Climara Pro Estradiol and Levonorgestrel .045 mg/d; .015 mg/d Patch — NDC 50419-491-04 (Billing 50419-0491-04)
This is a package of Climara Pro Estradiol and Levonorgestrel .045 mg/d; .015 mg/d Patch from Bayer HealthCare Pharmaceuticals Inc., marketed since Nov 2003 and currently FDA-listed; retail pharmacies pay about $59.64 per unit (NADAC). It is the main listing for this product, which comes in 2 package sizes.
NDC database record
One package, one record: these facts belong to NDC 50419-491-04 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 50419 labeler · 491 product · 04 package
- Package marketed since
- Nov 21, 2013
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2027
- Barcode (UPC-A, from the NDC)
- 3 5041949104 4
- Medicaid fills, this package
- 11,284 prescriptions in the last four reported quarters
- FDA record last changed
- Jul 24, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 053383
- GCN: 20849
- GPI-14 (Medi-Span): 24993002588820
- HICL (First Databank): 012871
- AHFS class code: 68:16.04.00
- RxCUI (RxNorm): 402250
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Radioactive Diagnostic Agent class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Estrogen and progestin transdermal patches are used to treat certain symptoms of menopause. Estrogen and progestin patches are also used to treat certain conditions in women before they reach menopause if they are not making these hormones naturally. Estrogen and progestin patches are also used to prevent thinning of the bones (osteoporosis) in menopausal women. Your doctor will select the product that is best to treat your condition. Estrogen and progestin are two sex hormones. Hormone replacement therapy works by replacing hormones that are no longer being made by the body. Estrogen reduces...
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $59.645 | $238.58 / 4 patch |
| Medicaid paysCMS SDUD · 12 mo | $60.90 | $243.59 / 4 patch |
| Medicare drug plans payPart D · Q2 2026 | $63.71 | $254.83 / 4 patch |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 50419-0491-04 You're viewing this Main listing | 4 PATCH in 1 CARTON / 7 d in 1 PATCH | $59.64 / ea | $238.58 | 2013-11-21 | — | Active |
| 50419-0491-73 50419-491-73 | 1 PATCH in 1 CARTON / 7 d in 1 PATCH | — | — | 2017-04-12 | — | Active |
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in this package?
What NDC number is used to bill for this package of Climara Pro Estradiol and Levonorgestrel .045 mg/d; .015 mg/d Patch?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Climara Pro .045 mg/d; .015 mg/dthis 50419-0491-04 | Bayer | 4 patches | $59.645 | — | Availability likely | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.- FDA label on DailyMed · label index refreshed Oct 5, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from Bayer HealthCare Pharmaceuticals Inc. labeler code 50419
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- Biltricide praziquantel 600 mg Tablet, Film Coated NDC 50419-747-01
- Lampit nifurtimox 30 mg Tablet, Film Coated NDC 50419-750-01
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia The Women's Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo [see Warnings and Precautions (5.1) , and Clinical Studies (14.5) ].
The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions (5.3) , Use in Specific Populations (8.5) , and Clinical Studies (14.6) ]. Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1 , 5.3) , and Clinical Studies (14.5 , 14.6) ] .
Breast Cancer The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.2) , and Clinical Studies (14.5) ] . Only daily oral 0.625 mg CE and MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not known.
Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen plus progestogen therapy, taking into account her individual risk profile. Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2) ] .
Cardiovascular Disorders and Probable Dementia The WHI estrogen-alone substudy reported increased risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral CE (0.625 mg)-alone, relative to placebo [see Warnings and Precautions (5.1) , and Clinical Studies (14.5) ]. The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo.
It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions (5.3) , Use in Specific Populations (8.5) , and Clinical Studies (14.6) ] . Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1 , 5.3) , and Clinical Studies (14.5 , 14.6) ]. Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI.
Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not… [Excerpted — this section continues on DailyMed.]
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Climara Pro is indicated for: Climara Pro is an estrogen plus progestin indicated in a woman with a uterus for: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause ( 1.1 ) Prevention of Postmenopausal Osteoporosis ( 1.2 ) Limitations of Use: When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis.
