Etonogestrel/Ethinyl Estradiol

Description

Etonogestrel/Ethinyl Estradiol Vaginal Ring is a non-biodegradable, flexible, transparent, and colorless to almost colorless combination contraceptive vaginal ring. It contains two active components: etonogestrel, a progestin with the chemical structure 13-ethyl-17-hydroxy-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3-one, and ethinyl estradiol, an estrogen with the structure 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol.

When inserted into the vagina, the ring releases an average of 0.120 mg/day of etonogestrel and 0.015 mg/day of ethinyl estradiol over a three-week usage period. The ring is composed of ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate, containing a total of 11.7 mg of etonogestrel and 2.7 mg of ethinyl estradiol. It is important to note that the ring is not made with natural rubber latex.

The outer diameter of the Etonogestrel/Ethinyl Estradiol Vaginal Ring measures 54 mm, with a cross-sectional diameter of 4 mm. The molecular weights of the active ingredients are 324.46 g/mol for etonogestrel and 296.40 g/mol for ethinyl estradiol.

Uses and Indications

Etonogestrel/Ethinyl Estradiol Vaginal Ring is indicated for use by women for the prevention of pregnancy.

This product does not provide protection against HIV infection (AIDS) or other sexually transmitted diseases.

Dosage and Administration

One Etonogestrel/Ethinyl Estradiol Vaginal Ring should be inserted into the vagina. The ring must remain in place continuously for a duration of three weeks. Following this period, a one-week ring-free interval is required. It is essential that healthcare professionals ensure patients understand the importance of adhering to this schedule for optimal efficacy.

Contraindications

Use of Etonogestrel/Ethinyl Estradiol Vaginal Ring is contraindicated in the following situations:

Patients with a high risk of arterial or venous thrombotic diseases due to the potential for exacerbating these conditions.

Individuals with breast cancer, as the hormonal components may promote tumor growth.

Patients with liver tumors or liver disease, given the risk of hepatic complications.

Those experiencing undiagnosed abnormal uterine bleeding, which requires further evaluation before treatment.

Pregnant individuals, as the safety of the product has not been established in this population.

Patients with hypersensitivity to any components of the Etonogestrel/Ethinyl Estradiol Vaginal Ring, including a history of anaphylaxis or angioedema.

Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, is contraindicated due to potential drug interactions.

Warnings and Precautions

Women over 35 years of age who smoke are advised against the use of Etonogestrel/Ethinyl Estradiol Vaginal Ring due to the increased risk of serious cardiovascular events associated with cigarette smoking and combination hormonal contraceptive (CHC) use.

In terms of general precautions, it is imperative to discontinue the use of Etonogestrel/Ethinyl Estradiol Vaginal Ring if a thrombotic event occurs. Additionally, the use of this contraceptive should be halted at least 4 weeks prior to and maintained through 2 weeks after any major surgical procedure. For women who are not breastfeeding, initiation of the ring should not occur earlier than 4 weeks postpartum.

Healthcare professionals should be vigilant for signs and symptoms of Toxic Shock Syndrome (TSS) in patients using the vaginal ring. If TSS is suspected, appropriate medical evaluation and treatment should be initiated promptly. In cases of liver disease, the use of Etonogestrel/Ethinyl Estradiol Vaginal Ring must be discontinued if jaundice develops.

For women with well-controlled hypertension, it is essential to monitor blood pressure regularly. Should there be a significant rise in blood pressure, the use of the vaginal ring should be stopped. Furthermore, prediabetic and diabetic women require careful monitoring of carbohydrate and lipid metabolism, and an alternative contraceptive method should be considered for those with uncontrolled dyslipidemia.

Healthcare providers should also evaluate any significant changes in headache patterns, discontinuing the use of the vaginal ring if warranted. Irregular uterine bleeding or amenorrhea should be assessed to determine the appropriate course of action.

Laboratory tests should include regular blood pressure monitoring for women with well-controlled hypertension, as well as monitoring for prediabetic and diabetic patients to ensure their metabolic status remains stable.

Side Effects

Patients using Etonogestrel/Ethinyl Estradiol Vaginal Ring may experience a range of adverse reactions. Common adverse reactions occurring in 2% or more of participants include vaginitis, headache (including migraine), mood changes (such as depression, mood swings, and affect lability), device-related events (including expulsion, discomfort, and foreign body sensation), nausea/vomiting, vaginal discharge, increased weight, vaginal discomfort, breast pain or tenderness, dysmenorrhea, abdominal pain, acne, and decreased libido.

