gigantic [0.001:<0.001 --- Week 12 Mean (SD) 30.7 (47.7) 12.2 (18.7) 12.4 (26.3) 47.5 (49.8) Mean Change from Baseline (SE) -66.3 (4.6) -84.6 (4.4) -82.6 (4.5) -48.3 (4.5) p-value versus placebo> <0.001> <0.001> <0.001 --- ITT= Intent to treat; LOCF= Last Observation Carried Forward, SD= Standard Deviation; SE= Standard Error Table 6: Mean Change in Severity of Moderate to Severe Hot Flushes Per Week, ITT Population with LOCF 0.3 mg n=66 0.625 mg n=71 1.25 mg n=69 Placebo n=70 Baseline Mean (SD) 2.5 (0.3) 2.5 (0.3) 2.5 (0.3) 2.5 (0.3) Week 4 Mean (SD) 2.1 (0.8) 1.9 (1.0) 1.5 (1.1) 2.2 (0.8) Mean Change from Baseline (SE) -0.5 (0.1) -0.6 (0.1) -1.0 (0.1) -0.3 (0.1) p-value versus placebo 0.036 0.002> <0.001 --- Week 12 Mean (SD) 1.5 (1.2) 1.1 (1.2) 1.0 (1.1) 1.9 (1.1) Mean Change from Baseline (SE) -1.0 (0.1) -1.4 (0.1) -1.5 (0.1) -0.6 (0.1) p-value versus placebo 0.023> <0.001> <0.001 --- ITT= Intent to treat; LOCF= Last Observation Carried Forward, SD= Standard Deviation; SE= Standard Error Effects on Vulvar and Vaginal Atrophy A randomized, double-blind, placebo-controlled, multi-center clinical study was conducted to evaluate the safety and effectiveness of Enjuvia 0.3 mg tablets for the treatment of symptoms of vulvar and vaginal atrophy in 248 naturally or surgically postmenopausal women between 32 to 81 years of age (mean 58.6 years) who at baseline had 5% superficial cells on a vaginal smear, a vaginal pH > 5.0, and who identified their most bothersome moderate-to-severe symptom of vulvar and vaginal atrophy. The majority (82%) of the women were Caucasian (n=203), 11% were Hispanic (n=26), 4% were Black (n=9), and 3% were Asian (n=6). All patients were assessed for improvement in the mean change from baseline to Week 12 for three co-primary efficacy variables: most bothersome symptom of vulvar and vaginal atrophy (defined as the moderate to severe symptom that had been identified by the patient as most bothersome to her at baseline); percentage of vaginal superficial cells and percentage of vaginal parabasal cells; and vaginal pH. In this study, a statistically significant mean change between baseline and Week 12 for the group treated with Enjuvia 0.3 mg tablets compared to placebo was observed for the symptoms, vaginal dryness and pain with intercourse. See Table 7 . Enjuvia 0.3 mg tablets increased superficial cells by a mean of 17.1% as compared to 2.0% for placebo (statistically significant). A corresponding statistically significant mean reduction from baseline in parabasal cells (41.7% for Enjuvia 0.3 mg tablets and 6.8% for placebo) was observed at Week 12. The mean reduction between baseline and Week 12 in the pH was 1.69 in the Enjuvia 0.3 mg tablets group and 0.45 in the placebo group (statistically significant). Table 7: Change from Baseline to Week 12 in the Severity of Vaginal Dryness and Pain with Intercourse, Symptoms That Were Identified by the Menopausal Woman as Her Most Bothersome Symptom of Vulvar and Vaginal Atrophy at Baseline Most Bothersome Symptom at Baseline* Enjuvia 0.3 mg Placebo Vaginal Dryness n 56 54 Baseline Severity 2.52 2.54 Mean Severity at Week 12 0.80 1.81 Mean Change in Severity from Baseline (s.d.) -1.71 (0.85) -0.72 (0.66) p-value versus placebo> <0.001 --- Pain With Intercourse n 35 40 Baseline Severity 2.74 2.70 Mean Severity at Week 12 0.94 1.95 Mean Change in Severity from Baseline (s.d.) -1.80 (1.02) -0.75 (0.95) p-value versus placebo> <0.001 --- * Treatment differences assessed by ANCOVA or rank ANCOVA (% cell data) with baseline as covariate for the modified intent-to-treat population, last-observation-carried-forward data set. Women s Health Initiative Studies The WHI enrolled approximately 27,000 predominantly healthy postmenopausal women in two substudies to assess the risks and benefits of either the use of daily oral CE (0.625 mg)-alone or in combination with MPA (2.5 mg) compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of CHD (defined as nonfatal MI, silent MI, and CHD death), with invasive breast cancer as the primary adverse outcome. A global index included the earliest occurrence of CHD, invasive breast cancer, stroke, PE, endometrial cancer (only in the CE plus MPA substudy), colorectal cancer, hip fracture, or death