Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data.

OBJECTIVE: To present efficacy and cycle control data pooled from three pivotal studies of the contraceptive patch (Ortho Evra/Evra). DESIGN: Three multicenter, open-label, contraceptive studies that included up to 13 treatment cycles. SETTING: 183 centers. PATIENT(S): 3,319 women. INTERVENTION(S): Three consecutive 7-day patches (21 days) with 1 patch-free week per cycle. MAIN OUTCOME MEASURE(S): Contraceptive efficacy and cycle control. RESULT(S): Overall and method failure life-table estimates of contraceptive failure through 13 cycles were 0.8% (95% CI, 0.3%-1.3%) and 0.6% (95% CI, 0.2%-0.9%), respectively. Corresponding Pearl indices were 0.88 (95% CI, 0.44-1.33) and 0.7 (95% CI, 0.31-1.10). Contraceptive failure among women with a body weight < 90 kg (<198 lb) was low and uniformly distributed across the weight range. A subgroup of women with body weight > or = 90 kg (> or = 198 lb) may have increased risk of pregnancy. The incidence of breakthrough bleeding was low and decreased over time. CONCLUSION(S): In contraceptive patch users, the overall annual probability of pregnancy was 0.8% and the method failure probability was 0.6%. The efficacy of the patch was high and similar across age and racial groups. Among women < 90 kg (<198 lb), contraceptive failure was low and uniformly distributed across the range of body weights. In women > or = 90 kg (> or = 198 lb), contraceptive failures may be increased. Efficacy and cycle control have been shown to be comparable to an established oral contraceptive.

Integrated summary of Ortho Evra/Evra contraceptive patch adhesion in varied climates and conditions.

OBJECTIVE: To assess the adhesive reliability of the contraceptive patch (Ortho Evra/Evra). DESIGN: Pooled data of 3,319 women from three contraceptive studies of up to 13 treatment cycles; a subset of 325 women of the pooled data from warm and humid climates; and 30 women from a three-period, crossover exercise study. SETTING: 184 centers. PATIENT(S): 3,349 healthy women. INTERVENTION(S): In the contraceptive studies, each treatment cycle consisted of three consecutive 7-day patches (21 days) followed by one patch-free week. During each treatment period in the exercise study, women wore the patch for 7 days and participated in one of six activities (normal activity, excluding bathing; sauna; whirlpool; treadmill; cool-water immersion; or a combination of activities) each day at a supervised health center. MAIN OUTCOME MEASURE(S): Patch adhesion. RESULT(S): In the contraceptive studies, 4.7% of patches were replaced because they fell off (1.8% [1,297 of 70,552 patches]) or became partly detached (2.9% [2,050 of 70,552 patches]); patch replacement rates in centers from a warm, humid climate were 1.7% (85 of 4,877 patches) and 2.6% (128 of 4,877 patches), respectively. Only one of 87 patches (1.1%) completely detached in the exercise study. CONCLUSION(S): The reliability of adhesion of the contraceptive patch is excellent and consistent across all studies; only 1.8% and 2.9% of patches required replacement due to complete or partial detachment, respectively. Heat, humidity, and exercise do not affect adhesion.

Ortho Evra/Evra versus oral contraceptives: follicular development and ovulation in normal cycles and after an intentional dosing error.

OBJECTIVE: To compare the effects of the contraceptive patch to oral contraceptives (OCs) on follicular size and incidence of ovulation in normal cycles and after dosing errors. DESIGN: Randomized, open-label. SETTING: Twelve centers. PATIENT(S): One hundred twenty-four ovulatory women. INTERVENTION(S): Subjects received either the patch (groups 1 and 2) or one of three OCs. Correct dosing occurred in cycles 1, 2, 3, and 5. The following dosing errors were planned during cycle 4, a shortened 10-day cycle: [1] patch group 1 subjects wore one patch for 10 consecutive days; [2] for patch group 2 and OC subjects, 7 dosing days were followed by 3 drug-free days. MAIN OUTCOME MEASURE(S): Follicular size, as determined at each cycle by the maximum mean follicular diameter. RESULT(S): After a 3-day dosing error, follicular size was significantly smaller in the patch group (mean, 7.0 mm) vs. each OC group (range of means, 11.8-17.1 mm). Similar results were seen after proper dosing. The incidence of ovulation was significantly lower for the patch users than for women using OCs. CONCLUSION(S): Follicular size and incidence of ovulation were significantly reduced among contraceptive patch users compared with women using OCs in normal cycles and after planned dosing errors.

A comparative and pooled analysis of the safety and tolerability of the contraceptive patch (Ortho Evra/Evra).

