Urofollitropin

Medically reviewed by Drugs.com. Last updated on Aug 31, 2023.

Pronunciation

(yoor oh fol li TROE pin)

Index Terms

• Follicle-Stimulating Hormone, Human
• FSH
• hFSH

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Injection:

Bravelle: 75 units (1 ea [DSC])

Brand Names: U.S.

• Bravelle [DSC]

Pharmacologic Category

• Gonadotropin
• Ovulation Stimulator

Pharmacology

Urofollitropin is a preparation of highly purified follicle-stimulating hormone (FSH) extracted from the urine of postmenopausal women. Follitropins stimulate ovarian follicular growth in women who do not have primary ovarian failure. FSH is required for normal follicular growth, maturation, gonadal steroid production, and spermatogenesis.

Time to Peak

IM: 17 hours (single dose), 11 hours (multiple doses)

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

Half-Life Elimination

IM: 37 hours (single dose), 15 hours (multiple doses)

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

Use: Labeled Indications

Multifollicular development during Assisted Reproductive Technologies: Development of multiple follicles with Assisted Reproductive Technologies (ART) in women who have previously received pituitary suppression.

Limitations of use: Prior to therapy, perform a complete gynecologic exam and endocrinologic evaluation and diagnose cause of fertility; exclude the possibility of pregnancy; evaluate the fertility status of the male partner; exclude women with primary ovarian failure

Ovulation induction: Ovulation induction in women who previously received GnRH agonist or antagonist for pituitary suppression.

Limitations of use: Prior to therapy, perform a complete gynecologic exam (including demonstration of tubal patency) and endocrinologic evaluation; exclude the possibility of pregnancy; evaluate the fertility status of the male partner; exclude a diagnosis of primary ovarian failure

Contraindications

Hypersensitivity to follitropins or any component of the formulation; high levels of FSH indicating primary ovarian failure; uncontrolled nongonadal endocrinopathies (eg, thyroid, adrenal, or pituitary disorders); sex hormone-dependent tumors of the reproductive tract and accessory organ; tumors of pituitary gland or hypothalamus; abnormal uterine bleeding of undetermined origin; ovarian cysts or enlargement not due to polycystic ovary syndrome; pregnancy

Dosing: Adult

Note: Bravelle injection has been discontinued in the United States for >1 year.

Note: Dose should be individualized. Use the lowest dose consistent with the expectation of good results. Over the course of treatment, doses may vary depending on individual patient response.

Assisted reproductive technologies (ART): Adults: Females: SubQ: Starting on day 2 or 3 of cycle, administer 225 units once daily for the first 5 days; urofollitropin may be administered together with menotropins 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 based on ultrasound monitoring of ovarian response and measurement of serum estradiol levels. Do not make additional adjustments more frequently than once every 2 days or by >75 to 150 units. Maximum daily dose: 450 units (of urofollitropin, or menotropins plus urofollitropin); treatment >12 days is not recommended; once adequate follicular development is evident, hCG should be administered. Withhold the hCG dose if ovarian monitoring suggests an increased risk of OHSS.

Ovulation induction: Adults: Females: IM, SubQ: Initial: 150 units once daily 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 based on ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels; maximum daily dose: 450 units; treatment >12 days is not recommended. If response to follitropin is appropriate, administer 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 determined based on historical ovarian response.

Reconstitution

Dissolve contents of vial in sodium chloride 0.9% 1 mL (provided); gently swirl (do not shake). Do not use if solution is not clear or contains particles. If more than 1 vial is required for a single dose, up to 6 vials can be reconstituted with sodium chloride 0.9% 1 mL and administered as a single injection. This is done by first reconstituting 1 vial with sodium chloride 0.9% as previously described, withdrawing the entire contents of the reconstituted vial, and (using this as the diluent for the second vial) injecting into the second vial, etc. Use immediately after reconstitution. May mix with Menopur (menotropins for injection).

Administration

Administer IM or SubQ.

IM administration should be given by a health care provider.

SubQ: Administer to alternating sites on lower abdomen.

Storage

Lyophilized powder may be stored in the refrigerator or at room temperature of 3°C to 25°C (37°F to 77°F). Protect from light. Discard unused portion.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Percentage may vary by indication or route of administration.

>10%:

Central nervous system: Headache

Endocrine & metabolic: Ovarian hyperstimulation syndrome, ovary enlargement

Gastrointestinal: Abdominal cramps

1% to 10%:

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

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Hypersensitivity and anaphylactic reactions have been reported; discontinue use for serious reactions and treat appropriately.

