Ethinyl estradiol/Etonogestrel

Description

Etonogestrel and 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 vaginal ring is not manufactured 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) for the prevention of 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 that the ring is not removed during the three-week usage period to ensure optimal efficacy.

Contraindications

Use of the product 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 is a contraindication, as the product may influence tumor growth. Individuals with liver tumors or liver disease are also contraindicated, given the risk of hepatic complications.

Undiagnosed abnormal uterine bleeding warrants avoidance of this product until a definitive diagnosis is established. The use of this product during pregnancy is contraindicated due to potential harm to the fetus.

Patients with hypersensitivity to any components of the Etonogestrel and ethinyl estradiol vaginal ring, including anaphylaxis and angioedema, should not use this product. Additionally, co-administration with Hepatitis C drug combinations containing 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 use of the Etonogestrel and ethinyl estradiol vaginal ring should be discontinued immediately if a thrombotic event occurs. Additionally, it is recommended to stop usage at least 4 weeks prior to and throughout a period of 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 use of the Etonogestrel and ethinyl estradiol vaginal ring must be discontinued immediately.

Hypertension For women with well-controlled hypertension, it is essential to monitor blood pressure regularly. The use of the 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. An alternative contraceptive method should be considered for those with uncontrolled dyslipidemia.

Headaches Significant changes in headache patterns should be evaluated, and the use of the Etonogestrel and ethinyl estradiol vaginal ring should be discontinued if warranted.

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 patients exhibit signs or symptoms of TSS, immediate medical evaluation and treatment are necessary. Furthermore, the Etonogestrel and ethinyl estradiol vaginal ring should be discontinued if a thrombotic event occurs, if jaundice develops, if there is a significant rise in blood pressure, or if there are significant 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 2% or more of participants, include vaginitis, headache (including migraine), mood changes such as depression and mood swings, 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 old who smoke are advised against using this combination hormonal contraceptive due to an increased risk of serious cardiovascular events. In the event of a thrombotic event, it is crucial to discontinue use of the vaginal ring. Additionally, it is recommended to stop use at least 4 weeks prior to 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 function should also be monitored, and the use of the vaginal ring should be discontinued if jaundice develops. For women with well-controlled hypertension, blood pressure should be regularly monitored, and the vaginal 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 be evaluated, and discontinuation of the vaginal ring may be necessary if indicated. Irregular bleeding or amenorrhea should also be assessed to determine the appropriate course of action.

Drug Interactions

Drugs or herbal products that induce cytochrome P450 3A4 (CYP3A4) enzymes 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 during such co-administration.

Packaging & NDC

The table below lists all NDC Code configurations of Etonogestrel and Ethinyl Estradiol Vaginal, 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 therefore is not indicated for use in this population. Healthcare providers should exercise caution when considering the use of this medication in geriatric patients, as the lack of clinical data in this demographic limits the ability to assess safety and efficacy. Monitoring for potential adverse effects is advised if the medication is considered for use in patients under 65 years of age.

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 on the importance of discussing any plans for pregnancy or potential exposure during pregnancy with their healthcare provider.

Lactation

Etonogestrel and ethinyl estradiol vaginal ring is not indicated for use during pregnancy. Lactating mothers should be informed that if pregnancy is planned or occurs while using the vaginal ring, it is essential to discontinue its use immediately.

There is no specific data available 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 advising lactating mothers about the use of this contraceptive method.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

Hepatic Impairment

Patients with hepatic impairment should be closely monitored during treatment with the etonogestrel and ethinyl estradiol vaginal ring. In the event that jaundice develops, the use of the vaginal ring must be discontinued immediately. It is essential for healthcare providers to assess liver function regularly and to evaluate any signs of liver disease throughout the course of therapy. Adjustments to the treatment regimen may be necessary based on the patient's liver status and overall clinical condition.

Overdosage

In cases of overdosage with combined hormonal contraceptives (CHCs), there have been no documented instances of serious adverse effects. However, it is important to be aware of potential symptoms that may arise from an overdose.

Potential Symptoms Overdosage may lead to withdrawal bleeding in females, as well as nausea. These symptoms should be monitored closely in patients who may have ingested an excessive amount of the product.

Management of Overdosage In the event of a suspected overdose, it is recommended that all Etonogestrel and ethinyl estradiol vaginal rings be removed immediately. Following removal, symptomatic treatment should be administered as necessary to address any symptoms that may occur.

It is noteworthy that if the vaginal ring breaks, it does not result in the release of a higher dose of hormones, which may alleviate concerns regarding hormonal excess in such scenarios.

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

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use. Healthcare providers should counsel patients regarding the increased risk of cardiovascular events associated with the use of Etonogestrel and ethinyl estradiol vaginal ring. It is important to inform patients that cigarette smoking significantly increases the risk of serious cardiovascular events when using this contraceptive method. Specifically, women who are over 35 years old and smoke should be advised against using the Etonogestrel and ethinyl estradiol vaginal ring.

Additionally, patients should be made aware that the risk of venous thromboembolism (VTE) is heightened compared to non-users of combined hormonal contraceptives (CHCs), particularly after initially starting a CHC or after a 4-week or longer CHC-free interval when restarting the same or a different CHC.

In terms of use and administration, patients must be informed that the Etonogestrel and ethinyl estradiol vaginal ring does not provide protection against HIV infection (AIDS) or other sexually transmitted infections. Healthcare providers should advise patients on the proper usage of the vaginal ring, including what actions to take if they do not adhere to the labeled timing for insertion and removal. Furthermore, patients should be encouraged to regularly check for the presence of the vaginal ring in the vagina, for instance, before and after intercourse.

Storage and Handling

The Etonogestrel and ethinyl estradiol vaginal ring is supplied in a manner that ensures optimal storage and handling. It should be stored refrigerated at a temperature range of 2-8°C (36-46°F) prior to dispensing. Once dispensed, 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 crucial to avoid exposure to direct sunlight or temperatures exceeding 30°C (86°F).

After use, the ring must be returned to its aluminum laminate sachet 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. When dispensing the product, healthcare professionals are required to place an expiration date on the label, which should not exceed 4 months from the date of dispensing or the product's original expiration date, whichever is sooner.

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 as submitted by AvKARE. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)