![Gonal-f RFF Redi-ject FOLLITROPIN 450 [iU]/.75mL Injection, Solution, 75 mL — NDC 44087-1116-01 package photo](https://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=b6d11c45-b502-478e-bb28-2ff596ea259c&name=gonal-32.jpg)
Gonal-f RFF Redi-ject FOLLITROPIN 450 [iU]/.75mL Injection, Solution, 75 mL
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Gonadotropins class.
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🏭 Manufacturer & labeler
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🩺 Clinical
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII GGO4Y809LO
Metacresol is a preservative derived from coal tar or petroleum. It prevents bacterial and fungal growth in liquid medicines, helping keep the product safe and stable during storage.
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UNII AE28F7PNPL
Methionine is an amino acid used as a nutrient supplement and pH buffer in medicines. It helps stabilize the formulation and supports the product's overall composition.
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UNII LQA7B6G8JG
A synthetic polymer made by combining water-soluble compounds. It acts as a surfactant and solubilizer to help mix oil and water-based ingredients, improving the medicine's texture and how active ingredients dissolve.
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UNII 94255I6E2T
Sodium phosphate dibasic dihydrate is a salt that helps control the acidity level of a medicine. It acts as a buffer and pH regulator to keep the medication stable and effective.
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UNII 593YOG76RN
A salt made from sodium and phosphate that helps regulate acidity and maintain proper pH balance in the medicine. It also acts as a buffer to keep the product stable.
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UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
6 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Gonal-f RFF Redi-ject 450 [iU]/.75mLthis 44087-1116-01 | EMD | 75 ml | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 44087-1116-01 You're viewing this | 1 PACKAGE in 1 CARTON (44087-1116-1) / .75 mL in 1 PACKAGE | 2013-10-16 | Active |
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE GONAL-f ® RFF Redi-ject ® is a prefilled gonadotropin-containing auto-injection device indicated for: Induction of ovulation and pregnancy in oligo-anovulatory women in whom the cause of infertility is functional and not due to primary ovarian failure ( 1.1 ) Development of multiple follicles in ovulatory women as part of an Assisted Reproductive Technology (ART) cycle ( 1.2 )
1.1Induction of Ovulation and Pregnancy in Oligo-Anovulatory Women in whom the Cause of Infertility is Functional and Not Due to Primary Ovarian Failure. Prior to initiation of treatment with GONAL-f ® RFF Redi-ject ® : 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
1.2Development of Multiple Follicles in Ovulatory Women as Part of an Assisted Reproductive Technology (ART) Cycle. Prior to initiation of treatment with GONAL-f ® RFF Redi-ject ® : 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
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Ovulation Induction ( 2.2 ) Initial starting dose of the first cycle - 75 International Units of GONAL-f ® RFF Redi-ject ® per day for 14 days, administered subcutaneously Individualization doses after 14 days Doses larger than 300 International Units of FSH per day are not recommended Assisted Reproductive Technology ( 2.3 ) Initial starting dose of the first cycle - 150 International Units per day, administered subcutaneously Dosage adjustments after 3-5 days and by 75-150 International Units at each adjustment Do not administer doses greater than 450 International Units per day
2.1General Dosing Information Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. GONAL-f ® RFF Redi-ject ® is a pre-filled disposable auto-injection device intended for multiple dose use. GONAL-f ® RFF Redi-ject ® can be set in
12.5International Units increments. Administer GONAL-f ® RFF Redi-ject ® subcutaneously in the abdomen as described in Instructions for Use Do not attempt to mix any other medications inside of the device with GONAL-f ® RFF Redi-ject ® . Instruct women to remove the GONAL-f ® RFF Redi-ject ® from the refrigerator at least 30 minutes prior to use in order to allow GONAL-f ® RFF Redi-ject ® to warm to room temperature and avoid the discomfort of a cold injection.
2.2Recommended Dosing for Ovulation Induction The dosing scheme is stepwise and is individualized for each woman [see Clinical Studies (14.1) ] . Starting doses less than
37.5International Units have not been studied in clinical trials and are not recommended. A starting daily dose of 75 International Units of GONAL-f ® RFF Redi-ject ® is administered subcutaneously daily for 14 days in the first cycle of use. In subsequent cycles of treatment, the starting dose (and dosage adjustments) of GONAL-f ® RFF Redi-ject ® should be determined based on the history of the ovarian response to GONAL-f ® RFF Redi-ject ® .
