Norgestimate and Ethinyl Estradiol
Generic: NORGESTIMATE AND ETHINYL ESTRADIOL
Basic Information
Manufacturer
AvKARE
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
FDA Set ID
a3c0c983-7ec7-244a-e053-2995a90adbe4
Indications & Usage
1 INDICATIONS AND USAGE Norgestimate and Ethinyl Estradiol Tablets are an estrogen/progestin COCs, indicated for use by women to prevent pregnancy.
( 1.1 ) 1.1 Oral Contraceptive Norgestimate and Ethinyl Estradiol Tablets are indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14) ] .
( 1.1 ) 1.1 Oral Contraceptive Norgestimate and Ethinyl Estradiol Tablets are indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14) ] .
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions with the use of COCs are discussed elsewhere in 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 (5.2) ] Adverse reactions commonly reported by COC users are: Irregular uterine bleeding Nausea Breast tenderness Headache The most common adverse reactions reported during clinical trials (≥2%) were: Norgestimate and ethinyl estradiol: headache/migraine, abdominal/gastrointestinal pain, vaginal infection, genital discharge, breast issues (including breast pain, discharge, and enlargement), mood disorders (including depression and mood altered), flatulence, nervousness, rash.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993; email DRUGSAFETY@AVKARE.COM or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trial 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 safety of norgestimate and ethinyl estradiol was evaluated in 1,647 healthy women of child-bearing potential who participated in 3 clinical trials and received at least 1 dose of norgestimate and ethinyl estradiol for contraception.
Two trials were randomized active-controlled trials and 1 was an uncontrolled open-label trial.
In all 3 trials, subjects were followed for up to 24 cycles.
Common Adverse Reactions (≥ 2% of subjects): The most common adverse reactions reported by at least 2% of the 1,647 women were the following in order of decreasing incidence: headache/migraine (32.9%), abdominal/gastrointestinal pain (7.8%), vaginal infection (8.4%), genital discharge (6.8%), breast issues (including breast pain, discharge, and enlargement) (6.3%), mood disorders (including depression and mood altered) (5%), flatulence (3.2%), nervousness (2.9%), and rash (2.6%).
Adverse Reactions Leading to Study Discontinuation: Over the three trials, between 11 to 21% of subjects discontinued the trial due to an adverse reaction.
The most common adverse reactions (≥1%) leading to discontinuation were: metrorrhagia (6.9%), nausea/vomiting (5%), headache (4.1%), mood disorders (including depression and mood altered) (2.4%), premenstrual syndrome (1.7%), hypertension (1.4%), breast pain (1.4%), nervousness (1.3%), amenorrhea (1.1%), dysmenorrhea (1.1%), weight increased (1.1%), and flatulence (1.1%).
Serious Adverse Reactions: breast cancer (1 subject), mood disorders including depression, irritability, and mood swings (1 subject), myocardial infarction (1 subject), and venous thromboembolic events including pulmonary embolism (1 subject) and deep vein thrombosis (DVT) (1 subject).
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.
For your reference, below are the studies reviewed by FDA to inform the breast cancer risk: References: 1.
Marchbanks PA, McDonald JA, Wilson HG, et al.
Oral contraceptives and the risk of breast cancer.
N Engl J Med.
2002;346(26):2025-2032.
2.
Dumeaux V, Fournier A, Lund E, Clavel-Chapelon F.
Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women.
Cancer Causes Control.
2005;16(5):537-544.
3.
Dorjgochoo T, Shu XO, Li HL, et al.
Use of oral contraceptives, intrauterine devices and tubal sterilization and cancer risk in a large prospective study, from 1996 to 2006.
Int J Cancer.
2009;124(10):2442- 2449.
4.
Hunter DJ, Colditz GA, Hankinson SE, et al.
Oral contraceptive use and breast cancer: a prospective study of young women.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.
2010;19(10):2496-2502.
5.
Vessey M, Yeates D.
Oral contraceptive use and cancer.
Final report from the Oxford-Family Planning Association contraceptive study.
Contraception.
2013; 88(6): 678-683.
6.
Morch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard O.
Contemporary Hormonal Contraception and the Risk of Breast Cancer.
N Engl J Med.
2017;377(23):2228-2239.
2
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993; email DRUGSAFETY@AVKARE.COM or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trial 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 safety of norgestimate and ethinyl estradiol was evaluated in 1,647 healthy women of child-bearing potential who participated in 3 clinical trials and received at least 1 dose of norgestimate and ethinyl estradiol for contraception.
Two trials were randomized active-controlled trials and 1 was an uncontrolled open-label trial.
In all 3 trials, subjects were followed for up to 24 cycles.
Common Adverse Reactions (≥ 2% of subjects): The most common adverse reactions reported by at least 2% of the 1,647 women were the following in order of decreasing incidence: headache/migraine (32.9%), abdominal/gastrointestinal pain (7.8%), vaginal infection (8.4%), genital discharge (6.8%), breast issues (including breast pain, discharge, and enlargement) (6.3%), mood disorders (including depression and mood altered) (5%), flatulence (3.2%), nervousness (2.9%), and rash (2.6%).
Adverse Reactions Leading to Study Discontinuation: Over the three trials, between 11 to 21% of subjects discontinued the trial due to an adverse reaction.
The most common adverse reactions (≥1%) leading to discontinuation were: metrorrhagia (6.9%), nausea/vomiting (5%), headache (4.1%), mood disorders (including depression and mood altered) (2.4%), premenstrual syndrome (1.7%), hypertension (1.4%), breast pain (1.4%), nervousness (1.3%), amenorrhea (1.1%), dysmenorrhea (1.1%), weight increased (1.1%), and flatulence (1.1%).
Serious Adverse Reactions: breast cancer (1 subject), mood disorders including depression, irritability, and mood swings (1 subject), myocardial infarction (1 subject), and venous thromboembolic events including pulmonary embolism (1 subject) and deep vein thrombosis (DVT) (1 subject).
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.
For your reference, below are the studies reviewed by FDA to inform the breast cancer risk: References: 1.
Marchbanks PA, McDonald JA, Wilson HG, et al.
Oral contraceptives and the risk of breast cancer.
N Engl J Med.
2002;346(26):2025-2032.
2.
Dumeaux V, Fournier A, Lund E, Clavel-Chapelon F.
Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women.
Cancer Causes Control.
2005;16(5):537-544.
3.
Dorjgochoo T, Shu XO, Li HL, et al.
Use of oral contraceptives, intrauterine devices and tubal sterilization and cancer risk in a large prospective study, from 1996 to 2006.
Int J Cancer.
2009;124(10):2442- 2449.
4.
Hunter DJ, Colditz GA, Hankinson SE, et al.
Oral contraceptive use and breast cancer: a prospective study of young women.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.
2010;19(10):2496-2502.
5.
Vessey M, Yeates D.
Oral contraceptive use and cancer.
Final report from the Oxford-Family Planning Association contraceptive study.
Contraception.
2013; 88(6): 678-683.
6.
Morch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard O.
Contemporary Hormonal Contraception and the Risk of Breast Cancer.
N Engl J Med.
2017;377(23):2228-2239.
2