Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Theramex Ireland Limited 3<sup>rd</sup> Floor, Kilmore House, Park Lane, Spencer Dock, Dublin 1, D01 YE64, Ireland
In adult women:
In adult men:
Treatment with follitropin alfa should be initiated under the supervision of a physician experienced in the treatment of fertility disorders.
The dose recommendations given for follitropin alfa are those in use for urinary FSH. Clinical assessment of follitropin alfa indicates that its daily doses, regimens of administration and treatment monitoring procedures should not be different from those currently used for urinary FSH-containing medicinal products. It is advised to adhere to the recommended starting doses indicated below.
Comparative clinical studies have shown that on average patients require a lower cumulative dose and shorter treatment duration with follitropin alfa compared with urinary FSH. Therefore, it is considered appropriate to give a lower total dose of follitropin alfa than generally used for urinary FSH, not only in order to optimise follicular development but also to minimise the risk of unwanted ovarian hyperstimulation (see section 5.1).
Follitropin alfa may be given as a course of daily injections. In menstruating women treatment should commence within the first 7 days of the menstrual cycle.
A commonly used regimen commences at 75-150 IU FSH daily and is increased preferably by 37.5 or 75 IU at 7 or preferably 14 day intervals if necessary, to obtain an adequate, but not excessive, response. Treatment should be tailored to the individual patient’s response as assessed by measuring follicle size by ultrasound and/or oestrogen secretion. The maximal daily dose is usually not higher than 225 IU FSH. If a patient fails to respond adequately after 4 weeks of treatment, that cycle should be abandoned and the patient should undergo further evaluation after which she may recommence treatment at a higher starting dose than in the abandoned cycle.
When an optimal response is obtained, a single injection of 250 micrograms recombinant human choriogonadotropin alfa (r-hCG) or 5,000 IU up to 10,000 IU hCG should be administered 24-48 hours after the last follitropin alfa injection. The patient is recommended to have coitus on the day of, and the day following, hCG administration. Alternatively intrauterine insemination (IUI) may be performed.
If an excessive response is obtained, treatment should be stopped and hCG withheld (see section 4.4). Treatment should recommence in the next cycle at a dose lower than that of the previous cycle.
A commonly used regimen for superovulation involves the administration of 150-225 IU of follitropin alfa daily, commencing on days 2 or 3 of the cycle. Treatment is continued until adequate follicular development has been achieved (as assessed by monitoring of serum oestrogen concentrations and/or ultrasound examination), with the dose adjusted according to the patient’s response, to usually not higher than 450 IU daily. In general adequate follicular development is achieved on average by the tenth day of treatment (range 5 to 20 days).
A single injection of 250 micrograms r-hCG or 5,000 IU up to 10,000 IU hCG is administered 24-48 hours after the last follitropin alfa injection to induce final follicular maturation.
Down-regulation with a gonadotropin-releasing hormone (GnRH) agonist or antagonist is now commonly used in order to suppress the endogenous LH surge and to control tonic levels of LH. In a commonly used protocol, follitropin alfa is started approximately 2 weeks after the start of agonist treatment, both being continued until adequate follicular development is achieved. For example, following two weeks of treatment with an agonist, 150-225 IU follitropin alfa are administered for the first 7 days. The dose is then adjusted according to the ovarian response.
Overall experience with IVF indicates that in general the treatment success rate remains stable during the first four attempts and gradually declines thereafter.
In LH and FSH deficient women (hypogonadotropic hypogonadism), the objective of follitropin alfa therapy in association with lutropin alfa is to develop a single mature Graafian follicle from which the oocyte will be liberated after the administration of hCG. Follitropin alfa should be given as a course of daily injections simultaneously with lutropin alfa. Since these patients are amenorrhoeic and have low endogenous oestrogen secretion, treatment can commence at any time.
A recommended regimen commences at 75 IU of lutropin alfa daily with 75-150 IU FSH. Treatment should be tailored to the individual patient’s response as assessed by measuring follicle size by ultrasound and oestrogen response.
If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7-14 day intervals and preferably by 37.5-75 IU increments. It may be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.
