The following Structured Product Label (SPL) was submitted to the FDA by Emd Serono, Inc. for the product Gonal-f Rff Redi-ject (NDC 44087-1116). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding 1.1 induction of ovulation and pregnancy in oligo-anovulatory women in whom the cause of infertility is functional and not due to primary ovarian failure., 1.2 development of multiple follicles in ovulatory women as part of an assisted reproductive technology (art) cycle., 2.1 general dosing information, 2.2 recommended dosing for ovulation induction, 2.3 recommended dosing for assisted reproductive technology, 3 dosage forms and strengths, 4 contraindications, 5 warnings and precautions, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
Prior to initiation of treatment with Gonal-f® RFF Redi-ject®:
Prior to initiation of treatment with Gonal-f® RFF Redi-ject®:
The dosing scheme is stepwise and is individualized for each woman [see Clinical Studies (14.1)]. Starting doses less than 37.5 International Units have not been studied in clinical trials and are not recommended.
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®.
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)].
Discourage intercourse when the risk for OHSS is increased [see Warnings and Precautions (5.2, 5.3)].
The dosing scheme follows a stepwise approach and is individualized for each woman.
| • Injection: | Gonal-f® RFF Redi-ject® 300 International Units per 0.5 mL in prefilled, multiple dose disposable delivery system |
| • Injection: | Gonal-f® RFF Redi-ject® 450 International Units per 0.75 mL in prefilled, multiple dose disposable delivery system |
| • Injection: | Gonal-f® RFF Redi-ject® 900 International Units per 1.5 mL in prefilled, multiple dose disposable delivery system |
Gonal-f® RFF Redi-ject® is contraindicated in women who exhibit:
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)].
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, pruritis, 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.
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)].
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 Warnings and Precautions (5.2)], the hCG must be withheld. Cases of OHSS are more common, more severe, and more protracted if pregnancy occurs; therefore, women should be assessed for the development of OHSS for at least two weeks after hCG administration.
If serious OHSS occurs, gonadotropins, including hCG, should be stopped and consideration should be given as to whether the woman needs to be hospitalized. Treatment is primarily symptomatic and overall should consist of bed rest, fluid and electrolyte management, and analgesics (if needed). Because the use of diuretics can accentuate the diminished intravascular volume, diuretics should be avoided except in the late phase of resolution as described below. The management of OHSS may be divided into three phases as follows:
Ascitic, pleural, and pericardial fluid should not be removed unless there is the necessity to relieve symptoms such as pulmonary distress or cardiac tamponade.
OHSS increases the risk of injury to the ovary. Pelvic examination or intercourse may cause rupture of an ovarian cyst, which may result in hemoperitoneum, and should therefore be avoided.
If bleeding occurs and requires surgical intervention, the clinical objective should be to control the bleeding and retain as much ovarian tissue as possible. A physician experienced in the management of this syndrome, or who is experienced in the management of fluid and electrolyte imbalances should be consulted.
During clinical trials with Gonal-f® RFF, OHSS occurred in 7.2% of 83 women and 4.6% of 237 women treated with Gonal-f® RFF for ovulation induction and during Assisted Reproductive Technology, respectively.
Serious pulmonary conditions (e.g., atelectasis, acute respiratory distress syndrome and exacerbation of asthma) have been reported in women treated with gonadotropins. In addition, thromboembolic events both in association with, and separate from OHSS have been reported in women treated with gonadotropins including Gonal-f® RFF. Intravascular thrombosis and embolism, which may originate in venous or arterial vessels, can result in reduced blood flow to critical organs or the extremities. Women with generally recognized risk factors for thrombosis, such as personal or family history, severe obesity, or thrombophilia, may have an increased risk of venous or arterial thromboembolic events, during or following treatment with gonadotropins. Sequelae of such reactions have included venous thrombophlebitis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion (stroke), and arterial occlusion resulting in loss of limb and rarely in myocardial infarctions. In rare cases, pulmonary complications and/or thromboembolic reactions have resulted in death. In women with recognized risk factors, the benefits of ovulation induction and assisted reproductive technology need to be weighed against the risks. It should be noted that pregnancy also carries an increased risk of thrombosis.
