The safety of Ovidrel® (choriogonadotropin alfa injection) was examined in four clinical studies that treated 752 patients of whom 335 received Ovidrel® (choriogonadotropin alfa injection) 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® (choriogonadotropin alfa injection) or an approved urinary-derived hCG, 14.6 % (49 of 335 patients) in the Ovidrel® (choriogonadotropin alfa injection) 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® (choriogonadotropin alfa injection) 250 µg occurring in at least 2% of patients (regardless of causality) are listed in Table 9 for the 3 ART studies and in Table 10 for the single OI study.
Table 9: Incidence of Adverse Events of r-hCG in ART (Studies 7648, 7927, 9073)
| Body System
| Ovidrel® (choriogonadotropin alfa injection) 250 µg
Incidence Rate % (n)
|At Least One Adverse Event||33.1% (78)|
|INJECTION SITE PAIN||7.6% (18)|
|INJECTION SITE BRUISING||4.7% (11)|
|GASTRO-INTESTINAL SYSTEM DISORDERS||8.5% (20)|
|ABDOMINAL PAIN||4.2% (10)|
|SECONDARY TERMS (POST-OPERATIVE PAIN)||4.7% (11)|
|POST-OPERATIVE PAIN||4.7% (11)|
Adverse events not listed in Table 9 that occurred in less than 2% of patients treated with Ovidrel® (choriogonadotropin alfa injection) 250 µg whether or not considered causally related to Ovidrel® (choriogonadotropin alfa injection) , 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 10: Incidence of Adverse Events of r-hCG in Ovulation Induction (Study 8209)
| Body System
|Ovidrel® 250 µg (n=99) Incidence Rate % (n)|
|At Least One Adverse Event||26.2% (26)|
|APPLICATION SITE DISORDERS||16.2% (16)|
|INJECTION SITE PAIN||8.1% (8)|
|INJECTION SITE INFLAMMATION||2.0% (2)|
|INJECTION SITE BRUISING||3.0% (3)|
|INJECTION SITE REACTION||3.0% (3)|
|REPRODUCTIVE DISORDERS, FEMALE||7.1% (7)|
|OVARIAN CYST||3.0% (3)|
|OVARIAN HYPERSTIMULATION||3.0% (3)|
|GASTRO—INTESTINAL SYSTEM DISORDERS||4.0% (4)|
|ABDOMINAL PAIN||3.0% (3)|
Additional adverse events not listed in Table 10 that occurred in less than 2% of patients treated with Ovidrel® (choriogonadotropin alfa injection) 250 µg, whether or not considered causally related to Ovidrel® (choriogonadotropin alfa injection) , 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:
- Spontaneous Abortion
- Ectopic Pregnancy
- Premature Labor
- Postpartum Fever
- Congenital abnormalities
Of 125 clinical pregnancies reported following treatment with FSH and Ovidrel® (choriogonadotropin alfa injection) 250 µg or 500 µg, three were associated with a congenital anomaly of the fetus or newborn. Among patients receiving Ovidrel® (choriogonadotropin alfa injection) 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® (choriogonadotropin alfa injection) 500 ug, 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:
- Pulmonary and vascular complications (see WARNINGS)
- Adnexal torsion (as a complication of ovarian enlargement)
- Mild to moderate ovarian enlargement
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.
In addition to adverse events reported from clinical trials, the following events have been reported during post-marketing use of Ovidrel® (choriogonadotropin alfa injection) . Therefore, these events were reported from a population of uncertain size, the frequency or causal relationship to Ovidrel® (choriogonadotropin alfa injection) cannot be reliably determined.
- Cases of allergic reactions, including anaphylactic reactions and mild reversible skin rashes have been reported in patients treated with Ovidrel® (choriogonadotropin alfa injection) since market introduction. The causal relationship is unknown.
- Thromboembolic events both in association with, and separate from, the Ovarian Hyperstimulation Syndrome (see “WARNINGS”)