EMD Serono Fertility Treatment HCP FAQs
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Answers to common questions for patients starting or continuing with treatment

We know callbacks from patients are a common occurrence in your daily routine—and that you often hear the same questions time and time again. These answers to frequently asked questions will help explain medication usage during consults or respond to any follow-up calls with ease.

Additionally, see the individual product's Prescribing Information, Patient Information, and IFUs for further information to help answer common questions.

GONAL-F RFF* Redi-ject (follitropin alfa injection)

GONAL-F RFF* Redi-ject (follitropin alfa injection) is indicated for:

Induction of ovulation and pregnancy in oligo-anovulatory women in whom the cause of infertility is functional and not due to primary ovarian failure.

Prior to initiation of treatment with GONAL-F RFF* Redi-ject:

  • Perform a complete gynecologic and endocrinologic evaluation
  • Exclude primary ovarian failure
  • Exclude the possibility of pregnancy
  • Demonstrate tubal patency
  • Evaluate the fertility status of the male partner

Development of multiple follicles in ovulatory women as part of an assisted reproductive technology (ART) cycle.

Prior to initiation of treatment with GONAL-F RFF* Redi-ject:

  • Perform a complete gynecologic and endocrinologic evaluation, and diagnose the cause of infertility
  • Exclude the possibility of pregnancy
  • Evaluate the fertility status of the male partner

Patients ask: How will I be monitored when taking GONAL-F RFF* Redi-ject?

Possible Response: When taking GONAL-F RFF* Redi-ject, your ovaries need to be monitored to see how they respond to treatment. Ultrasounds and hormone levels are used to:

  • monitor follicle growth
  • determine when to trigger ovulation
  • verify that ovulation has taken place
  • detect ovarian enlargement
  • minimize the risk of OHSS and multiple gestation

 

Patients ask: Am I at increased risk for ovarian hyperstimulation syndrome (OHSS) after taking GONAL-F RFF* Redi-ject?

Possible Response: OHSS can occur after you’ve stopped taking GONAL-F RFF* Redi-ject. It may develop quickly. In clinical trials with GONAL-F RFF* Redi-ject, OHSS occurred in 7.2% of ovulation induction cycles and 4.6% of assisted reproductive technology cycles.

If your ovaries are abnormally enlarged on the last day of GONAL-F RFF* Redi-ject therapy, the ovulation trigger shot may not be given to reduce the chances of OHSS.

Be aware of the risks of OHSS and OHSS associated symptoms including lung and blood vessel problems and ovarian torsion with the use of GONAL-F RFF* Redi-ject.

 

Patients ask: Does treatment with GONAL-F RFF* Redi-ject increase my chance of multiples?

Possible Response: Multifetal gestation and births have been reported with all gonadotropin therapy, including GONAL-F RFF* Redi-ject.

In clinical trials for GONAL-F RFF* Redi-ject, live births of multiples occurred in 20% of ovulation induction cycles and 35.1% of assisted reproductive technology cycles.


Patients ask:
Can I still use my pen if I left it outside in a car during hot or cold weather?

Possible Response: GONAL-F RFF* Redi-ject must be stored with the cap attached and away from light. New pens should be kept in the refrigerator between 36 °F and 46 °F until the expiration date, or at room temperature between 68 °F and 77 °F for up to 3 months or until the expiration date, whichever comes first.

If medicine is left in the pen after injecting, it may be stored in the refrigerator or at room temperature for up to 28 days before safely discarding.

Be aware of the risk of multi-fetal gestation and birth with the use of GONAL-F RFF Redi-ject.

 

Patients ask: How do I know the pen is totally empty?

Possible Response: GONAL-F RFF* Redi-ject is available in 3 different dosage amounts: 300 IU/0.5 mL, 450 IU/0.75 mL, and 900 IU/1.5 mL. When your combined injected doses equal the number of IUs available in your pen, your device is empty.

