Medically reviewed on Nov 15, 2018
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- Follicle Stimulating Hormone, Recombinant
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Follistim AQ: 75 units/0.5 mL (0.5 mL [DSC]); 150 units/0.5 mL (0.5 mL [DSC])
Follistim AQ: 300 units/0.36 mL (0.42 mL); 600 units/0.72 mL (0.78 mL); 900 units/1.08 mL (1.17 mL) [contains benzyl alcohol]
Brand Names: U.S.
- Follistim AQ
- Ovulation Stimulator
Follitropin beta 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.
Females: IM: 76%; SubQ: 78%
Females: 8 L
Onset of Action
Peak effect: Females: Follicle development: Within cycle
Time to Peak
Females: SubQ: 13 hours
Females: IM: 44 hours (single dose), 27-30 hours (multiple doses); SubQ: 33 hours (single dose)
Use: Labeled Indications
Females: Induction of ovulation and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not caused by primary ovarian failure; induction of pregnancy in normal ovulatory women undergoing Assisted Reproductive Technology (ART) (eg, in vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI])
Males: Induction of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure.
Hypersensitivity to follitropins, streptomycin, neomycin, or any component of the formulation; high levels of FSH indicating primary gonadal failure; uncontrolled nongonadal endocrinopathies (eg, adrenal, pituitary, or thyroid disorders); tumor of the ovary, breast, uterus, testis, hypothalamus, or pituitary gland
Females: Additional contraindications: Abnormal vaginal bleeding of undetermined origin; ovarian cysts or enlargement not due to polycystic ovary syndrome; pregnancy
Canadian labeling: Additional contraindications (not in the US labeling): Lactation; conditions incompatible with pregnancy (eg, malformation of reproductive organs, uterine fibroid tumors); use in children
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:
Follistim AQ (vials): IM, SubQ: Stepwise approach: Initiate therapy with 75 units/day for at least the first 7 days. Increase dose by 25 or 50 units at weekly intervals until follicular growth or serum estradiol levels indicate an adequate response. The maximum (individualized) daily dose that has been safely used for ovulation induction in patients during clinical trials is 300 units. 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 the ovaries are abnormally enlarged, or if abdominal pain occurs.
Follistim AQ Cartridge: SubQ: Stepwise approach: Initiate therapy with 50 units/day for at least the first 7 days. Increase dose by 25 or 50 units at weekly intervals until follicular growth and/or serum estradiol levels indicate an adequate response. The maximum (individualized) daily dose that has been safely used for ovulation induction in patients during clinical trials is 250 units. 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 the ovaries are abnormally enlarged, or if abdominal pain occurs. See "Note" for dosage adjustment for the pen with cartridge.
Puregon (vials) [Canadian product] (IM, SubQ), Puregon Cartridge [Canadian product] (SubQ): Stepwise approach: Initiate therapy with 50 units/day for at least the first 7 days. Increase dose gradually until follicular growth and/or plasma estradiol levels indicate an adequate response (daily increase of estradiol levels of 40% to 100% is considered optimal). If response to follitropin is appropriate, hCG is given 1 day following the last dose to induce final oocyte maturation and ovulation. Decrease hCG dose if the number of responding follicles is too high or estradiol levels increase too rapidly (eg, greater than daily doubling for estradiol for 2 or 3 consecutive days); withhold hCG if the ovaries are abnormally enlarged or if abdominal pain occurs. See "Note" for dosage adjustment for the pen with cartridge.
Follistim AQ (vials): IM, SubQ: Stepwise approach: A starting dose of 150 to 225 units is recommended for at least the first 4 days of treatment. The dose may be adjusted for the individual patient based upon their ovarian response. The maximum daily dose used in clinical studies is 600 units. When a sufficient number of follicles of adequate size are present, the final maturation of the follicles is induced by administering hCG. Oocyte retrieval is performed 34 to 36 hours later. Withhold hCG in cases where the ovaries are abnormally enlarged on the last day of follitropin beta therapy.
Follistim AQ Cartridge: SubQ: Stepwise approach: A starting dose of 200 units is recommended for at least the first 7 days of treatment. The dose may be adjusted for the individual patient based upon their ovarian response. The maximum daily dose used in clinical studies is 500 units. When a sufficient number of follicles of adequate size are present, the final maturation of the follicles is induced by administering hCG. Oocyte retrieval is performed 34 to 36 hours later. Withhold hCG in cases where the ovaries are abnormally enlarged on the last day of follitropin beta therapy. See "Note" for dosage adjustment for the pen with cartridge.
Puregon vials [Canadian product] (IM, SubQ), Puregon Cartridge [Canadian product] (SubQ): A starting dose of 150 to 225 units is recommended for at least the first 4 days of treatment. The dose may be adjusted for the individual patient based upon their ovarian response. The maximum daily dose safely used in clinical studies is 450 units (limited experience with higher doses). When a sufficient number of follicles of adequate size are present, the final maturation of the follicles is induced by administering hCG 30 to 40 hours after the last follitropin beta dose. Withhold hCG in cases where the ovaries are abnormally enlarged on the last day of follitropin beta therapy. See "Note" for dosage adjustment for the pen with cartridge.