• Ovarian enlargement: May be accompanied by abdominal distention and/or abdominal pain. If ovaries are abnormally enlarged on the last day of treatment, withhold hCG to reduce the risk of ovarian hyperstimulation syndrome (OHSS). Intercourse should be avoided with significant ovarian enlargement.

• Ovarian hyperstimulation syndrome: Ovarian hyperstimulation syndrome (OHSS) is a rare exaggerated response to ovulation induction therapy (Fiedler 2012; SOGC-CFAS 2011). This syndrome may begin within 24 hours of treatment but may become most severe 7 to 10 days after therapy (SOGC-CFAS 2011). Symptoms of mild/moderate OHSS may include abdominal distention/discomfort, diarrhea, nausea, and/or vomiting. Severe OHSS symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, or nausea/vomiting (intractable). Decreased creatinine clearance, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM 2016; Fiedler 2012; SOGC-CFAS 2011). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (ASRM 2016; SOGC-CFAS 2011). Therapy with gonadotropins should be stopped.

• Ovarian neoplasms: Benign and malignant neoplasms have been reported (infrequently) in women receiving multiple-drug therapy for controlled ovarian stimulation; causal effect has not been established.

• Ovarian torsion: Has been reported following gonadotropin treatment; may be related to OHSS, prior ovarian torsion, prior or current ovarian cyst, polycystic ovaries, pregnancy, or prior abdominal surgery. Early diagnosis and prompt detorsion may limit the extent of ovarian damage.

• Pulmonary effects: Serious pulmonary conditions (atelectasis, acute respiratory distress syndrome, and exacerbation of asthma) have been reported.

• Thromboembolic events: In association with and separate from ovarian hyperstimulation syndrome (OHSS), thromboembolic events have been reported. Use caution in women with personal or family risk factors for thrombosis.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; safety and efficacy have not been established.

• Renal impairment: Use with caution in patients with renal impairment; safety and efficacy have not been established.

Other warnings/precautions:

• Appropriate use: To minimize risks, use only at the lowest effective dose. Monitor ovarian response with serum estradiol and vaginal ultrasound on a regular basis.

• Experienced physician: These medications should only be used by physicians who are thoroughly familiar with infertility problems and their management.

• Multiple births: May result from the use of these medications; advise patient of the potential risk of multifetal gestation and multiple births before starting the treatment.

Monitoring Parameters

Monitor sufficient follicular growth and maturation. This may be directly estimated by transvaginal sonographic visualization of the ovaries and endometrial lining. The combination of both ultrasonography and measurement of estradiol levels is useful for monitoring for the growth and development of follicles and timing hCG administration.

The clinical evaluation of estrogenic activity (changes in vaginal cytology and changes in appearance and volume of cervical mucus) provides an indirect estimate of the estrogenic effect upon the target organs and, therefore, it should only be used adjunctively with more direct estimates of follicular development (ultrasonography and serum estradiol determinations).

The clinical confirmation of ovulation is obtained 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 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 2 weeks following hCG administration.

OHSS: Monitoring of hospitalized patients should include abdominal circumference, albumin, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, serum creatinine, urine output, urine specific gravity, vital signs, weight (all daily or as necessary) and liver enzymes (weekly) (SOGC-CFAS 2011).

Pregnancy Risk Factor X Pregnancy Considerations

Urofollitropin is used for the induction of ovulation and with assisted reproductive technologies (ART); use is contraindicated in women who are already pregnant.

Ectopic pregnancy, congenital abnormalities, spontaneous abortion, and multifetal gestations/births have been reported. The incidence of congenital abnormality may be slightly higher after ART than with spontaneous conception; higher incidence may be related to parental characteristics (maternal age, genetics, sperm characteristics).

Patient Education

What is this drug used for?

• It is used to help women get pregnant.

• It may be given to you for other reasons. Talk with the doctor.

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:

• Injection site irritation

• Nausea

• Headache

• Abdominal pain

• Bloating

• Abdominal cramps

• Hot flashes

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Ovarian hyperstimulation syndrome like severe abdominal pain or bloating; severe nausea, vomiting, or diarrhea; excessive weight gain; shortness of breath; or change in how much urine is passed.

• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood.

• Abnormal vaginal bleeding

• Pelvic pain

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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