Important Risk Information for Gonal-f^® RFF* Redi-ject^® (follitropin alfa injection)

Contraindications:

• Prior hypersensitivity to rhFSH preparations or excipients
• high levels of FSH indicating primary gonadal failure
• pregnancy – apprise women of the potential hazard to the fetus if administered during pregnancy
• uncontrolled non-gonadal endocrinopathies (thyroid, adrenal, pituitary disorders)
• 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.

Warnings and Precautions:

• For use by physicians specializing in fertility treatment or reproductive health and only when appropriate monitoring facilities are available. 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. Careful selection should be given to the diagnosis of infertility and the selection so candidates for therapy. The lowest effective dose should be used.
  
• Hypersensitivity Reactions and Anaphylaxis: Serious systemic hypersensitivity reactions, including anaphylaxis, have been reported in post-marketing experience. 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.
• Abnormal Ovarian Enlargement: Treatment should be individualized and the lowest effective dose should be used. Use of ultrasound monitoring of ovarian response and/or measurement of serum estradial levels is important to minimize the risk of ovarian stimulation. If the ovaries are enlarged on the last day of therapy, hCG should not be administered to reduce the risk of developing OHSS. Prohibit intercourse in women with significant ovarian enlargement.
• Ovarian Hyperstimulation Syndrome (OHSS): OHSS occurs after gonadotropin treatment discontinuation and can develop rapidly. If there is evidence that OHSS may be developing prior to hCG administration, hCG must be withheld. If serious OHSS occurs, gonadotropins, including hCG, should be stopped and consider if hospitalization is needed.
• Pulmonary and Vascular Complications: Serious pulmonary complications (e.g., atelectasis, acute respiratory distress syndrome and exacerbation of asthma) have been reported in women treated with gonadotropins. Thromboembolic events both in association with, and separate from OHSS have been reported in women treated with gonadotropins including Gonal-f^® RFF*. 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 OI and ART need to be weighed against the risks.
• 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 Birth: During clinical trials, 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^®.
• Congenital Malformations: 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.
• Ectopic Pregnancy: Since women undergoing ART often have tubal abnormalities, the incidence of ectopic pregnancy may be increased.
• Spontaneous Abortion: The incidence of spontaneous abortion (miscarriage) may be increased. However, causality has not been established. This may be a factor of the underlying infertility.
• Ovarian Neoplasms: Both benign and malignant ovarian neoplasms have been infrequently reported in women who have had multiple drug therapy for controlled ovarian stimulation; causality has not been established.
• Laboratory Tests: Both ultrasound and serum estradiol measurement should be used to monitor follicular growth and maturation, timing of the ovulatory trigger, detecting ovarian enlargement, and minimizing the risk of the OHSS and multiple gestation.

Adverse Reactions:
The most common adverse reactions (≥5%) in OI include: headache, abdominal pain, and ovarian hyperstimulation. The most common adverse reactions (≥5%) in ART include: abdominal pain, nausea, abdominal enlargement, headache, and injection site reactions (pain, bruising).

Patient Counseling:

In addition to advising patients about the proper use of treatment, the duration and necessity of monitoring, handling of missed doses, OHSS, and multi-fetal gestation and birth, patients should be advised to review the Patient Information Leaflet which contains risk information, follow the Instructions for Use for the Gonal-f^® RFF* Redi-ject^®, not share the device or reuse needles, and to ask their Healthcare Provider about questions.

For more information, please see the full Prescribing Information and Instructions for Use for Gonal-f^® RFF* Redi-ject^®

Indications and Usage:

• Induction of ovulation (OI) and pregnancy in oligo-anovulatory women in whom the cause of infertility is functional and not due to primary ovarian failure
• Development of multiple follicles in ovulatory women as part of an Assisted Reproductive Technology (ART) cycle.

Prior to treatment complete an evaluation of female and male partners to determine infertility diagnosis and fertility status. Primary ovarian failure and pregnancy should be excluded.

*RFF = revised formulation female.