Ortho Evra Contraindications and Precautions
- breast cancer
- cerebrovascular disease
- cervical cancer
- coronary artery disease
- coronary thrombosis
- endometrial cancer
- hepatic disease
- hepatocellular cancer
- jaundice
- myocardial infarction
- pregnancy
- stroke
- thromboembolic disease
- thrombophlebitis
- vaginal bleeding
- vaginal cancer
- valvular heart disease
- acquired immunodeficiency syndrome (AIDS)
- breast-feeding
- children
- cholestasis
- contact lenses
- depression
- diabetes mellitus
- gallbladder disease
- headache
- human immunodeficiency virus (HIV) infection
- hypercalcemia
- hypercholesterolemia
- hyperlipidemia
- hypertension
- hypertriglyceridemia
- hypothyroidism
- incomplete abortion
- menstrual irregularity
- migraine
- obesity
- obstetric delivery
- ocular disease
- porphyria
- renal disease
- surgery
- systemic lupus erythematosus (SLE)
- thyroid disease
- tobacco smoking
- uterine leiomyomata
Ortho Evra Contraindications and Precautions
NOTE: The pharmacokinetic profile for ethinyl estradiol; norelgestromin (Ortho Evra®) transdermal patch is different from the profile for oral contraceptives; overall exposure (i.e., AUC and steady-state concentrations) for ethinyl estrogen is higher for transdermal patch users while peak concentrations are lower. In general, women are exposed to approximately 60% more estrogen when using the transdermal patch. In addition, inter-subject variability in women using the transdermal patch is high, and some women may be exposed to even higher concentrations of estrogen. It is possible that increased estrogen exposure may be associated with an increased risk of serious adverse events. Health care professionals should balance the higher estrogen exposure of the transdermal patch against the chance of conception if an oral contraceptive pill is not taken daily.
Ortho Evra does not protect against human immunodeficiency virus (HIV) infection or other sexually transmitted diseases. Conversely, patients with known HIV infection or acquired immunodeficiency syndrome (AIDS) should be aware that the use of Ortho Evra™ will not prevent the transmission of HIV or other diseases to their partner(s).
Hormonal contraceptives are contraindicated during pregnancy and are labeled FDA pregnancy risk category X. Increased risk of a wide variety of fetal abnormalities, including modified development of sexual organs, cardiovascular anomalies and limb defects, have been reported following the use of estrogens or synthetic progestins alone in pregnant women. With the exception of effects on sexual development, the majority of recent studies do not indicate a teratogenic effect of combined hormonal contraceptives when taken inadvertently during early pregnancy. In any patient in whom pregnancy is suspected, pregnancy should be ruled out before continuing hormonal contraceptive use. In addition, hormonal contraceptive use may change folate metabolism, and women who discontinue combined hormonal contraceptives to pursue pregnancy should preferably wait 3 months for folate concentrations to normalize if possible. Folate supplementation should be given before and during pregnancy to reduce the risk of neural tube defects. Recent studies have found no increased risks of birth defects among women who have inadvertently continued to take birth control pills after they unknowingly became pregnant. Combination hormonal contraceptives should not be used to induce withdrawal bleeding as a test for pregnancy and should not be used to treat threatened or habitual abortion.
Because of an increased risk of thromboembolism in the immediate post-partum period, combination hormonal contraceptives should be used no earlier than 4 weeks following obstetric delivery, provided the mother is not breast-feeding. Because estrogens and progestins distribute to breast milk in small quantities and may interfere with the quality and quantity of lactation, combination hormonal contraceptives should be avoided if possible while breast-feeding. In general, other forms of contraception are preferred until the infant has been weaned. While occasionally a few acute adverse events in infants have been reported, long-term follow-up of infants whose mothers used combined hormonal contraceptives during lactation has shown no deleterious effects.
Although the effects appear to be minimal in most non-diabetic patients receiving hormone therapy with estrogen-progestin combinations, altered glucose tolerance secondary to decreased insulin sensitivity has been reported. Patients with hyperglycemia or diabetes mellitus should be observed for changes in glucose tolerance when initiating or discontinuing therapy. Because of the increased potential for embolic risk, Ortho Evra™ is contraindicated in patients with diabetes with vascular involvement.
Obesity may present risks for women considering the Ortho Evra contraceptive patch. Results of clinical trials suggest that the Ortho Evra patch may be less effective in women with body weight > 198 pounds (> 90 kg) than in women with lower body weights. Contraceptive failure may occur in these women. Additionally, pre-existing morbid obesity can be one factor that may increase cardiovascular or thromboembolic risks associated with combination hormonal contraceptive use in selected individuals.
Estrogens generally have a favorable effect on blood lipids, and reduce LDL and increase HDL cholesterol concentrations. Progestins, however, may attenuate some of these effects by raising LDL and may make control of pre-existing hyperlipidemia more difficult. Serum triglycerides increase with estrogen administration. A small proportion of women may have persistent hypertriglyceridemia while using combined hormonal contraceptives.
