MENOPUR is indicated for the treatment of infertility in the following clinical situations:
Women
- MENOPUR is indicated for the treatment of women undergoing assisted reproduction to induce multiple follicular development and in w omen
with anovulation, including polycystic ovarian disease 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)).
- Stimulation of follicle growth in women with hypo- or normogonadotrophic ovarian insuciency.
Men
Sterility in men with hypo- or normogonadotrophic hypogonadism, spermatogenesis stimulation (it is used in combination with hCG – human
chorionic gonadotrophin).

Treatment with MENOPUR should be initiated under the supervision of a physician experienced in the treatment of fertility problems.
Posology
Dosage regime described below is identical for S.C. and I.M. administration. MENOPUR 600 IU and M ENOPUR 1200 may be adm inistered by
S.C. only because the syringe which is a part of a package is for S.C. administration only.
There are great inter-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 Graaan follicle from which the oocyte will be liberated after the administration of
human chorionic gonadotrophin (hCG).
MENOPUR therapy should start within the initial 7 day s of the menstrual cycle. The recommended initial dose of MENOPUR is 75 - 150 IU
daily, which should be maintained for at least 7 day s. 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 da ys. 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. I f a patient fails to respond adequately after 4 weeks o f 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 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)
In a protocol of women using down-regulation with a GnRH agonist, MENOPUR therapy should start approximately 2 weeks af ter the start of
agonist treatment. In a protocol of women 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 IU d aily for at least the rst 5 days o f 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 IU pe r adjustment. The maximum daily dose given should not
be higher than 450 IU daily and in most cases dosing beyond 20 day s is not recommended.
When a suitable number of follicles have reached an appropriate size a single injection of up to 10.000 IU hCG should be administered to induce
nal 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.
Sterility in men
First, doses of 1.000 to 3.000 IU hCG are applied three times a week until the normal blood testosterone level is obtained. Then, 1 to 2 bottl es
of HMG (75 – 150 IU FSH + 75 – 150 IU LH) are administered three times a week for a period of several months.
Paediatric population: There is no relevant use of MENOPUR in the paediatric population.
Method of administration
MENOPUR 600 IU and 1200 IU are intended for subcutaneous (S.C.) injection after reconstitution with the solvent provided because the syringe
which is a part of a package is for S.C. administration only. The powder should be reconstituted prior to use. The reconstituted solution can
be used for up to 28 d ays.
General: Shaking should be avoided. The solution should not be used if it contains particles or if it is not clear.

 

 

Hypersensitivity to the active substance or to any of the excipients. 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; - Premature menopause; - 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 in case of: - Primary ovarian failure; - Malformation of sexual organs incompatible with pregnancy; - Fibroid tumours of the uterus incompatible with pregnancy. MENOPUR is contraindicated in men who have: - prostatic carcinoma, testicular tumours; - tumours of the pituitary gland or hypothalamus.

MENOPUR contains a high potent gonadotrophic substance capable of causing mild to severe adverse reactions, and therefore it can be used
only under the supervision of 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 eective
dose in relation to the treatment objective should be used.
The rst 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 deciency, hyperprolactinaemia and pituitary or hypothalamic
tumours, and appropriate specic treatment given.
Patients undergoing stimulation of follicular growth, whether in the frame of a treatment for an ovulatory infertility or ART procedures, may
experience ovarian enlargement or develop hyperstimulation. Adherence to recommended MENOPUR dosage and regime of administration,
and careful monitoring of therapy will minimise the incidence of such events. Acute interpretation of the indices of follicle development and
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 uid 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 eusions, 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 hou rs 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, regime 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 hyperstirnulation.
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 specic 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.
In patients undergoing ovulation induction with gonadotrophins, the incidence of multiple pregnancies is increased compared with natural
conception. 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 abortion 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
dierences 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 benets 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.

In men spermiogram should be monitored during the treatment.

 

 

 

No interaction studies have been performed with MENOPUR in humans. In male infertility treatment, HMG may be injected together
with hCG.

Fertility
MENOPUR is indicated for use in infertility.

