The following serious adverse reactions are discussed elsewhere in the labeling:
- Hypersensitivity and Anaphylactic Reactions [see WARNINGS AND PRECAUTIONS]
- Abnormal Ovarian Enlargement [see WARNINGS AND PRECAUTIONS]
- Ovarian Hyperstimulation Syndrome [see WARNINGS AND PRECAUTIONS]
- Thromboembolic events [see WARNINGS AND PRECAUTIONS]
- Ovarian Torsion [see WARNINGS AND PRECAUTIONS]
- Multi-fetal Gestation and Birth [see WARNINGS AND PRECAUTIONS]
- Congenital Malformations [see WARNINGS AND PRECAUTIONS]
- Ectopic Pregnancy [see WARNINGS AND PRECAUTIONS]
- Spontaneous Abortion [see WARNINGS AND PRECAUTIONS]
- Ovarian Neoplasms [see WARNINGS AND PRECAUTIONS]
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.
The safety of BRAVELLE® was examined in four clinical studies that enrolled a total of 222 women who received BRAVELLE® .
Ovulation Induction
In a randomized, multi-center, active controlled study, a total of 72 women received BRAVELLE® (35 in a subcutaneous administration arm and 37 in an intramuscular administration arm) for induction of ovulation. Adverse reactions occurring at an incidence of ≥ 2% incidence in women receiving BRAVELLE® are shown in Table 1.
Table 1: Ovulation Induction Safety Profile
Adverse Events (%) | All Patients with Adverse Events ≥ 2% | |
BRAVELLE® subcutaneous N=35 |
BRAVELLE® intramuscular N=37 |
|
Genitourinary/Reproductive | ||
OHSS | 4 (11.4) | 2 (5.4) |
Vaginal Hemorrhage | 3 (8.6) | 0 (0.0) |
Ovarian Disorder (Pain, Cyst) | 1 (2.9) | 3 (8.1) |
Urinary tract infection | 0 | 1 (2.7) |
Cervix disorder | 1 (2.9) | 0 |
Gastrointestinal | ||
Nausea | 2 (5.7) | 0 (0.0) |
Enlarged Abdomen | 1 (2.9) | 1 (2.7) |
Abdominal Pain | 1 (2.9) | 2 (5.4) |
Vomiting | 0 | 1 (2.7) |
Constipation | 0 | 1 (2.7) |
Diarrhea | 0 | 1 (2.7) |
Metabolic/Nutritional | ||
Dehydration | 0 | 1 (2.7) |
Weight gain | 1 (2.9) | 0 |
Skin/Appendages | ||
Acne | 1 (2.9) | 0 |
Exfoliative dermatitis | 0 | 1 (2.7) |
Other Body Systems | ||
Headache | 4 (11.4) | 3 (8.1) |
Pain | 2 (5.7) | 0 (0.0) |
Neck pain | 0 | 1 (2.7) |
Respiratory Disorder | 2 (5.7) | 0 (0.0) |
Hot Flashes | 2 (5.7) | 0 (0.0) |
Fever | 0 | 1 (2.7) |
Hypertension | 0 | 1 (2.7) |
Emotional lability | 0 | 1 (2.7) |
Depression | 0 | 1 (2.7) |
Accidental injury | 0 | 1 (2.7) |
Assisted Reproductive Technology
Three studies examined the safety profile of BRAVELLE® in ART. A total of 150 women received treatment with BRAVELLE® in these studies. Adverse reactions occurring at an incidence of ≥ 2% incidence for this integrative assessment are presented in Table 2.
Table 2: Integrated IVF Safety Profile
All Patients with Adverse Events ≥ 2% | |
Adverse Events (%) | BRAVELLE® subcutaneous N=150 |
Genitourinary/Reproductive | |
Vaginal hemorrhage | 7 (4.7) |
Post retrieval pain | 12 (8.0) |
Pelvic pain/cramps | 10 (6.7) |
OHSS | 9 (6.0) |
Uterine spasms | 4 (2.7) |
Vaginal spotting | 4 (2.7) |
Urinary tract infection | 5 (3.3) |
Ovarian disorder | 3 (2.0) |
Breast tenderness | 3 (2.0) |
Vaginal Discharge | 4 (2.7) |
Infection fungal | 3 (2.0) |
Gastrointestinal | |
Abdominal cramps | 21 (14.0) |
Nausea | 13 (8.7) |
Abdominal pain | 7 (4.7) |
Abdominal fullness/enlargement | 10 (6.7) |
Constipation | 3 (2.0) |
Other Body Systems | |
Headache | 19 (12.7) |
Pain | 8 (5.3) |
Rash | 4 (2.7) |
Respiratory disorder | 6 (4.0) |
Sinusitis | 3 (2.0) |
Injection site reaction | 6 (4.0) |
Hot flash | 6 (4.0) |
Emotional lability | 3 (2.0) |
Postmarketing Experience
The following adverse reactions have been reported during postmarketing use of gonadotropins. Because these reactions were reported voluntarily from a population of uncertain size, the frequency or a causal relationship to BRAVELLE® cannot be reliably determined.
Gastrointestinal disorders: Abdominal pain, Nausea, Vomiting, Abdominal distension, Abdominal discomfort, Diarrhea, Constipation
General disorders and administration site conditions: Pain, Injection site reactions (redness, bruising, swelling and/or pruritus)
Infections and infestations: Urinary tract infection, Nasopharyngitis
Musculoskeletal and connective tissue disorders: Muscle spasm
Nervous system disorders: Headache
Reproductive system disorders: Vaginal hemorrhage, OHSS [see WARNINGS AND PRECAUTIONS], Pelvic pain, Breast tenderness, Vaginal discharge. Ovarian enlargement, Multiple pregnancies [see WARNINGS AND PRECAUTIONS]
Skin and subcutaneous tissue disorders: Rash
Vascular disorders: Hot flushes