Ovarian torsion has been reported after treatment with gonadotropins. This may be related to OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst and polycystic ovaries. Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.
Multi-fetal gestation and births have been reported with all gonadotropin therapy including therapy with Gonal-f® RFF.
During clinical trials with Gonal-f® RFF, multiple births occurred in 20% of live births in women receiving therapy for ovulation induction and 35.1 % of live births in women undergoing ART.
The woman and her partner should be advised of the potential risk of multi-fetal gestation and birth before beginning therapy with Gonal-f® RFF Redi-ject®.
The incidence of congenital malformations after some ART [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 the higher incidence of multi-fetal gestations after IVF or ICSI. There are no indications that the use of gonadotropins during IVF or ICSI is associated with an increased risk of congenital malformations.
Since infertile women undergoing ART often have tubal abnormalities, the incidence of ectopic pregnancy may be increased. Early confirmation of intrauterine pregnancy should be determined by β-hCG testing and transvaginal ultrasound.
The risk of spontaneous abortion (miscarriage) is increased with gonadotropin products. However, causality has not been established. The increased risk may be a factor of the underlying infertility.
There have been infrequent reports of ovarian neoplasms, both benign and malignant, in women who have had multiple drug therapy for controlled ovarian stimulation, however, a causal relationship has not been established.
In most instances, treatment of women with Gonal-f® RFF Redi-ject® will result only in follicular growth and maturation. In the absence of an endogenous LH surge, hCG is given when monitoring of the woman indicates that sufficient follicular development has occurred. This may be estimated by ultrasound alone or in combination with measurement of serum estradiol levels. The combination of both ultrasound and serum estradiol measurement are useful for monitoring follicular growth and maturation, timing of the ovulatory trigger, detecting ovarian enlargement and minimizing the risk of the OHSS and multiple gestation.
The clinical confirmation of ovulation is obtained by direct or indirect indices of progesterone production as well as sonographic evidence of ovulation.
Direct or indirect indices of progesterone production:
Sonographic evidence of ovulation:
The following serious adverse reactions are discussed elsewhere in the labeling:
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.
| System Organ Class/Adverse Reactions | Gonal-f® RFF N=83 total number of women treated with Gonal-f® RFF (176 treatment cyclesup 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.
| 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%) |
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.
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.
Manufactured for: EMD Serono, Inc., Rockland, MA 02370 U.S.A.
Manufactured for:
EMD Serono, Inc.
Rockland, MA 02370
Revised: January 2014
The following adverse reactions have been reported during postmarketing use of Gonal-f® RFF. Because these reactions were reported voluntarily from a population of uncertain size, the frequency or a causal relationship to Gonal-f® RFF cannot be reliably determined.
Body as a Whole - General: hypersensitivity reactions including anaphylactoid reactions [see Warnings and Precautions (5.1)]
Respiratory System: asthma
Vascular disorders: thromboembolism [see Warnings and Precautions (5.4)]
No drug-drug interaction studies have been performed.
Teratogenic effects
[see Contraindications (4)].
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in the nursing infant from Gonal-f® RFF Redi-ject®, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in pediatric patients have not been established.
Safety, efficacy, and pharmacokinetics of Gonal-f® RFF Redi-ject® in women with renal or hepatic insufficiency have not been established.
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®.
Gonal-f® RFF Redi-ject® contains human follicle stimulating hormone (hFSH), a glycoprotein hormone manufactured by recombinant DNA technology. The active drug substance, follitropin alfa, has a dimeric structure consisting of two non-covalently linked, non-identical glycoproteins designated as the α-and β-subunits. The α-and β-subunits have 92 and 111 amino acids, respectively, and their primary and tertiary structures are indistinguishable from those of human follicle stimulating hormone.
