DailyMed Label: GONAL-F RFF

DailyMed Label: GONAL-F RFF

2023

DailyMed Prescription

GONAL-F RFF

follitropin alfa

EMD Serono, Inc.

NDC: 44087-9005

NDC: 44087-9005

Follitropin alpha, a gonadotropin [human follicle stimulating hormone (FSH)], is a glycoprotein hormone produced by recombinant DNA technology in 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 structure 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 (follitropin alfa) for injection is a sterile, white lyophilized powder intended for subcutaneous injection after reconstitution. Each GONAL-F RFF single-dose vial delivers 75 International Units (5.5 mcg) and contains dibasic sodium phosphate (0.89 mg), methionine (0.1 mg), monobasic sodium phosphate (0.39 mg), polysorbate 20 (0.05 mg), and sucrose (30 mg). Phosphoric acid and/or sodium hydroxide may be used prior to lyophilization for pH adjustment. Vials are reconstituted with Sterile Water for Injection, USP, resulting in concentration of 75 IU/mL with a pH of approximately 7 Under current storage conditions, GONAL-F RFF may contain up to 10% of oxidized follitropin alfa.

Gonal-F RFF is indicated for:

Induction of Ovulation ( 2.2 ) Initial starting dose of the first cycle: 75 International Units of GONAL-F RFF per day for 14 days, administered subcutaneously Individualize doses after 14 days Do not administer doses greater than 300 International Units per day Development of Multiple Follicles in Assisted Reproductive Technology (ART) ( 2.3 ) Initial starting dose of the first cycle: 150 International Units per day, administered subcutaneously Dosage adjustments after 3 to 5 days and by 75 to 150 International Units at each adjustment Do not administer doses greater than 450 International Units per day

For Injection: 75 International Units lyophilized powder in a singledose vial for reconstitution co-packaged with 1-mL prefilled syringe(s) of Sterile Water for Injection, USP. ( 3 )

GONAL-F RFF is contraindicated in women who exhibit: Prior hypersensitivity to recombinant FSH products or one of their excipients. Reactions have included anaphylaxis [see Warnings and Precautions (5.1) ]. High levels of FSH indicating primary gonadal failure The presence of uncontrolled non-gonadal endocrinopathies (for example, thyroid, adrenal, or pituitary disorders) Sex hormone dependent tumors of the reproductive tract and accessory organs Tumors of the pituitary gland or hypothalamus Abnormal uterine bleeding of undetermined origin Ovarian cyst or enlargement of undetermined origin

Hypersensitivity Reactions and Anaphylaxis: If occurs, initiate appropriate therapy, including supportive measures, and discontinue use of GONAL-F RFF ( 5.1 ) Ovarian Hyperstimulation Syndrome (OHSS): If serious, stop gonadotropins, including hCG, and determine if the woman needs to be hospitalized. Treatment is primarily symptomatic and consists of bed rest, fluid and electrolyte management, and analgesics ( 5.2 ) Pulmonary and Vascular Complications: In women with recognized risk factors, the benefits of induction of ovulation and ART need to be weighed against the risks. During or after use of GONAL-F RFF, monitor for venous or arterial thromboembolic events ( 5.3 ) Ovarian Torsion: Early diagnosis and immediate detorsion limit damage to the ovary due to reduced blood supply ( 5.4 ) Abnormal Ovarian Enlargement: If the ovaries are abnormally enlarged on the last day of GONAL-F RFF therapy, inform women not to administer hCG and to avoid intercourse ( 5.5 ) Multi-fetal Gestation and Births: The rate of multiple births is dependent on the number of embryos transferred. Advise the woman and her partner of the potential risk of multi-fetal gestation and birth before beginning therapy with GONAL-F RFF ( 5.6 ) Embryofetal Toxicity: Inform women that the incidence of congenital malformations (birth defects) after some Assisted Reproductive Technology [(ART) specifically in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)] may be slightly higher than after spontaneous conception. There is no evidence that the use of gonadotropins during IVF or ICSI is associated with an increased risk of congenital malformations ( 5.7 ) Ectopic Pregnancy: Advise women who become pregnant following ART and have: abdominal/pelvic pain (particularly on one side); shoulder, neck or rectal pain; and nausea and vomiting to seek immediate medical attention. Confirm the presence of an intrauterine pregnancy early by β-hCG testing and transvaginal ultrasound ( 5.8 ) Spontaneous Abortion: The risk of spontaneous abortion (miscarriage) is increased with gonadotropin products, however, causality has not been established ( 5.9 ) Ovarian Neoplasm: Both benign and malignant ovarian neoplasms are reported in women who have had multiple drug therapy for controlled ovarian stimulation, however, causality has not been established ( 5.10 )

