Bravelle

Name: Bravelle

Bravelle and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Bravelle crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, you and your healthcare provider should decide if you will use Bravelle or breastfeed. You should not do both. 

Bravelle Dosage

Use this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

  • other medical conditions you have
  • other medications you are taking
  • how you respond to this medication
  • your weight
  • your age

The recommended dose of Bravelle to promote ovulation is 150 International Units per day for 5 days, administered under the skin (subcutaneously) or into the muscle (intramuscularly). After 5 days, your doctor will individualize the dose for you. The maximum dose is 450 International Units per day. 

The recommended dose of Bravelle for use in the Assisted Reproductive Technology (ART) fertility treatment program is 225 International Units per day for 5 days, administered under the skin (subcutaneously). After 5 days, your doctor will individualize the dose for you. The maximum dose is 450 International Units per day. 

What are some other side effects of Bravelle?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Irritation where the shot is given.
  • Upset stomach.
  • Headache.
  • Stomach cramps.
  • Hot flashes.
  • Bloating.
  • Belly pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Dosage Forms and Strengths

Lyophilized powder for Injection containing 82.5 International Units of FSH, to deliver 75 International Units of FSH after reconstituting with the diluent, supplied in sterile vials with diluent vials and Q•Cap® vial adapters.

Adverse Reactions

The following serious adverse reactions are discussed elsewhere in the labeling:

  • Hypersensitivity and Anaphylactic Reactions [see Warnings and Precautions (5.1)]
  • Abnormal Ovarian Enlargement [see Warnings and Precautions (5.2)]
  • Ovarian Hyperstimulation Syndrome [see Warnings and Precautions (5.3)]
  • Thromboembolic events [see Warnings and Precautions (5.4)]
  • Ovarian Torsion [see Warnings and Precautions (5.5)]
  • Multi-fetal Gestation and Birth [see Warnings and Precautions (5.6)]
  • Congenital Malformations [see Warnings and Precautions (5.7)]
  • Ectopic Pregnancy [see Warnings and Precautions (5.8)]
  • Spontaneous Abortion [see Warnings and Precautions (5.9)]
  • Ovarian Neoplasms [see Warnings and Precautions (5.10)]

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
All Patients with Adverse Events ≥ 2%
Adverse Events (%) Bravelle® subcutaneous Bravelle® intramuscular
N=35 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 (5.3)], Pelvic pain, Breast tenderness, Vaginal discharge. Ovarian enlargement, Multiple pregnancies [see Warnings and Precautions (5.6)]

Skin and subcutaneous tissue disorders: Rash

Vascular disorders: Hot flushes

Bravelle Description

Bravelle® is a product containing a highly purified preparation of human follicle stimulating hormone (hFSH) extracted from the urine of postmenopausal women. Human FSH is a gonadotropin and consists of two non-covalently linked glycoproteins designated as the α and β subunits. The α subunit has 92 amino acids of which two are modified by attachment of carbohydrates. The β subunit has 111 amino acids of which two are modified by attachment of carbohydrates.

Bravelle® is a sterile, lyophilized powder intended for subcutaneous or intramuscular injection after reconstitution with sterile 0.9% Sodium Chloride Injection, USP. Each vial of Bravelle® contains 82.5 International Units (IU) of Follicle Stimulating Hormone (FSH) activity, 23 mg Lactose Monohydrate, 0.005 mg Polysorbate 20, and Sodium Phosphate buffer (Sodium Phosphate dibasic, Heptahydrate and Phosphoric acid) for pH adjustments, which, when reconstituted with diluent, will deliver 75 International Units of FSH. Bravelle® contains up to 2% luteinizing hormone (LH) activity based on bioassay. Human Chorionic Gonadotropin (hCG) is not detected in Bravelle®. When stored at 3° to 25°C, up to 40% of the α-subunits may be oxidized.

The in vivo biological activity of urofollitropin for injection, purified is determined by using reference standards calibrated against the First International Standard for follicle-stimulating hormone, (FSH, Urofollitropin), Urinary, Human for Bioassay, National Institute for Biological Standards and Control (NIBSC) at its 46th meeting in 1995.

FSH is a glycoprotein that is acidic and water-soluble.

Bravelle® has been mixed in vitro with MENOPUR® with no evidence of aggregation.

Therapeutic class: Infertility

How Supplied/Storage and Handling

How Supplied

Bravelle® (urofollitropin for injection, purified) is supplied in a sterile, lyophilized, single dose vial containing 82.5 International Units of FSH, to deliver 75 International Units FSH after reconstituting with the diluent.

Each vial is available with an accompanying vial of sterile diluent containing 2 mL of 0.9% Sodium Chloride Injection, USP.

75 International Units FSH activity, supplied as:
NDC 55566-8505-2: Box of 5 vials + 5 vials diluent.
NDC 55566-8505-6: Box of 5 vials + 5 vials diluent + 5 Q•Cap® vial adaptors.

Storage and Handling

Lyophilized powder may be stored refrigerated or at room temperature (3° to 25° C/37° to 77°F). Protect from light. Use immediately after reconstitution. Discard unused material.

Patient Counseling Information

See FDA-approved patient labeling (Patient Information and Instructions for Use)

Dosing and Use

Instruct women on the correct usage and dosing of MENOPUR® [see Dosage and Administration (2.2)]. Caution women not to change the dosage or the schedule of administration unless she is told to do so by her healthcare provider.

Duration and Monitoring Required

Prior to beginning therapy with Bravelle®, inform women about the time commitment and monitoring procedures necessary for treatment.

Instructions Regarding a Missed Dose

Inform the woman that if she misses or forgets to take a dose of Bravelle®, the next dose should not be doubled and she should call her healthcare provider for further dosing instructions.

Ovarian Hyperstimulation Syndrome (OHSS)

Inform women regarding the risks of OHSS [see Warnings and Precautions (5.3)] and OHSS-associated symptoms including lung and blood vessel problems [see Warnings and Precautions (5.4)] and ovarian torsion [see Warnings and Precautions (5.5)] with the use of Bravelle®.

Multi-fetal Gestation and Birth

Inform women regarding the risk of multi-fetal gestation and birth with the use of Bravelle® [see Warnings and Precautions (5.6)].

Vials of sterile diluent of 0.9% Sodium Chloride Injection, USP, manufactured for Ferring Pharmaceuticals Inc.

MANUFACTURED FOR:

FERRING PHARMACEUTICALS INC.
PARSIPPANY, NJ 07054

6317-06
Revised: February 2014

Dose Adjustments

Data not available

Other Comments

Administration advice:
-Inspect for particulate matter and discoloration prior to administration.
-Alternate injection site daily.
-Administer subcutaneously in the abdomen or intramuscularly.
-If using intramuscularly, a healthcare provider should administer the product.

Storage requirements:
-Store refrigerated or at room temperature; protect from light.
-Use immediately after reconstitution. Discard unused material.

Reconstitution/preparation techniques: The manufacturer product information should be consulted.

Patient advice:
-Prior to beginning therapy, inform women about the time commitment and monitoring procedures necessary for treatment.
-Instruct women on the correct usage and dosing.
-If a dose is missed, the next dose should not be doubled. The patient should call her healthcare provider for further dosing instructions.
-Caution women not to change the dosage or the schedule of administration unless told to do so by her healthcare provider.

Urofollitropin Pregnancy Warnings

Use during pregnancy is contraindicated AU TGA pregnancy category: B2 US FDA pregnancy category: X

Animal studies did not reveal teratogenic effects. There are no adequate or well-controlled studies in pregnant women. AU TGA pregnancy category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage. US FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

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