Pregnancy
MENOPUR is contraindicated in women who are pregnant.
There are no or limited amount of data from the use of menotrophins in pregnant women. No animal studies have been carried out to evaluate
the eects of MENOPUR during pregnancy.
Lactation
MENOPUR is contraindicated in women who are lactating.

No studies on the eects on the ability to drive and use machines have been performed. However, MENOPUR is unlikely to have inuence on
the patient’s ability to drive and use machines.

The most frequently reported adverse drug reactions reported during treatment with MENOPUR in clinical trials are abdominal pain, headache,
injection site reactions and injection site pain, with an incidence rate up to 5%.
Common (> 1/100 to <1/10): Abdominal pain, abdominal distension, nausea, injection site reactions b, headache, OHSS e, pelvic pain f
Uncommon (> 1/1000 to <1/100 ): Vomiting, abdominal discomfort, diarrhoea, fatigue, dizziness, ovarian cyste, breast complaintsg, hot ush
Rare (>1/10000 to <1/1000 ): Acne, Rash
Unknown (cannot be determined from available data): Visual disorders a, pyrexia, lassitude, hypersensitivity reactionsc, weight increased, musculoskeletal paind, ovarian torsion e, pruritus, urticaria, thromboembolisme.

a Individual cases of temporary amaurosis, diplopia, mydriasis, scotoma, photopsia (lighting and sparks), vitreous oaters, vision blurred and
vision impairment have been reported as visual disorders during the post-marketing period.
b Most frequently reported injection site reaction was injection site pain.
c Cases of localised or generalised allergic reactions, including anaphylactic reactio n , along with associated symptomatology have been
reported rarely.
d Musculoskeletal pain includes arthralgia, back pain, neck pain and pain in extremities.
e Gastrointestinal symptoms associated with OHSS such as abdominal distension and discomfort, nausea, vomiting, diarrhoea have been
reported with MENOPUR in clinical trials. In cases of severe OHSS ascites and pelvic uid collection, pleural eusion, dyspnoea, oliguria,
thromboembolic events and ovarian torsion have been reported as rare complications.
f Pelvic area problems include ovarian pain and uterine pendants.
g Problems aecting breasts include breast pain, increased tactile sensitivity, unrest, nipples pain and breast swelling.

Eect of overdose is not known, however ovarian hyperstimulation may be expected, which will manifest itself clinically only after the application
of HCG to promote ovulation.
Moderate hyperstimulation (grade I) will manifest itself by moderate ovarian enlargement (ovary size 5 – 7 cm), ex cessive steroid secretion, and
abdominal pain. Treatment is not necessary, the patient should be instructed, however, and followed up carefully.
Medium grade hyperstimulation (grade II) with ovarian cysts (ovary size 8 – 10 cm) m anifests itself by abdominal pain, nausea, and vomiting. In
this case symptomatic treatment and perhaps intravenous volume substitution may be necessary.
Serious hyperstimulation (grade III) with large ovarian cysts (ovary size more than 10 cm) a ccompanied by ascites, hydrothorax, abdominal
expansion, abdominal pain, dyspnoea, salt retention, increased haemoglobin concentration, increased blood viscosity, and platelet aggregation
with the risk of thromboembolism requires hospitalisation.

Pharmaco- therapeutical group – gonadotrophins and other substances stimulating ovulation. ATC code: G03GA02
HMG acts directly on the ovaries and testicles with a gametotropic and steroidogenic eect.
Menotrophin, which contains both FSH and LH activity, induces 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 is involved in the physiological events leading to the development of a competent pre-ovulatory
follicle. Follicular growth can be stimulated by FSH in the total absence of LH, but the resulting follicles develop abnormally and are associated
with low oestradiol levels and inability to luteinize to a normal ovulatory stimulus.
In line with the action of LH activity in enhancing stereoidogenesis, oestradiol 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 oestradiol levels. The dierence in oestradiol levels is not found when using low dose o- vulation induction protocols in anovulatory patients.
In the testicles, FSH provokes the ripening of Sertoli cells. This entails above all ripening of spermatic channels and sperm development. An
essential condition is high androgen concentration in the testicles, which can be achieved by preceding HCG treatment.