The following serious adverse reactions are discussed elsewhere in the labeling:

Lactation: Advise not to breastfeed ( 8.2 )

GONAL-F RFF (follitropin alfa) for injection is supplied as a sterile, white, lyophilized powder of 75 International Units per single-dose vial. The following package combinations are available: 1 vial GONAL-F RFF 75 International Units and 1 pre-filled syringe Sterile Water for Injection, USP, 1 mL, 1 reconstitution needle (18 gauge), 1 administration needle (29 gauge), NDC 44087-9005-1 10 vials GONAL-F RFF 75 International Units and 10 pre-filled syringes Sterile Water for Injection, USP, 1 mL, 10 reconstitution needles (18 gauge), 10 administration needles (29 gauge), NDC 44087-9005-6

GONAL-F RFF stimulates ovarian follicular growth in women who do not have primary ovarian failure. In order to bring about final maturation of the follicle and ovulation in the absence of an endogenous LH surge, human chorionic gonadotropin (hCG) must be given, following the administration of GONAL-F RFF, when monitoring of the patient indicates that sufficient follicular development is achieved.

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of GONAL-F RFF. 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.

Induction of Ovulation was evaluated in a randomized, assessor-blind, multinational, multicenter, active-controlled trial in oligo-anovulatory infertile women. Women were randomized to either GONAL-F RFF (n=83), administered subcutaneously, or a comparator recombinant human FSH product. The use of insulin-sensitizing agents was allowed during the trial. The trial was designed to evaluate and compare mean ovulation rates in the first cycle of treatment. Results for GONAL-F RFF are presented in Table 3. Also presented in this table are secondary outcome results from cycle 1 through 3. The trial was not powered to demonstrate differences in any of the secondary outcomes. Table 3: Cumulative Ovulation and Clinical Pregnancy Rates in Induction of Ovulation Cycle GONAL-F RFF (n=83) Cumulative Cumulative rates were determined per woman over cycles 1, 2, and 3. Percent Ovulation Cumulative Clinical Pregnancy 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 trial was not powered to demonstrate differences in these outcomes. Cycle 2   89%   41% Cycle 3   92%   45%

