Ovulation Induction

Bravelle® (urofollitropin injection) administered SC or IM in conjunction with hCG, is indicated for ovulation induction in patients who have previously received pituitary suppression.

Multifollicular Development during ART

Bravelle® (urofollitropin injection) administered SC in conjunction with hCG is indicated for multiple follicular development (controlled ovarian stimulation) during ART cycles in patients who have previously received pituitary suppression.

Selection of Patients

1. Before treatment with Bravelle® (urofollitropin injection) is instituted, a thorough gynecologic and endocrinologic evaluation must be performed. Except for those patients enrolled in an in vitro fertilization program, this should include a hys-terosalpingography (to rule out uterine and tubal pathology) and documentation of anovulation by means of basal body temperature, serial vaginal smears, examination of cervical mucus, determination of serum (or urine) progesterone, urinary pregnanediol and endometrial biopsy. Patients with tubal pathology should receive Bravelle® (urofollitropin injection) only if enrolled in an in vitro fertilization program.
2. Primary ovarian failure should be excluded by the determination of gonadotropin levels.
3. Careful examination should be made to rule out the presence of an early pregnancy.
4. Patients in late reproductive life have a greater predilection to endometrial carcinoma as well as a higher incidence of anovulatory disorders. Cervical dilation and curettage should always be done for diagnosis before starting Bravelle® (urofollitropin injection) therapy in such patients who demonstrate abnormal uterine bleeding or other signs of endometrial abnormalities.
5. Evaluation of the husband's fertility potential should be included in the workup.

Dosage:

Infertile patients with oligo-anovulation: The dose of Bravelle® (urofollitropin injection) to stimulate development of ovarian follicles must be individualized for each patient. The lowest dose consistent with achieving good results based on clinical experience and reported clinical data should be used.

The recommended initial dose of Bravelle® (urofollitropin injection) for patients who have received GnRH agonist or antagonist pituitary suppression is 150 IU daily administered SC or IM for the first 5 days of treatment. Based on clinical monitoring (including serum estradiol levels and vaginal ultrasound results) subsequent dosing should be adjusted according to individual patient response. Adjustments in dose should not be made more frequently than once every 2 days and should not exceed more than 75 to 150 IU per adjustment. The maximum daily dose of Bravelle® (urofollitropin injection) should not exceed 450 IU and in most cases dosing beyond 12 days is not recommended.

If patient response to Bravelle® (urofollitropin injection) is appropriate, hCG (5000 to 10,000 USP units) should be given 1 day following the last dose of Bravelle® (urofollitropin injection) . The hCG should be withheld if the serum estradiol is greater than 2000 pg/mL, if the ovaries are abnormally enlarged or if abdominal pain occurs, and the patient should be advised to refrain from intercourse. These precautions may reduce the risk of Ovarian Hyperstimulation Syndrome and multiple gestations. Patients should be followed closely for at least 2 weeks after hCG administration. If there is inadequate follicle development or ovulation without subsequent pregnancy, the course of treatment with Bravelle® (urofollitropin injection) may be repeated. The couple should be encouraged to have intercourse daily, beginning on the day prior to the administration of hCG until ovulation becomes apparent from the indices employed for the determination of progestational activity. In the light of the foregoing indices and parameters mentioned, it should become obvious that, unless a physician is willing to devote considerable time to these patients and be familiar with and conduct the necessary laboratory studies, he/she should not use Bravelle® (urofollitropin injection) .

Assisted Reproductive Technologies: The recommended initial dose of Bravelle® (urofollitropin injection) for patients undergoing IVF and donor egg patients who have received GnRH agonist or antagonist pituitary suppression is 225 IU daily administered SC for the first 5 days of treatment. Based on clinical monitoring (including serum estradiol levels and vaginal ultrasound results) subsequent dosing should be adjusted according to individual patient response. Adjustments in dose should not be made more frequently than once every 2 days and should not exceed more than 75 to 150 IU per adjustment. The maximum daily dose of Bravelle® (urofollitropin injection) given should not exceed 450 IU and in most cases dosing beyond 12 days is not recommended.

Once adequate follicular development is evident, hCG (5,000-10,000 USP units) should be administered to induce final follicular maturation in preparation for oocyte retrieval. The administration of hCG must be withheld in cases where the ovaries are abnormally enlarged on the last day of therapy. This should reduce the chance of developing OHSS.

Bravelle® (urofollitropin for injection, purified) is supplied in a sterile, lyophilized, single dose vial containing 82.5 IU of FSH, to deliver 75 IU FSH after reconstituting with the diluent.

Each vial is available with an accompanying vial of sterile diluent containing 2 ml_ of 0.9% Sodium Chloride Injection, USP.

75 IU FSH activity, supplied as:

NDC 55566-8505-2: Box of 5 vials + 5 vials diluent.
NDC 55566-8505-6: Box of 5 vials + 5 vials diluent + 5
Q*Cap™ vial adapters.

Lyophilized powder may be stored refrigerated or at room temperature (3° to 25° C/37° to 77°F). Protect from light. Use immediately after reconstitu-tion. Discard unused material.

Vials of sterile diluent of 0.9% Sodium Chloride Injection, USP, manufactured for Ferring Pharmaceuticals Inc.

Manufactured for: FERRING PHARMACEUTICALS INC., PARSIPPANY, NJ 07054.08/07. FDA rev date: 11/14/2002

Last reviewed on RxList: 11/18/2008
This monograph has been modified to include the generic and brand name in many instances.