Etonogestrel And Ethinyl Estradiol Vaginal
FDA Drug Information • Also known as: Enilloring, Etonogestrel And Ethinyl Estradiol Vaginal
- Brand Names
- Enilloring, Etonogestrel And Ethinyl Estradiol Vaginal
- Drug Class
- Estrogen [EPC], Progestin [EPC]
- Route
- VAGINAL
- Dosage Form
- RING
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive (CHC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, CHCs, including EnilloRing , should not be used by women who are over 35 years of age and smoke. [ see Contraindications ( 4 )] WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS See full prescribing information for complete boxed warning. Women over 35 years old who smoke should not use EnilloRing ( 4 ) Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive (CHC) use. ( 4 ) BOXED WARNING What is the most important information I should know about EnilloRing ? Do not use EnilloRing if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects (heart and blood vessel problems) from combination hormonal contraceptives (CHCs), including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke.
Description
11 DESCRIPTION EnilloRing (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. EnilloRing 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. EnilloRing is not made with natural rubber latex. EnilloRing 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:
What Is Etonogestrel And Ethinyl Estradiol Vaginal Used For?
1 INDICATIONS AND USAGE FOR VAGINAL USE ONLY EnilloRing is indicated for use by females of reproductive age to prevent pregnancy. EnilloRing is an estrogen/progestin combination hormonal contraceptive (CHC) indicated for use by women to prevent pregnancy. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION One EnilloRing is inserted in the vagina. The ring must remain in place continuously for three weeks, followed by a one-week ring-free interval. ( 2 ) 2.1 How to Use EnilloRing To achieve maximum contraceptive effectiveness, EnilloRing must be used as directed [ see Dosage and Administration ( 2.2 )]. One EnilloRing is inserted in the vagina. The ring is to remain in place continuously for three weeks. It is removed for a one-week break, during which a withdrawal bleed usually occurs. A new ring is inserted one week after the last ring was removed. The user can choose the insertion position that is most comfortable to her, for example, standing with one leg up, squatting, or lying down. The ring is to be compressed and inserted into the vagina. An optional alternative is to insert the ring using the applicator for EnilloRing [see Applicator for EnilloRing Instructions for Use ]. The exact position of EnilloRing inside the vagina is not critical for its function. The vaginal ring must be inserted on the appropriate day and left in place for three consecutive weeks. This means that the ring should be removed three weeks later on the same day of the week as it was inserted and at about the same time. EnilloRing can be removed by hooking the index finger under the forward rim or by grasping the rim between the index and middle finger and pulling it out. The used ring should be placed in the sachet (foil pouch) and discarded in a waste receptacle out of the reach of children and pets (do not flush in toilet). After a one-week break, during which a withdrawal bleed usually occurs, a new ring is inserted on the same day of the week as it was inserted in the previous cycle. The withdrawal bleed usually starts on Day 2-3 after removal of the ring and may not have finished before the next ring is inserted. In order to maintain contraceptive effectiveness, the new ring must be inserted exactly one week after the previous one was removed even if menstrual bleeding has not finished. 2.2 How to Start Using EnilloRing IMPORTANT: Consider the possibility of ovulation and conception prior to the first use of EnilloRing. No Hormonal Contraceptive Use in the Preceding Cycle: The woman should insert EnilloRing on the first day of her menstrual bleeding. EnilloRing may also be started on Days 2-5 of the woman’s cycle, but in this case a barrier method, such as male condoms with spermicide, should be used for the first seven days of EnilloRing use in the first cycle. Changing From a CHC: The woman may switch from her previous CHC on any day, but at the latest on the day following the usual hormone-free interval, if she has been using her hormonal method consistently and correctly, or if it is reasonably certain that she is not pregnant. Changing From a Progestin-Only Method (progestin-only pill [POP], Implant, or Injection or a Progestin-Releasing Intrauterine System [IUS]): The woman may switch from the POP on any day; instruct her to...
