norgestimate and ethinyl estradiol
Generic: NORGESTIMATE AND ETHINYL ESTRADIOL
Basic Information
Manufacturer
PD-Rx Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
FDA Set ID
2385591b-70ee-0577-e063-6394a90a9357
Indications & Usage
1 INDICATIONS AND USAGE Tri-Lo-Marzia is an estrogen/progestin COC, indicated for use by women to prevent pregnancy.
( 1.1 ) 1.1 Oral Contraception Tri-Lo-Marzia™ Tablets are indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES ( 14 )].
( 1.1 ) 1.1 Oral Contraception Tri-Lo-Marzia™ Tablets are indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES ( 14 )].
Adverse Reactions
6 ADVERSE REACTIONS The most common adverse reactions reported during clinical trials (≥2%) were: headache/migraine, nausea/vomiting, breast issues, abdominal pain, menstrual disorders, mood disorders, acne, vulvovaginal infection, abdominal distension, weight increased, fatigue.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc.
at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
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 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 Tri-Lo-Marzia was evaluated in 1,723 subjects who participated in a randomized, partially blinded, multicenter, active-controlled clinical trial of Tri-Lo-Marzia for contraception.
This trial examined healthy, nonpregnant, volunteers aged 18 to 45 (nonsmoker if 35 to 45 years of age), who were sexually active with regular coitus.
Subjects were followed for up to 13 28-day cycles.
Common Adverse Reactions (≥ 2% of subjects) The most common adverse reactions reported by at least 2% of the 1,723 women using the 28-day regimen were the following in order of decreasing incidence: headache/migraine (30.5%), nausea/vomiting (16.3%); breast issues (including tenderness, pain, enlargement, swelling, discharge, discomfort, cyst, and nipple pain) (10.3%), abdominal pain (9.2%), menstrual disorders (including dysmenorrhea, menstrual discomfort, menstrual disorder) (9.2%), mood disorders (including depression, mood altered, mood swings and depressed mood) (7.6%); acne (5.1%), vulvovaginal infection (3.5%), abdominal distension (2.8%), weight increased (2.4%), fatigue (2.1%).
Adverse Reactions Leading to Study Discontinuation In the clinical trial of Tri-Lo-Marzia 4% of subjects discontinued the trial due to an adverse reaction.
The most common adverse reactions leading to discontinuation were headache/migraine (1.2%), nausea/vomiting (0.7%), cervical dysplasia (0.7%), abdominal pain (0.4%), ovarian cyst (0.3%), acne (0.2%), flatulence (0.2%) and depression (0.2%).
Serious Adverse Reactions Carcinoma of the cervix in situ (1 subject) and cervical dysplasia (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 1).
Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1).
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 1: Risk of Breast Cancer with Combined Oral Contraceptive Use 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 additional adverse drug reactions have been reported from worldwide postmarketing experience with norgestimate/ethinyl estradiol.
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.
Infections and Infestations Urinary tract infection Neoplasms Benign, Malignant and Unspecified (Including Cysts and Polyps) Breast cancer, benign breast neoplasm, hepatic adenoma, focal nodular hyperplasia, breast cyst Immune System Disorders Hypersensitivity Metabolism and Nutrition Disorders Dyslipidemia Psychiatric Disorders Anxiety, insomnia Nervous System Disorders Syncope, convulsion, paresthesia, dizziness Eye Disorders Visual impairment, dry eye, contact lens intolerance Ear and Labyrinth Disorders Vertigo Cardiac Disorders Tachycardia, palpitations Vascular Events Deep vein thrombosis, pulmonary embolism, retinal vascular thrombosis, hot flush Arterial Events Arterial thromboembolism, myocardial infarction, cerebrovascular accident Respiratory, Thoracic and Mediastinal Disorders Dyspnea Gastrointestinal Disorders Pancreatitis, abdominal distension, diarrhea, constipation Hepatobiliary Disorders Hepatitis Skin and Subcutaneous Tissue Disorders Angioedema, erythema nodosum, hirsutism, night sweats, hyperhidrosis, photosensitivity reaction, urticaria, pruritus, acne Musculoskeletal, Connective Tissue, and Bone Disorders Muscle spasms, pain in extremity, myalgia, back pain Reproductive System and Breast Disorders Ovarian cyst, suppressed lactation, vulvovaginal dryness General Disorders and Administration Site Conditions Chest pain, asthenic conditions.
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( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc.
at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
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 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 Tri-Lo-Marzia was evaluated in 1,723 subjects who participated in a randomized, partially blinded, multicenter, active-controlled clinical trial of Tri-Lo-Marzia for contraception.
This trial examined healthy, nonpregnant, volunteers aged 18 to 45 (nonsmoker if 35 to 45 years of age), who were sexually active with regular coitus.
Subjects were followed for up to 13 28-day cycles.
Common Adverse Reactions (≥ 2% of subjects) The most common adverse reactions reported by at least 2% of the 1,723 women using the 28-day regimen were the following in order of decreasing incidence: headache/migraine (30.5%), nausea/vomiting (16.3%); breast issues (including tenderness, pain, enlargement, swelling, discharge, discomfort, cyst, and nipple pain) (10.3%), abdominal pain (9.2%), menstrual disorders (including dysmenorrhea, menstrual discomfort, menstrual disorder) (9.2%), mood disorders (including depression, mood altered, mood swings and depressed mood) (7.6%); acne (5.1%), vulvovaginal infection (3.5%), abdominal distension (2.8%), weight increased (2.4%), fatigue (2.1%).
Adverse Reactions Leading to Study Discontinuation In the clinical trial of Tri-Lo-Marzia 4% of subjects discontinued the trial due to an adverse reaction.
The most common adverse reactions leading to discontinuation were headache/migraine (1.2%), nausea/vomiting (0.7%), cervical dysplasia (0.7%), abdominal pain (0.4%), ovarian cyst (0.3%), acne (0.2%), flatulence (0.2%) and depression (0.2%).
Serious Adverse Reactions Carcinoma of the cervix in situ (1 subject) and cervical dysplasia (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 1).
Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1).
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 1: Risk of Breast Cancer with Combined Oral Contraceptive Use 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 additional adverse drug reactions have been reported from worldwide postmarketing experience with norgestimate/ethinyl estradiol.
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.
Infections and Infestations Urinary tract infection Neoplasms Benign, Malignant and Unspecified (Including Cysts and Polyps) Breast cancer, benign breast neoplasm, hepatic adenoma, focal nodular hyperplasia, breast cyst Immune System Disorders Hypersensitivity Metabolism and Nutrition Disorders Dyslipidemia Psychiatric Disorders Anxiety, insomnia Nervous System Disorders Syncope, convulsion, paresthesia, dizziness Eye Disorders Visual impairment, dry eye, contact lens intolerance Ear and Labyrinth Disorders Vertigo Cardiac Disorders Tachycardia, palpitations Vascular Events Deep vein thrombosis, pulmonary embolism, retinal vascular thrombosis, hot flush Arterial Events Arterial thromboembolism, myocardial infarction, cerebrovascular accident Respiratory, Thoracic and Mediastinal Disorders Dyspnea Gastrointestinal Disorders Pancreatitis, abdominal distension, diarrhea, constipation Hepatobiliary Disorders Hepatitis Skin and Subcutaneous Tissue Disorders Angioedema, erythema nodosum, hirsutism, night sweats, hyperhidrosis, photosensitivity reaction, urticaria, pruritus, acne Musculoskeletal, Connective Tissue, and Bone Disorders Muscle spasms, pain in extremity, myalgia, back pain Reproductive System and Breast Disorders Ovarian cyst, suppressed lactation, vulvovaginal dryness General Disorders and Administration Site Conditions Chest pain, asthenic conditions.
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