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Follitropin Alfa

Medically reviewed by Drugs.com. Last updated on Jun 27, 2020.

Pronunciation

(foe li TRO pin AL fa)

Index Terms

  • Follicle Stimulating Hormone, Recombinant
  • FSH
  • rFSH-alpha
  • rhFSH-alpha

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

Gonal-f RFF Rediject: 300 units/0.5 mL (0.5 mL); 450 units/0.75 mL (0.75 mL); 900 units/1.5 mL (1.5 mL) [contains metacresol]

Solution Reconstituted, Injection:

Gonal-f: 450 units (1 ea); 1050 units (1 ea) [contains benzyl alcohol]

Solution Reconstituted, Subcutaneous:

Gonal-f RFF: 75 units (1 ea)

Brand Names: U.S.

  • Gonal-f
  • Gonal-f RFF
  • Gonal-f RFF Rediject

Pharmacologic Category

  • Gonadotropin
  • Ovulation Stimulator

Pharmacology

Follitropin alfa is a human FSH preparation of recombinant DNA origin. Follitropins stimulate ovarian follicular growth in women who do not have primary ovarian failure, and stimulate spermatogenesis in men with hypogonadotrophic hypogonadism. FSH is required for normal follicular growth, maturation, gonadal steroid production, and spermatogenesis.

Absorption

SubQ: Absorption rate is slower than the elimination rate

Distribution

Mean Vd: 0.7 L with in vitro fertilization/embryo transfer patients

Excretion

Clearance: IV: 0.6 L/hour in healthy female volunteers

Onset of Action

Peak effect:

Spermatogenesis, median: 6.8-12.4 months (range: 2.7-18.1 months)

Follicle development: Within cycle

Time to Peak

In healthy volunteers:

Females: SubQ: 8-16 hours

Males: SubQ: 11-20 hours

Half-Life Elimination

SubQ: 24-53 hours in healthy female volunteers; 32-41 hours in healthy male volunteers

Use: Labeled Indications

Multifollicular development during Assisted Reproductive Technology (ART): To stimulate the development of multiple follicles with ART

Ovulation induction: Induction of ovulation and pregnancy in oligo-anovulatory infertile patients in whom the cause of infertility is functional and not caused by primary ovarian failure

Spermatogenesis induction (Gonal-f only): Induction of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure

Contraindications

Hypersensitivity to follitropins or any component of the formulation; high levels of FSH indicating primary gonadal failure (ovarian or testicular); sex hormone dependent tumors of the reproductive tract and accessory organs; intracranial lesions (eg, pituitary or hypothalamus tumor); uncontrolled thyroid, pituitary or adrenal dysfunction; abnormal uterine bleeding of undetermined origin; ovarian cysts or enlargement of undetermined origin not due to polycystic ovary syndrome; pregnancy

Canadian labeling: Additional contraindications (not in US labeling): Presence of any cause for infertility other than anovulation (unless candidate for ART); lactation

Dosing: Adult

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.

Ovulation induction: Females: SubQ: Initial: 75 units daily; incremental dose adjustments of up to 37.5 units may be considered after 14 days; further dose increases of the same magnitude can be made, if necessary, every 7 days (maximum dose: 300 units daily). Treatment should be continued until follicular growth and/or serum estradiol levels indicate an adequate ovarian response. If response to follitropin is appropriate, hCG is given 1 day following the last dose to induce final oocyte maturation and ovulation. Withhold hCG if serum estradiol is >2000 pg/mL; discontinue if the ovaries are abnormally enlarged, or if abdominal pain occurs. In general, therapy should not exceed 35 days.

Multifollicular development during ART: Females: SubQ: Initiate therapy with follitropin alfa in the early follicular phase (cycle day 2 or day 3) at a dose of 150 units daily, until sufficient follicular development is attained. In most cases, therapy should not exceed 10 days. In patients ≥35 years whose endogenous gonadotropin levels are suppressed, initiate follitropin alfa at a dose of 225 units daily. Continue treatment until adequate follicular development is indicated as determined by ultrasound in combination with measurement of serum estradiol levels. Consider adjustments to dose after 5 days based on the patient's response; adjust subsequent dosage every 3-5 days by ≤75-150 units additionally at each adjustment. Doses >450 units daily are not recommended. Once adequate follicular development is evident, administer hCG to induce final follicular maturation in preparation for oocyte retrieval. Withhold hCG if the ovaries are abnormally enlarged.

