What is Gonal-F (follitropin alfa) Injection, and how does it work?
Generic drug: follitropin alfa
Brand name: Gonal-F
Gonal-F (follitropin alfa) Injection is a prescription medicine containing follicle-stimulating hormone (FSH).
Gonal-F is used in:
infertile women to:
- help healthy ovaries develop (mature) and release an egg to help you get pregnant
- cause your ovaries to make multiple (more than 1) eggs as part of an Assisted Reproductive Technology (ART) program
infertile men to:
- help develop and produce mature sperm
What are the side effects of Gonal-F?
Gonal-F may cause serious side effects in women and men, including:
- severe allergic reactions. Women or men who have used Gonal-F in the past may have a severe allergic reaction right away when they use Gonal-F again. This severe allergic reaction may lead to death. If you have any of the following symptoms of a severe allergic reaction, stop using Gonal-F and go to the nearest hospital emergency room right away:
- shortness of breath
- swelling of your face
- itchy, red bumps or rash on your skin (hives)
- lung problems. Gonal-F may cause serious lung problems including fluid in your lungs (atelectasis), trouble breathing (acute respiratory distress syndrome), and worsening of asthma.
- blood clots. Gonal-F may increase your chance of having blood clots in your blood vessels. Blood clots can cause:
- blood vessel problems (thrombophlebitis)
- stroke
- loss of your arm or leg
- blood clot in your lung (pulmonary embolus)
- heart attack
Gonal-F may cause serious side effects in women, including:
- ovarian hyperstimulation syndrome (OHSS). OHSS is both a serious and common side effect. Using Gonal-F may cause OHSS. OHSS is a serious medical condition that can happen when your ovaries produce too many eggs (overstimulated). OHSS can cause fluid to suddenly build up in the area of your stomach, chest, and heart, and can cause blood clots to form. In rare cases OHSS has caused death. OHSS may also happen after you stop using Gonal-F. Stop using Gonal-F and call your healthcare provider right away if you have symptoms of OHSS, including:
- trouble breathing
- severe lower stomach (pelvic) area pain
- weight gain
- nausea
- vomiting
- diarrhea
- decreased urine output
- twisting (torsion) of your ovary. Gonal-F may increase the chance of your ovary twisting if you already have certain conditions such as OHSS, pregnancy and previous abdominal surgery. Twisting of your ovary may lead to blood flow being cut off to your ovary.
- ovaries that are too large. Gonal-F may cause your ovaries to be abnormally large. Symptoms of large ovaries include bloating or pain in your lower stomach (pelvic) area.
- pregnancy with and birth of multiple babies. Gonal-F may increase your chance of having a pregnancy with more than 1 baby. Having a pregnancy and giving birth to more than 1 baby at a time increases the health risk for you and your babies. Your healthcare provider should tell you about your chances of multiple births.
- birth defects. A baby born after an ART cycle may have an increased chance of having birth defects. Your chances of having a baby with birth defects may increase depending on:
- your age
- certain sperm problems
- your genetic background and that of your partner
- a pregnancy with more than 1 baby at a time
- ectopic pregnancy (pregnancy outside your womb). Gonal-F may increase your chance of having a pregnancy that is abnormally outside of your womb. Your chance of having a pregnancy outside of your womb is increased if you also have fallopian tube problems. Call your healthcare provider right away if you have symptoms of an ectopic pregnancy including:
- stomach or pelvic pain especially on one side
- shoulder pain
- neck pain
- rectal pain
- nausea and vomiting
- miscarriage. Your chance of loss of an early pregnancy may be increased if you had difficulty becoming pregnant.
- tumors of the ovary. If you have used medicines like Gonal-F more than 1 time to get pregnant, you may have an increased chance of having tumors in your ovary(ies) (including cancer).
Common side effects of Gonal-F include:
in women:
- ovarian cyst
- headache
- OHSS
- stomach pain
- pelvic pain
- nausea
- gas
- bleeding between periods
in men:
Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Gonal-F. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is the dosage for Gonal-F?
