6 ADVERSE REACTIONS The following serious or important adverse reactions are discussed elsewhere in the labeling: Ectopic Pregnancy [see Warnings and Precautions ( 5.1 )] Intrauterine Pregnancy [see Warnings and Precautions ( 5.2 )] Group A Streptococcal Sepsis (GAS) [see Warnings and Precautions ( 5.3 )] Pelvic Inflammatory Disease or Endometritis [see Warnings and Precautions ( 5.4 )] Perforation [see Warnings and Precautions ( 5.5 )] Expulsion [see Warnings and Precautions ( 5.6 )] Ovarian Cysts [see Warnings and Precautions ( 5.7 )] Bleeding Pattern Alterations [see Warnings and Precautions ( 5.8 )] The most common adverse reactions reported in clinical studies (> 10% participants) are vulvovaginal mycotic infections, vaginal bacterial infections, acne, and nausea or vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Study Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The data described below reflect exposure of 1,751 generally healthy participants, 16 to 45 years of age, to LILETTA in a large, multi-center contraceptive study conducted in the US. Participants included 1,401 exposed for 1 year and 380 who completed 8 years of use; 58% were nulliparous (mean age 25.1 ± 4.3 years) and 42% were parous (mean age 30.3 ± 6.1 years). Most participants who received LILETTA were Caucasian (78.4%) or Black/African American (13.3%); 14.7% of participants were of Hispanic ethnicity. Mean BMI of LILETTA participants was 26.9 kg/m 2 (range 15.8 – 61.6 kg/m 2 ); 25.1% had a BMI ≥ 30 kg/m 2 of which 5.3% had a BMI ≥ 40 kg/m 2 . The data cover more than 80,221 28-day cycles of LILETTA exposure. The frequencies of reported adverse drug reactions represent crude incidences. The most common adverse reactions during the LILETTA clinical study on contraception (occurring in ≥ 5% of participants) are shown in Table 6. The most common adverse reactions during the first year of use were acne (11.4%), bacterial vaginitis (9.0%), and vulvovaginal mycotic infection (7.9%). Table 6: Adverse Reactions in ≥ 5% of LILETTA Participants in the Phase 3 Clinical Study on Contraception Adverse Reaction % LILETTA Participants (N = 1 , 751) Vulvovaginal mycotic infections 20.2% Vaginal bacterial infections 19.2% Acne 15.5% Nausea or vomiting 10.5% Headache 10.1% Breast tenderness or pain 10.1% Abdominal discomfort or pain 10.0% Dyspareunia 9.6% Anxiety 9.6% Depression 9.1% Pelvic discomfort or pain 8.7% Dysmenorrhea 7.3% Mood changes 6.5% Back pain 6.5% Weight increased 6.1% Vaginal discharge 5.8% In the clinical study, 20.1% of LILETTA participants discontinued prematurely due to an adverse reaction. The most common adverse reactions reported by participants as reason for discontinuation were expulsion (4.1%), bleeding complaints (2.5%), acne (1.4%), dysmenorrhea (1.0%), weight increased (1.0%), mood swings (0.8%), uterine spasm (0.7%), dyspareunia (0.6%) and pelvic pain (0.6%). Two participants discontinued the clinical study due to PID and one due to endometritis. The most common adverse reactions reported by participants as reason for discontinuation during the first year of use were expulsion (2.9%) and acne (0.7%). In the clinical study, serious adverse reactions related to LILETTA were ectopic pregnancies, ovarian cysts, and IUS perforation requiring laparoscopic surgery. In the LILETTA clinical study on heavy menstrual bleeding, which included 105 participants who were 18- to 50-years old, the adverse reaction profile was consistent with the adverse reaction profile for LILETTA participants in the contraception study as shown in Table 6. Approximately 11% of LILETTA study participants discontinued prematurely due to an adverse reaction. The most common adverse reactions leading to discontinuation were expulsions (4.8%) and bleeding pattern alterations (3.8%). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of LNG-releasing IUSs. 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. Arterial thrombotic and venous thromboembolic events, including cases of pulmonary emboli, deep vein thrombosis, and stroke Hypersensitivity (including rash, urticaria, and angioedema) Increased blood pressure Dizziness Device breakage