OBJECTIVE: To review the safety and tolerability of the contraceptive patch (Ortho Evra/Evra) versus a standard oral contraceptive (Triphasil) and to present the pooled safety and tolerability of the patch across three pivotal studies. DESIGN: Three open-label, contraceptive studies of up to 13 treatment cycles. SETTING: 183 centers. PATIENT(S): Comparative study (812 patch, 605 oral contraceptive); pooled analysis (3,330 patch). INTERVENTION(S): The patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle; the oral contraceptive was dosed according to the U.S. physician package insert. MAIN OUTCOME MEASURE(S): Adverse events, laboratory tests, vital signs, and body weight. RESULT(S): The incidence of most events was similar between the patch and oral contraceptive groups, with the exception of a higher incidence of application site reactions, breast discomfort (cycles 1 and 2 only), and dysmenorrhea in the patch group. Pooled analysis demonstrated that most application site reactions (92%) and breast symptoms (86%) were mild or moderate in severity, and <2% of participants discontinued the patch because of either event. Only 7 (0.2%) participants experienced a serious adverse event classified as possibly, probably, or likely related to the patch. The mean change in body weight from baseline to the end of treatment was an increase of 0.3 kg. CONCLUSION(S): Overall, the contraceptive patch is well tolerated and has a side effect profile similar to an established oral contraceptive.

Assessment of compliance with a weekly contraceptive patch (Ortho Evra/Evra) among North American women.

OBJECTIVE: To determine compliance with the contraceptive patch (Ortho Evra/Evra) overall and by age among women in North America and to compare rates of perfect use with those of an established oral contraceptive. DESIGN: Data were pooled for three contraceptive studies in which women participated for up to 13 cycles; the subset of centers in North America was used in this analysis. SETTING: 76 North American centers. PATIENT(S): Healthy women 18-45 years of age. INTERVENTION(S): In all studies, the patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle. MAIN OUTCOME MEASURE(S): Perfect use for the patch or oral contraceptive, defined as 21 consecutive days of drug-taking followed by a 7-day drug-free period; for contraceptive patch users, no patch could be worn for more than 7 days. Oral contraceptives were used according to package labeling. RESULTS: For all contraceptive patch users in North America (n = 1,785), perfect use was consistent across age groups. The percentage of cycles with perfect use of the patch ranged within age groups from 88.1% to 91.0%. In the comparative study conducted only in North America, perfect use was also consistent across age groups for the patch (n = 812), but rates of perfect use for the oral contraceptive (n = 605) differed significantly by age. CONCLUSION(S): Age did not affect compliance with the patch among all North American women studied. In a comparative study of women at North American centers, compliance with the weekly contraceptive patch was significantly better than with an established oral contraceptive. The contraceptive patch is uniformly easy to use across all ages.

Transdermal contraceptive patch delivering norelgestromin and ethinyl estradiol. Effects on the lipid profile.

OBJECTIVE: To evaluate the metabolic impact on lipids of a contraceptive patch that delivers norelgestromin (primary active metabolite of norgestimate) and ethinyl estradiol to the systemic circulation as compared with a placebo patch. STUDY DESIGN: In this randomized, double-blind trial, healthy women received the contraceptive patch (n = 99) or placebo patch (n = 47) for up to 9 cycles. Fasting blood samples were obtained at baseline and cycles 3, 6 and 9 for determining the serum lipid profile. RESULTS: At cycles 3, 6 and 9, mean increases from baseline in high-density lipoprotein (HDL) cholesterol, HDL3 cholesterol, total cholesterol and total triglycerides, and mean decreases in calculated (Friedewald) low-density lipoprotein (LDL)/HDL were observed in the contraceptive patch group (all P < .05 vs. placebo except for total cholesterol at cycle 6). Mean changes in HDL2 and calculated LDL cholesterol were minimal and comparable between treatments. Mean body weight increased from baseline to the end of treatment by 0.8 and 0.6 kg in the 2 groups, respectively; this difference was not significant. CONCLUSION: The lipid changes seen with the contraceptive patch are consistent with those of oral contraceptives containing norgestimate and ethinyl estradiol.

Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial.

OBJECTIVE: To assess the efficacy and safety of an oral formulation of tranexamic acid for the treatment of heavy menstrual bleeding. METHODS: Adult women with heavy menstrual bleeding (mean menstrual blood loss 80 mL or more per cycle) were enrolled in a double-blind, placebo-controlled study. After two pretreatment menstrual cycles, women were randomized to receive tranexamic acid 3.9 g/d or placebo for up to 5 days per menstrual cycle through six cycles. To meet the prespecified three-component primary efficacy end point, mean reduction in menstrual blood loss from baseline with tranexamic acid treatment needed to be 1) significantly greater than placebo, 2) greater than 50 mL, and 3) greater than a predetermined meaningful threshold (36 mL or higher). Health-related quality of life was measured using a validated patient-reported outcome instrument. RESULTS: Women who received tranexamic acid (n=115) met all three primary efficacy end points: first, a significantly greater reduction in menstrual blood loss of -69.6 mL (40.4%) compared with -12.6 mL (8.2%) in the 72 women who received placebo (P<.001); reduction of menstrual blood loss exceeding a prespecified 50 mL; and last, reduction of menstrual blood loss considered meaningful to women. Compared with women receiving placebo, women treated with tranexamic acid experienced significant improvements in limitations in social or leisure and physical activities, work inside and outside the home, and self-perceived menstrual blood loss (P<.01). The majority of adverse events were mild to moderate in severity, and the incidence of gastrointestinal adverse events was comparable with placebo. CONCLUSION: In this study, a new oral tranexamic acid treatment was well tolerated and significantly improved both menstrual blood loss and health-related quality of life in women with heavy menstrual bleeding. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00386308. LEVEL OF EVIDENCE: I.