BRAVELLE
Clinical safety rating
cautionComprehensive clinical and safety monograph for BRAVELLE (BRAVELLE).
Comprehensive clinical and safety monograph for BRAVELLE (BRAVELLE).
Ovulation induction in anovulatory women with polycystic ovary syndrome (PCOS)Controlled ovarian hyperstimulation for assisted reproductive technologies (ART) such as in vitro fertilization (IVF)
Bravelle (urofollitropin) is a purified preparation of follicle-stimulating hormone (FSH) that stimulates ovarian follicular growth and maturation by binding to FSH receptors on granulosa cells, increasing cAMP production and promoting follicular development.
| Metabolism | Primarily metabolized in the liver via renal excretion; metabolic pathways not fully characterized. |
| Excretion | Primarily renal: 95% of administered dose excreted unchanged in urine within 24 hours. Biliary/fecal: 5% eliminated via feces. |
| Half-life | Terminal elimination half-life approximately 5-6 hours in healthy adults. Extended in renal impairment (up to 24 hours with CrCl <30 mL/min). |
| Protein binding | Approximately 10-20% bound to plasma proteins (albumin and α-1 acid glycoprotein). |
| Volume of Distribution | Approximately 0.3-0.5 L/kg. Distributing primarily in extracellular fluid; does not extensively penetrate tissues. |
| Bioavailability | Subcutaneous: 90-95% bioavailable relative to intramuscular route. Oral: not clinically used due to enzymatic degradation. |
| Onset of Action | Subcutaneous: Serum FSH peaks 4-6 hours post-dose. Ovarian response detectable within 5-7 days of daily administration. |
| Duration of Action | Following single dose, serum FSH levels decline with half-life of ~5-6 hours. Clinical monitoring and dosing interval every 24 hours to maintain steady-state for follicular growth. |
| Molecular Weight | 17000 |
For ovulation induction: 150 IU subcutaneously or intramuscularly once daily for 5 days, starting on day 3 or 5 of menstrual cycle. For controlled ovarian hyperstimulation: 150-225 IU subcutaneously or intramuscularly once daily for 5-7 days, then adjust based on response.
| Dosage form | Injectable |
| Renal impairment | No specific guidelines exist for GFR-based dose modifications; use with caution in severe renal impairment (CrCl <30 mL/min) and monitor for adverse effects. |
| Liver impairment | No specific guidelines exist for Child-Pugh based modifications; use with caution in severe hepatic impairment and monitor for adverse effects. |
| 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 | May be used for controlled ovarian stimulation; pregnancy rates similar to natural cycles. No known teratogenicity from gonadotropins alone. |
| 2nd trimester | Not typically administered during established pregnancy; no specific fetal risks identified. |
| 3rd trimester | Not indicated during third trimester; potential for ovarian hyperstimulation syndrome if mistakenly given. |
Clinical note
Comprehensive clinical and safety monograph for BRAVELLE (BRAVELLE).
| Placental transfer | Unlikely to cross placenta significantly due to high molecular weight; no evidence of fetal harm in human data. |
| Breastfeeding | Excretion into breast milk is unknown; due to high molecular weight and protein nature, absorption by infant is unlikely. Use with caution, weighing benefits vs risks. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category X. Urofollitropin is contraindicated in pregnant women due to risk of fetal harm. First trimester: Ovarian hyperstimulation syndrome (OHSS) and multiple gestations. Second and third trimesters: No direct fetal effects reported, but risks associated with multiple gestation (preterm birth, low birth weight). Maternal OHSS may lead to thromboembolism. |
| Fetal Monitoring | Monitor ovarian response via ultrasound and serum estradiol levels every 1-3 days during stimulation. Assess for OHSS symptoms (abdominal pain, distension, nausea). In pregnancy, monitor for multiple gestation and congenital anomalies. Baseline and periodic assessment of thyroid and adrenal function due to potential for FSH-induced effects. |
| Fertility Effects | Induces follicular growth and maturation in anovulatory patients. Increases risk of multiple gestation, ovarian enlargement, and OHSS. No known adverse effects on subsequent fertility beyond cycle-specific risks. Not recommended for use in patients with primary ovarian insufficiency. |
■ FDA Black Box Warning
Bravelle should only be used by physicians who are experienced in infertility treatment and can manage potential serious adverse events, including ovarian hyperstimulation syndrome (OHSS) and multiple gestations.
| Serious Effects |
Hypersensitivity to urofollitropin or excipientsOvarian enlargement or cyst not due to polycystic ovary syndromeGynecological hemorrhage of unknown etiologyOvarian, uterine, or breast cancerPrimary ovarian failureUncontrolled thyroid or adrenal dysfunctionPregnancy
| Precautions | Ovarian enlargement and ovarian hyperstimulation syndrome (OHSS) – can lead to serious complications; discontinue treatment if OHSS is suspected., Multiple gestations – increased risk of multiple births., Ovarian torsion – report sudden abdominal pain., Pulmonary and vascular complications – thromboembolic events; discontinue if suspected., Ectopic pregnancy and spontaneous abortion – higher rates in ART patients., Neoplasms – risk of ovarian neoplasms with repeated use. |
| Food/Dietary | No known food interactions. Maintain normal diet and hydration. Avoid alcohol as it may exacerbate side effects like nausea. |
| Clinical Pearls | BRAVELLE (urofollitropin) is a purified FSH product used for controlled ovarian hyperstimulation. Administer subcutaneously; rotate injection sites. Monitor estradiol levels and follicle growth via ultrasound. Risk of ovarian hyperstimulation syndrome (OHSS); consider using GnRH antagonist protocols to reduce risk. Do not administer if patient has high baseline FSH levels (>15 IU/L) indicating poor ovarian reserve. |
| Patient Advice | Teach proper injection technique and site rotation (abdomen, thigh). · Report immediately if severe pelvic pain, nausea, vomiting, or rapid weight gain occurs (OHSS signs). · Avoid intercourse until instructed to prevent multiple pregnancy. · Inform of multiple pregnancy risk (especially twins). · Store vials in refrigerator (2-8°C) and protect from light. |
Loading safety data…