Norelgestromin/Ethinyl Estradiol Transdermal System—Ortho Evra—Ortho Pharmaceuticals
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
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The FDA has approved the first hormonal contraceptive skin patch. Ortho-McNeil’s Ortho Evra patch is a small (one-and-three-quarter-inch square) patch that delivers ethinyl estradiol and norelgestromin transdermally. The patch is worn for 1 week, then replaced. Similar to oral contraceptives, the patch is used for 3 weeks, then left off for the fourth week each month. Although the patch was developed by Ortho-McNeil, it will be marketed by RW Johnson.
Indications
The norelgestromin/ethinyl estradiol (NGMN/EE) transdermal system is indicated for the prevention of pregnancy.
Dosage
The patch is applied each week for 3 weeks. The fourth week is patch free. Every new patch should be applied on the same day each week. The start day may be during the first 24 hours of the menstrual cycle or on the first Sunday after menstruation begins. If therapy begins after the first day of the menstrual period, a back-up contraception should be used concurrently during the first 7 days of the first treatment cycle. The patch should be applied to clean, dry, intact, healthy skin on the buttock, abdomen, upper outer arm, or upper torso. It should not be applied to the breast. If the patch is partially or completely detached for more than 1 day or for an unknown period, a new cycle should be started immediately. Back-up contraception should be used for the first week of the new cycle. If the patient forgets to change her patch, she should consult the detailed patient labeling for instructions. Patients switching from oral contraceptives should wait until menstruation occurs.1
The patch delivers 150 µg of norelgestromin (progestin) and 20 µg of ethinyl estradiol (estrogen) (NGMN/EE) every 24 hours. It is supplied as cartons of 1 cycle (3 patches).
Potential Advantages
The NGMN/EE patch has been reported to have a higher rate of compliance than an oral contraceptive (levonorgestrel 125 µg/ethinyl estradiol 30 µg—Triphasil).2 The mean percent of patients with perfect compliance, patch vs. oral contraceptive, was 88.2% and 77.7%, respectively. Overall percentage of cycles with perfect compliance was 88.7% and 79.2%, respectively.2 About 60% of oral contraceptive users in this trial were recent users.
Potential Disadvantages
The NGMN/EE patch may be less effective in women with a body weight greater than 198 lbs. The most common side effect is skin reactions. About 3% of patients withdrew from the clinical trials due to this reaction. Greater increases in total cholesterol (15.8 mg/dL vs 8.1 mg/dL; P < 0.001) and triglyceride (9.7 mg/dL vs 0.9 mg/dL; P = 0.008) were observed with the patch compared to an oral contraceptive (levonorgestrel/ethinyl estradiol). An overall higher occurrence of breast discomfort was also observed with the patch, primarily with the first and second cycles.2 The incidence of the breakthrough bleeding and spotting (but not breakthrough bleeding alone) was higher with the patch in the first 2 cycles only. The incidence of patch becoming detached varied from 2-6%.1-3 In a clinical trial, about 5% of all patches were replaced for either complete or partial detachment.2
Comments
NGMN/EE is the first contraceptive patch to be marketed. The progestin component, norelgestromin, is the primary active (17-deacetylated) metabolite of norgestimate and is responsible for the progestogenic properties of norgestimate.4 The latter is in Ortho-Cyclen and Ortho-Tri-Cyclen. NGMN/EE patches have been tested in more than 3000 women world wide.1-3 A recent North American study compared NGMN/EE with levonorgestrel/ethinyl estradiol (Triphasil) on the basis of efficacy (Pearl Index and probability of pregnancy), cycle control, and safety. Subjects were randomized to the patch or oral contraceptive for 6 or 13 cycles. There was no statistical difference in efficacy in terms of overall Pearl Index between NGMN/EE patch and the oral contraceptive (1.24 vs 2.18), method-failure Pearl Index (0.99 vs 1.25), or the cumulative probability of pregnancy. The Pearl Index was defined as the number of pregnancies per 100 person-years of use. Method-failure pregnancy includes those where there was apparent dosing error (ie, compliance). Probability of pregnancy was estimated using the Kaplan-Meier method. In terms of cycle control, breakthrough bleeding and/or spotting were higher for the patch in cycle 1 and 2 only.
The cost of Ortho Evra is currently not available.
Clinical Implications
NGMN/EE provides an alternative to other methods of contraception but should not be used in patients with body weight greater than 198 lbs. Once-weekly administration may improve compliance in some patients.
References
1. Ortho Evra Product Information. Ortho Pharmaceuticals, Inc. November 2001.
2. Audet MC, et al. JAMA. 2001;285:2347-2354.
3. Smallwood GH, et al. Obstet Gynecol. 2001:95(5 pt 1):799-805.
4. Henzl MR. J Reprod Med. 2001;46:647-661.
Dr. Elliott, Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California-San Francisco, and Dr. Chan, Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA, are Associate Editors of Internal Medicine Alert.
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