and suppleness [0.025:<0.001 # NA> <0.001 # Table 4: Summary of Mean Severity of Moderate to Severe Hot Flushes-ITT * * ITT= Intent-to-Treat population A subject was included at baseline only if the subject had at least 1 post-baseline value. SD= standard deviation Severity scores are: 1 = Mild, 2 = Moderate, 3 = Severe. Mean severity of hot flushes by day is [(2X number of moderate hot flushes) + (3X number of severe hot flushes)] / total number of moderate to severe hot flushes on that day. If no moderate to severe hot flush was indicated, the mean severity was 0. p-value for comparison to placebo, adjusted by the method of Bonferroni p> <0.025 Baseline Week 4 (day 7) Week 8 (day 7) Week 12 (day 7) Placebo n 89 76 68 57 Mean (SD)d 2.42 (0.282) 1.99 (0.875) 1.93 (0.955) 1.8 (1.034) Mean Change from baseline (SD) NA -0.4 (0.865) -0.48 (0.922) -0.57 (1.044) 0.045/.03 n 92 83 72 55 Mean (SD) 2.48 (0.295) 1.1 (1.191) 0.82 (1.226) 0.44 (0.96) Mean Change from baseline (SD) NA -1.4 (1.164) -1.67 (1.245) -2.06 (1.005) p-value NA> <0.001 NA> <0.001 Effects on the Endometrium In a 1-year clinical trial of 412 postmenopausal women (with intact uteri) treated with a continuous regimen of Climara Pro or with an continuous estradiol-only transdermal system, results of evaluable endometrial biopsies show that no hyperplasia was seen with Climara Pro. Table 5 below summarizes these results (Intent-to-Treat populations). Table 5: Incidence of Endometrial Hyperplasia during Continuous Combined Treatment with Climara Pro, ITT * * ITT = Intent-to-Treat population n = number of intent-to-treat subjects. Defined as at least 180 days of treatment. Defined as 323 days of treatment. Includes hyperplasia occurring at any time after initiation of treatment as a proportion of patients with biopsies at 1 year. # p> <0.0167 p-value for comparison to unopposed estradiol dose using the Fisher Exact test. P-values were adjusted by the method of Bonferroni. Climara Pro E 2 0.045 mg / LNG 0.015 mg Estradiol E 2 0.045 mg n = 210 na = 202 No. of Patients with Biopsies at> 6 months 124 139 No. of Patients with Biopsies at 1 year 102 110 No. (%) of Patients with Hyperplasia 0 (0%) # 19 (17.3%) 95% Confidence Interval 0-3.55% 9.75 24.79% Effects on Uterine Bleeding or Spotting The effects of Climara Pro on uterine bleeding or spotting, as recorded using an interactive voice response system, were evaluated in one 12-month clinical trial. Results are shown in Figure 3. Figure 3: Cumulative Proportion of Subjects at Each Cycle with No Bleeding/Spotting Through the End of Cycle 13 Last Observation Carried Forward Percent based upon the number of subjects with data Last non-missing cycle carried forward through cycle 13 Bleeding associated with endometrial biopsies not included Effects on Bone Mineral Density The effects on bone mineral density (BMD) were studied in a randomized, double-blind, placebo-controlled clinical trial of transdermal systems (patches) containing only estradiol (E2). The patients were postmenopausal women with hysterectomies, 40 83 years of age (mean=51.4 years), and 77.3 percent Caucasian. Patients received calcium supplements if they appeared deficient on a questionnaire. Vitamin D supplements were not given. A total of 154 patients were randomized in a 2:2:3 ratio to weekly application of 22 cm 2 patches containing 2.2 mg E2, 4.4 mg E2, or placebo, for 728 days of continuous treatment (26 28-day cycles). Only the results for the estradiol dose in Climara Pro (4.4 mg E2) and for placebo are presented. Statistically significant increases in the primary efficacy variable, BMD of the lumbar spine (A-P view, L2-L4), were seen for 4.4 mg E 2 compared to placebo (see Table 5 and Figure 4). BMD was also measured at the hip (total, non-dominant side) and radius (midshaft, non-dominant side) with statistically significant treatment effects only observed for the hip (see Table 6). Table 6: Mean Bone Mineral Density (Standard Deviation) * * Intent-to-treat population with on-treatment efficacy data E 2 =estradiol; LOCF= Last Observation Carried Forward 4.4 mg E 2 Placebo Total Lumbar Spine Baseline (g/cm 2 ) n=36 1.1 (0.2) n=46 1.1 (0.2) % Change from baseline LOCF +1.7% (4.4) -2.9% (3.8) P-value compared to placebo <0.0001 Total Hip Baseline (g/cm 2 ) n=36 0.97 (0.1) n=48 0.94 (0.1) % Change from baseline LOCF +1.3% (4.2) -0.9% (5.2) P-value compared to placebo 0.05 Figure 4: Percent Change From Baseline in Bone Mineral Density (g/cm2) of Lumbar Spine (A-P View, L2 L4) by Treatment Group and Cycle (Mean SE)* * Data in the figure is for 21 patients on 4.4 mg E2 and 27 placebo patients who completed the study; approximately 44 percent of randomized patients. 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 cause. These substudies did not evaluate the effects of CE plus MPA or CE-alone on menopausal symptoms. 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 7. These results reflect centrally adjudicated data after an average follow-up of 5.6 years. Table 7: 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 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. 