OVIDREL SIDE EFFECTS

SIDE EFFECTS

The safety of Ovidrel® was examined in four clinical studies that treated 752 patients of whom 335 received Ovidrel® 250 μg following follicular recruitment with gonadotropins. When patients enrolled in four clinical studies (3 in ART and one in OI) were injected subcutaneously with either Ovidrel® or an approved urinary-derived hCG, 14.6 % (49 of 335 patients) in the Ovidrel® 250 μg group experienced application site disorders compared to 28% (92 of 328 patients) in the approved u-Hcg group. Adverse events reported for Ovidrel® 250 μg occurring in at least 2% of patients (regardless of causality) are listed in Table 1 for the 3 ART studies and in Table 10 for the single OI study.

Table 1: Incidence of Adverse Events of r-hCG in ART (Studies 7648, 7927, 9073)

Adverse events not listed in Table 9 that occurred in less than 2% of patients treated with Ovidrel® 250 μg whether or not considered causally related to Ovidrel® , included: injection site inflammation and reaction, flatulence, diarrhea, hiccup, ectopic pregnancy, breast pain, intermenstrual bleeding, vaginal hemorrhage, cervical lesion, leukorrhea, ovarian hyperstimulation, uterine disorders, vaginitis, vaginal discomfort, body pain, back pain, fever, dizziness, headache, hot flashes, malaise, paraesthesias, rash, emotional lability, insomnia, upper respiratory tract infection, cough, dysuria, urinary tract infection, urinary incontinence, albuminuria, cardiac arrhythmia, genital moniliasis, genital herpes, leukocytosis, heart murmur and cervical carcinoma.

Table 2: Incidence of Adverse Events of r-hCG in Ovulation Induction (Study 8209)

Additional adverse events not listed in Table 10 that occurred in less than 2% of patients treated with Ovidrel® 250 μg, whether or not considered causally related to Ovidrel® , included: breast pain, flatulence, abdominal enlargement, pharyngitis, upper respiratory tract infection, hyperglycemia and pruritis.

The following medical events have been reported subsequent to pregnancies resulting from hCG therapy in controlled clinical studies:

1. Spontaneous Abortion
2. Ectopic Pregnancy
3. Premature Labor
4. Postpartum Fever
5. Congenital Abnormalities

Of 125 clinical pregnancies reported following treatment with FSH and Ovidrel® 250 μg or 500 μg, three were associated with a congenital anomaly of the fetus or newborn. Among patients receiving Ovidrel® 250 μg, cranial malformation was detected in the fetus of one woman and a chromosomal abnormality (47, XXX) in another. These events were judged by the investigators to be of unlikely or unknown relation to treatment. These three events represent an incidence of major congenital malformations of 2.4%, which is consistent with the reported rate for pregnancies resulting from natural or assisted conception. In a woman who received Ovidrel® 500 μg, one birth in a set of triplets was associated with Down’s syndrome and atrial septal defect. This event was considered to be unrelated to the study drug.

The following adverse reactions have been previously reported during menotropin therapy:

1. Pulmonary and vascular complications
2. Adnexal torsion (as a complication of ovarian enlargement)
3. Mild to moderate ovarian enlargement
4. Hemoperitoneum

There have been infrequent reports of ovarian neoplasms, both benign and malignant, in women who have undergone multiple drug regimens for ovulation induction; however, a causal relationship has not been established.

Post-Marketing Experience

In addition to adverse events reported from clinical trials, the following events have been reported during post-marketing use of Ovidrel®. Therefore, these events were reported from a population of uncertain size, the frequency or causal relationship to Ovidrel® cannot be reliably determined.

• Cases of allergic reactions, including anaphylactic reactions and mild reversible skin rashes have been reported in patients treated with Ovidrel® since market introduction. The causal relationship is unknown.
• Thromboembolic events both in association with, and separate from, the Ovarian Hyperstimulation Syndrome.

SRC: NLM .