flats [0.001),:<0.001), and a statistically significant mean reduction between baseline and Week 12 in vaginal pH score (-1.3 compared to -0.4 for matching placebo, p> <0.001). Endometrial safety was assessed by endometrial biopsy at the screening and final study visit. Of the 172 subjects in the Vagifem 10 mcg group who had a biopsy performed at end of study, 92 subjects had endometrial tissue that was atrophic or inactive and 73 subjects had no tissue or tissue insufficient for diagnosis. There was one case of adenocarcinoma grade 2 and one case of complex hyperplasia without atypia. Three subjects exhibited polyps (two atrophic polyps and one adenomyomatus type polyp) and two others had adenomyosis and an atypical epithelial proliferation. Endometrial safety of Vagifem 10 mcg was additionally evaluated in a second, 12 month, open-label, multicenter safety study. Of the 297 subjects who had a biopsy performed at end of study, 183 subjects had endometrial tissue that was atrophic or inactive and 111 subjects had no tissue or tissue insufficient for diagnosis. There was one case of complex hyperplasia without atypia. Two subjects exhibited polyps. Vagifem 25 mcg A placebo-controlled comparison study was done in the U.S., in which 230 women were randomized to receive either placebo, Vagifem 25 mcg or 10 mcg estradiol vaginal inserts. Women inserted one insert intravaginally each day for 14 days, then one insert twice weekly for the remaining 10 weeks. All subjects were assessed for vaginal symptoms. Vagifem 25 mcg was superior to placebo in reducing the severity of a composite score of symptoms associated with atrophic vaginitis (see Table 6). An open-label, controlled comparison study was done in Canada in which 159 women were randomized to receive either Vagifem 25 mcg or a comparator drug. Two (2) grams of the comparator drug was given daily for 3 weeks, withheld for 1 week, then repeated cyclically (3 weeks on, 1 week off) for up to 24 weeks; Vagifem 25 mcg was administered daily for 2 weeks, then twice weekly for the remaining 22 weeks. In this study, subjects were assessed for relief of symptoms. Vagifem 25 mcg was equally effective as the approved comparator product at the 2.0 gm dose in the relief of symptoms. Table 6: Mean Change from Baseline to Week 7 and Week 12 in a Composite Score of Symptoms Compared to Placebo ITT Population * * All randomized subjects who received at least one dose of study drug and had at least one post-baseline evaluation. Placebo Vagifem 25 mcg ITT Population * N 47 91 Baseline mean 1.93 1.85 Change from baseline at Week 7 (LOCF) -0.85 -1.22 Change from baseline at Week 12 (LOCF) -0.83 -1.33 p-value versus Placebo Week 7 (LOCF) --- 0.016 p-value versus Placebo Week 12 (LOCF) --- 0.005 In the placebo-controlled study endometrial biopsies in non-hysterectomized women at week 12 were performed on 86 subjects (Vagifem 25 mcg: 32 subjects, estradiol 10 mcg: 33 subjects, Placebo: 21 subjects). Of these, 3 subjects each from the Vagifem 25 mcg and placebo groups and 8 from the 10 mcg estradiol group had insufficient tissue samples. Among those with biopsies that yielded sufficient tissue, results were normal with the exception of one subject in the Vagifem 25 mcg group, who had a simple hyperplasia without atypia. In the open-label study comparing Vagifem 25 mcg with a comparator vaginal cream on 49 women in each treatment group, endometrial biopsies were obtained at the screening visit and at the end of treatment. At the end of the study (Week 24), all subjects in the Vagifem treatment group whose biopsies yielded sufficient tissue showed an atrophic endometrium with the exception of one subject who had a proliferative endometrium. 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 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 7. Table 7: Relative and Absolute Risk Seen in the Estrogen-Alone Substudy of WHI * * 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, pulmonary embolism, colorectal cancer, hip fracture, or death due to other causes. Event Relative Risk CE vs. Placebo (95% nCI ) CE n=5,310 Placebo n=5,429 Absolute Risk per 10,000 Women-Years CHD events Non-fatal MI CHD death 0.95 (0.78-1.16) 0.91 (0.73-1.14) 1.01 (0.71-1.43) 54 40 16 57 43 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 (0.92-1.13) 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 non-significant 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. 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 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 50-59 years of age a non-significant 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 8. These results reflect centrally adjudicated data after an average follow-up of 5.6 years. Table 8: Relative and Absolute Risk Seen in the Estrogen Plus Progestin Substudy of WHI at an Average of 5.6 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 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. 