Choriogonadotropin alfa

# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider.  WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery.  The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements.  WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

# Overview
Choriogonadotropin alfa is a gonadotropin that is FDA approved for the treatment 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.   Common adverse reactions include injection site pain and multiple birth.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)

### Indications
- 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. Choriogonadotropin alfa 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.
- 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 choriogonadotropin alfa only if enrolled in an in vitro fertilization program.
- Primary ovarian failure should be excluded by the determination of gonadotropin levels.
- Appropriate evaluation should be performed to exclude pregnancy.
- 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 choriogonadotropin alfa therapy.
- Evaluation of the partner's fertility potential should be included in the initial evaluation.

### Dosage
- Choriogonadotropin alfa 250 g should be administered one day following the last dose of the follicle stimulating agent. Choriogonadotropin alfa 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.
- Choriogonadotropin alfa should not be administered until adequate follicular development is indicated by serum estradiol and vaginal ultrasonography.
- Choriogonadotropin alfa 250 g should be administered one day following the last dose of the follicle stimulating agent.
- Choriogonadotropin alfa 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.
- Choriogonadotropin alfa is intended for a single subcutaneous injection. Any unused material should be discarded.
- Choriogonadotropin alfa may be self-administered by the patient. Follow the directions below for injecting Ovidrel 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.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Choriogonadotropin alfa in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Choriogonadotropin alfa in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Choriogonadotropin alfa in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Choriogonadotropin alfa in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Choriogonadotropin alfa in pediatric patients.

# Contraindications
- Choriogonadotropin alfa injection is contraindicated in women who exhibit:
- Prior hypersensitivity to hCG preparations or one of their excipients.
- Primary ovarian failure.
- Uncontrolled thyroid or adrenal dysfunction.
- An uncontrolled organic intracranial lesion such as a pituitary tumor.
- Abnormal uterine bleeding of undetermined origin.
- Ovarian cyst or enlargement of undetermined origin.
- Sex hormone dependent tumors of the reproductive tract and accessory organs.
- Pregnancy.

# Warnings
- Gonadotropins, including choriogonado-tropin alfa injection, should only be used by physicians who are thoroughly familiar with infertility problems and their management.
- Like other hCG products, choriogonadotropin alfa is a potent gonadotropic substance capable of causing Ovarian Hyperstimulation Syndrome (OHSS) in women with or without pulmonary or vascular complications. The risks of gonadoptropin treatment should be considered for women with risk factors of thromboembolic events such as prior medical or family history. Gonadotropin therapy requires a certain time commitment by physicians and supportive health professionals, and requires the availability of appropriate monitoring facilities. Safe and effective induction of ovulation and use of choriogonadotropin alfa in women requires monitoring of ovarian response with serum estradiol and transvaginal ultrasound on a regular basis.

### Overstimulation of the Ovary Following hCG Therapy
- Mild to moderate uncomplicated ovarian enlargement which may be accompanied by abdominal distention and/or abdominal pain may occur in patients treated with FSH and hCG, and generally regresses without treatment within two or three weeks. Careful monitoring of ovarian response can further minimize the risk of overstimulation.
- If the ovaries are abnormally enlarged on the last day of FSH therapy, choriogonadotropin alfa should not be administered in this course of therapy. This will reduce the risk of development of Ovarian Hyperstimulation Syndrome.
- OHSS is a medical event distinct from uncomplicated ovarian enlargement. Severe OHSS may progress rapidly (within 24 hours to several days) to become a serious medical event. It is characterized by an apparent dramatic increase in vascular permeability which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium. The early warning signs of development of OHSS are severe pelvic pain, nausea, vomiting, and weight gain. The following symptomatology has been seen with cases of OHSS: abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting and diarrhea, severe ovarian enlargement, weight gain, dyspnea, and oliguria. Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events. Transient liver function test abnormalities suggestive of hepatic dysfunction, which may be accompanied by morphologic changes on liver biopsy, have been reported in association with Ovarian Hyperstimulation Syndrome (OHSS).
- OHSS occurred in 4 of 236 (1.7 %) patients treated with choriogonadotropin alfa 250g during clinical trials for ART and 3 of 99 (3.0%) patients treated in the OI trial. OHSS occurred in 8 of 89 (9.0%) patients who received choriogonadotropin alfa 500 g. Two patients treated with choriogonadotropin alfa 500 g developed severe OHSS.
- OHSS may be more severe and more protracted if pregnancy occurs. OHSS develops rapidly; therefore, patients should be followed for at least two weeks after hCG administration. Most often, OHSS occurs after treatment has been discontinued and reaches its maximum at about seven to ten days following treatment. Usually, OHSS resolves spontaneously with the onset of menses. If there is evidence that OHSS may be developing prior to hCG administration, the hCG must be withheld.
- If severe OHSS occurs, treatment with gonadotropins must be stopped and the patient should be hospitalized.
- A physician experienced in the management of this syndrome, or who is experienced in the management of fluid and electrolyte imbalances should be consulted.
- As with other hCG products, reports of multiple births have been associated with choriogonadotropin alfa treatment. In ART, the risk ofmultiple births correlates to the number of embryos transferred. Multiple births occurred in 17 of 55 live deliveries (30.9 %) experienced by women receiving choriogonadotropin alfa 250 g in the ART studies. In the ovulation induction clinical trial, 2 of 15 live deliveries (13.3%) were associated with multiple births in women receiving choriogonadotropin alfa. The patient should be advised of the potential risk of multiple births before starting treatment.
- As with other hCG products, a potential for the occurrence of arterial thromboembolism exists.

