Ortho Evra Adverse Reactions
- abdominal pain
- acne vulgaris
- alopecia
- amenorrhea
- anorexia
- anxiety
- appetite stimulation
- breakthrough bleeding
- breast discharge
- breast enlargement
- candidiasis
- cervical dysplasia
- cholecystitis
- cholelithiasis
- cholestasis
- depression
- diplopia
- dysmenorrhea
- edema
- elevated hepatic enzymes
- erythema nodosum
- fluid retention
- galactorrhea
- gingivitis
- headache
- hepatitis
- hepatoma
- hypertension
- jaundice
- keratoconus
- libido decrease
- maculopapular rash
- mastalgia
- melasma
- menstrual irregularity
- migraine
- myocardial infarction
- nausea/vomiting
- optic neuritis
- pancreatitis
- peliosis hepatis
- photosensitivity
- pulmonary embolism
- retinal thrombosis
- secondary malignancy
- stroke
- thromboembolism
- thrombosis
- urticaria
- vaginal bleeding
- vaginitis
- weight gain
Ortho Evra Adverse Reactions
Side effects and contraindications for Ortho Evra are similar to the combination hormonal oral contraceptives (OCs). In one US phase III trial, the most common adverse reactions to the ethinyl estradiol; norelgestromin (Ortho Evra™) patch were headache (21.9%); nausea/vomiting (20.4%/0%); mastalgia (breast tenderness or discomfort, 18.7%); dysmenorrhea (13.3%), and abdominal pain (8.1%). Breast discomfort was reported more frequently with the patch than with OCs in the first 2 cycles, but became comparable in subsequent cycles. Weight gain (roughly 0.41 kg) occurred in both treatment groups. Patch-related skin irritation (mild to moderate application site reaction) occurred in approximately 20% of patients, and was a reason for drug discontinuation in roughly 2.6% of those treated. A total of 4.6% of all patches were replaced for either complete or partial detachment during this trial. Ethinyl estradiol; norelgestromin, no clinically significant changes in laboratory parameters, vital signs, or other physical findings occurred. In both treatment groups total cholesterol concentrations increased (mean 15.8 mg/dL); triglyceride levels rose 9.7 mg/dl in the patch group vs. 0.9 mg/dl in the triphasic OC group. The patch has been reported not to change the LDL/HDL ratio.
Changes in vaginal bleeding patterns (e.g., menstrual irregularity) often occur after initiation of hormonal contraceptive therapy. As with OCs, breakthrough bleeding and spotting are common during the first 3 months of Ortho Evra patch administration. Spotting and breakthrough bleeding occur in roughly 18.3% of users initially. In one clinical trial, breakthrough bleeding in the patch group was comparable to an OC group by the third cycle, but was significantly higher than that of the OC group in the first two cycles. Amenorrhea occurred in 0.1% of patch users and 0.2% of OC users respectively. These changes usually subside and are replaced by a more predictable menstrual bleeding pattern with appropriate continuation of dosing. When breakthrough vaginal bleeding occurs cyclically after the first 3 months, the time the menstrual irregularity occurs in the cycle can indicate which component (i.e., estrogen or progestin) requires adjustment.
The following additional adverse event information relates primarily to the use of combination hormonal contraceptives as a class; the incidence of some of these side effects with the Ortho Evra™ patch is not known but similar risks should be expected:
The following adverse reactions are generally common during the initiation of any combination hormonal contraceptive regimen and often subside after the first few months of routine use and require medical attention only if prolonged or bothersome: appetite stimulation, fluid retention or edema, and fatigue. The Ortho Evra patch appears to have a low occurrence of these side effects.
Vaginal discharge or vaginal irritation due to candidiasis or vaginitis can occur during therapy with hormonal contraceptive agents.
Mood or personality changes occur commonly in women taking hormonal contraceptive agents. These changes include emotional lability, mental depression, anxiety, libido decrease, frustration, anger, or other emotional outbursts. In some cases, women discontinue hormonal contraceptives due to mood changes or emotional lability. However, hormonal contraceptives have also been reported to improve PMS and other cyclic emotional changes in some patients.
