Version May 2024
Note: Dose should be individualized. Use the lowest effective dose. Over the course of treatment, doses may vary depending on individual patient response. Doses may need adjustment when changing between products and/or methods of administration.
Ovulation induction, anovulatory patients:
Follistim AQ Cartridge: SUBQ: Stepwise approach: Initiate therapy with 50 units per day for at least the first 7 days. Increase dose by 25 or 50 units at weekly intervals until follicular growth and/or estradiol levels indicate an adequate ovarian response. Adjust dose to prevent multiple follicular growth and cycle cancellation. Continue treatment until ultrasonic visualizations and/or serum estradiol determinations approximate the preovulatory conditions based on follicular development. Maximum (individualized) daily dose: 250 units. If response to follitropin is appropriate, human chorionic gonadotropin (hCG) is given 1 day following the last dose to induce final oocyte maturation and ovulation. Follow current clinical practice to reduce the risk of ovarian hyperstimulation syndrome (OHSS). See "Follitropin Beta Dosing Conversion table" for dosage adjustment between the pen and the cartridge.
Puregon (vials) [Canadian product] (IM, SUBQ), Puregon Cartridge [Canadian product] (SUBQ): Stepwise approach: Initiate therapy with 50 units per 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 "Follitropin Beta Dosing Conversion table"for dosage adjustment between the pen and the cartridge.
Controlled ovarian stimulation, ovulatory patients:
Follistim AQ Cartridge: SUBQ: Stepwise approach: A starting dose of 200 units is recommended for at least the first 7 days of treatment. Adjust dose up or down for the individual patient based upon ovarian response. Maximum daily dose: 500 units. When a sufficient number of follicles of adequate size are present, dosing of follitropin beta is stopped and the final maturation of the follicles is induced by administering hCG. Oocyte retrieval is performed 34 to 36 hours later. Follow current clinical practice to reduce the risk of OHSS. See "Follitropin Beta Dosing Conversion table"for dosage adjustment between the pen and the 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. Adjust dose for the individual patient based upon ovarian response. Maximum daily dose: 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 "Follitropin Beta Dosing Conversion table"for dosage adjustment between the pen and the cartridge.
Spermatogenesis induction: 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.
Follistim AQ Cartridge, Puregon (vials) [Canadian product], Puregon Cartridge [Canadian product]: SUBQ: 450 units/week (administered as 225 units twice weekly or 150 units 3 times/weekly). Combination therapy with follitropin beta and hCG should be continued for at least 3 to 4 months before any improvement in spermatogenesis can be expected. If no response is noted after this period, combination therapy may be continued. Treatment response has been noted at up to 12 months. See "Follitropin Beta Dosing Conversion table"for dosage adjustment between the pen and the cartridge.
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Follitropin Beta Dosing Conversion Among Formulationsa | |
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a Values listed are rounded to the nearest 25 unit increment. | |
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The follitropin beta cartridge contains a prefilled solution that is administered via a pen injector device; it delivers on average an 18% higher amount of follitropin beta when compared to lyophilized and reconstituted follitropin beta delivered using a conventional syringe and needle. If the above starting doses were previously used when administering lyophilized follitropin beta via a conventional syringe, lower starting and maintenance doses should be considered when switching to the follitropin pen with cartridge. The following dose conversion may be used: | |
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Dose Administered Using Powder for Solution/Conventional Syringe |
Dose Administered Using Pen |
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75 units |
50 units |
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150 units |
125 units |
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225 units |
175 units |
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300 units |
250 units |
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375 units |
300 units |
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450 units |
375 units |
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Dermatologic: Acne vulgaris (7%), skin rash (3%)
Endocrine & metabolic: Gynecomastia (3%)
Gastrointestinal: Abdominal distention (≥2%), abdominal distress (3%), abdominal pain (3%), constipation (≥2%), diarrhea (≥2%), lower abdominal pain (3%), nausea (4%)
Genitourinary: Ovarian cyst (3%), ovarian hyperstimulation (6% to 8%), pelvic pain (6%), pelvic symptoms (discomfort: 8%), uterine hypertrophy (≥2%), vaginal hemorrhage (≥2%)
Local: Injection-site reaction (7%), pain at injection site (7%)
Nervous system: Fatigue (2%), headache (7%)
Miscellaneous: Cyst (dermoid: 3%)
Postmarketing:
Cardiovascular: Thromboembolism
Genitourinary: Breast tenderness, ovarian torsion, ovary enlargement, uterine hemorrhage
Hypersensitivity to recombinant human follicle-stimulating hormone (FSH) products, 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; heavy or 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.
Concerns related to adverse effects:
• Ovarian enlargement: The lowest effective dose should be used to decrease the risk of abnormal ovarian enlargement. If ovaries are abnormally enlarged on the last day of follitropin beta treatment, follow current clinical practice to reduce the risk of ovarian hyperstimulation syndrome (OHSS).