1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause
1.2Prevention of Postmenopausal Osteoporosis Limitation of Use When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Use estrogen-alone, or in combination with a progestogen, at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual women. Reevaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary. One Climara Pro transdermal system is available for use.
Apply Climara Pro 0.045 mg per day/0.015 mg per day once-weekly to the lower abdomen ( 2.3 )
2.1Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Start therapy with Climara Pro 0.045 mg per day/0.015 mg per day applied to the skin once weekly. Start therapy at the lowest effective dose and the shortest duration consistent with the treatment goals. Attempts to discontinue Climara Pro should be made at 3 to 6 month intervals.
2.2Prevention of Postmenopausal Osteoporosis Apply Climara Pro 0.045 mg per day/0.015 mg per day applied to the skin once weekly.
2.3Application of the Climara Pro Transdermal System Initiation of Therapy Women not currently using continuous estrogen-alone therapy or estrogen plus progestogen therapy may start therapy with Climara Pro at any time. However, women currently using continuous estrogen-alone therapy or estrogen plus progestogen therapy should complete the current cycle of therapy before initiating Climara Pro therapy. Women often experience withdrawal bleeding at the completion of the cycle.
The first day of this bleeding would be an appropriate time to begin Climara Pro therapy. Site Selection Place the adhesive side of Climara Pro on a smooth (fold free), clean, dry area of the skin on the lower abdomen or the upper quadrant of the buttock. Do not apply Climara Pro to or near the breasts.
Select an area selected that is not oily (which can impair adherence of the system), damaged, or irritated. Avoid the waistline; tight clothing may rub Climara Pro off or modify drug delivery. Avoid application to areas where sitting would dislodge Climara Pro.
Rotate the sites of application, with an interval of at least 1-week allowed between applications to the same site. Application Apply Climara Pro immediately after opening the pouch and removing the protective lining. Press Climara Pro firmly in place with the fingers for at least 10 seconds, making sure there is good contact, especially around the edges.
If the system lifts, apply pressure to maintain adhesion. In the event that a system should fall off, reapply the same system to another area of the lower abdomen. If the system cannot be reapplied, a new system may be applied, in which case, the original treatment schedule should be continued.
Only one system should be worn at any one time during 7-day dosing interval. Do not expose the applied transdermal system to the sun for prolonged periods of time. Swimming, bathing, or using a sauna while using Climara Pro has not been studied, and these activities may decrease the adhesion of the system and the delivery of the estrogen and progestin.
2.4Removal of the Climara Pro Transdermal System Remove Climara Pro carefully and slowly to avoid irritation of the skin. If any adhesive remain on the skin after removal of Climara Pro, allow the area to dry for 15 minutes and then gently rub the area with an oil-based cream or lotion should remove the adhesive residue. Used patches still contain some active hormones. Carefully fold each patch in half so that it sticks to itself before throwing it away.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 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. Transdermal system: 0.045 mg/day estradiol and 0.015 mg/day levonorgestrel ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Climara Pro is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.2) ] Breast cancer or history of breast cancer [see Warnings and Precautions (5.2) ] Estrogen-dependent neoplasia [see Warnings and Precautions (5.2) ] Active DVT, PE or a history of these conditions [see Warnings and Precautions (5.1) ] Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions [ see Warnings and Precautions (5.1) ] Known anaphylactic reaction, or angioedema, or hypersensitivity to Climara Pro Hepatic impairment or disease Protein C, protein S, or antithrombin deficiency, or other thrombophilic disorders Undiagnosed abnormal genital bleeding ( 4 , 5.2 ) Breast cancer or a history of breast cancer ( 4 , 5.2 ) Estrogen-dependent neoplasia ( 4 , 5.2 ) Active DVT, PE or a history of these conditions ( 4 , 5.1 ) Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions ( 4 , 5.1 ) Known anaphylactic reaction or angioedema or hypersensitivity to Climara Pro ( 4 ) Hepatic impairment or disease ( 4 , 5.10 ) Protein C, protein S, or antithrombin deficiency, or other thrombophilic disorders ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Estrogens increase the risk of gallbladder disease ( 5.4 ) Discontinue estrogens if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.5 , 5.6 , 5.9 , 5.10 ) Monitor thyroid function in women on thyroid hormone replacement therapy ( 5.11 , 5.18 )
5.1Cardiovascular Disorders Increased risks of PE, DVT, stroke and MI are reported with estrogen plus progestin therapy. Increased risks of stroke and DVT are reported with estrogen-alone therapy. Immediately discontinue estrogen with or without progestogen therapy if any of these occur or are suspected.
