NUVARING (etonogestrel/ethinyl estradiol vaginal ring)
NuvaRing Information
Product Code 0052-0273 Company Name Organon Pharmaceuticals USA Dosage From INSERT, EXTENDED RELEASE Strength 11.7 mg Active Ingredient etonogestrel
Nuvaring (Etonogestrel and ethinyl estradiol) Description
Nuvaring (Etonogestrel and ethinyl estradiol) (etonogestrel/ethinyl estradiol vaginal ring) is a non-biodegradable, flexible, transparent, colorless to almost colorless, combination contraceptive vaginal ring containing two active components, a progestin, etonogestrel (13-ethyl-17-hydroxy-11-methylene-18,19-dinor-17-pregn-4-en-20-yn-3-one) and an estrogen, ethinyl estradiol (19-nor-17-pregna-1,3,5(10)-trien-20-yne-3, 17-diol).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. Nuvaring (Etonogestrel and ethinyl estradiol) is made of ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate and contains 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol. Nuvaring (Etonogestrel and ethinyl estradiol) is latex-free. Nuvaring (Etonogestrel and ethinyl estradiol) has an outer diameter of 54 mm and a cross-sectional diameter of 4 mm. The molecular weights for etonogestrel and ethinyl estradiol are 324.46 and 296.40, respectively.
The structural formulas are as follows:
Nuvaring (Etonogestrel and ethinyl estradiol) Clinical Pharmacology
Combination hormonal contraceptives act by suppression of gonadotropins. Although the primary effect of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).
Receptor binding studies, as well as studies in animals, have shown that etonogestrel, the biologically active metabolite of desogestrel, combines high progestational activity with low intrinsic androgenicity. The relevance of this latter finding in humans is unknown.
Nuvaring (Etonogestrel and ethinyl estradiol) Indications And Usage
Nuvaring (Etonogestrel and ethinyl estradiol) is indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Like oral contraceptives, Nuvaring (Etonogestrel and ethinyl estradiol) is highly effective if used as recommended in this label.
In three large clinical trials of 13 cycles of Nuvaring (Etonogestrel and ethinyl estradiol) use, pregnancy rates were between one and two per 100 women-years of use. Table III lists the pregnancy rates for users of various contraceptive methods.
Nuvaring (Etonogestrel and ethinyl estradiol) Contraindications
Nuvaring (Etonogestrel and ethinyl estradiol) should not be used in women who currently have the following conditions:
Nuvaring (Etonogestrel and ethinyl estradiol) Warnings
Cigarette smoking increases the risk of serious cardiovascular side effects from combination oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use combination hormonal contraceptives, including Nuvaring (Etonogestrel and ethinyl estradiol) , should be strongly advised not to smoke.
Nuvaring (Etonogestrel and ethinyl estradiol) and other contraceptives that contain both an estrogen and a progestin are called combination hormonal contraceptives. There is no epidemiologic data available to determine whether safety and efficacy with the vaginal route of administration of combination hormonal contraceptives would be different than the oral route.
The use of oral contraceptives is associated with increased risks of several serious conditions including venous and arterial thrombotic and thromboembolic events (such as myocardial infarction, thromboembolism, and stroke), hepatic neoplasia, gallbladder disease, and hypertension, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as certain inherited thrombophilias, hypertension, hyperlipidemias, obesity, and diabetes.
The information contained in this package insert is principally based on studies carried out in women who used oral contraceptives with formulations of higher doses of estrogens and progestogens than those in common use today. The effect of long-term use of oral contraceptives with lower doses of both estrogens and progestogens remains to be determined.
Throughout this labeling, epidemiologic studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a of the incidence of a disease among oral contraceptive users to that among non-users. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the in the incidence of disease between oral contraceptive users and non-users. The attributable risk does provide information about the actual occurrence of a disease in the population. For further information, the reader is referred to a text on epidemiologic methods.
One study gathered data from a variety of sources that have estimated the mortality rate associated with different methods of contraception at different ages (Table V). These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risks. The study concluded that with the exception of oral contraceptive users age 35 and older who smoke and age 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth.
The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970's, but not reported until 1983. However, current clinical practice involves the use of lower estrogen-dose formulations combined with careful restriction of hormonal contraceptive use to women who do not have the various risk factors listed in this labeling.
Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy non-smoking women (even with the newer low-dose formulations), there are also greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception. Therefore, the Committee recommended that the benefits of low-dose hormonal oral contraceptive use by healthy non-smoking women over 40 may outweigh the possible risks. Older women, as all women who take hormonal contraceptives, should take the lowest possible dose formulation that is effective and meets the individual patient needs.
