Sterility in women:
 Anovulation (including polycystic ovarian syndrome, PCOS) in women who have been
unresponsive to treatment with clomifene citrate.
 Controlled ovarian hyperstimulation to induce the development of multiple follicles in Assisted
Reproductive Technologies (ART) such as in vitro fertilisation (IVF), Gamete Intra-fallopian
Transfer (GIFT) and Zygotes Intra-fallopian Transfer (ZIFT).

Posology
Treatment with FOSTIMON should be initiated under the supervision of a physician experienced
in the treatment of infertility problems.

There are great inter- and intra-individual variations in the response of the ovaries to exogenous
gonadotropins. This makes it impossible to set a uniform dosage scheme. The dosage should,
therefore, be adjusted individually depending on the ovarian response. This requires
ultrasonography and may also include monitoring of oestradiol levels.
 Anovulation (including PCOS):
The objective of a treatment with FOSTIMON is to develop a single mature de Graaf follicle from
which the ovum will be released after the administration of human chorionic gonadotropin (hCG).
FOSTIMON can be administered by daily injection. In menstruating patients the treatment should
begin within the first 7 days of the menstrual cycle.
A commonly used regimen starts at 75 to 150 IU of FSH per day and is increased if necessary by
37.5 IU (up to 75 IU), with intervals of 7 or 14 days preferably, in order to achieve an adequate
but not excessive response.
The treatment should be adjusted to the individual patient's response, assessed by measuring the
follicle size by ultrasonography and/or oestrogen levels.
The daily dose is then maintained until pre-ovulatory conditions are reached. Usually, 7 to 14 days
of treatment is sufficient to reach this state.
The administration of FOSTIMON is then discontinued and ovulation can be induced by
administering human chorionic gonadotropin (hCG).
If the number of responding follicles is too high or oestradiol levels increase too rapidly, i.e. more
than a daily doubling for oestradiol for two or three consecutive days, the daily dose should be
decreased. Since follicles of over 14 mm may lead to pregnancies, multiple pre-ovulatory follicles
exceeding 14 mm carry the risk of multiple gestations. In that case hCG should be withheld and
pregnancy should be avoided in order to prevent multiple gestations. The patient should use a
barrier method of contraception or refrain from having coitus until the next menstrual bleeding has
started (see section 4.4). The treatment should recommence in the next treatment cycle at a lower
dose than in the previous cycle.
Maximum daily dosages of FSH should generally not exceed 225 IU.
If a patient fails to adequately respond after 4 weeks of treatment, the cycle should be abandoned
and the patient should recommence at a higher initial dose than in the previous cycle.
Once the ideal response is obtained, a single injection of 5 000 IU to 10 000 IU of hCG should be
administered 24 to 48 hours after the last FOSTIMON injection.
The patient is recommended to have coitus on the day of hCG injection and the following day.
Alternatively, intrauterine insemination may be performed.
 Controlled ovarian hyperstimulation during ART
Pituitary down-regulation in order to suppress the endogenous LH peak and to control basal levels
of LH is now commonly achieved by administration of a gonadotropin releasing hormone agonist
(GnRH agonist).
In a commonly used protocol the administration of FOSTIMON begins approximately two weeks
after the start of the agonist treatment, both treatments are then continued until adequate follicular
development has been achieved. For example, following two weeks of pituitary down-regulation
with agonist, 150 to 225 IU of FSH are administered for the first seven days. The dose is then
adjusted according to the patient's ovarian response.

An alternative protocol for superovulation involves the administration of 150 to 225 IU of FSH
daily starting on the 2nd or 3rd day of the cycle. The treatment is continued until sufficient
follicular development has been achieved (assessed by monitoring of serum oestrogen
concentrations and/or ultrasound) with the dose adjusted according to the patient's response
(usually not higher than 450 IU daily). Adequate follicular development is usually achieved on
average around the tenth day of treatment (5 to 20 days).
When an optimal response is obtained a single injection of 5 000 IU to 10 000 IU of hCG
administered 24 to 48 hours after the last FOSTIMON injection, to induce final follicular
maturation.
Oocyte retrieval is performed 34-35 hours later.
Method of administration
FOSTIMON is intended for intramuscular and subcutaneous administration.
The powder should be reconstituted immediately prior to use with the solvent provided.
To prevent painful injections and minimize leakage from the injection site FOSTIMON should be
slowly administered subcutaneously. The subcutaneous injection site should be alternated to
prevent lipo-atrophy. Any unused solution should be discarded.
Subcutaneous injections can be self-administered by the patient, provided the physician's
instructions and recommendations are strictly followed.

Self-injections of FOSTIMON should be performed only by motivated, trained and well informed
patients. Prior to self-injections, the patient must be shown how to perform a subcutaneous
injection, showing her where the injection can be given and how to prepare the solution to be
injected. The first injection of FOSTIMON should be performed under direct medical supervision.
Particularly, in patients with known hypersensitivity to gonadotropins anaphylactic reactions might
occur. In these patients, the first injection of FOSTIMON should be performed by a physician in
settings with facilities for cardio-pulmonary resuscitation.
Before starting the 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, hyperprolactinemia and pituitary or hypothalamic
tumours, for which appropriate specific treatments are given.