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 34 31 25 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 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 to 59 years of age, a non-significant trend toward reduced risk for overall mortality [hazard ratio (HR) 0.69 (95 percent CI, 0.44 1.07)] . 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 age of 63 years, 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 * * 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/probable CHD, PE or cerebrovascular disease. # 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 0.95 (0.78-1.16) 54 57 Non-fatal 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 # 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 to 59 years of age, a non-significant trend toward reduced risk for CHD [HR 0.63 (95 percent CI, 0.36-1.09)] and overall mortality [HR 0.71 (95 percent CI, 0.46-1.11)] . Women's Health Initiative Memory Study The WHIMS estrogen plus progestin ancillary study of WHI enrolled 4,532 predominantly healthy postmenopausal women 65 to 79 years of age (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 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 was 45 versus 22 cases per 10,000 women-years. Probable dementia as defined in this study included Alzheimer s disease (AD), vascular dementia (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 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-alone ancillary study of WHI enrolled 2,947 predominantly healthy hysterectomized postmenopausal women 65 years of age and older (45 percent were age 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 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 type (having features of both AD and VaD). The most common classification of probable dementia in the treatment group and the placebo groups 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 )] . 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 Rossouw JE, et al. Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause. JAMA. 2007;297:1465-1477. Hsia J, et al. Conjugated Equine Estrogens and Coronary Heart Disease. Arch Int Med. 2006;166:357-365. Cushman M, et al. Estrogen Plus Progestin and Risk of Venous Thrombosis. JAMA. 2004;292:1573-1580. Curb JD, et al. Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus. Arch Int Med. 2006;166:772-780. Chlebowski RT, et al. Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women. JAMA. 2003;289:3234-3253. 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. Anderson GL, et al. Effects of Estrogen Plus Progestin on Gynecologic Cancers and Associated Diagnostic Procedures. JAMA. 2003;290:1739-1748. Shumaker SA, et al. Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women. JAMA. 2004;291:2947-2958. 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. 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 Individual Carton of 4 systems Climara Pro (estradiol/levonorgestrel transdermal system) 0.045 mg/day estradiol and 0.015 mg/day levonorgestrel each 22 cm 2 system contains 4.4 mg of estradiol and 1.39 mg of levonorgestrel. NDC 50419-491-04 Storage and Handling Store at 20 C to 25 C (68 F to 77 F); excursions permitted to 15 C to 30 C (59 F to 86 F) [see USP controlled Room Temperature]. Do not store unpouched. Apply immediately upon removal from the protective pouch. Used transdermal systems still contain active hormones. To discard, fold the sticky side of the transdermal system together, place it in a sturdy child-proof container, and place this container in the trash. Used transdermal systems should not be flushed in the toilet Patient Counseling Information See FDA-approved patient labeling (Patient Information and Instructions for Use) Abnormal Vaginal Bleeding Inform postmenopausal women of the importance of reporting abnormal vaginal bleeding to their healthcare provider as soon as possible [see Warning and Precautions ( 5.2 )]. Possible Serious Adverse Reactions with Estrogen Plus Progestin Therapy Inform postmenopausal women of possible serious adverse reactions of estrogen plus progestin therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warning and Precautions ( 5.1 , 5.2 , 5.3 )] . Possible Less Serious but Common Adverse Reactions with Estrogen plus Progestin Therapy Inform postmenopausal women of possible less serious but common adverse reactions of estrogen plus progestin therapy such as headache, breast pain and tenderness, nausea and vomiting. Patient Package Insert Climara Pro (Klī-mâr-uh prō) (estradiol/levonorgestrel transdermal system) Read this Patient Information before you start using Climara Pro and each time you get a refill. 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 Climara Pro (combinations of estrogen and a progestin)? Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes, or dementia (declines of brain function). 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. Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia. Using estrogen-alone may increase your chance of getting cancer of the uterus (womb). 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. You and your healthcare provider should talk regularly about whether you still need treatment with Climara Pro. What is Climara Pro? Climara Pro is a prescription medicine patch (Transdermal System) that contains two kinds of hormones, an estrogen and a progestin. What is Climara Pro used for? Climara Pro is used after menopause to: Reduce moderate to 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 the estrogen levels begin dropping, some women get very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden strong feelings 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. You and your healthcare provider should talk regularly about whether or not you still need treatment with Climara Pro. Help reduce your chances of getting osteoporosis (thin weak bones) If you use Climara Pro only to prevent osteoporosis due to menopause, talk with your healthcare provider about whether a different treatment or medicine without estrogens might be better for you. You and your healthcare provider should talk regularly about whether you still need treatment with Climara Pro. Who should not use Climara Pro? Do not use Climara Pro if you have had your uterus (womb) removed (hysterectomy). Climara Pro contains a progestin to decrease the chance of getting cancer of the uterus. If you do not have a uterus, you do not need a progestin and you should not use Climara Pro. Do not start using Climara Pro 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 chance 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 Climara Pro. 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 Climara Pro or any of its ingredients See the list of ingredients in Climara Pro at the end of this leaflet. think you may be pregnant Climara Pro is not for pregnant women. If you think you may be pregnant, you should have a pregnancy test and know the results. Do not use Climara Pro if the test is positive and talk to your healthcare provider. What should I tell my healthcare provider before I use Climara Pro? Before you use Climara Pro, 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. 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), diabetes, migraine, endometriosis, lupus, angioedema (swelling of 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 using Climara Pro. are breastfeeding The hormones in Climara Pro can pass into your breast milk. Tell your healthcare provider about all the medicines you take , including prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may affect how Climara Pro works. Climara Pro 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 use Climara Pro? For detailed instructions, see the step-by-step instructions for using Climara Pro at the end of this Patient Information. Use Climara Pro exactly as your healthcare provider tells you to use it. Climara Pro is for skin use only. Change your Climara Pro patch 1 time each week or every 7 days. Apply your Climara Pro patch to a clean, dry area on your lower abdomen or buttocks. This area must be clean, dry, and free of powder, oil or lotion for your patch to stick to your skin. Apply your Climara Pro patch to a different area of your abdomen or your buttocks each time. Do not use the same application site 2 times in the same week. Do not apply Climara Pro to your breasts. If you forget to apply a new Climara Pro, you should apply a new patch as soon as possible. You and your healthcare provider should talk regularly (every 3 to 6 months) about the dose you are using and whether you still need treatment with Climara Pro. How do I change Climara Pro? When changing Climara Pro, peel off the used patch slowly from the skin. After removal of Climara Pro, people usually have either no adhesive residue or light adhesive residue. If any adhesive residue remains on your skin after removing the patch, allow the area to dry for 15 minutes. Then, gently rub the area with an oil-based cream or lotion to remove the adhesive from your skin. Keep in mind, the new patch must be applied to a different skin area of your lower abdomen or buttocks. This area must be clean, dry, and free of powder, oil or lotion. The same site should not be used again for at least 1 week after removal of the patch. What are the possible side effects of Climara Pro? 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 pain irregular vaginal bleeding or spotting stomach or abdominal cramps, bloating nausea and vomiting hair loss fluid retention vaginal yeast infection redness or irritation at the patch placement site These are not all the possible side effects of Climara Pro. 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 Bayer Healthcare Pharmaceuticals at 1-888-842-2937 or to FDA at 1-800-FDA-1088. What can I do to lower my chances of a serious side effect with Climara Pro? Talk with your healthcare provider regularly about whether you should continue using Climara Pro. See your healthcare provider right away if you get vaginal bleeding while using Climara Pro. 