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)
Pharmacology
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.
Pharmacokinetics/Pharmacodynamics
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.
Use: Off Label
Spermatogenesis induction associated with hypogonadotropic hypogonadismyes
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: 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 reproductive organs incompatible with pregnancy; fibroid tumors of the uterus incompatible with pregnancy; abnormal (not menstrual) vaginal bleeding without a known/diagnosed cause.
Dosage and Administration
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
Hypogonadotropic hypogonadism, puberty induction: Limited data available: Children ≥12 years and Adolescents: Males: IM: 500 to 3,000 units 2 to 3 times weekly; adjust dose based on serum testosterone levels, every 3 to 6 months (AACE 2002; Sato 2015; Sperling 2014)
Prepubertal cryptorchidism: Children ≥4 years and Adolescents: Males: IM: Various regimens reported by manufacturer:
Note: Therapy is usually instituted between the ages of 4 and 9 years:
4,000 units 3 times weekly for 3 weeks or
5,000 units every second day for 4 injections or
500 units 3 times weekly for 4 to 6 weeks (if not successful may repeat course one month later using 1,000 units/dose) or
15 injections of 500 to 1,000 units administered over 6 weeks
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
IM: 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: Arterial thrombosis, edema
Central nervous system: Depression, fatigue, headache, irritability, restlessness
Endocrine & metabolic: Gynecomastia, ovarian hyperstimulation syndrome
Genitourinary: Precocious puberty, rupture of ovarian cyst
Local: Pain at injection site
<1%, postmarketing, and/or case reports: Anaphylaxis, hypersensitivity reaction (local or systemic; including angioedema, dyspnea, erythema, skin rash, urticaria), testicular neoplasm
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
Pregnancy Considerations
Studies in animals have shown evidence of fetal abnormalities at doses intended to induce superovulation (used in combination regimens).
When needed for ovulation induction, should only be used by physicians who are thoroughly familiar with infertility problems and their management. Multiple births may result from use of this medication.
Testicular tumors in otherwise healthy men have been reported when treating secondary infertility.
Patient Education
What is this drug used for?
- It is used to help women get pregnant.
- It is used to help the body make more testosterone in some people.
- It is used to treat delays in a male's normal growth pattern.
- It may be given to you for other reasons. Talk with the doctor.
Frequently reported side effects of this drug
- Injection site pain
- Headache
- Loss of strength and energy
- Agitation
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes
- DVT like swelling, warmth, numbness, change in color, or pain in the extremities
- Swelling
- Irritability
- Enlarged breasts
- Chest pain
- Depression
- Weight gain
- Trouble breathing
- Puberty
- Ovarian hyperstimulation syndrome like severe abdominal pain or bloating; severe nausea, vomiting, or diarrhea; excessive weight gain; shortness of breath; or change in amount of urine passed
- Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