due to other causes. These substudies did not evaluate the effects of CE-alone or CE plus MPA on menopausal symptoms. WHI Estrogen-Alone Substudy The WHI estrogen-alone substudy was stopped early because an increased risk of stroke was observed, and it was deemed that no further information would be obtained regarding the risks and benefits of estrogen alone in predetermined primary endpoints. Results of the estrogen-alone substudy, which included 10,739 women (average 63 years of age, range 50 to 79; 75.3 percent White, 15.1 percent Black, 6.1 percent Hispanic, 3.6 percent Other), after an average follow-up of 7.1 years are presented in Table 8 . Table 8: Relative and Absolute Risk Seen in the Estrogen-Alone Substudy of WHI * Event Relative Risk CE vs. Placebo (95% nCI † ) CE n = 5,310 Placebo n = 5,429 Absolute Risk per 10,000 Women-Years * Adapted from numerous WHI publications. WHI publications can be viewed at www.nhlbi.nih.gov/whi. † Nominal confidence intervals unadjusted for multiple looks and multiple comparisons. ‡ Results are based on centrally adjudicated data for an average follow-up of 7.1 years. Not included in global index . Results are based on an average follow-up of 6.8 years. # All deaths, except from breast or colorectal cancer, definite or probable CHD, PE, or cerebrovascular disease. Þ A subset of the events was combined in a global index , defined as the earliest occurrence of CHD events, invasive breast cancer, stroke, PE, colorectal cancer, hip fracture, or death due to other causes. CHD events ‡ 0.95 (0.78-1.16) 54 57 Nonfatal MI ‡ 0.91 (0.73-1.14) 40 43 CHD death ‡ 1.01(0.71-1.43) 16 16 All strokes ‡ 1.33 (1.05-1.68) 45 33 Ischemic stroke ‡ 1.55 (1.19-2.01) 38 25 Deep vein thrombosis ‡ , 1.47 (1.06-2.06) 23 15 Pulmonary embolism ‡ 1.37 (0.90-2.07) 14 10 Invasive breast cancer ‡ 0.80 (0.62-1.04) 28 34 Colorectal cancer 1.08 (0.75-1.55) 17 16 Hip fracture ‡ 0.65 (0.45-0.94) 12 19 Vertebral fractures ‡ , 0.64 (0.44-0.93) 11 18 Lower arm/wrist fractures ‡ , 0.58 (0.47-0.72) 35 59 Total fractures ‡ , 0.71 (0.64-0.80) 144 197 Death due to other causes , # 1.08 (0.88-1.32) 53 50 Overall mortality ‡ , 1.04 (0.88-1.22) 79 75 Global index Þ 1.02 (0.91-1.13) 206 201 For those outcomes included in the WHI global index that reached statistical significance, the absolute excess risk per 10,000 women-years in the group treated with CE-alone was 12 more strokes, while the absolute risk reduction per 10,000 women-years was 7 fewer hip fractures. 9 The absolute excess risk of events included in the global index was a nonsignificant 5 events per 10,000 women-years. There was no difference between the groups in terms of all-cause mortality. No overall difference for primary CHD events (nonfatal MI, silent MI, and CHD death) and invasive breast cancer incidence in women receiving CE-alone compared with placebo was reported in final centrally adjudicated results from the estrogen-alone substudy, after an average follow up of 7.1 years (see Table 8 ). Centrally adjudicated results for stroke events from the estrogen-alone substudy, after an average follow-up of 7.1 years, reported no significant difference in distribution of stroke subtype or severity, including fatal strokes, in women receiving CE-alone compared to placebo. Estrogen alone increased the risk for ischemic stroke, and this excess risk was present in all subgroups of women examined 10 (see Table 8 ). Timing of the initiation of estrogen-alone therapy relative to the start of menopause may affect the overall risk benefit profile. The WHI estrogen-alone substudy stratified by age showed in women 50 to 59 years of age, a nonsignificant trend toward reduced risk for CHD (hazard ratio [HR] 0.63 [95 percent CI, 0.36-1.09]) and overall mortality (HR 0.71 [95 percent CI, 0.46-1.11]). WHI Estrogen Plus Progestin Substudy The WHI estrogen plus progestin substudy was stopped early. According to the predefined stopping rule, after an average follow-up of 5.6 years of treatment, the increased risk of invasive breast cancer and cardiovascular events exceeded the specified benefits included in the global index . The absolute excess risk of events included in the global index was 19 per 10,000 women-years. For those outcomes included in