Follitropin Alfa

G03G - Gonadotropins and other ovulation stimulants ATC G03GA05 Protein approved 1995

JFDA label: GONAL-f

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

Hypogonadotropic hypogonadism

Contraindications

Source: Lexicomp

Hypersensitivity to follitropin alfa, lutropin alfa or any component of the formulation Absolute
current pregnancy or lactation Absolute
gynecological hemorrhages of undetermined origin Absolute
ovarian enlargement or cyst of undetermined origin Absolute
primary ovarian failure or anovulation with normal levels of LH and FSH Absolute
sex hormone dependent tumors of the reproductive tract and accessory organs Absolute
tumors of the hypothalamus or pituitary gland Absolute
uncontrolled thyroid or adrenal dysfunction 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)

Not Known fatigue · Headache

Renal and urinary disorders (2)

Not Known Mastalgia · pelvic pain

Metabolism and nutrition disorders (2)

Not Known ovarian cyst · Ovarian hyperstimulation

Gastrointestinal disorders (4)

Not Known Abdominal pain · constipation · flatulence · nausea

General disorders and administration site conditions (1)

Not Known Injection site reaction

Dosing

Source: Lexicomp

Note: Prior to initiation of therapy, a thorough gynecologic and endocrinologic evaluation must be performed; pregnancy should be ruled out. Confirm that LH Hypogonadotropic hypogonadism: Females: SubQ: FSH 150 units/LH 75 units once daily. If an increase in FSH is necessary, dose may be adjusted in increments of FSH 37.5 to 75 units every 7 to 14 days using an approved follitropin alfa preparation. Duration of stimulation in any one cycle may be extended up to 5 weeks (treatment should be individualized based on response to prior cycle). Administer hCG 24 to 48 hours after the last dose of FSH/LH. Patients should have intercourse the day of, and on the day following hCG administration or alternatively, intrauterine insemination may be performed. If response to therapy is excessive, stop FSH/LH and withhold hCG. If therapy is resumed in the next cycle, decrease FSH dose. If the ovaries are abnormally enlarged or if abdominal pain occurs, withhold hCG, discontinue FSH/LH, and advise patient to avoid intercourse and consult health care provider.

Not indicated for use in elderly women.

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

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 and generally regresses without treatment within 2 to 3 weeks; more common in women with polycystic ovarian syndrome. 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 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. Disease-related concerns:

Porphyria

Gonadotropins may increase the risk of an acute porphyric attack in patients with porphyria or a family history of porphyria; discontinuation of therapy may be necessary with onset or worsening of condition. Special populations:

Elderly

Not indicated for use in elderly females.

Pediatric

Not indicated for use in females 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 patients of the potential risk of multiple births before starting the treatment. Discontinuation of therapy is recommended if there is a high risk for multiple pregnancies.

Pregnancy & Lactation

Pregnancy

Use is contraindicated in women who are already pregnant. See individual agents.

Lactation

Contraindicated

Use is contraindicated in breast-feeding women. See individual agents.

Monitoring

Clinical pearl	Prior to therapy: Baseline LH 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. The indices most generally used are: rise in basal body temperature, increase in serum progesterone, and menstruation following the shift in basal body temperature. 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).

Clinical pearl

Prior to therapy: Baseline LH 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. The indices most generally used are: rise in basal body temperature, increase in serum progesterone, and menstruation following the shift in basal body temperature. 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).

Registered Products (5)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
GONAL-f	Pre-filled Syringe 75 IU	1 PFS	THE ARAB DRUG STORE P.S.C	26.500
Pergoveris 150iu/75iu	Vial 75 IU, 150 IU	1 Powder Vial + 1 Solvent Vial	THE ARAB DRUG STORE P.S.C	63.980
Gonal-f	Pre-filled Pen 300 IU/0.5 ml	1 Pre-Filled Pen + 8 Needles	THE ARAB DRUG STORE P.S.C	88.320
Gonal-f	Pre-filled Pen 450 IU/0.75 ml	1 Pre-Filled Pen + 12 Needles	THE ARAB DRUG STORE P.S.C	132.480
Gonal-f	Pre-filled Pen 900 IU/1.5 ml	1 Pre-Filled Pen +20 Needles	THE ARAB DRUG STORE P.S.C	—