Label: ACTIVELLA- estradiol/norethindrone acetate tablet, film coated

  • NDC Code(s): 60846-231-01, 60846-232-01
  • Packager: Amneal Pharmaceuticals LLC
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: New Drug Application

Drug Label Information

Updated November 30, 2023

If you are a consumer or patient please visit this version.

  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use ACTIVELLA safely and effectively. See full prescribing information for ACTIVELLA.  ACTIVELLA® (estradiol/norethindrone acetate ...
  • Table of Contents
    Table of Contents
  • BOXED WARNING (What is this?)

    WARNING: CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER

    Estrogen Plus Progestin Therapy

    Cardiovascular Disorders and Probable Dementia

    The Women’s Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogen (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo [see Warnings and Precautions (5.1), and Clinical Studies (14.5)].

    The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions (5.3), Use in Specific Populations (8.5), and Clinical Studies (14.6)].

     

    Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1, 5.3), and Clinical Studies (14.5, 14.6)].

    Breast Cancer

     

    The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.2), and Clinical Studies (14.5)].

    Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen plus progestogen therapy, taking into account her individual risk profile.

    Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

    Estrogen-Alone Therapy

    Endometrial Cancer

    There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2)].

    Cardiovascular Disorders and Probable Dementia

    The WHI estrogen-alone substudy reported increased risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral CE (0.625 mg)-alone, relative to placebo [see Warnings and Precautions (5.1), and Clinical Studies (14.5)].

    The WHIMS estrogen-alone ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions (5.3), Use in Specific Populations (8.5), and Clinical Studies (14.6)].

    Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1, 5.3), and Clinical Studies (14.5, 14.6)].

    Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile.

    Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

    Close
  • 1 INDICATIONS AND USAGE
    Activella is indicated for: 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 ...
  • 2 DOSAGE AND ADMINISTRATION
    Use estrogen-alone, or in combination with a progestogen, at the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate ...
  • 3 DOSAGE FORMS AND STRENGTHS
    Activella is available in two strengths: Activella 1 mg/ 0.5 mg contains 1 mg of estradiol and 0.5 mg of norethindrone acetate. The tablets are white, round, biconvex, film-coated tablets ...
  • 4 CONTRAINDICATIONS
    Activella is contraindicated in women with any of the following conditions:   Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.2)] Breast cancer or history of breast ...
  • 5 WARNINGS AND PRECAUTIONS
    5.1 Cardiovascular Disorders - Increased risks of PE, DVT, stroke and MI are reported with estrogen plus progestin therapy. Increased risks of stroke and DVT are reported with estrogen-alone ...
  • 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 ...
  • 7 DRUG INTERACTIONS
    Co-administration of estradiol with norethindrone acetate did not elicit any apparent influence on the pharmacokinetics of norethindrone acetate. Similarly, no relevant interaction of ...
  • 8 USE IN SPECIFIC POPULATIONS
    8.1 Pregnancy - Risk Summary - Activella is not indicated for use in pregnancy. There are no data with the use of Activella in pregnant women; however, epidemiologic studies and meta-analyses ...
  • 10 OVERDOSAGE
    Overdosage of estrogen plus progestogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose ...
  • 11 DESCRIPTION
    Activella 1 mg/0.5 mg is a single tablet for oral administration containing 1 mg of estradiol and 0.5 mg of norethindrone acetate and the following excipients: lactose monohydrate, starch (corn) ...
  • 12 CLINICAL PHARMACOLOGY
    12.1 Mechanism of Action - Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although ...
  • 13 NONCLINICAL TOXICOLOGY
    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility - Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas ...
  • 14 CLINICAL STUDIES
    14.1 Effects on Vasomotor Symptoms in Postmenopausal Women - In a 12-week randomized clinical trial involving 92 subjects, Activella 1 mg/0.5 mg was compared to 1 mg of estradiol and to placebo ...
  • 15 REFERENCES
    1.         Rossouw JE, et al. Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause. JAMA. 2007;297:1465-1477. 2.         Hsia J, et al. Conjugated ...
  • 16 HOW SUPPLIED/STORAGE AND HANDLING
    16.1 - How Supplied - Activella (estradiol/norethindrone acetate) tablets, 1 mg/0.5 mg are available as white, round, biconvex, film-coated tablets, debossed with “ALH” on the one side and plain ...
  • 17 PATIENT COUNSELING INFORMATION
    Advise women to read the FDA-approved patient labeling (Patient Information) Vaginal Bleeding - Inform postmenopausal women to report any vaginal bleeding to their healthcare provider as soon as ...
  • PATIENT INFORMATION
    Activella® (AK-ti-vel-la) (estradiol/norethindrone acetate) tablets, for oral use - Read this Patient Information before you start using ACTIVELLA and each time you get a refill. There may be ...
  • PRINCIPAL DISPLAY PANEL
    HD Carton
  • PRINCIPAL DISPLAY PANEL
    HD Pouch
  • PRINCIPAL DISPLAY PANEL
    HD Face Card
  • PRINCIPAL DISPLAY PANEL
    LD CARTON
  • PRINCIPAL DISPLAY PANEL
    LD POUCH
  • PRINCIPAL DISPLAY PANEL
    LD FACE CARD
  • INGREDIENTS AND APPEARANCE
    Product Information