Follitropin Beta

G03G - Gonadotropins and other ovulation stimulants ATC G03GA06 Protein approved 1996 Parenteral

JFDA label: Puregon Cartridges

Mechanism of Action

Agonist of Follicle-stimulating hormone receptor — Follicle stimulating hormone receptor agonist

Target	Action	Gene / class
Follicle-stimulating hormone receptor efficacy	AGONIST	FSHR

Indications

Approved

Females
Males

Contraindications

Source: Lexicomp

Hypersensitivity to follitropins, streptomycin, neomycin, or any component of the formulation Absolute
high levels of FSH indicating primary gonadal failure Absolute
ovarian cysts or enlargement not due to polycystic ovary syndrome Absolute
tumor of the ovary, breast, uterus, testis, hypothalamus, or pituitary gland Females: Additional contraindications: Abnormal vaginal bleeding of undetermined origin Absolute
uncontrolled nongonadal endocrinopathies (eg, adrenal, pituitary, or thyroid disorders) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (2)

Common fatigue · Headache

Renal and urinary disorders (2)

Common pelvic pain · Pelvic symptoms

Metabolism and nutrition disorders (3)

Common gynecomastia · ovarian cyst · Ovarian hyperstimulation

Gastrointestinal disorders (3)

Common abdominal distress · abdominal pain · Nausea

Skin and subcutaneous tissue disorders (2)

Common Acne vulgaris · skin rash

General disorders and administration site conditions (2)

Common Injection site reaction · pain at injection site

Dosing

Source: Lexicomp

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: 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 this product. ART: Females: Follistim AQ: 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 this product. Spermatogenesis induction: Males: Follistim AQ, Follistim AQ Cartridge: 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

No dosage adjustment provided in manufacturer's labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

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. 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.

Pregnancy & Lactation

Pregnancy

FDA category X Contraindicated

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.

Lactation

It is not known if follitropin beta is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.

Monitoring

Clinical pearl	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 circumferenc

Clinical pearl

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 circumferenc

Biology & Pharmacokinetics

Pharmacokinetics

Half-life	35.666666666666664 h

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Puregon Cartridges	Cartridge 300 IU/0.36 ml	1 Cartridge with 6 Pen Needles	Sabbagh Drug Store	92.670
Puregon Cartridges	Cartridge 600 IU/0.72 ml	1 Cartridge with 6 Pen Needles	Sabbagh Drug Store	—