Estradiol / Norethindrone Acetate
Generic: ESTRADIOL AND NORETHINDRONE ACETATE
Basic Information
Manufacturer
Breckenridge Pharmaceutical, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
44125b2f-10ac-435c-bdb4-a29bf8450dbf
Indications & Usage
1 INDICATIONS AND USAGE Estradiol/Norethindrone Acetate Tablets are indicated for: Estradiol/Norethindrone Acetate Tablets are an estrogen and progestin combination indicated in a woman with a uterus for: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause ( 1.1 ) Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause ( 1.2 ) Limitations of Use : When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, first consider the use of topical vaginal products.
Prevention of Postmenopausal Osteoporosis ( 1.3 ) Limitations of Use : When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications.
Consider estrogen therapy only for women at significant risk of osteoporosis.
1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause 1.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Limitation of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, first consider the use of topical vaginal products.
1.3 Prevention of Postmenopausal Osteoporosis Limitation of Use When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications.
Consider estrogen therapy only for women at significant risk of osteoporosis.
Prevention of Postmenopausal Osteoporosis ( 1.3 ) Limitations of Use : When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications.
Consider estrogen therapy only for women at significant risk of osteoporosis.
1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause 1.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Limitation of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, first consider the use of topical vaginal products.
1.3 Prevention of Postmenopausal Osteoporosis Limitation of Use When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications.
Consider estrogen therapy only for women at significant risk of osteoporosis.
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning , Warnings and Precautions (5.1) ] Malignant Neoplasms [see Boxed Warning , Warnings and Precautions (5.2) ] The most common adverse reactions (incidence ≥ 5 percent) with Estradiol/Norethindrone Acetate Tablets are: back pain, headache, pain in the extremity, nausea, diarrhea, gastroenteritis, insomnia, emotional lability, upper respiratory tract infection, sinusitis, nasopharyngitis, weight increase, breast pain, post-menopausal bleeding, uterine fibroid vaginal hemorrhage, ovarian cyst, endometrial thickening, viral infection, moniliasis genital, and accidental injury.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Breckenridge Pharmaceutical, Inc.
at 1-800-367-3395 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 practice.
Adverse reactions reported with Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg by investigators during clinical trials regardless of causality assessment are shown in Table 1.
TABLE 1 ALL TREATMENT-EMERGENT ADVERSE REACTIONS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥ 5 PERCENT WITH ESTRADIOL/NORETHINDRONE ACETATE TABLETS 1 MG/0.5 MG Endometrial Hyperplasia Study (12-Months) Vasomotor Symptoms Study (3-Months) Osteoporosis Study (2-Years) Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg 1 mg E 2 Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg Placebo Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg Placebo (n=295) (n=296) (n=29) (n=34) (n=47) (n=48) Body as a Whole Back Pain 6% 5% 3% 3% 6% 4% Headache 16% 16% 17% 18% 11% 6% Digestive System Nausea 3% 5% 10% 0% 11% 0% Gastroenteritis 2% 2% 0% 0% 6% 4% Nervous System Insomnia 6% 4% 3% 3% 0% 8% Emotional Lability 1% 1% 0% 0% 6% 0% Respiratory System Upper Respiratory Tract Infection 18% 15% 10% 6% 15% 19% Sinusitis 7% 11% 7% 0% 15% 10% Metabolic and Nutritional Weight Increase 0% 0% 0% 0% 9% 6% Urogenital System Breast Pain 24% 10% 21% 0% 17% 8% Post-Menopausal Bleeding 5% 15% 10% 3% 11% 0% Uterine Fibroid 5% 4% 0% 0% 4% 8% Ovarian Cyst 3% 2% 7% 0% 0% 8% Resistance Mechanism Infection Viral 4% 6% 0% 3% 6% 6% Moniliasis Genital 4% 7% 0% 0% 6% 0% Secondary Terms Injury Accidental 4% 3% 3% 0% 17% including one upper extremity fracture in each group 4% Other Events 2% 3% 3% 0% 6% 4% Adverse reactions reported with Estradiol/Norethindrone Acetate Tablets 0.5 mg/0.1 mg by investigators during clinical trials regardless of causality assessment are shown in Table 2.
TABLE 2 ALL TREATMENT-EMERGENT ADVERSE REACTIONS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥ 5 PERCENT WITH ESTRADIOL/NORETHINDRONE ACETATE TABLETS 0.5 MG/0.1 MG Estradiol/Norethindrone Acetate Tablets 0.5 mg/0.1 mg (n=194) Placebo (n=200) Body as a Whole Back Pain 10% 4% Headache 22% 19% Pain in extremity 5% 4% Digestive System Nausea 5% 4% Diarrhea 6% 6% Respiratory System Nasopharyngitis 21% 18% Urogenital System Endometrial thickening 10% 4% Vaginal hemorrhage 26% 12% 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Estradiol/Norethindrone Acetate Tablets.