Spermatogenesis induction: Males: Gonal-f: SubQ: Therapy should begin with hCG pretreatment until serum testosterone is in normal range, then initiate Gonal-f at 150 units 3 times weekly with hCG 3 times weekly; continue with lowest dose needed to induce spermatogenesis (maximum dose: 300 units 3 times weekly); may be given for up to 18 months

Dosing: Geriatric

Refer to adult dosing. Clinical studies did not include patients >65 years.

Reconstitution

Gonal-f: Dissolve the contents of vial by slowly injecting provided diluent; do not shake. If bubbles appear, allow to settle prior to use. Final concentration: 600 units/mL.

Gonal-f RFF: Powder: Dissolve contents of one or more vials using diluent provided in prefilled syringe. Total concentration should not exceed 450 units/mL. Slowly inject diluent into vial, and gently rotate vial until powder is dissolved; do not shake vial. If bubbles appear, allow to settle prior to use. Use immediately after reconstitution.

Gonal-f RFF Rediject: Allow to warm to room temperature prior to use. Do not attempt to mix any other medications inside of the device.

Administration

SubQ: Administer SubQ. Contents of multidose vials (Gonal-f or Gonal-f RFF) should be administered using the calibrated syringes provided by the manufacturer. Do not shake solution; allow any bubbles to settle prior to administration. Allow Gonal-f RFF Rediject to warm to room temperature for at least 30 minutes prior to administration to avoid discomfort from cold injection. Do not mix other medications inside of the Gonal-f RFF Rediject device.

Storage

Gonal-f: Store powder refrigerated or at room temperature of 2°C to 25°C (36°F to 77°F). Protect from light; do not freeze. Following reconstitution, multidose vials may be stored under refrigeration or at room temperature for up to 28 days.

Gonal-f RFF:

Powder: Store at room temperature or under refrigeration of 2°C to 25°C (36°F to 77°F). Protect from light. Discard unused drug.

Rediject: Prior to dispensing, store under refrigeration at 2°C to 8°C (36°F to 46°F). Upon dispensing, patient may store under refrigeration until product expiration date or at room temperature of 20°C to 25°C (68°F to 77°F) for up to 3 months. Do not freeze. Protect from light. After first use, store pen in the refrigerator (2°C to 8°C [36°C to 46°F]) or at room temperature (20°C to 25°C [68°F to 77°F]); discard unused portion after 28 days.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Percentage may vary by indication, product formulation

>10%:

Cardiovascular: Varicocele (15%)

Central nervous system: Headache (13% to 27%)

Dermatologic: Acne vulgaris (males 59%)

Endocrine & metabolic: Ovarian cyst (4% to 15%)

Gastrointestinal: Abdominal pain (9% to 23%), nausea (4% to 14%), enlargement of abdomen (1% to 14%)

Genitourinary: Mastalgia (males 14%)

Local: Injection site reaction (males 15%; females 1% to 4%)

Respiratory: Upper respiratory tract infection (4% to 12%)

1% to 10%:

Cardiovascular: Chest pain (1% to 2%), hypotension (1% to 2%), palpitations (1% to 2%)

Central nervous system: Fatigue (males 9%; females 1% to 2%), pain (2% to 6%), emotional lability (5%), migraine (1% to 4%), dizziness (1% to 3%), malaise (2%), anxiety (1% to 2%), drowsiness (1% to 2%), nervousness (1% to 2%), paresthesia (1% to 2%)

Dermatologic: Acne vulgaris (females 4%), pruritus (1% to 2%)

Endocrine & metabolic: Gynecomastia (9%), intermenstrual bleeding (4% to 9%), ovarian hyperstimulation syndrome (5% to 7%; severe: <1%), weight gain (4%), menstrual disease (3%), hot flash (2%), ovarian disease (2%), increased thirst (1% to 2%)