Important Dosage And Administration Information
- Only physicians who
are experienced in infertility treatment, should treat women with Gonal-F. - Gonal-F is a gonadotropins product capable of causing in women, Ovarian
Hyperstimulation Syndrome (OHSS) with or without pulmonary or vascular
complications and multiple births. - Gonadotropin therapy requires the
availability of appropriate monitoring facilities. Use the lowest effective dose of
Gonal-F. - Give careful attention to the diagnosis of infertility and the selection of candidates for
Gonal-F therapy [see Dosing For Ovulation Induction, Dosing For Multiple Follicle Development As Part Of An Assisted Reproductive Technology (ART) Cycle
below].
Preparation Of Gonal-F And Selection Of Injection Site
27-gauge injection syringe – Illustration
- Store lyophilized Multi-Dose vials refrigerated or at room temperature (2°25°C /36°-77°F) and protected from light.
- Prior to administration, visually inspect parenteral drug products for particulate matter and discoloration, whenever solution and container permit.
- Instruct women and men to use the accompanying syringes, calibrated in International Units FSH for administration. The 27-gauge injection syringe (see figure below) has unit dose markings from 37.5 International Units to 600 International Units FSH for use with
Gonal-F Multi-Dose. Instruct women and men to take a specific dose of Gonal-F Multi-Dose. Show women and men how to locate the syringe marking that corresponds to the prescribed dose. - Each
Gonal-F Multi-Dose Vial delivers 450 International Units or 1050 International Units of follitropin alfa, respectively- Multi-Dose 450 International Units Vial:
- Dissolve the contents of one Multi-Dose vial (450 International Units) with 1 mL Bacteriostatic Water for Injection (0.9% benzyl alcohol), USP. Resulting concentration will be 600 International Units/mL. Following reconstitution as directed, product will deliver the equivalent of six 75 International Units doses.
- Multi-Dose 1050 International Units Vial:
- Dissolve the contents of one Multi-Dose vial (1050 International Units) with 2 mL Bacteriostatic Water for Injection (0.9% benzyl alcohol), USP. Resulting concentration will be 600 International Units/mL. Following reconstitution as directed, product will deliver the equivalent of fourteen 75 International Units doses.
- Multi-Dose 450 International Units Vial:
- Discard unused reconstituted solution after 28 days.
- Administer
Gonal-F subcutaneously in the abdomen, upper arm, or upper leg as described in Patient Information and Instructions for Use.
Dosing For Ovulation Induction
Prior to initiation of treatment with
Gonal-F:
- Perform a complete gynecologic and endocrinologic evaluation
- Exclude primary ovarian failure
- Exclude the possibility of pregnancy
- Demonstrate tubal patency
- Evaluate the fertility status of the male partner
The dosing scheme is stepwise and is individualized for each woman.
- Administer a starting dose of 75 International Units of
Gonal-F subcutaneously daily for 14 days in the first cycle of use. - In subsequent cycles of treatment, determine the starting dose (and dosage adjustments) of
Gonal-F based on the woman's history of the ovarian response to Gonal-F. - If indicated by the ovarian response after the initial 14 days, make an incremental adjustment in dose of up to 37.5 International Units.
- If indicated by the ovarian response, make additional incremental adjustments in the dose, up to 37.5 International Units, every 7 days.
- Continue treatment until follicular growth an*d/or serum estradiol levels indicate an adequate ovarian response.
- Consider the following when planning the woman's individualized dose:
- Use the lowest dose of Gonal-F consistent with the expectation of good results.
- Use appropriate
Gonal-F dose adjustment(s) to prevent multiple follicular growth and cycle cancellation. - The maximum, individualized, daily dose of
Gonal-F is 300 International Units per day. - In general, do not exceed 35 days of treatment, unless an estradiol rise indicates imminent follicular development.
- When pre-ovulatory conditions are reached, administer human chorionic gonadotropin (hCG) to induce final oocyte maturation and ovulation. Human chorionic gonadotropin, hCG, (5,000 USP units) should be given 1 day after the last dose of
Gonal-F. - Encourage the woman and her partner to have intercourse daily, beginning on the day prior to the administration of hCG and until ovulation becomes apparent.
- Withhold hCG in cases where the ovarian monitoring suggests an increased risk of
ovarian hyperstimulation syndrome (OHSS) on the last day of Gonal-F therapy for
example estradiol greater than 2,000 pg per mL).- Discourage intercourse
when the risk for OHSS is increased.