The pharmacokinetic prole of the FSH in MENOPUR has been documented. After 7 days of repeated dosing with 150 IU MENOP UR 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 SC and IM administration, respectively. Maximum FSH concentrations were reached within 7 hours fo r both routes of
administration.
After repeated administration, FSH was eliminated with a half -life T1/2 (mean ± SD) of 30 ± 11 hou rs and 27 ± 9 hou rs for the SC and IM
administration, respectively. Although the individual LH concentration versus time curves shows 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.

Non-clinical data reveal no special hazard for a human, which is not known from the extensive clinical experience.
Reproduction toxicity studies have not been carried out to evaluate the eects of MENOPUR during pregnancy or post partum as MENOPUR
is not indicated during these periods.
MENOPUR consist of naturally occurring hormones and should be expected to be non-genotoxic. Carcinogenicity studies have not been carried
out as the indication is for short term treatment.

Powder : Lactose monohydrate, polysorbate 20, sodium phosphate dibasic heptahydrate, phosphoric acid (85%).
Solvent : Metacresol, water for injection.

MENOPUR should not be administered in the same injection with other products, except Ferring’s urofollitrophin (FSH) BRAVELLE. Studies
have shown that co-administration of BRAVELLE and MENOPUR does not signicantly alter the expected bioactivity.

See outer carton. After reconstitution, the solution may be stored for a maximum of 28 days at not more than 25°C. Do not freeze.

Store in a refrigerator (2°C - 8°C). Do not freeze. Store in original container in a box to protect against light. For storage conditions after
reconstitution of the medical product, see section 6.3.

MENOPUR 600 IU :
Powder: 2 m l colourless glass (type I glass) vial with a rubber stopper and an aluminium cover closed with an orange plastic cap.
Solvent: 1 m l pre -lled syringe (type I glass) with a rubber tip cap and a plunger rubber stopper.
The product is supplied as a pack of 1 vial of powder, 1 p re-lled syringe with solvent for reconstitution, 1 ne edle for reconstitution and
9 disposable syringes for administration graduated in FSH/LH units with prexed needles, 9 alcoho l pads.
The strength (600IU) in product name on carton is stated in orange colour.
Package size: 1x 600IU + 1 pre lled syringe with solvent
MENOPUR 1200 IU :
Powder: 2 ml colourless glass (type I glass) vial with a rubber stopper and an aluminium cover closed with a white plastic cap.
Solvent: 1 ml pre -lled syringe (type I glass) with a rubber tip cap and a plunger rubber stopper.
The product is supplied as a pack of 1 vial of powder, 2 pre - lled syringes with solvent for reconstitution, 1 needl e for reconstitution and
18 disposable syringes for administration graduated in FSH/LH units with pre - xed needles, 18 alcoh ol pads.
The strength (1200IU) in product name on carton is stated in blue colour.
Package size: 1x 1200IU + 2 pre lled syringe with solvent

The powder should only be reconstituted with the solvent provided in the package.
MENOPUR 600 IU and 1200 IU
Attach the reconstitution needle to the prelled syringe. Inject the total contents of solvent into the vial containing the powder. When reconstituting
MENOPUR 1200 IU use the solvent of both prelled syringes. The powder should dissolve quickly to a clear solution. If not, roll the vial gently
between the hands until the solution is clear. Shaking should be avoided.
Do not apply the prepared solution if it contains particles or is not clear.
The administration syringes are graduated in FSH/LH units from 37.5 – 600 IU and supplied with needles in the MENOPUR 600 IU and 120 0 IU
multidose box.
Draw up the reconstituted solution from the vial into the administration syringe for injection according to the prescribed dose and apply immediately.
Each ml of reconstituted solution contains 600 IU FSH and LH.
Each reconstituted MENOPUR 600 IU or 1200 IU v ial should be for individual patient use only.
Any unused product or waste material should be disposed in accordance with local requirements.