The following should be considered when planning the woman's individualized dose: Appropriate GONAL-f ® RFF Redi-ject ® dose adjustment(s) should be used to prevent multiple follicular growth and cycle cancellation. The maximum, individualized, daily dose of GONAL-f ® RFF Redi-ject ® is 300 International Units per day. In general, do not exceed 35 days of treatment.
If indicated by the ovarian response after the initial 14 days, make an incremental adjustment in dose, up to
37.5International Units. If indicated by the ovarian response, make additional adjustments in dose, up to
37.5International Units, every 7 days. Treatment should continue until follicular growth and/or serum estradiol levels indicate an adequate ovarian response. When pre-ovulatory conditions are reached, administer human chorionic gonadotropin (hCG) to induce final oocyte maturation and ovulation.
Withhold hCG in cases where the ovarian monitoring suggests an increased risk of ovarian hyperstimulation syndrome (OHSS) on the last day of GONAL-f ® RFF Redi-ject ® therapy [see Warnings and Precautions (5.2 , 5.3 , 5.11) ] . 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. Discourage intercourse when the risk for OHSS is increased [see Warnings and Precautions (5.2 , 5.3) ] .
2.3Recommended Dosing for Assisted Reproductive Technology The dosing scheme follows a stepwise approach and is individualized for each woman. Beginning on cycle day 2 or 3, a starting dose of 150 International Units of GONAL-f ® RFF Redi-ject ® is administered subcutaneously 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 10 days.
In women under 35 years of age whose endogenous gonadotropin levels are suppressed, initiate GONAL-f ® RFF Redi…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS GONAL-f® RFF Redi-ject is a clear and colorless to slightly yellow solution available as: • Injection: GONAL-f ® RFF Redi-ject ® 300 International Units per 0.48 mL in prefilled, single-patient-use pen • Injection: GONAL-f ® RFF Redi-ject ® 450 International Units per 0.72 mL in prefilled, single-patient-use pen • Injection: GONAL-f ® RFF Redi-ject ® 900 International Units per 1.44 mL in prefilled, single-patient-use pen Injection: GONAL-f ® RFF Redi-ject ® 300 International Units per 0.48 mL in prefilled, single-patient-use pen ( 3 ) Injection: GONAL-f ® RFF Redi-ject ® 450 International Units per 0.72 mL in prefilled, single-patient-use pen ( 3 ) Injection: GONAL-f ® RFF Redi-ject ® 900 International Units per 1.44 mL in prefilled single-patient-use pen ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS GONAL-f ® RFF Redi-ject ® is contraindicated in women who exhibit: Prior hypersensitivity to recombinant FSH products High levels of FSH indicating primary gonadal failure Presence of uncontrolled non-gonadal endocrinopathies (e.g., thyroid, adrenal, or pituitary disorders) [see Indications and Usage (1.1 , 1.2) ] Sex hormone dependent tumors of the reproductive tract and accessory organs Tumors of pituitary gland or hypothalamus Abnormal uterine bleeding of undetermined origin Ovarian cyst or enlargement of undetermined origin, not due to polycystic ovary syndrome GONAL-f ® RFF Redi-ject ® is contraindicated in women who exhibit ( 4 ): Hypersensitivity to recombinant FSH preparations or one of their excipients High levels of FSH indicating primary gonadal failure Uncontrolled non-gonadal endocrinopathies Sex hormone dependent tumors of the reproductive tract and accessory organ.
Tumors of pituitary gland or hypothalamus Abnormal uterine bleeding of undetermined origin Ovarian cyst or enlargement of undetermined origin, not due to polycystic ovary syndrome
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS GONAL-f ® RFF Redi-ject ® should only be used by physicians who are experienced in infertility treatment. GONAL-f ® RFF Redi-ject ® contains a gonadotropic substance capable of causing Ovarian Hyperstimulation Syndrome (OHSS) in women with or without pulmonary or vascular complications [see Warnings and Precautions (5.2 , 5.3 , 5.4 , 5.5) ] and multiple births [see Warnings and Precautions (5.6) ] . Gonadotropin therapy requires the availability of appropriate monitoring facilities [see Warnings and Precautions (5.11) ] .