the WHI global index that reached statistical significance after 5.6 years of follow-up, the absolute excess risks per 10,000 women-years in the group treated with CE plus MPA were 7 more CHD events, 8 more strokes, 10 more PEs, and 8 more invasive breast cancers, while the absolute risk reductions per 10,000 women-years were 6 fewer colorectal cancers and 5 fewer hip fractures. Results of the CE plus MPA substudy, which included 16,608 women (average 63 years of age, range 50 to 79; 83.9 percent White, 6.8 percent Black, 5.4 percent Hispanic, 3.9 percent Other) are presented in Table 9 . These results reflect centrally adjudicated data after an average follow-up of 5.6 years. Table 9: Relative and Absolute Risk Seen in the Estrogen Plus Progestin Substudy of WHI at an Average of 5.6 Years * † Event Relative Risk CE/MPA vs. Placebo (95% nCI ‡ ) CE/MPA n = 8,506 Placebo n = 8,102 Absolute Risk per 10,000 Women-Years * Adapted from numerous WHI publications. WHI publications can be viewed at www.nhlbi.nih.gov/whi. † Results are based on centrally adjudicated data. ‡ Nominal confidence intervals unadjusted for multiple looks and multiple comparisons. Not included in global index . Includes metastatic and non-metastatic breast cancer, with the exception of in situ breast cancer. # All deaths, except from breast or colorectal cancer, definite or probable CHD, PE, or cerebrovascular disease. Þ A subset of the events was combined in a global index , defined as the earliest occurrence of CHD events, invasive breast cancer, stroke, pulmonary embolism, colorectal cancer, hip fracture, or death due to other causes. CHD events 1.23 (0.99-1.53) 41 34 Non-fatal MI 1.28 (1.00-1.63) 31 25 CHD death 1.10 (0.70-1.75) 8 8 All strokes 1.31 (1.03-1.68) 33 25 Ischemic stroke 1.44 (1.09-1.90) 26 18 Deep vein thrombosis 1.95 (1.43-2.67) 26 13 Pulmonary embolism 2.13 (1.45-3.11) 18 8 Invasive breast cancer 1.24 (1.01-1.54) 41 33 Colorectal cancer 0.61 (0.42-0.87) 10 16 Endometrial cancer 0.81 (0.48-1.36) 6 7 Cervical cancer 1.44 (0.47-4.42) 2 1 Hip fracture 0.67 (0.47-0.96) 11 16 Vertebral fractures 0.65 (0.46-0.92) 11 17 Lower arm/wrist fractures 0.71 (0.59-0.85) 44 62 Total fractures 0.76 (0.69-0.83) 152 199 Overall Mortality # 1.00 (0.83-1.19 52 52 Global Index Þ 1.13 (1.02-1.25) 184 165 Timing of the initiation of estrogen therapy relative to the start of menopause may affect the overall risk benefit profile. The WHI estrogen plus progestin substudy stratified by age showed in women 50 to 59 years of age, a non-significant trend toward reduced risk for overall mortality (HR 0.69 [95 percent CI, 0.44-1.07]). Women s Health Initiative Memory Study The WHIMS estrogen-alone ancillary study of WHI enrolled 2,947 predominantly healthy postmenopausal women 65 to 79 years of age (45 percent were 65 to 69 years of age; 36 percent were 70 to 74 years of age; and 19 percent were 75 years of age and older) to evaluate the effects of daily CE (0.625 mg)-alone on the incidence of probable dementia (primary outcome) compared with placebo. After an average follow-up of 5.2 years, the relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent CI, 0.83-2.66). The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10,000 woman-years. Probable dementia as defined in this study included Alzheimer s disease (AD), vascular dementia (VaD), and mixed types (having features of both AD and VaD). The most common classification of probable dementia in both the treatment group and the placebo group was AD. Since the ancillary study was conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women [see Warnings and Precautions ( 5.3 ), and Use in Specific Populations ( 8.5 )]. The WHIMS estrogen-plus-progestin ancillary study enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older (47 percent were 65 to 69 years of age, 35 percent were 70 to 74 years of age, and 18 percent were 75 years of age and older) to evaluate the effects of daily CE (0.625 mg) plus MPA (2.5 mg) on the incidence of probable dementia (primary outcome) compared with placebo. After an average follow-up of 4 years, the relative risk of probable dementia for CE plus MPA versus placebo was 2.05 (95 percent CI, 1.21-3.48). The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 