Side Effects (Adverse Reactions)
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 The most common adverse reactions (≥2%) in clinical trials were: vaginitis, headache (including migraine), mood changes (e.g., depression, mood swings, mood altered, depressed mood, affect lability), device-related events (e.g., expulsion/discomfort/foreign body sensation), nausea/vomiting, vaginal discharge, increased weight, vaginal discomfort, breast pain/discomfort/tenderness, dysmenorrhea, abdominal pain, acne, and decreased libido. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Xiromed, LLC at 844-XIROMED (844-947-6633) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Trials with a duration of 6 to 13 28-day cycles provided safety data. In total, 2,501 women, aged 18 to 41 contributed 24,520 cycles of exposure. Common Adverse Reactions (≥ 2%): vaginitis (13.8%), headache (including migraine) (11.2%), mood changes (e.g., depression, mood swings, mood altered, depressed mood, affect lability) (6.4%), device-related events (e.g., expulsion/discomfort/foreign body sensation) (6.3%), nausea/vomiting (5.9%), vaginal discharge (5.7%), increased weight (4.9%), vaginal discomfort (4.0%), breast pain/discomfort/tenderness (3.8%), dysmenorrhea (3.5%), abdominal pain (3.2%), acne (2.4%), and decreased libido (2.0%). Adverse Reactions (≥ 1%) Leading to Study Discontinuation: 13.0% of the women discontinued from the clinical trials due to an adverse reaction; the most common adverse reactions leading to discontinuation were device-related events (2.7%), mood changes (1.7%), headache (including migraine) (1.5%) and vaginal symptoms (1.2%). Serious Adverse Reactions: deep vein thrombosis [ see Warnings and Precautions ( 5.1 ) ], anxiety, cholelithiasis, and vomiting. 6.2 Postmarketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 2). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use. Figure 2: Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptives RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs. The following adverse reactions have been identified during post-approval use of EnilloRing. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders : hypersensitivity reactions, including anaphylaxis and angioedema Nervous system disorders : stroke/cerebrovascular accident Vascular disorders : arterial events...
Drug Interactions
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. Drugs or herbal products that induce certain enzymes, such as CYP3A4, may decrease the effectiveness of CHCs or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with CHCs. ( 7 ) 7.1 Effects of Other Drugs on CHCs Substances decreasing the plasma concentrations of CHCs and potentially diminishing the effectiveness of CHCs Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of CHCs and potentially diminish the effectiveness of CHCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include: phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John's wort. Interactions between CHCs and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative non-hormonal method of contraception or a back-up method when enzyme inducers are used with EnilloRing, and to continue back-up non-hormonal contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Note: EnilloRing may interfere with the correct placement and position of certain female barrier methods such as a diaphragm or female condom. These methods are not recommended as back-up methods with EnilloRing use [see Dosage and Administration ( 2.5 )] . 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. The effects of other antibiotics on etonogestrel or ethinyl estradiol concentrations have not been evaluated. Substances increasing the plasma concentrations of CHCs Co-administration of atorvastatin and certain CHCs containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20-25%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol concentrations, possibly by inhibition of conjugation. Concomitant administration of strong or moderate CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma estrogen and/or progestin concentrations. Co-administration of vaginal miconazole nitrate and EnilloRing increases the serum concentrations of etonogestrel and ethinyl estradiol by up to 40% [see Clinical Pharmacology ( 12.3 )]. Human immunodeficiency virus (HIV) / Hepatitis C Virus (HCV) protease inhibitors and nonnucleoside reverse transcriptase inhibitors Significant changes in the plasma concentrations of the...
Contraindications
4 CONTRAINDICATIONS EnilloRing is contraindicated in females who are known to have or develop the following conditions: 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 )] Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions ( 5.14 )] Hypersensitivity reactions, including anaphylaxis and angioedema, to any of the components of EnilloRing [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 )]. A high risk...
Overdosage
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 EnilloRing should be removed and symptomatic treatment given.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Each EnilloRing (etonogestrel/ethinyl estradiol vaginal ring) is individually packaged in an 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 foil pouch after use and discarded in a waste receptacle out of the reach of children and pets. It should not be flushed down the toilet. Box of 3 sachets : NDC 70700-156-91 16.1 Storage Prior to dispensing to the user, store refrigerated 2-8°C (36-46°F). After dispensing to the user, EnilloRing can be stored for up to 4 months at 25°C (77°F); excursions permitted between 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature]. Avoid storing EnilloRing in direct sunlight or at temperatures above 30°C (86°F). For the Dispenser: When EnilloRing is dispensed to the user, place an expiration date on the label. The date should not exceed either 4 months from the date of dispensing or the expiration date, whichever comes first.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.