1 INDICATIONS AND USAGE

FOR VAGINAL USE ONLY

NuvaRing® is indicated for use by females of reproductive age to prevent pregnancy.

2 DOSAGE AND ADMINISTRATION

3 DOSAGE FORMS AND STRENGTHS

NuvaRing (etonogestrel/ethinyl estradiol vaginal ring) is a non-biodegradable, flexible, transparent, colorless to almost colorless, combination contraceptive vaginal ring, with an outer diameter of 54 mm and a cross-sectional diameter of 4 mm. It is made of ethylene vinylacetate copolymers and magnesium stearate, and contains 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol. When placed in the vagina, 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 not made with natural rubber latex.

4 CONTRAINDICATIONS

Do not prescribe NuvaRing to women who are known to have or use the following:

• A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:
  • Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1)]
  • Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1)]
  • Have cerebrovascular disease [see Warnings and Precautions (5.1)]
  • Have coronary artery disease [see Warnings and Precautions (5.1)]
  • Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions (5.1)]
  • Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1)]
  • Have uncontrolled hypertension [see Warnings and Precautions (5.5)]
  • Have diabetes mellitus with vascular disease [see Warnings and Precautions (5.9)]
  • Have headaches with focal neurological symptoms or migraine headaches with aura [see Warnings and Precautions (5.10)]
    • Women over age 35 with any migraine headaches [see Warnings and Precautions (5.10)]
• Liver tumors, benign or malignant or liver disease [see Warnings and Precautions (5.3) and Use in Specific Populations (8.6)]
• Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.11)]
• Pregnancy, because there is no reason to use CHCs during pregnancy [see Use in Specific Populations (8.1)]
• Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past [see Warnings and Precautions (5.14)]
• Hypersensitivity reactions, including anaphylaxis and angioedema, to any of the components of NuvaRing [see Warnings and Precautions (5.6) and Adverse Reactions (6)]
• Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions (5.4)]

5 WARNINGS AND PRECAUTIONS

5.1 Thromboembolic Disorders and Other Vascular Problems

Stop NuvaRing use if an arterial thrombotic or venous thromboembolic event (VTE) occurs. Stop NuvaRing use if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately. [See Adverse Reactions (6).]

If feasible, stop NuvaRing at least four weeks before and through two weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism, and during and following prolonged immobilization.

Start NuvaRing no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.

The use of CHCs increases the risk of VTE. Known risk factors for VTE include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs [see Contraindications (4)].

Two epidemiologic studies1, 2, 3 that assessed the risk of VTE associated with the use of NuvaRing are described below.

In these studies, which were required or sponsored by regulatory agencies, NuvaRing users had a risk of VTE similar to Combined Oral Contraceptives (COCs) users (see Table 1 for adjusted hazard ratios). A large prospective, observational study, the Transatlantic Active Surveillance on Cardiovascular Safety of NuvaRing (TASC), investigated the risk of VTE for new users, and women who were switching to or restarting NuvaRing or COCs in a population that is representative of routine clinical users. The women were followed for 24 to 48 months. The results showed a similar risk of VTE among NuvaRing users (VTE incidence 8.3 per 10,000 WY) and women using COCs (VTE incidence 9.2 per 10,000 WY). For women using COCs that did not contain the progestins desogestrel (DSG) or gestodene (GSD), VTE incidence was 8.9 per 10,000 WY.

A retrospective cohort study using data from 4 health plans in the US (FDA-funded Study in Kaiser Permanente and Medicaid databases) showed the VTE incidence for new users of NuvaRing to be 11.4 events per 10,000 WY, for new users of a levonorgestrel (LNG)-containing COC 9.2 events per 10,000 WY, and for users of other COCs available during the course of the study1 8.2 events per 10,000 WY.

Table 1: Estimates (Hazard Ratios) of Venous Thromboembolism Risk in Users of NuvaRing Compared to Users of Combined Oral Contraceptives (COCs)

Epidemiologic Study (Author, Year of Publication) Population Studied	Comparator Product(s)	Hazard Ratios (HR) (95% CI)
* Includes low-dose COCs containing the following progestins: chlormadinone acetate, cyproterone acetate, desogestrel, dienogest, drospirenone, ethynodiol diacetate, gestodene, levonorgestrel, norethindrone, norgestimate, or norgestrel † Adjusted for age, BMI, duration of use, VTE history ‡ Includes low-dose COCs containing the following progestins: norgestimate, norethindrone, or levonorgestrel § Adjusted for age, site, year of entry into study
TASC (Dinger, 2012) Initiators, including new users, switchers and restarters	All COCs available during the course of the study * COCs available excluding DSG- or GSD -containing OCs	HR†: 0.8 (0.5-1.5) HR†: 0.8 (0.4-1.7)
FDA-funded Study in Kaiser Permanente and Medicaid databases (Sidney, 2011)
First use of a combined hormonal contraceptive (CHC) during the study period	COCs available during the course of the study‡	HR§: 1.1 (0.6-2.2)
	LNG/0.03 mg ethinyl estradiol	HR§: 1.0 (0.5-2.0)

An increased risk of thromboembolic and thrombotic disease associated with the use of CHCs is well-established. Although the absolute VTE rates are increased for users of CHCs compared to non-users, the rates associated with pregnancy are even greater, especially during the post-partum period (see Figure 1).

