- If the woman has not adhered to the prescribed regimen (Etonogestrel/Ethinyl Estradiol Vaginal Ring has been out of the vagina for more than three hours or the preceding ring-free interval was extended beyond one week), consider the possibility of pregnancy at the time of the first missed period and discontinue Etonogestrel/Ethinyl Estradiol Vaginal Ring use if pregnancy is confirmed.
- If the woman has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy.
- If the woman has retained one Etonogestrel/Ethinyl Estradiol Vaginal Ring for longer than four weeks, rule out pregnancy.
Etonogestrel/Ethinyl Estradiol Vaginal Ring may interfere with the correct placement and position of certain female barrier methods such as a diaphragm, cervical cap or female condom. These methods are not recommended as back-up methods with Etonogestrel/Ethinyl Estradiol Vaginal Ring use.
Pharmacokinetic data show that the use of tampons has no effect on the systemic absorption of the hormones released by Etonogestrel/Ethinyl Estradiol Vaginal Ring.
Etonogestrel/Ethinyl Estradiol Vaginal Ring is a non-biodegradable, flexible, transparent, colorless to almost colorless, combination contraceptive vaginal ring, with an outer diameter of 54 mm and a cross-sectional diameter of 4 mm. It is made of ethylene vinylacetate copolymers and magnesium stearate, and contains 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol. When placed in the vagina, each ring releases on average 0.120 mg/day of etonogestrel and 0.015 mg/day of ethinyl estradiol over a three-week period of use. Etonogestrel/Ethinyl Estradiol Vaginal Ring is not made with natural rubber latex.
Do not prescribe Etonogestrel/Ethinyl Estradiol Vaginal Ring to women who are known to have or use the following:
- A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:
- Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1)]
- Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1)]
- Have cerebrovascular disease [see Warnings and Precautions (5.1)]
- Have coronary artery disease [see Warnings and Precautions (5.1)]
- Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions (5.1)]
- Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1)]
- Have uncontrolled hypertension [see Warnings and Precautions (5.5)]
- Have diabetes mellitus with vascular disease [see Warnings and Precautions (5.9)]
- Have headaches with focal neurological symptoms or migraine headaches with aura [see Warnings and Precautions (5.10)]
- Women over age 35 with any migraine headaches [see Warnings and Precautions (5.10)]
- Liver tumors, benign or malignant or liver disease [see Warnings and Precautions (5.3) and Use in Specific Populations (8.6)]
- Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.11)]
- Pregnancy, because there is no reason to use CHCs during pregnancy [see Use in Specific Populations (8.1)]
- Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past [see Warnings and Precautions (5.14)]
- Hypersensitivity reactions, including anaphylaxis and angioedema, to any of the components of Etonogestrel/Ethinyl Estradiol Vaginal Ring [see Warnings and Precautions (5.6) and Adverse Reactions (6)]
- Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions (5.4)]
Stop Etonogestrel/Ethinyl Estradiol Vaginal Ring use if an arterial thrombotic or venous thromboembolic event (VTE) occurs. Stop Etonogestrel/Ethinyl Estradiol Vaginal Ring use if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately. [See Adverse Reactions (6).]
If feasible, stop Etonogestrel/Ethinyl Estradiol Vaginal Ring at least four weeks before and through two weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism, and during and following prolonged immobilization.
Start Etonogestrel/Ethinyl Estradiol Vaginal Ring no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.
The use of CHCs increases the risk of VTE. Known risk factors for VTE include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs [see Contraindications (4)].
Two epidemiologic studies1, 2, 3 that assessed the risk of VTE associated with the use of Etonogestrel/Ethinyl Estradiol Vaginal Ring are described below.
In these studies, which were required or sponsored by regulatory agencies, Etonogestrel/Ethinyl Estradiol Vaginal Ring users had a risk of VTE similar to Combined Oral Contraceptives (COCs) users (see Table 1 for adjusted hazard ratios). A large prospective, observational study, the Transatlantic Active Surveillance on Cardiovascular Safety of Etonogestrel/Ethinyl Estradiol Vaginal Ring (TASC), investigated the risk of VTE for new users, and women who were switching to or restarting Etonogestrel/Ethinyl Estradiol Vaginal Ring or COCs in a population that is representative of routine clinical users. The women were followed for 24 to 48 months. The results showed a similar risk of VTE among Etonogestrel/Ethinyl Estradiol Vaginal Ring users (VTE incidence 8.3 per 10,000 WY) and women using COCs (VTE incidence 9.2 per 10,000 WY). For women using COCs that did not contain the progestins desogestrel (DSG) or gestodene (GSD), VTE incidence was 8.9 per 10,000 WY.
A retrospective cohort study using data from 4 health plans in the US (FDA-funded Study in Kaiser Permanente and Medicaid databases) showed the VTE incidence for new users of Etonogestrel/Ethinyl Estradiol Vaginal Ring to be 11.4 events per 10,000 WY, for new users of a levonorgestrel (LNG)-containing COC 9.2 events per 10,000 WY, and for users of other COCs available during the course of the study 1 8.2 events per 10,000 WY.
|Epidemiologic Study(Author, Year of Publication)Population Studied||Comparator Product(s)||Hazard Ratios (HR)(95% CI)|
|Initiators, including new users, switchers and restarters||All COCs available during the course of the study *||HR †: 0.8(0.5-1.5)|
|COCs available excluding DSG- or GSD -containing OCs||HR †: 0.8(0.4-1.7)|
|FDA-funded Study in Kaiser Permanente and Medicaid databases(Sidney, 2011)|
|First use of a combined hormonal contraceptive (CHC) during the study period||COCs available during the course of the study ‡||HR §: 1.1(0.6-2.2)|
|LNG/0.03 mg ethinyl estradiol||HR §: 1.0(0.5-2.0)|
An increased risk of thromboembolic and thrombotic disease associated with the use of CHCs is well-established. Although the absolute VTE rates are increased for users of CHCs compared to non-users, the rates associated with pregnancy are even greater, especially during the post-partum period (see Figure 1).
The frequency of VTE in women using CHCs has been estimated to be 3 to 12 cases per 10,000 women-years.
The risk of VTE is highest during the first year of CHC use and after restarting a CHC following a break of at least four weeks. The risk of VTE due to CHCs gradually disappears after use is discontinued.
Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use CHCs, for women who use CHCs, for pregnant women, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use CHCs are followed for one year, between 1 and 5 of these women will develop a VTE.
|*CHC=combination hormonal contraception**Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.|
Several epidemiology studies indicate that third generation oral contraceptives, including those containing desogestrel (etonogestrel, the progestin in Etonogestrel/Ethinyl Estradiol Vaginal Ring, is the biologically active metabolite of desogestrel), may be associated with a higher risk of VTE than oral contraceptives containing other progestins. Some of these studies indicate an approximate two-fold increased risk. However, data from other studies have not shown this two-fold increase in risk.
Use of CHCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. CHCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes). In general, the risk is greatest among older (>35 years of age), hypertensive women who also smoke.
Use Etonogestrel/Ethinyl Estradiol Vaginal Ring with caution in women with cardiovascular disease risk factors.
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