Pharmacy & Therapeutics - June 2008 - (Page 338)

DRUG FORECAST pregnant or lactating, if their weight was outside 80% to 130% of the ideal, or if they were using any liver enzyme inducers (e.g., anticonvulsants). Before insertion of the implant, the investigators obtained a baseline medical and gynecological history, conducted a pelvic examination, and obtained a Papanicolaou (Pap) smear. Weight, blood pressure, implant site, and adverse effects were assessed every three months over the entire study period. Medical physical examinations and Pap smears were performed yearly. The primar y efficacy endpoint was pregnancy. No pregnancies were re corded in any of the study participants over the three-year period. Upon removal of the implant, normal menses resumed within 90 days for approximately 91% of subjects. Fertility returned quickly, with 20 pregnancies reported within three months of implant removal. Zheng et al.9 Table 1 Common Treatment-EmerAn open-label, comparative, randomized, multicenter study gent Adverse Drug Events in 1% or was performed to compare the More Subjects in Clinical Trials of efficacy, tolerability, and bleeding Etonogestrel (Implanon) patterns in Implanon versus Norplant (Wyeth), which contains levAll Studies onorgestrel, a progestin. During Adverse Drug Event (N = 942) the course of the study, from 1991 Bleeding irregularities 11.0% to 1996, 200 women were ob• Amenorrhea served for two years with an op• Prolonged bleeding tional extension to four years. • Frequent bleeding To be eligible for inclusion in • Infrequent bleeding the study, the women had to be Emotional lability 2.3% healthy, 20 to 25 years of age, and Weight gain 2.3% sexually active with proven fertilHeadache 24.9% ity and with menstrual cycles of 24 Acne 1.3% to 35 days’ duration. Patients were Depression 1.0% excluded if they were pregnant, were breast-feeding, or had taken Data from Implanon package insert, 2006.4 oral or hormonal contraceptives within a specified period before the start of the study. Before the study of patients reported a decrease, and 70% began, each patient underwent a pregreported no change.8 A higher incidence nancy test, a urine glucose determinaof acne, occurring in 18.5% of patients, tion, and a gynecological examination. was reported in Brache’s three-year comThe implant site, blood pressure, body parative trial of etonogestrel and levoweight, and hemoglobin levels were asnorgestrel implants.10 sessed every 90 days. A physical examiHeadache. Headache was the most nation and a Pap smear were performed frequently reported ADE among women at the end of the study. using implantable contraceptives.4 In the The effectiveness of the contraceptives Flores study, headache was reported in was based on the number of pregnan25% of the patients receiving etonogestrel cies reported during the study. No pregimplants.11 Similarly, other clinical trials nancies were reported in either treat- reported an incidence of headache in ment group, and no statistically sig- 24.9% of patients who received the etononificant difference existed between the gestrel implant.4 groups in terms of the contraceptive’s Headaches were also reported in more efficacy or tolerability. However, it took than 5% of women in clinical trials of slightly less time to insert and remove injectable Depo-Provera (medroxyproImplanon than Norplant. gesterone acetate, Pfizer), the NuvaRing vaginal ring (etonogestrel/ethinyl estraADVERSE DRUG EVENTS diol, Organon), Ortho Evra patch (norelgestromin/ethinyl estradiol, OrthoEtonogestrel was generally well tolerated in clinical trials.4 The most frequent McNeil), and the Mirena IUD (levonorgestrel, Bayer).5,6 A causative associadverse drug events (ADEs) reported in the trials were acne, headache, weight ation between headaches and the use of gain, emotional lability, depression, and oral contraceptives has not been conbleeding irregularities (Table 1). Most of firmed, but the incidence is higher in the ADEs were mild to moderate.4 women taking progestin-only formulaDermatological problems. Acne is tions.5,6 a side effect that is associated with the Weight gain. Most long-term contraandrogenic effects of progestins. In clinceptive use leads to some degree of ical trials, the incidence of new-onset weight gain.4,6 In clinical trials, increased acne was reported in 13.5% of patients, weight was reported in 13.7% of women with 1.3% of patients reporting treatmentreceiving the etonogestrel implant, with emergent acne.4 Similar reports of acne 2.3% of patients reporting weight gain as the reason for implant removal.4 were reported by Funk et al., with an incidence of new-onset acne of 14.5%; 16% In a three-year comparative trial con- Funk et al.8 In another open-label, multicenter study, the investigators observed women for up to two years between 1993 and 1996. The study included 330 sexually active women 18 to 40 years of age who resided in the U.S. These participants also had normal menses and a body weight between 80% and 130% of ideal. Subjects were excluded from the study if they had hey had an abnormal Pap smear, liver function abnormalities, or hypertension; if they had used hormonal contraception or had been pregnant within the previous month; or if any of the women 35 years of age and older had a history of smoking. After insertion of the implant, participants visited the clinic every three months. Physical and gynecological examinations were performed at 12 and 24 months. Efficacy and safety assessments were based on pregnancy rates, medical examinations, and vital signs. The investigators also assessed the return of the menstrual cycle and fertility upon removal of the implant. None of the women became pregnant while the implant was in place. After removal of the implant, normal menstrual cycles resumed in 88% of patients within three months. After treatment, 11 pregnancies were documented between 7 and 131 days after implant removal. 338 P&T® • June 2008 • Vol. 33 No. 6

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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

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