You may discuss keeping a treatment diary to help you keep better track of your injections.


Patients ask:
How do I finish an incomplete injection using a new pen?

Possible Response: If you’ve finished your injection and the dose information display on your pen doesn’t read 0, your injection was incomplete. A second GONAL-F RFF* Redi-ject pen will be needed to finish your dose. On the new pen, dial the number that appears in the dose information display on the empty pen, then complete your dose.

 

Patients ask: How do I properly dispose of the pen?

Possible Response: All used needles and empty pens should be discarded in an FDA-cleared sharps disposal container immediately after use.

If you do not have a sharps container, do not throw away loose needles and pens in your household trashcan. Instead, use a container that is:

  • made of heavy-duty plastic
  • able to be closed with a tight-fitting, puncture-resistant lid
  • upright and stable during use
  • leak resistant
  • properly labeled to warn of hazardous waste inside the container

For more information, visit fda.gov/safesharpsdisposal.


GONAL-F® Multi-Dose (follitropin alfa for injection)

GONAL-F Multi-Dose (follitropin alfa for injection) is indicated for:

 

In women:

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

Prior to initiation of treatment with GONAL-F Multi-Dose:

  • Perform a complete gynecologic and endocrinological evaluation
  • Exclude primary ovarian failure
  • Exclude the possibility of pregnancy
  • Demonstrate tubal patency
  • Evaluate the fertility status of the male partner

 

In men:

  • Induction of spermatogenesis in infertile men with primary and secondary hypogonadotropic hypogonadism for whom the cause of infertility is not due to primary testicular failure

Prior to initiation of treatment with GONAL-F Multi-Dose: 

  • Confirm azoospermia
  • Perform a thorough medical and endocrinologic evaluation to exclude other treatable etiologies of azoospermia
  • Confirm hypogonadotropic hypogonadism
  • Exclude primary testicular failure
  • Normalize serum testosterone levels


Patients ask:
Am I at increased risk for ovarian hyperstimulation syndrome (OHSS) after taking GONAL-F Multi-Dose?

Possible Response: OHSS can occur after you’ve stopped taking GONAL-F Multi-Dose. It may develop quickly.

If your ovaries are abnormally enlarged on the last day of GONAL-F Multi-Dose therapy, the ovulation trigger shot may not be given to reduce the chances of OHSS.

 

Patients ask: Does treatment with GONAL-F® Multi-Dose increase my chance of multiples?

Possible Response: Multifetal gestation and births have been reported with all gonadotropin therapy, including GONAL-F Multi-Dose.

During clinical trials with GONAL-F Multi-Dose, 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.

 

Patients ask: Can I still use my medication if I left it outside in a car during hot or cold weather?

Possible Response: GONAL-F Multi-Dose must be stored away from light. Vials (mixed or unmixed) can be stored in the refrigerator or at room temperature between 36 °F and 77 °F. Safely discard any mixed solution after 28 days.

 

Patients ask: How do I properly dispose of medicine products? 

Possible Response: All used needles and vials should be discarded in an FDA-cleared sharps disposal container immediately after use.

If you do not have a sharps container, do not throw away loose needles and vials in your household trashcan. Instead, use a container that is:

  • made of heavy-duty plastic
  • able to be closed with a tight-fitting, puncture-resistant lid
  • upright and stable during use
  • leak resistant
  • properly labeled to warn of hazardous waste inside the container

For more information, visit fda.gov/safesharpsdisposal.


Cetrotide® (cetrorelix acetate for injection)

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.

Patients ask: Am I at increased risk for ovarian hyperstimulation syndrome (OHSS) after taking Cetrotide®?

Possible Response: OHSS can occur after treatment with Cetrotide®. In clinical trials, OHSS occurred in 3.5% of patients.

When assessment by ultrasound shows a sufficient number of follicles of adequate size, hCG is administered to induce ovulation and final maturation of the oocytes. No hCG should be administered if the ovaries show an excessive response to the treatment with gonadotropins to reduce the chance of developing ovarian hyperstimulation syndrome (OHSS).