Numerous epidemiologic studies have been performed on the incidence of breast, endometrial, ovarian, and cervical cancer in women using combination oral contraceptives. Although the risk of breast cancer may be slightly increased among current users of oral contraceptives (RR = 1.24), this excess risk decreases over time after oral contraceptive discontinuation and by 10 years after cessation the increased risk disappears. The risk does not increase with duration of use, and no relationships have been found with dose or type of steroid. The patterns of risk are also similar regardless of a woman's reproductive history or her family breast cancer history. The subgroup for whom risk has been found to be significantly elevated is women who first used oral contraceptives before age 20, but because breast cancer is so rare at these young ages, the number of cases attributable to this early oral contraceptive use is extremely small. Breast cancers diagnosed in current or previous oral contraceptive users tend to be less advanced clinically than in never-users. Women who currently have or have had breast cancer should not use hormonal contraceptives because breast cancer is a hormone-sensitive tumor.
Some studies suggest that combination oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.
In spite of many studies of the relationship between oral contraceptive use and breast and cervical cancers, a cause-and-effect relationship has not been established.
It is unknown whether Nuvaring (Etonogestrel and ethinyl estradiol) is distinct from oral contraceptives with regard to the above statements.
Benign hepatic adenomas are associated with oral contraceptive use, although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases per 100,000 for users, a risk that increases after four or more years of use. Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.
Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long term (>8 years) oral contraceptive users. However, these cancers are extremely rare in the US and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users. It is unknown whether Nuvaring (Etonogestrel and ethinyl estradiol) is distinct from oral contraceptives in this regard.
Hormonal contraceptives should not be used during pregnancy.
Extensive epidemiologic studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when oral contraceptives are taken inadvertently during early pregnancy.
Combination hormonal contraceptives, such as Nuvaring (Etonogestrel and ethinyl estradiol) , should not be used to induce withdrawal bleeding as a test for pregnancy. Nuvaring (Etonogestrel and ethinyl estradiol) should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any woman who has not adhered to the prescribed regimen for use of Nuvaring (Etonogestrel and ethinyl estradiol) and has missed a menstrual period or who has missed two consecutive periods, pregnancy should be ruled out.
Hormonal contraceptives have been shown to cause a decrease in glucose tolerance in some users. However, in the non-diabetic woman, combination hormonal contraceptives appear to have no effect on fasting blood glucose. Prediabetic and diabetic women should be carefully observed while taking combination hormonal contraceptives, such as Nuvaring (Etonogestrel and ethinyl estradiol) . In a clinical study involving 37 Nuvaring (Etonogestrel and ethinyl estradiol) -treated subjects, glucose tolerance tests showed no clinically significant changes in serum glucose levels from baseline to cycle six.
A small proportion of women will have persistent hypertriglyceridemia while using oral contraceptives. Changes in serum triglycerides and lipoprotein levels have been reported in combination hormonal contraceptive users.
Women with severe hypertension should not be started on hormonal contraceptives. An increase in blood pressure has been reported in women taking oral contraceptives and this increase is more likely in older oral contraceptive users and with continued use. Data from the Royal College of General Practitioners and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens.
Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception. If these women elect to use Nuvaring (Etonogestrel and ethinyl estradiol) , they should be monitored closely and if significant elevation of blood pressure occurs, Nuvaring (Etonogestrel and ethinyl estradiol) should be discontinued. For most women, elevated blood pressure will return to normal after stopping hormonal contraceptives, and there is no difference in the occurrence of hypertension between former and never-users.
Nuvaring (Etonogestrel and ethinyl estradiol) Precautions
Women should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Women who are being treated for hyperlipidemias should be followed closely if they elect to use Nuvaring (Etonogestrel and ethinyl estradiol) . Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult.
In women with familial defects of lipoprotein metabolism receiving estrogen-containing preparations, there have been case reports of significant elevations of plasma triglycerides leading to pancreatitis.
Changes in contraceptive effectiveness associated with co-administration of other drugs:
Nuvaring (Etonogestrel and ethinyl estradiol) may not be suitable for women with conditions that make the vagina more susceptible to vaginal irritation or ulceration. Vaginal/cervical erosion or ulceration in women using Nuvaring (Etonogestrel and ethinyl estradiol) has been rarely reported. In some cases, the ring adhered to vaginal tissue, necessitating removal by a healthcare provider.
