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to flamable Choriogonadotropin Alfa Class: Gonadotropins and Antigonadotropins ATC Class: G03GA08 VA Class: HS900 Chemical Name: Gonadotropin, chorionic (human α-subunit protein moiety reduced), complex with chorionic gonadotropin (human β-subunit protein moiety reduced) Molecular Formula: C 437 H 682 N 122 O 134 S 13 CAS Number: 177073-44-8 Brands: Ovidrel Overview Side Effects Dosage Professional Interactions More Pregnancy Warnings User Reviews Support Group Q & A Pricing & Coupons Introduction Gonad-stimulating hormone; biosynthetic (recombinant DNA-derived) form of human chorionic gonadotropin (hCG). 1 Slideshow 8 Reasons Why Obesity Needs To Be Tackled Now Uses for Choriogonadotropin Alfa Female Infertility Used in conjunction with other infertility agents (e.g., gonadotropin-releasing hormone agonist, FSH) for induction of final follicular maturation and early luteinization in ovulatory, infertile women during assisted reproductive technology (ART) programs. 1 2 3 6 7 8 9 Use in patients with tubal obstruction only if participating in ART programs. 1 Choriogonadotropin alfa (r-hCG) is equivalent to urinary-derived hCG with regard to number of oocytes recovered, fertilized oocytes or embryos, and live births. 1 2 3 Used in conjunction with follicle-stimulating agent to induce ovulation in anovulatory, infertile women in whom anovulation is functional and not due to primary ovarian failure. 1 4 5 h Choriogonadotropin alfa (r-hCG) is similar to urinary-derived hCG with regard to ovulation rates. 1 h Choriogonadotropin Alfa Dosage and Administration General Should be prescribed only by clinicians experienced in infertility treatment and who are familiar with cautions, precautions, and contraindications associated with such therapy. 1 4 5 Prior to treatment initiation with choriogonadotropin alfa, perform a thorough gynecologic and endocrinologic evaluation; assess pelvic anatomy and rule out early pregnancy, primary ovarian failure (as indicated by increased serum concentrations of FSH and LH and low serum estrogen concentrations), and neoplasms. 1 4 5 6 7 c (See Contraindications under Cautions.) Perform a thorough diagnostic evaluation in patients who demonstrate abnormal uterine bleeding and other signs of endometrial abnormalities. 1 4 (See Contraindications under Cautions.) Evaluate partner s infertility. 1 4 5 6 h When ultrasound assessment and serum estradiol concentrations show sufficient follicular maturation, administer choriogonadotropin alfa 1 day after last dose of follicle-stimulating agent to complete final follicular maturation and induce ovulation. 1 4 5 Withhold further follicle-stimulating therapy and delay or withhold choriogonadotropin alfa if ovaries show an excessive response to treatment with gonadotropins because of increased risk of ovarian hyperstimulation syndrome (OHSS). 1 4 5 6 i j (See Ovarian Hyperstimulation Syndrome under Cautions.) Encourage daily sexual intercourse beginning 1 day prior to administration of choriogonadotropin alfa until ovulation occurs (as determined by rise in basal body temperature, increase in serum progesterone concentrations, and menstruation following shift in basal body temperature). l (See Adequate Patient Evaluation and Monitoring under Cautions.) Examine ovaries by ultrasound for persistent cysts, particularly when attempts at stimulation of ovulation follow immediately after unsuccessful stimulated cycle. 6 9 Administration Sub-Q Administration Administer by sub-Q injection, generally into abdomen using commercially available prefilled syringe; 1 may be self-administered by patient. 1 c Dosage Adults Female Infertility ART Sub-Q 250 mcg, given 1 day following last dose of follicle-stimulating agent. 1 2 3 (See General under Dosage and Administration.) Ovulation Induction Sub-Q 250 mcg, given 1 day following last dose of follicle-stimulating agent. 1 h (See General under Dosage and Administration.) If stimulation of ovulation is unsuccessful, adjust dosage of follicle-stimulating agent administered in subsequent cycles based on woman s response in preceding cycle. 6 9 Prescribing Limits Adults Female Infertility Sub-Q Maximum 500-mcg single dose studied in clinical trials. f Cautions for Choriogonadotropin Alfa Contraindications Known hypersensitivity to human chorionic gonadotropin preparations (including urinary-derived hCG) or any ingredient in formulation. 