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 CHD events Non-fatal MI CHD death 1.23 (0.99-1.53) 1.28 (1.00-1.63) 1.10 (0.70-1.75) 41 31 8 34 25 8 All Strokes Ischemic stroke 1.31 (1.03-1.68) 1.44 (1.09-1.90) 33 26 25 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 plus progestin 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 50-59 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 predominately healthy hysterectomized postmenopausal women 65 to 79 years of age and older (45 percent were 65 to 69 years of age; 36 percent were 70 to 74 years of age; 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 to 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 women-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 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 (5.4) , and Use in Specific Populations (8.5) ] . The WHIMS estrogen plus progestin ancillary study of WHI 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; 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 to 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 women-years. Probable dementia as defined in this study included AD, VaD and mixed types (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 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women [ see Warnings and Precautions (5.4) , 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 (5.4) , 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 Each Vagifem (estradiol vaginal inserts), 10 mcg and 25 mcg, is contained in a disposable, single-use applicator, packaged in a blister pack. Cartons contain 8 or 18 applicators with inset inserts. Vagifem 25 mcg 8 applicators: NDC 0169-5173-03 18 applicators: NDC 0169-5173-04 Vagifem 10 mcg 8 applicators: NDC 0169-5176-03 18 applicators: NDC 0169-5176-04 Keep out of reach of children Storage and Handling Store at 25ºC (77ºF), excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). Do not refrigerate. [See USP Controlled Room Temperature.] Patient Counseling Information See FDA-Approved Patient Labeling. Vaginal Bleeding Inform postmenopausal women of the importance of reporting vaginal bleeding to their healthcare provider as soon as possible [ see Warnings and Precautions (5.3) ] . 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 (5.2 , 5.3 , 5.4) ] . Possible Less Serious but Common Adverse Reactions with Estrogen-Alone Therapy Inform postmenopausal women of possible less serious but common adverse reactions of estrogen-alone therapy such as headache, breast pain and tenderness, nausea and vomiting. Instructions for Use of Applicator Step 1: Tear off a single applicator. Step 2: Separate the plastic wrap and remove the applicator from the plastic wrap as shown in Figure A. If after opening the package you see that the insert has come out of the applicator but has not fallen out of the package, carefully put it back into the applicator for insertion. Please keep your hands clean and dry while handling the insert. Figure A Step 3: Hold the applicator so that the finger of one hand can press the applicator plunger as shown in Figure B. Figure B Step 4: Next select the best position for vaginal insertion of Vagifem (estradiol vaginal inserts) that is most comfortable for you. See suggested reclining Figure C or standing Figure D position illustrated below: Figure C Figure D Step 5: Using the other hand, guide the applicator gently and comfortably through the vaginal opening (see Figures C and D above). If prior to insertion the insert falls out of the applicator, throw the insert and applicator away and use a new insert-filled applicator. Step 6: The applicator should be inserted (without forcing) as far as comfortably possible, or until half of the applicator is inside your vagina, whichever is less. Step 7: Once the insert-filled applicator has been inserted, gently press the plunger until the plunger is fully depressed. This will eject the insert inside your vagina where it will dissolve slowly over several hours. Step 8: After depressing the plunger, gently remove the applicator and dispose of it the same way you would a plastic tampon applicator. The applicator is of no further use and should be discarded properly. Insertion may be done at any time of the day. It is advisable to use the same time daily for all applications of Vagifem (estradiol vaginal inserts). If you have any questions, please consult your healthcare provider or pharmacist. FDA-Approved Patient Labeling Vagifem (estradiol vaginal inserts) Read this PATIENT INFORMATION before you start using Vagifem and read what you get each time you refill your Vagifem 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 Vagifem (an estrogen hormone) Using estrogen-alone may increase your chance of getting cancer of the uterus (womb) Report any unusual vaginal bleeding right away while you are using Vagifem. 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 of 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 attack, strokes or dementia Using estrogens with progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots Using estrogens with progestin 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 Vagifem What is Vagifem? Vagifem is a medicine that contains estradiol (an estrogen hormone) in a vaginal insert. What is Vagifem used for? Vagifem is used after menopause to: Treat menopausal changes in and around the vagina You and your healthcare provider should talk regularly about whether you still need treatment with Vagifem to control these problems. Who should not use Vagifem? Do not start using Vagifem if you: Have unusual vaginal bleeding 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 use Vagifem. 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 Vagifem or any of its ingredients See the list of ingredients in Vagifem at the end of this leaflet. Think you may be pregnant 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 unusual vaginal bleeding to find out the cause. About all of your medical problems Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis, lupus, problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood. About all the medicines you take This includes prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may affect how Vagifem works. Vagifem may also affect how your other medicines work. If you are going to have surgery or will be on bed rest You may need to stop using Vagifem. If you are breast feeding The hormone in Vagifem can pass into your breast milk. How should I use Vagifem? Vagifem is an insert that you place in your vagina with an applicator. Take the dose recommended by your healthcare provider and talk to him or her about how well