Pregnyl

Gonadotropins

Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Urine-derived HCG products
The FDA-approved route of administration is by intramuscular injection. Do not inject intravenously.
 
Reconstitution for intramuscular (IM) injection:
Withdraw sterile air from the vial containing the lyophilized powder.
Withdraw 1 mL to 10 mL of the sterile diluent provided and add to the lyophilized vial; agitate gently until powder is completely dissolved in the diluent. Do not shake. The amount of diluent to be used will be dependent on the dosage to be administered and indication for use.
Storage of reconstituted multiple-dose vials: May be stored in the refrigerator at 2 to 8 degrees C (36 to 46 degrees F) for up to 30 days (Novarel) and up to 60 days (Pregnyl) after reconstitution. Do not freeze.
 
Intramuscular injection:
Refer to the manufacturer provided "Instructions for Use".
For adults and adolescents, inject deeply into a large muscle; the usual site is the upper outer region of the right or left buttock below the hipbone.
For children, inject deeply into a large muscle, preferably the anterolateral aspect of the thigh.

Choriogonadotropin Alfa Solution for injection (Ovidrel) ONLY
Administer by subcutaneous injection only. Do not inject intravenously or intramuscularly.
Review the manufacturer supplied "Instructions for Use". The injection may be self-administered by the patient after proper training by the care team.
Inject subcutaneously as directed taking care not to inject intradermally or into a blood vessel.
Subcutaneous injection should be made in the abdomen, at least 1 to 2 inches away from the navel.
For single-use only; promptly discard of used syringe and needle in an appropriate sharps safety container.
Storage: Preferably store the pre-filled syringe refrigerated at 2 to 8 degrees C (36 to 46 degrees F). Do not freeze. If needed, the prefilled syringe may be stored for no more than 30 days at room temperature, up to 25 degrees C (77 degrees F), but must be used within those 30 days. Protect from light. Store in original package until use.

ovarian hyperstimulation syndrome / Delayed / 1.7-9.0
ectopic pregnancy / Delayed / 0-2.0
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
thromboembolism / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 3.0-10.0
ovarian enlargement / Delayed / 3.0-3.0
vaginitis / Delayed / 0-2.0
vaginal bleeding / Delayed / 0-2.0
hot flashes / Early / 0-2.0
edema / Delayed / Incidence not known
erythema / Early / Incidence not known
dyspnea / Early / Incidence not known
precocious puberty / Delayed / Incidence not known
depression / Delayed / Incidence not known

gynecomastia / Delayed / 0-30.0
injection site reaction / Rapid / 14.0-16.2
abdominal pain / Early / 3.0-4.2
nausea / Early / 3.4-3.4
vomiting / Early / 2.5-2.5
breakthrough bleeding / Delayed / 0-2.0
leukorrhea / Delayed / 0-2.0
rash / Early / 0-2.0
pruritus / Rapid / 0-2.0
mastalgia / Delayed / 0-2.0
malaise / Early / 0-2.0
headache / Early / 0-2.0
dizziness / Early / 0-2.0
insomnia / Early / 0-2.0
emotional lability / Early / 0-2.0
diarrhea / Early / 0-2.0
flatulence / Early / 0-2.0
back pain / Delayed / 0-2.0
urticaria / Rapid / Incidence not known
restlessness / Early / Incidence not known
irritability / Delayed / Incidence not known
fatigue / Early / Incidence not known
pelvic pain / Delayed / Incidence not known

Novarel, Ovidrel, Pregnyl

Rx

Gonad-stimulating hormone secreted by the placenta during pregnancy; obtained from the urine of pregnant women; recombinant form now available; HCG mimics the actions of LH; HCG induces an LH surge after the use of ovulation induction protocols in women; also used to treat hypogonadism and oligospermia in men.