When an optimal response is obtained, a single injection of 250 micrograms r-hCG or 5,000 IU up to 10,000 IU hCG should be administered 24-48 hours after the last follitropin alfa and lutropin alfa injections. The patient is recommended to have coitus on the day of, and on the day following, hCG administration. Alternatively, IUI may be performed.
Luteal phase support may be considered since lack of substances with luteotropic activity (LH/hCG) after ovulation may lead to premature failure of the corpus luteum.
If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment should recommence in the next cycle at a dose of FSH lower than that of the previous cycle.
Follitropin alfa should be given at a dose of 150 IU three times a week, concomitantly with hCG, for a minimum of 4 months. If after this period, the patient has not responded, the combination treatment may be continued; current clinical experience indicates that treatment for at least 18 months may be necessary to achieve spermatogenesis.
There is no relevant use of follitropin alfa in the elderly population. Safety and effectiveness of follitropin alfa in elderly patients have not been established.
Safety, efficacy and pharmacokinetics of follitropin alfa in patients with renal or hepatic impairment have not been established.
There is no relevant use of follitropin alfa in the paediatric population.
Ovaleap is intended for subcutaneous use. The first injection should be performed under direct medical supervision. Self-administration should only be performed by patients who are well motivated, adequately trained and have access to expert advice.
As the multidose cartridge is intended for several injections, clear instructions should be provided to the patients to avoid misuse of the medicine.
The Ovaleap cartridge is designed for use in conjunction with the Ovaleap Pen only, which is separately available. For instructions on the administration with the Ovaleap Pen, see section 6.6.
The effects of an overdose of follitropin alfa are unknown, nevertheless, there is a possibility that OHSS may occur (see section 4.4).
3 years.
Shelf life and storage conditions after first opening:
The cartridge in-use in the pen may be stored for a maximum of 28 days. Do not store above 25°C. The patient should write down in the patient diary provided with the Ovaleap Pen the date of first use.
The pen cap must be put back on the pen after each injection in order to protect from light.
Store in a refrigerator (2°C-8°C).
Do not freeze.
Keep the cartridge in the outer carton in order to protect from light.
Before opening and within its shelf life, the medicinal product may be removed from the refrigerator, without being refrigerated again, for up to 3 months. Do not store above 25°C. The medicinal product must be discarded if it has not been used after 3 months.
For storage conditions after first opening of the medicinal product, see section 6.3.
Ovaleap 300 IU/0.5 mL solution for injection:
Cartridge (type I glass) with a rubber piston (bromobutyl rubber) and a crimp-cap (aluminium) with a septum (bromobutyl rubber), containing 0.5 mL of solution. Injection needles (stainless steel; 0.33 mm x 12 mm, 29 G x ½").
Pack size of 1 cartridge and 10 injection needles.
Not all pack sizes may be marketed.
Ovaleap 450 IU/0.75 mL solution for injection:
Cartridge (type I glass) with a rubber piston (bromobutyl rubber) and a crimp-cap (aluminium) with a septum (bromobutyl rubber), containing 0.75 mL of solution. Injection needles (stainless steel; 0.33 mm x 12 mm, 29 G x ½").
Pack size of 1 cartridge and 10 injection needles.
Not all pack sizes may be marketed.
Ovaleap 900 IU/1.5 mL solution for injection:
Cartridge (type I glass) with a rubber piston (bromobutyl rubber) and a crimp-cap (aluminium) with a septum (bromobutyl rubber), containing 1.5 mL of solution. Injection needles (stainless steel; 0.33 mm x 12 mm, 29 G x ½").
Pack size of 1 cartridge and 20 injection needles.
Not all pack sizes may be marketed
No special requirements for disposal.
The solution must not be used if it contains particles or if the solution is not clear.
Ovaleap is designed for use in conjunction with the Ovaleap Pen only. The instructions for use of the pen must be followed carefully.
Each cartridge must be used by a single patient only.
Empty cartridges must not be refilled. Ovaleap cartridges are not designed to allow any other medicinal product to be mixed in the cartridges. Discard used needles immediately after injection.
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