The frequency of VTE in women using CHCs has been estimated to be 3 to 12 cases per 10,000 women-years.

The risk of VTE is highest during the first year of CHC use and after restarting a CHC following a break of at least four weeks. The risk of VTE due to CHCs gradually disappears after use is discontinued.

Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use CHCs, for women who use CHCs, for pregnant women, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use CHCs are followed for one year, between 1 and 5 of these women will develop a VTE.

Figure 1: Likelihood of Developing a VTE

*CHC=combination hormonal contraception

**Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.

Several epidemiology studies indicate that third generation oral contraceptives, including those containing desogestrel (etonogestrel, the progestin in NuvaRing, is the biologically active metabolite of desogestrel), may be associated with a higher risk of VTE than oral contraceptives containing other progestins. Some of these studies indicate an approximate two-fold increased risk. However, data from other studies have not shown this two-fold increase in risk.

Use of CHCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. CHCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes). In general, the risk is greatest among older (>35 years of age), hypertensive women who also smoke.

Use NuvaRing with caution in women with cardiovascular disease risk factors.

---

1

Includes low-dose COCs containing the following progestins: norgestimate, norethindrone, or levonorgestrel.

6 ADVERSE REACTIONS

The following serious adverse reactions with the use of CHCs are discussed elsewhere in the labeling.

• Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions (5.1)]
• Vascular events [see Warnings and Precautions (5.1)]
• Liver disease [see Warnings and Precautions (5.3)]

Adverse reactions commonly reported by CHC users are:

• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache

7 DRUG INTERACTIONS

Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

8 USE IN SPECIFIC POPULATIONS

10 OVERDOSAGE

There have been no reports of serious ill effects from overdose of CHCs. Overdosage may cause withdrawal bleeding in females and nausea. If the ring breaks, it does not release a higher dose of hormones. In case of suspected overdose, all NuvaRing rings should be removed and symptomatic treatment given.

11 DESCRIPTION

NuvaRing (etonogestrel/ethinyl estradiol vaginal ring) is a non-biodegradable, flexible, transparent, colorless to almost colorless, combination contraceptive vaginal ring containing two active components, a progestin, etonogestrel (13-ethyl-17-hydroxy-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3-one) and an estrogen, ethinyl estradiol (19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol). When placed in the vagina, 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 made of ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate and contains 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol. NuvaRing is not made with natural rubber latex. NuvaRing has an outer diameter of 54 mm and a cross-sectional diameter of 4 mm. The molecular weights for etonogestrel and ethinyl estradiol are 324.46 and 296.40, respectively.

The structural formulas are as follows:

12 CLINICAL PHARMACOLOGY

12.3 Pharmacokinetics

Absorption

Etonogestrel: Etonogestrel released by NuvaRing is rapidly absorbed. The bioavailability of etonogestrel after vaginal administration is approximately 100%. The serum etonogestrel and ethinyl estradiol concentrations observed during three weeks of NuvaRing use are summarized in Table 2.

Ethinyl estradiol: Ethinyl estradiol released by NuvaRing is rapidly absorbed. The bioavailability of ethinyl estradiol after vaginal administration is approximately 56%, which is comparable to that with oral administration of ethinyl estradiol. The serum ethinyl estradiol concentrations observed during three weeks of NuvaRing use are summarized in Table 2.

Table 2: Mean (SD) Serum Etonogestrel and Ethinyl Estradiol Concentrations (n=16)

	1 week	2 weeks	3 weeks
etonogestrel (pg/mL)	1578 (408)	1476 (362)	1374 (328)
ethinyl estradiol (pg/mL)	19.1 (4.5)	18.3 (4.3)	17.6 (4.3)

The pharmacokinetic profile of etonogestrel and ethinyl estradiol during use of NuvaRing is shown in Figure 2.

Figure 2: Mean Serum Concentration-Time Profile of Etonogestrel and Ethinyl Estradiol during Three Weeks of NuvaRing Use

The pharmacokinetic parameters of etonogestrel and ethinyl estradiol were determined during one cycle of NuvaRing use in 16 healthy female subjects and are summarized in Table 3.

Table 3: Mean (SD) Pharmacokinetic Parameters of NuvaRing (n=16)

Hormone	Cmax pg/mL	Tmax hr	t1/2 hr	CL L/hr
Cmax- maximum serum drug concentration Tmax- time at which maximum serum drug concentration occurs t1/2 - elimination half-life, calculated by 0.693/Kelim CL - apparent clearance
etonogestrel	1716 (445)	200.3 (69.6)	29.3 (6.1)	3.4 (0.8)
ethinyl estradiol	34.7 (17.5)	59.3 (67.5)	44.7 (28.8)	34.8 (11.6)

Prolonged use of NuvaRing: The mean serum etonogestrel concentration at the end of the fourth week of continuous use of NuvaRing was 1272 ± 311 pg/mL compared to a mean concentration range of 1578 ± 408 to 1374 ± 328 pg/mL at the end of weeks one to three. The mean serum ethinyl estradiol concentration at the end of the fourth week of continuous use of NuvaRing was 16.8 ± 4.6 pg/mL compared to a mean concentration range of 19.1 ± 4.5 to 17.6 ± 4.3 pg/mL at the end of weeks one to three.

