MENOPUR POWDER AND SOLVENT FOR SOLUTION FOR INJECTION 75IU [SIN13356P]

Product Info

MENOPUR POWDER AND SOLVENT FOR SOLUTION FOR INJECTION 75IU

[SIN13356P]

4.1 Therapeutic indications
MENOPUR® is indicated for the treatment of infertility in the following clinical situations:

Anovulation, including polycystic ovarian disease (PCOD), in women who have been unresponsive to treatment with clomiphene citrate.

Controlled ovarian hyperstimulation to induce the development of multiple follicles for assisted reproductive technologies (ART) (e.g. in vitro fertilisation/embryo transfer (IVF/ET), gamete intra-fallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)).

Sterility in females with hypo- or normogonadotropic ovarian insufficiency: Stimulation of follicular growth.

4.2 Posology and method of administration
Treatment with MENOPUR® should be initiated under the supervision of a physician experienced in the treatment of fertility problems.

Posology
Dosage regimens described below are identical for S.C. and I.M. administration.

The inter-individual variations in the response of the ovaries to exogenous gonadotrophins is high. This makes it impossible to set a uniform dosage scheme. The dosage should, therefore, be adjusted individually depending on the ovarian response. MENOPUR® can be given alone or in combination with a gonadotrophin-releasing hormone (GnRH) agonist or antagonist.

Recommendations about dosage and duration of treatment may change depending on the actual treatment protocol.

Women with anovulation (including PCOD):
The objective of MENOPUR® therapy is to develop a single Graafian follicle from which the oocyte will be liberated after the administration of human chorionic gonadotrophin (hCG).
MENOPUR® therapy should start within the initial 7 days of the menstrual cycle. The recommended initial dose of MENOPUR® is 75–150 international units 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 international units per adjustment, and should not exceed 75 international units. The maximum daily dose should not be higher than 225 international units. If a patient fails to respond adequately after 4 weeks of treatment, that cycle should be abandoned and the patient should recommence treatment at a higher starting dose than in the abandoned cycle.

When an optimal response is obtained, a single injection of 5,000 international units to 10,000 international units hCG should be given 1 day after the last MENOPUR® 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 to MENOPUR® is obtained treatment should be stopped and hCG withheld (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information) and the patient should use a barrier method of contraception or refrain from having coitus until the next menstrual bleeding has started.

Women undergoing controlled ovarian hyperstimulation for multiple follicular development for assisted reproductive technologies (ART) (e.g. in vitro fertilisation/embryo transfer (IVF/ET), gamete intra-fallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)):
In a protocol using down-regulation with a GnRH agonists, MENOPUR® therapy should start approximately 2 weeks after the start of agonist treatment. In a protocol using down-regulation with a GnRH antagonist, MENOPUR® therapy should start on day 2 or 3 of the menstrual cycle. The recommended initial dose of MENOPUR® is 150–225 international units 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 more than 150 international units per adjustment. The maximum daily dose given should not be higher than 450 international units daily and in most cases dosing beyond 20 days is not recommended.

When a suitable number of follicles have reached an appropriate size a single injection of up to 10,000 international units 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 MENOPUR® is obtained treatment should be stopped and hCG withheld (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information) and the patient should use a barrier method of contraception or refrain from having coitus until the next menstrual bleeding has started.

Women with hypo- or normogonadotropic ovarian insufficiency:
The dose of MENOPUR® required to induce follicular growth in normo- or hypogonadotrophic women must be adjusted individually for each patient. The amount depends on ovarian reaction and should be checked by ultra-sound examinations of the ovaries and measuring estradiol levels. If the MENOPUR® dosage is too high for the treated individual, multiple uni and bilateral follicle growth can occur.

MENOPUR® is administered intramuscularly or subcutaneously and in general, the therapy is begun with a daily dosage of corresponding to 75–150 international units FSH (1–2 vials MENOPUR® per day). If there is no ovarian reaction, the dose can be gradually increased until there is evidence of estradiol secretion or follicular growth. The dose of HMG should be maintained until the pre-ovulation estradiol serum level is achieved. The dose should be reduced if the level increases too rapidly.

As a measure of follicle maturity the following values can be taken:

• total urinary oestrogen: 75–150 micrograms (270–540 nmol)/24 hours

• plasma 17 beta-oestradiol: 400–800 picograms/ml (1500–3000 pmol/L).

To induce ovulation, 5,000–10,000 international units hCG should be administered by intramuscular injection 1–2 days after the last dose of HMG.

Note:
Unintentional hyperstimulation of the ovaries can be induced by the administration of hCG after an excessive dose of MENOPUR®. Duration of treatment depends on the individual situation of the patient (estradiol level, ultra-sound). For intramuscular or subcutaneous injection after dissolving the dry substance in the solvent included.

Renal/hepatic impairment
Patients with renal and hepatic impairment have not been included in clinical trials (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Paediatric population
There is no relevant use of MENOPUR® in the paediatric population.

Elderly population (more than 65 years of age)
There is no relevant use of MENOPUR® in the elderly population.

Method of administration
MENOPUR® 75 international units is intended for subcutaneous (S.C.) or intramuscular (I.M.) 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 3 vials of the powder may be dissolved in 1 ml of the solvent provided.

The reconstituted solution should be clear and colourless by visual inspection.

The solution should not be used if it contains particles or if it is not clear. Shaking should be avoided.

4.3 Contraindications
MENOPUR® is contraindicated in women who have:

• Tumours of the pituitary gland or hypothalamus

• Ovarian, uterine or mammary carcinoma

• Pregnancy and lactation

• Gynaecological haemorrhage of unknown aetiology

• Hypersensitivity to the active substance or 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

• Ovarian cysts or enlarged ovaries not due to polycystic ovarian disease.

In the following situations treatment outcome is unlikely to be favourable, and therefore MENOPUR® should not be administered:

• Primary ovarian failure

• Malformation of sexual organs incompatible with pregnancy

• Fibroid tumours of the uterus incompatible with pregnancy