"The U.S. Food and Drug Administration today announced that it has approved an amended application submitted by Teva Women's Health, Inc. to market Plan B One-Step (active ingredient levonorgestrel) for use without a prescription by women 15 years"...
The following serious adverse reactions with the use of combination hormonal contraceptives, including ORTHO EVRA, are discussed elsewhere in the labeling:
- Serious cardiovascular events and stroke [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
- Vascular events, including venous and arterial thromboembolic events [see WARNINGS AND PRECAUTIONS]
- Liver disease [see WARNINGS AND PRECAUTIONS]
Adverse reactions commonly reported by users of combination hormonal contraceptives are:
- Irregular uterine bleeding
- Breast tenderness
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The data described below reflect exposure to ORTHO EVRA in 3330 sexually active women (3322 of whom had safety data) who participated in three Phase 3 clinical trials designed to evaluate contraceptive efficacy and safety. These subjects received six or 13 cycles of contraception (ORTHO EVRA or an oral contraceptive comparator in 2 of the trials). The women ranged in age from 18 to 45 years and were predominantly white (91%).
The most common adverse reactions ( ≥ 5%) reported during clinical trials were breast symptoms, nausea/vomiting, headache, application site disorder, abdominal pain, dysmenorrhea, vaginal bleeding and menstrual disorders, and mood, affect and anxiety disorders. The most common events leading to discontinuation were application site reaction, breast symptoms (including breast discomfort, engorgement and pain), nausea and/or vomiting, headache and emotional lability.
Adverse drug reactions reported by ≥ 2.5% of ORTHO EVRA-treated subjects in these trials are shown in Table 3.
Table 3: Adverse Drug Reactions Reported by ≥
2.5% of ORTHO EVRA-treated Subjects in Three Phase 3 Clinical Trials
|ORTHO EVRA (n=3322)|
|Reproductive system and breast disorders|
|Vaginal bleeding and menstrual disordersf||6.4%|
|Nervous system disorders|
|General disorders and administration site conditions|
|Application site disorder†||17.1%|
|Mood, affect and anxiety disorders†||6.3%|
|Skin and subcutaneous tissue disorders|
|Infections and infestations|
|Vaginal yeast infection†||3.9%|
|* MedDRA version 10.0
† Represents a bundle of similar terms
Additional adverse drug reactions that occurred in < 2.5% of ORTHO EVRA-treated subjects in the above clinical trials datasets are:
- Gastrointestinal disorders: Abdominal distension
- General disorders and administration site conditions: Fluid retention1, malaise
- Hepatobiliary disorders: Cholecystitis
- Investigations: Blood pressure increased, lipid disorders1
- Musculoskeletal and connective tissue disorders: Muscle spasms
- Psychiatric disorders: Insomnia, libido decreased, libido increased
- Reproductive system and breast disorders: Galactorrhea, genital discharge, premenstrual syndrome, uterine spasm, vaginal discharge, vulvovaginal dryness
- Respiratory, thoracic and mediastinal disorders: Pulmonary embolism
- Skin and subcutaneous tissue disorders: Chloasma, dermatitis contact, erythema, skin irritation
The following adverse reactions (Table 4) have been identified during postapproval use of ORTHO EVRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Table 4: Alphabetical List of Adverse Drug Reactions
Identified During Postmarketing Experience with ORTHO EVRA/EVRA by System Organ
|System Organ Class||Adverse Drug Reactions|
|Cardiac disorders||Myocardial infarctiont|
|Endocrine disorders||Hyperglycemia, insulin resistance|
|Eye disorders||Contact lens intolerance or complication|
|General disorders and administration site conditions||Application site reaction†, edemat†|
|Hepatobiliary disorders||Blood cholesterol abnormal, cholelithiasis, cholestasis, hepatic lesion, jaundice cholestatic, low density lipoprotein increased|
|Immune system disorders||Allergic reaction†, urticaria|
|Investigations||Blood glucose abnormal, blood glucose decreased|
|Metabolism and nutrition disorders||Increased appetite|
|Neoplasms benign, malignant and unspecified (Incl. cysts and polyps)||Breast cancer†, cervix carcinoma, hepatic adenoma, hepatic neoplasm|
|Nervous system disorders||Dysgeusia, migraine with aura|
|Psychiatric disorders||Anger, emotional disorder, frustration, irritability|
|Reproductive system and breast disorders||Breast mass, cervical dysplasia, fibroadenoma of breast, menstrual disorder† suppressed lactation, uterine leiomyoma|
|Skin and subcutaneous tissues disorders||Alopecia, eczema, erythema multiforme, erythema nodosum, photosensitivity reaction, pruritus generalized, rasht, seborrheic dermatitis, skin reaction|
|Vascular disorders||Arterial thrombosis† cerebrovascular accident† deep vein thrombosis†, hemorrhage intracranial†, hypertension, hypertensive crisis, pulmonary embolism† thrombosist|
|* MedDRA version 10.0
† Represents a bundle of similar terms
1Represents a bundle of similar terms
Read the Ortho Evra (norelgestromin, ethinyl estradiol transdermal) Side Effects Center for a complete guide to possible side effects
Consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.
Effects of Other Drugs on Combined Hormonal Contraceptives
Substances decreasing the plasma concentrations of CHCs and potentially diminishing the efficacy of CHCs
Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of CHCs and potentially diminish the effectiveness of CHCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John's wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with CHCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.
Substances increasing the plasma concentrations of CHCs
Co-administration of atorvastatin or rosuvastatin and certain CHCs containing EE increase AUC values for EE by approximately 20-25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations.
Human immunodeficiency virus (HIV)/Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors
Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritnoavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir])/HCV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]).
Effects of Combined Hormonal Contraceptives on Other Drugs
CHCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. CHCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, and temazepam. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.
Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentration of thyroid-binding globulin increases with use of CHCs [see WARNINGS AND PRECAUTIONS].
Interference with Laboratory Tests
Last reviewed on RxList: 7/12/2013
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