FOSTIMON PFS

Posology Treatment with Fostimon PFS 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 PFS 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 PFS can be administered by daily injection. In menstruating patients the treatment should begin within the first 7 days of the menstrual cycle. 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 PFS is then discontinued and ovulation can be induced by administering human chorionic gonadotropin (hCG). 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.

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 PFS 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 PFS 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 PFS injection, to induce final follicular maturation.

Oocyte retrieval is performed 34-35 hours later. Method of administration Fostimon PFS is intended for 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 PFS 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.

Adverse reactions (ADRs) reported in clinical trials with Fostimon PFS 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. 4. MedDRA System Organ Class Frequency Adverse Drug Reaction (MedDRA Preferred term) Endocrine disorders Uncommon Hyperthyroidism Psychiatric disorders Uncommon Mood swings Common HeadacheNervous system disorders Uncommon Lethargy Dizziness Respiratory, thoracic and mediastinal disorders Uncommon Dyspnoea Epistaxis Common Constipation Abdominal distension Gastro-intestinal disorders Uncommon Nausea Abdominal pain Dyspepsia Skin and subcutaneous tissue disorders Uncommon Erythema Pruritus Renal and urinary disorders Uncommon Cystitis Common Ovarian hyperstimulation syndrome Reproductive system and breast disorders Uncommon Breast enlargement Breast pain Hot flush Common PainGeneral disorders and administration site conditions 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 and venous thromboembolism have 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.

Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system detailed below: UNITED KINGDOM: Yellow Card Scheme. uk/yellowcard

Self-injections of Fostimon PFS 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 PFS 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 PFS 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 tumors, 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.

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. e. not as part of controlled ovarian hyperstimulation in medically assisted reproduction programs), the administration of Fostimon PFS 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. 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 tumors in infertile women.

Congenital malformation The prevalence of congenital malformations after ART may be slightly higher than after spontaneous conceptions. 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.

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.

e. essentially ‘sodium-free’.

• Hypersensitivity to FSH or to any of the excipients • Ovarian enlargement or cysts not related to polycystic ovarian syndrome • Gynaecological bleeding of unknown cause • Ovarian, uterine or breast carcinoma • Tumours of the hypothalamus or pituitary gland Fostimon PFS is contraindicated when an effective response cannot be achieved, for example: • Primary ovarian failure • Malformations of sexual organs incompatible with pregnancy • Fibroid tumours of the uterus incompatible with pregnancy