Summary of Contraindications
Gonal-f® RFF* Redi-ject®, Gonal-f® Multi-Dose and Gonal-f® RFF* 75 IU are contraindicated in patients with prior hypersensitivity to rhFSH or excipients, high levels of FSH indicating primary gonadal failure, pregnancy, uncontrolled thyroid, adrenal or pituitary disorders, sex hormone dependent tumors of the reproductive tract/accessory organs, tumors of pituitary gland or hypothalamus, abnormal uterine bleeding of undetermined origin and ovarian cyst or enlargement of undetermined origin.
Please scroll for full IMPORTANT RISK INFORMATION or see full Prescribing Information for Gonal-f® RFF* Redi-ject®, Gonal-f® Multi-Dose and Gonal-f® RFF* 75 IU.
* RFF: Revised Formulation Female
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.
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.
 For more information, please see the full Prescribing Information and Instructions for Use for Gonal-f® RFF* Redi-ject®
* RFF: Revised Formulation Female
Important Risk Information for Gonal-f® Multi-Dose (follitropin alfa for injection)
Contraindications:
- 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
- Pregnancy
WARNINGS
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.
Multiple Births
- 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
PRECAUTIONS
- 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
Adverse Reactions:
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:
Women
- 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.
Men
- 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
Important Risk Information for Gonal-f® RFF* 75 IU (follitropin alfa for injection)
Contraindications:
- 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
- Pregnancy
WARNINGS
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® RFF* 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® RFF*. 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.
Multiple Births
- In Study 2240 for women receiving Gonal-f® RFF* over three treatment cycles, 20% of live births were multiple births. In Study 21884, 35.1% of live births were multiple births in women receiving Gonal-f® RFF*. The rate of multiple births is dependent on the number of embryos transferred. The patient should be advised of the potential risk of multiple births before starting treatment
PRECAUTIONS
- 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
Adverse Reactions:
The most common adverse reactions (≥5%) in OI include: headache, abdominal pain, ovarian hyperstimulation, breast pain, vaginal hemorrhage, sinusitis, pharyngitis and rhinitis. The most common adverse reactions (≥5%) in ART include: abdominal pain, nausea, abdominal enlargement, headache, and injection site reactions (pain, bruising).
Indications and Usage:
- Induction of ovulation and pregnancy in the oligo-anovulatory infertile patient in whom the cause of infertility is functional and not due to primary ovarian failure
- Development of multiple follicles in the ovulatory patient 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. 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.
For more information, please see the full Prescribing Information and Instructions for Use for Gonal-f® RFF* 75 IU
* RFF: Revised Formulation Female
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Important Risk Information for Cetrotide® (cetrorelix acetate for injection)
Cetrotide® is contraindicated in women who are pregnant, are nursing, or have severe renal impairment. Cetrotide® is also contraindicated in women who exhibit or have known hypersensitivity to cetrorelix acetate, mannitol, extrinsic peptide hormone, GnRH or any other GnRH analogs. Treatment with Cetrotide® is not advised in women with severe allergic conditions. Cases of hypersensitivity reactions, including anaphylactoid reactions have been reported. Other adverse events reported include ovarian hyperstimulation syndrome, nausea, headache, and local injection site reactions. Multiple births and congenital abnormalities have been reported.
Indication
Cetrotide® (cetrorelix acetate for injection) is indicated for the inhibition of premature LH surges in women undergoing controlled ovarian stimulation. Cetrotide® should only be prescribed by physicians who are experienced with infertility problems and their management.
For complete information, please see full Prescribing information here.
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Important Risk Information for Ovidrel® PreFilled Syringe (choriogonadotropin alfa injection)
Ovidrel® PreFilled Syringe should only be used by physicians who are experienced with infertility problems, their management and appropriate selection and monitoring of patients. Ovidrel® PreFilled Syringe is contraindicated in women who exhibit prior sensitivity to hCG preparations, mannitol, or one of their other excipients, primary ovarian failure, uncontrolled thyroid or adrenal dysfunction, an uncontrolled intracranial lesion, abnormal uterine bleeding of an undetermined origin, an ovarian cyst or enlargement of an undetermined origin. Women who are pregnant or nursing should not use Ovidrel® PreFilled Syringe.
Ovidrel® PreFilled Syringe is a potent gonadotropic substance capable of causing Ovarian Hyperstimulation Syndrome (OHSS) and ovarian enlargement with or without pulmonary and vascular complications. Adverse reactions reported include injection site reactions, GI disorders, abdominal pain, nausea, vomiting, ovarian cyst, ovarian hyperstimulation, and thromboembolic events. Multiple births and congenital abnormalities have been reported.
Indication
Ovidrel® PreFilled Syringe (choriogonadotropin alfa injection) is indicated for the induction of final follicular maturation and early luteinization in infertile women who have undergone pituitary desensitization and who have been appropriately pretreated with follicle stimulating hormones as part of an Assisted Reproductive Technology (ART) program such as in vitro fertilization (IVF) and embryo transfer. Ovidrel® PreFilled Syringe is also indicated for the induction of ovulation (OI) and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not due to primary ovarian failure.
For complete information, please see full Prescribing information here.
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