The lowest effective dose should be used. Careful attention should be given to the diagnosis of infertility and the selection of candidates for GONAL-f ® RFF Redi-ject ® therapy [see Indications and Usage (1.1 , 1.2) and Dosage and Administration (2.2 , 2.3) ]. Hypersensitivity Reactions and Anaphylaxis ( 5.1 ) Abnormal Ovarian Enlargement ( 5.2 ) Ovarian Hyperstimulation Syndrome ( 5.3 ) Pulmonary and Vascular Complications ( 5.4 ) Ovarian Torsion ( 5.5 ) Multi-fetal Gestation and Births ( 5.6 ) Congenital Malformation ( 5.7 ) Ectopic Pregnancy ( 5.8 ) Spontaneous Abortion ( 5.9 ) Ovarian Neoplasms ( 5.10 )
5.1Hypersensitivity Reactions and Anaphylaxis Serious systemic hypersensitivity reactions, including anaphylaxis, have been reported in the postmarketing experience with GONAL-f ® and GONAL-f ® RFF. Symptoms have included dyspnea, facial edema, pruritus, and urticaria. If an anaphylactic or other serious allergic reaction occurs, initiate appropriate therapy including supportive measures if cardiovascular instability and/or respiratory compromise occur, and discontinue further use.
5.2Abnormal Ovarian Enlargement In order to minimize the hazards associated with abnormal ovarian enlargement that may occur with GONAL-f ® RFF Redi-ject ® therapy, treatment should be individualized and the lowest effective dose should be used [see Dosage and Administration (2.2 , 2.3) ]. Use of ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels is important to minimize the risk of ovarian stimulation [see Warnings and Precautions (5.11) ] . If the ovaries are abnormally enlarged on the last day of GONAL-f ® RFF Redi-ject ® therapy, hCG should not be administered in order to reduce the chance of developing Ovarian Hyperstimulation Syndrome (OHSS) [see Warnings and Precautions (5.3) ] .
Intercourse should be prohibited in women with significant ovarian enlargement after ovulation because of the danger of hemoperitoneum resulting from rupture of ovarian cysts [see Warnings and Precautions (5.3) ] .
5.3Ovarian Hyperstimulation Syndrome (OHSS) OHSS is a medical entity distinct from uncomplicated ovarian enlargement and may progress rapidly to become a serious medical event. OHSS is characterized by a dramatic increase in vascular permeability, which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium. The early warning signs of development of OHSS are severe pelvic pain, nausea, vomiting, and weight gain.
Abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting and diarrhea, severe ovarian enlargement, weight gain, dyspnea, and oliguria have been reported with OHSS. Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic reactions [see Warnings and Precautions (5.4) ] . Transient liver function test abnormalities suggestive of hepatic dysfunction with or without morphologic changes on liver biopsy, have been reported in association with OHSS.
OHSS occurs after gonadotropin treatment has been discontinued and it can develop rapidly, reaching its maximum about seven to ten days following treatment. Usually, OHSS resolves spontaneously with the onset of menses. If there is evidence that OHSS may be developing prior to hCG administration [see Warni…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Hypersensitivity Reactions and Anaphylaxis [see Warnings and Precautions (5.1) ] Abnormal Ovarian Enlargement [see Warnings and Precautions (5.2) ] Ovarian Hyperstimulation Syndrome [see Warnings and Precautions (5.3) ] Atelectasis, acute respiratory distress syndrome and exacerbation of asthma [see Warnings and Precautions (5.4) ] Thromboembolic events [see Warnings and Precautions (5.4) ] Ovarian Torsion [see Warnings and Precautions (5.5) ] Multi-fetal Gestation and Birth [see Warnings and Precautions (5.6) ] Congenital Malformations [see Warnings and Precautions (5.7) ] Ectopic Pregnancy [see Warnings and Precautions (5.8) ] Spontaneous Abortion [see Warnings and Precautions (5.9) ] Ovarian Neoplasms [see Warnings and Precautions (5.10) ] The most common adverse reactions (≥5%) in ovulation induction include: headache, abdominal pain, ovarian hyperstimulation ( 6.1 ) The most common adverse reactions (≥5%) in ART include: abdominal pain, nausea, abdominal enlargement, headache, injection site bruising ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact EMD Serono at 1-800-283-8088, Ext 5563 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Study Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice. The safety of GONAL-f ® RFF was examined in two clinical studies (one ovulation induction study and one ART study). Ovulation Induction In a multiple cycle (3), assessor-blind, multinational, multicenter, active comparator study vs. a recombinant FSH comparator, a total of 83 oligo-anovulatory infertile women were randomized and underwent ovulation induction with GONAL-f ® RFF.
