Ethinyl estradiol/Etonogestrel

Description

Etonogestrel and ethinyl estradiol vaginal ring is a non-biodegradable, flexible, transparent, 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 chemical 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 device has an outer diameter of 54 mm and 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 and ethinyl estradiol vaginal ring is indicated for use by women as a combination hormonal contraceptive (CHC) to prevent pregnancy.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

One etonogestrel and 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 to ensure that the ring is properly positioned within the vaginal canal to maintain its efficacy.

Contraindications

Use of the etonogestrel and ethinyl estradiol vaginal ring is contraindicated in the following situations:

Patients with a high risk of arterial or venous thrombotic diseases should not use this product due to the potential for exacerbating these conditions. The presence of breast cancer or liver tumors, as well as any significant liver disease, contraindicates use because of the risk of tumor growth and liver function impairment.

Undiagnosed abnormal uterine bleeding is a contraindication, as it may mask serious underlying conditions. The product is also contraindicated in pregnancy due to potential harm to the developing fetus.

Patients with a known hypersensitivity to any components of the vaginal ring, including anaphylaxis and angioedema, should avoid its use. Additionally, co-administration with Hepatitis C drug combinations that include ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, is contraindicated due to the risk of significant drug interactions.

Warnings and Precautions

Women over 35 years of age who smoke are advised against the use of the etonogestrel and ethinyl estradiol vaginal ring due to an increased risk of serious cardiovascular events associated with cigarette smoking and combination hormonal contraceptive (CHC) use.

Vascular Risks The etonogestrel and ethinyl estradiol vaginal ring should be discontinued immediately if a thrombotic event occurs. Additionally, it is recommended to stop use at least 4 weeks prior to and through 2 weeks following major surgery. For women who are not breastfeeding, initiation of the ring should not occur earlier than 4 weeks postpartum.

Toxic Shock Syndrome (TSS) Healthcare professionals should be vigilant for signs or symptoms of Toxic Shock Syndrome (TSS). If such symptoms are present, appropriate medical evaluation and treatment should be initiated promptly.

Liver Disease In patients who develop jaundice, the etonogestrel and ethinyl estradiol vaginal ring must be discontinued.

Hypertension For women with well-controlled hypertension, it is essential to monitor blood pressure regularly. The etonogestrel and ethinyl estradiol vaginal ring should be stopped if there is a significant rise in blood pressure.

Metabolic Effects Monitoring is recommended for women with prediabetes or diabetes, as the etonogestrel and ethinyl estradiol vaginal ring may affect carbohydrate and lipid metabolism. An alternative contraceptive method should be considered for women with uncontrolled dyslipidemia.

Headaches Significant changes in headache patterns should be evaluated, and the etonogestrel and ethinyl estradiol vaginal ring should be discontinued if indicated.

Uterine Bleeding Irregular bleeding or amenorrhea should be assessed to determine the appropriate course of action.

Laboratory Tests Regular monitoring of blood pressure is advised for women with well-controlled hypertension. Additionally, prediabetic and diabetic women should be closely monitored for any metabolic changes.

In cases where signs or symptoms of Toxic Shock Syndrome (TSS) are observed, immediate medical evaluation and treatment are warranted.

Patients should be instructed to stop using the etonogestrel and ethinyl estradiol vaginal ring and contact their healthcare provider if any of the following occur: a thrombotic event, jaundice, significant increases in blood pressure, or notable changes in headache patterns.

Side Effects

Patients using the etonogestrel and ethinyl estradiol vaginal ring may experience a range of adverse reactions. Common adverse reactions occurring in clinical trials at a frequency of 2% or greater 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 and 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 of age who smoke are advised against using the etonogestrel and ethinyl estradiol vaginal ring due to an increased risk of serious cardiovascular events associated with combination hormonal contraceptive (CHC) use. In the event of a thrombotic event, it is recommended to discontinue use of the vaginal ring. Additionally, the use of the ring should be halted at least 4 weeks prior to and through 2 weeks after major surgery, and it should not be initiated 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. The vaginal ring should also be discontinued if jaundice develops, indicating potential liver disease. For women with well-controlled hypertension, blood pressure should be monitored, and the ring should be stopped if significant increases in blood pressure occur. Furthermore, prediabetic and diabetic women should be monitored for carbohydrate and lipid metabolic effects, and alternative contraceptive methods should be considered for those with uncontrolled dyslipidemia.

Significant changes in headache patterns should prompt an evaluation, and discontinuation of the vaginal ring may be necessary if indicated. Irregular bleeding or amenorrhea should also be evaluated to determine the appropriate course of action.

Contraindications for the use of the etonogestrel and 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 to any components of the ring, and co-administration with Hepatitis C drug combinations containing ombitasvir, paritaprevir, ritonavir, with or without dasabuvir.