Recombinant human FSH production occurs in genetically modified Chinese Hamster Ovary (CHO) cells cultured in bioreactors. Purification by immunochromatography using an antibody specifically binding FSH results in a highly purified preparation with a consistent FSH isoform profile, and a high specific activity. The protein content is assessed by size exclusion high pressure liquid chromatography. The biological activity of follitropin alfa is determined by measuring the increase in ovary weight in female rats. The in vivo biological activity of follitropin alfa has been calibrated against the first International Standard for recombinant human follicle stimulating hormone established in 1995 by the Expert Committee on Biological Standards of the World Health Organization. Gonal-f® RFF Redi-ject® contains no luteinizing hormone (LH) activity. Based on available data derived from physico-chemical tests and bioassays, follitropin alfa and follitropin beta, another recombinant follicle stimulating hormone product, are indistinguishable.
Gonal-f® RFF Redi-ject® is a disposable, prefilled drug delivery system intended for the subcutaneous injection of multiple and variable doses of a liquid formulation of follitropin alfa.
Each Gonal-f® RFF Redi-ject® is filled with 415 International Units (30 mcg), 568 International Units (41 mcg), or 1026 International Units (75 mcg) follitropin alfa to deliver at least 300 International Units (22 mcg) in 0.5 mL, 450 International Units (33 mcg) in 0.75 mL, or 900 International Units (66 mcg) in 1.5 mL, respectively. Each Redi-ject® also contains 60 mg/mL sucrose, 3.0 mg/mL m-cresol, 1.1 mg/mL di-sodium hydrogen phosphate dihydrate, 0.45 mg/mL sodium dihydrogen phosphate monohydrate, 0.1 mg/mL methionine, 0.1 mg/mL Poloxamer 188. O-phosphoric acid and/or sodium hydroxide may be used for pH adjustment.
Under current storage conditions, Gonal-f® RFF Redi-ject® may contain up to 10% of oxidized follitropin alfa.
Therapeutic Class: Infertility
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.
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.
| Parameter | Healthy Volunteers (N=21) | |
|---|---|---|
| Mean | % CV | |
| Abbreviations are: Cmax: peak concentration (above baseline) tmax: time of Cmax t1/2: elimination half life | ||
| AUClast (IU hr/L) | 884 | 20% |
| Cmax (IU/L) | 9.83 | 23% |
| tmax (hr) | 15.5 | 43% |
| t1/2 (hr) | 53 | 52% |
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Gonal-f® RFF Redi-ject®. However, follitropin alfa showed no mutagenic activity in a series of tests performed to evaluate its potential genetic toxicity including, bacterial and mammalian cell mutation tests, a chromosomal aberration test and a micronucleus test.
Impaired fertility has been reported in rats, exposed to pharmacological doses of follitropin alfa (greater than or equal to 40 International Units per kg per day, greater than or equal to 5 times the lowest clinical dose of 75 International Units) for extended periods, through reduced fecundity.
The safety and efficacy of Gonal-f® RFF were examined in two clinical studies (one ovulation induction study and one ART study).
Ovulation induction was evaluated in a randomized, assessor-blind, multinational, multicenter, active-controlled, study in oligo-anovulatory infertile women. Women were randomized to either Gonal-f® RFF (n=83), administered subcutaneously, or a comparator recombinant human FSH. The use of insulin-sensitizing agents was allowed during the study. The study was designed to evaluate and compare mean ovulation rates in the first cycle of treatment. Results for Gonal-f® RFF are presented in Table 4. Also presented in this table are secondary outcome results from cycle 1 through cycle 3. The study was not powered to demonstrate differences in any of the secondary outcomes.
