Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Antibiotic hypersensitivity reactions
•    Puregon may contain traces of streptomycin and/or neomycin. These antibiotics may cause hypersensitivity reactions in susceptible persons.

Infertility evaluation before starting treatment
•     Before starting treatment, the couple's infertility should be assessed as appropriate. In particular, patients should be evaluated for hypothyroidism, adrenocortical insufficiency, hyperprolactinemia and pituitary or hypothalamic tumours, and appropriate specific treatment given.


In females
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, diarrhoea, 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, dyspnoea, oliguria, haematological 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 Puregon. 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.

Follow current clinical practice for reducing the risk of OHSS during Assisted Reproductive Technology (ART). Adherence to the recommended Puregon dose and treatment regimen and careful monitoring of ovarian response is important to reduce the risk of OHSS. To monitor 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 oestradiol 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.

If OHSS develops, standard and appropriate management of OHSS should be implemented and followed.

Multiple Pregnancy
Multiple pregnancies and births have been reported for all gonadotropin treatments, including Puregon.
Multiple gestation, especially high order, carries an increased risk of adverse maternal (pregnancy and delivery complications) and perinatal (low birth weight) outcomes. For anovulatory women undergoing ovulation induction, monitoring follicular development with transvaginal ultrasonography may aid in determining whether or not to continue the cycle in order to reduce the risk of multiple pregnancies. The concurrent determination of serum oestradiol levels may also be useful. The patients should be advised of the potential risks of multiple births before starting treatment.

In women undergoing Assisted Reproduction Technologies (ART) procedures, the risk of a multiple pregnancy is mainly related to the number of embryos transferred. When used for an ovulation induction cycle, appropriate FSH dose adjustment(s) should prevent multiple follicle development.

Ectopic Pregnancy
Infertile women undergoing ART have an increased incidence of ectopic pregnancies. Early ultrasound confirmation that a pregnancy is intrauterine is therefore important.

Spontaneous Abortion
Rates of pregnancy loss in women undergoing assisted reproduction techniques are higher than in the normal population.

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

Congenital Malformations
The incidence 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 gestations.

Ovarian Torsion
Ovarian torsion has been reported after treatment with gonadotropins, including Puregon. Ovarian torsion may be associated with other risk factors such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst and polycystic ovaries.
Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.

Ovarian and other Reproductive System Neoplasms
There have been reports of ovarian and other reproductive system neoplasms, both benign and malignant, in women who have undergone multiple treatment regimens for infertility treatment. It is not established whether or not treatment with gonadotrophins increases the risk of these tumours in infertile women.

Other Medical Conditions
Medical conditions that contraindicate pregnancy should also be evaluated before starting treatment with Puregon.

In males

Primary Testicular Failure
Elevated endogenous FSH levels in men are indicative of primary testicular failure. Such patients are unresponsive to Puregon/hCG therapy.

Benzyl alcohol
Benzyl alcohol may cause anaphylactoid reactions.
Large amounts of benzyl alcohol may cause metabolic acidosis. Special precautions should be taken when prescribing Puregon to pregnant or breast-feeding women and patients with liver or kidney disease.

Sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per injection, that is to say essentially ‘sodium-free’.

Effects on Driving

4.7 Effects on ability to drive and use machines

Puregon has no or negligible influence on the ability to drive and use machines.