Some women are aware of the ring at random times during the 21 days of use or during intercourse. During intercourse some sexual partners may feel Nuvaring (Etonogestrel and ethinyl estradiol) in the vagina. However, clinical studies revealed that 90% of couples did not find this to be a problem.
Nuvaring (Etonogestrel and ethinyl estradiol) may interfere with the correct placement and position of a diaphragm. A diaphragm is therefore not recommended as a back-up method with Nuvaring (Etonogestrel and ethinyl estradiol) use.
Nuvaring (Etonogestrel and ethinyl estradiol) Adverse Reactions
The most common adverse events reported by five to 14% of women using Nuvaring (Etonogestrel and ethinyl estradiol) in clinical trials (n=2501) were the following: vaginitis, headache, upper respiratory tract infection, vaginal secretion, sinusitis, weight gain, and nausea.
The most frequent system-organ class adverse events leading to discontinuation in one to 2.5% of women using Nuvaring (Etonogestrel and ethinyl estradiol) in the trials included the following: device-related events (foreign body sensation, coital problems, device expulsion), vaginal symptoms (discomfort/vaginitis/vaginal secretion), headache, emotional lability, and weight gain.
Listed below are adverse reactions that have been associated with the use of combination hormonal contraceptives. These are also likely to apply to combination vaginal hormonal contraceptives, such as Nuvaring (Etonogestrel and ethinyl estradiol) .
An increased risk of the following serious adverse reactions has been associated with the use of combination hormonal contraceptives (see and ):
There is evidence of an association between the following conditions and the use of combination hormonal contraceptives:
The following additional adverse reactions have been reported in users of combination hormonal contraceptives and are believed to be drug-related:
The following additional adverse reactions have been reported in users of combination hormonal contraceptives and a causal association has been neither confirmed nor refuted:
Nuvaring (Etonogestrel and ethinyl estradiol) Overdosage
Overdosage of combination hormonal contraceptives may cause nausea, vomiting, vaginal bleeding, or other menstrual irregularities. Given the nature and design of Nuvaring (Etonogestrel and ethinyl estradiol) it is unlikely that overdosage will occur. If Nuvaring (Etonogestrel and ethinyl estradiol) is broken, it does not release a higher dose of hormones. Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. There are no antidotes and further treatment should be symptomatic.
Nuvaring (Etonogestrel and ethinyl estradiol) Dosage And Administration
To achieve maximum contraceptive effectiveness, Nuvaring (Etonogestrel and ethinyl estradiol) must be used as directed (see ). One Nuvaring (Etonogestrel and ethinyl estradiol) is inserted in the vagina. It is removed for a one-week break, during which a withdrawal bleed usually occurs. A new ring is inserted one week after the last ring was removed.
The user can choose the insertion position that is most comfortable to her, for example, standing with one leg up, squatting, or lying down. The ring is to be compressed and inserted into the vagina. The exact position of Nuvaring (Etonogestrel and ethinyl estradiol) inside the vagina is not critical for its function. The vaginal ring must be inserted on the appropriate day and left in place for three consecutive weeks. This means that the ring is removed three weeks later on the same day of the week as it was inserted and at about the same time. Nuvaring (Etonogestrel and ethinyl estradiol) can be removed by hooking the index finger under the forward rim or by grasping the rim between the index and middle finger and pulling it out. The used ring should be placed in the sachet (foil pouch) and discarded in a waste receptacle out of the reach of children and pets (do not flush in toilet). After a one-week break, during which a withdrawal bleed usually occurs, a new ring is inserted on the same day of the week as it was inserted in the previous cycle. The withdrawal bleed usually starts on day 2–3 after removal of the ring and may not have finished before the next ring is inserted. In order to maintain contraceptive effectiveness, the new ring must be inserted one week after the previous one was removed even if menstrual bleeding has not finished.
Nuvaring (Etonogestrel and ethinyl estradiol) How Supplied
Each Nuvaring (Etonogestrel and ethinyl estradiol) (etonogestrel/ethinyl estradiol vaginal ring) is individually packaged in a reclosable aluminum laminate sachet consisting of three layers, from outside to inside: polyester, aluminum foil, and low-density polyethylene. The ring should be replaced in this reclosable sachet after use for convenient disposal.
Nuvaring (Etonogestrel and ethinyl estradiol) Principal Display Panel - Ring Carton
For Vaginal Use
Keep out of the reach of children.
This product is intended to preventpregnancy. It does not protect againstHIV infection (AIDS) and other sexuallytransmitted diseases.