Multiple Pregnancies
In patients undergoing ART procedures the risk of multiple pregnancies is related mainly to the
number of replaced embryos. In patients undergoing a treatment for ovulation induction the
incidence of multiple pregnancies and births is increased as compared to natural conception. The
majority of multiple conceptions are twins. To minimise the risk of multiple pregnancy, careful
monitoring of ovarian response is recommended.
Unwanted ovarian hyperstimulation
In the treatment of female patients, ultrasonographic assessment of follicular development, and
determination of oestradiol levels should be performed prior to treatment and at regular intervals
during treatment. Apart from the development of a high number of follicles, oestradiol levels may
rise very rapidly, e.g. more than a daily doubling for two or three consecutive days, and possibly
reaching excessively high values. The diagnosis of ovarian hyperstimulation may be confirmed by
ultrasound examination. If this unwanted ovarian hyperstimulation occurs (i.e. not as part of
controlled ovarian hyperstimulation in medically assisted reproduction programs), the
administration of FOSTIMON should be discontinued. In that case pregnancy should be avoided
and hCG must be withheld, because it may induce, in addition to multiple ovulation, the ovarian
hyperstimulation syndrome (OHSS). Clinical symptoms and signs of mild ovarian
hyperstimulation syndrome are abdominal pain, nausea, diarrhoea, and mild to moderate
enlargement of ovaries and ovarian cysts. In rare cases severe ovarian hyperstimulation syndrome
occurs, which may be life-threatening. This is characterised by large ovarian cysts (prone to
rupture), ascites, often hydrothorax and weight gain. In rare instances, venous or arterial
thromboembolism may occur in association with OHSS (see section 4.8).
Pregnancy wastage
The incidence of spontaneous miscarriage is higher in patients treated with FSH than in the general
population, but it is comparable to the incidence found in women with other fertility disorders.
Ectopic pregnancy
Since infertile women undergoing assisted reproduction, and particularly IVF, often have tubal
abnormalities the incidence of ectopic pregnancies might be increased. Early ultrasound
confirmation that a pregnancy is intrauterine is therefore important.
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 gonadotropins 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
gonadotropins. In these women, the benefits of gonadotropin administration need to be weighed
against the risks (see section 4.8).
Infectious diseases
When medicinal products prepared from human urine are administered, the possibility of
transmitting infective agents cannot be totally excluded.
This also applies to unknown or emerging viruses and other pathogens.
However, this risk is limited by the extraction/purification process, which includes viral
inactivation/removal steps. These steps have been validated using model viruses, and particularly
HIV, Herpes virus and Papillomavirus.
Up to now there is reassuring clinical experience with follitropin products regarding the lack of
virus transmission associated with the administration of gonadotropins extracted from human
urine.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially
‘sodium-free’.

No drug/drug interaction studies have been conducted for FOSTIMON in humans. Although there
is no clinical experience, it is expected that the concomitant use of FOSTIMON and clomifene
citrate may enhance the follicular response.

Pregnancy
Pregnancy category X
FOSTIMON is not indicated during pregnancy and lactation.
No teratogenic risk has been reported following controlled ovarian stimulation, in clinical use
with urinary gonadotropins. To date no other relevant epidemiological data are available.
Animal studies do not indicate teratogenic effect.

Lactation
During lactation the secretion of prolactin can entail a poor response to ovarian stimulation.

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

Adverse reactions (ADRs) reported in clinical trials with FOSTIMON are listed in the table below
by body system and frequency. Most events were of mild to moderate severity.
Within each system organ class, the ADRs are ranked under headings of frequency, most frequent
reactions first, using the following convention:
Very common ( 1/10); common (1/100 to 1/10); uncommon (1/1,000 to 1/100); rare
(1/10,000 to 1/1,000); very rare (1/10,000), not known (cannot be estimated form the available
data).
Within each frequency grouping, adverse reactions are presented in order of decreasing
seriousness.
For other undesirable effects which may be associated with the use of gonadotropins such as FSH,
see section 4.4.
MedDRA System Organ Class Frequency Adverse Drug Reaction (MedDRA
Preferred term)
Endocrine disorders Uncommon Hyperthyroidism
Psychiatric disorders Uncommon Mood swings
Nervous system disorders Common Headache
Uncommon Lethargy
Dizziness
Respiratory, thoracic and
mediastinal disorders
Uncommon Dyspnoea
Epistaxis
Gastro-intestinal disorders Common Constipation
Abdominal distension
Uncommon Nausea
Abdominal pain
Dyspepsia
Skin and subcutaneous tissue
disorders
Uncommon Erythema
Pruritus
Renal and urinary disorders Uncommon Cystitis
Reproductive system and breast
disorders
Common Ovarian hyperstimulation syndrome
Uncommon Breast enlargement
Breast pain
Hot flush
General disorders and
administration site conditions
Common Pain
Uncommon Fatigue
Investigations Uncommon Bleeding time prolonged

Local reactions at the site of injection (pain, redness and haematoma) have been rarely observed.
In rare cases, arterial thromboembolism has been associated with a treatment with human
menotrophins/chorionic gonadotropins.
The incidence of miscarriage with gonadotropins therapy is comparable to the incidence in women
with other fertility disorders. A slightly increased risk of ectopic pregnancy and multiple gestations
has been observed.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product.
To report any side effects:
 Saudi Arabia:
The National Pharmacovigilance and Drug Safety Centre (NPC)
o SFDA Call Center: 19999.
o E-mail: npc.drug@sfda.gov.sa
o Website: www.sfda.gov.sa/npc

 Other GCC States:
Please contact the relevant competent authority.

