ortho-evra and Venous-Thromboembolism

Combined hormonal contraceptives (CHCs) place women at increased risk of venous thromboembolic events (VTEs) and arterial thrombotic events (ATEs), including acute myocardial infarction and ischemic stroke. There is concern that three recent CHC preparations [drospirenone-containing pills (DRSPs), the norelgestromin-containing transdermal patch (NGMN) and the etonogestrel vaginal ring (ETON)] may place women at even higher risk of thrombosis than other older low-dose CHCs with a known safety profile.. All VTEs and all hospitalized ATEs were identified in women, ages 10-55 years, from two integrated health care programs and two state Medicaid programs during the time period covering their new use of DRSP, NGMN, ETON or one of four low-dose estrogen comparator CHCs. The relative risk of thrombotic and thromboembolic outcomes associated with the newer CHCs in relation to the comparators was assessed with Cox proportional hazards regression models adjusting for age, site and year of entry into the study.. The hazards ratio for DRSP in relation to low-dose estrogen comparators among new users was 1.77 (95% confidence interval 1.33-2.35) for VTE and 2.01 (1.06-3.81) for ATE. The increased risk of DRSP was limited to the 10-34-year age group for VTE and the 35-55-year group for ATE. Use of the NGMN patch and ETON vaginal ring was not associated with increased risk of either thromboembolic or thrombotic outcomes.. In new users, DRSP was associated with higher risk of thrombotic events (VTE and ATE) relative to low-dose estrogen comparator CHCs, while the use of the NGMN patch and ETON vaginal ring was not.

Topics: Adolescent; Adult; Androstenes; Arteries; California; Child; Contraceptive Agents, Female; Desogestrel; Drug Combinations; Estrogens; Ethinyl Estradiol; Female; Hospitalization; Humans; Incidence; Middle Aged; Myocardial Infarction; Norgestrel; Proportional Hazards Models; Risk Factors; Stroke; Tennessee; Thromboembolism; Time Factors; Venous Thromboembolism; Washington; Young Adult

To date, 13 studies have provided data on the risk of venous thromboembolism associated with combined oral contraceptives containing drospirenone or the norelgestromin-containing contraceptive patch. The studies varied in their conclusions about whether these methods are associated with higher risks than combined oral contraceptives containing other progestins: the primary reported measures of association (adjusted odds ratios, incidence rate ratios, or hazard ratios) ranged from 0.9 to 3.3. All of the studies had weaknesses in population selection, data validity or completeness, or analysis that may have led to biased or spurious findings. Venous thromboembolism is rare; if the contraceptive methods of interest do confer a higher risk of thromboembolism, only an additional 5-10 per 10,000 users per year would be affected. The important message for patients, clinicians, and policy makers is that the benefits of all contraceptive methods markedly outweigh their risks, primarily because they prevent pregnancy, an inherently hazardous condition. Product labels for hormonal contraceptives should emphasize their substantial health benefits and established safety.

Topics: Androstenes; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Combinations; Drug Labeling; Ethinyl Estradiol; Female; Humans; Norgestrel; Risk Assessment; Venous Thromboembolism

Concern has been raised that the risk of venous thromboembolism (VTE) in users of the ORTHO EVRA patch is higher compared to users of oral contraceptives (OCs).. We identified idiopathic cases of VTE and controls, matched on age and index date, from among women in the United States PharMetrics/IMS and MarketScan databases who were current users of the patch or levonorgestrel-containing OCs with 30 mcg of ethinyl estradiol. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).. The ORs (95% CI) for VTE in users of the patch compared to levonorgestrel-containing OCs were 2.0 (0.9-4.1) and 1.3 (0.8-2.1) in the PharMetrics and MarketScan databases, respectively. ORs (95% CI) restricted to women aged 39 years or younger were 1.4 (0.6-3.0) and 1.2 (0.7-2.0), respectively.. These results provide evidence that the risk of idiopathic VTE in users of the patch is not materially different than that of users of levonorgestrel-containing OCs in women aged 39 years or younger. We cannot rule out some increase in the risk in women aged 40 years or older.

Topics: Adolescent; Adult; Case-Control Studies; Confidence Intervals; Contraceptives, Oral; Databases, Factual; Drug Combinations; Ethinyl Estradiol; Female; Humans; Incidence; Levonorgestrel; Norgestrel; Odds Ratio; Product Surveillance, Postmarketing; United States; Venous Thromboembolism

We extended an earlier study that found a twofold higher risk of venous thromboembolism (VTE) associated with the transdermal contraceptive system relative to norgestimate-containing oral contraceptives (NGM-OC).. This case-control study identified potential cases of VTE, acute myocardial infarction (AMI) and stroke from 24 months of additional health care claims, with adjudication via medical records. Randomly selected controls were matched to cases on age (15-44 years) and characteristics of contraception use. Conditional logistic regression models provided odds ratios (ORs) and 95% confidence intervals (CIs).. The transdermal contraceptive system was associated with a twofold higher risk of VTE (OR 2.0; 95% CI 1.2-3.3) compared with users of NGM-OC. The OR for stroke was 0.6 (95% CI 0.1-3.2) and for AMI 1.2 (95% CI 0.3-4.7).. This extension was consistent with the earlier study, showing a twofold increased risk of VTE associated with use of the transdermal contraceptive system relative to NGM-OC.

Topics: Administration, Cutaneous; Adult; Case-Control Studies; Contraceptives, Oral, Combined; Drug Combinations; Ethinyl Estradiol; Female; Humans; Myocardial Infarction; Norgestrel; Risk Assessment; Stroke; Venous Thromboembolism

Topics: Contraceptive Agents, Female; Drug Combinations; Ethinyl Estradiol; Female; Humans; Norgestrel; Venous Thromboembolism

Recent changes in U.S. Food and Drug Administration (FDA) labeling and news reports of lawsuits resulting in million-dollar settlements understandably may deter gynecologists from prescribing the transdermal contraceptive patch Ortho Evra (Ortho-McNeil Pharmaceutical, Inc., Titusville, NJ). Gynecologists who, with all good intentions, prescribe an FDA-approved drug such as the contraceptive patch potentially could find themselves liable for an adverse drug reaction. Although much of the current focus by plaintiff attorneys and the news media is on the contraceptive patch, no prescription contraceptive method is without medical risks to the patient or legal risks to the prescribing gynecologist. The purpose of this commentary is to provide an overview of the medical-legal controversies and pitfalls in prescribing the contraceptive patch as well as to outline how gynecologists can avert legal liability by providing proper informed consent. Despite FDA labeling changes and ongoing litigation, with proper informed consent, the contraceptive patch still may be the best choice for many patients who prefer the convenience of a weekly patch over a daily oral contraceptive. Also, regardless of the contraceptive option chosen, the principles of providing and documenting proper informed consent in medical records are applicable not only to providing quality care to patients, but also to protecting the legal interests of the prescribing gynecologist. By documenting proper informed consent in medical records, gynecologists should feel more at ease in prescribing the contraceptive method that best fits their individual patients' needs, even in the presence of ongoing litigation.

Topics: Contraceptives, Oral, Combined; Drug Approval; Drug Combinations; Drug Labeling; Ethinyl Estradiol; Gynecology; Humans; Informed Consent; Legislation, Drug; Liability, Legal; Norgestrel; Physicians; United States; Venous Thromboembolism