REKOVELLE SOLUTION FOR INJECTION IN A PRE-FILLED PEN 12MCG/0.36ML [SIN15650P]

Product Info

REKOVELLE SOLUTION FOR INJECTION IN A PRE-FILLED PEN 12MCG/0.36ML

[SIN15650P]

4.1 Therapeutic indications
Controlled ovarian stimulation for the development of multiple follicles in women undergoing assisted reproductive technologies (ART) such as an in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycle.

4.2 Posology and method of administration
Treatment with REKOVELLE should be initiated under the supervision of a physician experienced in the treatment of fertility problems. Patients must be educated on how to use the REKOVELLE injection pen and to perform injections.

Posology
The posology of REKOVELLE is individualised for each patient to obtain an ovarian response with a favourable safety/efficacy profile i.e. aims to achieve an adequate number of oocytes retrieved and reduce the interventions to prevent ovarian hyperstimulation syndrome (OHSS) (see Section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

REKOVELLE is dosed in micrograms (μg) and not in international units (IU) of biological activity (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The dosing regimen is specific for REKOVELLE and the microgram dose cannot be applied to other gonadotropins.

For the first treatment cycle, the individual daily dose will be determined on the basis of the woman’s serum anti-Müllerian hormone (AMH) concentration, which is a biomarker of ovarian response to gonadotropins, and her body weight. The dose should be based on a recent determination of AMH (i.e. within the last 12 months) measured by the following diagnostic tests: Elecsys® AMH Plus immunoassay from Roche (i.e. assay used in clinical development trials), or alternatively the ACCESS AMH Advanced from Beckman Coulter (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The individual daily dose is to be maintained throughout the stimulation period. For women with AMH <15 pmol/L the daily dose is 12 micrograms, irrespective of body weight. For women with AMH ≥15 pmol/L the daily dose decreases from 0.19 to 0.10 micrograms/kg by increasing AMH concentration (Table 1). The dose is to be rounded off to the nearest 0.33 micrograms to match the dosing scale on the injection pen. The maximum daily dose for the first treatment cycle is 12 micrograms.

The AMH concentration is to be expressed in pmol/L and is to be rounded off to the nearest integer (Table 1). If the AMH concentration is in ng/mL, the concentration should be converted to pmol/L by multiplying with 7.14 (ng/mL x 7.14 = pmol/L) before use.

For calculation of the REKOVELLE dose, the body weight is to be measured without shoes and overcoat just prior to start of stimulation.

Potential high responders (patients with AMH >35 pmol/L) have not been studied in a protocol using down-regulation with GnRH agonist.

Time of initiating treatment with REKOVELLE depends on the type of protocol.

• in a protocol using a gonadotropin-releasing hormone (GnRH) antagonist, the treatment with REKOVELLE should be initiated on day 2 or 3 after start of menstrual bleeding;

• in a protocol using down-regulation with a GnRH agonist, the treatment with REKOVELLE should be initiated approximately 2 weeks after the start of agonist treatment.

Treatment should continue until adequate follicular development (≥3 follicles ≥17 mm) has been achieved, which on average is by the ninth or tenth day of treatment (range 5 to 20 days). With pituitary desensitisation caused by a GnRH agonist, a longer duration of stimulation and therefore a higher total dose of REKOVELLE may be necessary to achieve adequate follicular response. A single injection of 250 micrograms recombinant human chorionic gonadotropin (hCG) or 5,000 international units hCG is administered to induce final follicular maturation. In patients with excessive follicular development (of ≥25 follicles ≥12 mm), treatment with REKOVELLE should be stopped and triggering of final follicular maturation with hCG should not be performed.

For subsequent treatment cycles, the daily dose of REKOVELLE should be maintained or modified according to the patient’s ovarian response in the previous cycle. If the patient had adequate ovarian response in the previous cycle without developing OHSS, the same daily dose of REKOVELLE should be used. In case of ovarian hypo-response in the previous cycle, the daily dose of REKOVELLE in the subsequent cycle should be increased by 25% or 50%, according to the extent of response observed. In case of ovarian hyper-response in the previous cycle, the daily dose of REKOVELLE in the subsequent cycle should be decreased by 20% or 33%, according to the extent of response observed. In patients who developed OHSS or were at risk of OHSS in a previous cycle, the daily dose of REKOVELLE for the subsequent cycle is 33% lower than the dose used in the cycle where OHSS or risk of OHSS occurred. The maximum daily dose is 24 micrograms.

Elderly (more than 65 years)
There is no relevant use of REKOVELLE in the elderly population. Safety and efficacy of REKOVELLE in elderly patients have not been established.

Patients with renal and hepatic impairment
Safety, efficacy and pharmacokinetics of REKOVELLE in patients with renal or hepatic impairment have not been established.

Polycystic ovarian syndrome patients with anovulatory disorders
Anovulatory patients with polycystic ovarian syndrome have not been studied. Ovulatory patients with polycystic ovaries have been included in clinical trials.

Paediatric population
There is no relevant use of REKOVELLE in the paediatric population for the indication.

Method of administration
REKOVELLE is intended for subcutaneous administration, preferably in the abdominal wall. The first injection of REKOVELLE should be performed under direct medical supervision. Self-administration of REKOVELLE should only be performed by patients who are well motivated, adequately trained and have access to expert advice.

For instructions on the administration with the pre-filled pen, see the “Instructions for Use”.

4.3 Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information

• Tumours of the hypothalamus or pituitary gland

• Ovarian enlargement or ovarian cyst not due to polycystic ovarian syndrome

• Gynaecological haemorrhages of unknown aetiology

• Ovarian, uterine or mammary carcinoma

• Pregnancy and lactation

REKOVELLE must not be used when an effective response cannot be obtained, such as:

• Primary ovarian failure

• Malformations of sexual organs incompatible with pregnancy

• Fibroid tumours of the uterus incompatible with pregnancy