Adverse reactions occurring in at least 2.0% of women receiving GONAL-f ® RFF are listed in Table 1. Table 1: Common Adverse Reactions Reported at a Frequency of ≥ 2% in an Ovulation Induction Study System Organ Class/Adverse Reactions GONAL-f ® RFF N=83 total number of women treated with GONAL-f ® RFF (176 treatment cycles up to 3 treatment cycles per woman ) n number of women with the adverse reaction (%) Central and Peripheral Nervous System Headache 22 (26.5%) Gastrointestinal System Abdominal Pain 10 (12.0%) Nausea 3 (3.6%) Flatulence 3 (3.6%) Diarrhea 3 (3.6%) Neoplasm Ovarian Cyst 3 (3.6%) Reproductive, Female Ovarian Hyperstimulation 6 (7.2%) Application Site Injection Site Pain 4 (4.8%) Injection Site Inflammation 2 (2.4%) Assisted Reproductive Technology In a single cycle, assessor-blind, multinational, multicenter, active comparator study vs. a recombinant FSH comparator, a total of 237 normal ovulatory infertile women were randomized and received GONAL-f ® RFF as part of an ART [in vitro fertilization (IVF) or intracytoplasmic sperm injection cycle (ICSI)] cycle.
All women received pituitary down-regulation with gonadotropin releasing hormone (GnRH) agonist before stimulation. Adverse Reactions occurring in at least 2.0% of women are listed in Table 2. Table 2: Common Adverse Reactions Reported at a Frequency of ≥ 2% in an Assisted Reproductive Technologies Study System Organ Class/Adverse Reactions GONAL-f ® RFF N=237 total number of women treated with GONAL-f ® RFF n number of women with the adverse reaction (%) Gastrointestinal System Abdominal Pain 55 (23.2%) Nausea 19 (8.0%) Body as a Whole- General Abdomen Enlarged 33 (13.9%) Central and Peripheral Nervous System Headache 44 (18.6%) Application Site Disorders Injection Site Bruising 23 (9.7%) Injection Site Pain 13 (5.5%) Injection Site Inflammation 10 (4.2%) Injection Site Reaction 10 (4.2%) Application Site Edema 6 (2.5%) Reproductive, Female Ovarian Hyperstimulation 11 (4.6%)
6.2 Postmarketing Experience The following adverse reactions have been reporte…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No drug-drug interaction studies have been performed.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Do not use GONAL-f ® RFF Redi-ject ® in pregnant women ( 4 , 8.1 ), Nursing Mothers: It is not known whether this drug is excreted in human milk. ( 8.3 ) Pediatric Use: Safety and efficacy not established. ( 8.4 ) Renal and Hepatic Insufficiency: Safety, efficacy, and pharmacokinetics of GONAL-f ® RFF Redi-ject ® in women with renal or hepatic insufficiency have not been established. ( 8.6 )
8.1Pregnancy Risk Summary GONAL-f ® RFF Redi-ject ® is not indicated in pregnant women. The incidence of congenital malformations after some Assisted Reproductive Technology (ART), procedures, specifically in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)], may be slightly higher than 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 ® RFF Redi-ject ® ), 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 ® RFF Redi-ject ® ) to achieve pregnancy. In animal studies, the continuous administration of recombinant human FSH during pregnancy resulted in a decrease in the number of viable fetuses and difficult and prolonged delivery.
No teratogenic effect has been observed. In the US general population, the estimated background risk of major birth defects and miscarriage after spontaneous clinically recognized pregnancies, is 2% to 4% and 15% to 20%, respectively. Data Human Data Data on a limited number of exposed pregnancies indicate no adverse reactions of gonadotropins on pregnancy, embryonal or fetal development, parturition or postnatal development following controlled ovarian stimulation.
