Urofollitropin

Urofollitropin is a purified form of a hormone called follicle-stimulating hormone (FSH). This hormone is important in the development of follicles (eggs) that are produced by the ovaries in women.

Urofollitropin is used together with other medicines to treat infertility in women with FSH deficiency. Urofollitropin is also used to help the ovaries produce multiple eggs for use in "in-vitro" fertilization.

Urofollitropin alone will not cause ovulation (production of an egg by the ovaries). You will need to receive other medicines to stimulate ovulation.

Urofollitropin may also be used for purposes not listed in this medication guide.

You should not use this medicine if you have primary ovarian failure, abnormal vaginal bleeding, uncontrolled thyroid or adrenal gland disorders, an ovarian cyst, breast cancer, uterine or ovarian cancer, a pituitary gland tumor, or infertility that is not caused by lack of ovulation.

Do not use urofollitropin if you are pregnant.

Stop using urofollitropin, do not have sexual intercourse, and call your doctor right away if you have any of the following symptoms: stomach pain, bloating, nausea, vomiting, diarrhea, rapid weight gain, little or no urinating, or pain when you breathe, rapid heart rate, or shortness of breath.

You should not use this medicine if you are allergic to urofollitropin or similar medicines (such as follitropin, lutropin alfa, menotropin), or if you have:

• a condition called primary ovarian failure;
• cancer of the breast, uterus, or ovary;
• an untreated or uncontrolled disorder of your thyroid or adrenal gland;
• infertility that is not caused by lack of ovulation;
• abnormal vaginal bleeding that has not been checked by a doctor;
• an ovarian cyst;
• a tumor of your pituitary gland; or
• if you are pregnant.

Your doctor will perform blood tests and a pelvic exam to make sure you do not have conditions that would prevent you from safely using urofollitropin.

Your male sexual partner's fertility should also be checked before you are treated with urofollitropin.

To make sure urofollitropin is safe for you, tell your doctor if you have:

• asthma;
• a history of stomach surgery;
• a history of ovarian cyst or "torsion" (twisting) of your ovary; or
• risk factors for blood clots (such as diabetes, smoking, heart disease, coronary artery disease, being overweight, having a family history of coronary artery disease).

Using urofollitropin can increase your chances of having a multiple pregnancy (twins, triplets, quadruplets, etc). A multiple pregnancy is a high-risk pregnancy for the mother and for the babies. Follow your doctor's instructions about any special care you may need during your pregnancy.

Urofollitropin may also increase your risk of tubal pregnancy, miscarriage, stillbirth, premature labor, birth defects, or fever after childbirth if you become pregnant after being treated with this medicine. Talk with your doctor if you are concerned about these risks.

Urofollitropin may increase your risk of developing uterine cancer. Ask your doctor about your specific risk. Report any unusual vaginal bleeding right away.

FDA pregnancy category X. Although urofollitropin can help you become pregnant, this medicine can harm an unborn baby or cause birth defects. Do not use urofollitropin if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

It is not known whether urofollitropin passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

FertinexTM (urofollitropin for injection, purified) is a preparation of highly purified Follicle Stimulating Hormone (FSH) extracted from the urine of post-menopausal women. Purification is by immunoaffinity chromatography using murine monoclonal antibody to human FSH. The purification process results in a consistent FSH isoform profile, significantly enhanced specific activity (8,500-13, 500 IU FSH/mg protein), and ≥95% purity. Each ampule of Fertinex (urofollitropin) TM contains either 75 IU or 150 IU of highly purified FSH and 10 mg lactose in a sterile, lyophilized form. If required, pH is adjusted with 0.1 M hydrochloric acid and/or 0.1 M sodium hydroxide. Fertinex (urofollitropin) TM is administered by subcutaneous injection.

Fertinex (urofollitropin) TM contains an acidic, water soluble glycoprotein biologically standardized for FSH gonadotropin activity in terms of the Second International Reference Preparation for Human Menopausal Gonadotropins established in September, 1964 by the Expert Committee on Biological Standards of the World Health Organization. Negligible amounts (≤ 0.1 IU LH/1000 IU FSH) of leutinizing hormone (LH) activity are contained in Fertinex (urofollitropin) TM.

