Menopur is indicated for the treatment of female 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-Follopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)]

Treatment with Menopur should be initiated under the supervision of a physician
experienced in the treatment of fertility problems.

Dosage
Dosage regimens described below are identical for subcutaneous and intramuscular administration.
There are great inter- and intra individual variations in the response of the ovaries to exogenous
gonadotrophins. 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 object of Menopur therapy is to develop a single Graafian follicle from which the oocyte
will be liberated after the administration of hCG. Menopur therapy should start within the
initial 7 days of the menstrual cycle. The recommended initial dose of Menopur is 75 - 150 IU
daily, which should be maintained for at least 7 days. Based on routine clinical monitoring
(including ovarian ultrasound, preferably in combination with measurement of oestradiol levels)
subsequent treatment 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 (maximum 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 and the patient should recommence treatment at a higher starting
dose than in the abandoned cycle. When an optimal stimulation is obtained, a single injection of
5,000 IU to 10,000 IU 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 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)
0n a protocol using downregulation with a GnRH agonist,
Menopur therapy should start approximately 2 weeks after the start of agonist treatment.
In a protocol using downregulation 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 IU
daily for at least the first 5 days of treatment. Based on routine clinical monitoring (including ovarian
ultrasound, in combination with measurement of oestradiol levels) subsequent treatment should be
adjusted according to individual patient response, and should not exceed more than 150 IU per
adjustment. The maximum daily dose given should not be higher than 450 IU daily and in most
cases dosing beyond 20 days is not recommended. When an optimal response is obtained, a single
injection of 5,000 up to 10,000 IU hCG should be administered to induce 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 and the patient should use a barrier method of contraception or refrain from having
coitus until the next menstrual bleeding has started.
Paediatric population
There is no relevant use of Menopur in the paediatric population.
Method of administration
Menopur 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 Menopur may be dissolved in 1 ml of the
solvent provided. Shaking should be avoided. The solution should not be used if it contains particles or
if it is not clear.

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 - 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

Menopur is a potent gonadotrophic substance capable of causing mild to severe adverse reactions,
and should only be used by physicians who are thoroughly familiar with infertility problems and their
management. Gonadotrophin therapy requires a certain time commitment by physicians and
supportive health professionals, and calls for monitoring of ovarian response with ultrasound, alone
or in combination with measurement of serum oestradiol levels, on a regular basis.There is
considerable inter-patient variability in response to menotrophin administration, with a poor
response to menotrophin in some patients. The lowest effective dose in relation to the treatment
objective should be used. The first injection of Menopur should be performed under direct medical
supervision. Before starting treatment, the couple’s infertility should be assessed as appropriate and
putative contraindications for pregnancy evaluated. In particular, patients should be evaluated for
hypothyroidism, adrenocortical deficiency, hyperprolactinaemia and pituitary or hypothalamic tumours,
and appropriate specific treatment given. Patients undergoing stimulation of follicular growth, whether
in the frame of a treatment for anovulatory infertility or ART procedures may experience ovarian
enlargement or develop hyperstimulation. Adherence to recommended Menopur dosage and regimen
