Enilloring

Description

EnilloRing (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 chemical structure 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol.

When inserted into the vagina, EnilloRing 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. EnilloRing is free from natural rubber latex and has an outer diameter of 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

EnilloRing 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 EnilloRing 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 remains in place throughout the three-week usage period to maintain its efficacy.

Contraindications

Use of EnilloRing 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 significant liver disease, which could lead to severe hepatic complications.

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

Pregnant individuals, due to potential risks to fetal development.

Patients with hypersensitivity reactions, including anaphylaxis and angioedema, to any components of EnilloRing, as this may result in severe allergic responses.

Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, is contraindicated due to the risk of drug interactions that may lead to adverse effects.

Warnings and Precautions

Women over 35 years of age who smoke are advised against the use of EnilloRing due to the increased risk of serious cardiovascular events associated with combination hormonal contraceptive (CHC) use. Healthcare professionals should counsel patients on the risks of cigarette smoking in conjunction with CHC.

In terms of general precautions, it is imperative to monitor for vascular risks. EnilloRing should be discontinued immediately if a thrombotic event occurs. Additionally, it is recommended to stop the use of EnilloRing at least 4 weeks prior to and throughout a period of 2 weeks following major surgery. For women who are not breastfeeding, initiation of EnilloRing should not occur earlier than 4 weeks postpartum.

Healthcare providers should be vigilant for signs of Toxic Shock Syndrome (TSS). If a patient presents with symptoms suggestive of TSS, appropriate medical evaluation and treatment should be initiated promptly. In cases of liver disease, EnilloRing must be discontinued if jaundice develops.

For women with well-controlled hypertension, regular monitoring of blood pressure is essential. If there is a significant rise in blood pressure, EnilloRing should be stopped. Furthermore, prediabetic and diabetic women require careful monitoring of carbohydrate and lipid metabolism. An alternative contraceptive method should be considered for women with uncontrolled dyslipidemia.

Significant changes in headache patterns should be evaluated, and EnilloRing use should be discontinued if warranted. Irregular uterine bleeding or amenorrhea should also be assessed to determine the appropriate course of action.

Laboratory tests should include monitoring for prediabetic and diabetic women to ensure safe use of EnilloRing.

In summary, healthcare professionals must remain vigilant regarding these warnings and precautions to ensure the safe use of EnilloRing in their patients.

Side Effects

Patients using EnilloRing may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

Common adverse reactions occurring in clinical trials (≥2%) 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 warnings are associated with the use of EnilloRing, particularly regarding cardiovascular risks. Women over 35 years old who smoke are advised against using this product, as cigarette smoking significantly increases the risk of serious cardiovascular events when using combination hormonal contraceptives.

Additional adverse reactions and important considerations include the need to discontinue EnilloRing if a thrombotic event occurs. It is recommended to stop use at least 4 weeks before and through 2 weeks after major surgery, and to wait at least 4 weeks after delivery in women who are not breastfeeding. Patients should be monitored for signs of Toxic Shock Syndrome (TSS), and if symptoms arise, appropriate medical evaluation and treatment should be initiated. Liver disease is another critical concern; EnilloRing should be discontinued if jaundice develops.

For women with well-controlled hypertension, blood pressure should be monitored, and EnilloRing use should cease if significant increases in blood pressure are observed. Additionally, 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 evaluation, and EnilloRing should be discontinued if necessary. Irregular uterine bleeding or amenorrhea should also be evaluated.

Contraindications for EnilloRing 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 EnilloRing, 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 Enilloring (etonogestrel and ethinyl estradiol vaginal), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Efficacy is expected to be the same for postpubertal adolescents under the age of 18 and for users 18 years and older. However, the use of this product before menarche is not indicated.

Geriatric Use

Elderly patients, particularly those who are postmenopausal, have not been studied in clinical trials involving EnilloRing. Therefore, the safety and efficacy of this medication in this specific population remain undetermined. As a result, EnilloRing is not indicated for use in postmenopausal women.

Healthcare providers should exercise caution when considering treatment options for geriatric patients, particularly those aged 65 and older, due to the lack of clinical data supporting the use of EnilloRing in this demographic. Monitoring for potential adverse effects and evaluating the appropriateness of alternative therapies is recommended.

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 risks and benefits. Women of childbearing potential should be counseled accordingly, and alternative treatment options should be considered if necessary.

Lactation

Lactating mothers should be informed that EnilloRing is not to be used during pregnancy. If a pregnancy is planned or occurs while using EnilloRing, it is advised that the patient discontinue use of the product. There is no specific data available regarding the excretion of EnilloRing in breast milk or its effects on breastfed infants. Therefore, healthcare professionals should exercise caution and consider the potential risks and benefits when prescribing EnilloRing 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 during treatment with EnilloRing. In the event that jaundice develops, the use of EnilloRing must be discontinued immediately. It is essential to assess liver function regularly to ensure patient safety and to determine the appropriateness of continued therapy. No specific dosage adjustments have been established for patients with hepatic impairment; however, the potential risks associated with liver dysfunction 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 note that overdosage may lead to withdrawal bleeding in females and symptoms such as nausea.

In the event of a suspected overdose, it is recommended that all EnilloRing devices be removed immediately. Following removal, symptomatic treatment should be administered as necessary to address any adverse symptoms experienced by the patient.

It is also pertinent to clarify that if the ring breaks, it does not result in the release of a higher dose of hormones, mitigating concerns regarding hormonal excess from a broken 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 EnilloRing, 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 with etonogestrel 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

Postmarketing experience has identified an increased risk of cardiovascular events associated with the use of EnilloRing. It has been reported that cigarette smoking significantly elevates the risk of serious cardiovascular events in users of EnilloRing, 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 longer.

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 EnilloRing. It is important to inform patients that cigarette smoking significantly elevates the risk of serious cardiovascular events when using EnilloRing. Specifically, women over 35 years of age who smoke should be advised against using EnilloRing, 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 EnilloRing does not provide protection against HIV infection (AIDS) or other sexually transmitted infections. Healthcare providers should advise patients on the correct usage of EnilloRing, 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 EnilloRing in the vagina, for instance, before and after intercourse, to ensure proper placement and effectiveness.

Storage and Handling

EnilloRing is supplied in individual aluminum laminate sachets, ensuring optimal protection and integrity of the product. The recommended storage conditions prior to dispensing require refrigeration at a temperature range of 2-8°C (36-46°F).

Once dispensed to the user, EnilloRing can be stored at room temperature, not exceeding 25°C (77°F), for a maximum duration of 4 months. 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 above 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 dispensing date or the original expiration date, whichever is earlier. After use, the EnilloRing should be returned to its foil pouch to maintain its quality. Used EnilloRings must be discarded in a waste receptacle that is out of reach of children and pets and 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 Enilloring as submitted by Xiromed, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)