 

Patients ask: Can I still use my medication if I left it outside in a car during hot or cold weather?

Possible Response: Cetrotide® must be stored away from light and in the refrigerator between 36 ºF and 46 ºF.



Patients ask: How do I properly dispose of medicine products?  

Possible Response: All used needles and vials should be discarded in an FDA-cleared sharps disposal container immediately after use.

If you do not have a sharps container, do not throw away loose needles and vials in your household trashcan. Instead, use a container that is:

  • made of heavy-duty plastic
  • able to be closed with a tight-fitting, puncture-resistant lid
  • upright and stable during use
  • leak resistant
  • properly labeled to warn of hazardous waste inside the container

For more information, visit fda.gov/safesharpsdisposal.


Ovidrel® (choriogonadotropin alfa injection)

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.

Patients ask: How will I be monitored when taking Ovidrel®?

Possible Response: When taking Ovidrel®, your ovaries need to be monitored to see how they respond to treatment. Ultrasounds and hormone levels are used to:

  • determine when to trigger ovulation
  • verify that ovulation has taken place
  • detect ovarian enlargement
  • minimize the risk of OHSS and multiple gestation
     

Patients ask: Am I at increased risk for ovarian hyperstimulation syndrome (OHSS) after taking Ovidrel®?

Possible Response: OHSS can occur after you’ve stopped taking gonadotropin treatments. It may develop quickly. In women receiving Ovidrel® 250 μg treatment, OHSS occurred in 1.7% of patients in ART clinical trials and 3.0% of patients in OI clinical trials.

If your patient’s ovaries are abnormally enlarged on the last day of FSH therapy, Ovidrel® should not be administered to reduce the chances of OHSS.


Patients ask: Does treatment with Ovidrel® increase my chance of multiples?

Possible Response: Reports of multiple births have been associated with Ovidrel® treatment. During ART, the risk of multiples correlates to the number of embryos transferred.

In ART clinical studies of Ovidrel® 250 μg treatment, multiple births occurred in 30.9% of live deliveries. In an OI clinical trial, 13.3% of women experienced multiples.



Patients ask:
Can I still use my medication if I left it outside in a car during hot or cold weather?

Possible Response: Ovidrel® must be stored away from light. Store your prefilled syringe in the refrigerator between 36 ºF and 46 ºF to allow it to be used until the expiration date shown on the carton. If kept at room temperature (up to 77 ºF), Ovidrel® PreFilled Syringe must be discarded after 30 days.

 

Patients ask: How do I properly dispose of medicine products? 

Possible Response: All used needles and vials should be discarded in an FDA-cleared sharps disposal container immediately after use.

If you do not have a sharps container, do not throw away loose needles and vials in your household trashcan. Instead, use a container that is:

  • made of heavy-duty plastic
  • able to be closed with a tight-fitting, puncture-resistant lid
  • upright and stable during use
  • leak resistant
  • properly labeled to warn of hazardous waste inside the container

For more information, visit fda.gov/safesharpsdisposal.

 

*RFF = revised formulation female.

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QUESTIONS OR REQUESTS?

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IMPORTANT RISK INFORMATION & INDICATIONS AND USAGE

Summary of Contraindications

Gonal-f® (follitropin alfa injection) RFF* Redi-ject® and Gonal-f® (follitropin alfa for injection) Multi-Dose are contraindicated in patients with prior hypersensitivity to r-hFSH 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 for Gonal-f® RFF* Redi-ject®, Gonal-f® Multi-Dose and click here for full Prescribing Information for each individual product.