Distribution

Etonogestrel: Etonogestrel is approximately 32% bound to sex hormone-binding globulin (SHBG) and approximately 66% bound to albumin in blood.

Ethinyl estradiol: Ethinyl estradiol is highly but not specifically bound to serum albumin (98.5%) and induces an increase in the serum concentrations of SHBG.

Metabolism

In vitro data shows that both etonogestrel and ethinyl estradiol are metabolized in liver microsomes by the cytochrome P450 3A4 isoenzyme. Ethinyl estradiol is primarily metabolized by aromatic hydroxylation, but a wide variety of hydroxylated and methylated metabolites are formed. These are present as free metabolites and as sulfate and glucuronide conjugates. The hydroxylated ethinyl estradiol metabolites have weak estrogenic activity. The biological activity of etonogestrel metabolites is unknown.

Excretion

Etonogestrel and ethinyl estradiol are primarily eliminated in urine, bile and feces.

Drug Interactions

[See also Drug Interactions (7).]

The drug interactions of NuvaRing were evaluated in several studies.

A single-dose vaginal administration of an oil-based 1200-mg miconazole nitrate capsule increased the serum concentrations of etonogestrel and ethinyl estradiol by approximately 17% and 16%, respectively. Following multiple doses of 200 mg miconazole nitrate by vaginal suppository or vaginal cream, the mean serum concentrations of etonogestrel and ethinyl estradiol increased by up to 40%.

A single-dose vaginal administration of 100-mg water-based nonoxynol-9 spermicide gel did not affect the serum concentrations of etonogestrel or ethinyl estradiol.

The serum concentrations of etonogestrel and ethinyl estradiol were not affected by concomitant administration of oral amoxicillin or doxycycline in standard dosages during 10 days of antibiotic treatment.

Tampon Use

The use of tampons had no effect on serum concentrations of etonogestrel and ethinyl estradiol during use of NuvaRing [see Dosage and Administration (2.5)].

13 NONCLINICAL TOXICOLOGY

14 CLINICAL STUDIES

In three large one-year clinical trials enrolling 2,834 women aged 18-40 years, in North America, Europe, Brazil, and Chile, the racial distribution was 93% Caucasian, 5.0% Black, 0.8% Asian, and 1.2% Other. Women with BMI ≥ 30 kg/m2 were excluded from these studies.

Based on pooled data from the three trials, 2,356 women aged < 35 years completed 23,515 evaluable cycles of NuvaRing use (cycles in which no back-up contraception was used). The pooled pregnancy rate (Pearl Index) was 1.28 (95% CI [0.8, 1.9]) per 100 women-years of NuvaRing use. In the US study, the Pearl Index was 2.02 (95% CI [1.1, 3.4]) per 100 women-years of NuvaRing use.

Study data indicate the return of ovulation and spontaneous menstrual cycles in most women within a month after discontinuation of NuvaRing use.

15 REFERENCES

1. Dinger, J et. al., Cardiovascular risk associated with the use of an etonogestrel-containing vaginal ring. Obstetrics & Gynecology 2013; 122(4): 800-808.
2. Sidney, S. et. al., Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users. Contraception 2013; 87: 93–100.
3. Combined hormonal contraceptives (CHCs) and the risk of cardiovascular endpoints. Sidney, S. (primary author) http://www.fda.gov/downloads/Drugs/DrugSafety/UCM277384.pdf, accessed 23-Aug-2013.

16 HOW SUPPLIED/STORAGE AND HANDLING

Each NuvaRing (etonogestrel/ethinyl estradiol vaginal ring) is individually packaged in a reclosable aluminum laminate sachet consisting of three layers, from outside to inside: polyester, aluminum foil, and low-density polyethylene. The ring should be replaced in this reclosable sachet after use and discarded in a waste receptacle out of the reach of children and pets. It should not be flushed down the toilet.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Counsel patients regarding the following:

Manufactured for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

Manufactured by: N.V. Organon, Oss, The Netherlands, a subsidiary of
Merck & Co., Inc., Whitehouse Station, NJ 08889, USA

For patent information: www.merck.com/product/patent/home.html

Copyright © 2001-2020 Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc.
All rights reserved.

uspi-mk8342a-rng-2001r014

Patient Information

NuvaRing® (NEW-vah-ring)
(etonogestrel/ethinyl estradiol vaginal ring)

Hormonal birth control methods help to lower the chances of becoming pregnant. They do not protect against HIV infection (AIDS) and other sexually transmitted infections.

What is NuvaRing?

NuvaRing (NEW-vah-ring) is a flexible birth control vaginal ring used to prevent pregnancy.

NuvaRing contains a combination of a progestin and estrogen, 2 kinds of female hormones. Birth control methods that contain both an estrogen and a progestin are called combination hormonal contraceptives (CHCs).

How well does NuvaRing work?

Your chance of getting pregnant depends on how well you follow the directions for using NuvaRing. The better you follow the directions, the less chance you have of getting pregnant.