that dose is working for you 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 using and whether you still need treatment with Vagifem. Step 1: Tear off a single applicator. Step 2: Separate the plastic wrap and remove the applicator from the plastic wrap as shown in Figure A. If after opening the package you see that the insert has come out of the applicator but has not fallen out of the package, carefully put it back into the applicator for insertion. Please keep your hands clean and dry while handling the insert. Figure A Step 3: Hold the applicator so that the finger of one hand can press the applicator plunger as shown in Figure B. Figure B Step 4: Next select the best position for vaginal insertion of Vagifem (estradiol vaginal inserts) that is most comfortable for you. See suggested reclining Figure C or standing Figure D position illustrated below: Figure C Figure D Step 5: Using the other hand, guide the applicator gently and comfortably through the vaginal opening (see Figures C and D above). If prior to insertion the insert falls out of the applicator, throw the insert and applicator away and use a new insert-filled applicator. Step 6: The applicator should be inserted (without forcing) as far as comfortably possible, or until half of the applicator is inside your vagina, whichever is less. Step 7: Once the insert-filled applicator has been inserted, gently press the plunger until the plunger is fully depressed. This will eject the insert inside your vagina where it will dissolve slowly over several hours. Step 8: After depressing the plunger, gently remove the applicator and dispose of it the same way you would a plastic tampon applicator. The applicator is of no further use and should be discarded properly. Insertion may be done at any time of the day. It is advisable to use the same time daily for all applications of Vagifem (estradiol vaginal inserts). If you have any questions, please consult your healthcare provider or pharmacist. Dosage Vagifem therapy consists of the following dosing regimen: One (1) Vagifem insert intravaginally once daily for the first two (2) weeks, then one (1) insert twice weekly (for example Tuesday and Friday) for as long as you use Vagifem. What are the possible side effects of Vagifem? Vagifem is only used in the vagina; however, the risks associated with oral estrogens should be taken into account. 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 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 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 Vagifem. For more information, ask your healthcare provider or pharmacist for advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What can I do to lower my chances of a serious side effect with Vagifem? Talk with your healthcare provider regularly about whether you should continue using Vagifem If you have a uterus, talk with 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. See your healthcare provider right away if you get vaginal bleeding while using Vagifem. 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 higher chances for getting heart disease Ask your healthcare provider for ways to lower your chances for getting heart disease. General information about the safe and effective use of Vagifem. Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Vagifem for conditions for which it was not prescribed. Do not give Vagifem to other people, even if they have the same symptoms you have. It may harm them. Keep Vagifem out of the reach of children. This leaflet provides a summary of the most important information about Vagifem. If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about Vagifem that is written for health professionals. You can get more information by calling the toll free number 1-888-824-4336. What are the ingredients in Vagifem? Vagifem (estradiol vaginal inserts) are small, white, film-coated inserts containing estradiol. Each insert also contains hypromellose, lactose monohydrate, maize starch and magnesium stearate. The film coating contains hypromellose and polyethylene glycol. Each Vagifem insert is contained in a disposable applicator, packaged in a blister pack. Cartons contain 8 or 18 applicators with inset inserts. Store at 25ºC (77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). Do not refrigerate. [see USP Controlled Room Temperature]. Vagifem is a registered trademark owned by Novo Nordisk Health Care AG . 2003-2017 Novo Nordisk Date of Issue: 11/2017 For information contact: Novo Nordisk Inc. 800 Scudders Mill Road Plainsboro, NJ 08536, USA 1-888-824-4336 Manufactured by: Novo Nordisk A/S 2880 Bagsvaerd, Denmark Principal Display panel - Vagifem 10 MCG NDC 0169-5176-04 Vagifem (estradiol vaginal inserts) 10mcg 18 vaginal inserts novo nordisk Vagifem estradiol insert Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0169-5176 Route of Administration VAGINAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ESTRADIOL (ESTRADIOL) ESTRADIOL 10 ug Packaging # Item Code Package Description 1 NDC:0169-5176-04 18 APPLICATOR in 1 CARTON 1 1 INSERT in 1 APPLICATOR 2 NDC:0169-5176-03 8 APPLICATOR in 1 CARTON 2 1 INSERT in 1 APPLICATOR 3 NDC:0169-5176-99 6 APPLICATOR in 1 CARTON 3 1 INSERT in 1 APPLICATOR Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020908 01/11/2010 Labeler - Novo Nordisk (622920320) Establishment Name Address ID/FEI Operations Novo Nordisk A/S 305914798 MANUFACTURE(0169-5176) Establishment Name Address ID/FEI Operations Novo Nordisk A/S 586793291 MANUFACTURE(0169-5176) Revised: 11/2017 Novo Nordisk Print this page> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Recently Approved Lonhala Magnair Lonhala Magnair (glycopyrrolate) is a long-acting muscarinic antagonist (LAMA) bronchodilator for... 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