Nuvaring

Description

NuvaRing (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, NuvaRing 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. NuvaRing is not manufactured with natural rubber latex. It 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

NuvaRing is indicated for use by women to prevent pregnancy. There are no teratogenic or nonteratogenic effects associated with its use.

Dosage and Administration

One NuvaRing 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 instruct patients on the proper insertion technique to ensure the ring is positioned correctly and remains effective throughout the three-week usage period.

Contraindications

Use of NuvaRing 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.

• Individuals with undiagnosed abnormal uterine bleeding, as this may mask underlying conditions.

• Pregnant patients, due to potential harm to the fetus.

• Patients with hypersensitivity to any components of NuvaRing, including those with 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 NuvaRing 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 discontinue NuvaRing immediately if a thrombotic event occurs. Additionally, NuvaRing should be stopped at least 4 weeks prior to and maintained through 2 weeks after any major surgical procedure. For women who are not breastfeeding, initiation of NuvaRing should not occur earlier than 4 weeks postpartum.

Healthcare providers should be vigilant for signs and symptoms of Toxic Shock Syndrome (TSS) in patients using NuvaRing. If TSS is suspected, appropriate medical evaluation and treatment should be initiated promptly.

Patients with liver disease should discontinue the use of NuvaRing if jaundice develops. For women with well-controlled hypertension, regular monitoring of blood pressure is essential, and NuvaRing should be stopped if there is a significant increase in blood pressure.

Monitoring is also recommended for prediabetic and diabetic women, as NuvaRing may affect carbohydrate and lipid metabolism. An alternative contraceptive method should be considered for women with uncontrolled dyslipidemia.

Healthcare professionals should evaluate any significant changes in headache patterns in patients using NuvaRing, and discontinue use if warranted. Irregular uterine bleeding or amenorrhea should also be assessed to determine the need for continued use of NuvaRing.

Regular laboratory tests should be conducted to monitor prediabetic and diabetic women to ensure their safety while using NuvaRing.

Side Effects

Patients using NuvaRing 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 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 NuvaRing, particularly regarding cigarette smoking and serious cardiovascular events. Women over 35 years of age who smoke are advised against using NuvaRing, as cigarette smoking significantly increases the risk of serious cardiovascular events related to combination hormonal contraceptive use.

Additional adverse reactions and important considerations include vascular risks; patients should discontinue NuvaRing if a thrombotic event occurs and should stop use at least 4 weeks before and through 2 weeks after major surgery. It is recommended to start NuvaRing no earlier than 4 weeks after delivery in women who are not breastfeeding. Toxic Shock Syndrome (TSS) is a potential risk; if a patient exhibits signs or symptoms of TSS, appropriate medical evaluation and treatment should be initiated.

Patients with liver disease should discontinue NuvaRing if jaundice develops. For women with well-controlled hypertension, blood pressure should be monitored, and NuvaRing should be stopped if blood pressure rises significantly. Carbohydrate and lipid metabolic effects should be monitored in prediabetic and diabetic women, and an alternate contraceptive method should be considered for those with uncontrolled dyslipidemia. Significant changes in headache patterns should be evaluated, and NuvaRing should be discontinued if indicated. Irregular bleeding or amenorrhea should also be evaluated.

Contraindications for NuvaRing 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 NuvaRing, 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 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 is also recommended during such co-administration.

Packaging & NDC

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

Pediatric Use

Safety and efficacy of NuvaRing have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older. The use of this product before menarche is not indicated.

Geriatric Use

Elderly patients, specifically those aged 65 and older, have not been studied in relation to the use of NuvaRing. As such, the safety and efficacy of this product in geriatric patients, particularly postmenopausal women, remain undetermined. Therefore, NuvaRing is not indicated for use in this population. Healthcare providers should exercise caution when considering the use of this product in elderly patients and should monitor for any potential adverse effects or complications that may arise due to the lack of clinical data in this demographic.

Pregnancy

NuvaRing 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 the combination of desogestrel and 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.

However, caution is warranted as the 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, while no adverse embryofetal effects were observed at doses that were 2/5 times the anticipated vaginal human dose.

If pregnancy is confirmed, it is recommended to discontinue the use of NuvaRing.

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.

Healthcare professionals should consider the developmental and health benefits of breastfeeding alongside the mother's clinical need for NuvaRing and any potential adverse effects on the breastfed child from NuvaRing or from the underlying maternal condition.

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 while using NuvaRing. In the event that jaundice develops, it is recommended that the use of NuvaRing be discontinued immediately. There are no specific dosage adjustments 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 cases of overdosage with combined hormonal contraceptives (CHCs), there have been no reports of serious ill effects. However, it is important to be aware of potential symptoms that may arise. Overdosage may lead to withdrawal bleeding in females and nausea.

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

It is noteworthy that if the NuvaRing breaks, it does not result in the release of a higher dose of hormones, mitigating concerns regarding hormone overdose 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 NuvaRing, 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 NuvaRing. It is important to inform patients that cigarette smoking significantly elevates the risk of serious cardiovascular events when using NuvaRing. Specifically, women over 35 years of age who smoke should be advised against using NuvaRing, 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 during the initial use of 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.

It is crucial to inform patients that NuvaRing does not provide protection against HIV infection (AIDS) or other sexually transmitted infections. Healthcare providers should also advise patients on the correct usage of NuvaRing, 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.

Lastly, patients should be encouraged to regularly check for the presence of NuvaRing in the vagina, for instance, before and after intercourse, to ensure proper placement and effectiveness, as specified in the Dosage and Administration guidelines.

Storage and Handling

NuvaRing is supplied in a reclosable sachet. Prior to dispensing, it must be stored refrigerated at a temperature range of 2°C to 8°C (36°F to 46°F). Once dispensed to the user, NuvaRing 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 essential to avoid exposure to direct sunlight and to ensure that the storage temperature does not exceed 30°C (86°F). Upon dispensing, an expiration date must be affixed to the label, which should not exceed either 4 months from the dispensing date or the product's original expiration date, whichever is sooner.

After use, the ring should be returned to the reclosable sachet and disposed of in a waste receptacle that is out of reach of children and pets. It is important to note that NuvaRing 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 Nuvaring as submitted by Advanz Pharma (US) Corp.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)