Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2016 Publisher: Ferring Pharmaceuticals Ltd., Drayton Hall, Church Road, West Drayton, UB7 7PS, United Kingdom
BRAVELLE is indicated for the treatment of female infertility in the following clinical situations:
Treatment with BRAVELLE should be initiated under the supervision of a physician experienced in the treatment of fertility problems.
There are great inter- and intra-individual variations in the response of the ovaries to exogenous gonadotropins. This makes it impossible to set a uniform dosage scheme. The dosage should, therefore, be adjusted individually depending on the ovarian response. This requires monitoring of ovarian response by ultrasonography alone or preferably in combination with measurement of oestradiol levels. BRAVELLE can be given alone or in combination with a gonadotropin-releasing hormone (GnRH) agonist or antagonist for controlled ovarian hyperstimulation. There is no clinical trial experience with the use of BRAVELLE in combination with GnRH antagonists in this indication. Recommendations about dosage and duration of treatment may change depending on the actual treatment protocol.
Clinical trial experience with BRAVELLE is based upon one treatment cycle in both indications.
The object of BRAVELLE therapy is to develop a single Graafian follicle from which the oocyte will be liberated after the administration of human chorionic gonadotropin (hCG).
BRAVELLE therapy should start within the initial 7 days of the menstrual cycle. The recommended initial dose of BRAVELLE is 75 IU daily, which should be maintained for at least 7 days. Based on clinical monitoring (including ovarian ultrasound alone or in combination with measurement of oestradiol levels) subsequent dosing should be adjusted according to individual patient response. Adjustments in dose should not be made more frequently than every 7 days. The recommended dose increment is 37.5 IU per adjustment and should not exceed 75 IU. The maximum daily dose should not be higher than 225 IU. If a patient fails to respond adequately after 4 weeks of treatment, that cycle should be abandoned.
When an optimal response is obtained a single injection of 5,000 to 10,000 IU hCG should be given 1 day following the last BRAVELLE injection. The patient is recommended to have coitus on the day of and the day following hCG administration. Alternatively intrauterine insemination may be performed. Patients should be followed closely for at least 2 weeks after hCG administration. If an excessive response to BRAVELLE is obtained treatment should be stopped and hCG withheld (see section 4.4), and the patient should use a barrier method of contraception or refrain from having coitus until the next menstrual bleeding has started.
In line with clinical trials with BRAVELLE that involved down regulation with GnRH agonists, BRAVELLE therapy should start approximately 2 weeks after the start of agonist treatment. The recommended initial dose of BRAVELLE is 150-225 IU daily for at least the first 5 days of treatment. Based on clinical monitoring (including ovarian ultrasound alone or in combination with measurement of oestradiol levels) subsequent dosing should be adjusted according to individual patient response, and should not exceed 150 IU per adjustment. The maximum daily dose given should not be higher than 450 IU daily and in most cases dosing beyond 12 days is not recommended.
In protocols not involving down regulation, BRAVELLE therapy should start on day 2 or 3 of the menstrual cycle. It is recommended to use the dose ranges and regimen of administration suggested above for protocols with down regulation with GnRH agonists.
When an optimal response is obtained a single injection of up to 10,000 IU hCG should be administered to induce final follicular maturation in preparation for oocyte retrieval. Patients should be followed closely for at least 2 weeks after hCG administration. If an excessive response to BRAVELLE is obtained treatment should be stopped and hCG withheld (see section 4.4), and the patient should use a barrier method of contraception or refrain from having coitus until the next menstrual bleeding has started.
There is no relevant use of BRAVELLE in the paediatric population.
BRAVELLE is intended for subcutaneous (SC) injection after reconstitution with the solvent provided. The powder should be reconstituted immediately prior to use. In order to avoid the injection of large volumes up to 6 vials of the powder may be dissolved in the solvent provided. The solution should not be used if it contains particles or if it is not clear.
Appearance of reconstituted solution: clear solution
For instructions of reconstitution of the medicinal product before administration, see section 6.6.
The effects of an overdose is unknown, nevertheless ovarian hyperstimulation syndrome could be expected to occur (see section 4.4).
2 years.
After reconstitution: use immediately.
Do not store above 25°C. Do not freeze. Store in the original container in order to protect from light.
Powder: The powder for solution for injection is supplied in a 2 mL single dose colourless type I glass vial with a bromobutyl
rubber stopper closed with an aluminium/polypropen cap.
Solvent: The solvent for solution for injection is provided in a 1 mL single dose colourless type I glass ampoule.
BRAVELLE is supplied in the following pack sizes:
Not all pack sizes may be marketed.
BRAVELLE should only be reconstituted with the solvent provided prior to use.
Attach the reconstitution needle to the syringe. Withdraw the entire content from the ampoule with solvent and inject the total contents into the vial containing the powder. The powder should dissolve within 2 minutes to a clear solution. If not, roll the vial gently between the hands until the solution is clear. Vigorous shaking should be avoided.
After reconstitution, the solution can be mixed with Ferring’s menotrophin (hMG) MENOPUR powder for solution for injection before administration. Studies have shown that co-administration of BRAVELLE and MENOPUR does not significantly alter the expected bioactivity.
If needed, the solution can be drawn up into the syringe again to transfer it to the next vial with powder until the prescribed dose has been reached. Up to six powder vials (450 IU) can be dissolved in one ampoule of solvent.
When the prescribed dose has been reached, draw up the mixed solution from the vial into the syringe, change to the hypodermic needle and administer immediately.
The solution should not be used if it contains particles or if it is not clear.
BRAVELLE should be administered immediately after reconstitution. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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