ORTHO EVRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORTHO EVRA (ORTHO EVRA).
Combination hormonal contraceptive containing ethinyl estradiol and norelgestromin. Ethinyl estradiol suppresses gonadotropin (FSH and LH) release, preventing ovulation. Norelgestromin is a progestin that also inhibits ovulation and induces changes in cervical mucus and endometrium to impede sperm penetration and implantation.
| Metabolism | Ethinyl estradiol is primarily metabolized by CYP3A4, with conjugation to sulfate and glucuronide. Norelgestromin is extensively metabolized via reduction to norgestrel and conjugation, with CYP3A4/5 involved in minor pathways. |
| Excretion | Renal: ~50% (as glucuronide conjugates of norelgestromin and ethinyl estradiol); Fecal: ~35% (as metabolites); Biliary: minor |
| Half-life | Norelgestromin: ~28 hours (range 21-36) allowing weekly dosing; Ethinyl estradiol: ~17 hours (range 13-21) |
| Protein binding | Norelgestromin: >99% bound (albumin and SHBG); Ethinyl estradiol: ~97% bound (albumin, not SHBG) |
| Volume of Distribution | Norelgestromin: ~2.4 L/kg; Ethinyl estradiol: ~4.3 L/kg; indicates extensive tissue distribution |
| Bioavailability | Transdermal: ~100% systemic absorption; oral norelgestromin: ~60% (not administered orally) |
| Onset of Action | Transdermal: Within 24 hours for contraceptive effects; ovulation suppression achieved by day 2 of first cycle |
| Duration of Action | 7 days per patch; contraceptive efficacy maintained for full week; replace weekly for 3 weeks then 1 week patch-free |
Transdermal: Apply one patch (releases 150 mcg norelgestromin and 20 mcg ethinyl estradiol per 24 hours) weekly for 3 weeks, followed by 1 patch-free week. Apply to clean, dry, intact skin on lower abdomen, buttock, upper arm, or upper torso (excluding breasts).
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment. Contraindicated in severe renal impairment or end-stage renal disease (CrCl <30 mL/min). |
| Liver impairment | Contraindicated in acute or chronic hepatic disease, including Child-Pugh class A, B, or C cirrhosis. Discontinue if jaundice develops. |
| Pediatric use | Not indicated for use prior to menarche. For postmenarchal adolescents, dosing is same as adults: apply patch weekly for 3 weeks, then 1 week off. |
| Geriatric use | Not indicated for use after menopause. No specific geriatric dosing studies; use not recommended due to lack of need for contraception in this population. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORTHO EVRA (ORTHO EVRA).
| Breastfeeding | CHCs reduce milk production and may affect composition. The manufacturer recommends avoiding use until breastfeeding is fully established (typically 6 months postpartum). Norelgestromin and ethinyl estradiol are excreted in breast milk; milk-to-plasma ratio not specified. Use an alternative contraceptive method during breastfeeding. |
| Teratogenic Risk | First trimester: Epidemiologic studies have not found an increased risk of major birth defects following inadvertent use of combination hormonal contraceptives (CHCs) in early pregnancy. Second and third trimesters: Use is contraindicated; exposure during gestation has been associated with fetal harm, including cardiovascular anomalies and masculinization of female fetuses (androgenic effects from progestin). |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives. This risk increases with age, especially in women over 35 years, and with the number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
["Thrombophlebitis, venous thromboembolism, or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use","Hepatic adenoma or carcinoma, or active liver disease","Known or suspected pregnancy","Hypersensitivity to ethinyl estradiol, norelgestromin, or any component of the patch","Heavy smoking (≥15 cigarettes/day) in women over 35 years of age"]
| Precautions | ["Increased risk of venous thromboembolism (VTE) including deep vein thrombosis and pulmonary embolism, especially in women with risk factors","Increased risk of arterial thrombotic events (e.g., myocardial infarction, stroke) particularly in smokers and women with hypertension or migraine with aura","Hepatic neoplasia (benign and malignant) reported; discontinue if jaundice or liver function abnormalities develop","Elevated blood pressure; monitor and discontinue if hypertension becomes significant","Gallbladder disease and cholestasis","Glucose intolerance; use with caution in diabetic women","Headache including migraine; discontinue if new or worsening migraine develops","Ocular lesions (e.g., retinal thrombosis); discontinue if sudden partial or complete vision loss occurs","Depression; monitor and discontinue if severe","Reduced efficacy in women weighing ≥90 kg (198 lbs); consider alternative contraception","Detachment or incomplete adhesion of patch; instruct on proper use"] |
Loading safety data…
| Fetal Monitoring | Monitor blood pressure monthly; if hypertension develops, discontinue. Assess for signs of thromboembolism, headache, visual disturbances, and jaundice. Perform pregnancy test if pregnancy suspected before initiating or continuing use. |
| Fertility Effects | CHCs suppress ovulation. After discontinuation, fertility returns rapidly; there is no delay in conception compared to baseline. No permanent negative impact on fertility. |