Based on the results of a US clinical study, approximately 1 to 3 women out of 100 women may get pregnant during the first year they use NuvaRing.

The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.

Who should not use NuvaRing?

Do not use NuvaRing if you:

• smoke and are over 35 years old
• have or have had blood clots in your arms, legs, eyes, or lungs
• have an inherited problem with your blood that makes it clot more than normal
• have had a stroke
• have had a heart attack
• have certain heart valve problems or heart rhythm problems that can cause blood clots to form in the heart
• have high blood pressure that medicine can't control
• have diabetes with kidney, eye, nerve, or blood vessel damage
• have certain kinds of severe migraine headaches with aura, numbness, weakness, or changes in vision, or have any migraine headaches if you are over age 35
• have liver disease, including liver tumors
• take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme "alanine aminotransferase" (ALT) in the blood
• have unexplained vaginal bleeding
• are pregnant or think you may be pregnant. NuvaRing is not for pregnant women.
• have or have had breast cancer or any cancer that is sensitive to female hormones
• are allergic to etonogestrel, ethinyl estradiol or any of the ingredients in NuvaRing. See the list of ingredients in NuvaRing at the end of this leaflet.

Hormonal birth control methods may not be a good choice for you if you have ever had jaundice (yellowing of the skin or eyes) caused by pregnancy or related to previous use of hormonal birth control.

Tell your healthcare provider if you have ever had any of the conditions listed above. Your healthcare provider can suggest another method of birth control.

What should I tell my healthcare provider before using NuvaRing?

Before you use NuvaRing tell your healthcare provider if you:

• have any medical conditions
• smoke
• are pregnant or think you are pregnant
• recently had a baby
• recently had a miscarriage or abortion
• have a family history of breast cancer
• have or have had breast nodules, fibrocystic disease, an abnormal breast x-ray, or abnormal mammogram
• use tampons and have a history of toxic shock syndrome
• have been diagnosed with depression
• have had liver problems including jaundice during pregnancy
• have or have had elevated cholesterol or triglycerides
• have or have had gallbladder, liver, heart, or kidney disease
• have diabetes
• have a history of jaundice (yellowing of the skin or eyes) caused by pregnancy (also called cholestasis of pregnancy)
• have a history of scanty or irregular menstrual periods
• have any condition that makes the vagina become irritated easily
• have or have had high blood pressure
• have or have had migraines or other headaches or seizures
• are scheduled for surgery. NuvaRing may increase your risk of blood clots after surgery. You should stop using NuvaRing at least 4 weeks before you have surgery and not restart it until at least 2 weeks after your surgery.
• are scheduled for any laboratory tests. Certain blood tests may be affected by hormonal birth control methods.
• are breastfeeding or plan to breastfeed. Hormonal birth control methods that contain estrogen, like NuvaRing, may decrease the amount of milk you make. A small amount of hormones from NuvaRing may pass into your breast milk. Consider another non-hormonal method of birth control until you are ready to stop breastfeeding.
• have (or have ever had) an allergic reaction while using NuvaRing, including hives, swelling of the face, lips, tongue, and/or throat causing difficulty in breathing or swallowing (anaphylaxis and/or angioedema).

Tell your healthcare provider about all medicines and herbal products you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Some medicines and herbal products may make hormonal birth control less effective, including, but not limited to:

• certain anti-seizure medicines (such as barbiturates, carbamazepine, felbamate, oxcarbazepine, phenytoin, rufinamide and topiramate)
• medicine to treat fungal infections (griseofulvin)
• certain combinations of HIV medicines, (such as nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir)
• certain hepatitis C (HCV) medicines (such as boceprevir and telaprevir)
• non-nucleoside reverse transcriptase inhibitors (such as efavirenz and nevirapine)
• medicine to treat tuberculosis (such as rifampicin and rifabutin)
• medicine to treat high blood pressure in the vessels of the lung (bosentan)
• medicine to treat chemotherapy-induced nausea and vomiting (aprepitant)
• St John's wort

Use an additional barrier contraceptive method (such as a male condom with spermicide) when you take medicines that may make NuvaRing less effective. Since the effect of another medicine on NuvaRing may last up to 28 days after stopping the medicine, it is necessary to use the additional barrier contraceptive method for that long to help prevent you from becoming pregnant. While using NuvaRing, you should not use certain female barrier contraceptive methods such as a vaginal diaphragm, cervical cap or female condom as your back-up method of birth control because NuvaRing may interfere with the correct placement and position of a diaphragm, cervical cap or female condom.

Some medicines and grapefruit juice may increase the level of ethinyl estradiol in your blood if used together, including:

• the pain reliever acetaminophen
• ascorbic acid (vitamin C)
• medicines that affect how your liver breaks down other medicines (such as itraconazole, ketoconazole, voriconazole, fluconazole, clarithromycin, erythromycin, and diltiazem)
• certain HIV medicines (atazanavir/ritonavir and indinavir)
• non-nucleoside reverse transcriptase inhibitors (such as etravirine)
• medicines to lower cholesterol such as atorvastatin and rosuvastatin

Hormonal birth control methods may interact with lamotrigine, a medicine used for seizures. This may increase the risk of seizures, so your healthcare provider may need to adjust your dose of lamotrigine.

Women on thyroid replacement therapy may need increased doses of thyroid hormone.

Ask your healthcare provider if you are not sure if you take any of the medicines listed above. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I use NuvaRing?

• Read the Instructions for Use at the end of this Patient Information that comes with your NuvaRing for information about the right way to use NuvaRing.
• Use NuvaRing exactly as your healthcare provider tells you to use it.
• NuvaRing is used in a 4-week cycle.
  • Insert 1 NuvaRing in the vagina and keep it in place for 3 weeks (21 days).

    Regularly check that NuvaRing is in your vagina (for example, before and after intercourse) to ensure that you are protected from pregnancy.

  • Remove the NuvaRing for a 1-week break (7 days). During the 1-week break (7 days), you will usually have your menstrual period.
    

    Note: Insert and remove NuvaRing on the same day of the week and at the same time:

    • For example, if you insert your NuvaRing on a Monday at 8:00 am, you should remove it on the Monday 3 weeks later at 8:00 am.
    • After your 1-week (7 days) break, you should insert a new NuvaRing on the next Monday at 8:00 am.
• While using NuvaRing, you should not use certain female barrier contraceptive methods such as a vaginal diaphragm, cervical cap or female condom as your back-up method of birth control because NuvaRing may interfere with the correct placement and position of a diaphragm, cervical cap or female condom.
• Ring breakage has occurred when also using a vaginal product such as a lubricant or treatment for infection (see "What should I do if my NuvaRing comes out of my vagina?"). Use of spermicides or vaginal yeast products will not make NuvaRing less effective at preventing pregnancy.
• Use of tampons will not make NuvaRing less effective or stop NuvaRing from working.
• If NuvaRing has been left inside your vagina for more than 4 weeks (28 days), you may not be protected from pregnancy and you should see your healthcare provider to be sure you are not pregnant. Until you know the results of your pregnancy test, you should use an extra method of birth control, such as male condoms with spermicide, until the new NuvaRing has been in place for 7 days in a row.
• Do not use more than 1 NuvaRing at a time. Too much hormonal birth control medicine in your body may cause nausea, vomiting, or vaginal bleeding.

Your healthcare provider should examine you at least 1 time a year to see if you have any signs of side effects from using NuvaRing.

What are the possible side effects of using NuvaRing?

See "What is the most important information I should know about NuvaRing?"

NuvaRing may cause serious side effects, including:

 

blood clots. Like pregnancy, combination hormonal birth control methods increase the risk of serious blood clots (see following graph), especially in women who have other risk factors, such as smoking, obesity, or age greater than 35. This increased risk is highest when you first start using a combination hormonal birth control method or when you restart the same or different combination hormonal birth control method after not using it for a month or more. Talk with your healthcare provider about your risk of getting a blood clot before using NuvaRing or before deciding which type of birth control is right for you.
 

 

In some studies of women who used NuvaRing, the risk of getting a blood clot was similar to the risk in women who used combination birth control pills.
 

 

Other studies have reported that the risk of blood clots was higher for women who use combination birth control pills containing desogestrel (a progestin similar to the progestin in NuvaRing) than for women who use combination birth control pills that do not contain desogestrel.
 

 

It is possible to die or be permanently disabled from a problem caused by a blood clot, such as heart attack or stroke. Some examples of serious blood clots are blood clots in the:

• legs (deep vein thrombosis)
• lungs (pulmonary embolus)
• eyes (loss of eyesight)
• heart (heart attack)
• brain (stroke)
   

 

To put the risk of developing a blood clot into perspective: If 10,000 women who are not pregnant and do not use hormonal birth control are followed for one year, between 1 and 5 of these women will develop a blood clot. The figure below shows the likelihood of developing a serious blood clot for women who are not pregnant and do not use hormonal birth control, for women who use hormonal birth control, for pregnant women, and for women in the first 12 weeks after delivering a baby.

 

Likelihood of Developing a Serious Blood Clot (Venous Thromboembolism [VTE])

 

*CHC=combination hormonal contraception

 

**Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.
 

 

Call your healthcare provider right away if you have:

• leg pain that does not go away
• sudden shortness of breath
• sudden blindness, partial or complete
• severe pain or pressure in your chest
• sudden, severe headache unlike your usual headaches
• weakness or numbness in an arm or leg, or trouble speaking
• yellowing of the skin or eyeballs

Other serious risks include:

• Toxic Shock Syndrome (TSS). Some of the symptoms are much the same as the flu, but they can become serious very quickly. Call your healthcare provider or get emergency treatment right away if you have the following symptoms:

  sudden high fever vomiting diarrhea a sunburn-like rash

  muscle aches dizziness fainting or feeling faint when standing up

• allergic reaction, including hives, swelling of the face, lips, tongue, and/or throat causing difficulty in breathing or swallowing (anaphylaxis and/or angioedema)
• liver problems, including liver tumors
• high blood pressure
• gallbladder problems
• accidental insertion into bladder
• symptoms of a problem called angioedema if you already have a family history of angioedema

The most common side effects of NuvaRing are:

• tissue irritation inside your vagina or on your cervix
• headache (including migraine)
• mood changes (including depression, especially if you had depression in the past). Call your healthcare provider immediately if you have any thoughts of harming yourself.
• NuvaRing problems, including the ring slipping out or causing discomfort
• nausea and vomiting
• vaginal discharge
• weight gain
• vaginal discomfort
• breast pain, discomfort, or tenderness
• painful menstrual periods
• abdominal pain
• acne
• less sexual desire

Some women have spotting or light bleeding during NuvaRing use. If these symptoms occur, do not stop using NuvaRing. The problem will usually go away. If it doesn't go away, check with your healthcare provider.

Other side effects seen with NuvaRing include breast discharge; vaginal injury (including pain, discomfort, and bleeding) associated with broken rings; and penis discomfort of the partner (such as irritation, rash, itching).

Less common side effects seen with combination hormonal birth control include:

• Blotchy darkening of your skin, especially on your face
• High blood sugar, especially in women who already have diabetes
• High fat (cholesterol, triglycerides) levels in the blood

There have been reports of the ring becoming stuck to the vaginal tissue and having to be removed by a healthcare provider. Call your healthcare provider if you are unable to remove your NuvaRing.

Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of NuvaRing. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store NuvaRing and throw away used NuvaRings?

• Store NuvaRing at room temperature between 68°F to 77°F (20°C to 25°C).
• Store NuvaRing at room temperature for up to 4 months after you receive it. Throw NuvaRing away if the expiration date on the label has passed.
• Do not store NuvaRing above 86°F (30°C).
• Avoid direct sunlight.
• Place the used NuvaRing in the re-closable foil pouch and properly throw it away in your household trash out of the reach of children and pets. Do not flush your used NuvaRing down the toilet.

Keep NuvaRing and all medicines out of the reach of children.

General information about the safe and effective use of NuvaRing

Medicines are sometimes prescribed for purposes other than those listed in the Patient Information. Do not use NuvaRing for a condition for which it was not prescribed. Do not give NuvaRing to other people. It may harm them.

This leaflet summarizes the most important information about NuvaRing. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NuvaRing that is written for health professionals.

For more information on NuvaRing and the applicator for NuvaRing, go to www.nuvaring.com or call 1-800-622-4477.

What are the ingredients in NuvaRing?

Active ingredients: etonogestrel and ethinyl estradiol

Inactive ingredients: ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate.

NuvaRing is not made with natural rubber latex.

Do Hormonal Birth Control Methods Cause Cancer?

Hormonal birth control methods do not seem to cause breast cancer. However, if you have breast cancer now or have had it in the past, do not use hormonal birth control, including NuvaRing, because some breast cancers are sensitive to hormones.

Women who use hormonal birth control methods may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners.

What should I know about my period when using NuvaRing?

When you use NuvaRing you may have bleeding and spotting between periods, called unplanned bleeding. Unplanned bleeding may vary from slight staining between menstrual periods to breakthrough bleeding, which is a flow much like a regular period. Unplanned bleeding occurs most often during the first few months of NuvaRing use, but may also occur after you have been using NuvaRing for some time. Such bleeding may be temporary and usually does not indicate any serious problems. It is important to continue using the ring on schedule. If the unplanned bleeding or spotting is heavy or lasts for more than a few days, you should discuss this with your healthcare provider.

What if I miss my regular scheduled period when using NuvaRing?

Some women miss periods on hormonal birth control, even when they are not pregnant. Consider the possibility that you may be pregnant if:

1. you miss a period and NuvaRing was out of the vagina for more than 3 hours during the 3 weeks (21 days) of ring use
2. you miss a period and waited longer than 1 week to insert a new ring
3. you have followed the instructions and you miss 2 periods in a row
4. you have left NuvaRing in place for longer than 4 weeks (28 days)

What if I want to become pregnant?

You may stop using NuvaRing whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop using NuvaRing.

Instructions for Use

NuvaRing (NEW-vah-ring)
(etonogestrel/ethinyl estradiol vaginal ring)

Read these Instructions for Use before you start using NuvaRing and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your treatment.

How should I start using NuvaRing?

If you are not currently using hormonal birth control, you have 2 ways to start using NuvaRing. Choose the best way for you:

• First Day Start: Insert NuvaRing on the first day of your menstrual period. You will not need to use another birth control method since you are using NuvaRing on the first day of your menstrual period.
• Day 2 to Day 5 Cycle Start: You may choose to start NuvaRing on days 2 to 5 of your menstrual period. Make sure you also use an extra method of birth control (barrier method), such as male condoms with spermicide for the first 7 days of NuvaRing use in the first cycle.

If you are changing from a birth control pill or patch to NuvaRing:

If you have been using your birth control method correctly and are certain that you are not pregnant, you can change to NuvaRing any day. Do not start NuvaRing any later than the day you would start your next birth control pill or apply your patch.

If you are changing from a progestin-only birth control method, such as a minipill, implant or injection or from an intrauterine system (IUS):

• You may switch from a minipill on any day. Start using NuvaRing on the day that you would have taken your next minipill.
• You should switch from an implant or the IUS and start using NuvaRing on the day that you remove the implant or IUS.
• You should switch from an injectable and start using NuvaRing on the day when your next injection would be due.