• 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 human chorionic gonadotropin treatment but may become most severe 7 to 10 days after therapy (Corbett 2014). Mild/moderate OHSS signs/symptoms may include abdominal distention/discomfort, diarrhea, nausea, vomiting, and mild/moderate enlargement of ovaries/ovarian cysts. Severe OHSS signs/symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, hydrothorax, nausea/vomiting (intractable), pleural effusion, rapid weight gain, venous thrombosis, and large ovarian cysts. Decreased CrCl, 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; Shmorgun 2017).
• 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, including acute respiratory distress syndrome, have been reported.
• Thromboembolic events: In association with and separate from OHSS, thromboembolic events have been reported. Risk may be increased in patients with a personal or family history of thromboembolic events, severe obesity, or thrombophilia.
Dosage form specific issues:
• Multiple dose injection pens: According to the Centers for Disease Control and Prevention, 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 transvaginal ultrasound; concurrent measurement of estradiol levels may also be useful.
• 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous:
Follistim AQ: 300 units/0.36 mL (0.36 mL, 0.42 mL); 600 units/0.72 mL (0.72 mL, 0.78 mL); 900 units/1.08 mL (1.08 mL, 1.17 mL) [contains benzyl alcohol]
No
Solution (Follistim AQ Subcutaneous)
300 units/0.36 mL (per 0.36 mL): $1,044.00
600 units (per 0.72 mL): $2,088.00
900 units/1.08 mL (per mL): $2,900.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection:
Puregon: 100 units/0.5 mL ([DSC])
Solution, Subcutaneous:
Puregon: 300 units/0.36 mL (0.36 mL) [contains benzyl alcohol]
SUBQ: Follistim AQ Cartridge, Puregon Cartridge (Canadian product): Administer by SUBQ injection only, using the Follistim Pen or the Puregon Pen, which can be set to deliver the appropriate dose. Allow to reach room temperature prior to administration to avoid discomfort. Injection may be given in the abdomen just below the navel or upper outer area of thigh. Avoid areas that are tender, red, bruised, or hard.
IM, SUBQ: Puregon (Canadian product): Vials: Administer by IM or SUBQ injection. IM injection may be given in the upper outer quadrant of the buttock. IM administration has not been evaluated in males.
Controlled ovarian stimulation, ovulatory patients: Induction of pregnancy in normal ovulatory patients undergoing controlled ovarian stimulation as part of in vitro fertilization or intracytoplasmic sperm injection.
Limitations of use: Prior to therapy, perform a complete gynecologic exam and endocrinologic evaluation to diagnose the cause of infertility; exclude the possibility of pregnancy; evaluate the fertility status of the partner.
Ovulation induction, anovulatory patients: Induction of ovulation and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not caused by primary ovarian failure.
Limitations of use: Prior to therapy, perform a complete gynecologic exam and endocrinologic evaluation; exclude the possibility of pregnancy; evaluate the fertility status of the partner; exclude a diagnosis of primary ovarian failure; confirm tubal patency.
Spermatogenesis induction: Induction of spermatogenesis in patients with primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure.
Limitations of use: Prior to therapy, perform a complete medical exam and endocrinologic evaluation; confirm hypogonadotropic hypogonadism and exclude primary testicular failure; normalize serum testosterone levels with human chorionic gonadotropin; evaluate the fertility status of the partner.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
None known.
There are no known significant interactions.
Follitropin beta is used for ovulation induction or spermatogenesis induction in couples planning a pregnancy; the fertility status of both partners should be evaluated prior to therapy.
Ectopic pregnancies, congenital abnormalities, and multiple births have been reported. The incidence of congenital abnormality may be slightly higher after in vitro fertilization or intracytoplasmic sperm injection 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 patients who are already pregnant.
It is not known if follitropin beta is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Ovulation induction: Monitor follicular growth by transvaginal ultrasound along with concurrent measurement of estradiol levels to determine adequate ovarian response and timing of human chorionic gonadotrophin (hCG) administration.
Monitor for signs and symptoms of ovarian hyperstimulation syndrome (OHSS) for at least 2 weeks following hCG administration. Initial symptoms of moderate to severe OHSS may include a sensation of bloating, abdominal pain, rapid weight gain, and decreased urine output (Shmorgun 2017).
OHSS: Monitoring of hospitalized patients should include albumin, degree of ascites, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, serum creatinine, urine output, urine specific gravity, signs of thromboembolism, vital signs, weight (all daily or as necessary), and liver enzymes (weekly) (Shmorgun 2017).
Spermatogenesis: 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 monograph).
Follitropin beta is a human follicle-stimulating hormone (FSH) preparation of recombinant DNA origin. Follitropins stimulate ovarian follicular growth in patients who do not have primary ovarian failure and stimulate spermatogenesis in patients with hypogonadotropic hypogonadism. FSH is required for normal follicular growth, maturation, gonadal steroid production, and spermatogenesis.
Note: Data are presented from studies conducted by the manufacturer in pituitary suppressed but otherwise healthy females following SUBQ injection. Pharmacokinetic studies were not conducted in males.
Absorption: ~78%.
Distribution: IV: 8 L.
Half-life elimination: ~33 hours.
Time to peak: 13 hours.
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