| Gonal-f® RFF (n=83) | ||
|---|---|---|
| Cycle | Cumulative Cumulative rates were determined per woman over cycles 1, 2, and 3. Percent Ovulation | Cumulative Clinical pregnancy was defined as a pregnancy for which a fetal sac (with or without heart activity) was visualized by ultrasound on day 34-36 after hCG administration. Rate |
| Cycle 1 | 72% Non-inferior to comparator recombinant human FSH based on a two-sided 95% confidence interval, intent-to-treat analysis. | 28% Secondary efficacy outcomes. The study was not powered to demonstrate differences in these outcomes. |
| Cycle 2 | 89% | 41% |
| Cycle 3 | 92% | 45% |
The efficacy of Gonal-f® RFF was evaluated in a randomized, assessor-blind, multinational, multicenter, active controlled study in healthy normal ovulatory, infertile women treated for one cycle with controlled ovarian stimulation, as part of an ART [in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI)] cycle. Women were randomized to either Gonal-f® RFF (n=237), administered subcutaneously, or a comparator recombinant human FSH. Randomization was stratified by insemination technique, (IVF vs. ICSI). All women received pituitary down-regulation with a GnRH agonist before stimulation with recombinant FSH. Efficacy was assessed using the mean number of fertilized oocytes the day after insemination. The initial doses of Gonal-f® RFF were 150 International Units per day for women less than 35 years of age and 225 International Units per day for women 35 years of age and older. The maximum dose given for both age groups was 450 International Units per day. Treatment outcomes for Gonal-f® RFF are summarized in Table 5.
| Study Outcome | value (n) |
|---|---|
| Mean number of 2PN oocytes per woman | 6.3 (237) Non-inferior to comparator recombinant human FSH based on a two-sided 95% confidence interval, intent-to-treat analysis. |
| Mean number of 2PN oocytes per subject receiving IVF | 6.1 (88) Subgroup analyses. The study was not powered to demonstrate differences in subgroups. |
| Mean number of 2PN oocytes per subject receiving ICSI | 6.5 (132) |
| Clinical pregnancy A clinical pregnancy was defined as a pregnancy during which a fetal sac (with or without heart activity) was visualized by ultrasound on day 35-42 after hCG administration. rate per attempt | 33.5% (218) Secondary efficacy outcomes. The study was not powered to demonstrate differences in these outcomes. |
| Clinical pregnancy | 35.8% (204) |
| Mean treatment duration in days (range) | 9.7 [3-21] (230) |
Gonal-f® RFF Redi-ject® is a disposable, prefilled multiple-dose delivery system containing a sterile, ready-to-use liquid formulation of follitropin alfa. Each Redi-ject® is supplied in a carton containing 29G × 1/2 inch disposable needles to be used for administration.
The following package presentations are available:
NDC 44087-1115-1 - One Gonal-f® RFF Redi-ject® contains 415 International Units of follitropin alfa to deliver 300 International Units per 0.5 mL and 5 single-use disposable 29G × ½" needles
NDC 44087-1116-1 - One Gonal-f® RFF Redi-ject® contains 568 International Units of follitropin alfa to deliver 450 International Units per 0.75 mL and 7 single-use disposable 29G × ½" needles
NDC 44087-1117-1 - One Gonal-f® RFF Redi-ject® contains 1026 International Units of follitropin alfa to deliver 900 International Units per 1.5 mL and 14 single-use disposable 29G × ½" needles
Store the Gonal-f® RFF Redi-ject® refrigerated 2°C to 8°C (36°F to 46°F) until dispensed. Upon dispensing, store Redi-ject® refrigerated 2°C to 8°C (36°F to 46°F) until the expiration date, or at room temperature 20° to 25°C (68° to 77°F) for up to three months or until the expiration date, whichever occurs first. After the first injection, store refrigerated 2°C to 8°C (36°F to 46°F) or at room temperature 20°C to 25°C (68°F to 77°F) for up to 28 days. Protect from light. Do not freeze. Discard unused material after 28 days.
