Fertigyn

Fertigyn consists of a freeze-dried powder for injection and a solvent for reconstitution. The active ingredient [Fertigyn (hCG)] which is obtained from the urine of pregnant women, has luteinizing hormone (LH) activity. The powder is a white, dry powder or cake. The solvent is a clear and colourless aqueous solution.

Each ampoule also contains the following excipients: Mannitol, disodium hydrogen phosphate, sodium dihydrogen phosphate and sodium carboxymethylcellulose. Each ampoule of solvent contains sodium chloride 9 mg and water for injection 1 mL.

Fertigyn® 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 and embryo transfer. Fertigyn® 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.

Selection Of Patients

1. Before treatment with gonadotropins is instituted, a thorough gynecologic and endocrinologic evaluation must be performed. This should include an assessment of pelvic anatomy. Patients with tubal obstruction should receive Fertigyn® PreFilled Syringe only if enrolled in an in vitro fertilization program.
2. Primary ovarian failure should be excluded by the determination of gonadotropin levels.
3. Appropriate evaluation should be performed to exclude pregnancy.
4. Patients in later reproductive life have a greater predisposition to endometrial carcinoma as well as a higher incidence of anovulatory disorders. A thorough diagnostic evaluation should always be performed in patients who demonstrate abnormal uterine bleeding or other signs of endometrial abnormalities before starting FSH and Fertigyn® PreFilled Syringe therapy.
5. Evaluation of the partner's fertility potential should be included in the initial evaluation.

Treating fertility problems in certain women who have not gone through menopause. Treating certain testicular development problems and stimulating the development of secondary sexual characteristics in certain patients. It is also used to treat boys 4 to 9 years old who have testicles that have not moved into the scrotum.

Fertigyn is a hormone. Fertigyn (HCG) stimulates cells in the testicles to produce androgens and in the ovaries to produce progesterone. Androgens cause the development of male secondary sexual characteristics (eg, hair growth, deepening voice) and may cause the testicles to drop. HCG acts like luteinizing hormone (LH) by stimulating ovulation (release of an egg) in women.

For Subcutaneous Use Only

Infertile Women Undergoing Assisted Reproductive Technologies (ART)

Fertigyn® PreFilled Syringe 250 µg should be administered one day following the last dose of the follicle stimulating agent. Fertigyn® PreFilled Syringe should not be administered until adequate follicular development is indicated by serum estradiol and vaginal ultrasonography. Administration should be withheld in situations where there is an excessive ovarian response, as evidenced by clinically significant ovarian enlargement or excessive estradiol production.

Infertile Women Undergoing Ovulation Induction (OI)

Fertigyn® PreFilled Syringe should not be administered until adequate follicular development is indicated by serum estradiol and vaginal ultrasonography.

Fertigyn® PreFilled Syringe 250 µg should be administered one day following the last dose of the follicle stimulating agent.

Fertigyn® PreFilled Syringe administration should be withheld in situations where there is an excessive ovarian response, as evidenced by multiple follicular development, clinically significant ovarian enlargement or excessive estradiol production.

Directions for Administration of Fertigyn® Prefilled Syringe

Fertigyn® PreFilled Syringe is intended for a single subcutaneous injection. Any unused material should be discarded.

Fertigyn® PreFilled Syringe may be self-administered by the patient. Follow the directions below for injecting Fertigyn® PreFilled Syringe.

Step 1: Wash your hands thoroughly with soap and water.

Step 2: Carefully clean the injection site.

Make yourself comfortable by sitting or lying down. Carefully clean the injection site on the stomach with an alcohol wipe and allow it to air-dry.

Step 3: Administer your injection.

Carefully remove the needle cap from the syringe. Do not touch the needle or allow the needle to touch any surface. Inject the prescribed dose as directed by your doctor, nurse or pharmacist.

Step 4: Gently withdraw the needle.

Discard the needle and syringe into your safety container. Place gauze over the injection site. If any bleeding occurs, apply gentle pressure. If bleeding does not stop within a few minutes, place a clean piece of gauze over the injection site and cover it with an adhesive bandage.

Step 5: Storage and clean up.

Remember that your injection materials must be kept sterile and cannot be reused.

See also:
What is the most important information I should know about Fertigyn?

Hypersensitivity to choriogonadotropin α or to any of the excipients of Fertigyn. Tumors of the hypothalamus and pituitary gland; ovarian enlargement or cyst due to reasons other than polycystic ovarian disease; gynecological hemorrhages of unknown etiology; ovarian, uterine or mammary carcinoma; extrauterine pregnancy in the previous 3 months; active thromboembolic disorders.

Fertigyn must not be used when an effective response cannot be obtained eg, primary ovarian failure, malformations of sexual organs incompatible with pregnancy, fibroid tumors of the uterus incompatible with pregnancy, postmenopausal women.

Use Fertigyn as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Fertigyn is usually administered as an injection at your doctor's office, hospital, or clinic. If you are using Fertigyn at home, carefully follow the injection procedures taught to you by your health care provider.
• If Fertigyn contains particles or is discolored, or if the vial is cracked or damaged in any way, do not use it.
• Using the technique described to you by your doctor, add the diluent to the vial that contains the medicine. Mix the solution by gently rotating the vial. DO NOT SHAKE. The solution should be clear and free of particles.
• Wipe the rubber stopper of the vial with an alcohol swab. Insert the needle straight through the center circle of the rubber stopper. Draw up the solution for injection. After drawing up the solution, switch needles. Be sure all air bubbles are tapped out of the syringe.
• Wipe the appropriate injection site (usually the upper thigh or buttocks) with an alcohol swab, then insert the syringe. To be sure that the needle is not in a vein, pull back on the plunger of the syringe while holding the syringe in place. If the syringe begins to fill with blood, the needle is in a vein. If this happens, remove the needle from the skin, throw the syringe away, and start the procedure again using new materials (drugs, syringes, etc.).
• After giving the injection, cover the injection site with a small bandage if necessary.
• Keep this product, as well as syringes and needles, out of the reach of children. Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor or pharmacist to explain local regulations for proper disposal.
• If you miss a dose of Fertigyn, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Fertigyn.

