Bravelle (Urofollitropin) is a preparation of highly purified follicle-stimulating hormone (FSH) extracted from the urine of postmenopausal women.

It is used to treat the following conditions:

• Multifollicular development during Assisted Reproductive Technologies:

  • It is used in development of multiple follicles with Assisted Reproductive Technologies (ART) in women who have previously received pituitary suppression.

  • Before therapy, do a complete gynecologic exam and endocrinologic evaluation and diagnose the cause of fertility; exclude the possibility of pregnancy;

  • Look for the fertility status of the male partner;

  • Exclude women with primary ovarian failure

• Ovulation induction:

  • It is used in ovulation induction in women who previously received GnRH agonist or antagonist for pituitary suppression.

  • Before therapy, perform a complete gynecologic exam (including demonstration of tubal patency) and endocrinologic evaluation;

  • Rule out the possibility of pregnancy;

  • Primary ovarian failure should be excluded first

  • The male partner should be evaluated prior to initiating therapy.

Bravelle (Urofollitropin) Dose in Adults

• The dose should be individualized.
• The lowest possible dose should be used
• Over the course of treatment, doses may vary depending on individual patient response.

Dose in the Assisted reproductive technologies (ART):

• Adults:
  • Females: SubQ:
    • Starting on day 2 or 3 of the cycle, give 225 units once daily for the first 5 days
    • urofollitropin and menotropins can be administered together and the total initial dose of both products combined should not exceed 225 units (menotropins 150 units and urofollitropin 75 units; or menotropins 75 units and urofollitropin 150 units).
    • Adjust dose after 5 days according to ultrasound monitoring of ovarian response and measurement of serum estradiol levels.
    • Adjustments should not be done more frequently than once every 2 days or by >75 to 150 units.
    • The maximum daily dose is 450 units (of urofollitropin, or menotropins plus urofollitropin)
    • treatment more than 12 days is not recommended
    • once adequate follicular development is evident, hCG should be given.
    • HCG treatment should be withheld if OHSS is suspected.

Bravelle dose in the treatment of Ovulation induction:

• Adults:
  • Females: IM, SubQ:
    • 150 units once daily given initially for 5 days in the first cycle of treatment.
    • After 5 days, dose adjustments up to 75 to 150 units can be made every ≥2 days according to  ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels
    • The maximum daily dose is 450 units
    • Treatment of more than 12 days is not recommended.
    • If the response to follitropin is appropriate, give hCG
    • withhold the hCG dose if ovarian monitoring suggests an increased risk of OHSS and advise the patient to refrain from intercourse.
    • For subsequent cycles, the starting dose and dosage adjustments should be given based on historical ovarian response.

Bravelle (Urofollitropin) Dose in Childrens

Not recommended

Pregnancy Risk Factor X

• Congenital abnormalities, spontaneous abortion, ectopic pregnancy and multi-fetal births/genders have all been documented.
• Congenital abnormalities may be slightly more common after ART than spontaneous conception.
• Congenital abnormalities can be more likely due to genetics and parental traits like maternal age and sperm characteristics.
• Women who are pregnant or planning to become pregnant should not use it.

Urofollitropin use during breastfeeding:

• It is unknown if urofollitropin can be excreted in breastmilk.
• It is important to weigh the risks and benefits of drug exposure for nursing infants.

Bravelle (Urofollitropin) Dose in Renal Disease:

• There are no dosage adjustments given in manufacturer's labeling.

Bravelle (Urofollitropin) Dose in Liver Disease:

• There are no dosage adjustments given in manufacturer's labeling.

Common Side Effects of Bravelle (Urofollitropin) Include:

• Central nervous system:

  • Headache

• Endocrine & metabolic:

  • Ovarian hyperstimulation syndrome
  • Ovary enlargement

• Gastrointestinal:

  • Abdominal cramps

Less Common Side Effects of Bravelle (Urofollitropin) Include:

• Cardiovascular:

  • Hypertension

• Central Nervous System:

  • Depression
  • Emotional Lability
  • Pain (Including Post-Retrieval Pain)

• Dermatologic:

  • Acne Vulgaris
  • Exfoliative Dermatitis
  • Skin Rash

• Endocrine & Metabolic:

  • Dehydration
  • Hot Flash
  • Ovarian Disease (Cyst Pain)
  • Weight Gain

• Gastrointestinal:

  • Abdominal Pain
  • Constipation
  • Diarrhea
  • Enlargement Of Abdomen
  • Nausea
  • Vomiting

• Genitourinary:

  • Breast Tenderness
  • Cervix Disease
  • Pelvic Cramps
  • Pelvic Pain
  • Spotting
  • Urinary Tract Infection
  • Uterine Spasm
  • Vaginal Discharge
  • Vaginal Hemorrhage

• Infection:

  • Infection

• Local:

  • Injection Site Reaction

• Neuromuscular & Skeletal:

  • Neck Pain

• Respiratory:

  • Respiratory Tract Disease
  • Sinusitis

• Miscellaneous:

  • Fever

Contraindication to Bravelle (Urofollitropin) Include:

• Hypersensitivity to follitropins, or any part thereof
• High levels of FSH indicate primary ovarian failure.
• Nongonadal endocrine conditions such as thyroid, adrenal or pituitary problems that are not treated can result in permanent disability.
• Tumors of the reproductive tract or accessory organs that are sexhormone-dependent
• Tumors of the hypothalamus or pituitary gland
• Undetermined cause: abnormal uterine bleeding
• Cysts or ovarian enlargement that is not caused by PCOS.
• pregnancy

Warnings and precautions

• Hypersensitivity

  • Anaphylactic reactions and hypersensitivity have been observed
  • Stop using if you experience serious reactions.