Hormonal contraceptive agents have been associated with thromboembolic disease such as deep venous thrombosis (DVT). A positive relationship between estrogen dosage and thromboembolic disease has been demonstrated. Oral products containing 50-mcg ethinyl estradiol should not be used unless medically indicated. In addition, certain progestins (e.g., desogestrel) may increase thromboembolic risk. Data about increased thromboembolic risk with norelgestromin are lacking. Because tobacco smoking increases the risk of DVT, myocardial infarction, stroke and other thromboembolic disease, estrogen-progestin contraceptives should be used cautiously, if at all, in smokers. Risk is especially high for female smokers >= 35 years of age or those females who smoke >= 15 cigarettes per day. Women receiving combination hormonal contraceptives should be advised not to smoke. Pre-existing high blood pressure, renal disease, hypercholesterolemia, hyperlipidemia, morbid obesity or diabetes may increase embolic risks. Hormonal contraceptive agents are contraindicated in patients with a current or past history of stroke, cerebrovascular disease, coronary artery disease, coronary thrombosis, thrombophlebitis, thromboembolic disease or valvular heart disease with complications. Patients undergoing elective surgery of a type associated with an increased risk of thromboembolism should stop combination hormonal contraceptives at least 4 weeks prior and 2 weeks after surgery. Combination hormonal contraceptives should also be stopped during and after any prolonged immobilization.
Approximately 85% of patients diagnosed with systemic lupus erythematosus (SLE) are females, giving support to the notion that hormonal influences contribute to the pathophysiology of SLE. Accordingly, combined hormonal contraceptive use has been reported to induce, unmask, and exacerbate lupus; case reports and other anecdotal data indicate that a temporal relationship between combined hormonal contraceptive use and lupus flares exist. However, several retrospective studies dispute a relationship between combined hormonal contraceptives causing or exacerbating lupus, and a large prospective, randomized clinical trial (SELENA) evaluating the safety of estrogen therapy (both as oral contraceptives and hormone replacement therapy in postmenopausal women) has been completed and is being analyzed. Determining the risk of combined hormonal contraceptive use in SLE patients is important as women with lupus benefit from contraception; not only does it offer reliable birth control, but it also possibly protects patients requiring chronic corticosteroid therapy from bone fractures and osteoporosis. Women with hypercoagulable states are at increased risk of venous thromboembolism when taking combined hormonal contraceptives; given the increased prevalence of hypercoagulable states in patients with SLE (in particular antiphospholipid antibodies and lupus anticoagulant), presence of a hypercoagulable state should be determined prior to initiation of combined hormonal contraceptives in this population. Combined hormonal contraceptives should be avoided in SLE patients with a history of venous or arterial thrombosis or the presence of a hypercoagulable state. If combined hormonal contraceptives are initiated in SLE patients without hypercoagulable states, low-dose estrogen contraceptives (i.e., 30 - 35 mcg of ethinyl estradiol or equivalent) should be used and consideration to a progestin-only contraceptive should be given. In addition, it may be prudent to avoid combined hormonal contraceptive therapy in patients with unstable or severe SLE or a history of SLE exacerbation with estrogen therapy until more data regarding the use of hormonal contraception in this population are available.
Because of their association with elevations in blood pressure, hormonal contraceptive agents like the ethinyl estradiol; norelgestromin (Ortho Evra™) contraceptive patch should be used cautiously in patients with mild to moderate hypertension or kidney disease; use is contraindicated in patients with severe hypertension. Norelgestromin has minimal androgenic activity; there is some evidence that the risk of myocardial infarction associated with hormonal contraceptives is lower when the progestogen has minimal androgenic activity than when the activity is greater. Oral products containing 50-mcg ethinyl estradiol should not be used unless medically indicated. Blood pressure should be monitored closely in these individuals. Any significant increase in blood pressure while on hormonal contraceptives may require discontinuation of the medication. Hormonal contraceptives may also cause fluid retention, and patients predisposed to complications from edema should be closely monitored.
The Fertility and Maternal Health Drugs Advisory Committee concluded in 1989 that even though cardiovascular disease risks may be increased in healthy nonsmoking women >= 40 years, the risk of pregnancy or associated surgical or medical procedures are also high in women >= 40 years. The Committee recommended that the benefits of low-dose oral contraceptives might outweigh the risks. The data were primarily obtained with oral contraceptives, but may apply to the ethinyl estradiol; norelgestromin (Ortho Evra™) contraceptive patch as well. Females of all ages should use the lowest possible dose formulation that is effective and meets the needs of the individual patient.
The onset or exacerbation of migraine or the development of headache with a new pattern that is recurrent, persistent or severe requires evaluation of the cause. Do not use hormonal contraceptives in those patients with migraines or other headaches that include focal neurologic symptoms as part of their presentation.