The International Health Foundation has advocated a dosage of 1000 USP units IM 2 times per week for a total of 5 weeks. NOTE: various dosage regimens have been advocated for male children >= 4 years old. The following alternative regimens have been employed; however, the total dosage and length of the treatment course may vary widely: 1) 4000 USP units IM 3 times per week for 3 weeks; 2) 5000 USP units IM every other day for 4 doses; 3) 15 doses of 500—1000 USP units IM given over a period of 6 weeks; or 4) administer 500 USP units IM 3 times per week for 4—6 weeks. If not successful, then another course of HCG 1 month later may be administered at doses of 1000 USP units IM 3 times per week for 4—6 weeks.

The International Health Foundation has advocated a dosage of 500 USP units IM 2 times per week for a total of 5 weeks.

The International Health Foundation has advocated a dosage of 250 USP units IM 2 times per week for a total of 5 weeks.

NOTE: various dosage regimens have been advocated. The following alternative regimens have been employed; however, the total dosage and length of the treatment course may vary widely: 1) 500—1000 USP units IM or subcutaneous 3 times per week for 3 weeks, followed by the same dose twice per week for 3 weeks; 2) 4000 USP units IM or subcutaneous 3 times per week for 6—9 months, then reduced to 2000 USP units 3 times a week for an additional 3 months; or 3) HCG 2500 units subcutaneous 2 times per week in combination with FSH 150 International Units subcutaneous 3 times per week for at least 6 months.

Pretreatment with 1000—2250 USP units IM/subcutaneous 2—3 times per week; dosages up to 5000 USP units of HCG IM 3 times per week. Administer until normal serum testosterone concentrations are achieved and masculinization (development of secondary sex characteristics) occurs. Pretreatment may require 4—6 months, followed by combined therapy with menotropins (hMg) or follitropin (r-hFSH). See the following regimens. In some patients with appropriate testicular volumes (i.e., > 4 mL), HCG treatment alone may produce adequate spermatogenesis.

NOTE: various dosage regimens have been advocated. The following alternative regimens have been employed; however, the total dosage and length of the treatment course may vary widely. ONE REGIMEN: HCG 1000—1500 USP units administered IM/subcutaneous in combination with menotropins 75—150 International Units IM/subcutaneous. Both are administered every other day, but at separate sites. Combination therapy should be continued for at least 4 months to ensure detection of spermatozoa in the ejaculate and to increase testicular volume. Most men in clinical trials to date are noted to have sperm output by 6 months; target goals are reached with a median 9 months of treatment. ALTERNATIVE REGIMEN: HCG 2000 USP units administered IM/subcutaneous 2 times per week in combination with menotropins 75 International Units IM/subcutaneous given 3 times per week at a separate injection site. Combination therapy should be continued for at least 4 months to ensure detection of spermatozoa in the ejaculate. If an increase in spermatogenesis has not occurred in 4 months, the dosage of menotropins can be increased to 150 International Units IM 3 times per week or continued while the dose of HCG remains the same.

FSH must be given in conjunction with hCG. Both drugs are administered roughly 3 times per week (i.e., every other day) but at separate sites. The recommended dose is HCG 1000—1500 USP units (or the dose required to maintain normal serum testosterone) administered IM or subcutaneous 3 times per week in combination with follitropin-alfa 150 International Units subcutaneous 3 times per week at different sites. The lowest dose of FSH which induces spermatogenesis should be utilized. If azoospermia persists, the dose of FSH may be increased to a maximum dose of 300 International Units 3 times per week. Combination therapy should be continued for at least 4 months to ensure detection of spermatozoa in the ejaculate and to increase testicular volume. Most men in clinical trials to date were noted to have sperm output by 6 months; target goals adequate for fertilization are reached with a median 9 months of treatment. The drugs may need to be administered for up to 18 months to achieve adequate spermatogenesis.

FSH must be given in conjunction with hCG. Initially, give hCG 1500 International Units subcutaneous twice per week. If serum testosterone concentrations have not normalized after 8 weeks, the hCG dose may be increased to 3000 International Units subcutaneous twice per week. Give hCG at the dose needed to normalize serum testosterone concentrations in combination with follitropin-beta 225 International Units subcutaneous twice weekly or 150 International Units subcutaneous 3 times per week.