The relationship of migraine headache and the administration of hormonal contraceptives is not clearly defined. A number of changes can occur when a woman initiates hormonal contraceptive therapy and include 1) migraines can appear for the first time, 2) a change in frequency, severity and duration of migraine headaches may be seen, or 3) an improvement or decrease in the occurrence of migraine headaches may occur. When initiating therapy an individual’s headache pattern should be observed and if headaches worsen or if focal neurologic findings are present, consider discontinuing therapy.
No episodes of venous thromboembolism were reported in the users of Ortho Evra patch in one US phase III trial, although one patient developed pain and paresthesia in the left arm that resulted in patch discontinuation. However, combined hormonal contraceptive use has traditionally been associated with various thromboembolic disorders. The risk for the development of deep venous thrombosis and/or pulmonary embolism is approximately 3 - 6 times greater in OC users than in nonusers. In several studies, the risk was reported to be higher in smokers compared with nonsmokers. Both hormone amount and hormone type may be important factors regarding rates of thromboembolic disorders. Estrogens decrease levels of antithrombin-III and increase the production of blood clotting factors VII, VIII, IX and X; risks increase with ethinyl estradiol doses > 50 mcg/day. The additional effects of progestin in combination with the estrogen may also influence embolic risk. Regarding stroke and OC use, risk may be related to the amount of estrogen as well as the type of progestin, although this issue is controversial. Early epidemiological studies of OCs showed an increased risk for stroke, however these studies assessed OCs containing more than 50 mcg/day of ethinyl estradiol. Recent literature has shown that the use of the lower dose (i.e., <= 35 mcg/day ethinyl estradiol) OCs available today do not increase a healthy woman’s risk of heart attack or stroke. Smoking remains the largest risk factor for embolic events while on hormonal contraceptives.
Patients with chronic hypertension (BP > 140/90 mmHg) were excluded from enrollment in the US clinical trials of Ortho Evra patch; no clinically significant changes in vital signs were noted in enrolled patients. However, hypertension can occur within a few months of initiating hormonal contraceptive therapy and the prevalence appears to increase with duration of use and patient age. Close monitoring of blood pressures is recommended for patients at risk for hypertension; blood pressures usually return to normal after discontinuation of therapy.
In a recent pooled-data analysis from 2 large United States sites, women between the ages of 18 - 44 years old who had no prior incidence of coronary heart disease (CHD) or cerebrovascular disease prior to their MI event were studied for relative risk related to low-dose oral contraceptives. After adjustment for ethnicity and major established risk factors for CHD, there was no evidence of increased risk of myocardial infarction associated with OC use. Most other recent studies have concurred. One major exception was the WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. This international multicenter case-control study found a 5-fold increased risk of MI associated with current OC use. The authors, however, concluded that the increased risk might reflect more frequent use of OCs internationally in populations at higher risk, such as smokers and those with pre-existing cardiovascular risk factors. No increased risk of MI was noted in women who were non-smokers and in whom blood pressure was screened prior to OC use. Smoking is a well known additive risk to hormonal contraceptive therapy, increasing the relative risk of MI by five-fold. There is a 10 - 12 fold increase in risk of MI in patients who use hormonal contraceptive therapy and smoke compared to females who do not smoke or use OCs. Thus one would expect a higher incidence of MI in any woman taking combined hormonal contraceptives with concurrent known risk factors.
Ocular disorders can occur during therapy with hormonal contraceptive agents. These can include optic neuritis, diplopia, loss of vision, or retinal thrombosis. Estrogens can cause keratoconus. A conical cornea develops from steepening or increased curvature of the cornea, caused by thinning of the stroma. Patients with contact lenses may develop intolerance to their lenses. 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.
The Ortho Evra patch has not been associated with photoallergy or phototoxicity in dermal studies. However, estrogens can cause a variety of dermatological reactions. Melasma, in the form of tan or brown patches, may develop on the forehead, cheeks, temples and upper lip. These patches may persist after the drug is discontinued. Photosensitivity has been reported with combined contraceptive use and protective clothing and sunscreens should be employed when exposed to sunlight or UV light. Other dermatologic reactions are infrequent and include maculopapular rash, urticaria, erythema nodosum, alopecia, or hirsutism. Other erythematous eruptions may occur. Although combined hormonal contraceptives have been used to treat acne vulgaris, in some cases they may induce or aggravate an existing acne vulgaris. Combined hormonal contraceptives have not been shown to increase the incidence of skin cancer, including melanoma.
