DESCRIPTIONChorionic Gonadotropin for Injection, USP (hCG) isextracted from the urine of pregnant women. It is awater-soluble polypeptide hormone produced by thehuman placenta composed of an alpha and a beta sub-unit. The alpha sub-unit is essentially identical to the alpha sub-units of the human pituitarygonadotropins, luteinizing hormone (LH) and folliclestimulating 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 aminoacid sequence.

Chorionic Gonadotropin for Injection (hCG) is biologicallystandardized and the potency is declared in terms of theUSP Reference Standard.

ACTIONSThe action of hCG is virtually identical to that of pituitaryLH, although hCG appears to have a small degree ofFSH activity as well.

Male: Chorionic Gonadotropin for Injection, USP is given to males in an effort to stimulate the interstitialcells of the testes (cells of Leydig) to produce androgen.The response to hCG may be considered similar to theeffect caused by the interstitial cell stimulating hormone(ICSH) from the anterior lobe of the pituitary. Androgenstimulation in the male leads to the development ofsecondary sex characteristics and may stimulatetesticular descent when no anatomical impediment todescent is present. This descent is usually reversiblewhen hCG is discontinued.

Chorionic Gonadotropin for Injection is likely to be ofbenefit in all conditions directly related to insufficientsecretion of androgen, provided the interstitial cells ofthe testes are capable of stimulation.

Female: Chorionic Gonadotropin for Injection is given in the second phase of the cycle in an effort to maintainthe functional integrity of the corpus luteum and tostimulate its secretion of progesterone. Response to hCG may be considered similar to the effect caused by the luteotrophic hormone from the pituitary gland.

During the normal menstrual cycle, LH participates withFSH in the development and maturation of the normalovarian follicle, and the mid-cycle LH surge triggersovulation. hCG can substitute for LH in this function.

During a normal pregnancy, hCG secreted by theplacenta maintains the corpus luteum after LH secretiondecreases, supporting continued secretion of estrogenand progesterone and preventing menstruation.

hCG has no known effect on fat mobilization, appetite or sense of hunger, or body fat distribution.

INDICATIONS AND CLINICAL USENote: hCG has not been shown to be an effectiveadjunctive therapy in the treatment of obesity. There is no substantial evidence that it increases weight lossbeyond that resulting from caloric restriction, that itproduces a more attractive or “normal” distribution of fat, or that it reduces the hunger and discomfortassociated with calorie-restricted diets.

Male:Chorionic Gonadotropin for Injection, USP is indicated forthe treatment of:

1. Prepubertal Cryptorchidism (not due to anatomical obstruction)In general, hCG is thought to induce testiculardescent in situations when descent would haveoccurred at puberty. Thus, hCG may help predictwhether or not orchiopexy will be needed in thefuture. In most cases the response is temporary,although, in some cases, descent after hCGadministration is permanent. Age of initiation oftreatment: various ages ranging from early childhoodto immediately before expected puberty have beensuggested. On the average, however, 12 yearsappears to be the appropriate age.

2. Delayed AdolescenceChorionic gonadotropin will almost invariably set in motion the normal mechanism of puberty bystimulating the interstitial cells to secrete androgen.Normal development is likely to continue aftertherapy ceases.

3. Dwarfism (pituitary)Before epiphyseal closure, the stimulative effects ofchorionic gonadotropin on the interstitial cells of thetestes may prove beneficial. Therapy has producedacceleration of longitudinal bone growth as well assexual and somatic maturation in some cases.

4. Hypogonadotropic EunuchoidismChorionic gonadotropin therapy is directed to thedevelopment of primary and secondary sex charac-teristics through its ability to stimulate the interstitialcells of the testes to secrete androgen. The responseto hCG is usually dramatic in patients of pubertalage. The adult patient does not respond as readily,but in light of the permanent effects frequentlyobserved after hCG therapy, it is recommended that in either group, treatment be initiated with thissubstance, and that androgen be used only if hCGproves ineffective.

5. Selected Cases of HypogonadotropicHypogonadism (hypogonadism secondary to a pituitary deficiency) in MalesOn clinical grounds alone, it is often impossible todetermine whether the hypogonadism is the result of primary testicular failure. When testicular biopsiesand urinary gonadotropin assays are not available,a therapeutic trial with hCG will assist in establishinga diagnosis and indicate the type of treatmentrequired.

Lack of response to Chorionic Gonadotropin forInjection therapy may be considered as an indicationthat the hypogonadism is not of pituitary origin, orthat the testes are unresponsive to stimulation. If thisis the case, substitution therapy with androgen isindicated.

Female:Chorionic Gonadotropin for Injection is indicated for:

1. Ovulation InductionInduction of ovulation and pregnancy in theanovulatory, infertile woman in whom the cause of anovulation is secondary and not due to primaryovarian failure, and who has been appropriately pre-treated with human gonadotropins.

2. Abortion (habitual)Recurrent abortion at the end of the first three to sixweeks of pregnancy may be due to inadequate pro-duction of chorionic gonadotropin. The administrationof large daily doses of Chorionic Gonadotropin forInjection may provide a beneficial luteotropic effectin the habitual aborter. Preconceptional treatmentwith hCG may encourage nidation and promote amore favourable environment for implantation andearly development of the ovum.

