Pharmacy & Therapeutics - June 2008 - (Page 339)

DRUG FORECAST Table 2 Progestin-Related Side Effects • Breast tenderness • Edema • Abdominal cramping • Emotional lability • Depression • Weight gain • Headache • Bloating • Dysmenorrhea • Amenorrhea • Decreased libido • Acne • Insomnia ducted by Brache et al., weight gain occurred in 6.5% of patients using etonogestrel implants and in 7% of patients using levonorgestrel implants.10 A significant number of women in clinical trials also reported weight gain with the use of Depo-Provera, NuvaRing, Mirena, and oral contraceptives.5,6 Psychiatric effects. In clinical trials, psychiatric ADEs, including depression, emotional lability, and anxiety, were reported in 3% to 14% of patients. Emotional lability was the most common ADE with etonogestrel therapy.4,5 These psychiatric ADEs have also been reported in women using Depo-Provera, NuvaRing, Ortho Evra, Mirena, and oral contraceptives.5,6 Emotional lability led to discontinuation of the medication in 1% to 2.5% of women enrolled in clinical trials for NuvaRing and Ortho Evra.5,6 Bleeding irregularities. Irregular bleeding was the most frequently reported ADE and the most common reason for discontinuing treatment of the etonogestrel implant in clinical trials. In a study by Bitzer et al.,12 the most common treatment-emergent ADEs that led to premature removal of the etonogestrel implant were bleeding abnormalities, including amenorrhea; dysmenorrhea; and frequent, prolonged, or infrequent bleeding. No patterns were associated with the incidence of bleeding (any type of bleeding irregularity can occur spontaneously). Discontinuation of therapy generally occurred within the first two years of etonogestrel use. The incidence of bleeding irregularities with Implanon was reported in 45% of patients, and 14% of women discontinued therapy pre maturely. 2 Croxatto et al. 7 reported a higher percentage of patients discontinuing therapy (17.2%) because of bleeding irregularities during the first two years of Implanon use. medications are inducers of CYP 3A4 and increase the metabolism of etonogestrel.3 Anticonvulsants, barbiturates, St. John’s wort, nevirapine (Viramune, Boehringer Ingelheim), and rifampin act as CYP 3A4 inducers to increase hepatic metabolism of this contraceptive.3 The reverse is also true for CYP 3A4 inhibitors, including azole antifungals.3 CYP 3A4 inhibitors decrease the clearance of etonogestrel and increase plasma concentrations, thus raising the likelihood of progestin-related side effects (Table 2).3 Retinoids, such as Roche’s acitretin (Soriatane) and isotretinoin (Accutane), interfere with the contraceptive action of oral progestin regimens.4,5 Thus, two forms of reliable birth control are recommended with the use of a progestin-only contraceptive and retinoids, given the confirmed incidence of birth defects with these products.3,5 Other medications have been linked to a decline in the effectiveness of progestin contraception by an alternate mechanism.3,5 Protease inhibitors, modafinil (Provigil, Cephalon), and mycophenolate mofetil (CellCept, Roche) resulted in a significant decline in the area-underthe-concentration-time curve (AUC) and, consequently, in the etonogestrel plasma concentration (Table 3).3,5 DRUG INTERACTIONS Etonogestrel, a progestin, is a substrate of the CYP 3A4 oxidase system.4–6 CYP 3A4 is involved in the metabolism of the largest quantity of substrates and comprises the largest quantity of all the cytochrome substrates in the liver.3 Many PREGNANCY AND LACTATION Studies have been performed in both rats and rabbits with etonogestrel doses of up to 790 times the human dose with Table 3 Significant Drug Interactions with Implanon Drugs that decrease contraceptive effectiveness • Acitretin (Soriatane)* • Amprenavir (Agenerase) • Carbamazepine (Tegretol) • Darunavir (Prezista) • Felbamate (Felbatol) • Griseofulvin (Fulvicin) • Isotretinoin (Accutane) • Modafinil (Provigil) • Mycophenolate mofetil (CellCept) • Nelfinavir (Viracept)* • Nevirapine (Viramune)* • Oxcarbazepine (Trileptal) • Phenobarbital • Phenytoin (Dilantin) • Primidone (Mysoline) • Rifampin (Rifadin) • St. John’s wort • Topiramate (Topamax) Drugs that increase contraceptive concentrations • Atazanavir (Rayataz) • Fluconazole (Diflucan) • Rosuvastatin (Crestor) * Drugs associated with contraceptive failure. Data from Implanon package insert, 2006.4 continued on page 346 Vol. 33 No. 6 • June 2008 • P&T® 339

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.