norgestimate and ethinyl estradiol
Generic: NORGESTIMATE AND ETHINYL ESTRADIOL
Basic Information
Manufacturer
AvKARE
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
FDA Set ID
a3cfd79e-a344-1dfc-e053-2995a90a1ab7
Indications & Usage
1 INDICATIONS AND USAGE Norgestimate and Ethinyl Estradiol Tablets, USP is an estrogen/progestin COCs, indicated for use by women to prevent pregnancy.
( 1.1 ) Norgestimate and Ethinyl Estradiol Tablets, USP is also indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche.
Norgestimate and Ethinyl Estradiol Tablets, USP should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control.
( 1.2 ) 1.1 Oral Contraceptive Norgestimate and Ethinyl Estradiol Tablets, USP is indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14) ] .
1.2 Acne Norgestimate and Ethinyl Estradiol Tablets, USP is indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche.
Tri-Estarylla™ should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control [see CLINICAL STUDIES ( 14 )].
( 1.1 ) Norgestimate and Ethinyl Estradiol Tablets, USP is also indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche.
Norgestimate and Ethinyl Estradiol Tablets, USP should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control.
( 1.2 ) 1.1 Oral Contraceptive Norgestimate and Ethinyl Estradiol Tablets, USP is indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14) ] .
1.2 Acne Norgestimate and Ethinyl Estradiol Tablets, USP is indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche.
Tri-Estarylla™ should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control [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: N orgestimate and ethinyl estradiol: headache/migraine, breast issues (including breast pain, enlargement, and discharge), vaginal infection, abdominal/gastrointestinal pain, mood disorders (including mood alteration and depression), genital discharge, changes in weight (including weight increased or decreased).
( 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 4,826 healthy women of child-bearing potential who participated in 6 clinical trials and received at least 1 dose of norgestimate and ethinyl estradiol for contraception.
Two trials were randomized active-controlled trials and 4 were uncontrolled open-label trials.
In 3 trials, subjects were followed for up to 24 cycles; in 2 trials, subjects were followed for up to 12 cycles; and in 1 trial, subjects were followed for up to 6 cycles.
Common Adverse Reactions (≥ 2% of subjects): The most common adverse reactions reported by at least 2% of the 4,826 women were the following in order of decreasing incidence: headache/migraine (33.6%), breast issues (including breast pain, enlargement, and discharge) (8%), vaginal infection (7.1%), abdominal/gastrointestinal pain (5.6%), mood disorders (including mood alteration and depression) (3.8%), genital discharge (3.2%), and changes in weight (including weight fluctuation, increased or decreased) (2.5%).
Adverse Reactions Leading to Study Discontinuation: Over the trials, between 9 to 27% of subjects discontinued the trial due to an adverse reaction.
The most common adverse reactions (≥1%) leading to discontinuation were: metrorrhagia (4.3%), nausea/vomiting (2.8%), headache/migraine (2.4%), mood disorders (including depression and mood altered) (1.1%), and weight increased (1.1%).
Serious Adverse Reactions: breast cancer (1 subject), carcinoma of the cervix in situ (1 subject), hypertension (1 subject), and migraine (2 subjects).
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 4,826 healthy women of child-bearing potential who participated in 6 clinical trials and received at least 1 dose of norgestimate and ethinyl estradiol for contraception.
Two trials were randomized active-controlled trials and 4 were uncontrolled open-label trials.
In 3 trials, subjects were followed for up to 24 cycles; in 2 trials, subjects were followed for up to 12 cycles; and in 1 trial, subjects were followed for up to 6 cycles.
Common Adverse Reactions (≥ 2% of subjects): The most common adverse reactions reported by at least 2% of the 4,826 women were the following in order of decreasing incidence: headache/migraine (33.6%), breast issues (including breast pain, enlargement, and discharge) (8%), vaginal infection (7.1%), abdominal/gastrointestinal pain (5.6%), mood disorders (including mood alteration and depression) (3.8%), genital discharge (3.2%), and changes in weight (including weight fluctuation, increased or decreased) (2.5%).
Adverse Reactions Leading to Study Discontinuation: Over the trials, between 9 to 27% of subjects discontinued the trial due to an adverse reaction.
The most common adverse reactions (≥1%) leading to discontinuation were: metrorrhagia (4.3%), nausea/vomiting (2.8%), headache/migraine (2.4%), mood disorders (including depression and mood altered) (1.1%), and weight increased (1.1%).
Serious Adverse Reactions: breast cancer (1 subject), carcinoma of the cervix in situ (1 subject), hypertension (1 subject), and migraine (2 subjects).
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