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 of getting heart disease. How should I store and throw away used Climara Pro? Store at room temperature between 68 F to 77 F (20 C to 25 C). Do not store Climara Pro patches outside of their pouches. Apply immediately after removal from the protective pouch. Used patches still contain estrogen. To throw away the patch, fold the sticky side of the patch together, place it in a sturdy child-proof container, and place this container in the trash. Used patches should not be flushed in the toilet. KEEP Climara Pro and all medicines out of the reach of children. General information about the safe and effective use of Climara Pro. Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Climara Pro for conditions for which it was not prescribed. Do not give Climara Pro to other people, even if they have the same symptoms you have. It may harm them. This leaflet summarizes the most important information about Climara Pro. If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about Climara Pro that is written for health professionals. For more information, go to www.climara-us.com or call Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937. What are the ingredients in Climara Pro? Active ingredient: estradiol and levonorgestrel Inactive ingredient: acrylate copolymer adhesive, and polyvinylpyrrolidone/vinyl acetate copolymer. Instructions for Use Climara Pro (Klī-mâr-uh prō) (estradiol transdermal system) Read this Patient Information before you start using Climara Pro and each time you get a refill. 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. You will need the following supplies: See Figure A Figure A Step 1: Pick the days you will change your Climara Pro. You will need to change your patch 1 time each week or every 7 days. Step 2. Remove the Climara Pro patch from the pouch. Remove patch from its protective pouch by tearing at the notch (do not use scissors). See Figure B Do not remove your patch from the protective pouch until you are ready to apply it. Figure B Step 3. Remove the adhesive liner. See Figure C You will see that Climara Pro is an oval shaped clear patch that is attached to a thick, hard-plastic adhesive liner and covered by a clear, plastic film. See Figure C To apply your patch you must first remove the protective, clear plastic film that is attached to the clear thicker plastic backing. See Figure D There is a silver foil-sticker attached to the inside of the pouch. Do not remove the silver foil sticker from the pouch. See Figure E Figure C Figure D Figure E Step 4. Placing the patch on your skin. Apply the sticky side of the patch to one of the areas of skin shown below. See Figure F and Figure G Avoid touching the sticky side of the patch with your fingers. Figure F Figure G Note: Avoid the waistline, since clothing and belts may cause the patch to be rubbed off. Do not apply Climara Pro to your breasts. Only apply Climara Pro to skin that is clean, dry, and free of any powder, oil, or lotion. You should not apply the patch to injured, burned, or irritated skin, or areas with skin conditions (such as birth marks, tattoos, or that is very hairy). Step 5. Press the patch firmly onto your skin. Press the patch firmly in place with your fingers for at least 10 seconds Rub the edges of the patch to make sure that it will stick to your skin. (See Figure H) Figure H Note: Contact with water while you are swimming, using a sauna, bathing, or showering may cause the patch to fall off. If your patch falls off reapply it. If you cannot reapply the patch, apply a new patch to another area ( See Figures F and G ) and continue to follow your original application schedule. If you stop using your Climara Pro or forget to apply a new patch as scheduled, you may have spotting, or bleeding, and your symptoms may come back. Step 6: Throwing away your used patch. When it is time to change your patch, remove the old patch before you apply a new patch. To throw away the patch, fold the sticky side of the patch together, place it in a sturdy child-proof container, and place this container in the trash. Used patches should not be flushed in the toilet. This Patient Information and Instructions for Use have been approved by the U.S Food and Drug Administration. 2013, Bayer HealthCare Pharmaceuticals Inc. All rights reserved. Made In USA Manufactured for: Bayer HealthCare Pharmaceuticals Inc. Whippany, NJ 07981 Manufactured by: 3M Drug Delivery Systems Northridge CA, 91324 PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Climara Pro estradiol and levonorgestrel patch Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50419-491 Route of Administration TRANSDERMAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ESTRADIOL (ESTRADIOL) ESTRADIOL 0.045 mg in 1 d LE fee
is important Climara Pro i thought
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