Serious adverse reactions warrant particular attention. Women over 35 years old who smoke are advised against using this contraceptive method due to an increased risk of serious cardiovascular events associated with combination hormonal contraceptive (CHC) use. Additionally, if a thrombotic event occurs, Etonogestrel/Ethinyl Estradiol Vaginal Ring use should be discontinued. It is also recommended to stop use at least 4 weeks before and through 2 weeks after major surgery, and to initiate use no earlier than 4 weeks postpartum in women who are not breastfeeding.

Patients should be monitored for signs of Toxic Shock Syndrome (TSS); if symptoms arise, appropriate medical evaluation and treatment should be initiated. Liver disease is another critical consideration; Etonogestrel/Ethinyl Estradiol Vaginal Ring use should be discontinued if jaundice develops. For women with well-controlled hypertension, blood pressure should be monitored, and the use of the ring should cease if significant increases in blood pressure are observed.

Furthermore, prediabetic and diabetic women should be monitored for carbohydrate and lipid metabolic effects, and an alternative contraceptive method should be considered for those with uncontrolled dyslipidemia. Significant changes in headache patterns should prompt evaluation, and discontinuation of the ring may be necessary if indicated. Irregular bleeding or amenorrhea should also be evaluated.

Contraindications for the use of Etonogestrel/Ethinyl Estradiol Vaginal Ring include a high risk of arterial or venous thrombotic diseases, breast cancer, liver tumors or liver disease, undiagnosed abnormal uterine bleeding, pregnancy, hypersensitivity (including anaphylaxis and angioedema) to any of the components, and co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir.

Drug Interactions

Drugs or herbal products that induce cytochrome P450 3A4 (CYP3A4) may reduce the effectiveness of combined hormonal contraceptives (CHCs) and increase the risk of breakthrough bleeding. It is advised that patients using CHCs concurrently with enzyme inducers be counseled to employ a backup or alternative method of contraception to ensure adequate contraceptive efficacy. Monitoring for signs of reduced contraceptive effectiveness or breakthrough bleeding is recommended in these situations.

Packaging & NDC

The table below lists all NDC Code configurations of Etonogestrel/Ethinyl Estradiol (etonogestrel and ethinyl estradiol), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and efficacy of Etonogestrel/Ethinyl Estradiol Vaginal Ring have been established in women of reproductive age. Efficacy is expected to be comparable for postpubertal adolescents under the age of 18 and for users aged 18 years and older. The use of this product is not indicated for individuals before menarche.

Geriatric Use

Etonogestrel/Ethinyl Estradiol Vaginal Ring has not been studied in elderly patients, specifically those who are postmenopausal, and is not indicated for use in this population. Therefore, healthcare providers should exercise caution when considering this medication for geriatric patients, particularly those aged 65 and older.

Due to the lack of clinical data in this demographic, it is essential to monitor for potential adverse effects and to consider alternative therapies that have been established as safe and effective for postmenopausal women.

Pregnancy

Etonogestrel/Ethinyl Estradiol Vaginal Ring is contraindicated during pregnancy, as there is no need for pregnancy prevention in women who are already pregnant. Epidemiologic studies and meta-analyses have not demonstrated an increased risk of genital or non-genital birth defects, including cardiac anomalies and limb-reduction defects, following maternal exposure to low-dose combined hormonal contraceptives (CHCs) prior to conception or during early pregnancy.

Animal studies have shown that no adverse developmental outcomes were observed in pregnant rats and rabbits when etonogestrel was administered during organogenesis at doses approximately 300 times the anticipated daily vaginal human dose (~0.002 mg/kg/day). Similarly, the co-administration of desogestrel/ethinyl estradiol during organogenesis at doses at least 2/5 times, respectively, the anticipated daily vaginal human dose did not result in adverse developmental outcomes in these animal models.

However, it is important to note that co-administration of a maternally toxic dose of desogestrel/ethinyl estradiol to pregnant rats was associated with embryolethality and wavy ribs at doses that were 40/130 times, respectively, the anticipated vaginal human dose. In contrast, no adverse embryofetal effects were observed when the combination was administered to pregnant rats at doses that were 4/13 times, respectively, the anticipated vaginal human dose. In pregnant rabbits, pre-implantation loss was noted at a desogestrel/ethinyl estradiol dose that was 3/10 times, respectively, the anticipated vaginal human dose; however, no adverse embryofetal effects were observed at doses that were 2/5 times the anticipated vaginal human dose.

Healthcare professionals should discontinue the use of Etonogestrel/Ethinyl Estradiol Vaginal Ring if pregnancy is confirmed.

Lactation

Small amounts of contraceptive steroids and/or metabolites, including etonogestrel and ethinyl estradiol, are transferred to human milk. However, harmful effects have not been observed in breastfed infants exposed to combined hormonal contraceptives (CHCs) through breast milk.

