Infertility

Gonarex (HCG)


Pharmacologic Category

Gonadotropin; Ovulation Stimulator

Dosing: Adult

Ovulation induction: Females: IM: 5,000 to 10,000 units 1 day following last dose of menotropins

Hypogonadotropic hypogonadism: Males: IM: Various regimens:

500 to 1,000 units 3 times/week for 3 weeks, followed by the same dose twice weekly for 3 weeks or

4,000 units 3 times/week for 6 to 9 months, then reduce dosage to 2,000 units 3 times/week for additional 3 months

Spermatogenesis induction associated with hypogonadotropic hypogonadism (off-label use): Males: IM: 1,000 to 2,000 units 2 to 3 times/week. Administer hCG until serum testosterone levels are normal (may require 2 to 3 months of therapy), then may add menopausal gonadotropin of FSH if needed to induce spermatogenesis; continue hCG at the dose required to maintain testosterone levels (AACE 2002).

Dosing: Pediatric

Prepubertal cryptorchidism: Children ≥4 years and Adolescents (males): IM: Note: Therapy is usually instituted between the ages of 4 and 9:

4,000 units 3 times/week for 3 weeks or

5,000 units every second day for 4 injections or

500 units 3 times/week for 4 to 6 weeks or

15 injections of 500 to 1,000 units administered over 6 weeks

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosage Form

5000IU

Administration

For IM administration only.

Use

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.

Use: Off-Label

Spermatogenesis induction associated with hypogonadotropic hypogonadism

Adverse Reactions

Frequency not defined.

Cardiovascular: Edema

Central nervous system: Depression, fatigue, headache, irritability, restlessness

Endocrine & metabolic: Gynecomastia

Genitourinary: Precocious puberty

Hypersensitivity: Hypersensitivity reaction (local or systemic)

Local: Injection site reaction, pain at injection site

<1%, postmarketing, and/or case reports: Arterial thrombosis, ovarian hyperstimulation syndrome, rupture of ovarian cyst

Contraindications

Hypersensitivity to chorionic gonadotropin or any component of the formulation; precocious puberty; prostatic carcinoma or other androgen-dependent neoplasms

Canadian labeling (Pregnyl): Additional contraindications (not in US labeling): Prepubertal males with signs of anatomical obstruction; sex hormone-dependent tumors (eg, ovary, breast and uterine carcinoma in females; breast carcinoma males); malformations of the sexual organs incompatible with pregnancy; fibroid tumors of the uterus incompatible with pregnancy

Warnings/Precautions

Concerns related to adverse effects:

Hypersensitivity: Anaphylaxis has been reported with urinary-derived hCG products.

Thromboembolism: Arterial or venous thromboembolism may occur; patients with a history of family history of thrombosis, severe obesity, or thrombophilia are at an increased risk.

Disease-related concerns:

Asthma: Use with caution in patients with asthma.

Cardiovascular disease: Use with caution in patients with cardiovascular disease.

Cryptorchidism: May induce precocious puberty in children being treated for cryptorchidism; discontinue if signs of precocious puberty occur.

Migraine: Use with caution in patients with a history of migraines.

Renal impairment: Use with caution in patients with renal impairment.

Seizure disorders: Use with caution in patients with a history of seizure disorders.

Dosage form specific issues:

Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP [“Inactive” 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

Obesity: Not effective adjunctive therapy in the treatment of obesity.

Ovulation induction: Appropriate use: These medications should only be used by physicians who are thoroughly familiar with infertility problems and their management. May cause ovarian hyperstimulation syndrome (OHSS). OHSS is a rare exaggerated response to ovulation induction therapy (Corbett 2014; Fiedler 2012). This syndrome may begin within 24 hours of treatment but may become most severe 7 to 10 days after therapy (Corbett 2014). Symptoms of mild/moderate OHSS may include abdominal distention/discomfort, diarrhea, nausea, and/or vomiting. Severe OHSS symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, or nausea/vomiting (intractable). Decreased creatinine clearance, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM 2016; Corbett 2014; Fiedler 2012). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (ASRM 2016; SOGC-CFAS 2011). Multiple births may result from the use of these medications; advise patients of the potential risk of multiple births before starting the treatment.

Drug Interactions

There are no known significant interactions.

Pregnancy Risk Factor

X

Breast-Feeding Considerations

It is not known if chorionic gonadotropin (human) is excreted in breast milk. The manufacturer recommends that caution be exercised when administering chorionic gonadotropin (human) to breastfeeding women.

Monitoring Parameters

Male: Serum testosterone levels, semen analysis (AACE 2002)

Female: Ultrasound and/or estradiol levels to assess follicle development; ultrasound to assess number and size of follicles; ovulation (basal body temperature, serum progestin level, menstruation, sonography)

OHSS: Monitoring of hospitalized patients should include abdominal circumference, albumin, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, serum creatinine, urine output, urine specific gravity, vital signs, weight (all daily or as necessary) and liver enzymes (weekly) (SOGC-CFAS 2011)

Mechanism of Action

Human chorionic gonadotropin (hCG) is produced by the human placenta; available preparations provide purified luteinizing hormone obtained from the urine of pregnant women. hCG stimulates production of gonadal steroid hormones by causing production of androgen by the testes and the development of secondary sex characteristics in males. In females, hCG acts as a substitute for luteinizing hormone (LH) to stimulate ovulation.

Pharmacodynamics/Kinetics

Duration: IM: ~36 hours

Distribution: Distributes mainly into the testes in males and into the ovaries in females

Half-life elimination: Biphasic: Initial: 6 to 11 hours; Terminal: 23 to 37 hours

Time to peak, plasma: IM: Within 6 hours

Excretion: Urine (~10% to 12 %) within 24 hours

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