Manage appropriately any risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus). Stroke The WHI estrogen plus progestin substudy reported a statistically significant increased risk of stroke in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 strokes per 10,000 women-years, respectively) [see Clinical Studies (14.5) ] .
The increase in risk was demonstrated after the first year and persisted. 1 Immediately discontinue estrogen plus progestogen therapy if a stroke occurs or is suspected. The WHI estrogen-alone substudy, reported a statistically significant increased risk of stroke in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 strokes per 10,000 women-years, respectively).
The increase in risk was demonstrated in year 1 and persisted [see Clinical Studies (14.5) ] . Immediately discontinue estrogen-alone therapy if a stroke occurs or is suspected. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years).
1 Coronary Heart Disease The WHI estrogen plus progestin substudy reported an increased risk (not statistically significant) of coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years). 1 An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5 [see Clinical Studies (14.5) ] . The WHI estrogen-alone substudy reported no overall effect on CHD events in women receiving estrogen-alone compared to placebo 2 [see Clinical Studies (14.5 ] .
Subgroup analyses of women 50 to 59 years of age, who were less than 10 years since menopause, suggest a reduction (not statistically significant) of CHD events in those women receiving CE (0.625 mg)-alone compared to placebo (8 versus 16 per 10,000 women-years). 1 In postmenopausal women with documented heart disease (n = 2,763), average 66.7 years of age, in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study; HERS), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit.
During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established CHD. There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand three hundred twenty-one (2,321) women from the original HERS trial agreed to participate in an open label extension of HERS, HERS II.
Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE plus MPA group and the placebo group in… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [ see Boxed Warning , Warnings and Precautions (5.1) ] Malignant Neoplasms [see Boxed Warning , Warnings and Precautions (5.2) ] The most common adverse reactions (≥5 percent) with Climara Pro are: application site reaction, vaginal bleeding, breast pain, upper respiratory infection, back pain, depression, pain, headache and flu syndrome. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-84-BAYER (1-888-842-2937) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below is from a one-year, prospective, multicenter, double blind, double dummy, randomized, controlled trial investigating the effect of three different dosage combinations of E 2 /LNG versus E 2 alone on the development of endometrial hyperplasia.
All women were postmenopausal, had a serum estradiol level of less than 20 pg/mL, and the sample included both symptomatic and asymptomatic women. The data below includes all adverse reactions reported at a frequency of >3% in the E 2 /LNG 0.045 / 0.015 group (the approved dosage for Climara Pro, N=212) and the E 2 alone group (N=204). Table 1: All Treatment Emergent Reactions Regardless of Relationship Reported at a Frequency of >3% with Climara Pro in the 1-year Endometrial Hyperplasia Study Body System Adverse Reaction Climara Pro 0.045 / 0.015 E 2 N N = total number of subjects in a treatment group; n = number of subjects with event. = 212 N = 204 Body as a Whole Abdominal pain 9 (4.2) 11 (5.4) Accidental injury 7 (3.3) 6 (2.9) Back pain 13 (6.1) 12 (5.9) Flu syndrome 10 (4.7) 13 (6.4) Infection 7 (3.3) 10 (4.9) Pain 11 (5.2) 13 (6.4) Cardiovascular System Hypertension 7 (3.3) 9 (4.4) Digestive System Flatulence 8 (3.8) 11 (5.4) Metabolic and Nutritional Edema 8 (3.8) 5 (2.5) Weight gain 6 (2.8) 10 (4.9) Musculoskeletal System Arthralgia 9 (4.2) 10 (4.9) Nervous System Depression 12 (5.7) 7 (3.4) Headache 11 (5.2) 14 (6.9) Respiratory System Bronchitis 9 (4.2) 7 (3.4) Sinusitis 8 (3.8) 12 (5.9) Upper respiratory infection 28 (13.2) 26 (12.7) Skin and Appendages Application site reaction 86 (40.6) 69 (33.8) Breast pain 40 (18.9) 20 (9.8) Rash 5 (2.4) 10 (4.9) Urogenital System Urinary Tract Infection 7 (3.3) 8 (3.9) Vaginal Bleeding 78 (36.8) 44 (21.6) Vaginitis 4 (1.9) 6 (2.9) Irritation potential of Climara Pro was assessed in a 3-week irritation study.
The study compared the irritation of a Climara Pro placebo patch (22 cm 2 ) to a placebo (25 cm 2 ). Visual assessments of irritation were made on Day 7 of each wear period, approximately 30 minutes after patch removal using a 7-point scale (0 = no evidence of irritation; 1 = minimal erythema, barely perceptible; 2 = definite erythema, readily visible, or minimal edema, or minimal papular response; 3–7 = erythema and papules, edema, vesicles, strong extensive reaction). The mean irritation scores were 0.13 (week 1), 0.12 (week 2), and 0.06 (week 3) for the Climara Pro.
The mean scores for the placebo group were 0.2 (week 1), 0.26 (week 2), 0.12 (week 3). There were no irritation scores greater than 2 at any timepoint in any woman. In controlled clinical trials, withdrawals due to application site reactions occurred in 6 (2.1 percent) of women in the 12-week symptom study and in 71 (8.5 percent) of subjects in the 1-year endometrial protection study.
6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of Climara Pro. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliab… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St.
John's wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in adverse reactions. Hydroxylation of levonorgestrel is a conversion step, which is mediated by cytochrome P450 enzymes.
Based on in-vitro and in vivo studies, it can be assumed that CYP3A, CYP2E and CYP2C are involved in the metabolism of levonorgestrel. Likewise, inducers or inhibitors of these enzymes may either, respectively, decrease the therapeutic effects or result in adverse reactions. Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration.
( 7 ) Hydroxylation of levonorgestrel may interact with inhibitors of CYP3A, CYP2E and CYP2C and decrease the therapeutic effects. ( 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Climara Pro is not indicated for use in pregnancy. There are no data with the use of Climara Pro in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
8.2Lactation Risk Summary Estrogens plus progestogens are present in human milk and can reduce milk production in breast-feeding women. This reduction can occur at any time but is less likely to occur once breast-feeding is well-established. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Climara Pro and any potential adverse effects on the breastfed child from Climara Pro or from the underlying maternal condition.
8.4Pediatric Use Climara Pro is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population.
8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing Climara Pro to determine whether those over 65 years of age differ from younger subjects in their response to Climara Pro. The Women's Health Initiative Studies In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Clinical Studies (14.5) ] .
In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see Clinical Studies (14.5) ] . The Women's Health Initiative Memory Study In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen plus progestin or estrogen-alone when compared to placebo [see Warnings and Precautions (5.3) , and Clinical Studies (14.6) ] .
Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 (see Warnings and Precautions (5.3) , and Clinical Studies (14.6) ] .
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Climara Pro is not indicated for use in pregnancy. There are no data with the use of Climara Pro in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
🧒 Pediatric Use ▾
8.4Pediatric Use Climara Pro is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population.
🧓 Geriatric Use ▾
8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing Climara Pro to determine whether those over 65 years of age differ from younger subjects in their response to Climara Pro. The Women's Health Initiative Studies In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Clinical Studies (14.5) ] .
In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see Clinical Studies (14.5) ] . The Women's Health Initiative Memory Study In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen plus progestin or estrogen-alone when compared to placebo [see Warnings and Precautions (5.3) , and Clinical Studies (14.6) ] .
Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 (see Warnings and Precautions (5.3) , and Clinical Studies (14.6) ] .
🆘 Overdosage ▾
10 OVERDOSAGE Overdosage of estrogen plus progestogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of Climara Pro therapy with institution of appropriate symptomatic care.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion of androstenedione, which is secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.
To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and FSH, through a negative feedback mechanism.
Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. Levonorgestrel inhibits gonadotropin production resulting in retardation of follicular growth and inhibition of ovulation. Studies to assess the potency of progestins using estrogen-primed postmenopausal endometrial biochemistry and morphologic features have shown that levonorgestrel counteracts the proliferative effects of estrogens on the endometrium.
12.2Pharmacodynamics Generally, a serum estrogen concentration does not predict an individual woman's therapeutic response to Climara nor her risk for adverse outcomes. Likewise, exposure comparisons across different estrogen products to infer efficacy or safety for the individual woman may not be valid.
12.3Pharmacokinetics Absorption Transdermal administration of Climara Pro produces mean maximum estradiol concentrations in serum in about 2 to 2.5 days. Estradiol concentrations equivalent to the normal ranges observed at the early follicular phase in premenopausal women are achieved within 12–24 hours after the first application. In one study, steady state estradiol concentrations in serum were measured during week 4 in 44 healthy, postmenopausal women during four consecutive Climara Pro applications of two formulations (0.045 mg estradiol/0.03 mg levonorgestrel and 0.045 mg estradiol/0.015 mg levonorgestrel) to the abdomen (each dose was applied for four 7-day periods).
Both formulations were bioequivalent in terms of estradiol and estrone C max and AUC parameters. A summary of Climara Pro single and multiple applications estradiol, estrone and levonorgestrel pharmacokinetic parameters is shown in Table 2. Table 2: Summary of Mean Pharmacokinetic Parameters Summary of Mean (± SD) Pharmacokinetic Parameters Following a Single Application of Climara Pro in 24 Healthy Postmenopausal Women Parameter Units Estradiol Estrone Levonorgestrel All mean parameters are arithmetic means except T max which is expressed as the median.
Single application Week 1 Data C ave Pg/mL 37.7 ± 10.4 41 ± 15 136 ±
52.7C max Pg/mL 54.3 ± 18.9 43.9 ± 14.9 138 ±
51.8T max Hours 42 84 90 C min Pg/mL 27.2 ± 7.66 32.6 ± 14.3 110 ±
41.7AUC Pg.h/mL 6340 ± 1740 6890 ± 2520 22900 ± 8860 Summary of Mean (± SD) Pharmacokinetic Parameters (Week 4) Following Four Consecutive Weekly Applications of Climara Pro in 44 Healthy Postmenopausal Women Multiple application Week 4 Data C ave Pg/mL 35.7 ± 11.4 45.5 ± 62.6 166 ±
97.8C max Pg/mL 50.7 ± 28.6 81.6 ± 252 194 ± 111 T max Hours 36 48 48 C min Pg/mL 33.8 ± 28.7 72.5 ± 253 153 ±
69.6AUC Pg.h/mL 6002 ± 1919 7642 ± 10518 27948 ± 16426 At steady state, Climara Pro maintains during the application period an average serum estradio… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion of androstenedione, which is secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.
To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and FSH, through a negative feedback mechanism.
Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. Levonorgestrel inhibits gonadotropin production resulting in retardation of follicular growth and inhibition of ovulation. Studies to assess the potency of progestins using estrogen-primed postmenopausal endometrial biochemistry and morphologic features have shown that levonorgestrel counteracts the proliferative effects of estrogens on the endometrium.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How 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
16.2Storage 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.
📦 Storage and Handling ▾
16.2Storage 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.
📋 Description ▾
11 DESCRIPTION Climara Pro (estradiol/levonorgestrel transdermal system) is an adhesive-based matrix transdermal patch designed to release both estradiol and levonorgestrel, a progestational agent, continuously upon application to intact skin. The 22 cm 2 Climara Pro system contains 4.4 mg estradiol and 1.39 mg levonorgestrel and provides a nominal delivery rate (mg per day) of 0.045 estradiol and 0.015 levonorgestrel. Estradiol USP has a molecular weight of 272.39 and the molecular formula is C 18 H 24 O 2 .
Levonorgestrel USP has a molecular weight of 312.4 and a molecular formula of C 21 H 28 O 2 . The structural formulas for estradiol and levonorgestrel are: The Climara Pro transdermal system comprises 3 layers. Proceeding from the visible surface towards the surface attached to the skin, these layers are: A translucent polyethylene backing film.