RFF : Revised Formulation Female

 


 

Important Risk Information for Gonal-f® Multi-Dose (follitropin alfa for injection)

Contraindications:

GONAL-F® Multi-Dose is contraindicated in women and men who exhibit:

  • Prior hypersensitivity to recombinant follicle stimulating hormone (FSH) products or one of their excipients. Reactions have included anaphylaxis.
  • High levels of FSH indicating primary gonadal failure
  • The presence of uncontrolled non-gonadal endocrinopathies (e.g., thyroid, adrenal, or pituitary disorders)
  • Sex hormone dependent tumors of the reproductive tract and accessory organs
  • Tumors of pituitary gland or hypothalamus

GONAL-F Multi-Dose is also contraindicated in women who exhibit:

  • Abnormal uterine bleeding of undetermined origin
  • Ovarian cyst or enlargement of undetermined origin

WARNINGS
Hypersensitivity Reactions and Anaphylaxis
In the post-marketing experience, serious systemic hypersensitivity reactions, including anaphylaxis, have been reported with use of GONAL-F Multi-Dose 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.

Overstimulation of the Ovary During FSH Therapy:
Serious pulmonary conditions (for example, atelectasis, acute respiratory distress syndrome and exacerbation of asthma) have been reported in women treated with gonadotropins, including GONAL-F Multi-Dose. In addition, thromboembolic events both in association with, and separate from OHSS have been reported in women treated with gonadotropins, including GONAL-F Multi-Dose. 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 (ART) need to be weighed against the risks. It should be noted that pregnancy also carries an increased risk of thrombosis

Ovarian Torsion
Ovarian torsion has been reported after treatment with gonadotropins, including GONAL-F Multi-Dose. This may be related to OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst and polycystic ovaries. Early diagnosis and immediate detorsion limit damage to the ovary due to reduced blood supply.

Abnormal Ovarian Enlargement
I
n order to minimize the hazards associated with abnormal ovarian enlargement that may occur with GONAL-F Multi-Dose, individualize treatment and use the lowest effective doseUse of ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels is important to minimize the risk of ovarian stimulation

Multi-fetal Gestation and Birth
Multi-fetal gestation and births have been reported with all gonadotropin therapy, including therapy with GONAL-F Multi-Dose.
During clinical trials with GONAL-F Multi-Dose, 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. Advise the woman and her partner of the potential risk of multi-fetal gestation and birth before beginning therapy with GONAL-F Multi-Dose.

Embryofetal toxicity
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.

Ectopic Pregnancy
Since infertile women undergoing ART often have tubal abnormalities, the incidence of ectopic pregnancy may be increased in women who become pregnant as a result of ART. 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.

Spontaneous Abortion
The risk of spontaneous abortion (miscarriage) is increased with gonadotropin products, including GONAL-F Multi-Dose. However, causality has not been established. The increased risk may be a factor of the underlying infertility.

Ovarian Neoplasms
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.

Laboratory Tests

In most instances, treatment of women with GONAL-F Multi-Dose will result only in follicular recruitment and development. In the absence of an endogenous LH surge, hCG is given to trigger ovulation 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.

ADVERSE REACTIONS
Women - Adverse events occurring in more than 5% of women were ovarian cyst, headache, abdominal pain, ovarian hyperstimulation, nausea, flatulence, and intermenstrual bleeding in the U.S. ovulation induction trial. In the U.S. ART trial, adverse event occurring in more than 5% of women were headache, nausea, pelvic pain and abdominal pain.

Men - There was one serious adverse reaction of gynecomastia requiring surgical excision of breast tissue in a 50-year-old man who received 9 months of therapy with GONAL-F Multi-Dose. Pathology report showed gynecomastia with no atypia. Adverse reactions reported in ≥ 2 patients were acne, injection site pain, gynecomastia, seborrhea, fatigue and libido decreased.

Specific Populations:

Pregnancy: GONAL-F Multi-Dose is not indicated in pregnant women. There is no human data that the use of gonadotropins (including GONAL-F Multi-Dose) alone or as part of IVF or ICSI cycles, increases the risk of congenital malformations.

