Important Risk Information for Gonal-f® Multi-Dose (follitropin alfa for injection)
- Prior hypersensitivity to rhFSH preparations or excipients
- High levels of FSH indicating primary gonadal failure
- Uncontrolled thyroid or adrenal dysfunction
- Sex hormone dependent tumors of the reproductive tract and accessory organs
- Organic intracranial lesion such as a pituitary tumor
- Abnormal uterine bleeding of undetermined origin
- Ovarian cyst or enlargement of undetermined origin
For use by physicians specializing in fertility treatment or reproductive health and only when appropriate monitoring facilities are available. Gonal-f® is a potent gonadotropic substance capable of causing Ovarian Hyperstimulation Syndrome (OHSS) in women with or without pulmonary or vascular complications. Monitor ovarian response with serum estradiol and vaginal ultrasound on a regular basis. The lowest effective dose should be used.
Overstimulation of the Ovary During FSH Therapy:
- Ovarian Enlargement: If the ovaries are abnormally enlarged on the last day of Gonal-f® therapy, hCG should not be administered in this course of therapy
- Ovarian Hyperstimulation Syndrome (OHSS): OHSS is a medical event distinct from uncomplicated ovarian enlargement. Severe OHSS may progress rapidly to become a serious medical event. If severe OHSS occurs, treatment must be stopped and the patient should be hospitalized.
Pulmonary and Vascular Complications
- Serious pulmonary complications (e.g., atelectasis, acute respiratory distress syndrome and exacerbation of asthma) have been reported. Thromboembolic events both in association with, and separate from OHSS have been reported in women treated with gonadotropins including Gonal-f®. Sequelae of such events have included venous thrombophlebitis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion (stroke), and arterial occlusion resulting in loss of limb. In rare cases, pulmonary complications and/or thromboembolic reactions have resulted in death.
- In ovulation induction trials, 12.3% of live births were multiple births in women receiving Gonal-f® and 14.5% in women receiving urofollitropin. In IVF/ET clinical trials, 44% of live births in women receiving Gonal-f® and 41% in women receiving urofollitropin and is dependent on the number of embryos transferred. The patient should be advised of the potential risk of multiple births before starting treatment
- General: Careful attention given to the diagnosis of infertility
- Information for Patients: Inform patients of duration of treatment, required monitoring of their condition, risks of ovarian hyperstimulation syndrome and multiple births
- 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.
- Nursing Mothers: It is not known whether this drug is excreted in human milk and because of the potential for serious adverse reactions in the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother
Women - Adverse events occurring in more than 5% of women were headache, ovarian cyst, nausea, and upper respiratory infection intermenstrual bleeding, abdominal pain, diarrhea, flatulence, ovarian hyperstimulation, Pain, Back pain sinusitis and emotional lability in the U.S. ovulation induction trial. In the U.S. ART trial, adverse event occurring in more than 5% of women were headache, abdominal pain, pelvic pain and nausea.
Men – In Study 5844 events occurring in more than one patient were varicocele (4) and injection site reactions (4), serious adverse reactions were testicular surgery for cryptorchidism, which existed pre-study, hemoptysis, an infection pilonidal cyst, and lymphadenopathy associated with an Epstein-Barr viral infection. In study 4610 3 adverse events were reported in 2 of 8 patients (24%) and one serious event of surgery for gynecomastia which existed at baseline. In the interim analysis of Study 6793, 18 of 22 patients (81.8%) reported a total of 99 events. The most common in more than 2 patients were acne, breast pain, fatigue, gynecomastia and injection site pain. Two serious adverse events (hospitalization for drug abuse and depression) were reported by a single patient.
Indications and Usage:
- Induction of ovulation (OI) and pregnancy in anovulatory women in whom the cause of infertility is functional anxd 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 to determine infertility diagnosis and fertility status. Patients with a tubal obstruction should receive Gonal-f® only if enrolled in an in vitro fertilization program. Primary ovarian failure and pregnancy should be excluded.
- Induction of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure.
Prior to treatment perform thorough medical and endocrinologic evaluation, confirm hypogonadotropic hypogonadism, exclude primary testicular failure and serum testosterone levels should be normalized.
For more information, please see the full Prescribing Information and Instructions for Use for Gonal-f® Multi-Dose