Cetrotide · 4.4 Special warnings and precautions for use · 1

HOS-083906 · has-adverse-reaction-information · PDF-Seite 4

Summary of the safety profile The most commonly reported adverse reactions are local injection site reactions such as erythema, swelling and pruritus that are usually transient in nature and mild in intensity. In clinical trials, these effects were observed with a frequency of 9.4% following multiple injections of Cetrotide 0.25 mg. Mild to moderate OHSS (WHO grade I or II) have been commonly reported and should be considered as an intrinsic risk of the stimulation procedure. Inversely, severe OHSS remains uncommon. Uncommonly, cases of hypersensitivity reactions including pseudo-allergic/anaphylactoid reactions have been reported. 4 List of adverse reactions The adverse reactions reported below are classified according to frequency of occurrence as follows: 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). Immune system disorders Uncommon: Systemic allergic/pseudo-allergic reactions including life-threatening anaphylaxis. Nervous system disorders Uncommon: Headache Gastrointestinal disorders Uncommon: Nausea Reproductive system and breast disorders Common: Mild to moderate OHSS (WHO grade I or II) can occur which is an intrinsic risk of the stimulation procedure (see section 4.4). Uncommon: Severe OHSS (WHO grade III) General disorders and administration site conditions Common: Local reactions at the injection site (e.g. erythema, swelling and pruritus). 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 listed in Appendix V.

HOS-083902 · has-contraindication-information · PDF-Seite 3

Cetrorelix is not to be used in the presence of any of the conditions listed below: • Hypersensitivity to the active substance or any structural analogues of gonadotropin-releasing hormone (GnRH), extrinsic peptide hormones or to any of the excipients listed in section 6.1. • During pregnancy and lactation. • Patients with severe renal impairment.

HOS-083901 · has-indication-information · PDF-Seite 2

Prevention of premature ovulation in patients undergoing a controlled ovarian stimulation, followed by oocyte pick-up and assisted reproductive techniques. In clinical trials Cetrotide was used with human menopausal gonadotropin (HMG), however, limited experience with recombinant follicle-stimulating hormone (FSH) suggested similar efficacy.

HOS-083904 · has-interaction-information · PDF-Seite 4

No formal drug-drug interaction studies have been performed with cetrorelix. In vitro investigations have shown that interactions are unlikely with medicinal products that are metabolised by cytochrome P450 or glucuronised or conjugated in some other way. However, the possibility of interactions with gonadotropins or medicinal products that may induce histamine release in susceptible individuals, cannot be totally excluded.

HOS-083905 · has-pregnancy-information · PDF-Seite 4

Pregnancy and breast-feeding Cetrotide is not intended to be used during pregnancy and lactation (see section 4.3). Fertility Studies in animals have indicated that cetrorelix exerts a dose related influence on fertility, reproductive performance and pregnancy. No teratogenic effects occurred when the medicinal product was administered during the sensitive phase of gestation.

HOS-083903 · has-warning-information · PDF-Seite 3

Allergic conditions Cases of allergic/pseudoallergic reactions, including life-threatening anaphylaxis with the first dose have been reported (see section 4.8). Special care should be taken in women with signs and symptoms of active allergic conditions or known history of allergic predisposition. Treatment with Cetrotide is not advised in women with severe allergic conditions. Ovarian Hyperstimulation Syndrome (OHSS) During or following ovarian stimulation an ovarian hyperstimulation syndrome can occur. This event must be considered as an intrinsic risk of the stimulation procedure with gonadotropins An OHSS should be treated symptomatically, e.g. with rest, intravenous electrolytes/colloids and heparin therapy. Luteal phase support should be given according to the reproductive medical centre´s practice. 3 Repeated ovarian stimulation procedure There is limited experience up to now with the administration of cetrorelix during a repeated ovarian stimulation procedure. Therefore, cetrorelix should be used in repeated cycles only after a careful benefit/risk evaluation. Congenital anomalies The prevalence of congenital anomalies after the use of assisted reproductive technologies (ART) with or without GnRH antagonists may be slightly higher than after spontaneous conceptions although it is unclear whether this is related to factors inherent to the couple's infertility or the ART procedures. Limited data from clinical follow-up studies in 316 newborns of women administered cetrorelix for infertility treatments suggest that cetrorelix does not increase the risk of congenital anomalies in the offsprings. Hepatic impairment Cetrorelix has not been studied in patients with hepatic impairment and caution is therefore warranted. Renal impairment Cetrorelix has not been studied in patients with renal impairment and caution is therefore warranted. Cetrorelix is contraindicated in patients with severe renal impairment (see section 4.3).