impairment (Child-Pugh C) due to limited data. |
| Pediatric use | Not FDA-approved for pediatric use; off-label doses: 75-150 IU subcutaneously daily, weight-based titration (1.5-2.25 IU/kg/day) for adolescent males with hypogonadotropic hypogonadism. |
| Geriatric use | Not indicated for geriatric use; no dose adjustment recommended, but limited data in elderly >65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FOLLISTIM (FOLLISTIM).
| Breastfeeding | FOLLISTIM is not recommended for use during breastfeeding. It is not known whether follitropin beta is excreted in human milk. Given the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. No M/P ratio is available. |
| Teratogenic Risk | FOLLISTIM (follitropin beta) is classified as Pregnancy Category X. There is no indication for use during pregnancy. Animal studies have shown evidence of fetal abnormalities, and use is contraindicated in pregnant women. In the first trimester, exposure may cause fetal harm; however, no well-controlled studies exist. The drug is not used after conception, as its sole indication is for ovulation induction and controlled ovarian stimulation prior to assisted reproductive technologies. |
■ FDA Black Box Warning
Follistim should be used only by physicians experienced in infertility treatment. It may cause ovarian hyperstimulation syndrome (OHSS) and multiple gestations. Serious pulmonary and vascular events have been reported.
| Serious Effects |
Hypersensitivity to follitropin beta or any component. High levels of FSH indicating primary ovarian failure. Uncontrolled thyroid or adrenal dysfunction. Ovarian cyst or enlargement unrelated to PCOS. Pregnancy. Sex hormone-dependent tumors (e.g., ovarian, breast, uterine, pituitary). Abnormal genital bleeding of undetermined origin.
| Precautions | Ovarian hyperstimulation syndrome (OHSS) can be severe; monitor ovarian response. Risk of multiple gestation and ectopic pregnancy. Ovarian torsion and adnexal torsion reported. Thromboembolic events. Ovarian enlargement may occur. Patients with porphyria may exacerbate condition. |
Loading safety data…
| Fetal Monitoring | Monitoring includes: baseline transvaginal ultrasound for follicular count and endometrial thickness; serial serum estradiol levels during stimulation; ultrasound monitoring of follicular growth until criteria for hCG administration; monitoring for ovarian hyperstimulation syndrome (OHSS) including daily weight, abdominal girth, urine output, and hematocrit; beta-hCG for conception confirmation; if pregnancy occurs, early ultrasound for multiple gestations. |
| Fertility Effects | FOLLISTIM is a gonadotropin used to induce ovulation in anovulatory women and stimulate multifollicular development in ART. It directly stimulates ovarian follicular growth. Adverse effects on fertility are not intended; however, overstimulation can lead to OHSS. Multiple pregnancies are a known risk due to multifollicular development. |