 

Lactation: There are no data on the presence of GONAL-F Multi-Dose in human milk, the effects on the breastfed infant, or the effects on milk production. Because the secretion of prolactin during lactation can result in inadequate response to ovarian stimulation, advise women not to breast feed during treatment with GONAL-F Multi-Dose.

 

Females and Males of Reproductive Potential: Because GONAL-F Multi-Dose is not indicated in pregnant women, verify a negative pregnancy test before administering GONAL-F Multi-Dose to a woman

 

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Safety and effectiveness of GONAL-F Multi-Dose in postmenopausal women have not been established and it is not indicated in this population.

 

Patient Counseling:

Instruct women and men on the correct usage and dosing of GONAL-F Multi-Dose. Caution against changing the dosage or the schedule of administration unless instructed to do so by a healthcare provider.

Prior to beginning therapy with GONAL-F Multi-Dose, inform women and men about the time commitment and monitoring procedures necessary for treatment

Inform women and men that if they miss or forget to take a dose of GONAL-F Multi-Dose, they should not double the next dose and should call their healthcare provider for further dosing instructions.

For more information, please see the full Prescribing Information and Instructions for Use for GONAL-F Multi-Dose

Indications and Usage:

  • Induction of ovulation (OI) and pregnancy in oligo-anovulatory infertile women for whom the cause of infertility is functional and not due to primary ovarian failure
  • Development of multiple follicles in ovulatory infertile women as part of an Assisted Reproductive Technology (ART) cycle
  • Induction of spermatogenesis in infertile men with primary and secondary hypogonadotropic hypogonadism for whom the cause of infertility is not due to primary testicular failure

 

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.

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.

IMPORTANT RISK INFORMATION & INDICATIONS AND USAGE

Summary of Contraindications

Gonal-f® (follitropin alfa injection) RFF* Redi-ject® and Gonal-f® (follitropin alfa for injection) Multi-Dose are contraindicated in patients with prior hypersensitivity to r-hFSH 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 for Gonal-f® RFF* Redi-ject®, Gonal-f® Multi-Dose and click here for full Prescribing Information for each individual product.

RFF : Revised Formulation Female

 


 

Important Risk Information for Gonal-f® Multi-Dose (follitropin alfa for injection)

Contraindications:

GONAL-F® Multi-Dose is contraindicated in women and men who exhibit:

  • Prior hypersensitivity to recombinant follicle stimulating hormone (FSH) products or one of their excipients. Reactions have included anaphylaxis.
  • High levels of FSH indicating primary gonadal failure
  • The presence of uncontrolled non-gonadal endocrinopathies (e.g., thyroid, adrenal, or pituitary disorders)
  • Sex hormone dependent tumors of the reproductive tract and accessory organs
  • Tumors of pituitary gland or hypothalamus

GONAL-F Multi-Dose is also contraindicated in women who exhibit:

  • Abnormal uterine bleeding of undetermined origin
  • Ovarian cyst or enlargement of undetermined origin

WARNINGS
Hypersensitivity Reactions and Anaphylaxis
In the post-marketing experience, serious systemic hypersensitivity reactions, including anaphylaxis, have been reported with use of GONAL-F Multi-Dose 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.

Overstimulation of the Ovary During FSH Therapy:
Serious pulmonary conditions (for example, atelectasis, acute respiratory distress syndrome and exacerbation of asthma) have been reported in women treated with gonadotropins, including GONAL-F Multi-Dose. In addition, thromboembolic events both in association with, and separate from OHSS have been reported in women treated with gonadotropins, including GONAL-F Multi-Dose. 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 (ART) need to be weighed against the risks. It should be noted that pregnancy also carries an increased risk of thrombosis

Ovarian Torsion
Ovarian torsion has been reported after treatment with gonadotropins, including GONAL-F Multi-Dose. This may be related to OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst and polycystic ovaries. Early diagnosis and immediate detorsion limit damage to the ovary due to reduced blood supply.

