Norelgestromin/ Ethinyl Estradiol (Ortho Evra)

Author: Ali J. Olyaei, PharmD, BCPS

Introduction
The population of developing countries is growing at a rate of 1.9%, compared with a rate of 0.7% per year in the United States. In this country, 1 of 10 women aged 15 to 19 becomes pregnant annually. Periodic abstinence is an effective method to prevent unintended pregnancy, but only if it is used consistently and correctly. Hormonal manipulation is also an effective method of preventing pregnancy. First-generation oral contraceptives were introduced to the US market in early 1970. At that time, the original oral contraceptive agents were associated with significant side effects and complications. In 1988, the FDA recommended the withdrawal of all oral contraceptives with mestranol 50 mcg. Today, in the United States, most oral contraceptives contain a mixture of low-dose estrogen and/or progestin. The FDA recently approved the norelgestromin/ethinyl estradiol (EE) transdermal system (Ortho Evra, Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) for birth control. Ortho Evra is the first transdermal patch approved for birth control. (1)

Mechanism of Action
Although the mechanisms of action of combination contraceptives are not completely understood, these agents are believed to inhibit gonadotropins. Combination contraceptives suppress ovulation, alter cervical mucus, and potentially decrease implantation of sperm. Following application of the transdermal patch, a therapeutic plasma concentration is achieved after 48 hours. The rates of absorption for EE and norelgestromin are equivalent following application to the abdomen, arm, or buttock. Activities such as exercise or using a sauna or whirlpool do not change the rate and extent of absorption, compared with normal wear. If the transdermal system is removed for more than 1 day, a new 4-week cycle of the transdermal system is recommended. (1,2)

Trial Highlights
The efficacy and safety of Ortho Evra were assessed in three major clinical trials involving 3,330 women (aged 18 to 45). These women were randomized to receive either the Ortho Evra transdermal patch or birth control pills. A total of 22,155 cycles were completed. Similar to the birth control pill, Ortho Evra was effective in preventing pregnancy. The pregnancy rate was 1% in the Ortho Evra group. However, subgroup analysis demonstrated a higher rate of pregnancy among overweight women (>198 lb). (2,3)

Adverse Reactions
Skin irritation was the most common side effect reported in the Ortho Evra group, compared with the oral combined-contraceptive group. However, only 2% of patients withdrew from the study because of this complication. In 5% of the women, the transdermal system did not stay attached to the skin for at least 1 application. As with other combination contraceptives, cigarette smoking may significantly increase the risk of cardiovascular complications (myocardial infarction, thromboem-bolism, and stroke) that are possible from Ortho Evra. Combination contraceptives also substantially increase the influence that hypertension, hyperlip-idemia, age, and obesity have as cardiovascular risk factors. Finally, some epi-demiologic studies suggest that there is an increased risk of breast cancer, hepatic neoplasia, and carcinoma of the reproductive system similar to that from other combination oral contraceptives. (4-6)

Dosing
Ortho Evra is available in folding cartons containing 1 patch with a once-weekly dosing schedule. Studies in women have revealed many clinically significant interactions with other drugs metabolized by the liver, including some antibiotics, antifun-gals, and anticonvulsants. (2)

Outlook
Ortho Evra is the first transdermal system approved for birth control in the United States. Once-weekly application may improve overall compliance and provide longer-acting birth control.

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