1 c Primary ovarian failure. 1 c Uncontrolled thyroid or adrenal dysfunction. 1 c Uncontrolled organic intracranial lesions (e.g., pituitary neoplasms). 1 c Abnormal intrauterine or vaginal bleeding of undetermined origin. 1 c Ovarian cysts or enlargement of undetermined origin. 1 c Sex-hormone-dependent neoplasms of reproductive tract and accessory organs. 1 c Pregnancy. 1 c Warnings/Precautions Warnings Ovarian Enlargement Risk of mild to moderate uncomplicated ovarian enlargement; may be accompanied by abdominal distention and/or pain, but generally regresses without treatment within 2 3 weeks. 1 Careful monitoring of ovarian response recommended. 1 If ovaries are abnormally enlarged during controlled ovarian stimulation, withhold choriogonadotropin alfa during current course of therapy to minimize risk of OHSS. 1 4 5 6 j (See Ovarian Hyperstimulation Syndrome under Cautions.) Ovarian Hyperstimulation Syndrome Risk of potentially severe OHSS, characterized by apparent dramatic increase in vascular permeability that may result in rapid accumulation of fluid in peritoneal cavity, thorax, and potentially, pericardium. 1 i j May progress rapidly (within 24 hours to several days). 1 Initial manifestations include severe pelvic pain, nausea, vomiting, and weight gain. 1 i Other symptoms include abdominal pain/distention, diarrhea, severe ovarian enlargement, dyspnea, and oliguria. 1 j Hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events may occur. 1 i j Transient liver function test abnormalities, which may be accompanied by morphologic changes (as detected by liver biopsy), reported. 1 i j Occurs most often after completion of gonadotropin therapy, reaching maximum severity after 7 10 days; usually resolves spontaneously with onset of menses. 1 i Monitor patients for 2 weeks after hCG administration. 1 l OHSS may be more severe and protracted if pregnancy occurs. 1 i If severe OHSS develops, discontinue therapy, hospitalize patient, and consult clinician experienced in management of OHSS or fluid and electrolyte imbalances. 1 i Multiple Births Multiple ovulations resulting in multiple gestations reported in 30.9 or 13.3% of women during ART programs or ovulation induction, respectively. 1 Risk of multiple births correlates with number of embryos transferred. 1 6 Thromboembolism Potential for arterial thromboembolism exists. 1 Fetal/Neonatal Morbidity and Mortality May cause fetal harm; exclude pregnancy before initiating treatment. d Animal studies indicate adverse effects on pregnancy outcomes and/or labor. d (See Contraindications under Cautions.) General Precautions Adequate Patient Evaluation and Monitoring Administer only under supervision of qualified clinicians experienced in fertility disorders and interpretation of indices of ovulation. 1 Monitor follicular development (e.g., using transvaginal ultrasound, serum estradiol concentrations) to correctly identify follicular maturation, determine timing of choriogonadotropin alfa administration, detect ovarian enlargement, and minimize risks of OHSS and multiple gestation. 1 4 5 Obtain clinical confirmation of ovulation from direct and indirect indices of progesterone production, including rise in basal body temperature, an increase in serum progesterone concentrations, and menstruation following shift in basal body temperature. 1 2 6 7 Sonographic evidence of ovulation includes findings of fluid in cul-de-sac, ovarian stigmata, collapsed follicle, and secretory endometrium. 1 Specific Populations Pregnancy Category X. 1 (See Fetal/Neonatal Morbidity and Mortality and also Contraindications under Cautions.) Lactation Not known whether choriogonadotropin alfa is distributed into milk. 1 Use caution. 1 Pediatric Use Safety and efficacy not established. 1 Geriatric Use Safety and efficacy not established. 1 Hepatic Impairment Safety and efficacy not established. 1 Renal Impairment Safety and efficacy not established. 