• Ovarian enlargement:

  • This could be accompanied with abdominal distention or abdominal pain.
  • Stop hCG if your ovaries become abnormally large on the last day. This will reduce the chance of ovarian hyperstimulation syndrome.
  • In the event of significant ovarian enlargement, it is important to avoid having sex.

• Ovarian hyperstimulation syndrome:

  • Ovarian hyperstimulation Syndrome (OHSS), is a rare, exaggerated response for ovulation-induction therapy
  • This syndrome can develop within 24 hours after treatment, but may become more severe 7-10 days later.
  • Symptoms of mild/moderate OHSS might include abdominal distention/discomfort, diarrhea, nausea, and/or vomiting.
  • Severe symptoms of OHSS include severe abdominal pain, severe dyspnea and ascites/oliguria, severe dyspnea, severe dyspnea and hypotension.
  • A possible cause of low creatinine clearance, decreased hemoconcentration, hypoproteinemia and elevated liver enzymes could also be present.
  • Treatment is mainly symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications
  • Therapy with gonadotropins is stopped.

• Ovarian neoplasms

  • Women who have received multiple-drug therapy to control their ovarian stimulation have had malignant and benign neoplasms.
  • It has not been proven that causality exists.

• Ovarian torsion

  • This was seen after gonadotropin treatment
  • It could be due to OHSS or prior ovarian torsion or current ovarian cyst.
  • Ovarian damage can be limited by early diagnosis and prompt treatment.

• Effects on the pulmonary system:

  • Severe pulmonary conditions such as acute respiratory distress syndrome, acute pulmonary emboli syndrome and exacerbation asthma have been reported.

• Events that are thromboembolic:

  • Thromboembolic events have been observed in association with and apart from ovarian hyperstimulation Syndrome (OHSS).
  • Women with family or personal risk factors for thrombosis should be cautious.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious
  • Safety and efficacy are not known.

• Renal impairment

  • Patients with impaired renal function should be cautious
  • Safety and efficacy are not known 

Monitoring Parameters:

• Monitor sufficient follicular growth and maturation.
• This can be directly estimated by transvaginal sonographic visualization of the ovaries and endometrial lining.
• Monitoring for the growth and development of follicles and timing hCG administration should be guided by estradiol levels and ultrasonography. Indirect evaluation of estrogenic activity like changes in vaginal cytology and changes in appearance and volume of cervical mucus may be assessed clinically.
• The clinical confirmation of ovulation is done by direct and indirect indices of progesterone production as well as sonographic evidence of ovulation.
• Direct or indirect indices of progesterone production most generally used are: rise in serum or urine LH, rise in basal body temperature, increase in serum progesterone, and menstruation following the shift in basal body temperature.
• Sonographic evidence of ovulation mainly includes collapsed follicle, fluid in the cul-de-sac, features consistent with corpus luteum formation, and secretory endometrium.
• Monitor for signs and symptoms of OHSS for at least 14 days following hCG administration.

• OHSS: Monitoring of hospitalized patients should include:

  • abdominal circumference
  • albumin
  • cardiorespiratory status
  • electrolyte
  • fluid balance
  • hematocrit
  • hemoglobin
  • serum creatinine
  • urine output
  • urine specific gravity
  • vital signs
  • weight (all daily or as necessary)
  • liver enzymes (weekly).

How to administer Bravelle (Urofollitropin)?

• Administer IM or SubQ.
• IM administration should be done by a health care provider.

SubQ:

• Administer to alternating sites on the lower abdomen.

Mechanism of action of Bravelle (Urofollitropin):

• Bravelle (Urofollitropin), a highly purified Follicle-stimulating Hormone (FSH), is extracted from the urine postmenopausal females.
• Women who aren't experiencing primary ovarian failure can stimulate ovarian growth with follitropins.
• FSH is required for normal follicular development, maturation, gonadal steroids production and spermatogenesis.

Half-life elimination: IM:

• 37 hours (single dose), 15 hours (multiple doses)
• SubQ:
  • 32 hours (single dose), 21 hours (multiple doses)

Time to peak, plasma: IM:

• 17 hours (single dose), 11 hours (multiple doses)
• SubQ:  
  • 21 hours (single dose), 10 hours (multiple doses)

International Brands of Urofollitropin:

• Bravelle
• Foliculin-75 HP
• Foligem
• Follegon
• Follimon
• Follitrin
• Fostimon
• Fostimon HP
• Fostimonkit
• Fostipur
• Lishenbao
• Metrodin
• Metrodin HP
• Postine

Urofollitrophin brands in Pakistan: