Nuvaring

Description

NuvaRing (etonogestrel/ethinyl estradiol vaginal ring) is a non-biodegradable, flexible, transparent, colorless to almost colorless, combination contraceptive vaginal ring. The active components are etonogestrel (13-ethyl-17-hydroxy-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3-one) and ethinyl estradiol (19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol). Each ring releases on average 0.120 mg/day of etonogestrel and 0.015 mg/day of ethinyl estradiol over a three-week period of use. NuvaRing is composed of ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate. It contains 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol. NuvaRing is not made with natural rubber latex. The outer diameter of NuvaRing is 54 mm, and the cross-sectional diameter is 4 mm. The molecular weights for etonogestrel and ethinyl estradiol are 324.46 and 296.40, respectively.

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 the ring is not removed during the three-week usage period to ensure effective contraceptive action.

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 of Toxic Shock Syndrome (TSS). If symptoms suggestive of TSS arise, appropriate medical evaluation and treatment should be initiated promptly. In patients with liver disease, NuvaRing 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, NuvaRing should be discontinued. 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 NuvaRing 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 NuvaRing.

In summary, healthcare professionals must remain vigilant in monitoring patients for the aforementioned conditions and take appropriate action, including discontinuation of NuvaRing, when necessary.

Side Effects

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

Common adverse reactions occurring in 2% or more of patients 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 old who smoke are advised against using NuvaRing due to an increased risk of serious cardiovascular events associated with combination hormonal contraceptive (CHC) use. Additionally, if a thrombotic event occurs, NuvaRing use should be discontinued immediately. It is also recommended to stop NuvaRing at least 4 weeks prior to and through 2 weeks after major surgery, and to wait at least 4 weeks after delivery before resuming use 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. NuvaRing should be discontinued if jaundice develops, indicating potential liver disease. For women with well-controlled hypertension, blood pressure should be monitored, and NuvaRing use should cease if significant increases in blood pressure occur. Additionally, prediabetic and diabetic women should be monitored for carbohydrate and lipid metabolic effects, and an alternative contraceptive method should be considered for those with uncontrolled dyslipidemia.

Significant changes in headache patterns should be evaluated, and NuvaRing use should be discontinued if indicated. Irregular uterine bleeding or amenorrhea should also be assessed.

In summary, while many patients tolerate NuvaRing well, it is essential to be vigilant regarding both common and serious adverse reactions, ensuring appropriate monitoring and intervention as necessary.

Drug Interactions

Drugs or herbal products that induce enzymes, particularly CYP3A4, may reduce the effectiveness of combined hormonal contraceptives (CHCs) and potentially lead to increased instances of breakthrough bleeding. It is advisable for healthcare providers to counsel patients on the necessity of utilizing a back-up or alternative method of contraception during the concurrent use of enzyme inducers with CHCs to ensure continued contraceptive efficacy.

No specific drug and laboratory test interactions have been reported.

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 this demographic remain undetermined. Furthermore, NuvaRing is not indicated for use in postmenopausal women. Healthcare providers should exercise caution when considering the use of NuvaRing in elderly patients, and alternative therapies should be evaluated to ensure appropriate care. Regular monitoring and assessment of treatment outcomes are recommended for any geriatric patients who may be considered for therapy with this product.

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 the administration of etonogestrel during organogenesis in pregnant rats and rabbits at doses approximately 300 times the anticipated daily vaginal human dose (~0.002 mg/kg/day) did not result in adverse developmental outcomes. 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 also did not lead to 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

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 for any signs of liver dysfunction while using NuvaRing. In the event that jaundice develops, it is recommended that NuvaRing use 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

Overdosage may lead to withdrawal bleeding in females, as well as nausea. In the event of a suspected overdose, it is imperative that all NuvaRing devices are removed immediately. Following the removal, appropriate symptomatic treatment should be administered to manage any adverse effects experienced by the patient. Healthcare professionals are advised to monitor the patient closely and provide supportive care as necessary.

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

Reports from postmarketing surveillance have identified several adverse events associated with the use of NuvaRing. Instances of the device becoming adhered to vaginal tissue have been documented, necessitating removal by healthcare professionals.

Epidemiological studies indicate that the risk of venous thromboembolism in women using NuvaRing is comparable to that observed in users of combination oral contraceptives. However, some studies suggest an elevated risk of blood clots in women using combination birth control pills containing desogestrel, a progestin similar to that in NuvaRing, compared to those using formulations without desogestrel. Serious complications related to blood clots, such as heart attack or stroke, may result in severe outcomes, including death or permanent disability.

Additional serious risks associated with NuvaRing include Toxic Shock Syndrome (TSS), allergic reactions manifesting as hives or swelling of the face, lips, tongue, and/or throat (potentially leading to anaphylaxis or angioedema), liver complications including tumors, hypertension, gallbladder issues, and accidental insertion into the bladder. Symptoms of angioedema may occur, particularly in individuals with a familial history of the condition.

Common side effects reported include tissue irritation within the vagina or on the cervix, headaches (including migraines), and mood alterations, particularly in individuals with a prior history of depression. Other noted side effects encompass breast discharge, vaginal injuries related to broken rings, and discomfort experienced by partners, such as irritation or rash.

Less frequently reported side effects associated with combination hormonal contraceptives include skin hyperpigmentation, particularly on the face, elevated blood glucose levels in women with pre-existing diabetes, and increased lipid levels in the blood.

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 increases this risk, particularly in women over 35 years of age, who should not use NuvaRing.

Patients should be made aware that the risk of venous thromboembolism (VTE) is heightened compared to non-users of combined hormonal contraceptives (CHCs), especially after initially starting or restarting a CHC following a break of four weeks or more. Additionally, it should be communicated that NuvaRing does not provide protection against HIV infection (AIDS) or other sexually transmitted infections.

Healthcare providers should instruct patients on the proper usage of NuvaRing, including what actions to take if they do not adhere to the recommended timing for insertion and removal. Patients should be advised to regularly check for the presence of NuvaRing in the vagina, particularly before and after intercourse.

It is crucial to inform patients that NuvaRing is contraindicated during pregnancy. If a patient plans to become pregnant or discovers she is pregnant while using NuvaRing, she should discontinue its use immediately. Furthermore, patients need to be instructed to use a barrier method of contraception if the ring is out for more than three continuous hours until NuvaRing has been used continuously for at least seven days.

Patients should also be informed about the need for a back-up or alternative method of contraception when using enzyme inducers alongside NuvaRing. For those who start using NuvaRing postpartum and have not yet had a normal menstrual period, it is essential to use an additional non-hormonal method of contraception for the first seven days.

Healthcare providers should discuss the potential impact of CHCs on breast milk production, noting that this is less likely to occur if breastfeeding is well established. Patients should be informed that amenorrhea may occur and that pregnancy should be ruled out in specific situations, such as if NuvaRing has been out of the vagina for more than three consecutive hours, if the ring-free interval exceeds one week, if the patient has missed periods for two or more consecutive cycles, or if the ring has been retained for longer than four weeks.

Finally, patients should receive guidance on the proper disposal of a used NuvaRing to ensure safe and responsible handling.

Storage and Handling

NuvaRing is supplied in a manner that ensures optimal storage and handling conditions. 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 room temperature, specifically at 25°C (77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F).

It is critical to avoid exposure to direct sunlight and to refrain from storing NuvaRing at temperatures exceeding 30°C (86°F). Upon dispensing, healthcare professionals are required to label the product with an expiration date, which should not exceed either 4 months from the date of dispensing or the product's original expiration date, whichever is sooner.

After use, the ring should be returned to its 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 Organon LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)