Bravelle® (urofollitropin injection) administered for 7 to 12 days produces ovarian follicular growth in women who do not have primary ovarian failure. Treatment with Bravelle® (urofollitropin injection) in most instances results only in follicular growth and maturation. When sufficient follicular maturation has occurred, hCG must be given to induce ovulation.

Pharmacokinetics

Single doses of 225 IU and multiple daily doses (7 days) of 150 IU of Bravelle® (urofollitropin injection) were administered to healthy volunteer female subjects while their endogenous FSH was suppressed. Sixteen subjects received Bravelle® (urofollitropin injection) SC and 12 received the drug IM. Serum FSH concentrations were determined. Based on the steady state ratio of FSH Cmax and AUC, SC and IM administration of Bravelle® (urofollitropin injection) were not bioequivalent. Multiple doses of Bravelle® (urofollitropin injection) IM resulted in Cmax and AUC of 77.7% and 81.8% compared to multiple doses of Bravelle® (urofollitropin injection) SC. The FSH pharmacokinetic parameters for single and multiple dose Bravelle® (urofollitropin injection) , administered SC and IM are in Table 1.

Table 1. FSH Pharmacokinetic Parameters Following Bravelle® (urofollitropin injection) Administration

Absorption

The maximum plasma concentration of FSH was attained at 20.5 and 17.4 hours following SC and IM single dose administration, respectively. However, following multiple dosing, it was attained at approximately 10 hours following both routes of administration.

Distribution

Human tissue or organ distribution of FSH has not been studied for Bravelle® (urofollitropin injection) .

Metabolism

Metabolism of FSH has not been studied for Bravelle® (urofollitropin injection) in humans.

Elimination

The mean elimination half-lives of FSH for SC and IM single dosing are 31.8 and 37 hours, respectively. However, following multiple dosing (X 7 days) they are 20.6 and 15.2 hours for SC and IM, respectively.

Pediatric Populations

Bravelle® (urofollitropin injection) is not indicated in pediatric populations.

Geriatric Populations

Bravelle® (urofollitropin injection) is not indicated in geriatric populations.

Special Populations

The safety and efficacy of Bravelle® (urofollitropin injection) in renal and hepatic insufficiency have not been studied.

Drug Interactions

No drug/drug interaction studies have been conducted for Bravelle® (urofollitropin injection) in humans.

Clinical Studies

The efficacy of Bravelle® (urofollitropin injection) was established in two randomized, active controlled, multi-center studies, one for in-vitro fertilization [IVF] and one for ovulation induction [01].

Ovulation Induction

In the randomized, controlled ovulation induction study, patients underwent pituitary suppression with a GnRH agonist before being randomized to Bravelle® (urofollitropin injection) SC, Bravelle® (urofollitropin injection) IM or a commercial recombinant FSH product administered SC. A total of 111 oligo-anovulatory patients were randomized of whom 72 received Bravelle® (urofollitropin injection) , starting at a dose of 150 IU daily for 5 days. This was followed by individual titration of the dose from 75 to 450 IU daily based on ultrasound and estradiol (E₂) levels. The total duration of dosing did not exceed 12 days. Results for the Intent-To-Treat Population are summarized in Table 2.

Table 2. Efficacy Outcome by Treatment Groups in Ovulation Induction for Study FPI FSH 99-03 (one cycle of treatment)

Assisted Reproductive Technologies [ART]

In the randomized, controlled IVF study FPI FSH 2001-01, patients underwent pituitary suppression with a GnRH agonist before being randomized to Bravelle® (urofollitropin injection) SC or a commercial recombinant FSH product administered SC. A total of 120 patients were randomized of whom 60 received Bravelle® (urofollitropin injection) , starting at a dose of 225 IU daily for 5 days. This was followed by individual titration of the dose from 75 to 450 IU daily based on ultrasound and estradiol (E2) levels. The total duration of dosing did not exceed 12 days. Results are summarized in Table 3 for the Intent-To-Treat population.

Table 3. Efficacy Outcome for IVF Study FPI FSH 2001-01 (one cycle of treatment)

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