HUMAN CHORIONIC GONADOTROPHIN
DESCRIPTION:
Human chorionic gonadotropin (HCG), a polypeptide hormone produced by the human
placenta, is composed of an alpha and a beta sub-unit. The alpha sub-unit is
essentially identical to the alpha sub-units of the human pituitary
gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH),
as well as to the alpha sub-unit of human thyroid-stimulating hormone (TSH). The
beta sub-units of these hormones differ in amino acid sequence.
Chorionic Gonadotropin is a water soluble glycoprotein derived from human
pregnancy urine. The sterile lyophilized powder is stable. When reconstituted,
the solution should be refrigerated and used within 30 days.
ACTIONS/CLINICAL PHARMACOLOGY:
The action of HCG is virtually identical to that of pituitary LH, although HCG
appears to have a small degree of FSH activity as well. It stimulates production
of gonadal steroid hormones by stimulating the interstitial cells (Leydig cells)
of the testis to produce androgens and the corpus luteum of the ovary to produce
progesterone. Androgen stimulation in the male leads to the development of
secondary sex characteristics and may stimulate testicular descent when no
anatomical impediment to descent is present. This descent is usually reversible
when HCG is discontinued. During the normal menstrual cycle, LH participates
with FSH in the development and maturation of the normal ovarian follicle, and
the mid-cycle LH surge triggers ovulation. HCG can substitute for LH in this
function.
During a normal pregnancy, HCG secreted by the placenta maintains the corpus
luteum after LH secretion decreases, supporting continued secretion of estrogen
and progesterone, and preventing menstruation. HCG HAS NO KNOWN EFFECT ON FAT
MOBILIZATION, APPETITE OR SENSE OF HUNGER, OR BODY FAT DISTRIBUTION.
INDICATIONS AND USAGE:
HCG HAS NOT BEEN DEMONSTRATED TO BE EFFECTIVE ADJUNCTIVE THERAPY IN THE
TREATMENT OF OBESITY. THERE IS NO SUBSTANTIAL EVIDENCE THAT IT INCREASES WEIGHT
LOSS BEYOND THAT RESULTING FROM CALORIC RESTRICTION, THAT IT CAUSES A MORE
ATTRACTIVE OR "NORMAL" DISTRIBUTION OF FAT, OR THAT IT DECREASES THE HUNGER AND
DISCOMFORT ASSOCIATED WITH CALORIE-RESTRICTED DIETS.
1. Prepubertal cryptorchidism not due to anatomic obstruction. In general, HCG
is thought to induce testicular descent in situations when descent would have
occurred at puberty. HCG thus may help to predict whether or not orchiopexy will
be needed in the future. Although, in some cases, descent following HCG
administration is permanent, in most cases the response is temporary. Therapy is
usually instituted between the ages of 4 and 9.
2. Selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a
pituitary deficiency) in males.
3. Induction of ovulation and pregnancy in the anovulatory, infertile woman in
whom the cause of anovulation is secondary and not due to primary ovarian
failure, and who has been appropriately pretreated with human menotropins.
CONTRAINDICATIONS:
Precocious puberty, prostatic carcinoma or other androgen-dependent neoplasm,
prior allergic reaction to HCG. HCG may cause fetal harm when administered to a
pregnant woman. Combined HCG/PMS (pregnant mare's serum) therapy has been noted
to induce high incidences of external congenital anomalies in the offspring of
mice, in a dose-dependent manner. The potential extrapolation to humans has not
been determined.
WARNINGS:
HCG should be used in conjunction with human menopausal gonadotropins only by
physicians experienced with infertility problems who are familiar with the
criteria for patient selection, contraindications, warnings, precautions, and
adverse reactions described in the package insert for menotropins. The principal
serious adverse reactions during this use are: (1) Ovarian hyperstimulation, a
syndrome of sudden ovarian enlargement, ascites with or without pain, and/or
pleural effusion; (2) Enlargement of preexisting ovarian cysts or rupture of
ovarian cysts with resultant hemoperitoneum; (3) Multiple births, and (4)
Arterial thromboembolism.