It is important to note that CHCs can reduce milk production in breastfeeding mothers. This reduction is less likely to occur once breastfeeding is well-established; however, it can happen at any time in some women. Therefore, when possible, it is advisable to recommend that nursing mothers use non-estrogen-containing contraception until they have completely weaned their child.

The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for Etonogestrel/Ethinyl Estradiol Vaginal Ring and any potential adverse effects on the breastfed child from the use of this contraceptive method or from the underlying maternal condition.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular monitoring of renal function may be warranted in patients with reduced kidney function to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment should be closely monitored during treatment with Etonogestrel/Ethinyl Estradiol Vaginal Ring. In the event that jaundice develops, the use of the vaginal ring must be discontinued immediately. There are no specific dosage adjustments recommended for patients with compromised liver function; however, the potential for altered pharmacokinetics in this population necessitates careful observation for any signs of liver dysfunction. Regular assessment of liver function is advised to ensure patient safety throughout the course of therapy.

Overdosage

In the event of an overdose of the Etonogestrel/Ethinyl Estradiol Vaginal Ring, there have been no documented cases of serious adverse effects. However, potential symptoms of overdosage may include withdrawal bleeding in females and nausea.

It is important to note that if the vaginal ring is broken, it does not result in the release of a higher dose of hormones, mitigating concerns regarding increased hormonal exposure.

In cases of suspected overdose, it is recommended that all Etonogestrel/Ethinyl Estradiol Vaginal Rings be removed promptly. Following removal, symptomatic treatment should be administered as necessary to address any adverse symptoms experienced by the patient.

Nonclinical Toxicology

In a 24-month carcinogenicity study conducted in rats with subdermal implants releasing 10 and 20 mcg of etonogestrel per day, which corresponds to approximately 0.3 and 0.6 times the systemic steady-state exposure observed in women using the Etonogestrel/Ethinyl Estradiol Vaginal Ring, no drug-related carcinogenic potential was identified.

Etonogestrel demonstrated a lack of genotoxicity in several assays, including the in vitro Ames/Salmonella reverse mutation assay, the chromosomal aberration assay in Chinese hamster ovary cells, and the in vivo mouse micronucleus test.

A fertility study involving etonogestrel was performed in rats at a dose approximately 600 times the anticipated daily vaginal human dose (approximately 0.002 mg/kg/day). The results indicated that treatment did not adversely affect litter parameters following the cessation of treatment, thereby supporting the return to fertility after suppression with etonogestrel.

Postmarketing Experience

No specific postmarketing experience details have been reported. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use. It is essential to counsel patients about the increased risk of cardiovascular events associated with the use of Etonogestrel/Ethinyl Estradiol Vaginal Ring. Specifically, patients should be informed that cigarette smoking significantly heightens the risk of serious cardiovascular events when using this contraceptive method. Women over the age of 35 who smoke should be strongly advised against using the Etonogestrel/Ethinyl Estradiol Vaginal Ring.

Additionally, healthcare providers should inform patients that the risk of venous thromboembolism (VTE) is notably higher compared to non-users of combined hormonal contraceptives (CHCs), particularly during the initial use or upon restarting a CHC after a break of four weeks or more.

In terms of use and administration, it is crucial to inform patients that the Etonogestrel/Ethinyl Estradiol Vaginal Ring does not offer protection against HIV infection (AIDS) or other sexually transmitted infections. Providers should ensure that patients understand the proper usage of the vaginal ring, including the necessary steps to take if they do not adhere to the recommended timing for insertion and removal. Furthermore, patients should be advised to regularly check for the presence of the vaginal ring in the vagina, particularly before and after intercourse, to ensure its proper placement and effectiveness.

Storage and Handling

Etonogestrel/Ethinyl Estradiol Vaginal Ring is supplied in a manner that ensures optimal storage and handling. Prior to dispensing, the product must be stored refrigerated at a temperature range of 2°C to 8°C (36°F to 46°F). Once dispensed to the user, the ring can be stored for up to 4 months at a controlled room temperature of 25°C (77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F).

It is crucial to avoid exposure to direct sunlight and to refrain from storing the ring at temperatures exceeding 30°C (86°F). Upon dispensing, a label must be affixed to the product indicating an expiration date, which should not exceed 4 months from the dispensing date or the product's original expiration date, whichever is sooner.

After use, the ring should be returned to its reclosable sachet and disposed of in a waste receptacle that is out of reach of children and pets. The ring must not be flushed down the toilet.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Etonogestrel/Ethinyl Estradiol as submitted by Prasco Laboratories. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)