Estrogen-progestin agents are relatively contraindicated in gallbladder disease and acute or intermittent porphyria. Because of their association with the development of cholestasis, jaundice, and hepatic neoplasms, hormonal contraceptive agents should be used cautiously in patients with any pre-existing hepatic disease. Estrogens are contraindicated in the presence of hepatocellular cancer, hepatic adenoma or in markedly impaired liver function (e.g., uncompensated cirrhosis); those patients with a history of cholestatic jaundice/pruritus of pregnancy or jaundice due to prior hormonal treatments should not use this drug. If jaundice develops in any woman using the ethinyl estradiol; norelgestromin (Ortho Evra™) contraceptive patch, the product should be discontinued.
Mood disorders, like depression, may be aggravated in women using exogenous hormones. Women with a history of depression may need special monitoring. Low-dose hormonal contraceptive products may have minimal effect on depressive symptoms. If significant depression occurs, the ethinyl estradiol; norelgestromin (Ortho Evra™) contraceptive patch should be discontinued.
Estrogens can increase the curvature of the cornea and may lead to intolerance of contact lenses. There have been clinical case reports of retinal thrombosis. Any change in vision or visual acuity should be examined by an ophthalmologist. Hormonal contraceptive agents should be discontinued in patients developing any unexplained visual disturbance or ocular disease.
The safety and efficacy of hormonal contraceptive products like the ethinyl estradiol; norelgestromin (Ortho Evra™) contraceptive patch have only been established in females of reproductive age. Safety and efficacy of hormonal birth control is expected to be the same for postpubertal children under the age of 16 and for users 16 years of age and older. Use of hormonal contraceptive products in female children before menarche is not indicated.
The ethinyl estradiol; norelgestromin (Ortho Evra™) contraceptive patch is not indicated in elderly women >= 65 years of age.
Estrogens are generally contraindicated in patients with pre-existing breast cancer. The issue of prescribing combination hormonal contraceptives to women with a family history of breast cancer is controversial. In all patients, individual risk versus benefit must be performed. However, several large, well designed observational studies have provided reassurance that OC use, even for long periods, is not associated with an increased risk of breast cancer. A landmark case control study, the Cancer and Steroid Hormone (CASH) study, was published in 1986 and reported a lack of association between OC use and breast cancer. However, in 1996, the results of a meta-analysis of 54 studies specifically looking at the effects of OCs in more than 150,000 women were published. A small, statistically significant (but slight) risk for breast carcinoma existed for women taking OCs; the risk steadily diminished to baseline over 10 years following discontinuation. The value of the data from this meta-analysis was limited because of variances in study designs and patient follow up; however, the controversy over steroid hormone exposure and the risk of breast cancer continued. In 2002, the results of the Women’s CARE trial were reported. No associations between past or present use of OCs and breast cancer were observed; the study included 4575 women with breast cancer and 4682 controls between the ages of 35 - 64 years old; > 75% of the study participants had used OCs. The studies noted evaluated the use of OCs for the purpose of contraception, and may not apply to the use of combination hormonal contraceptives as hormone-replacement therapy alternatives in the perimenopausal woman (i.e., use of hormones later in life).
Hormonal contraceptives containing estrogen are not recommended in patients with hypercalcemia associated with tumors or metabolic bone disease because estrogens influence the metabolism of calcium and phosphorus.
Hormonal contraceptives are contraindicated in patients with pre-existing cervical cancer. An association between hormonal contraceptive use and cervical cancer has been demonstrated. Generally, the risk of invasive cervical cancer in women who use oral contraceptives is greatest in women who take OCs for more than 5 years. (see Adverse Reactions) Data detailing the risk in users of this Ortho Evra patch are not available. Evaluate cervical cytology prior to hormonal contraceptive use.
Since 1970, at least 35 epidemiological studies have examined the association of exogenous estrogen and an increased incidence of cancer of the endometrium. A recent meta-analysis of 10 studies indicates a significant trend in decreasing endometrial and ovarian carcinoma risk with increasing duration of combined OC use. The beneficial effects of the OCs in this regard may persist for 15 years after OC use ceases. However, in those women with known endometrial cancer or other estrogen-dependent tumors (e.g., vaginal cancer), estrogen-containing contraceptives are contraindicated, as administration of exogenous estrogen may worsen the condition. Hormonal contraceptive agents are relatively contraindicated in women with undiagnosed menstrual irregularity including undiagnosed vaginal bleeding, or incomplete abortion. Relative contraindication exists also for uterine leiomyomata (fibroids) because the drug can cause the fibroids to increase in size.
Use estrogens with caution in patients with thyroid disease, particularly hypothyroidism. Estrogens can increase thyroid-binding globulin (TBG) levels. Patients with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.
[ Last revised: 11/14/2005 4:59:00 PM ]
References
. Collaborative Group of Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Lancet 1996;347:1713 - 27.
. Schlesselman J. Net effect of oral contraceptive use on the risk of cancer in women in the United States. Obstet Gynecol 1995;85:793 - 801.
. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. Oral Contraceptive use and the risk of breast cancer. N Engl J Med 1986;315:405 - 11.
. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. [Women’s Contraceptive and Reproductive Experiences (Women’s CARE) Study]. N Engl J Med 2002;346:2025 - 32.
. Askanase AD. Estrogen therapy in systemic lupus erythematosus. Treat Endocrinol 2004;3:19 - 26.
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