# Adverse Reactions

## Clinical Trials Experience
- The safety of choriogonadotropin alfa was examined in four clinical studies that treated 752 patients of whom 335 received choriogonadotropin alfa 250 g following follicular recruitment with gonadotropins. When patients enrolled in four clinical studies (3 in ART and one in OI) were injected subcutaneously with either choriogonadotropin alfa or an approved urinary-derived hCG, 14.6 % (49 of 335 patients) in the choriogonadotropin alfa 250 g group experienced application site disorders compared to 28% (92 of 328 patients) in the approved u-hCG group.
- Adverse events reported for choriogonadotropin alfa 250 g 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.
- Additional adverse events not listed in Table 10 that occurred in less than 2% of patients treated with choriogonadotropin alfa 250 g, whether or not considered causally related to choriogonadotropin alfa, 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:
- Spontaneous Abortion
- Ectopic Pregnancy
- Postpartum Fever
- Congenital Abnormalities
- Of 125 clinical pregnancies reported following treatment with FSH and choriogonadotropin alfa 250 g or 500 g, three were associated with a congenital anomaly of the fetus or newborn. Among patients receiving choriogonadotropin alfa 250 g, 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 choriogonadotropin alfa 500 g, 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:
- Pulmonary and vascular complications
- Adnexal torsion (as a complication of ovarian enlargement)
- Mild to moderate ovarian enlargement
- 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.

## Postmarketing Experience
- In addition to adverse events reported from clinical trials, the following events have been reported during post-marketing use of choriogonadotropin alfa. Therefore, these events were reported from a population of uncertain size, the frequency or causal relationship to choriogonadotropin alfa cannot be reliably determined.
- Cases of allergic reactions, including anaphylactic reactions and mild reversible skin rashes have been reported in patients treated with choriogonadotropin alfa since market introduction. The causal relationship is unknown.
- Thromboembolic events both in association with, and separate from, the Ovarian Hyperstimulation Syndrome.

# Drug Interactions
There is limited information regarding Choriogonadotropin alfa Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): X
- Intrauterine death and impaired parturition were observed in pregnant rats given a dose of urinary-hCG (500 IU) equivalent to three times the maximum human dose of 10,000 USP, based on body surface area.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Choriogonadotropin alfa in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Choriogonadotropin alfa during labor and delivery.

### Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if hCG is administered to a nursing woman.

### Pediatric Use
There is no FDA guidance on the use of Choriogonadotropin alfa with respect to pediatric patients.

### Geriatic Use
There is no FDA guidance on the use of Choriogonadotropin alfa with respect to geriatric patients.

### Gender
There is no FDA guidance on the use of Choriogonadotropin alfa with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Choriogonadotropin alfa with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Choriogonadotropin alfa in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Choriogonadotropin alfa in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Choriogonadotropin alfa in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Choriogonadotropin alfa in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Subcutaneous

### Monitoring
- Safe and effective induction of ovulation and use of choriogonadotropin alfa in women requires monitoring of ovarian response with serum estradiol and transvaginal ultrasound on a regular basis.
- Careful monitoring of ovarian response can further minimize the risk of overstimulation.
- The combination of both ultrasound and serum estradiol measurement are useful for monitoring the development of follicles, for timing of the ovulatory trigger, as well as for detecting ovarian enlargement and minimizing the risk of the Ovarian Hyperstimulation Syndrome and multiple gestation.

