urofollitropin [IM/SC]

Adult Dosing

Ovulation Induction

Patients who have received gonadotropin-releasing hormone (GnRH) agonist or antagonist pituitary suppression

Start 150 IU/day SC/IM x 5 days. Then adjust dose no more than 75-150 IU/day q2 days
Max: 450 IU/day and 12 days
If appropriate response, give hCG 5000-10,000 IU 1 day following the last dose of urofollitropin. Withhold hCG if serum estradiol >2000 pg/mL
Closely monitor patients for 2 wks after hCG administration; if inadequate follicle development or ovulation without subsequent pregnancy, repeat course of treatment

Assisted reproductive technology

Patients undergoing in vitro fertilization and donor egg patients who have received GnRH agonist or antagonist pituitary suppression

Start 225 IU/day SC x 5 days. Then adjust dose no more than 75-150 IU/day q2 days
Max: 450 IU/day and 12 days
If adequate follicular development is evident, give hCG 5000 to 10,000. Withhold hCG administration in cases where ovaries are abnormally enlarged on the last day of therapy to reduce the chance of developing OHSS

Pediatric Dosing

Safety and effectiveness in pediatric patients have not been established

[Outline]

Adult Dosing
Pediatric Dosing

Indications ⬆ ⬇

In conjunction with human chorionic gonadotropin (hCG), for ovulation induction in patients who have previously received pituitary suppression
In conjunction with hCG, for multiple follicular development (controlled ovarian stimulation) during assisted reproductive technologies (ART) cycles in patients who have previously received pituitary suppression

Contraindications ⬆ ⬇

Known hypersensitivity to urofollitropin
Women with high FSH levels (primary ovarian failure)
Uncontrolled thyroid and adrenal function impairment
Organic intracranial lesion (eg, pituitary tumor)
Presence of any cause of infertility other than anovulation
Abnormal bleeding of undetermined origin
Ovarian cysts or enlargement (not due to polycystic ovary syndrome)
Sex hormone dependent tumors of the reproductive
Pregnancy

Black Box Warnings ⬆ ⬇

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Renal impairment: Dose adjustments not defined

Hepatic Dose Adjustment

Hepatic impairment: Dose adjustments not defined

Warnings/Precautions ⬆ ⬇

Urofollitropin should only be used by physicians who are thoroughly familiar with infertility problems and their management
A thorough gynecologic and endocrinologic evaluation must be performed before enrolling patients for therapy. Investigations include: Hysterosalpingography (to rule out uterine and tubal pathology), documentation of anovulation by means of basal body temperature, serial vaginal smears, examination of cervical mucus, serum progesterone, urinary pregnanediol and endometrial biopsy
Mild to moderate uncomplicated ovarian enlargement may occur in approximately 20% of women treated with follitropin and hCG and generally regresses w/out tx within 2-3 wks
Ovarian Hyperstimulation Syndrome(OHSS) with/without pulmonary and vascular complications may occur in patients receiving urofollitropin alone or in combination with other gonadotropins. Warning signs include difficulty breathing, severe pelvic pain, nausea, vomiting, rapid weight gain, stomach pain or bloating, diarrhea, or infrequent urination. May progress within 24 hrs to several days to become a serious medical event; discontinue and hospitalize patient in severe OHSS
Ovarian torsion has been reported after treatment with gonadotropins. This may be related to OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst and polycystic ovaries
Multi-fetal gestation and births have been reported with all gonadotropin therapy including therapy with urofollitropin
Since infertile women undergoing ART often have tubal abnormalities, the incidence of ectopic pregnancy may be increased. Early confirmation of intrauterine pregnancy should be determined by beta-hCG testing and transvaginal ultrasound
Increased risk of spontaneous abortion has been reported with therapy
Severe cases of atelectasis, ARDS, have occurred. In addition, thromboembolic events both in association with, and separate from, the Ovarian Hyperstimulation Syndrome have been reported; risk of VTE, PE, pulmonary infarction, CVA, peripheral artery occlusion
Multiple pregnancies have occurred following treatment with urofollitropin SC and IM
Hypersensitivity reactions, manifesting as generalized urticaria, facial edema, angioneurotic edema, and/or dyspnea, have occurred with administration of follitropins

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category:X

Breastfeeding: Safety unknown. Manufacturer recommends discontinuation of breastfeeding, or discontinuation of treatment (taking into account the importance of the drug to the mother).

Adverse Reactions ⬆ ⬇

GU: Vaginal hemorrhage, ovarian pain/cyst, post retrieval pain, pelvic cramps, uterine spasms, vaginal spotting/discharge, breast tenderness, fungal infections, UTI, hot flashes, cervix disorder
REPRODUCTIVE: Spontaneous abortion, ectopic pregnancy, multiple pregnancy, OHSS,
GI: Nausea, abdominal fullness/enlargement, abdominal pain, abdominal cramps, constipation, vomiting, diarrhea
METABOLISM: Dehydration, weight gain
CV: Hypertension
CNS: Headache, emotional lability, depression
DERM: Acne, rash, exfoliative dermatitis
RESP: Respiratory disorder, sinusitis, thromboembolism, pulmonary complications
LOCAL: Injection site reaction
MISC: Anaphylactoid reactions, pain, neck pain, fever, accidental injury, anaphylactic reactions

Clinical Pharmacology ⬆ ⬇

Gonadotropin; stimulates ovarian follicular growth in women who do not have primary ovarian failure
Metabolism: Unknown
Excretion: Unknown
Half-life:

Single dose

SC: 31.8 hrs
IM: 37 hrs

Multiple dose

SC: 20.6 hrs
IM: 15.2 hrs

Brands and Availability ⬆ ⬇

US Trade Name(s)

Bravelle

US Availability

Bravelle

INJ: 75 IU/vial

Canadian Trade Name(s)

Bravelle

Canadian Availability

Bravelle

INJ: 75 U/vial

UK Trade Name(s)

Fostimon

UK Availability

Fostimon

INJ: 75 U/vial
INJ: 150 U/vial

Australian Trade Name(s)

Australian Availability