NUVARING- etonogestrel and ethinyl estradiol insert, extended release
Organon Pharmaceuticals USA
delivers 0.120 mg/0.015 mg per day
Women should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
FOR VAGINAL USE ONLY
DESCRIPTION
NuvaRing� (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� 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� is latex-free. NuvaRing� 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:
Chemical Structure
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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.
Pharmacokinetics
Absorption
Etonogestrel
Etonogestrel released by NuvaRing� is rapidly absorbed. The bioavailability of etonogestrel after vaginal administration is approximately 100%. The serum etonogestrel and ethinyl estradiol concentrations observed during three weeks of NuvaRing� use are summarized in Table I.
Ethinyl estradiol
Ethinyl estradiol released by NuvaRing� is rapidly absorbed. The bioavailability of ethinyl estradiol after vaginal administration is approximately 56%, which is comparable to that with oral administration of ethinyl estradiol. NuvaRing Indications and Usage
NuvaRing� is indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Like oral contraceptives, NuvaRing� is highly effective if used as recommended in this label.
In three large clinical trials of 13 cycles of NuvaRing� 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. 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� , should be strongly advised not to smoke.
NuvaRing� 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 ratio 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 difference 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.