# IV Compatibility
There is limited information regarding IV Compatibility of Choriogonadotropin alfa in the drug label.

# Overdosage
There is limited information regarding Choriogonadotropin alfa overdosage.  If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

# Pharmacology
There is limited information regarding Choriogonadotropin alfa Pharmacology in the drug label.

## Mechanism of Action
- The physicochemical, immunological, and biological activities of recombinant hCG are comparable to those of placental and human pregnancy urine-derived hCG.
- Choriogonadotropin alfa stimulates late follicular maturation and resumption of oocyte meiosis, and initiates rupture of the pre-ovulatory ovarian follicle. - Choriogonadotropin alfa, the active component of choriogonadotropin alfa , is an analogue of Luteinizing Hormone (LH) and binds to the LH/hCG receptor of the granulosa and theca cells of the ovary to effect these changes in the absence of an endogenous LH surge. In pregnancy, hCG, secreted by the placenta, maintains the viability of the corpus luteum to provide the continued secretion of estrogen and progesterone necessary to support the first trimester of pregnancy. Choriogonadotropin alfa is administered when monitoring of the patient indicates that sufficient follicular development has occurred in response to FSH treatment for ovulation induction.

## Structure
- Choriogonadotropin alfa injection is a sterile liquid preparation of choriogonadotropin alfa (recombinant human Chorionic Gonadotropin, r-hCG).
- Choriogonadotropin alfa is a water soluble glycoprotein consisting of two non-covalently linked subunits - designated  and  - consisting of 92 and 145 amino acid residues, respectively, with carbohydrate moieties linked to ASN-52 and ASN-78 (on alpha subunit) and ASN-13, ASN-30, SER-121, SER-127, SER-132 and SER-138 (on beta subunit). The primary structure of the  - chain of r-hCG is identical to that of the  - chain of hCG, FSH and LH. The glycoform pattern of the  - subunit of r-hCG is closely comparable to urinary derived hCG (u-hCG), the differences mainly being due to the branching and sialylation extent of the oligosaccharides. The  - chain has both O- and N-glycosylation sites and its structure and glycosylation pattern are also very similar to that of u-hCG.
- The production process involves expansion of genetically modified Chinese Hamster Ovary (CHO) cells from an extensively characterized cell bank into large scale cell culture processing. Choriogonadotropin alfa is secreted by the CHO cells directly into the cell culture medium that is then purified using a series of chromatographic steps. This process yields a product with a high level of purity and consistent product characteristics including glycoforms and biological activity. The biological activity of choriogonadotropin alfa is determined using the seminal vesicle weight gain test in male rats described in the "Chorionic Gonadotrophins" monograph of the European Pharmacopoeia. The in vivo biological activity of choriogonadotropin alfa has been calibrated against the third international reference preparation IS75/587 for chorionic gonadotropin.
- Choriogonadotropin alfa is a sterile, liquid intended for subcutaneous (SC) injection. Each choriogonadotropin alfa is filled with 0.515 mL containing 257.5 g of choriogonadotropin alfa, 28.1 mg mannitol, 505 g 85% O-phosphoric acid, 103 g L-methionine, 51.5 g Poloxamer 188, Sodium Hydroxide (for pH adjustment), and Water for Injection to deliver 250 g of choriogonadotropin alfa in 0.5 mL. The pH of the solution is 6.5 to 7.5.

