Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN, Haarlem, The Netherlands
For males and females:
Additionally for females:
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Puregon may contain traces of streptomycin and/or neomycin. These antibiotics may cause hypersensitivity reactions in susceptible persons.
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.
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 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.
Infertile women undergoing ART have an increased incidence of ectopic pregnancies. Early ultrasound confirmation that a pregnancy is intrauterine is therefore important.
Rates of pregnancy loss in women undergoing assisted reproduction techniques are higher than in the normal population.
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.
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 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.
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.
Medical conditions that contraindicate pregnancy should also be evaluated before starting treatment with Puregon.
Elevated endogenous FSH levels in men are indicative of primary testicular failure. Such patients are unresponsive to Puregon/hCG therapy.
This medicinal product contains less than 1 mmol sodium (23 mg) per injection, that is to say essentially ‘sodium-free’.
Concomitant use of Puregon and clomifene citrate may enhance the follicular response. After pituitary desensitisation induced by a GnRH agonist, a higher dose of Puregon may be necessary to achieve an adequate follicular response.
Puregon is used in the treatment of women undergoing ovarian induction or controlled ovarian hyperstimulation in assisted reproduction programmes. In males Puregon is used in the treatment of deficient spermatogenesis due to hypogonadotrophic hypogonadism. For posology and method of administration, see section 4.2.
The use of Puregon during pregnancy is not indicated. In case of inadvertent exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of recombinant FSH. However, to date, no particular malformative effect has been reported. No teratogenic effect has been observed in animal studies.
There is no information available from clinical or animal studies on the excretion of follitropin beta in milk. It is unlikely that follitropin beta is excreted in human milk due to its high molecular weight. If follitropin beta would be excreted in human milk, it would be degraded in the gastrointestinal tract of the child. Follitropin beta may affect milk production.
Puregon has no or negligible influence on the ability to drive and use machines.
Clinical use of Puregon by the intramuscular or subcutaneous routes may lead to local reactions at the site of injection (3% of all patients treated). The majority of these local reactions are mild and transient in nature. Generalised hypersensitivity reactions been observed uncommonly (approximately 0.2% of all patients treated with follitropin beta).
In approximately 4% of the women treated with follitropin beta in clinical trials, signs and symptoms related to ovarian hyperstimulation syndrome (OHSS) have been reported (see section 4.4). Adverse reactions related to this syndrome include pelvic pain and/or congestion, abdominal pain and/or distension, breast complaints and ovarian enlargement.
The table below lists the adverse reactions with follitropin beta reported in clinical trials in females, according to system organ class and frequency; common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100).
Common: Headache
Common: Abdominal distension, Abdominal pain
Uncommon: Abdominal discomfort, Constipation, Diarrhoea, Nausea
Common: OHSS, Pelvic pain
Uncommon: Breast complaints1, Metrorrhagia, Ovarian cyst, Ovarian enlargement, Ovarian torsion, Uterine enlargement, Vaginal haemorrhage
Common: Injection site reaction2
Uncommon: Generalised hypersensitivity reaction3
1 Breast complaints include tenderness, pain and/or engorgement and nipple pain.
2 Local reactions at the site of injection include: bruising, pain, redness, swelling and itching.
3 Generalised hypersensitivity reaction include erythema, urticaria, rash and pruritus.
In addition, ectopic pregnancy, miscarriage and multiple gestations have been reported. These are considered to be related to ART or subsequent pregnancy.
In rare instances, thromboembolism has been associated with follitropin beta/hCG therapy as with other gonadotrophins.
The table below lists the adverse reactions with follitropin beta reported in a clinical trial in males (30 patients dosed), according to system organ class and frequency; common (≥1/100 to <1/10).
Common: Headache
Common: Acne, Rash
Common: Epididymal cyst, Gynaecomastia
Common: Injection site reaction2
1 Adverse reactions that are reported only once are listed as common because a single report raises the frequency above 1%.
2 Local reactions at the site of injection include induration and pain.
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 listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