5000—10,000 USP units of HCG IM as a single dose at the appropriate day, as determined by exam and ultrasound, after the last dose of clomiphene (usually 3—4 days after the last clomiphene dose).

5000—10,000 USP units of HCG IM as a single dose 1 day after the last dose of menotropins or FSH pre-treatment. The labeling for menotropins recommends an HCG dosage of 10,000 USP units for anovulation.

250 mcg subcutaneous as a single dose 1 day after the last dose of menotropins or FSH pre-treatment.

2500 USP units of HCG IM given as a single dose 8 days after the initial dose of HCG was given.

When a sufficient number of follicles of adequate size are present with FSH therapy, FSH is discontinued and the final maturation of the follicles is induced by administering 5000—10,000 USP units of HCG IM as a single dose 1 day after the last dose of FSH. Oocyte retrieval is usually performed 34—36 hours later, before ovulation can occur.

When a sufficient number of follicles of adequate size are present with follicle-stimulating therapy, the follicle-stimulating hormone is discontinued and the final maturation of the follicles is induced by administering 250 mcg subcutaneous of Ovidrel as a single dose 1 day after the last dose of of the follicle-stimulating agent. Oocyte retrieval is usually performed 34—36 hours later, before ovulation can occur.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Human Chorionic Gonadotropin, HCG products.

Chorionic Gonadotropin/Novarel/Pregnyl Intramuscular Inj Pwd F/Sol: 5000U, 10000U
Ovidrel Subcutaneous Inj Sol: 0.5mL, 250mcg

No specific maximum dosage limit recommendations are available. Dosage regimens of urine-derived human chorionic gonadotropin (HCG) depend upon the patient's age, sex, weight, condition being treated, product chosen, and the prescribing clinician's judgment. Therefore, doses may vary widely and must be carefully individualized.

The mechanism of action of human chorionic gonadotropin (hCG) depends upon the purpose for which it is being used, the sex of the patient, and the level of maturity of the patient to whom it is administered.
 
•Activity - adult females: In select females with infertility , human chorionic gonadotropin has actions essentially identical to those of luteinizing hormone (LH). Human chorionic gonadotropin (hCG) also appears to have additional, though minimal, follicle-stimulating hormone (FSH) activity. By administering hCG after follitropin, menotropins, or clomiphene, the normal LH surge that precedes ovulation can be mimicked. Human chorionic gonadotropin (hCG) promotes the development and maintenance of the corpus lutetium and the production of progesterone. Following hCG administration, final luteinization or maturation of the oocytes occurs and either ovulation can ensue for timed insemination techniques, or oocyte retrieval can take place for assisted reproductive technology (ART) procedures such as in vitro fertilization (IVF). Once pregnancy takes place, endogenous hCG is normally secreted by the placenta to support the continued secretion of female hormones and the corpus luteum.
 
•Activity - adult and adolescent males: In adult and adolescent men with hypogonadotropic hypogonadism, hCG acts like LH and stimulates testosterone production in the Leydig cells and spermatogenesis in the seminiferous tubules. Stimulation of androgen production by hCG causes development of secondary sex characteristics in males (e.g., deepening of voice, facial hair, etc.). Human chorionic gonadotropin (hCG) also stimulates the Leydig cells to produce estrogens; increased estrogen levels may produce gynecomastia in some males. Once hCG is initiated, it takes at least 70—80 days for germ cells to reach the spermatozoal stage. Response to treatment is also noted by the development of masculine features and the normalization of serum testosterone levels. Induction of testicular growth and increased sperm volumes may help to restore fertility in these men after many months to years of treatment, which is then sometimes combined with the use of either menotropins or follitropin.
 