Animal Data Embryofetal development studies with recombinant human FSH in rats, where dosing occurred during organogenesis, showed a dose dependent increase in difficult and prolonged parturition in dams, and dose dependent increases in resorptions, pre- and post-implantation losses, and stillborn pups at doses representing 5 and 41 times the lowest clinical dose of 75 IU based on body surface area. Pre-/post-natal development studies with recombinant human FSH in rats, where dosing occurred from mid-gestation through lactation, showed difficult and prolonged parturition in all dams dosed at 41 times the lowest clinical dose of 75 IU based on body surface area, along with maternal death and stillborn pups associated with the difficult and prolonged parturition.
This toxicity was not observed in dams and offspring dosed at a level 5 times the lowest clinical dose of 75 IU based on body surface area.
8.2Lactation There are no data on the presence of GONAL-F RFF 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, advise women not to breast feed during treatment with GONAL-f ® RFF Redi-ject ® .
8.3Females and Males of Reproductive Potential Since GONAL-f ® RFF Redi-ject ® is not indicated in pregnant women, verify a negative pregnancy test before administering GONAL-f ® RFF Redi-ject ® to a woman [see Dosage and Administration (2.2 , 2.3) ].
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
8.6Renal and Hepatic Insufficiency Safety, efficacy, and pharmacokinetics of GONAL-f ® RFF Redi-ject ® in women with renal or hepatic insufficiency have not been established.
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary GONAL-f ® RFF Redi-ject ® is not indicated in pregnant women. The incidence of congenital malformations after some Assisted Reproductive Technology (ART), procedures, specifically in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)], may be slightly higher than 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 ® RFF Redi-ject ® ), 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 ® RFF Redi-ject ® ) to achieve pregnancy. In animal studies, the continuous administration of recombinant human FSH during pregnancy resulted in a decrease in the number of viable fetuses and difficult and prolonged delivery.
No teratogenic effect has been observed. In the US general population, the estimated background risk of major birth defects and miscarriage after spontaneous clinically recognized pregnancies, is 2% to 4% and 15% to 20%, respectively. Data Human Data Data on a limited number of exposed pregnancies indicate no adverse reactions of gonadotropins on pregnancy, embryonal or fetal development, parturition or postnatal development following controlled ovarian stimulation.
Animal Data Embryofetal development studies with recombinant human FSH in rats, where dosing occurred during organogenesis, showed a dose dependent increase in difficult and prolonged parturition in dams, and dose dependent increases in resorptions, pre- and post-implantation losses, and stillborn pups at doses representing 5 and 41 times the lowest clinical dose of 75 IU based on body surface area. Pre-/post-natal development studies with recombinant human FSH in rats, where dosing occurred from mid-gestation through lactation, showed difficult and prolonged parturition in all dams dosed at 41 times the lowest clinical dose of 75 IU based on body surface area, along with maternal death and stillborn pups associated with the difficult and prolonged parturition.
This toxicity was not observed in dams and offspring dosed at a level 5 times the lowest clinical dose of 75 IU based on body surface area.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
🆘 Overdosage ▾
10 OVERDOSAGE Aside from possible OHSS [see Warnings and Precautions (5.3) ] and multiple gestations [see Warnings and Precautions (5.6) ], there is no additional information on the consequences of acute overdosage with GONAL-f ® RFF Redi-ject ® .
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Follicle stimulating hormone (FSH), the active component in GONAL-f ® RFF Redi-ject ® , is required for normal follicular growth, follicular maturation, and gonadal steroid production. The level of FSH is critical for the onset and duration of follicular development, and consequently for the timing and number of follicles reaching maturity. GONAL-f ® RFF Redi-ject ® stimulates ovarian follicular growth in women who do not have primary ovarian failure.
In order to effect the final phase of follicle maturation, resumption of meiosis, and rupture of the follicle in the absence of an endogenous LH surge, human chorionic gonadotropin (hCG) must be given following treatment with GONAL-f ® RFF Redi-ject ® when monitoring of the woman indicates that appropriate follicular development parameters have been achieved. There is inter-woman variability in response to FSH administration.