of administration, and careful monitoring of therapy will minimise the incidence of such events. Acute
interpretation of the indices of follicular maturation requires a physician who is experienced in the
interpretation of the relevant tests.
Ovarian hyperstimulation syndrome (OHSS)
OHSS is a medical event distinct from uncomplicated ovarian enlargement. OHSS is a syndrome
that can manifest itself with increasing degrees of severity. It comprises marked ovarian enlargement,
high serum sex steroids, and an increase in vascular permeability which can result in an accumulation
of fluid in the peritoneal, pleural and, rarely, in the pericardial cavities. The following symptoms may be
observed in severe cases of OHSS: abdominal pain, abdominal distension, severe ovarian enlargement,
weight gain, dyspnoea, oliguria and gastrointestinal symptoms including nausea, vomiting and diarrhoea.
Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites,
haemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic
events. Excessive ovarian response to gonadotrophin treatment seldom gives rise to OHSS unless
hCG is administered to trigger ovulation. Therefore in cases of ovarian hyperstimulation, it is prudent
to withhold hCG and advise the patient to refrain from coitus or to use barrier methods for at least
4 days. OHSS may progress rapidly (within 24 hours to several days) to become a serious medical
event, therefore patients should be followed for at least two weeks after the hCG administration.
Adherence to recommended Menopur dosage, regimen of administration and careful monitoring
of therapy will minimise the incidence of ovarian hyperstimulation and multiple pregnancy. In ART,
aspiration of all follicles prior to ovulation may reduce the occurrence of hyperstimulation. OHSS may
be more severe and more protracted if pregnancy occurs. Most often, OHSS occurs after hormonal
treatment has been discontinued and reaches its maximum severity at about seven to ten days
following treatment. Usually, OHSS resolves spontaneously with the onset of menses. If severe
OHSS occurs, gonadotrophin treatment should be stopped if still ongoing, the patient hospitalised
and specific therapy for OHSS started. This syndrome occurs with higher incidence in patients with
polycystic ovarian disease.
Multiple pregnancy
Multiple pregnancy, especially high order, carries an increased risk of adverse maternal and perinatal
outcomes. The incidence of multiple pregnancy is increased compared to normal conception in patients
who undergo ovulation induction with gonadotrophins. The majority of multiple conceptions are twins.
To minimise the risk of multiple pregnancy, careful monitoring of ovarian response is recommended.
In patients undergoing ART procedures the risk of multiple pregnancy is related mainly to the number
of embryos replaced, their quality and the age of the patient. The patient should be advised of the
potential risk of multiple births before starting treatment.
Pregnancy wastage
The incidence of pregnancy wastage by miscarriage or abortions is higher in patients undergoing
stimulation of follicular growth for ART procedures than in the normal population.
Ectopic pregnancy
Women with a history of tubal disease are at risk of ectopic pregnancy, whether the pregnancy is
obtained by spontaneous conception or with fertility treatment. The prevalence of ectopic pregnancy
after IVF has been reported to be 2 to 5%, as compared to 1 to 1.5% in the general population.
Reproductive system neoplasms
There have been reports of ovarian and other reproductive system neoplasms, both benign and
malignant, in women who have undergone multiple drug regimens for infertility treatment. It is
not yet established if treatment with gonadotrophins increases the baseline risk of these tumours
in infertile women.
Congenital malformation
The prevalence of congenital malformations after ART may be slightly higher than after
spontaneous conceptions. This is thought to be due to differences in parental characteristics
(e.g. maternal age, sperm characteristics) and multiple pregnancies.
Thromboembolic events
Women with generally recognised risk factors for thromboembolic events, such as personal
or family history, severe obesity (Body Mass Index > 30 kg/m2) or thrombophilia may have an