See FDA-approved patient labeling (Patient Information and Instructions for Use)
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.
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)].
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.
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®.
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)]
Gonal-f® RFF Redi-ject® (gon-AL-eff ar-eff-eff REH dee-jekt)
(follitropin alfa injection)
for subcutaneous use
Gonal-f® RFF* Redi-ject® (follitropin alfa injection) for subcutaneous use
*revised formulation female
Read this Patient Information before you start using Gonal-f® RFF Redi-ject® and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is Gonal-f® RFF Redi-ject®?
Gonal-f® RFF Redi-ject® is an injection Pen that delivers a prescription medicine containing follicle-stimulating hormone (FSH) used in infertile women to:
Who should not use Gonal-f® RFF Redi-ject®?
Do not use the Gonal-f® RFF Redi-ject® if you:
What should I tell my healthcare provider before using Gonal-f® RFF Redi-ject®?
Before you use Gonal-f® RFF Redi-ject®, tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I use Gonal-f® RFF Redi-ject®?
What are the possible side effects of Gonal-f® RFF Redi-ject®?
Gonal-f® RFF Redi-ject® may cause serious side effects, including:
The most common side effects of Gonal-f® RFF Redi-ject® include:
These are not all the possible side effects of Gonal-f® RFF Redi-ject®. For more information, call your healthcare provider or pharmacist.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Gonal-f® RFF Redi-ject®?
Keep Gonal-f® RFF Redi-ject® and all medicines out of the reach of children.
General Information about the safe and effective use of Gonal-f® RFF Redi-ject®.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Gonal-f® RFF Redi-ject® for a condition for which it was not prescribed. Do not give Gonal-f® RFF Redi-ject® to other people, even if they have the same condition that you have. It may harm them.
This Patient Information leaflet summarizes the most important patient information about Gonal-f® RFF Redi-ject®. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Gonal-f® RFF Redi-ject® that is written for health professionals.
For more information, go to www.fertilitylifelines.com, or call 1-866-538-7879.
What are the ingredients in Gonal-f® RFF Redi-ject®?
Active ingredient: follitropin alfa (r-hFSH)
Inactive ingredients: sucrose, meta-cresol, di-sodium hydrogen phosphate dihydrate, sodium dihydrogen phosphate monohydrate, methionine, Poloxamer 188, O-phosphoric acid, sodium hydroxide
This Patient Information has been approved by the U.S. Food and Drug Administration.
EMD Serono
GONAL-f® RFF Redi-ject®
(follitropin alfa injection)
INSTRUCTIONS FOR USE
Figure (Gonal F 01)
GONAL-f® RFF Redi-ject®
(follitropin alfa injection)
Important
Warning: Do not reuse needles.
Warning: Do not share the pen and needles with another person, because doing so can cause an infection.
Figure (Gonal F 02)
Gather your supplies
Figure (Gonal F 03)
Caution: Do not use a microwave or other heating element to warm up the pen.
Figure (Gonal F 04)
Get familiar with the parts of your pen and needle
Figure (Gonal F 05)
*The numbers on the Dose Information Display and reservoir represent the number of International Units (IU) of medicine.
Step 1 Get Ready
Figure (Gonal F 06)
Caution: Do not shake the pen. If you shake the pen, air bubbles may appear in the medicine.
Figure (Gonal F 07)
Figure (Gonal F 08)
Step 2 Choose and prepare your injection site
Note: Your healthcare provider should show you the injection sites to use around your stomach area.
Figure (Gonal F 09)
Step 3 Attach your needle
Figure (Gonal F 10)
Figure (Gonal F 11)
Figure (Gonal F 12)
Caution: Do not attach the needle too tightly, the needle could be difficult to remove after the injection.
