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Chorionic Gonadotropin (Human)

Pronunciation

(kor ee ON ik goe NAD oh troe pin, HYU man)

Index Terms

  • CG
  • hCG

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intramuscular:

Novarel: 5000 units (1 ea); 10,000 units (1 ea) [contains benzyl alcohol]

Pregnyl: 10,000 units (1 ea) [contains benzyl alcohol, sodium chloride]

Generic: 10,000 units (1 ea)

Brand Names: U.S.

  • Novarel
  • Pregnyl

Pharmacologic Category

  • Gonadotropin
  • Ovulation Stimulator

Pharmacology

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.

Distribution

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

Excretion

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

Time to Peak

Plasma: IM: Within 6 hours

Duration of Action

IM: ~36 hours

Half-Life Elimination

Biphasic: Initial: 6 to 11 hours; Terminal: 23 to 37 hours

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.

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

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: Geriatric

Refer to adult dosing.

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: 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.

Reconstitution

Depending on desired concentration, add 1 to 10 mL of provided diluent to lyophilized powder; agitate gently until powder is completely dissolved. Use immediately after reconstitution or store ≤60 days in the refrigerator (product dependent).

Administration

For IM administration only.

Storage

Store at intact vials at 15°C to 30°C (59°F to 86°F). Following reconstitution, solution is stable when refrigerated (2ºC to 8ºC [36ºF to 46ºF]) for 30 days (Novarel) or 60 days (Pregnyl).

Drug Interactions

There are no known significant interactions.

Test Interactions

Cross-reacts with radioimmunoassay of gonadotropins, especially LH

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% (Limited to important or life-threatening): Arterial thrombosis, ovarian hyperstimulation syndrome, rupture of ovarian cyst

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.

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)

Pregnancy Risk Factor

X

Pregnancy Considerations

Studies in animals have shown evidence of fetal abnormalities at doses intended to induce superovulation (used in combination regimens). Testicular tumors in otherwise healthy men have been reported when treating secondary infertility. The incidence of ectopic pregnancy and increased pregnancy loss may be increased in women undergoing assisted reproductive therapy. Congenital abnormalities have also been observed, however a causal association has not been established. In women undergoing ovulation induction, discontinue use after pregnancy is established.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience injection site irritation, headache, loss of strength and energy, or agitation. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), edema, breast pain, angina, depression, signs of puberty, or signs of ovarian hyperstimulation syndrome (severe abdominal pain or bloating; severe nausea, vomiting, or diarrhea; excessive weight gain; shortness of breath; or change in amount of urine passed) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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