Abnormal Ovarian Enlargement
I
n order to minimize the hazards associated with abnormal ovarian enlargement that may occur with GONAL-F Multi-Dose, individualize treatment and use the lowest effective doseUse of ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels is important to minimize the risk of ovarian stimulation

Multi-fetal Gestation and Birth
Multi-fetal gestation and births have been reported with all gonadotropin therapy, including therapy with GONAL-F Multi-Dose.
During clinical trials with GONAL-F Multi-Dose, 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. Advise the woman and her partner of the potential risk of multi-fetal gestation and birth before beginning therapy with GONAL-F Multi-Dose.

Embryofetal toxicity
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.

Ectopic Pregnancy
Since infertile women undergoing ART often have tubal abnormalities, the incidence of ectopic pregnancy may be increased in women who become pregnant as a result of ART. 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.

Spontaneous Abortion
The risk of spontaneous abortion (miscarriage) is increased with gonadotropin products, including GONAL-F Multi-Dose. However, causality has not been established. The increased risk may be a factor of the underlying infertility.

Ovarian Neoplasms
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.

Laboratory Tests

In most instances, treatment of women with GONAL-F Multi-Dose will result only in follicular recruitment and development. In the absence of an endogenous LH surge, hCG is given to trigger ovulation 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.

ADVERSE REACTIONS
Women - Adverse events occurring in more than 5% of women were ovarian cyst, headache, abdominal pain, ovarian hyperstimulation, nausea, flatulence, and intermenstrual bleeding in the U.S. ovulation induction trial. In the U.S. ART trial, adverse event occurring in more than 5% of women were headache, nausea, pelvic pain and abdominal pain.

Men - There was one serious adverse reaction of gynecomastia requiring surgical excision of breast tissue in a 50-year-old man who received 9 months of therapy with GONAL-F Multi-Dose. Pathology report showed gynecomastia with no atypia. Adverse reactions reported in ≥ 2 patients were acne, injection site pain, gynecomastia, seborrhea, fatigue and libido decreased.

Specific Populations:

Pregnancy: GONAL-F Multi-Dose is not indicated in pregnant women. There is no human data that the use of gonadotropins (including GONAL-F Multi-Dose) alone or as part of IVF or ICSI cycles, increases the risk of congenital malformations.

 

Lactation: There are no data on the presence of GONAL-F Multi-Dose in human milk, the effects on the breastfed infant, or the effects on milk production. Because the secretion of prolactin during lactation can result in inadequate response to ovarian stimulation, advise women not to breast feed during treatment with GONAL-F Multi-Dose.

 

Females and Males of Reproductive Potential: Because GONAL-F Multi-Dose is not indicated in pregnant women, verify a negative pregnancy test before administering GONAL-F Multi-Dose to a woman

 

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Safety and effectiveness of GONAL-F Multi-Dose in postmenopausal women have not been established and it is not indicated in this population.

 

Patient Counseling:

Instruct women and men on the correct usage and dosing of GONAL-F Multi-Dose. Caution against changing the dosage or the schedule of administration unless instructed to do so by a healthcare provider.

Prior to beginning therapy with GONAL-F Multi-Dose, inform women and men about the time commitment and monitoring procedures necessary for treatment

Inform women and men that if they miss or forget to take a dose of GONAL-F Multi-Dose, they should not double the next dose and should call their healthcare provider for further dosing instructions.

For more information, please see the full Prescribing Information and Instructions for Use for GONAL-F Multi-Dose

Indications and Usage:

  • Induction of ovulation (OI) and pregnancy in oligo-anovulatory infertile women for whom the cause of infertility is functional and not due to primary ovarian failure
  • Development of multiple follicles in ovulatory infertile women as part of an Assisted Reproductive Technology (ART) cycle
  • Induction of spermatogenesis in infertile men with primary and secondary hypogonadotropic hypogonadism for whom the cause of infertility is not due to primary testicular failure

 

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.

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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