Some women taking combination hormonal contraceptives notice tenderness, swelling, or minor bleeding of their gums, which may lead to gingivitis. Proper attention to oral care and regular dental visits are recommended.
Abdominal pain occurring with the use of combined hormonal contraceptives can indicate cholelithiasis, cholecystitis, or cholestasis. Hormonal contraceptive agents should be discontinued in any patient developing severe abdominal pain and/or jaundice until the patient has been evaluated. In one US trial of the Ortho Evra patch, two patients developed cholecystitis; one patient required cholecystectomy. Abdominal pain with anorexia occurring with the use of combined hormonal contraceptives can also indicate hepatitis (and elevated hepatic enzymes), hepatoma (benign liver tumor), peliosis hepatis, or pancreatitis. Most case-control studies have shown a relationship between oral contraceptives (OCs) and the incidence of benign hepatoma and hepatocellular cancer. Risk may increase with increasing duration of combined hormonal contraceptive use. It must be noted that many studies of hepatocellular cancer and OCs have not controlled for the presence of the hepatitis B virus. Infection with hepatitis B has a strong correlation with the pathogenesis of hepatic carcinoma, and exclusion of this important variable in the OC studies makes it difficult to interpret true risk. Only one case of death related to liver cancer has been reported in the past 20 years of studies of OCs. Given the overall rarity of hepatocellular cancer in any population, the risk to women taking OCs is probably negligible. However, because liver tumors may spontaneously rupture and produce life-threatening hemorrhage, it is important to be aware of the possibility that tumors could occur.
The relationship between combined hormonal contraceptive use and secondary malignancy is controversial. An association between oral contraceptive use and cervical cancer has been demonstrated. The results of studies of cervical dysplasia and carcinoma in situ have been difficult to interpret due to the presence of confounding factors, such as difference in sexual practices and the presence of human papillomavirus (HPV). There has been suggestion that OCs may in some way act as a promoter for HPV-induced carcinogenesis, but this is speculative. In most studies, risks of cervical cancer begin to increase after 2 years of use and become clinically significant after 5 years of use. Further study is needed to define the role of combined hormonal contraceptives in the pathogenesis of cervical cancer. Because a potential for increased adverse events of this type may exist, it is prudent to regularly evaluate patients taking these agents via cervical cytology screening on an annual basis. While there continues to be some controversy regarding the use of hormonal contraceptives and the risk of developing breast cancer, 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. The breast cancer studies noted pertain to the use of combined hormonal contraceptives for the purpose of contraception, and may not apply to the use of these agents as hormone-replacement therapy alternatives in the perimenopausal woman (i.e., use of hormones later in life). The issue of prescribing hormonal contraceptives to women with a family history of breast cancer remains controversial. All women should be advised to report breast enlargement, lumps or unusual breast discharge (e.g., galactorrhea) to their health care professionals. If breast cancer is suspected in a woman who is taking hormonal contraceptives, the contraceptive should be discontinued.
A meta-analysis of 10 studies indicated significant trends in decreasing endometrial and ovarian carcinoma risks with increased duration of combined hormonal contraceptive use. Risk of endometrial or ovarian cancers may be reduced by up to 60% with 4 or more years of use. Current evidence suggests combined hormonal contraceptives do not protect against hereditary forms of ovarian cancer (e.g., women who carry BRCA1 or BRCA2 gene alterations).
[ Last revised: 1/8/2003 12:19:00 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.
. Modan B, Hartge P, Hirsh-Yechezkel G, et al. Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. N Engl J Med 2001;345:235 - 40.)
. Sidney S, Siscovik DS, Petitti DB, et al. Myocardial infarction and use of low-dose oral contraceptives-a pooled analysis of 2 US studies. Circulation 1998;98:1058 - 63.
. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. Lancet 1997;349:1202 - 09.
. Shwartz S, Petitti DB, Siscovik DS, et al. Stroke and use of low-dose oral contraceptives in young women - a pooled analysis of two US studies. Stroke 1998;29:2277 - 84.
. Audet MC, Moreau M, Koltun WD et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive - a randomized controlled trial. JAMA 2001;285:2347 - 54.
. 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.
Related entries
Syndicate
|