Drug Interactions

Drugs or herbal products that induce specific enzymes, particularly CYP3A4, may reduce the effectiveness of combined hormonal contraceptives (CHCs) and potentially lead to increased breakthrough bleeding. It is advisable for healthcare providers to counsel patients on the importance of using a backup or alternative method of contraception when enzyme inducers are co-administered with CHCs. Monitoring for signs of reduced contraceptive efficacy is recommended during such combinations.

Packaging & NDC

The table below lists all NDC Code configurations of Etonogestrel and Ethinyl Estradiol Vaginal Ring, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and efficacy of the etonogestrel and 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. However, the use of this product is not indicated for individuals before menarche.

Geriatric Use

Etonogestrel and 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 treatment 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

There is no specific information available regarding the use of this medication during pregnancy, including safety concerns, dosage modifications, or special precautions that should be taken. Healthcare professionals are advised to consider the lack of data when prescribing this medication to pregnant patients and to weigh the potential benefits against any unknown risks to fetal outcomes. Women of childbearing potential should be counseled accordingly.

Lactation

Etonogestrel and ethinyl estradiol vaginal ring is not indicated for use during pregnancy. Lactating mothers who are planning to become pregnant or who become pregnant while using the vaginal ring should discontinue its use immediately.

For lactating mothers who initiate use of the etonogestrel and ethinyl estradiol vaginal ring postpartum and have not yet experienced a normal menstrual period, it is recommended to employ an additional non-hormonal method of contraception for the first seven days of use to ensure adequate contraceptive protection.

There is no specific data provided regarding the excretion of etonogestrel and ethinyl estradiol in breast milk or the effects on breastfed infants. Therefore, healthcare professionals should exercise caution and consider the potential risks and benefits when prescribing this contraceptive method to lactating mothers.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to this patient population.

Hepatic Impairment

Patients with hepatic impairment should be closely monitored for any signs of liver dysfunction during treatment with the etonogestrel and ethinyl estradiol vaginal ring. In the event that jaundice develops, it is recommended to discontinue the use of the vaginal ring immediately. No specific dosage adjustments are provided for patients with compromised liver function; however, the potential risks associated with hepatic impairment necessitate careful consideration and monitoring of liver function throughout the treatment period.

Overdosage

In the event of an overdose involving the etonogestrel and ethinyl estradiol vaginal ring, it is important to note that there have been no reports of serious ill effects associated with such occurrences. However, potential symptoms of overdosage may include withdrawal bleeding in females and nausea.

If a suspected overdose is identified, the immediate action recommended is the removal of all etonogestrel and ethinyl estradiol vaginal rings. Following removal, healthcare professionals should provide symptomatic treatment as necessary to manage any adverse effects experienced by the patient.

It is also pertinent to clarify that if the vaginal ring is broken, it does not result in the release of a higher dose of hormones, thereby mitigating concerns regarding increased hormonal exposure from a compromised device.

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 and ethinyl estradiol vaginal ring, no drug-related carcinogenic potential was identified.

Etonogestrel was evaluated for mutagenic potential and was found to be non-genotoxic 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 conclusion that fertility was restored after suppression with etonogestrel.

Postmarketing Experience

No specific postmarketing experience details are available. 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 and 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 cautioned against using the etonogestrel and ethinyl estradiol vaginal ring, as highlighted in the Boxed Warning.

Additionally, healthcare providers should inform patients about the increased risk of venous thromboembolism (VTE) compared to non-users of combined hormonal contraceptives (CHCs). This risk is particularly pronounced after initiating a CHC or after a break of four weeks or more from using the same or a different CHC, as detailed in the Warnings and Precautions section.

In terms of use and administration, it is crucial to inform patients that the etonogestrel and ethinyl estradiol vaginal ring does not provide protection against HIV infection (AIDS) or other sexually transmitted infections. Healthcare providers should also advise patients on the correct usage of the vaginal ring and the necessary steps to take if they do not adhere to the recommended timing for insertion and removal, as outlined in the Dosage and Administration section. Furthermore, patients should be encouraged to regularly check for the presence of the vaginal ring in the vagina, for instance, before and after intercourse, to ensure proper placement and effectiveness.

Storage and Handling

The etonogestrel and ethinyl estradiol vaginal ring is supplied in a foil pouch. It should be stored refrigerated at a temperature range of 2-8°C (36-46°F) prior to dispensing. After dispensing, the ring can be stored for up to 4 months at a controlled room temperature of 25°C (77°F). Temperature excursions are permissible between 15 to 30°C (59 to 86°F); however, it is critical to avoid exposure to direct sunlight and to ensure that the storage temperature does not exceed 30°C (86°F).

Upon dispensing, it is essential to label the product with an expiration date that does not exceed 4 months from the date of dispensing or the original expiration date, whichever is earlier. After use, the ring should be returned to its foil pouch and disposed of in a waste receptacle that is out of reach of children and pets. It is important to note that the ring should 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 and Ethinyl Estradiol Vaginal Ring as submitted by Northstar Rx LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)