increased risk of venous or arterial thromboembolic events, during or following treatment with
gonadotrophins. In these women, the benefits of gonadotrophin administration need to be
weighed against the risks. It should be noted however, that pregnancy itself also carries an
increased risk of thromboembolic events.
The use of Menopur may lead to positive results in doping tests.
The use of Menopur for doping purposes may endanger health.
Menopur contains sodium, but less than 1 mmol (23 mg) sodium per dose, i.e.
essentially “sodium-free”.

No drug/drug interaction studies have been conducted with Menopur in humans.
Although there is no controlled clinical experience, it is expected that the concomitant use
of Menopur and clomiphene citrate may enhance the follicular maturation.
When using GnRH agonist for pituitary desensitisation, a higher dose of Menopur may be
necessary to achieve adequate follicular maturation.

Fertility
Menopur is indicated for use in infertility-
Pregnancy
Menopur falls under pregnancy category X.
Menopur is contraindicated in women who are pregnant.
Lactation
Menopur is contraindicated in women who are lactating

No studies on the effects on the ability to drive and use machines have been performed.
However, Menopur is unlikely to have influence on the patient’s ability to drive and
use machines.

Eye disorders
Not known: Visual disorders
Gastrointestinal disorders
Common: Abdominal pain, abdominal distension, nausea
Uncommon: Emesis, abdominal discomfort, diarrhoea
General disorders and administration site conditions
Common: Injection site reactions
Uncommon: Fatigue
Not known: Pyrexia, Malaise
Immune system disorders
Not known: Hypersensitivity reactions
Investigations
Not known: Weight increased
Musculoskeletal and connective tissue disorders
Not known: Musculoskeletal pain
Nervous system disorders
Common: Headache
Uncommon: Dizziness
Reproductive system and breast disorders
Common: OHSS, pelvic pain
Uncommon: Ovarian cyst, breast complaints
Not known: Ovarian torsion
Skin and subcutaneous tissue disorders
Rare: Acne, rash
Not known: Pruritus, urticaria
Vascular disorders
Uncommon: Hot flushes
Unknown: Thromboembolism
Individual cases of temporary amaurosis, diplopia, mydiasis, scotoma, photopsia, vitreous
floaters, vision blurred and vision impairment have been reported as visual disorders during
the post-marketing period. Most frequently reported injection site reaction was injection site
pain. Cases of localised or generalised allergic reactions, including anaphylactic reaction,
along with associated symptomatology have been reported rarely. Musculoskeletal pain
includes arthralgia, back pain, neck pain and pain in extremities. Gastrointestinal symptoms
associated with OHSS such as abdominal distension and discomfort, nausea, vomiting and
diarrhoea have been reported with Menopur in clinical trials. In cases of severe OHSS
ascites and pelvic fluid collection, pleural effusion, dyspnoea, oliguria, thromboembolic
events and ovarian torsion have been reported as rare complications. Pelvic pain includes
ovarian pain and adnexa uteri pain. Breast complaints include breast pain, breast
tenderness, breast discomfort, nipple pain and breast swelling. Unwanted multiple pregnancy
is more common during treatment with HMG. Pregnancies which result from infertility
treatment with gonadotrophins such as Menopur may end more frequently in spontaneous
abortions than normal pregnancies.

The effects of an overdose are unknown, nevertheless one could expect
ovarian
hyperstimulation syndrome to occur

Pharmacotherapeutic group: Gonadotrophins, ATC code: G03G A02
MENOPUR contains Menotrophin (hMG) which is composed of follicle stimulating hormone
(FSH) and luteinizing hormone (LH). In addition, Human Chorionic Gonadotrophin (hCG), a
hormone occurring in postmenopausal urine, is present in MENOPUR and contributes to
the LH activity. Menotrophin, which contains both FSH and LH activity, includes ovarian
follicular growth and development as well as gonadal steroid production in women who
do not have primary ovarian failure. FSH is the primary driver of follicular recruitment and
growth in early folliculogenesis, while LH is important for ovarian steroidogenesis and
pre-ovulatory follicular maturation. Follicular growth can be stimulated by FSH in the
total absence of LH (e.g. in hypogonadotrophic hypogonadism), but the resulting follicles
develop abnormally and are associated with low estradiol levels and an insufficient follicular
maturation may occur. In line with the action of LH activity in enhancing stereoidogenesis,
estradiol levels associated with treatment with MENOPUR are higher than with recombinant
FSH preparations in downregulated IVF/ICSI cycles. This issue should be considered when
monitoring patients’ response based on estradiol levels. The difference in estradiol levels
is not found when using low􀀀dose ovulation induction protocols in unovulatory patients.

The pharmacokinetic profile of the FSH in MENOPUR has been documented. After 7 days
of repeated dosing with 150 IU MENOPUR in downregulated healthy female volunteers,
maximum plasma FSH concentrations (baseline-corrected) (mean ± SD) were 8.9 ± 3.5 IU/L
and 8.5 ± 3.2 IU/L for the subcutaneous and intramuscular administration,
Respectively. Maximum FSH concentrations were reached within 7 hours for both routes
of administration. After repeated administration, FSH was eliminated with a half􀀀life
(mean ± SD) of 30 ± 11 hours and 27 ± 9 hours for the subcutaneous and intramuscular
administration, respectively. Although the individual LH concentration versus time curves
show an increase in the LH concentration after dosing with MENOPUR, the data available
were too sparse to be subjected to a pharmacokinetic analysis. Menotrophin is excreted
primarily via the kidneys. The pharmacokinetics of MENOPUR in patients with renal or
hepatic impairment has not been investigated.

N/A

Powder: Lactose monohydrate, Polysorbate 20, Sodium hydroxide, Hydrochloric acid 36%
Solvent: Sodium chloride, Hydrochloric acid 10%, Water for injection

MENOPUR should not be administered in the same injection with other products, except
Ferring’s urofollitrophin Bravelle 75 IU. Studies have shown that co-administration of
MENOPUR and urofollitrophin does not significantly alter the expected bioavailability.
6.3 Shelf life: See outer carton. For immediate use following reconstitution.

See outer carton. For immediate use following reconstitution

Do not store above 30°C. Do not freeze. Store in the original container in order to protect
from light

Powder: 2 ml colorless glass (type I) injection bottle with rubber stopper closed with a cap.
Solvent: 1 ml colorless glass (type I) ampoule
Content of container:
- 1 vial powder + 1 ampoule solvent
- 5 vials powder + 5 ampoules solvent
- 10 vials powder + 10 ampoules solvent
Not all packs may be marketed in your country

Any unused product or waste material should be disposed in accordance with local
requirements.