An acrylate adhesive matrix containing estradiol and levonorgestrel. A protective liner of either siliconized or fluoropolymer coated polyester film. The protective liner is attached to the adhesive surface and must be removed before the system can be used.
The active components of the transdermal system are estradiol and levonorgestrel. The remaining components of the transdermal system (acrylate copolymer adhesive and polyvinylpyrrolidone/vinyl acetate copolymer) are pharmacologically inactive. Chemical Structure Image
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise women to read the FDA-approved patient labeling (Patient Information and Instructions for Use) Vaginal Bleeding Inform postmenopausal women to report any vaginal bleeding to their healthcare provider as soon as possible [see Warning and Precautions (5.2) ]. Possible Serious Adverse Reactions with Estrogen Plus Progestogen Therapy Inform postmenopausal women of possible serious adverse reactions of estrogen plus progestogen therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warning and Precautions (5.1 , 5.2 , 5.3) ] .
Possible Common Adverse Reactions with Estrogen plus Progestogen Therapy Inform postmenopausal women of possible less serious but common adverse reactions of estrogen plus progestogen therapy such as headache, breast pain and tenderness, nausea and vomiting.
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Absorption Transdermal administration of Climara Pro produces mean maximum estradiol concentrations in serum in about 2 to 2.5 days. Estradiol concentrations equivalent to the normal ranges observed at the early follicular phase in premenopausal women are achieved within 12–24 hours after the first application. In one study, steady state estradiol concentrations in serum were measured during week 4 in 44 healthy, postmenopausal women during four consecutive Climara Pro applications of two formulations (0.045 mg estradiol/0.03 mg levonorgestrel and 0.045 mg estradiol/0.015 mg levonorgestrel) to the abdomen (each dose was applied for four 7-day periods).
Both formulations were bioequivalent in terms of estradiol and estrone C max and AUC parameters. A summary of Climara Pro single and multiple applications estradiol, estrone and levonorgestrel pharmacokinetic parameters is shown in Table 2. Table 2: Summary of Mean Pharmacokinetic Parameters Summary of Mean (± SD) Pharmacokinetic Parameters Following a Single Application of Climara Pro in 24 Healthy Postmenopausal Women Parameter Units Estradiol Estrone Levonorgestrel All mean parameters are arithmetic means except T max which is expressed as the median.
Single application Week 1 Data C ave Pg/mL 37.7 ± 10.4 41 ± 15 136 ±
52.7C max Pg/mL 54.3 ± 18.9 43.9 ± 14.9 138 ±
51.8T max Hours 42 84 90 C min Pg/mL 27.2 ± 7.66 32.6 ± 14.3 110 ±
41.7AUC Pg.h/mL 6340 ± 1740 6890 ± 2520 22900 ± 8860 Summary of Mean (± SD) Pharmacokinetic Parameters (Week 4) Following Four Consecutive Weekly Applications of Climara Pro in 44 Healthy Postmenopausal Women Multiple application Week 4 Data C ave Pg/mL 35.7 ± 11.4 45.5 ± 62.6 166 ±
97.8C max Pg/mL 50.7 ± 28.6 81.6 ± 252 194 ± 111 T max Hours 36 48 48 C min Pg/mL 33.8 ± 28.7 72.5 ± 253 153 ±
69.6AUC Pg.h/mL 6002 ± 1919 7642 ± 10518 27948 ± 16426 At steady state, Climara Pro maintains during the application period an average serum estradiol concentration of 35.7 pg/mL as depicted in Figure 1. Figure 1: Mean Estradiol Concentration Profile (Week 4) Following Four Consecutive Weekly Applications of Climara Pro Following the application of the Climara Pro transdermal system, levonorgestrel concentrations are maximum in about 2.5 days. At steady state, Climara Pro maintains during the application period an average serum levonorgestrel concentration of 166 pg/mL as depicted in Figure 2.