## Pharmacodynamics
- In female subjects on oral contraception after an initial latency period, choriogonadotropin alfa induced a clear increase in androstenedione serum levels by 24 hours after dosing.
- Pharmacodynamic studies in females determined that the relationship of choriogonadotropin alfa pharmacokinetics to pharmacologic effect of choriogonadotropin alfa are complex and vary with the pharmacodynamic marker examined. In general pharmacologic effects are not proportional to exposure and in some cases appear to be near maximal at a 250 g dose.
- In patients undergoing in-vitro fertilization/embryo transfer given Ovidrel subcutaneously to trigger ovulation, the results of a population PK/PD analysis generally supported the data obtained in healthy subjects. Pharmacokinetic parameters for Ovidrel include a median elimination half-life of 29.2 hours, median apparent clearance (Cl/F) of 0.51 L/hr and median apparent volume of distribution (V/F) of 21.4 L.
- Choriogonadotropin alfa injection has been determined to be bioequivalent to choriogonadotropin alfa for injection based on the statistical evaluation of AUC and Cmax. A summary of the choriogonadotropin alfa pharmacokinetic parameters is presented in Table 2.
- Safety, efficacy, and pharmacokinetics of choriogonadotropin alfa in patients with renal or hepatic insufficiency have not been established.
- No drug-drug interaction studies have been conducted. Administration of choriogonadotropin alfa may interfere with the interpretation of pregnancy tests.

## Pharmacokinetics
- When given by intravenous administration, the pharmacokinetic profile of Ovidrel followed a biexponential model and was linear over a range of 25 g to 1000 g. Pharmacokinetic parameter estimates following SC administration of Ovidrel 250 g to females are presented in Table 1.
- Following subcutaneous administration of Ovidrel 250 g, maximum serum concentration (121  44 IU/L) is reached after approximately 12 to 24 hours. The mean absolute bioavailability of Ovidrel following a single subcutaneous injection to healthy female volunteers is about 40%.
- Following intravenous administration of Ovidrel 250 g to healthy down-regulated female volunteers, the serum profile of hCG is described by a two-compartment model with an initial half-life of 4.5  0.5 hours. The volume of the central compartment is 3.0  0.5 L and the steady state volume of distribution is 5.9  1.0 L.
- Following subcutaneous administration of Ovidrel, hCG is eliminated from the body with a mean terminal half-life of about 29  6 hours. After intravenous administration of Ovidrel 250 g to healthy down-regulated females, the mean terminal half-life is 26.5  2.5 hours and the total body clearance is 0.29  0.04 L/h. One-tenth of the dose is excreted in the urine.

## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Choriogonadotropin alfa in the drug label.

# Clinical Studies
- The safety and efficacy of Ovidrel have been examined in three well-controlled studies in women; two studies for assisted reproductive technologies (ART) and one study for ovulation induction (OI).
- The safety and efficacy of Ovidrel 250 g and Ovidrel 500 g administered subcutaneously versus 10,000 USP Units of an approved urinary-derived hCG product administered intramuscularly were assessed in a randomized, open-label, multicenter study in infertile women undergoing in vitro fertilization and embryo transfer (Study 7927). The study was conducted in 20 U.S. centers.
- The primary efficacy parameter in this single-cycle study was the number of oocytes retrieved. 297 patients entered the study, of whom 94 were randomized to receive Ovidrel 250 g. The number of oocytes retrieved was similar for the Ovidrel and urinary-derived hCG (10,000 USP Units) treatment groups. The efficacy of Ovidrel 250 g and Ovidrel 500 g were both found to be clinically and statistically equivalent to that of the approved urinary-derived hCG product and to each other. The efficacy results for the patients who received Ovidrel 250 g are summarized in Table 3.

# How Supplied
- Choriogonadotropin alfa injection is supplied in a sterile, liquid single dose pre-filled 1 mL syringe. Each choriogonadotropin alfa is filled with 0.515 mL containing 257.5 g of choriogonadotropin alfa, 28.1 mg mannitol, 505 g 85% O-phosphoric acid, 103 g L-methionine, 51.5 g Poloxamer 188, Sodium Hydroxide (for pH adjustment), and Water for Injection to deliver 250 g of choriogonadotropin alfa in 0.5 mL.
- The following package combination is available:
- 1 pre-filled syringe containing 250 g choriogonadotropin alfa NDC 44087-1150-1

## Storage
- The choriogonadotropin alfa must be stored refrigerated between 2-8C (36-46F) before being dispensed to the patient. Patients should store the pre-filled syringe refrigerated to allow the product to be used until the expiry date shown on the syringe or carton. The choriogonadotropin alfa may be stored by the patient for no more than 30 days at room temperature (up to 25C (77F) but must be used within those 30 days.
- Protect from light.
- Store in original package. Discard unused material.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Choriogonadotropin alfa in the drug label.

# Precautions with Alcohol
- Alcohol-Choriogonadotropin alfa interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- OVIDREL

# Look-Alike Drug Names
There is limited information regarding Choriogonadotropin alfa Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price