Cetrotide (Cetrorelix Acetate) - Side Effects and Adverse Reactions

ADVERSE REACTIONS SECTION

The safety of Cetrotide^® (cetrorelix acetate for injection) 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.  Cetrotide^® 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 Cetrotide^® treatment until confirmation of pregnancy by ultrasound at an incidence ≥1% in Cetrotide^® treated subjects undergoing COS.

Table 3: Adverse Events in ≥1%	Cetrotide® N=949
(WHO preferred term)	% (n)
# Intensity moderate or severe, or WHO Grade II or III, respectively
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, rare cases of hypersensitivity reactions including anaphylactoid reactions have been reported.

Two stillbirths were reported in Phase 3 studies of Cetrotide^®.

Congenital Anomalies

Clinical follow-up studies of 316 newborns of women administered Cetrotide^® 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 Cetrotide^® is unknown.  Multiple factors, genetic and others (including, but not limited to ICSI, IVF, gonadotropins, and progesterone) make causal attribution difficult to study.

REPORTS OF SUSPECTED CETROTIDE SIDE EFFECTS / ADVERSE REACTIONS

Possible Cetrotide side effects / adverse reactions in 19 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2012-01-03

Patient: 19 year old female

Reactions: Back Pain, Pelvic Pain

Adverse event resulted in: hospitalization

Suspect drug(s):
Lupron
    Indication: Assisted Fertilisation

Cetrotide
    Indication: Ovulation Induction

Gonal-F
    Indication: Ovulation Induction

Other drugs received by patient: Enoxaparin

Possible Cetrotide side effects / adverse reactions in 31 year old female

Reported by a health professional (non-physician/pharmacist) from France on 2012-03-07

Patient: 31 year old female

Reactions: Hyponatraemia, Ovarian Hyperstimulation Syndrome, Ascites

Adverse event resulted in: hospitalization

Suspect drug(s):
Puregon
    Indication: Product Used FOR Unknown Indication
    Start date: 2011-10-19
    End date: 2011-10-25

Cetrotide
    Indication: Product Used FOR Unknown Indication
    Start date: 2011-10-20
    End date: 2011-10-26

Chorionic Gonadotropin
    Indication: Product Used FOR Unknown Indication
    Start date: 2011-10-26
    End date: 2011-10-26

Possible Cetrotide side effects / adverse reactions in 38 year old female

Reported by a health professional (non-physician/pharmacist) from France on 2012-03-08

Patient: 38 year old female

Reactions: Gastrointestinal Perforation, Ovarian Torsion, Ovarian Hyperstimulation Syndrome

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Puregon
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-09-16
    End date: 2010-09-26

Gonadotrophine Chorionique Endo
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-09-27
    End date: 2010-09-27

Cetrotide
    Indication: Product Used FOR Unknown Indication
    Start date: 2010-09-16
    End date: 2010-09-27