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.
Genitourinary System Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; pre-menstrual-like syndrome; cystitis-like syndrome; ovarian cancer; endometrial hyperplasia; endometrial cancer.
Breast Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.
Cardiovascular Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction, stroke; increase in blood pressure.
Gastrointestinal Nausea, vomiting; changes in appetite; cholestatic jaundice; abdominal pain/cramps, flatulence, bloating; increased incidence of gallbladder disease and pancreatitis.
Skin Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; seborrhea; hirsutism; itching; skin rash; pruritus.
Eyes Retinal vascular thrombosis, intolerance to contact lenses.
Central Nervous System Headache; migraine; dizziness; mental depression; chorea; insomnia; nervousness; mood disturbances; irritability; exacerbation of epilepsy; dementia.
Miscellaneous Increase or decrease in weight; edema; leg cramps; changes in libido; fatigue; exacerbation of asthma; increased triglycerides; hypersensitivity; anaphylactoid/anaphylactic reactions.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Breckenridge Pharmaceutical, Inc.
at 1-800-367-3395 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 practice.
Adverse reactions reported with Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg by investigators during clinical trials regardless of causality assessment are shown in Table 1.
TABLE 1 ALL TREATMENT-EMERGENT ADVERSE REACTIONS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥ 5 PERCENT WITH ESTRADIOL/NORETHINDRONE ACETATE TABLETS 1 MG/0.5 MG Endometrial Hyperplasia Study (12-Months) Vasomotor Symptoms Study (3-Months) Osteoporosis Study (2-Years) Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg 1 mg E 2 Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg Placebo Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg Placebo (n=295) (n=296) (n=29) (n=34) (n=47) (n=48) Body as a Whole Back Pain 6% 5% 3% 3% 6% 4% Headache 16% 16% 17% 18% 11% 6% Digestive System Nausea 3% 5% 10% 0% 11% 0% Gastroenteritis 2% 2% 0% 0% 6% 4% Nervous System Insomnia 6% 4% 3% 3% 0% 8% Emotional Lability 1% 1% 0% 0% 6% 0% Respiratory System Upper Respiratory Tract Infection 18% 15% 10% 6% 15% 19% Sinusitis 7% 11% 7% 0% 15% 10% Metabolic and Nutritional Weight Increase 0% 0% 0% 0% 9% 6% Urogenital System Breast Pain 24% 10% 21% 0% 17% 8% Post-Menopausal Bleeding 5% 15% 10% 3% 11% 0% Uterine Fibroid 5% 4% 0% 0% 4% 8% Ovarian Cyst 3% 2% 7% 0% 0% 8% Resistance Mechanism Infection Viral 4% 6% 0% 3% 6% 6% Moniliasis Genital 4% 7% 0% 0% 6% 0% Secondary Terms Injury Accidental 4% 3% 3% 0% 17% including one upper extremity fracture in each group 4% Other Events 2% 3% 3% 0% 6% 4% Adverse reactions reported with Estradiol/Norethindrone Acetate Tablets 0.5 mg/0.1 mg by investigators during clinical trials regardless of causality assessment are shown in Table 2.
TABLE 2 ALL TREATMENT-EMERGENT ADVERSE REACTIONS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥ 5 PERCENT WITH ESTRADIOL/NORETHINDRONE ACETATE TABLETS 0.5 MG/0.1 MG Estradiol/Norethindrone Acetate Tablets 0.5 mg/0.1 mg (n=194) Placebo (n=200) Body as a Whole Back Pain 10% 4% Headache 22% 19% Pain in extremity 5% 4% Digestive System Nausea 5% 4% Diarrhea 6% 6% Respiratory System Nasopharyngitis 21% 18% Urogenital System Endometrial thickening 10% 4% Vaginal hemorrhage 26% 12% 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Estradiol/Norethindrone Acetate Tablets.
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.
Genitourinary System Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; pre-menstrual-like syndrome; cystitis-like syndrome; ovarian cancer; endometrial hyperplasia; endometrial cancer.
Breast Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.
Cardiovascular Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction, stroke; increase in blood pressure.
Gastrointestinal Nausea, vomiting; changes in appetite; cholestatic jaundice; abdominal pain/cramps, flatulence, bloating; increased incidence of gallbladder disease and pancreatitis.
Skin Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; seborrhea; hirsutism; itching; skin rash; pruritus.
Eyes Retinal vascular thrombosis, intolerance to contact lenses.
Central Nervous System Headache; migraine; dizziness; mental depression; chorea; insomnia; nervousness; mood disturbances; irritability; exacerbation of epilepsy; dementia.
Miscellaneous Increase or decrease in weight; edema; leg cramps; changes in libido; fatigue; exacerbation of asthma; increased triglycerides; hypersensitivity; anaphylactoid/anaphylactic reactions.