Norelgestromin And Ethinly Estradiol Side Effects

6 ADVERSE REACTIONS The following serious adverse reactions with the use of combination hormonal contraceptives, including norelgestromin and ethinyl estradiol, are discussed elsewhere in the labeling: Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions (5.1) ] Vascular events, including venous and arterial thromboembolic events [see Warnings and Precautions (5.1) ] Liver disease [see Warnings and Precautions (5.3) ] Adverse reactions commonly reported by users of combination hormonal contraceptives are: Irregular uterine bleeding Nausea Breast tenderness Headache The most frequent adverse reactions reported during clinical trials (≥ 5%) were breast symptoms, nausea/vomiting, headache, application site disorder, abdominal pain, dysmenorrhea, vaginal bleeding and menstrual disorders, and mood, affect and anxiety disorders.

(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 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 clinical practice.

The data described below reflect exposure to norelgestromin and ethinyl estradiol transdermal system in 3,330 sexually active women (3,322 of whom had safety data) who participated in three Phase 3 clinical trials designed to evaluate contraceptive efficacy and safety.

These subjects received six or 13 cycles of contraception (norelgestromin and ethinyl estradiol transdermal system or an oral contraceptive comparator in 2 of the trials).

The women ranged in age from 18 to 45 years and were predominantly white (91%).

The most common adverse reactions (≥ 5%) reported during clinical trials were breast symptoms, nausea/vomiting, headache, application site disorder, abdominal pain, dysmenorrhea, vaginal bleeding and menstrual disorders, and mood, affect and anxiety disorders.

The most common events leading to discontinuation were application site reaction, breast symptoms (including breast discomfort, engorgement and pain), nausea and/or vomiting, headache and emotional lability.

Adverse drug reactions reported by ≥ 2.5% of norelgestromin and ethinyl estradiol-treated subjects in these trials are shown in Table

Table 3: Adverse Drug Reactions Reported by ≥ 2.5% of Norelgestromin and Ethinyl Estradiol-treated Subjects in Three Phase 3 Clinical Trials System/Organ Class* Adverse reaction Norelgestromin and Ethinyl Estradiol (n=3,322) Reproductive system and breast disorders Breast symptoms † 22.4% Dysmenorrhea 7.8% Vaginal bleeding and menstrual disorders † 6.4% Gastrointestinal disorders Nausea 16.6% Abdominal pain † 8.1% Vomiting 5.1% Diarrhea 4.2% Nervous system disorders Headache 21.0% Dizziness 3.3% Migraine 2.7% General disorders and administration site conditions Application site disorder † 17.1% Fatigue 2.6% Psychiatric disorders Mood, affect and anxiety disorders † 6.3% Skin and subcutaneous tissue disorders Acne 2.9% Pruritus 2.5% Infections and infestations Vaginal yeast infection † 3.9% Investigations Weight increased 2.7% * MedDRA version 10.0 † Represents a bundle of similar terms Additional adverse drug reactions that occurred in < 2.5% of norelgestromin and ethinyl estradiol transdermal system-treated subjects in the above clinical trials datasets are: Gastrointestinal disorders: Abdominal distension General disorders and administration site conditions: Fluid retention 1 , malaise Hepatobiliary disorders: Cholecystitis Investigations: Blood pressure increased, lipid disorders 1 Musculoskeletal and connective tissue disorders: Muscle spasms Psychiatric disorders: Insomnia, libido decreased, libido increased Reproductive system and breast disorders: Galactorrhea, genital discharge, premenstrual syndrome, uterine spasm, vaginal discharge, vulvovaginal dryness Respiratory, thoracic and mediastinal disorders: Pulmonary embolism Skin and subcutaneous tissue disorders: Chloasma, dermatitis contact, erythema, skin irritation 1 Represents a bundle of similar terms 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 to 1.12 (Figure 2).