Therapeutic Class : Infertility.

• Getting Pregnant (Tips for Trying to Conceive)
• Infertility

• It is used to help women get pregnant.
• It may be given to you for other reasons. Talk with the doctor.

• If you have an allergy to urofollitropin or any other part of urofollitropin.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If your ovaries no longer make eggs (primary ovarian failure).
• If you have any of these health problems: Adrenal gland disease, brain tumor, pituitary gland disease, or thyroid gland disease.
• If you have any of these health problems: A tumor in your female organs, enlarged ovaries or ovarian cysts, or vaginal bleeding where the cause is not known.
• If you are pregnant or may be pregnant. Do not take this medicine if you are pregnant.

This is not a list of all drugs or health problems that interact with urofollitropin.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

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).

There are no known significant interactions.

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.

Applies to urofollitropin: powder for solution

Along with its needed effects, urofollitropin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking urofollitropin:

• Abdominal or pelvic pain
• bloating (mild)

• Abdominal or stomach pain (severe)
• bloating (moderate to severe)
• chest pain or trouble breathing
• decreased amount of urine
• feeling of indigestion
• headache, sudden and severe
• nausea, vomiting, or diarrhea (continuing or severe)
• pelvic pain (severe)
• shortness of breath or wheezing
• skin rash or hives
• swelling of the arms or lower legs
• weight gain (rapid)

Some side effects of urofollitropin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Breast tenderness
• diarrhea (mild)
• headache
• hot flashes
• nausea
• redness, pain, or swelling at the injection site
• vomiting

After you stop using this medicine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

• Abdominal or stomach pain (severe)
• bloating (moderate to severe)
• decreased amount of urine
• feeling of indigestion
• nausea, vomiting, or diarrhea (continuing or severe)
• pelvic pain (severe)
• shortness of breath
• swelling of the lower legs
• weight gain (rapid)

Applies to urofollitropin: injectable powder for injection, intramuscular powder for injection, subcutaneous powder for injection

General

The most common adverse events were multi-fetal gestation and birth, abdominal cramps, headache, and ovarian hyperstimulation syndrome (OHSS).[Ref]

Genitourinary

Very common (10% or more): Multi-fetal gestation and birth (up to 66.7%), ovarian hyperstimulation syndrome (OHSS) (11.4%)
Common (1% to 10%): Hot flashes, vaginal hemorrhage, ovarian disorder (pain, cyst), urinary tract infection, cervix disorder, post retrieval pain, uterine spasms, vaginal spotting, breast tenderness, vaginal discharge, infection fungal, pelvic pain
Frequency not reported: Abnormal ovarian enlargement
Postmarketing reports: Ovarian enlargement, pelvic pain, hot flushes[Ref]

Cardiovascular

Common (1% to 10%): Hypertension[Ref]

Dermatologic

Common (1% to 10%): Acne, exfoliative dermatitis, rash[Ref]

Gastrointestinal

Very common (10% or more): Abdominal cramps (14%), abdominal pain
Common (1% to 10%): Nausea, enlarged abdomen, vomiting, diarrhea, constipation, abdominal discomfort[Ref]

Local

Common (1% to 10%): Injection site pain and reactions (redness, bruising, swelling, and/or itching)[Ref]

Metabolic

Common (1% to 10%): Weight gain, dehydration[Ref]

Musculoskeletal

Common (1% to 10%): Neck pain
Postmarketing reports: Muscle spasm[Ref]

Nervous system

Very common (10% or more): Headache (12.7%)[Ref]

Other

Common (1% to 10%): Pain, fever, accidental injury[Ref]

Psychiatric

Common (1% to 10%): Emotional lability, depression[Ref]

Respiratory

Common (1% to 10%): Respiratory disorder, sinusitis
Postmarketing reports: Nasopharyngitis[Ref]

Hypersensitivity

Frequency not reported: Allergic, local or generalized skin reactions, delayed-type hypersensitivity[Ref]

Some side effects of urofollitropin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.