- Discourage intercourse
- Schedule a follow-up visit in the luteal phase.
- Individualize the initial dose administered in subsequent cycles based on the woman’s response in the preceding cycle.
- As in the initial cycle, do not administer doses larger than 300 International Units of FSH per day. Administer 5,000 USP units of hCG 1 day after the last dose of
Gonal-F to complete follicular development and induce ovulation. - Follow the above recommendations to minimize the chance of development of OHSS.
Dosing For Multiple Follicle Development As part Of An Assisted Reproductive Technology (ART) Cycle
Prior to initiation of treatment with
Gonal-F:
- Perform a complete gynecologic and endocrinologic evaluation, and diagnose the cause of infertility
- Exclude the possibility of pregnancy
- Evaluate the fertility status of the male partner
The dosing scheme follows a stepwise approach and is individualized for each woman.
- Beginning on cycle day 2 or 3, administersubcutaneously a starting dose of 150 International Units of
Gonal-F daily until sufficient follicular development, as determined by ultrasound in combination with measurement of serum estradiol levels, is attained. In most cases, therapy should not exceed ten days. - In women whose endogenous gonadotropin levels are suppressed, initiate
Gonal-F administration at a dose of 225 International Units per day. - Adjust the dose after 5 days based on the woman's ovarian response, as determined by ultrasound evaluation of follicular growth and serum estradiol levels.
- Do not make additional dosage adjustments more frequently than every 3-5 days or by more than 75-150 International Units at each adjustment.
- Continue treatment until adequate follicular development is evident, and then administer hCG (5,000 to 10,000 USP units) to induce final follicular maturation in preparation for oocyte retrieval.
-
Withhold hCG administration in cases where the ovarian monitoring suggests an
increased risk of OHSS on the last day of Gonal-F therapy. - Do not use doses greater than 450 International Units per day.
Dosing For Induction Of Spermatogenesis In Males With Azoospermia And Primary Or Secondary Hypogonadotropic Hypogonadism
Prior to initiation of treatment with
Gonal-F:
- Confirm azoospermia
- Perform a thorough medical and endocrinologic evaluation to exclude other treatable etiologies of azoospermia
- Confirm hypogonadotropic hypogonadism
- Exclude primary testicular failure
- Normalize serum testosterone levels
The dosing scheme follows a stepwise approach and is individualized for each man.
- Gonal-F must be given in conjunction with hCG.
- Prior to concomitant therapy with
Gonal-F and hCG, pretreatment with hCG alone (1,000 to 2,250 USP units two to three times per week) is required to normalize serum testosterone levels. - Treatment with hCG alone should continue until serum testosterone levels reach the normal range, which may take 3 to 6 months. The dose of hCG may also need to be increased during this time to achieve normal serum testosterone levels.
- After serum testosterone levels have normalized, administer
Gonal-F 150 International Units subcutaneously three times a week and hCG 1,000 USP units (or the dose required to maintain serum testosterone levels within the normal range) three times a week. The lowest dose of GONAl-F which induces spermatogenesis should be utilized. - If azoospermia persists, increase the dose of
Gonal-F up to a maximum dose of 300 International Units three times per week. Administer
Gonal-F for up to 18 months to achieve adequate spermatogenesis.
Missed Dose
Do not double the next dose if a woman or a man misses or forgets to take a dose of
Gonal-F.
What drugs interact with Gonal-F?
No Information Provided
Is Gonal-F safe to use while pregnant or breastfeeding?
- Gonal-F is 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)], may be slightly higher than that after spontaneous conception. This slightly higher incidence is thought to be related to differences in parental characteristics (e.g., 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 Gonal-F alone or as part of IVF or ICSI cycles, increases the risk of congenital malformations.
- The risk of spontaneous abortion (miscarriage) is increased in women who have used gonadotropins products (including
Gonal-F) to achieve pregnancy. - There are no data on the presence of Gonal-F in human milk, the effects on the breastfed infant, or the effects on milk production.
- Because the secretion of prolactin during lactation can result in inadequate response to ovarian stimulation, women
should not breast feed during treatment with Gonal-F.