Spermatogenesis induction: Males:
Follistim AQ (vials), Follistim AQ Cartridge, Puregon (vials) [Canadian product], Puregon Cartridge [Canadian product]: Note: Pretreatment with hCG monotherapy is required prior to concomitant therapy with follitropin beta and hCG. Follitropin beta therapy may be initiated after normal serum testosterone levels have been reached. SubQ: 450 units/week (administered as 225 units twice weekly or 150 units 3 times/weekly). A lower dose of Follistim AQ Cartridge may be considered. See "Note" for dosage adjustment for the pen with cartridge.
Note: Dose adjustment for follitropin beta pen with cartridge: When administered using the pen, the follitropin cartridge delivers on average 18% more follitropin beta when compared to dissolved lyophilized follitropin beta administered by a conventional syringe. If the above starting doses were previously used when administering a recombinant lyophilized gonadotropin product via a conventional syringe, lower starting and maintenance doses should be considered when switching to follitropin pen with cartridge. The following dose conversion may be used:
Dose Administered Using Powder for Solution/Conventional Syringe
Dose Administered Using Pen
1Values listed are rounded to the nearest 25 unit increment.
Table has been converted to the following text.
Follitropin Beta Dosing Conversion
(values listed are rounded to the nearest 25 unit increment)
Dose using powder for solution/conventional syringe: 75 units
Dose using pen: 50 units
Dose using powder for solution/conventional syringe: 150 units
Dose using pen: 125 units
Dose using powder for solution/conventional syringe: 225 units
Dose using pen: 175 units
Dose using powder for solution/conventional syringe: 300 units
Dose using pen: 250 units
Dose using powder for solution/conventional syringe: 375 units
Dose using pen: 300 units
Dose using powder for solution/conventional syringe: 450 units
Dose using pen: 375 units
Dosing: Renal Impairment
No dosage adjustment provided in manufacturer's labeling (has not been studied).
Dosing: Hepatic Impairment
No dosage adjustment provided in manufacturer's labeling (has not been studied).
SubQ injection may be given in the abdomen just below the navel or upper thigh. IM injection may be given in the upper outer quadrant of the buttock. Avoid areas that are tender, red, bruised, or hard.
Follistim AQ, Puregon [Canadian product]: Vials: Administer by IM or SubQ injection.
Follistim AQ Cartridge, Puregon Cartridge [Canadian product]: Cartridge: Administer by SubQ injection only, using the Follistim Pen or the Puregon Pen, which can be set to deliver the appropriate dose.
Prior to dispensing, store refrigerated at 2°C to 8°C (36°F to 46°F). After dispensed, may be stored under refrigeration at 2°C to 8°C (36°F to 46°F) or ≤25˚C (77˚F) for up to 3 months. Once cartridge is pierced, must be stored at 2°C to 25°C (36°F to 77°F) and used within 28 days. Do not freeze. Protect from light.
There are no known significant interactions.
Frequency may vary based on indication.
1% to 10%:
Central nervous system: Headache (7%), fatigue (2%)
Dermatologic: Acne vulgaris (7%), skin rash (3%)
Endocrine & metabolic: Ovarian hyperstimulation (6% to 8%), gynecomastia (3%), ovarian cyst (3%)
Gastrointestinal: Nausea (4%), abdominal distress (≤3%), abdominal pain (≤3%)
Genitourinary: Pelvic symptoms (discomfort: 8%), pelvic pain (6%)
Local: Injection site reaction (7%), pain at injection site (7%)
<1%, postmarketing, and/or case reports: Abdominal distention, breast tenderness, constipation, diarrhea, ovarian neoplasm, ovarian torsion, ovary enlargement, spontaneous abortion, thromboembolism, uterine hemorrhage, vaginal hemorrhage
Concerns related to adverse effects:
• Ovarian enlargement: 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: Ovarian hyperstimulation syndrome (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 torsion: May occur in relation to OHSS, pregnancy, previous or current ovarian cyst and polycystic ovaries, previous abdominal surgery, and previous history of ovarian torsion.
• 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, 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).
• Neomycin: May contain trace amounts of neomycin.
• Streptomycin: May contain trace amounts of streptomycin.
• 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.
Females: 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 ovarian hyperstimulation syndrome (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).
Males: Monitor for sufficient spermatogenesis. This can be directly estimated by semen analysis, or indirectly estimated by serum testosterone level. Semen analysis is recommended 4 to 6 months after starting treatment (Puregon Canadian product labeling 2015). Therapy should continue for 3 to 4 months before improvement in spermatogenesis can be expected.
Pregnancy Risk Factor
Ectopic pregnancies, congenital abnormalities, 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). Follitropin Beta is used for the induction of ovulation; use is contraindicated in women who are already pregnant.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea, acne, headache, loss of strength and energy, pelvic pain (females), or abdominal pain (females). Have patient report immediately to prescriber signs of ovarian hyperstimulation syndrome (severe abdominal pain or bloating; severe nausea, vomiting, or diarrhea; excessive weight gain; shortness of breath; or change in amount of urine passed), signs of blood clots (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; angina; shortness of breath; tachycardia; or coughing up blood), enlarged breasts (males), abnormal vaginal bleeding, severe injection site irritation, pale skin, or skin discoloration (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
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Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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- Drug class: gonadotropins