22 per 10,000 woman-years. Probable dementia as defined in this study included AD, VaD, and mixed type (having features of both AD and VaD). The most common classification of probable dementia in the treatment group and the placebo group was AD. Since the ancillary study was conducted in women 65 to79 years of age, it is unknown whether these findings apply to younger postmenopausal women [see Warnings and Precautions ( 5.3 ), and Use in Specific Populations ( 8.5 )] . When data from the two populations were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95 percent CI, 1.19-2.60). Differences between groups became apparent in the first year of treatment. It is unknown whether these findings apply to younger postmenopausal women [see Warnings and Precautions ( 5.3 ), and Use in Specific Populations ( 8.5 )] . 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 Equine Estrogens and Coronary Heart Disease. Arch Int Med. 2006;166:357-365. 3. Curb JD, et al. Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus. Arch Int Med. 2006;166:772-780. 4. Cushman M, et al. Estrogen Plus Progestin and Risk of Venous Thrombosis. JAMA. 2004;292:1573-1580. 5. Stefanick ML, et al. Effects of Conjugated Equine Estrogens on Breast Cancer and Mammography Screening in Postmenopausal Women With Hysterectomy. JAMA. 2006;295:1647-1657. 6. Chlebowski RT, et al. Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women. JAMA. 2003;289:3234-3253. 7. Anderson GL, et al. Effects of Estrogen Plus Progestin on Gynecologic Cancers and Associated Diagnostic Procedures. JAMA. 2003;290:1739-1748. 8. Shumaker SA, et al. Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women. JAMA. 2004;291:2947-2958. 9. Jackson RD, et al. Effects of Conjugated Equine Estrogen on Risk of Fractures and BMD in Postmenopausal Women With Hysterectomy: Results From the Women's Health Initiative Randomized Trial. J Bone Miner Res. 2006;21:817-828. 10. Hendrix SL, et al. Effects of Conjugated Equine Estrogen on Stroke in the Women's Health Initiative. Circulation. 2006;113:2425-2434. How Supplied/Storage and Handling How Supplied Enjuvia (synthetic conjugated estrogens, B) Tablets • 0.3 mg: The tablets are oval, white, film-coated, and debossed with E on one side and 1 on the reverse and are available in bottles of: 100 Tablets NDC 51285-406-02 • 0.45 mg: The tablets are oval, mauve, film-coated, and debossed with E on one side and 2 on the reverse and are available in bottles of: 100 Tablets NDC 51285-407-02 • 0.625 mg: The tablets are oval, pink, film-coated, and debossed with E on one side and 3 on the reverse and are available in bottles of: 100 Tablets NDC 51285-408-02 • 0.9 mg: The tablets are oval, light blue-green, film-coated, and debossed with E on one side and 5 on the reverse and are available in bottles of: 100 Tablets NDC 51285-409-02 • 1.25 mg: The tablets are oval, yellow, film-coated, and debossed with E on one side and 4 on the reverse and are available in bottles of: 100 Tablets NDC 51285-410-02 Storage and Handling Store at 20 to 25 C (68 to 77 F) ; excursions are permitted to 15 to 30 C (59 to 86 F) [See USP Controlled Room Temperature]. Keep this and all drugs out of the reach of children. Dispense in a tight container with a child-resistant closure. Pharmacist: Include one Patient Information leaflet with each prescription. Patient Counseling Information See FDA-approved patient labeling (Patient Information) Vaginal Bleeding Inform postmenopausal women of the importance of reporting vaginal bleeding to their healthcare provider as soon as possible [see Warnings and Precautions ( 5.2 )] . Possible Serious Adverse Reactions with Estrogen-Alone Therapy Inform postmenopausal women of possible serious adverse reactions of estrogen-alone therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] . Possible Less Serious, but More Common Adverse Reactions with Estrogen-Alone Therapy Inform postmenopausal women of possible less serious, but common adverse reactions of estrogen-alone therapy such as headaches, breast pain and tenderness, nausea, and vomiting. Manufactured By: Teva Women s Health, Inc. Subsidiary of Teva Pharmaceuticals USA, Inc. North Wales, PA 19454 Patient Information Enjuvia (en joo vē- ǝ) (synthetic conjugated estrogens, B) Tablets Read this Patient Informationbefore you start taking Enjuvia, and each time you refill your Enjuvia prescription. There may be new information. This information does not take the place of talking to your healthcare provider about your menopausal symptoms or your treatment. What is the most important information I should know about ENJUVUA (an estrogen mixture)? • Using estrogen-alone may increase your chance of getting cancer of the uterus (womb). Report any unusual vaginal bleeding right away while you are taking Enjuvia. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause. • Do not use estrogen-alone to prevent heart disease, heart attacks, strokes, or dementia (decline in brain function). • Using estrogen-alone may increase your chances of getting strokes or blood clots. • Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age or older. • Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes, or dementia. • Using estrogens with progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots. • Using estrogens with progestins may increase your chance of getting dementia, based on a study of women 65 years of age or older. • You and your healthcare provider should talk regularly about whether you still need treatment with Enjuvia. What is Enjuvia? Enjuvia is a prescription medicine that contains a mixture of estrogen hormones. What is Enjuvia used for? Enjuvia is used after menopause to: • reduce moderate or severe hot flashes Estrogens are hormones made by a woman's ovaries. The ovaries normally stop making estrogens when a woman is between 45 and 55 years old. This drop in body estrogen levels causes the change of life or menopause (the end of monthly menstrual periods). Sometimes, both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes surgical menopause . When estrogen levels begin dropping, some women get very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden intense episodes of heat and sweating ( hot flashes or hot flushes ). In some women, the symptoms are mild, and they will not need to take estrogens. In other women, symptoms can be more severe. • treat moderate to severe vaginal dryness and pain with sex, due to menopause You and your healthcare provider should talk regularly about whether you still need treatment with Enjuvia to control these problems. If you use Enjuvia only to treat your vaginal dryness, or pain with sex, talk with your healthcare provider about whether a topical vaginal product would be better for you. Who should not take Enjuvia? Do not take Enjuvia if you: • have unusual vaginal bleeding Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause. • currently have or have had certain cancers Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. If you have or have had cancer, talk with your healthcare provider about whether you should take Enjuvia. • had a stroke or heart attack • currently have or have had blood clots • currently have or have had liver problems • have been diagnosed with a bleeding disorder • are allergic to Enjuvia or any of its ingredients See the list of ingredients in Enjuvia at the end of this leaflet. • think you may be pregnant Enjuvia is not for pregnant women. If you think you may be pregnant, you should have a pregnancy test and know the results. Do not take Enjuvia if the test is positive and talk to your healthcare provider. What should I tell my healthcare provider before I take Enjuvia? Before you take Enjuvia, tell your healthcare provider if you: • have any unusual vaginal bleeding Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any vaginal bleeding to find out the cause. • have any other medical conditions Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), migraine, endometriosis, lupus, angioedema (swelling of the face and tongue), or problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood. • are going to have surgery or will be on bed rest Your healthcare provider will let you know if you need to stop taking Enjuvia. • are breastfeeding The hormones in Enjuvia can pass into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines may affect how Enjuvia works. Enjuvia may also affect how your other medicines work. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine. How should I take Enjuvia? • Take Enjuvia exactly as your healthcare provider tells you to take it. • Take one Enjuvia tablet by mouth at the same time each day. • If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your normal schedule. Do not take 2 doses at the same time. • Estrogens should be used at the lowest dose possible for your treatment only as long as needed. You and your healthcare provider should talk regularly (for example, every 3 to 6 months) about the dose you are taking and whether you still need treatment with Enjuvia. • Enjuvia may be taken with or without food. What are the possible side effects of Enjuvia? Side effects are grouped by how serious they are and how often they happen when you are treated. Serious, but less common side effects include: • heart attack • stroke • blood clots • dementia • breast cancer • cancer of the lining of the uterus (womb) • cancer of the ovary • high blood pressure • high blood sugar • gallbladder disease • liver problems • changes in your thyroid hormone levels • enlargement of benign tumors of the uterus ( fibroids ) Call your healthcare provider right away if you get any of the following warning signs, or any other unusual symptoms that concern you: • new breast lumps • unusual vaginal bleeding • changes in vision or speech • sudden new severe headaches • severe pains in your chest or legs with or without shortness of breath, weakness, and fatigue Less serious, but common side effects include: • headache • breast tenderness or pain • irregular vaginal bleeding or spotting • stomach or abdominal cramps, bloating • nausea and vomiting • hair loss • fluid retention • vaginal yeast infection These are not all the possible side effects of Enjuvia. For more information, ask your healthcare provider or pharmacist. Tell your healthcare provider if you have any side effects that bother you or does not go away. You may report side effects to Teva Pharmaceuticals at 1-888-483-8279 or to FDA at 1-800-FDA-1088. What can I do to lower my chances of a serious side effect with Enjuvia? • Talk with your healthcare provider regularly about whether you should continue taking Enjuvia. • If you have a uterus, talk to your healthcare provider about whether the addition of a progestin is right for you. The addition of a progestin is generally recommended for a woman with a uterus to reduce the chance of getting cancer of the uterus (womb). • See your healthcare provider right away if you get vaginal bleeding while taking Enjuvia. • Have a pelvic exam, breast exam, and mammogram (breast X-ray) every year unless your healthcare provider tells you something else. If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often. • If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have a higher chance of getting heart disease. Ask your healthcare provider for ways to lower your chance of getting heart disease. How should I store Enjuvia? • Store Enjuvia at room temperature between 59 F to 86 F (15 C to 30 C). Keep Enjuvia and all other medicines out of the reach of children. General information about safe and effective use of Enjuvia. Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not take Enjuvia for conditions for which it was not prescribed. Do not give Enjuvia to other people, even if they have the same symptoms you have. It may harm them. This leaflet provides a summary of the most important information about Enjuvia. If you would like more information, talk with your healthcare provider or pharmacist. You can ask your healthcare provider or pharmacist for information about Enjuvia that is written for healthcare professionals. You may also obtain further information by calling the toll free number 1-888-483-8279. What are the ingredients in Enjuvia? Active Ingredient: synthetic conjugated estrogens, B. Inactive Ingredients: ascorbyl palmitate, butylated hydroxyanisole, colloidal silicon dioxide, edetate disodium dehydrate, plasticized ethylcellulose, hypromellose, lactose monohydrate, magnesium stearate, purified water, iron oxide red, titanium dioxide, polyethylene glycol, polysorbate 80, triacetate and triacetin/glycerol. In addition, the • 0.45 mg tablets contain iron oxide black and iron oxide yellow; • 0.9 mg tablets also contain