3. Infrequent Scanty Bleeding (functional)Oligomenorrhea, amenorrhea (primary andsecondary), and Frohlich’s Syndrome.

4. Functional SterilityFunctional sterility may not be due to ovulatoryfailure but to corpus luteum development andfunction which is inadequate for proper implantationand early development of the fertilized ovum. In suchinstances, chorionic gonadotropin may be used in aneffort to stimulate progesterone secretion and toencourage a return to normal ovarian function.

CONTRAINDICATIONSChorionic Gonadotropin for Injection, USP is contra-indicated in the treatment of:• pituitary tumour, ovarian tumour, prostatic carcinoma

and androgen-dependent neoplasms, uncontrolledendocrine disorders (e.g., hyperprolactinaemia, thyroidand adrenal dysfunction);

• in female, primary ovarian failure (ovarian dysgenesisand premature menopause), tubal occlusion unlessthe patient is undergoing superovulation for in vitrofertilization;

• urinary-hCG (u-hCG) will not be effective in men,in cases where the FSH level is raised as this isindicative of primary testicular failure;

• u-hCG is not effective and is not indicated for weightreduction;

• precocious puberty;

• active thrombophlebitis or thromboembolic event;

• allergy to u-hCG.

WARNINGS

Female:• Ovarian hyperstimulation syndrome (OHSS)

An excessive ovarian response to follicular stimulatingagents, in women undergoing ovulation induction,may lead to the development of ovarian hyper-stimulation syndrome if u-hCG is given to induceovulation or to support the corpus luteum. It is ofutmost importance that u-hCG should be withheld in such cycles.

OHSS is generally categorized as mild, moderate orsevere.

Mild OHSS symptoms: some abdominal distension;nausea; vomiting; occasional diarrhea; ovariesenlarged to about 5 cm diameter appear 3 - 6 daysafter u-hCG administration. Therapy: rest; carefulobservation and symptomatic relief. Enlargement of the ovaries decreases quickly.

Moderate OHSS symptoms: more pronouncedabdominal distension; nausea; vomiting; occasionaldiarrhea; ovaries enlarge to about 12 cm. Therapy:bed rest; close observation in the case of conceptionoccurring to detect any progression to severe hyper-stimulation. In order to avoid rupture of ovarian cysts,pelvic examination of enlarged ovaries should begentle. Symptoms subside spontaneously over 2 - 3 weeks.

Severe OHSS is a rare (less than 2% of cases whenpatients are normally monitored) but serious compli-cation. Symptoms: ovaries enlarge to in excess of 12 cm diameter; pronounced abdominal distension;ascites; pleural effusion; decreased blood volume;reduced urine output; electrolyte imbalance andsometimes shock. Diuretics should not be used in the primary phase of the syndrome, since they mayprecipitate cardiovascular shock in a patient whoalready has plasma hypovolemia. However, diureticsmay be used during the resolution phase of OHSS tohelp mobilize and eliminate fluid sequestered duringthe first phase. Therapy: hospitalization, treatmentshould be conservative and concentrate on restoringfluid depletion and preventing shock. Acute symptomssubside over several days if conception has notoccurred. Symptoms may persist longer if conceptionhas occurred.

The risk of OHSS developing in women undergoingsuperovulation for an assisted conception techniquemay be lessened if all the follicles are aspirated priorto ovulation.

• Rupture of ovarian cysts with resultanthaemoperitoneum.

• Thromboembolic complications: Thromboembolicevents have been reported after gonadotropin/u-hCGtherapy both in association with and separated fromOHSS. These included thrombophlebitis, pulmonaryembolism, stroke, and arterial occlusion resulting inloss of a limb. In rare instances, thromboembolicevents have resulted in death.

• Multiple pregnancy: The incidence of multiplepregnancies and births increases aftergonadotropins/u-hCG therapy stimulation andovulation induction in patients attempting in vivoconception. The risk of multiple pregnancy following

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Chorionic Gonadotropinfor Injection, USP10,000 USP Units

Gonadotropin

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ART is related to the number of oocytes/embryosreplaced. However, the majority of multiplepregnancies are twins. Multiple pregnancies might result in premature deliveries.

• Pregnancy testing: A false positive test result maybe obtained if the patient has recently undergone(over the last 7 days) u-hCG administration or is stillreceiving the drug.

Male:• Fluid retention: If high doses of u-hCG are

administered in males, the androgens may cause fluid retention. In such instances, the dose should be reduced considerably, particularly in patients with cardiac or renal disease, epilepsy, migraine or asthma.

• Sexual precocity: u-hCG may cause sexual precocitywhen given to young patients for cryptorchidism.If signs are observed, cease treatment. If continuedtherapy is considered necessary, a reduced dosageregimen should be used.

• Gynecomastia: Gynecomastia may be induced by u-hCG.

PRECAUTIONSThe drug substance of this drug product is manu-factured from human urine. Although the risk istheoretical, and no case of transmission of aninfectious agent linked to the use of urine-derivedgonadotropins has ever been identified, the risk oftransmitting infectious agents cannot be completelyexcluded.

Drug Interaction: No clinically significant drug inter-actions have been reported during u-hCG therapy.

ADVERSE REACTIONSThe following adverse reactions have been associatedwith the administration of Chorionic Gonadotropin forInjection, USP: headache, irritability, restlessness,depression, fatigue, edema, precocious puberty,gynecomastia, pain at the site of injection.

Ovarian cancer has been reported in a very smallnumber of infertile women who have been treated withfertility drugs. A causal relationship has not been estab-lished between treatment with fertility drugs and ovariancancer.

DOSAGE AND ADMINISTRATION

DosageThe dosage regimen used in any particular casedepends upon the indication for use, the age and weightof the patient, and the physician’s preference.

Male:1. Prepubertal Cryptorchidism

(not due to anatomical obstruction)a) 4,000 USP units, three times weekly, for two to

three weeks; orb) 1,000 USP units, three times weekly, for six to

eight weeks.

The dosage schedule may vary to some extentdepending upon the age when treatment is given.If the dose is adequate, there will usually be someindication, following one such course of therapy,whether descent will occur or surgery be required.

A therapeutic trial with Chorionic Gonadotropin forInjection, USP may constitute a valuable diagnosticaid to determine the need for surgery. Lack ofresponse is usually an indication of anatomicobstruction. Furthermore, when surgery is required,this preliminary treatment may facilitate theprocedure by increasing the size of the testes andthe length of the cords. Postoperative gonadotropictherapy has also been suggested to preventretraction of the testes.

2. Delayed Adolescence4,000 to 5,000 USP units three times weekly for six to eight weeks with a rest period of two to threeweeks between courses of therapy.

3. Dwarfism (pituitary)1,000 to 5,000 USP units three times weekly.

4. Hypogonadotropic Eunuchoidism4,000 to 5,000 USP units three times weekly for six to eight weeks with a rest period of two to threeweeks between courses of therapy.

5. Hypogonadism (after sexual maturity)4,000 to 5,000 USP units three times weekly for six to eight weeks with a rest period of two to threeweeks between courses of therapy.

Female:1. Ovulation Induction

(For the gonadotropins dosage, see the prescribinginformation for that drug product.)

5,000 to 10,000 USP units one day following the lastdose of gonadotropins.

2. Abortion (habitual)1,000 to 2,000 USP units, or more, one or moretimes daily combined with other recognizedtherapeutic measures until the danger of abortionhas passed.

3. Infrequent Scanty Bleeding (functional)Oligomenorrhea, amenorrhea (primary andsecondary), and Frohlich’s Syndrome: see dosage for Functional Sterility.

4. Functional Sterility500 to 1,000 USP units Chorionic Gonadotropin forInjection may be given daily from the 15th to the24th day. An alternative schedule is 1,500 USP unitsevery other day, three times in all, on the 16th, 18th,and 20th day of the cycle.

AdministrationChorionic Gonadotropin for Injection is forsubcutaneous or intramuscular use only.

Preparation of Solution: Using a syringe, withdraw the sterile air from the vial containing the lyophilizedChorionic Gonadotropin for Injection and inject it into thediluent vial. Remove up to 10 mL from the diluent vial(see table below) and add to the Chorionic Gonadotropinfor Injection vial; mix gently until reconstitution iscomplete.

Parenteral drug products should be inspected visuallyprior to administration. Do not inject if the reconstitutedproduct contains particulate matter or is discoloured.

Chorionic Gonadotropin for Injection may bereconstituted by adding the required amount of diluent to obtain the desired dosage.

Table of Reconstitution and Administration Volumes

Desired Diluent InjectionDosage Volume Volume(units) Options (mL) (mL)

10,000 10 105 52.5 2.51.0 1.0

5,000 10 55 2.52.5 1.25

4,000 10 45 22.5 1

2,000 10 25 12.5 0.5

1,000 10 15 0.5

STORAGEChorionic Gonadotropin for Injection, USP sterilelyophilized powder should be stored at controlled room temperature (less than 25°C) until the expiry dateindicated on the label. When reconstituted, the solutionshould be kept refrigerated (2 - 8°C) and should be usedwithin 30 days.

Each vial of Chorionic Gonadotropin for Injection,USP contains:Chorionic gonadotropin 10,000 USP units; mannitol 100 mg; sodium phosphate monobasic and sodium

phosphate dibasic for adjustment of pH. In addition,when reconstituted with the diluent provided(Bacteriostatic Water for Injection, USP containing 0.9%benzyl alcohol), each vial contains benzyl alcohol 0.9%.

AVAILABILITY OF DOSAGE FORMSC25021 Each package contains one vial of Chorionic

Gonadotropin for Injection, USP (10,000 USPunits) and one 10 mL multiple-dose vial ofSterile Diluent (Bacteriostatic Water forInjection, USP containing 0.9% benzyl alcohol).

PHARMACEUTICAL PARTNERS OF CANADA INC.Richmond Hill, ON L4B 3P6? 1-877-821-7724