12.3Pharmacokinetics Single-dose pharmacokinetics of follitropin alfa were determined following subcutaneous administration of 300 International Units of GONAL-f ® RFF Redi-ject ® to 21 pre-menopausal healthy female volunteers who were pituitary down-regulated with a GnRH agonist. The descriptive statistics for the pharmacokinetic parameters are presented in Table 3. Table 3: Pharmacokinetic parameters of FSH following administration of GONAL-f ® RFF Redi-ject ® (300 International Units subcutaneously in a single dose) Parameter Healthy Volunteers (N=21) Mean % CV Abbreviations are: C max : peak concentration (above baseline) t max : time of C max t 1/2 : elimination half life AUC last (IU hr/L) 884 20% C max (IU/L) 9.83 23% t max (hr) 15.5 43% t 1/2 (hr) 53 52% Absorption The absorption rate of GONAL-f ® RFF Redi-ject ® following subcutaneous administration is slower than the elimination rate.
Hence, the pharmacokinetics of GONAL-f ® RFF Redi-ject ® are absorption rate-limited. Distribution Human tissue or organ distribution of FSH has not been determined for GONAL-f ® RFF Redi-ject ® . Metabolism/Excretion FSH metabolism and excretion following administration of GONAL-f ® RFF Redi-ject ® have not been studied in humans.
🧬 Mechanism of Action ▾
12.1Mechanism of Action Follicle stimulating hormone (FSH), the active component in GONAL-f ® RFF Redi-ject ® , is required for normal follicular growth, follicular maturation, and gonadal steroid production. The level of FSH is critical for the onset and duration of follicular development, and consequently for the timing and number of follicles reaching maturity. GONAL-f ® RFF Redi-ject ® stimulates ovarian follicular growth in women who do not have primary ovarian failure.
In order to effect the final phase of follicle maturation, resumption of meiosis, and rupture of the follicle in the absence of an endogenous LH surge, human chorionic gonadotropin (hCG) must be given following treatment with GONAL-f ® RFF Redi-ject ® when monitoring of the woman indicates that appropriate follicular development parameters have been achieved. There is inter-woman variability in response to FSH administration.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied GONAL-f ® RFF Redi-ject ® (follitropin alfa) injection is a disposable, prefilled single-patient-use pen containing a clear and colorless to slightly yellow solution. Each Redi-ject ® is supplied in a carton containing 31G × 5/16 inch disposable needles to be used for administration. The following package presentations are available: NDC 44087-1115-1 - One GONAL-f ® RFF Redi-ject ® delivers 300 International Units per 0.48 mL and 5 single-use disposable 31G × 5/16" needles NDC 44087-1116-1 - One GONAL-f ® RFF Redi-ject ® delivers 450 International Units per 0.72 mL and 7 single-use disposable 31G × 5/16" needles NDC 44087-1117-1 - One GONAL-f ® RFF Redi-ject ® delivers 900 International Units per 1.44 mL and 14 single-use disposable 31G × 5/16" needles
16.2Storage and Handling Pharmacy Storage: Refrigerate at 2°C to 8°C (36°F to 46°F) until dispensed. Patient Storage: Refrigerate at 2°C to 8°C (36°F to 46°F) until the expiration date, or store at room temperature at 20° to 25°C (68°F to 77°F) for up to three months or until the expiration date, whichever occurs first. Store pen in the original carton to protect from light.
After the first injection, store refrigerated at 2°C to 8°C (36°F to 46°F) or at room temperature at 20°C to 25°C (68°F to 77°F) for up to 28 days. Keep the cap on the pen to protect from light. Do not freeze.
Discard unused material after 28 days.
📦 Storage and Handling ▾
16.2Storage and Handling Pharmacy Storage: Refrigerate at 2°C to 8°C (36°F to 46°F) until dispensed. Patient Storage: Refrigerate at 2°C to 8°C (36°F to 46°F) until the expiration date, or store at room temperature at 20° to 25°C (68°F to 77°F) for up to three months or until the expiration date, whichever occurs first. Store pen in the original carton to protect from light.
After the first injection, store refrigerated at 2°C to 8°C (36°F to 46°F) or at room temperature at 20°C to 25°C (68°F to 77°F) for up to 28 days. Keep the cap on the pen to protect from light. Do not freeze.
Discard unused material after 28 days.