PATIENT INFORMATION GONAL-F ® RFF (gon-AL-eff ar-eff-eff) (follitropin alfa) for injection for subcutaneous use What is GONAL-F RFF? GONAL-F RFF is a prescription medicine containing follicle-stimulating hormone (FSH). GONAL-F RFF 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 Do not use GONAL-F RFF if you: are allergic to recombinant human FSH or any of the ingredients in GONAL-F RFF. See the end of this leaflet for a complete list of ingredients in GONAL-F RFF. have high levels of FSH in your blood that show your ovaries do not work at all. have uncontrolled thyroid, adrenal, or pituitary problems. have a tumor in your female organs, including your ovaries, uterus or breast that may get worse with high levels of estrogen. have a tumor in your brain, such as a tumor in your pituitary gland or hypothalamus. have abnormal bleeding from your uterus or vagina from an unknown cause. have ovarian cysts or large ovaries from an unknown cause. Before you start using GONAL-F RFF tell your healthcare provider about all of your medical conditions, including if you: have or have had asthma have been told by a healthcare provider that you have an increased risk for blood clots (thrombosis) have ever had a blood clot (thrombosis), or anyone in your family has ever had a blood clot (thrombosis) have had stomach (abdominal) surgery have had twisting of your ovary (ovarian torsion) had or have a cyst on your ovary have polycystic ovarian disease are pregnant or think you may be pregnant. GONAL-F RFF is not for pregnant women. Your healthcare provider will give you a pregnancy test before you start using GONAL-F RFF. are breastfeeding. It is not known if GONAL-F RFF passes into your breast milk. You and your healthcare provider should decide if you will take GONAL-F RFF or breastfeed. You should not do both. are not an adult. GONAL-F ® is not for children. It is not known if GONAL-F is safe or works in children. 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? Read the " Instructions for Use " that comes with GONAL-F RFF for information about the right way to use GONAL-F RFF. Use GONAL-F RFF exactly as your healthcare provider tells you to. GONAL-F RFF is given by injection under your skin. You can inject GONAL-F RFF under the skin in the stomach (abdomen), upper arm, or upper leg. Do not inject GONAL-F RFF at home until your healthcare provider has taught you the right way to inject it. Change your injection site as your healthcare provider showed you. Do not change your dose or the time you are scheduled to use GONAL-F RFF unless your healthcare provider tells you to. If you miss or forget to take a dose, do not double your next dose. Ask your healthcare provider for instructions. Your healthcare provider will do blood and urine hormone tests while you are using GONAL-F RFF. Make sure you follow-up with your healthcare provider to have your blood and urine tested when told to do so. Call your healthcare provider if you have any questions about your dose or how to use GONAL-F RFF. Your healthcare provider may do ultrasound scans of your ovaries. Make sure you follow-up with your healthcare provider to have your ultrasounds. What are the possible side effects of GONAL-F RFF? GONAL-F RFF may cause serious side effects, including: severe allergic reactions . Women who have used GONAL-F ® , GONAL-F ® RFF or GONAL-F ® Redi-Ject ® in the past may have a severe allergic reaction right away when they use GONAL-F RFF 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 RFF 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) ovarian hyperstimulation syndrome (OHSS). OHSS is both a serious and common side effect. Using GONAL-F RFF 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 RFF. Stop using GONAL-F RFF and call your healthcare provider right away if you have symptoms of OHSS, including: trouble breathing nausea diarrhea severe lower stomach (pelvic) area pain vomiting decreased urine output weight gain lung problems. GONAL-F RFF 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 RFF 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 twisting (torsion) of your ovary. GONAL-F RFF 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 RFF 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 RFF 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 RFF 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 neck pain nausea and vomiting shoulder pain rectal pain 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 RFF 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 RFF include: headache OHSS nausea stomach pain swelling and pain at the injection site gas stomach bloating diarrhea ovarian cyst 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 RFF. For more information, call 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. How should I store GONAL-F RFF? Before you use GONAL-F RFF for the first time, store your vials: in the refrigerator between 36°F to 46°F (2°C to 8°C) until the expiration date, or store your vials at room temperature between 68°F to 77°F (20°C to 25°C) until the expiration date. After you use GONAL-F RFF throw away (discard) unused material. Store your GONAL-F RFF vials in a safe place. Store GONAL-F RFF away from light. Keep GONAL-F RFF and all medicines out of the reach of children. General Information about the safe and effective use of GONAL-F RFF. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use GONAL-F RFF for a condition for which it was not prescribed. Do not give GONAL-F RFF to other people, even if they have the same condition that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about GONAL-F RFF 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? Active ingredient: follitropin alfa (r-hFSH) Inactive ingredients : dibasic sodium phosphate, methionine, monobasic sodium phosphate , phosphoric acid and/or sodium hydroxide, polysorbate 20, sucrose. Manufactured by: EMD Serono, Inc Rockland, MA 02370 USA US License No. 1773 EMD Serono, Inc. is an affiliate of Merck: KGaA, Darmstadt, Germany This Patient Package Insert has been approved by the U.S. Food and Drug Administration. 11/2023

GONAL-f ® RFF (follitropin alfa) for injection NDC 44087-9005-1 Rx Only 75 IU/vial Single-dose vial. Use immediately after reconstitution. Discard unused material. Lot: Exp: