PREGNYL- choriogonadotropin alfa   
Organon USA Inc.

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Pregnyl®
(chorionic gonadotropin for injection USP)

DESCRIPTION

Human chorionic gonadotropin (HCG), a polypeptide hormone produced by the human placenta, is composed of an alpha and a beta subunit. The alpha sub-unit is essentially identical to the alpha subunits of the human pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as to the alpha subunit of human thyroid-stimulating hormone (TSH). The beta subunits of these hormones differ in amino acid sequence.

PREGNYL® (chorionic gonadotropin for injection USP) is a highly purified pyrogen-free preparation obtained from the urine of pregnant females. It is standardized by a biological assay procedure. It is available for intramuscular injection in multiple dose vials containing 10,000 USP units of sterile dried powder with 5 mg monobasic sodium phosphate and 4.4 mg dibasic sodium phosphate. If required, pH is adjusted with sodium hydroxide and/or phosphoric acid. Each package also contains a 10-mL vial of solvent containing: water for injection with 0.56% sodium chloride and 0.9% BENZYL ALCOHOL, WHICH IS NOT FOR USE IN NEWBORNS. If required, pH is adjusted with sodium hydroxide and/or hydrochloric acid.

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 anatomical obstruction. In general, HCG is thought to induce testicular descent in situations when descent would have occurred at puberty. HCG thus may help 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 in children 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.

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.

Anaphylaxis has been reported with urinary-derived HCG products.

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) rupture of ovarian cysts with resultant hemoperitoneum, (3) multiple births, and (4) arterial thromboembolism.

PRECAUTIONS

General

Since androgens may cause fluid retention, HCG should be used with caution in patients with cardiac or renal disease, epilepsy, migraine, or asthma.

Pediatric Use

Induction of androgen secretion by HCG may induce precocious puberty in pediatric patients treated for cryptorchidism. Therapy should be discontinued if signs of precocious puberty occur.

Geriatric Use

Clinical studies of PREGNYL® (chorionic gonadotropin for injection USP) did not include subjects aged 65 and over.

ADVERSE REACTIONS

Headache, irritability, restlessness, depression, fatigue, edema, precocious puberty, gynecomastia, pain at the site of injection.

Hypersensitivity reactions, both localized and systemic in nature, have been reported.

DOSAGE AND ADMINISTRATION

For intramuscular use only. The dosage regimen employed in any particular case will depend upon the indication for the 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. Therapy is usually instituted in children between the ages of 4 and 9.

  1. 4000 USP units 3 times weekly for 3 weeks.
  2. 5000 USP units every second day for 4 injections.
  3. 15 injections for 500 to 1000 USP units over a period of 6 weeks.
  4. 500 USP units 3 times weekly for 4 to 6 weeks. If this course of treatment is not successful, another series is begun 1 month later, giving 1000 USP units per injection.

Selected cases of hypogonadotropic hypogonadism in males.

  1. 500 to 1000 USP units 3 times a week for 3 weeks, followed by the same dose twice a week for 3 weeks.
  2. 4000 USP units 3 times weekly for 6 to 9 months, following which the dosage may be reduced to 2000 USP units 3 times weekly for an additional 3 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 pretreated with human menotropins.

(See prescribing information for menotropins for dosage and administration for that drug product.)

5000 to 10,000 USP units 1 day following the last dose of menotropins. (A dosage of 10,000 USP units is recommended in the labeling for menotropins.)

Directions for Reconstitution

Two-vial package: Withdraw sterile air from lyophilized vial and inject into diluent vial. Remove 1–10 mL from diluent and add to lyophilized vial; agitate gently until powder is completely dissolved in solution.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

IMPORTANT: USE COMPLETELY AFTER RECONSTITUTION. RECONSTITUTED SOLUTION IS STABLE FOR 60 DAYS WHEN REFRIGERATED.

HOW SUPPLIED

Two-vial package containing:

1-10 mL lyophilized multiple dose vial containing: 10,000 USP units chorionic gonadotropin per vial, NDC 0052-0315-10.

1-10 mL vial of solvent containing: water for injection with sodium chloride 0.56% and benzyl alcohol 0.9%, NDC 0052-0325-10.

When reconstituted, each 10 mL vial contains:

Chorionic gonadotropin10,000 USP units
Monobasic sodium phosphate5 mg
Dibasic sodium phosphate4.4 mg
Sodium chloride0.56%
Benzyl alcohol0.9%

If required pH adjusted with sodium hydroxide and/or phosphoric acid.

Storage

Store at controlled room temperature 15–30°C (59–86°F). Reconstituted solution is stable for 60 days when refrigerated.

Manufactured for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

Manufactured by: Baxter Pharmaceutical Solutions LLC, Bloomington, IN 47403, USA

For patent information: www.merck.com/product/patent/home.html

Copyright © 1976, 2011 Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc.
All rights reserved.

Revised: 12/2013
uspi-mk8829-pwi-1312-r006

Rx only

PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton

NDC 0052-0315-10

10-mL multidose vial
with 10-mL vial of solvent

Pregnyl®
(chorionic gonadotropin
for injection USP)

10,000
USP Units/vial

For Intramuscular
Injection Only

Rx only

PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton
PREGNYL 
choriogonadotropin alfa kit
Product Information
Product TypeHUMAN PRESCRIPTION DRUG LABELItem Code (Source)NDC:0052-0315
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:0052-0315-101 in 1 CARTON
Quantity of Parts
Part #Package QuantityTotal Product Quantity
Part 11 VIAL, MULTI-DOSE 10 mL
Part 21 VIAL 10 mL
Part 1 of 2
PREGNYL 
choriogonadotropin alfa injection, powder, lyophilized, for solution
Product Information
Route of AdministrationINTRAMUSCULARDEA Schedule    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
CHORIOGONADOTROPIN ALFA (CHORIOGONADOTROPIN ALFA) CHORIOGONADOTROPIN ALFA10000 [USP'U]  in 10 mL
Inactive Ingredients
Ingredient NameStrength
SODIUM PHOSPHATE, MONOBASIC 
SODIUM PHOSPHATE, DIBASIC 
SODIUM HYDROXIDE 
PHOSPHORIC ACID 
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
110 mL in 1 VIAL, MULTI-DOSE
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA01769210/20/1976
Part 2 of 2
PREGNYL SOLVENT 
water, sodium chloride and benzyl alcohol injection, solution
Product Information
Route of AdministrationINTRAMUSCULARDEA Schedule    
Inactive Ingredients
Ingredient NameStrength
WATER 
SODIUM CHLORIDE 
BENZYL ALCOHOL 
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
110 mL in 1 VIAL
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA01769210/20/1976
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA01769210/20/1976
Labeler - Organon USA Inc. (078796541)
Establishment
NameAddressID/FEIBusiness Operations
Aspen Oss B.V.491013870API MANUFACTURE(0052-0315)
Establishment
NameAddressID/FEIBusiness Operations
BAXTER PHARMACEUTICAL SOLUTIONS, LLC604719430MANUFACTURE(0052-0315)
Establishment
NameAddressID/FEIBusiness Operations
Aspen Oss B.V.491017488API MANUFACTURE(0052-0315)
Establishment
NameAddressID/FEIBusiness Operations
Merck Sharp & Dohme Corp.101740835PACK(0052-0315)

Revised: 12/2013
Document Id: 3dab7afd-ea38-46bb-9c0d-f0af687f6e9d
Set id: 3e26b843-9c7a-4517-a1b6-9362aab0b86c
Version: 9
Effective Time: 20131217
 
Organon USA Inc.