Eluryng

Description

EluRyng (etonogestrel and ethinyl estradiol vaginal ring) is a non-biodegradable, flexible, transparent to translucent, 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, USP.

When inserted into the vagina, each ring releases an average of 0.120 mg/day of etonogestrel and 0.015 mg/day of ethinyl estradiol, USP 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 etonogestrel and 2.7 mg ethinyl estradiol, USP. EluRyng is not manufactured with natural rubber latex. The ring has an outer diameter of 54 mm and a cross-sectional diameter of 4 mm. The molecular weights of the active ingredients are 324.5 for etonogestrel and 296.40 for ethinyl estradiol, USP.

Uses and Indications

EluRyng is indicated for use by women as a combination hormonal contraceptive (CHC) to prevent pregnancy.

There are no teratogenic or nonteratogenic effects associated with the use of EluRyng.

Dosage and Administration

One EluRyng 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 and retained throughout the three-week usage to maintain its efficacy.

Contraindications

Use of EluRyng 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 product may promote tumor growth.

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

Those experiencing undiagnosed abnormal uterine bleeding, as this may mask underlying conditions.

Pregnant individuals, due to potential harm to the fetus.

Patients with hypersensitivity to any components of EluRyng, including a history of anaphylaxis or angioedema.

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 EluRyng, as cigarette smoking significantly increases the risk of serious cardiovascular events associated with combination hormonal contraceptive (CHC) use.

General Precautions

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

Toxic Shock Syndrome (TSS) is a serious condition that requires prompt attention. If a patient presents with signs or symptoms suggestive of TSS, it is crucial to consider this diagnosis and initiate appropriate medical evaluation and treatment.

In patients with liver disease, the use of etonogestrel and ethinyl estradiol vaginal ring should be discontinued if jaundice develops.

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

Women with prediabetes or diabetes should be monitored for carbohydrate and lipid metabolic effects. An alternative contraceptive method should be considered for those with uncontrolled dyslipidemia.

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

Irregular uterine bleeding or amenorrhea should be evaluated to determine the appropriate course of action.

Laboratory Tests

Monitoring of prediabetic and diabetic women is recommended to ensure safe use of the etonogestrel and ethinyl estradiol vaginal ring.

In summary, healthcare professionals should remain vigilant regarding the outlined warnings and precautions to ensure the safe use of etonogestrel and ethinyl estradiol vaginal ring in their patients.

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 warnings are associated with the use of this contraceptive method. Women over 35 years of age who smoke are advised against using the etonogestrel and ethinyl estradiol vaginal ring, as cigarette smoking significantly increases the risk of serious cardiovascular events related to combination hormonal contraceptive use. Additionally, if a thrombotic event occurs, the use of the vaginal ring should be discontinued immediately. It is also recommended to stop use at least 4 weeks prior to and through 2 weeks after major surgery, and not to initiate use earlier than 4 weeks postpartum in women who are not breastfeeding.

Other important considerations include the potential for Toxic Shock Syndrome (TSS); patients exhibiting signs or symptoms of TSS should undergo appropriate medical evaluation and treatment. The use of the vaginal ring should be discontinued if jaundice develops, indicating possible liver disease. Women with well-controlled hypertension should have their blood pressure monitored, and the vaginal ring should be stopped if there is a significant rise in blood pressure. 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 also prompt evaluation, and the vaginal ring should be discontinued if indicated. Irregular bleeding or amenorrhea should be assessed as well.

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 (including anaphylaxis and angioedema) to any of the components of EluRyng, 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 Eluryng (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 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 elderly patients.

Pregnancy

Etonogestrel and 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 no adverse developmental outcomes 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, no adverse developmental outcomes were observed with the co-administration of desogestrel and ethinyl estradiol during organogenesis at doses at least 2/5 times, respectively, the anticipated daily vaginal human dose.

However, it is important to note that the co-administration of a maternally toxic dose of desogestrel and 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 doses that were 3/10 times, respectively, the anticipated vaginal human dose, while 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 the etonogestrel and 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 occur 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 the etonogestrel and ethinyl estradiol vaginal ring, as well as any potential adverse effects on the breastfed child from the use of this contraceptive method or from the underlying maternal condition.

Renal Impairment

There is no specific information 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 for any signs of liver dysfunction 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. There are no specific dosage adjustments recommended for patients with compromised liver function; however, the potential risks associated with hepatic impairment necessitate careful consideration and monitoring throughout the treatment period.

Overdosage

In cases of overdosage with CHCs, there have been no documented instances of serious adverse effects. However, it is important to be aware of potential symptoms that may arise. Overdosage may lead to withdrawal bleeding in females, as well as nausea.

In the event of a suspected overdose, it is crucial to remove all EluRyng rings immediately. Following the removal, symptomatic treatment should be administered as necessary. It is noteworthy that if the ring breaks, it does not result in the release of a higher dose of hormones, which mitigates concerns regarding hormone excess from a broken device.

Healthcare professionals should monitor patients for any symptoms and provide appropriate care based on the clinical presentation.

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 EluRyng, 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 treatment did not result in any adverse effects on litter parameters following the cessation of treatment, indicating a return to fertility after suppression with etonogestrel.

Postmarketing Experience

Postmarketing experience has identified an increased risk of cardiovascular events associated with the use of EluRyng. It has been reported that cigarette smoking further elevates the risk of serious cardiovascular events in users of EluRyng, particularly in women over the age of 35, who are advised against its use. Additionally, data indicate that the risk of venous thromboembolism (VTE) is notably higher in individuals who have recently initiated or restarted combined hormonal contraceptives (CHCs), especially following a CHC-free interval of four weeks or more.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use. It is important to counsel patients about the increased risk of cardiovascular events associated with the use of EluRyng. Specifically, healthcare providers should inform patients that cigarette smoking significantly elevates the risk of serious cardiovascular events when using EluRyng. Women over the age of 35 who smoke should be advised against using EluRyng, as highlighted in the Boxed Warning.

Additionally, patients should be made aware that the risk of venous thromboembolism (VTE) is greater for those using combined hormonal contraceptives (CHCs) compared to non-users. 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, patients must be informed that EluRyng does not provide protection against HIV infection (AIDS) or other sexually transmitted infections. Healthcare providers should advise patients on the correct usage of EluRyng, including 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 EluRyng in the vagina, for instance, before and after intercourse, to ensure proper placement and effectiveness.

Storage and Handling

EluRyng is supplied in a reclosable pouch, which should be stored refrigerated at a temperature range of 2° to 8°C (36° to 46°F) prior to dispensing to the user. After dispensing, EluRyng can be stored for up to 4 months at ambient temperatures between 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F). It is essential to avoid exposure to direct sunlight and to ensure that the storage temperature does not exceed 30°C (86°F).

Upon dispensing, it is required 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 the reclosable pouch and disposed of in a waste receptacle that is out of reach of children and pets; it 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 Eluryng as submitted by Amneal Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)