📋 Description ▾
11 DESCRIPTION Follitropin alfa, a gonadotropin [human follicle stimulating hormone (hFSH)], is a glycoprotein hormone produced by recombinant DNA technology in a Chinese Hamster Ovary (CHO) cell line. It has a dimeric structure consisting of two glycoprotein subunits (alpha and beta). The alpha and beta subunits have 92 and 111 amino acids, respectively, and their primary and tertiary structures are indistinguishable from those of human follicle stimulating hormone.
The molecular weight is approximately 31 kDa (14 kDa for alpha subunit and 17 kDa for beta subunit). GONAL-f ® RFF Redi-ject ® (follitropin alfa) injection is a sterile, clear and colorless to slightly yellow solution in disposable, prefilled single-patient-use pen intended for the subcutaneous use. Each GONAL-f ® RFF Redi-ject ® pen delivers 300 International Units (22 mcg) follitropin alfa in 0.48 mL and the inactive ingredients: dibasic sodium phosphate (0.43 mg), m-cresol (1.47 mg), methionine (0.05 mg), monobasic sodium phosphate (0.19 mg), poloxamer (0.05 mg), sucrose (29.47 mg) and Water for Injection USP.
Phosphoric acid and/or sodium hydroxide may be used to adjust the pH to 7. Each GONAL-f ® RFF Redi-ject ® pen delivers 450 International Units (33 mcg) follitropin alfa in 0.72 mL and the inactive ingredients: dibasic sodium phosphate (0.65 mg), m-cresol (2.21 mg), methionine (0.07 mg), monobasic sodium phosphate (0.29 mg), poloxamer (0.07 mg), sucrose (44.20 mg) and Water for Injection USP. Phosphoric acid and/or sodium hydroxide may be used to adjust the pH to 7.
Each GONAL-f ® RFF Redi-ject ® pen delivers 900 International Units (66 mcg) follitropin alfa in 1.44 mL and the inactive ingredients: dibasic sodium phosphate (1.3 mg), m-cresol (4.42 mg), methionine (0.15 mg), monobasic sodium phosphate (0.58 mg), poloxamer (0.15 mg), sucrose (88.41 mg) and Water for Injection USP. Phosphoric acid and/or sodium hydroxide may be used to adjust the pH to 7. Under current storage conditions, GONAL-f ® RFF Redi-ject ® may contain up to 10% of oxidized follitropin alfa.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information and Instructions for Use)
17.1Dosing and Use of GONAL-f ® RFF Redi-ject ® Instruct women on the correct usage and dosing of GONAL-f ® RFF Redi-ject ® [see Dosage and Administration (2.2 , 2.3) ] . Instruct women to view the dose display in bright light and to adjust the position of the GONAL-f ® RFF Redi-ject ® to minimize dose window glare. Caution women not to change the dosage or the schedule of administration unless she is told to do so by her healthcare provider.
Instruct women to remove the GONAL-f ® RFF Redi-ject ® from the refrigerator at least 30 minutes prior to use in order to allow GONAL-f ® RFF Redi-ject ® to warm to room temperature and avoid the discomfort of a cold injection.
17.2Duration and Necessary Monitoring in Women Undergoing Therapy with GONAL-f ® RFF Redi-ject ® Prior to beginning therapy with GONAL-f ® RFF Redi-ject ® , inform women about the time commitment and monitoring procedures necessary for treatment [see Dosage and Administration (2.2 , 2.3) and Warnings and Precautions (5.11) ].
17.3Instructions Regarding a Missed Dose Inform the woman that if she misses or forgets to take a dose of GONAL-f ® RFF Redi-ject ® , the next dose should not be doubled and she should call her healthcare provider for further dosing instructions.
17.4Ovarian Hyperstimulation Syndrome Inform women regarding the risks of OHSS [see Warnings and Precautions (5.3) ] and OHSS-associated symptoms including lung and blood vessel problems [see Warnings and Precautions (5.4) ] and ovarian torsion [see Warnings and Precautions (5.5) ] with the use of GONAL-f ® RFF Redi-ject ® .
17.5Multi-fetal Gestation and Birth Inform women regarding the risk of multi-fetal gestation and birth with the use of GONAL-f ® RFF Redi-ject ® [see Warnings and Precautions (5.6) ]