follitropin alfa (Rx)

Frequency Not Defined

GONAL-f

• Intermenstrual bleeding
• Ovarian hyperstimulation
• Abdominal pain
• Acne
• Flatulence
• Diarrhea
• Back pain
• Emotional lability

Gonal-f RFF Pen

• Diarrhea
• Dizziness
• OHSS (for ovulation induction)
• Flatulence
• Acne
• Toothache
• Intermenstrual bleeding
• Breast pain, Injection site reactions, Ovarian cyst, Nausea, Sinusitis

Postmarketing Reports

Asthma exacerbation

Thromboembolism

Contraindications

Prior hypersensitivity to recombinant FSH preparations

High levels of FSH indicating primary gonadal failure

Uncontrolled thyroid or adrenal dysfunction

Sex hormone dependent tumors of the reproductive tract and accessory organs

Organic intracranial lesion (e.g. pituitary tumor)

Women with abnormal uterine bleeding of undetermined origin; ovarian cyst or enlargement of undetermined origin

Pregnancy

Cautions

May cause ovarian hyperstimulation syndrome (OHSS, dramatic increase in vascular permeability which can result in rapid fluid accumulation in peritoneal cavity, thorax and pericardium; accompanied by severe pelvic pain, nausea, vomiting and weight gain) in women with or without pulmonary or vascular complications

If ovaries are abnormally enlarged on last day of therapy, inform women not to administer hCG and to avoid intercourse

Pulmonary conditions (atelactasis, ARDS, & asthma exacerbation) have been reported; in women with recognized risk factors, the benefits of induction of ovulation and ART need to be weighed against risks; during or after use of drug, monitor for venous or arterial thromboembolic events

Possibility of multiple births (range 12.3%-44.0% live births)

In ovarian torsion, early diagnosis and immediate detorsion limit damage to ovary due to reduced blood supply

A thorough gynecologic & endocrinological evaluation should be conducted prior to treatment to rule out primary ovarian failure, early pregnancy & partner's fertility potential

The rate of multiple births is dependent on number of embryos transferred; advise the woman and her partner of the potential risk of multi-fetal gestation and birth before beginning therapy

Advise women who become pregnant following ART and have: abdominal/pelvic pain (particularly on one side); shoulder, neck or rectal pain; and nausea and vomiting to seek immediate medical attention; confirm the presence of an intrauterine pregnancy early by β-hCG testing and transvaginal ultrasound

The risk of spontaneous abortion (miscarriage) is increased with gonadotropin products, however, causality has not been established

Both benign and malignant ovarian neoplasms are reported in women who have had multiple drug therapy for controlled ovarian stimulation, however, causality has not been established

Pregnancy

Drug not indicated in pregnant women

The incidence of congenital malformations after some assisted reproductive technology, specifically in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)], maybe slightly higher than that after spontaneous conception; this slightly higher incidence is thought to be related to differences in parental characteristics (eg, maternal age, maternal and paternal genetic background, sperm characteristics) and to a higher incidence of multi-fetal gestations after IVF or ICSI; there is no human data that the use of gonadotropins (including drug alone or as part of IVF or ICSI cycles, increases risk of congenital malformations

Risk of spontaneous abortion (miscarriage) is increased in women who have used gonadotropins products (including GONAL-F) to achieve pregnancy

Verify a negative pregnancy test before administering drug

Animal data

• In animal studies, the continuous administration of recombinant human FSH during pregnancy resulted in a decrease in number of viable fetuses and difficult and prolonged delivery; no teratogenic effect observed

Lactation

There are no data on presence of drug in human milk, effects on breastfed infant, or on milk production; because secretion of prolactin during lactation can result in inadequate response to ovarian stimulation, advise women not to breastfeed during treatment

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant follicle stimulating hormone (FSH); stimulate ovarian follicular growth in women who do not have primary ovarian failure;

Stimulates spermatogenesis in men with hypogonadotrophic hypogonadism

Pharmacokinetics

Onset: 2.7-18 months (spermatogenesis); within cycle (females)

Vd: 10 L

Bioavailability: 66-76% (healthy female volunteers)

Half-life: 50 hr (IM in healthy female volunteers); 24 hr (SC in healthy female volunteers)

Peak plasma time: 8-16 hr (SC in females); 25 hr (IM in females); 11-20 hr (IM in males)

SC Administration

Gonal-f RFF Pen is a SC self-injectable pen for women

Remove pen from refridgerator at least 30 min before injection to warm to room temperature

Inject SC in abdomen

Storage

Pharmacy: Store the Gonal-f RFF Redi-ject refrigerated 2-8°C (36-46°F) until dispensed

Upon dispensing, store refrigerated 2-8°C (36-46°F) until the expiration date, or at room temperature 20-25°C (68-77°F) for up to 3 months or until the expiration date, whichever occurs first

After the first injection, store refrigerated 2-8°C (36-46°F) or at room temperature 20-25°C (68-77°F) for up to 28 days

Protect from light

Do not freeze

Once opened or stored at room temperature, discard unused material after 28 days