Pharmacy & Therapeutics - June 2008 - (Page 337)

DRUG FORECAST Etonogestrel (Implanon), Another Treatment Option for Contraception Dionne D. Maddox, PharmD, and Zahra Rahman, PharmD INTRODUCTION Consequences related to unintended pregnancies have both social and economic repercussions.1 The Centers for Disease Control and Prevention (CDC) reports that almost 850,000 legal abortions were performed in the U.S. in 2003, or about 241 abortions per 1,000 live births.2 This number does not reflect the procedures that took place in West Virginia, California, and New Hampshire, which did not report any data, or the unplanned pregnancies of mothers who decided to keep their babies.2 Contraceptives, therefore, still represent an area of pharmacotherapy in which improvements are needed. Several dosage forms of contraception are currently available for women in the U.S.; these include oral, injectable, and transdermal products; vaginal rings; and intrauterine devices (IUDs).3 One of the newest medications in the hormonal contraceptive class is an etonogestrel implant (Implanon, Organon).4 A single rod is placed in the upper arm and is replaced every three years. This implant offers women another option for preventing unplanned pregnancies.4–6 estin desogestrel,4–6 binds with high affinity to progesterone receptors in the target organs.4,5 Its contraceptive effect is accomplished by several mechanisms.4–6 Primarily, etonogestrel inhibits fertility by inhibiting the release of luteinizing hormone (LH), one of the reproductive hormones important in ovulation.4–6 It also increases the viscosity of cervical mucus, which hinders the passage of spermatozoa and alters the lining of the uterus to prevent implantation of a fertilized egg into the endometrium.4–6 Etonogestrel is a structural analogue of 19-nortestosterone, and its molecular weight is 324.6.4 The chemical formula for etonogestrel is C22H28O2 (Figure 1). P450 3A4 (CYP 3A4) isoenzymes.3–5 For the most par t, etonogestrel and its metabolites are excreted renally.4,5 The elimination half-life of etonogestrel is 25 hours; therefore, the contraceptive effects are reversible after the subdermal implant is removed.4,5 All clinical trials that were conducted in the U.S. enrolled women who were between 80% and 130% of their ideal body weight.4,7,8 Therefore, the implant’s pharmacokinetics in women above 130% of their ideal body weight has not been established.4–6 Theoretically, the implant might be less effective in overweight women, because body weight and serum concentrations are inversely related.4,5 PHARMACOKINETICS After Implanon is inserted subdermally, etonogestrel is rapidly absorbed into the circulation and becomes almost 100% bioavailable.4,5 During the initial six weeks, the rate of release is 60 to 70 mcg/day, gradually decreasing to a release rate of 35 to 45 mcg/day at the end of the first year.4,5 At the end of the second year, the release rate decreases to 30 to 40 mcg/day. By the end of the third year, the rate falls to about 25 to 30 mcg/ day.4,5 Etonogestrel is highly protein bound to serum proteins, predominantly albumin and, to a lesser extent, sex hormone– binding globulin.4,5 It undergoes extensive liver metabolism by cytochrome CLINICAL TRIALS Croxatto et al.7 An open-label, multicenter study was conducted to assess Implanon’s efficacy, safety, and ability to restore fertility. A total of 635 healthy women were followed for two to three years between 1991 and 1997 at 21 sites in nine countries. Of the initial patients, 147 from the largest two sites consented to the extended study of three years. To be included in the trial, patients had to be 18 to 40 years old and sexually active. They also had to satisfy recommendations for progestin-only contraceptives and have normal menstrual cycles. Subjects were excluded if they were CHEMISTRY AND PHARMACOLOGY Etonogestrel, a synthetic biologically active metabolite of the synthetic progDisclosure: The authors have no financial or commercial relationships to disclose with regard to this article. At the time of this writing , both authors were Managed Care Pharmacy Practice Residents at Kaiser Permanente in Atlanta, Georgia. Dr. Maddox is currently the Drug Informatics and Drug Information Specialist at Kaiser Permanente in Atlanta. Dr. Rahman is a Solid Organ Transplant Pharmacist with the University of Alabama at Birmingham. Drug Forecast is a regular column coordinated by Alan Caspi, PhD, PharmD, MBA, President of Caspi & Associates in New York, New York. HO H2C C CH O C22H28O2 Figure 1 Chemical structure of etonogestrel. (Data from Implanon package insert, 2006.4) Vol. 33 No. 6 • June 2008 • P&T® 337

Table of Contents Feed for the Digital Edition of Pharmacy & Therapeutics - June 2008

Editorial Aliskiren Reduces Plasma Renin Activity Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Challenges in Evaluating and Standardizing Medical Devices in Health Care Facilities California e-Pedigree Rules Pose Challenges For Pharmacies Pharmaceutical Approval Update American Psychiatric Association At a Glance: Dermatology Trends in Managed Care

Pharmacy & Therapeutics - June 2008

For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.