EnilloRing
Generic: ETONOGESTREL AND ETHINYL ESTRADIOL VAGINAL
Basic Information
Manufacturer
Xiromed, LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
VAGINAL
FDA Set ID
85a126f6-d3e0-9e12-73f9-6176ba36f58b
Indications & Usage
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 )
EnilloRing is an estrogen/progestin combination hormonal contraceptive (CHC) indicated for use by women to prevent pregnancy.
( 1 )
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 (including arterial thromboembolism and myocardial infarction), aggravation of varicose veins Skin and subcutaneous tissue disorders : exacerbations of hereditary and acquired angioedema, urticaria, chloasma Reproductive system and breast disorders : penile disorders, including local reactions on penis (in male partners of women usingEnilloRing ), galactorrhea General Disorders and Administration Site Conditions : device breakage (including with concomitant use of intravaginal antimycotic, antibiotic, and lubricant products) Injury, poisoning and procedural complications : vaginal injury (including associated pain, discomfort, and bleeding) associated with ring breakage enilloring-chart
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 (including arterial thromboembolism and myocardial infarction), aggravation of varicose veins Skin and subcutaneous tissue disorders : exacerbations of hereditary and acquired angioedema, urticaria, chloasma Reproductive system and breast disorders : penile disorders, including local reactions on penis (in male partners of women usingEnilloRing ), galactorrhea General Disorders and Administration Site Conditions : device breakage (including with concomitant use of intravaginal antimycotic, antibiotic, and lubricant products) Injury, poisoning and procedural complications : vaginal injury (including associated pain, discomfort, and bleeding) associated with ring breakage enilloring-chart