Gonal-F Dosage

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 multiple-dose vials refrigerated or at room temperature (2°-25°C /36°-77°F) and protected from light.
• Prior to administration, parenteral drug products should be inspected visually 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.