The diluent used for reconstitution contains benzyl alcohol. Benzyl alcohol has
been reported to be associated with a fatal "Gasping Syndrome" in premature
infants.
PRECAUTIONS:
GENERAL: 1. Induction of androgen secretion by HCG may induce precocious puberty
in patients treated for cryptorchidism. Therapy should be discontinued if signs
of precocious puberty occur.
2. Since androgens may cause fluid retention, HCG should be used with caution in
patients with cardiac or renal disease, epilepsy, migraine, or asthma.
DRUG/LABORATORY TEST: HCG can crossreact in the radioimmunoassay of
gonadotropins, especially luteinizing hormone. Each individual laboratory should
establish the degree of crossreactivity with their gonadotropin assay.
Physicians should make the laboratory aware of patients on HCG if gonadotropin
levels are requested.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: There have been sporadic
reports of testicular tumors in otherwise healthy young men receiving HCG for
secondary infertility. A causative relationship between HCG and tumor
development in these men has not been established. Defects of forelimbs and of
the central nervous system, as well as alterations in sex ratio, have been
reported in mice on combined gonadotropin and HCG regimens. The dose of
gonadotropin used was intended to induce superovulation. No mutagenic effect has
been clearly established in humans. Fertility--see "Indications and Usage."
PREGNANCY: TERATOGENIC EFFECTS--Category X: See "Contraindications" section.
Combined HCG/PMS (pregnant mare's serum) therapy has been noted to induce high
incidences of external congenital anomalies in the offspring of mice, in a dose-
dependent manner. The potential extrapolation to humans has not been determined.
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 when
HCG is administered to a nursing woman.
PEDIATRIC USE: Safety and effectiveness in children below the age of 4 have not
been established.
ADVERSE REACTIONS:
ADVERSE REACTIONS (See WARNINGS)
Headache, irritability, restlessness, depression, fatigue, edema, precocious
puberty, gynecomastia, pain at the site of injection. Hypersensitivity reactions
both localized and systemic in nature, including erythema, urticaria, rash,
angioedema, dyspnea and shortness of breath, have been reported. The
relationship of these allergic-like events to the polypeptide hormone or the
diluent containing benzyl alcohol is not clear.
DOSAGE AND ADMINISTRATION (Intramuscular Use Only):
The dosage regimen employed in any particular case will depend upon the
indication for use, the age and weight of the patient, and the physician's
preference. The following regimens have been advocated by various authorities.
Prepubertal cryptorchidism not due to anatomical obstruction:
(1) 4,000 USP Units three times weekly for three weeks.
(2) 5,000 USP Units every second day for four injections.
(3) 15 Injections of 500 to 1,000 USP Units over a period of six weeks.
(4) 500 USP Units three times weekly for four to six weeks. If this course of
treatment is not successful, another is begun one month later, giving
1,000 USP Units per injection.
Selected cases of hypogonadotropic hypogonadism in males:
(1) 500 to 1,000 USP Units three times a week for three weeks, followed by the
same dose twice a week for three weeks.
(2) 4,000 USP Units three times weekly for six to nine months, following which
the dosage may be reduced to 2,000 USP Units three times weekly for an
additional three months.
Induction of ovulation and pregnancy in the anovulatory, infertile woman in whom
the cause of anovulation is secondary and not due to primary ovarian failure and
who has been appropriately pre-treated with human menotropins (See prescribing
information for menotropins for dosage and administration for that drug
product).
5,000 to 10,000 USP Units one day following the last dose of menotropins. (A
dosage of 10,000 USP Units is recommended in the labeling for menotropins).
Parenteral drug products should be inspected visually for particulate matter and
discoloration prior to administration, whenever solution and container permit.
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