Gastrointestinal: Diarrhea (1% to 8%), flatulence (4% to 7%), toothache (1% to 4%), vomiting (1% to 3%), aphthous stomatitis (2%), constipation (2%), dyspepsia (2%), anorexia (1% to 2%)

Genitourinary: Pelvic pain (7%), mastalgia (females 4% to 6%), vaginal hemorrhage (1% to 6%), cervical lesion (3%), genital candidiasis (3%), dysmenorrhea (1% to 3%), cystitis (2%), gynecological pain (2%), urinary frequency (2%), urinary tract infection (2%), uterine hemorrhage (2%), leukorrhea (1% to 2%)

Infection: Viral infection (2%)

Local: Bruising at injection site (10%), pain at injection site (3% to 9%), inflammation at injection site (1% to 4%), swelling at injection site (3%)

Neuromuscular & skeletal: Back pain (4% to 5%), myalgia (1% to 2%)

Respiratory: Rhinitis (≤7%), pharyngitis (3% to 7%), sinusitis (5% to 6%), flu-like symptoms (4%), cough (2% to 3%), asthma (1% to 2%), dyspnea (1% to 2%)

Miscellaneous: Fever (2% to 4%)

Postmarketing and/or case reports: Anaphylactoid reaction, anaphylaxis, depression, Epstein-Barr infection, hemoperitoneum, hemoptysis, hypersensitivity reaction, ovarian torsion, ovarian neoplasm, ovary enlargement, pulmonary complications (including atelectasis, acute respiratory distress syndrome, exacerbation of asthma), thromboembolism, vascular disease

Warnings/Precautions

Concerns related to adverse effects:

• Abortion: Risk of spontaneous abortion is increased with the use of gonadotropins; causal effect has not been established.

• Ectopic pregnancy: Risk for ectopic pregnancy may be increased in women with tubal abnormalities; intrauterine pregnancy should be confirmed early with hCG testing and transvaginal ultrasound.

• Hypersensitivity: Serious hypersensitivity reactions including anaphylaxis have been reported; discontinue use for serious reactions and treat appropriately.

• Ovarian enlargement: May be accompanied by abdominal distention or abdominal pain, occurs in ~20% of those treated with urofollitropin and hCG, and generally regresses without treatment within 2 to 3 weeks. If ovaries are abnormally enlarged on the last day of treatment, withhold hCG to reduce the risk of ovarian hyperstimulation syndrome (OHSS).

• Ovarian hyperstimulation syndrome (OHSS): OHSS is a rare exaggerated response to ovulation induction therapy (Corbett 2014; Fiedler 2012). This syndrome may begin within 24 hours of treatment but may become most severe 7 to 10 days after therapy (Corbett 2014). 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; Corbett 2014; Fiedler 2012). 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.

Dosage form specific issues:

• Multiple-dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC, 2012).

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 multiple births before starting the treatment.

Monitoring Parameters

Monitor sufficient follicular maturation. This may be directly estimated by sonographic visualization of the ovaries and endometrial lining or measuring serum estradiol levels. 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 or by sonographic evidence. The indices of progesterone production most generally used are: urinary or serum luteinizing hormone (LH) rise, rise in basal body temperature, increase in serum progesterone, and menstruation following the shift in basal body temperature. The indices of sonographic evidence of ovulation include: Collapsed follicle, fluid in the cul-de-sac, features consistent with corpus luteum formation, or 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).

Spermatogenesis: Monitor serum testosterone levels, sperm count

Pregnancy Considerations

Follitropin Alfa is used for the induction of ovulation; use is contraindicated in women who are already pregnant.

Ectopic pregnancy, congenital abnormalities, spontaneous abortion, and multiple 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 parenteral characteristics (maternal age, sperm characteristics).

Patient Education

What is this drug used for?

• It is used to help women get pregnant.

• It is used to help make sperm.

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

• Acne

• Headache

• Abdominal pain

• Passing gas

• Diarrhea

• Loss of strength and energy

• Back pain

• Common cold symptoms

• Nose irritation

• Throat irritation

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 amount of urine 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

• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse

• Mood changes

• Abdominal swelling

• Breast pain

• Enlarged breasts (males)

• Abnormal heartbeat

• Blue/gray skin discoloration

• Pale skin

• Abnormal vaginal bleeding

• 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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.