FOSTIMON Powder and solvent for solution for injection Ref.[27708] Active ingredients: Urofollitropin

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 lifethreatening. 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 tumors 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

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 from 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.

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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system detailed below:

IRELAND: HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; e-mail: medsafety@hpra.ie.

UNITED KINGDOM: Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.

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