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