FDA label 1f143808-6446-45a1-9a8c-9e58a26c22cb

WARNINGS Cetrorelix acetate for injection should be prescribed by physicians who are experienced in fertility treatment. Before starting treatment with cetrorelix acetate, pregnancy must be excluded (see CONTRAINDICATIONS and PRECAUTIONS ).

ADVERSE REACTIONS The safety of cetrorelix acetate in 949 patients undergoing controlled ovarian stimulation in clinical studies was evaluated. Women were between 19 and 40 years of age (mean: 32). 94.0% of them were Caucasian. Cetrorelix acetate was given in doses ranging from 0.1 mg to 5 mg as either a single or multiple dose. Table 3 shows systemic adverse events, reported in clinical studies without regard to causality, from the beginning of cetrorelix acetate treatment until confirmation of pregnancy by ultrasound at an incidence ≥ 1% in cetrorelix acetate treated subjects undergoing COS. Table 3: Adverse Events in ≥1% * Intensity moderate or severe, or WHO Grade II or III, respectively (WHO preferred term) Cetrorelix Acetate N=949 % (n) Ovarian Hyperstimulation Syndrome * 3.5 (33) Nausea 1.3 (12) Headache 1.1 (10) Local site reactions (e.g. redness, erythema, bruising, itching, swelling, and pruritus) were reported. Usually, they were of a transient nature, mild intensity and short duration. During post-marketing surveillance, cases of mild to moderate Ovarian Hyperstimulation syndrome and cases of hypersensitivity reactions including anaphylactoid reactions have been reported. Two stillbirths were reported in Phase 3 studies of cetrorelix acetate. Congenital Anomalies Clinical follow-up studies of 316 newborns of women administered cetrorelix acetate were reviewed. One infant of a set of twin neonates was found to have anencephaly at birth and died after four days. The other twin was normal. Developmental findings from ongoing baby follow-up included a child with a ventricular septal defect and another child with bilateral congenital glaucoma. Four pregnancies that resulted in therapeutic abortion in Phase 2 and Phase 3 controlled ovarian stimulation studies had major anomalies (diaphragmatic hernia, trisomy 21, Klinefelter syndrome, polymalformation, and trisomy 18). In three of these four cases, intracytoplasmic sperm injection (ICSI) was the fertilization method employed; in the fourth case, in vitro fertilization (IVF) was the method employed. The minor congenital anomalies reported include: supernumerary nipple, bilateral strabismus, imperforate hymen, congenital nevi, hemangiomata, and QT syndrome. The causal relationship between the reported anomalies and cetrorelix acetate is unknown. Multiple factors, genetic and others (including, but not limited to ICSI, IVF, gonadotropins, and progesterone) make causal attribution difficult to study.

<table ID="t3" width="100%"><caption>Table 3: Adverse Events in &#x2265;1% </caption><colgroup><col width="50.000%" align="left"/><col width="50.000%" align="left"/></colgroup><tfoot><tr styleCode="First Last"><td colspan="2" align="left" valign="top"><paragraph styleCode="First Footnote">* Intensity moderate or severe, or WHO Grade II or III, respectively</paragraph></td></tr></tfoot><tbody><tr><td styleCode="Botrule Lrule Rrule Toprule" align="left" valign="top"><content styleCode="bold">(WHO preferred term)</content></td><td styleCode="Botrule Rrule Toprule" align="center" valign="top"><content styleCode="bold">Cetrorelix Acetate N=949 % (n)</content></td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top">Ovarian Hyperstimulation Syndrome^*</td><td styleCode="Botrule Rrule" align="center" valign="top">3.5 (33)</td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top">Nausea</td><td styleCode="Botrule Rrule" align="center" valign="top">1.3 (12)</td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top">Headache</td><td styleCode="Botrule Rrule" align="center" valign="top">1.1 (10)</td></tr></tbody></table>