No data on acute toxicity of FSH in humans is available, but the acute toxicity of urinary
gonadotropin preparations in animal studies has been shown to be very low. Too high a dosage of
FSH may lead to hyperstimulation of the ovaries (see section 4.4).

Pharmacotherapeutic group:
Gonadotropins.
ATC CODE: G03GA04
The active substance in FOSTIMON is highly purified Follicle Stimulating Hormone (FSH),
obtained from human Menopausal Gonadotropin (HMG). The main effect of a FSH injection is
the development and maturation of de Graaf follicles.

After subcutaneous injection of 300 IU of FOSTIMON, Cmax is 5.74 ± 0.95 IU/l, and Tmax is
21.33 ± 9.18 hours. AUC0-∞ is 541.22 ± 113.83 IU/l×hour, which is approximately the double of
that described in the literature after intramuscular administration of 150 IU uFSH: 258.6 ± 47.9
IU/lxhour (measurements of FSH plasmatic contents by RIA assays).
Elimination half-life is about 50 hours.
After intramuscular injection, literature reports that the bioavailability of FSH is about 70%.
The pharmacokinetics of FSH in patients with renal or hepatic impairment has not been
investigated.

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated
dose toxicity, with recombinant FSH.
The Ames test did not show any mutagenic activity of FSH.
No carcinogenicity study has been performed.
In a fertility study, high doses of recombinant FSH exerted marked pharmacological effects on the
ovary and other genital organs resulting in impaired fertility and increased embryo-foetal mortality
in the rat and in the rabbit.
FOSTIMON was well tolerated locally after subcutaneous administration in a study performed in
rabbits.

Powder: lactose monohydrate
Solvent: sodium chloride and water for injections

In the absence of compatibility studies, this product must not be mixed with other medicinal
products.

Do not store above 25°C. Keep the vial and the ampoule of solvent in the outer carton, in order to
protect from light.

Powder in a vial (type I glass), with a rubber stopper , with a seal (aluminium) and a flip-off cap
(plastic) + 1 ml of solvent in a type I glass ampoule.

Packs of 1 and 10 vials + solvent.
Not all pack sizes may be marketed

The solution must be prepared just before injection.
One vial is for single use only. The medicinal product must be reconstituted under aseptic
conditions.
FOSTIMON must only be reconstituted with the solvent provided in the package.
A clean surface should be prepared and hands should first be washed before the solution is
reconstituted.
Set out all the following items on the clean surface:
- two cotton-wool alcohol swabs (not provided)
- one vial containing FOSTIMON powder
- one ampoule with solvent
- one needle for preparing the injection and for the intramuscular injection (not provided)
- a fine bore needle for subcutaneous injection (not provided)
Reconstitution of the solution for injection using 1 vial of powder
Prepare the solution for injection:
Open the solvent ampoule containing the clear liquid.
A coloured mark is indicated on the tip of the solvent ampoule:
At this mark the ampoule neck is specifically designed to break more easily. Gently tap the top of
the ampoule to dislodge any liquid which may remain in the tip. Firmly press the ampoule above
the neck and break it while levering up at the coloured mark. Carefully place the open ampoule
onto the preparation area.
Withdraw the solvent:
Attach the reconstitution needle (long needle) to the syringe. With the syringe in one hand, hold
the previously opened solvent ampoule, place the needle into it and withdraw all the solvent.
Place the syringe very carefully on the preparation area and avoid touching the needle
Prepare the solution for injection:
1. Remove the aluminium capsule cover from the vial containing Fostimon powder and
disinfect the rubber area of the cap with a cotton-wool swab moistened with alcohol
2. Take the syringe and slowly inject the solvent into the powder vial through the rubber cap.
3. Gently roll the vial between the hands until the powder has completely dissolved, taking
care to avoid creating foam.
4. Once the powder has dissolved (which, in general, occurs immediately), slowly draw the
solution into the syringe.
Preparation of higher doses, using more than 1 vial of powder

When reconstituting more than 1 vial of FOSTIMON, draw back the reconstituted contents of the
first vial into the syringe and slowly inject into a second vial. Repeat steps 1 to 4 for the second
and subsequent vials, and until the contents of the required number of vials equivalent to the
prescribed dosage are dissolved (within the limits of the maximum total dosage of 450 IU).
The solution must be clear and colourless.
Any unused product or waste material should be disposed of in accordance with local requirements
(once the injection is ended, all the needles and empty syringes should be disposed of in an
appropriate container).