1 Common Adverse Effects ART: Injection site reactions (i.e., pain, bruising), 1 2 3 f abdominal pain, 1 nausea, 1 vomiting, 1 postoperative pain. 1 Ovulation induction: Injection site reactions (i.e., pain, inflammation, bruising, other injection site reaction), 1 h ovarian cysts, 1 ovarian hyperstimulation, 1 h abdominal pain. 1 Interactions for Choriogonadotropin Alfa No formal drug interaction studies to date. 1 Laboratory Tests Test Interaction Comments Radioimmunoassays for gonadotropins Possible cross-reaction with radioimmunoassays for gonadotropins, particularly LH 1 Individual laboratories should establish degree of cross-reactivity with their gonadotropin assay 1 When requesting gonadotropin concentration determinations, inform laboratory of choriogonadotropin alfa therapy 1 Choriogonadotropin Alfa Pharmacokinetics Absorption Bioavailability Following sub-Q administration, absolute bioavailability is 40%. 1 b Peak serum concentrations attained in 12 24 hours; detectable in serum for 10 days. 1 d e h Onset Following midcycle administration, peak stimulation of luteal-phase progesterone production (as indicated by serum progesterone concentrations) occurs in approximately 5 7 days. e h (See Actions.) Duration Following midcycle administration, stimulation of luteal-phase progesterone production persists for approximately 10 days. e h Distribution Extent Median apparent volume of distribution is 21.4 L in women undergoing in vitro fertilization. 1 Elimination Metabolism Urinary-derived hCG extensively metabolized, principally in the liver and kidneys, to active metabolites; urinary-derived choriogonadotropin alfa (r-hCG) exhibits similar pharmacokinetics as hCG. a k Elimination Route Excreted in urine principally as metabolites. a Half-life Biphasic; median terminal half-life is 29.2 hours in women undergoing in vitro fertilization. 1 Special Populations Pharmacokinetics not evaluated in patients with renal or hepatic impairment. 1 Stability Storage Parenteral Injection 2 8 C until dispensed. 1 Once dispensed, refrigerate prefilled syringe at 2 8 C, but may be stored at 25 C for 30 days; protect from light. 1 c Discard unused portion. 1 Actions A recombinant DNA-derived form of hCG prepared from genetically modified mammalian (Chinese hamster ovary) cells. 1 2 An analog of LH; has physicochemical, immunologic, and biologic activities comparable to those of urinary-derived hCG. 1 2 Substitutes for the endogenous LH surge responsible for ovulation and stimulates late maturation of the ovarian follicle, resumption of oocytic meiosis, and initiation of rupture of the preovulatory ovarian follicle. 1 2 3 f Spontaneous midcycle LH surges are inconsistent during controlled ovarian stimulation. g Induces and maintains corpus luteum (as evidenced by increased serum progesterone concentrations). 1 2 3 e f Advice to Patients Importance of informing patient of potential adverse effects (e.g., OHSS, multiple gestation). 1 c Importance of discussing duration of treatment and required monitoring procedures. 1 Importance of patients informing clinician if severe pain or bloating in abdominal or pelvic area, severe upset stomach, vomiting, or weight gain occurs. c Importance of patient informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses. c Importance of women informing their clinician if they plan to breast-feed. c Importance of informing patient of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Choriogonadotropin Alfa Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral Injection, for subcutaneous use only 257.5 mcg/0.515 mL (delivers 250 mcg) Ovidrel (available as a 0.515-mL, disposable prefilled syringe) Serono AHFS DI Essentials. Copyright 2017, Selected Revisions June 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Serono Inc. Ovidrel (choriogonadotropin alfa) injection prescribing information. Randolph, MA; 2004 Jan. 2. European Recombinant Human Chorionic Gonadotropin Study Group. Induction of final follicular maturation and early luteinization in women undergoing induction for assisted reproduction treatment recombinant HCG versus urinary HCG. Hum Reprod . 2000; 15:1446-51. [PubMed 10875887] 3. Driscoll GL, Tyler JP, Hanagan JT et al. A prospective, randomized, controlled, double-blind, double-dummy comparison of recombinant and urinary HCG for inducing oocyte maturation and follicular luteinization in ovarian stimulation. Hum Reprod . 2000; 15:1305-10. [PubMed 10831560] 4. Serono Laboratories Inc. Gonal-F (follitropin alfa) for injection prescribing information. Randolph, MA; 1997 Sep. 5. Organon. Follistim (follitropin beta) for injection prescribing information. West Orange, NJ; 1997 Sep. 6. Practice Committee, American Society of Reproductive Medicine. Induction of ovarian follicle development and ovulation with exogenous gonadotropins. A technical bulletin. Birmingham, AL; 1998. From ASRM website. 