PREGNYL 5000IU Powder for solution for injection Ref.[6665] Active ingredients: Chorionic gonadotrophin (human)

In males and females

Hypersensitivity reactions

Hypersensitivity reactions, both generalised and local; anaphylaxis; and angioedema have been reported. If a hypersensitivity reaction is suspected, discontinue Pregnyl and assess for other potential causes for the event (see section 4.3).

General

Pregnyl should not be used for body weight reduction. HCG has no effect on fat metabolism, fat distribution or appetite.

Additionally in females

Ectopic pregnancy

Infertile women undergoing Assisted Reproductive Technologies (ART) have an increased incidence of ectopic pregnancy. Early ultrasound confirmation that a pregnancy is intrauterine is therefore important.

Prior to treating patients for inadequate endogenous stimulation of the gonads, an examination should be performed to exclude anatomical abnormalities of the genital organs or nongonadal endocrinopathies (e.g. thyroid or adrenal disorders, diabetes). Primary ovarian failure should be excluded by the determination of gonadotrophin levels.

Multi-fetal gestation and birth

In the pregnancies occurring after induction of ovulation with gonadotrophic preparations, there is an increased risk of abortion and multiplets. Multiple pregnancy, especially high order, carries an increased risk in adverse maternal and perinatal outcomes. The parents should be advised of the potential risks of multiple pregnancies before starting treatment.

Congenital Malformations

The incidence of congenital malformations after Assisted Reproductive Technologies (ART) may be higher than after spontaneous conceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age, sperm characteristics) and an increased incidence of multiple gestations.

Vascular Complications

Thromboembolic events, both in association with and separate from OHSS, have been reported following treatment with gonadotropins, including Pregnyl. Intravascular thrombosis, which may originate in venous or arterial vessels, can result in reduced blood flow to vital organs or the extremities. Women with generally recognised risk factors for thrombosis, such as a personal or family history, severe obesity 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 IVF treatment need to be weighed against the risks. It should be noted, however, that pregnancy itself also carries an increased risk of thrombosis.

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 whether or not treatment with gonadotrophins increases the baseline risk of these tumours in infertile women.

Medical examinations

For up to ten days after administration of Pregnyl, a pregnancy test may give a false-positive result.

Ovarian Hyperstimulation Syndrome (OHSS)

OHSS is a medical event distinct from uncomplicated ovarian enlargement. Clinical signs and symptoms of mild and moderate OHSS are abdominal pain, nausea, diarrhea, mild to moderate enlargement of ovaries and ovarian cysts. Severe OHSS may be life-threatening. Clinical signs and symptoms of severe OHSS are large ovarian cysts, acute abdominal pain, ascites, pleural effusion, hydrothorax, dyspnea, oliguria, hematological abnormalities and weight gain. In rare instances, venous or arterial thromboembolism may occur in association with OHSS. Transient liver function test abnormalities suggestive of hepatic dysfunction with or without morphologic changes on liver biopsy have also been reported in association with OHSS.

OHSS may be caused by administration of human Chorionic Gonadotropin (hCG) and by pregnancy (endogenous hCG). Early OHSS usually occurs within 10 days after hCG administration and may be associated with an excessive ovarian response to gonadotropin stimulation. Late OHSS occurs more than 10 days after hCG administration, as a consequence of the hormonal changes with pregnancy. Because of the risk of developing OHSS, patients should be monitored for at least two weeks after hCG administration.

Women with known risk factors for a high ovarian response may be especially prone to the development of OHSS during or following treatment with Pregnyl. For women having their first cycle of ovarian stimulation, for whom risk factors are only partially known, close observation for early signs and symptoms of OHSS is recommended.

To reduce the risk of OHSS, ultrasonographic assessments of follicular development should be performed prior to treatment and at regular intervals during treatment. The concurrent determination of serum estradiol levels may also be useful. In ART, there is an increased risk of OHSS with 18 or more follicles of 11 mm or more in diameter. When there are 30 or more follicles in total, it is advised to withhold hCG administration.

Depending on the ovarian response, the following measures can be considered to reduce the risk of OHSS:

• withhold further stimulation with a gonadotropin for a maximum of 3 days (coasting);
• withhold hCG and cancel the treatment cycle;
• administer a dose lower than 10,000 IU of urinary hCG for triggering final oocyte maturation, e.g. 5,000 IU urinary hCG or 250 micrograms rec-hCG (which is equivalent to approximately 6,500 IU of urinary hCG);
• cancel the fresh embryo transfer and cryopreserve embryos;
• avoid administration of hCG for luteal phase support.

Adherence to the recommended Pregnyl dose and treatment regimen and careful monitoring of ovarian response is important to reduce the risk of OHSS. If OHSS develops, standard and appropriate management of OHSS should be implemented and followed.

Ovarian torsion

Ovarian torsion has been reported after treatment with gonadotropins, including Pregnyl. Ovarian torsion may be related to other conditions, such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, and previous or current ovarian cysts. Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.

Additionally in males

Antibody formation

Administration of hCG can provoke the formation of antibodies against hCG. In rare cases, this may result in an ineffective treatment.

Treatment with hCG leads to increased androgen production. Therefore:

Patients with latent or overt cardiac failure, renal dysfunction, hypertension, epilepsy or migraine (or a history of these conditions) should be kept under close medical supervision, since aggravation or recurrence may occasionally be induced as a result of increased androgen production.

Male paediatric patient

HCG should be used cautiously in prepubertal boys to avoid premature epiphyseal closure or precocious sexual development. Skeletal maturation should be monitored regularly.

No interaction studies have been performed; interactions with commonly used medicinal products can therefore not be excluded.

Not applicable.

As far as known Pregnyl has no influence on the ability to drive and use machines.

Frequency is unknown for all undesirable effects described below (cannot be determined with available data).

Immune system disorders: In rare cases generalized rash or fever may occur.

General disorders and administrative site conditions: Local site reactions such as bruising, pain, redness, swelling and itching. Oedema. Occasionally allergic reactions have
been reported, mostly manifesting as pain and/or rash at the injection site (see also section 4.4). Tiredness.

Nervous system disorders: Headache.

Psychiatric disorders: Mood changes.

In the female

Reproductive system and breast disorders:

Unwanted ovarian hyperstimulation, mild or severe ovarian hyperstimulation syndrome (OHSS, see section 4.4):

Mild OHSS:

Painful breasts
Mild to moderate enlargement of ovaries
Ovarian cysts
Abdominal pain
Abdominal discomfort
Gastrointestinal symptoms such as nausea, diarrhoea and bloating

Severe OHSS:

Large ovarian cysts (prone to rupture), Acute abdominal pain
Ascites
Weight gain
Hydrothorax
In rare instances, thromboembolism has been associated with FSH/hCG therapy.

Not all symptoms described are always associated to OHSS.

In the male

Metabolism and nutrition disorders: Water and sodium retention is occasionally seen after administration of high dosages; this is regarded as a result of excessive androgen production.

Reproduction system and breast disorders: HCG treatment may sporadically cause gynaecomastia.

Skin and subcutaneous tissue disorders: Acne may occur occasionally during hCG therapy.

Reporting of suspect adverse reactions

Reporting suspect 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 suspect adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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