•Activity - male infants and children: In the male infant, normal testicular descent is complete by 3 months of age. Testicular descent occurs secondary to an endogenous testosterone surge stimulated by pituitary gonadotropins in response to the discontinued exposure to maternal circulating estrogens upon birth; this testosterone surge peaks within 60 days postnatally. In male infants and children with cryptorchidism, hCG acts like LH and causes the Leydig cells of the testes to produce a testosterone surge and induce the descent of palpable testes. The hormonal stimulation by hCG may result in an early pseudopuberty, and in some cases, the response to hormonal therapy may be temporary in 10—20% of cases. Hormonal therapies like hCG have not replaced the primary surgical treatment for the condition, which is orchiopexy within the first 1—2 years of life. Early animal studies have suggested that hCG may be used as an adjunct to orchiopexy to help preserve fertility, but human data is lacking.
 
•Activity on body composition (all sexes): Human chorionic gonadotropin has no known effects on appetite, or on mobilization or distribution of body fat. It is not an effective treatment for obesity. In sport, athletes use HCG as an 'undetectable' anabolic steroid; hCG increases the body's production of testosterone and epitestosterone without increasing the ratio of the two hormones in the urine above normal values. Urinary testing is being developed which should allow for discriminate testing of hCG doping in sport.

Human chorionic gonadotropin is administered subcutaneously and intramuscularly. Similar to other polypeptides, gonadotropins are almost completely degraded in the gastrointestinal tract; therefore, parenteral administration is required.
Urine-derived products: In the body, human chorionic gonadotropin primarily distributes into the testes in males and into the ovaries in females. In the ovaries, hCG is concentrated in the fluid of the developing follicles. The metabolic fate of hCG has not been elucidated, but it is eliminated in a biphasic manner. The terminal half-life is approximately 23 hours. After a single IM injection, roughly 10—12% of a dose is excreted unchanged in the urine within 24 hours and can be detected for up to 3—4 days.
Recombinant hCG: The metabolic fate of r-hCG has not been elucidated, but it is eliminated in a biphasic manner. Recombinant-hCG is eliminated from the body with a mean terminal half-life of roughly 29 hours (range 23—35 hours), which is similar to urine-derived hCG. After a single subcutaneous injection, roughly 10% of the dose is excreted unchanged in the urine within 24 hours.

Urine-derived products: Urinary-derived human chorionic gonadotropin (hCG) is administered by the intramuscular (IM) route; however, one study has shown similar bioavailability with subcutaneous (SC) administration. Subjective observations in the literature have also supported the use of hCG by the SC route as equivalent to IM administration clinically. Serum concentrations of hCG are detectable within 2 hours of IM administration; peak concentrations are attained within 6 hours and persist for roughly 36 hours.

Urine-derived products: Urinary-derived human chorionic gonadotropin (hCG) is administered by the intramuscular (IM) route; however, one study has shown similar bioavailability with subcutaneous (SC) administration. Subjective observations in the literature have also supported the use of hCG by the subcutaneous (SC) route as equivalent to IM administration clinically.
Recombinant hCG: Recombinant hCG (Ovidrel) is administered subcutaneously (SC). Following a 250 mcg SC dose, Cmax is achieved within 12—24 hours, with an absolute bioavailability of roughly 40%.

Human chorionic gonadotropin is used for infertility treatments and is classified in FDA pregnancy category X and is contraindicated after conception has occurred. When administered to mice, animal derived formulations of exogenous HCG have induced a high incidence of external congenital anomalies. While animal data are not always indicative of the response in human gestation, the potential for serious fetal harm cannot be excluded. Therefore, pregnancy should be ruled out prior to the administration of HCG with each fertility treatment course. In addition to potential effects on the fetus, protocols using HCG inherently increase the risk of multiple gestation and the risks associated with such pregnancies.

Human chorionic gonadotropin, HCG should be used with caution in lactating women who are breast-feeding. Most endogenous gonadotropins are found in breast milk or tissues to some degree. It is neither known whether exogenous HCG is distributed into breast milk, nor what effect this would have on the breast-feeding infant.