7. Institute for Clinical Systems Improvement. Diagnosis and management of infertility. Bloomington, MN; 2000 July. From the ICSI website. 8. Yoshida TM. Infertility update: use of assisted reproductive technology. J Am Pharm Assoc . 1999; 39:65-72. 9. Serono Inc: Personal communication. a. Norman RJ, Buchholz MM, Somogyi AA et al. hCGβ core fragment is a metabolite of hCG: evidence from infusion of recombinant hCG. J Endocrinol . 2000; 164:299-305. [PubMed 10694369] b. Trinchard-Lugan I, Khan A, Porchet HC et al. Pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotropin in healthy male and female volunteers. Reprod Biomed Online . 2002; 4:106-15. c. EMD Serono. Ovidrel (choriogonadotropin alfa) prefilled syringe FAQ s. Rockland, MA; 2007. Available from website. Accessed 2007 Nov 27. d. Serono Inc. Ovidrel (choriogonadotropin alfa) injection prescribing information. Rockland MA; 2006 Jul. e. Beckers NGM, Macklon NS, Eijkemans MJ et al. Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment. J Clin Endocrinol Metab . 2003; 88:4186-92. [PubMed 12970285] f. Chan CCW, Ng EHY, Tang OS et al. A prospective, randomized, double-blind study to compare two doses of recombinant human chorionic gonadotropin in inducing final oocyte maturity and the hormonal profile during the luteal phase. J Clin Endocrinol Metab . 2005; 90:3933-8. [PubMed 15870129] g. European Recombinant LH Study Group. Recombinant human leuteinizing hormone is as effective as, but safer than, urinary human choriogonadotropin in inducing final follicular maturation and ovulation in in vitro fertilization procedures: results of a multicenter double-blind study. J Clin Endocrinol Metab . 2001; 86:2607-18. [PubMed 11397861] h. International Recombinant Human Chorionic Gonadotropin Study Group. Induction of ovulation in World Health Organization group II anovulatory women undergoing follicular stimulation with recombinant human follicle-stimulating hormone: a comparison of recombinant human chorionic gonadotropin (rHCG) and urinary HCG. Fertil Steril . 2001; 75:1111-8. [PubMed 11384635] i. Practice Committee, American Society of Reproductive Medicine. Ovarian hyperstimulation syndrome. An educational bulletin. Fertil Steril . 2006; 86:S178-83. [PubMed 17055817] j. Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update . 2002; 8:559-77. [PubMed 12498425] k. Stenman U, Tiitinen A, Alfthan H et al. The classification, functions and clinical use of different isoforms of HCG. Hum Reprod Update . 2006; 12:769-84. [PubMed 16877746] l. EMD Serono Laboratories Inc. Gonal-F (follitropin alfa) for injection prescribing information. Randolph, MA; 2005 Aug. m. AHFS Drug Information. McEvoy GK, ed. Choriogonadotropin Alfa. Bethesda, MD: American Society of Health-System Pharmacists. Next Interactions Print this page Add to My Med List More about chorionic gonadotropin (hcg) Side Effects During Pregnancy Dosage Information Drug Interactions Support Group Pricing & Coupons En Español 15 Reviews Add your own review/rating Drug class: gonadotropins Consumer resources Human chorionic gonadotropin (HCG) injectable ... +3 more Professional resources Gonadotropin, Chorionic (AHFS Monograph) Chorionic Gonadotropin (FDA) Chorionic Gonadotropin (Human) (Wolters Kluwer) Chorionic Gonadotropin (Recombinant) (Wolters Kluwer) Human Chorionic Gonadotropin (Advanced Reading) Other brands: Pregnyl , Ovidrel , Novarel Related treatment guides Obesity Female Infertility Hypogonadism, Male Ovulation Induction Prepubertal Cryptorchidism} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only X Pregnancy Category Not for use in pregnancy N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturer Fresenius Kabi USA, LLC Drug Class Gonadotropins Related Drugs Hypogonadism, Male testosterone , AndroGel , Depo-Testosterone , Axiron , Androderm , Testim , More... Ovulation Induction Clomid , clomiphene , HCG , Menopur , Pregnyl , Ovidrel , More... Female Infertility Clomid , clomiphene , HCG , Menopur , Pregnyl , Ovidrel , More... Prepubertal Cryptorchidism HCG , Pregnyl , Ovidrel , chorionic gonadotropin (hcg) , Novarel , Chorex , More... Chorionic gonadotropin (hcg) Rating 15 User Reviews 6.9 /10 15 User Reviews 6.9 Rate it!} } a fairly large


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