D&C yellow no. 10 aluminum lake, FD&C blue no. 1 aluminum lake and FD&C yellow no. 6 aluminum lake; • 1.25 mg tablets contain iron oxide yellow. This Patient Information has been approved by the U.S. Food and Drug Administration. Manufactured By: Teva Women s Health, Inc. Subsidiary of Teva Pharmaceuticals USA, Inc. North Wales, PA 19454 Revised: 06/2015 Package/Label Display Panel Enjuvia (synthetic conjugated estrogens, B) Tablets 0.3 mg, 100s Label Text 0.3 mg 100 Tablets NDC 51285- 406 -02 Enjuvia (synthetic conjugated estrogens, B) Tablets PHARMACIST: Dispense the Package Insert provided separately to each patient. Rx only TEVA TEVA WOMEN S HEALTH Package/Label Display Panel Enjuvia (synthetic conjugated estrogens, B) Tablets 0.45 mg, 100s Label Text 0.45 mg 100 Tablets NDC 51285- 407 -02 Enjuvia (synthetic conjugated estrogens, B) Tablets PHARMACIST: Dispense the Package Insert provided separately to each patient. Rx only TEVA TEVA WOMEN S HEALTH Package/Label Display Panel Enjuvia (synthetic conjugated estrogens, B) Tablets 0.625 mg, 100s Label Text 0.625 mg 100 Tablets NDC 51285- 408 -02 Enjuvia (synthetic conjugated estrogens, B) Tablets PHARMACIST: Dispense the Package Insert provided separately to each patient. Rx only TEVA TEVA WOMEN S HEALTH Package/Label Display Panel Enjuvia (synthetic conjugated estrogens, B) Tablets 0.9 mg, 100s Label Text 0.9 mg 100 Tablets NDC 51285- 409 -02 Enjuvia (synthetic conjugated estrogens, B) Tablets PHARMACIST: Dispense the Package Insert provided separately to each patient. Rx only TEVA TEVA WOMEN S HEALTH Package/Label Display Panel Enjuvia (synthetic conjugated estrogens, B) Tablets 1.25 mg, 100s Label Text 1.25 mg 100 Tablets NDC 51285- 410 -02 Enjuvia (synthetic conjugated estrogens, B) Tablets PHARMACIST: Dispense the Package Insert provided separately to each patient. Rx only TEVA TEVA WOMEN S HEALTH Enjuvia synthetic conjugated estrogens, b tablet, film coated Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:51285-406 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ESTROGENS, CONJUGATED SYNTHETIC B (ESTROGENS, CONJUGATED SYNTHETIC B) ESTROGENS, CONJUGATED SYNTHETIC B 0.3 mg Inactive Ingredients Ingredient Name Strength ASCORBYL PALMITATE BUTYLATED HYDROXYANISOLE SILICON DIOXIDE EDETATE DISODIUM ETHYLCELLULOSES HYPROMELLOSE 2910 (3 MPA.S) HYPROMELLOSE 2910 (6 MPA.S) HYPROMELLOSE 2910 (4000 MPA.S) LACTOSE MONOHYDRATE MAGNESIUM STEARATE WATER FERRIC OXIDE RED TITANIUM DIOXIDE POLYETHYLENE GLYCOL 400 POLYETHYLENE GLYCOL 8000 POLYSORBATE 80 TRIACETIN GLYCERIN Product Characteristics Color WHITE Score no score Shape OVAL Size 8mm Flavor Imprint Code E;1 Contains Packaging # Item Code Package Description 1 NDC:51285-406-02 100 TABLET, FILM COATED in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021443 04/24/2006 04/30/2017 Enjuvia synthetic conjugated estrogens, b tablet, film coated Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:51285-407 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ESTROGENS, CONJUGATED SYNTHETIC B (ESTROGENS, CONJUGATED SYNTHETIC B) ESTROGENS, CONJUGATED SYNTHETIC B 0.45 mg Inactive Ingredients Ingredient Name Strength ASCORBYL PALMITATE BUTYLATED HYDROXYANISOLE SILICON DIOXIDE EDETATE DISODIUM ETHYLCELLULOSES HYPROMELLOSE 2910 (6 MPA.S) HYPROMELLOSE 2910 (4000 MPA.S) LACTOSE MONOHYDRATE MAGNESIUM STEARATE WATER FERRIC OXIDE RED TITANIUM DIOXIDE POLYETHYLENE GLYCOL 400 POLYETHYLENE GLYCOL 8000 POLYSORBATE 80 TRIACETIN GLYCERIN FERROSOFERRIC OXIDE FERRIC OXIDE YELLOW Product Characteristics Color PINK (mauve) Score no score Shape OVAL Size 8mm Flavor Imprint Code E;2 Contains Packaging # Item Code Package Description 1 NDC:51285-407-02 100 TABLET, FILM COATED in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021443 04/24/2006 04/30/2017 Enjuvia synthetic conjugated estrogens, b tablet, film coated Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:51285-408 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ESTROGENS, CONJUGATED SYNTHETIC B (ESTROGENS, CONJUGATED SYNTHETIC B) ESTROGENS, CONJUGATED SYNTHETIC B 0.625 mg Inactive Ingredients Ingredient Name Strength ASCORBYL PALMITATE BUTYLA additionally it is
identical Enjuvia at present
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