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 [see Warnings and Precautions (5.2, 5.3)] and multiple births [see Warnings and Precautions (5.6)]. Gonadotropin therapy requires the availability of appropriate monitoring facilities [see Warnings and Precautions (5.11)]. 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 Dosage and Administration (2.3, 2.4)].

Preparation of GONAL-F and Selection of Injection Site

• ​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.
• 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 [see Clinical Studies (14.1)].

• 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 and/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) [see Warnings and Precautions (5.2, 5.3, 5.5, 5.11)].
  • Discourage intercourse when the risk for OHSS is increased [see Warnings and Precautions (5.2, 5.5)].
• 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, administer subcutaneously 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 [see Warnings and Precautions (5.2, 5.3, 5.4, 5.11)].
• 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.