Dosing and uses of Bravelle, Fertinorm HP (urofollitropin)
Ovulation Induction
Initial: 150 International units IM/SC qDay x 5 days
Titrate by 75-150 International units qODay
Maximum dose 450 International units, maximum time 12 days
If patient's response satisfactory, administer hCG one day following the last dose of follitropin
ART (Assisted Reproductive Technology)
Begin on cycle day 2 or 3
Initial dose for women who have received a GnRH agonist for pituitary suppression is 225 IU SC qDay
May be coadministered with menotropins (Menopur), and the total initial dose when the products are combined should not exceed 225 IU (ie, urofollitropin 150 IU and menotropins 75 IU OR urofollitropin 75 IU and menotropins 150 IU)
In most cases, therapy should not exceed 12 days
Consider adjusting the dose after 5 days based on ovarian response, as determined by ultrasound evaluation of follicular growth and serum estradiol levels
Do not make additional dosage adjustments more frequently than q2days or by >75 -150 IU at each adjustment
Continue treatment until adequate follicular development is evident, and then administer hCg
Withhold hCG in cases where the ovarian monitoring suggests an increased risk of ovarian hyperstimulation syndrome on the last day of urofollitropin therapy
Do not administer daily doses of urofollitropin or urofollitropin in combination with menotropins that exceed 450 IU
Spermatogenesis
Pretreat with hCG until serum testosterone is in normal range
Administer 150 units follitropin 3 times/week with hCG 3 times/week
Continue with lowest dose needed to stimulate spermatogenesis; not to exceed 300 units 3 times/week; may administer for up to 18 months
Pediatric dosage forms and strengths
Safety and efficacy not established
Bravelle, Fertinorm HP (urofollitropin) adverse (side) effects
>10%
Headache (11.1%)
OHSS (11.1%; severe pelvic pain, N/V, weight gain)
Frequency not defined
Hypertension
Ovarian enlargement
Abdominal cramps
Depression
Emotional lability
Fever
Pain
Breast tenderness
Hot flashes
Ovarian disorder (cyst, pain)
Abdomen enlarged
Abdominal pain
Nausea/vomiting
Weight gain
Uterine spasms
Vaginal discharge/hemorrhage/spotting
Injection site reaction
Postretrieval pain
Postmarketing Reports
Atelectasis
ARDs
Thromboembolic events
Anaphylaxis
Following pregnancy: spontaneous abortion, ectopic pregnancy, premature labor, postpartum fever, congenital abnormalities
Warnings
Contraindications
Pregnancy; may cause fetal harm
Hypersensitivity
High levels of FSH indicating primary ovarian failure
Presence of uncontrolled nongonadal endocrinopathies (eg, thyroid, adrenal, or pituitary disorders)
Sex hormone dependent tumors of the reproductive tract and accessory organ
Tumors of pituitary gland or hypothalamus
Abnormal uterine bleeding of undetermined origin
Ovarian cysts or enlargement of undetermined origin, not due to polycystic ovary syndrome
Cautions
Should be administered only by physicians thoroughly experienced in fertility disorders
Hypersensitivity/anaphylactic reactions reported
Ovarian hyperstimulation syndrome (OHSS) reported; OHSS is a medical event distinct from uncomplicated ovarian enlargement and may progress rapidly to become a serious medical event; characterized by dramatic increase in vascular permeability, which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium
Use lowest effect dose to minimize abnormal ovarian enlargement; if ovaries are enlarged on last day of therapy, do not administer hCG because of risk for OHSs
May cause pulmonary and vascular complications (eg, atelectasis, ARDS)
Ovarian torsion has been reported after treatment with gonadotropins
Multi-fetal gestation and births have been reported with all gonadotropin therapy
Incidence of congenital malformations after some ART (specifically IVF or ICSI) may be slightly higher than after spontaneous conception (likely due to parental characteristics)
Since infertile women undergoing ART often have tubal abnormalities, the incidence of ectopic pregnancy may be increased
Increased incidence of spontaneous abortion and ovarian neoplasms observed (without causality)
Pregnancy and lactation
Pregnancy category: X
Lactation: Not known if excreted in breast milk, avoid using in breast-feeding women
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Bravelle, Fertinorm HP (urofollitropin)
Mechanism of action
Human FSH (obtained from urine of postmenopausal women); stimulates ovarian follicular growth in women with no primary ovarian failure
FSH is responsible for normal follicular growth, gonadal steroid production, spermatogenesis, and follicular maturation
Pharmacokinetics
Half-life: 32-37 hr (single dose regimen); 15.2-20.6 hr (multi-dose regimen)
Peak plasma: 17.4-20.5 hr (single dose regimen); 9.6-11.3 hr (multi-dose regimen)
Vd: 4.4 and 75.9 L
Clearance: Renal: 0.57 ml/min