If you are changing from a minipill, implant or injection or from an intrauterine system (IUS), you should use an extra method of birth control, such as a male condom with spermicide during the first 7 days of using NuvaRing.

If you start using NuvaRing after an abortion or miscarriage:

• Following a first trimester abortion or miscarriage: You may start NuvaRing within 5 days following a first trimester abortion or miscarriage (the first 12 weeks of pregnancy). You do not need to use an additional birth control method.
• If you do not start NuvaRing within 5 days after a first trimester abortion or miscarriage, use a non-hormonal birth control method, such as male condoms and spermicide, while you wait for your period to start. Begin NuvaRing at the time of your next menstrual period. Count the first day of your menstrual period as "Day 1" and start NuvaRing one of the following 2 ways below.
  • First Day Start: Insert NuvaRing on the first day of your menstrual period. You will not need to use another birth control method since you are using NuvaRing on the first day of your menstrual period.
  • Day 2 to Day 5 Cycle Start: You may choose to start NuvaRing on Days 2 to 5 of your menstrual period. Make sure you also use an extra method of birth control (barrier method), such as male condoms with spermicide for the first 7 days of NuvaRing use in the first cycle.
• Following a second trimester abortion or miscarriage: You may start using NuvaRing no sooner than 4 weeks (28 days) after a second trimester abortion (after the first 12 weeks of pregnancy).

If you are starting NuvaRing after childbirth:

• You may start using NuvaRing no sooner than 4 weeks (28 days) after having a baby if you are not breastfeeding.
• If you have not gotten your menstrual period after childbirth, you should talk to your healthcare provider. You may need a pregnancy test to make sure you are not pregnant before you start using NuvaRing.
• Use another birth control method such as male condoms with spermicide for the first 7 days in addition to NuvaRing.

If you are breastfeeding you should not use NuvaRing. Use other birth control methods until you are no longer breastfeeding.

Step 1. Choose a position for insertion of NuvaRing.

• Choose the position that is comfortable for you. For example, lying down, squatting, or standing with 1 leg up (See Figures A, B, and C).

Positions for NuvaRing insertion

Step 2. Open the pouch to remove your NuvaRing.

• Each NuvaRing comes in a re-sealable foil pouch.
• Wash and dry your hands before removing NuvaRing from the foil pouch.
• Open the foil pouch at either notch near the top.
• Keep the foil pouch so you can place your used NuvaRing in it before you throw it away in your household trash.

Step 3. Prepare NuvaRing for insertion.

• Hold NuvaRing between your thumb and index finger and press the sides of the ring together (See Figures D and E).

Step 4. Insert NuvaRing into your vagina.

• Insert the folded NuvaRing into your vagina and gently push it further up into your vagina using your index finger (See Figures F and G). Alternatively, the applicator for NuvaRing (available separately) may be used to help you insert the ring [see Applicator for NuvaRing Instructions for Use].
• When you insert NuvaRing it may be in different positions in your vagina, but NuvaRing does not have to be in an exact position for it to work (See Figures H and I).
• NuvaRing may move around slightly within your vagina. This is normal. Although some women may be aware of NuvaRing in the vagina, most women do not feel it when it is in place.

	Figure F
Figure G	Figure H	Figure I

Inserting NuvaRing (Figure F, Figure G) and positioning NuvaRing (Figure H, Figure I)

Note:

• If the NuvaRing feels uncomfortable, you may not have pushed the ring into your vagina far enough. Use your finger to gently push the NuvaRing as far as you can into your vagina. There is no danger of NuvaRing being pushed too far up in the vagina or getting lost (See Figure G).
• Some women have accidentally inserted NuvaRing into their bladder. If you have pain during or after insertion and you cannot find NuvaRing in your vagina, call your healthcare provider right away.
• Regularly check that NuvaRing is in your vagina (for example, before and after intercourse) to ensure you are protected from pregnancy.

Step 5. How do I remove NuvaRing?

• Wash and dry your hands.
• Choose the position that is most comfortable for you (See Figures A, B, and C).
• Put your index finger into your vagina and hook it through the NuvaRing. Gently pull downward and forward to remove the NuvaRing and pull it out (See Figure J).

Step 6. Throw away the used NuvaRing.

• Place the used NuvaRing in the re-sealable foil pouch and put it in a trash can out of the reach of children and pets.
• Do not throw NuvaRing in the toilet.

What else should I know about using NuvaRing?

What if I leave NuvaRing in too long?

• If you leave NuvaRing in your vagina for up to 4 weeks (28 days) you will still be getting pregnancy protection. Remove your old NuvaRing for 1 week (7 days) and insert a new NuvaRing 1 week (7 days) later (See Steps 1 through 4).
• If you leave NuvaRing in your vagina longer than 4 weeks (28 days), remove the ring and check to make sure you are not pregnant.
  

  If you are not pregnant, insert a new NuvaRing (See Steps 1 through 4). You must use another birth control method, such as male condoms with spermicide, until the new NuvaRing has been used for 7 days in a row.

What should I do if my NuvaRing comes out of my vagina?