Use: Labeled Indications

Hypogonadotrophic hypogonadism: Treatment of hypogonadism secondary to a pituitary deficiency in males.

Ovulation induction: Induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause of anovulation is secondary and not caused by primary ovarian failure, and who has been appropriately pretreated with human menotropins.

Prepubertal cryptorchidism: Treatment of prepubertal cryptorchidism not caused by anatomic obstruction.

Off Label Uses

Spermatogenesis induction associated with hypogonadotropic hypogonadism

Based on the American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hypogonadism in Adult Male Patients, chorionic gonadotropin (human) given in combination with human menopausal gonadotropin (or follicle-stimulating hormone [FSH]) for spermatogenesis induction in male patients with hypogonadotropic hypogonadism of prepubertal onset is effective and recommended in this setting. Men with partial gonadotropin deficiency, men who have been peri-pubertally stimulated with chorionic gonadotropin (human), and men with postpubertal acquired hypogonadotropic hypogonadism who previously had normal production of sperm may be given chorionic gonadotropin (human) monotherapy.

See also:
What other drugs will affect Fertigyn?

No specific interaction studies with Fertigyn and other medicines have been performed, however, no clinically significant drug interactions have been reported during hCG therapy.

Following administration, Fertigyn may interfere for up to 10 days with the immunological determination of serum/urinary hCG, leading to a false-positive pregnancy test.

Incompatibilities: In the absence of incompatibility studies, Fertigyn must not be mixed with other medicinal products.

See also:
What are the possible side effects of Fertigyn?

The safety of Fertigyn® was examined in four clinical studies that treated 752 patients of whom 335 received Fertigyn® 250 μg following follicular recruitment with gonadotropins. When patients enrolled in four clinical studies (3 in ART and one in OI) were injected subcutaneously with either Fertigyn® or an approved urinary-derived hCG, 14.6 % (49 of 335 patients) in the Fertigyn® 250 μg group experienced application site disorders compared to 28% (92 of 328 patients) in the approved u-hCG group. Adverse events reported for Fertigyn® 250 μg occurring in at least 2% of patients (regardless of causality) are listed in Table 9 for the 3 ART studies and in Table 10 for the single OI study.

Table 9: Incidence of Adverse Events of r-hCG in ART (Studies 7648, 7927, 9073)

Adverse events not listed in Table 9 that occurred in less than 2% of patients treated with Fertigyn® 250 μg whether or not considered causally related to Fertigyn®, included: injection site inflammation and reaction, flatulence, diarrhea, hiccup, ectopic pregnancy, breast pain, intermenstrual bleeding, vaginal hemorrhage, cervical lesion, leukorrhea, ovarian hyperstimulation, uterine disorders, vaginitis, vaginal discomfort, body pain, back pain, fever, dizziness, headache, hot flashes, malaise, paraesthesias, rash, emotional lability, insomnia, upper respiratory tract infection, cough, dysuria, urinary tract infection, urinary incontinence, albuminuria, cardiac arrhythmia, genital moniliasis, genital herpes, leukocytosis, heart murmur and cervical carcinoma.

Table 10: Incidence of Adverse Events of r-hCG in Ovulation Induction (Study 8209)

Additional adverse events not listed in Table 10 that occurred in less than 2% of patients treated with Fertigyn® 250 μg, whether or not considered causally related to Fertigyn®, included: breast pain, flatulence, abdominal enlargement, pharyngitis, upper respiratory tract infection, hyperglycemia and pruritis.

The following medical events have been reported subsequent to pregnancies resulting from hCG therapy in controlled clinical studies:

1. Spontaneous Abortion
2. Ectopic Pregnancy
3. Premature Labor
4. Postpartum Fever
5. Congenital Abnormalities

Of 125 clinical pregnancies reported following treatment with FSH and Fertigyn® 250 μg or 500 μg, three were associated with a congenital anomaly of the fetus or newborn. Among patients receiving Fertigyn® 250 μg, cranial malformation was detected in the fetus of one woman and a chromosomal abnormality (47, XXX) in another. These events were judged by the investigators to be of unlikely or unknown relation to treatment. These three events represent an incidence of major congenital malformations of 2.4%, which is consistent with the reported rate for pregnancies resulting from natural or assisted conception. In a woman who received Fertigyn® 500 μg, one birth in a set of triplets was associated with Down's syndrome and atrial septal defect. This event was considered to be unrelated to the study drug.

The following adverse reactions have been previously reported during menotropin therapy:

1. Pulmonary and vascular complications
2. Adnexal torsion (as a complication of ovarian enlargement)
3. Mild to moderate ovarian enlargement
4. Hemoperitoneum

There have been infrequent reports of ovarian neoplasms, both benign and malignant, in women who have undergone multiple drug regimens for ovulation induction; however, a causal relationship has not been established.

Post-Marketing Experience

In addition to adverse events reported from clinical trials, the following events have been reported during post-marketing use of Fertigyn®. Therefore, these events were reported from a population of uncertain size, the frequency or causal relationship to Fertigyn® cannot be reliably determined.

• Cases of allergic reactions, including anaphylactic reactions and mild reversible skin rashes have been reported in patients treated with Fertigyn® since market introduction. The causal relationship is unknown.
• Thromboembolic events both in association with, and separate from, the Ovarian Hyperstimulation Syndrome