Figure (Gonal F 13)
Figure (Gonal F 14)
Warning: Do not recap the needle with the green inner needle shield you could get a needle stick injury.
| Important | |
| If | Then |
| Using a new pen | Check for a droplet of liquid at the tip of the needle. |
 Figure (Gonal F 15) | If you see a droplet go to Step 4 Dial your Dose |
| If no droplet is seen, or you are unsure, follow the instructions in Appendix B. | |
| Re-using a pen | You do not have to check for droplets of liquid at the tip of the needle. Go to Step 4 Dial your Dose |
Step 4 Dial your dose
Note: Call your healthcare provider if you are unsure of today's intended dose.
Caution: Do not push or pull the dose knob while you turn it to avoid damaging it.
Figure (Gonal F 16)
Note: You can turn the dose knob backward if you turn it past your intended dose.
Step 5 Inject your dose
Important
Example: If your intended dose is 150IU, confirm that the Dose Information Display reads 150.
Figure (Gonal F 17)
Figure (Gonal F 18)
Caution: You might bend the needle if you do not insert the needle straight in at a 90° angle.
Caution: Do not release the dose knob until you remove the needle from your skin. Hold the dose knob down for a slow count of 5 before you remove the needle from your skin. Then release the knob after removal of the needle from your skin.
Figure (Gonal F 19)
Warning: If the Dose Information Display does not show "0", you did not complete your dose.
Step 6 Remove and throw away your needle
Warning: You must remove the needle from the pen and throw away after each injection to avoid risk of infection.
Figure (Gonal F 20)
Figure (Gonal F 21)
Figure (Gonal F 22)
Figure (Gonal F 23)
Step 7 Record your injection
Important
Note: The pen contains extra medicine to ensure that you receive the full amount indicated on the pen (300 IU, 450 IU, or 900 IU).
Appendix A: Completing an incomplete dose
Appendix B: How to create a droplet of liquid
Figure (Gonal F 24)
Figure (Gonal F 25)
Figure (Gonal F 26)
Appendix C: How to throw away used needles and empty pens
Figure (Gonal F 27)
Warning: Do not throw away loose needles and pens in your household trash.
Appendix D: How to store your pen
For more information, call 1-866-538-7879.
To view the Instructions for Use video, please visit www.Rediject.com
Figure (Gonal F 28)
Figure (Gonal F 29)
EMD Serono, Inc
Rockland, MA 02370
EMD Serono, Inc. is an affiliate of Merck KGaA, Darmstadt, Germany
©2017 EMD Serono, Inc.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: February 2020
NDC 44087-1115-1
GONAL-f ® RFF Redi-ject®
300 IU / 0.5 mL
(follitropin alfa injection)
For subcutaneous injection
Do not shake
Rx only
1 Gonal-f® RFF Redi-ject®
5 needles for injection (29 gauge)
* revised formulation female
EMD
SERONO
Principal Display Panel (300 IU Kit Carton)
NDC 44087-1116-1
GONAL-f ® RFF Redi-ject®
450 IU / 0.75 mL
(follitropin alfa injection)
For subcutaneous injection
Do not shake
Rx only
1 Gonal-f® RFF Redi-ject®
7 needles for injection (29 gauge)
* revised formulation female
EMD
SERONO
Principal Display Panel (450 IU Kit Carton)
NDC 44087-1117-1
GONAL-f ® RFF Redi-ject®
900 IU / 1.5 mL
(follitropin alfa injection)
For subcutaneous injection
Do not shake
Rx only
1 Gonal-f® RFF Redi-ject®
14 needles for injection (29 gauge)
* revised formulation female
EMD
SERONO
Principal Display Panel (900 IU Kit Carton)
NDC 44087-1118-1
GONAL-f ® RFF Redi-ject®
150 IU / 0.25 mL
(follitropin alfa injection)
For subcutaneous injection
Do not shake
Rx only
1 Gonal-f® RFF Redi-ject®
4 needles for injection (29 gauge)
* revised formulation female
EMD
SERONO
* Please review the disclaimer below.