NuvaRing can slip or accidentally come out (expelled) of your vagina, for example, during sexual intercourse, bowel movements, use of tampons, or if it breaks.

• NuvaRing may break causing the ring to lose its shape. If the ring stays in your vagina this should not lower NuvaRing's effectiveness at preventing pregnancy.
  • If NuvaRing breaks and slips out of your vagina, throw the broken ring in your household trash out of the reach of children and pets.
  • Insert a new NuvaRing (See Steps 1 through 4).
• You should pay attention when removing a tampon to be sure that your NuvaRing is not accidentally pulled out.
  • Be sure to insert NuvaRing before inserting a tampon.
  • If you accidentally pull out your NuvaRing while using tampons, rinse your NuvaRing in cool to lukewarm (not hot) water and insert it again right away.
• NuvaRing can be pushed out of (expelled from) your vagina, for example, during sexual intercourse or during a bowel movement.
  • If the expelled ring has been out of your vagina for less than 3 hours, rinse the expelled NuvaRing in cool to lukewarm (not hot) water and insert it again right away.
  • If the expelled NuvaRing has been out of your vagina for more than 3 continuous hours:
    • During Weeks 1 and 2, you may not be protected from pregnancy. Reinsert the ring as soon as you remember (See Steps 1 through 4). Use another birth control method, such as male condoms with spermicide, until the ring has been in place for 7 days in a row.
    • During Week 3, do not reinsert the NuvaRing that has been out of your vagina; but throw it away in your household trash away from children and pets. Use another birth control method, such as male condoms with spermicide, until the new NuvaRing has been used for 7 days in a row, following one of the two options below:

      -

      Option 1. Insert a new ring right away to start your next 21 Day NuvaRing use cycle. You may not have your regular period, but you may have spotting or vaginal bleeding.

      -

      Option 2. Insert a new ring no later than 7 days from the time the previous ring was removed or expelled. During this time, you may have your period.

    Note: You should only choose to do option 2 if you used NuvaRing for 7 days in a row, prior to the day that your previous NuvaRing was accidentally removed or expelled.

• If NuvaRing was out of the vagina for an unknown amount of time, you may not be protected from pregnancy. Perform a pregnancy test prior to inserting a new ring and consult your healthcare provider.

This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.

Manufactured for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

Manufactured by: N.V. Organon, Oss, The Netherlands, a subsidiary of
Merck & Co., Inc., Whitehouse Station, NJ 08889, USA

For patent information: www.merck.com/product/patent/home.html

Copyright © 2001-2019 Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc.
All rights reserved.

Revised: 05/2019

usppi-mk8342a-rng-1905r013

Instructions for Use

Applicator for NuvaRing® (NEW-vah-ring)

For optional use to help insert NuvaRing.

NuvaRing is not included with the applicator.

Important:

• The applicator is designed for use with NuvaRing.
• Do not reuse the applicator; it is designed for one time use.
• Do not share the applicator with others.
• If you accidently drop the applicator, wash it with cool to lukewarm water. Do not use hot water to wash the applicator.
• Throw the applicator away in the trash immediately after use.
• Do not flush the applicator down the toilet.

The applicator is not made with natural rubber latex.

Store the applicators between 41°F to 86°F (5°C to 30°C).

1:

Prepare

Wash your hands before opening the package. Open the package only when you are ready to use the applicator. Do not use if the contents or packaging are visibly damaged.

Look at the picture of the applicator to familiarize yourself with the parts of the applicator. Plunger Finger Grip Barrel Barrel Opening NuvaRing (Not Included)

2:

Load & Position

Pull the plunger back gently until it stops.

Squeeze opposite sides of the ring together and insert the ring into the barrel opening.

Gently push the ring into the barrel. The tip of the ring should stick out slightly from the barrel opening.

Choose the position for inserting the ring that is most comfortable for you, like lying down, squatting, or standing with one leg up.

3:

Insert & Dispose

Place your thumb and middle finger on the finger grip.

Gently insert the barrel into the vagina until your fingers (on the finger grip) touch your body. Then use your index finger to gently push the plunger all the way into the barrel. Some women have experienced a brief mild pinching feeling when using the applicator.

The ring is pushed out of the applicator. Gently remove the applicator. Please also read the Patient Information and Instructions for Use for NuvaRing.

Make sure that the ring is not in the applicator. Dispose of (throw away) the used applicator in the trash can. Do not flush the applicator down the toilet. Do not reuse the applicator.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

Manufactured by: Sonoco Plastics B.V., Berkel en Rodenrijs, The Netherlands

For patent information: www.merck.com/product/patent/home.html

Copyright © 2016 Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc.
All rights reserved.

Revised: 09/2016

usifu-mkd920-1609r000

PRINCIPAL DISPLAY PANEL - 3 Ring Pouch Carton

For the Dispenser: Store refrigerated 2-8°C (36- 46°F).

NDC 0052-0273-05

NUVARING®
(etonogestrel/ethinyl estradiol vaginal ring)
delivers 0.120 mg/0.015 mg per day

For Vaginal Use

Keep out of the reach of children.

This product is intended to prevent
pregnancy. It does not protect against
HIV infection (AIDS) and other sexually
transmitted diseases.

Rx only

Contains 3 Rings