Dosing and uses of GONAL f, Gonal-f RFF (follitropin alfa)
Adult dosage forms and strengths
multi-dose viaL
- 600units/mL
single-dose ampules
- 75units
solution reconstituted
- 450units
- 1050units
Ovulation Induction
Initial dose of first cycle: 75 units SC qDay; after 14 days, increase dose by increments of up to 37.5 International Units; further dose increases, as necessary every 7 days
Dose based on effect, with lowest effective dose; maximum recommended dose 300 International Units qDay
Treatment maximum of 35 days, unless E2 rise indicates imminent follicular developement
To complete follicular development in absence of endogenous LH surge, give chorionic gonadatropin (hCG)- 5000 units 1 day after last dose
Withhold if serum estradiol >2,000 pg/mL or if abnormal ovarian enlargement/abdominal pain
Advise patient against intercourse
Initial dose in subsequent cycles based on response in previous cycle
Advise daily intercourse beginning on day prior to hCG until ovulation apparent from lab tests
Assisted Reproductive Technologies
Initial dose on cycle day 2 or 3: 150 International Units SC qDay until sufficient follicular development. In most cases, therapy should not exceed 10 days
If endogenous gonadotropin levels are suppressed, should be started at 225 International Units qDay
Continue until adequate follicular development based on ultrasound and serum estradiol levels; dose adjustments of 75-150 units may be made q3-5Days
Maximum recommended dose 450 international units qDay
Once adequate follicular development, administer hCG (5,000-10,000 USP); withhold if ovaries abnormally enlarged on last day of treatment
Male Patients with Hypogonadotropic Hypogonadism (Gonal-f Only)
Pretreat with hCG (1,000- 2,250 USP Units 2-3 x/week) until serum testosterone within normal range (may require 3-6 months of treatment)
Treatment- GONAL-f used in conjunction with hCG GONAL-f 150 international units SC 3 x/week
hCG 1000 USP Units (or dose to maintain normal serum testosterone levels) 3 x/week
If azoospermia persists, may increase GONAL-f to maximum of 300 international units 3 x/week
May need to administer for up to 18 months for adequate response
Administration
Gonal-f RFF Pen (Follitropin Alfa) & Follistim AQ (Follitropin Beta) are SC self-injectable pens for women only; check manufacturer's package insert for dosage & administration
Pediatric dosage forms and strengths
Safety and efficacy not established
GONAL f, Gonal-f RFF (follitropin alfa) adverse (side) effects
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
Follistim AQ
- Headache
- Ovarian pain
- Back pain
- Constipation
- OHSS (for ovulation induction)
- URI
- Sinusitis
Warnings
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 & 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 GONAL-f therapy, do not administer hCg
Pulmonary conditions (atelactasis, ARDS, & asthma exacerbation) have been reported
Possibility of multiple births (range 12.3%-44.0% live births)
A thorough gynecologic & endocrinological evaluation should be conducted prior to treatment to rule out primary ovarian failure, early pregnancy & partner's fertility potentiaL
Pregnancy and lactation
Pregnancy category: X
Lactation: Excretion in milk unknown; not recommended
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.
Pharmacology of GONAL f, Gonal-f RFF (follitropin alfa)
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)