The mean levonorgestrel pharmacokinetic parameters of Climara Pro are summarized in Table 2. Figure 2: Mean Levonorgestrel Concentration Profile (Week 4) Following Four Consecutive Weekly Applications of Climara Pro Distribution The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs.
Estrogens circulate in the blood largely bound to SHBG and albumin. Levonorgestrel in serum is bound to both SHBG and albumin. Following four consecutive weekly applications of Climara Pro mean (± SD) SHBG concentrations declined from a predose value of 47.5 (25.8) to 41.2 (22.4) nmol/L at week 4.
Metabolism Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver.
Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is a major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the intestine followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens.
The most important metabolic pathway for levonor… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Generally, a serum estrogen concentration does not predict an individual woman's therapeutic response to Climara nor her risk for adverse outcomes. Likewise, exposure comparisons across different estrogen products to infer efficacy or safety for the individual woman may not be valid.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Effects on Vasomotor Symptoms in Postmenopausal Women The efficacy of 0.045 mg estradiol/0.03 mg levonorgestrel administered weekly versus placebo in the relief of moderate to severe vasomotor symptoms in postmenopausal women was studied in one 12-week clinical trial (n=183, average age 52.1 ± 4.93, 82 percent Caucasian). The 0.045 mg estradiol/0.03 mg levonorgestrel dosage strength was shown to be statistically better than placebo at weeks 4 and 12 for relief of both the number and severity of moderate to severe hot flushes.
See Tables 3 and 4 . Climara Pro and the 0.045 mg estradiol/0.03 mg levonorgestrel dosage strength are bioequivalent in terms of estradiol delivery [See Clinical Pharmacology (12.3) ] . Table 3: Summary of Mean Daily Number of Moderate to Severe Hot Flushes-ITT ITT = Intent-to-Treat population Baseline A participating woman was included at baseline only if she had a post-baseline mean score.
The post-baseline mean score required 3 days in one week. Week 4 Week 8 Week 12 Placebo n n = Number of participating women in a treatment group in a cycle; number of women varied from cycle to cycle due to missing data 88 82 73 69 Mean (SD) SD = standard deviation 10.8 (5.803) 6.13 (4.311) 5.35 (4.095) 5.59 (4.93) Mean Change from baseline (SD) NA -4.23 (4.374) -4.8 (4.448) -4.55 (5.407) 0.045/.03 n 92 88 80 73 Mean (SD) 10.13 (3.945) 2.69 (4.455) 1.22 (2.804) 1.06 (3.187) Mean Change from baseline (SD) NA -7.4 (4.715) -8.68 (4.146) -8.82 (4.336) p-Value p-value for comparison to placebo, adjusted by the method of Bonferroni NA <0.001 p <0.025 NA <0.001 Table 4: Summary of Mean Severity of Moderate to Severe Hot Flushes-ITT ITT= Intent-to-Treat population Baseline A participating woman was included at baseline only if she had at least 1 post-baseline value.
Week 4 (day 7) Week 8 (day 7) Week 12 (day 7) Placebo n n= Number of participating women in a treatment group in a cycle; number of women varied from cycle to cycle due to missing data 89 76 68 57 Mean (SD) 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.
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 p-value for comparison to placebo, adjusted by the method of Bonferroni NA <0.001 p <0.025 NA <0.001
14.2Effects on the Endometrium in Postmenopausal Women 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.
Climara Pro E 2 0.045 mg / LNG 0.015 mg Estradiol E 2 0.045 mg n n = number of intent-to-treat participating women. = 210 n = 202 No. of Patients with Biopsies at >6 months Defined as at least 180 days of treatment. 124 139 No. of Patients with Biopsies at 1 year Defined as ≥ 323 days of treatment. 102 110 No.
(%) of Patients with Hyperplasia Includes hyperplasia occurring at any time after initiation of treatment as a proportion of patients with biopsies at 1 year. 0 (0%) 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.
19 (17.3%) 95% Confidence Interval 0-3.55% 9.75–24.79%
14.3Effects on Uterine Bleedi… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.
📚 References ▾
15 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.
📄 Patient Package Insert ▾
Patient Information 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 (a combination of estrogen and progestogen)? Do not use estrogens with or without progestogens to prevent heart disease, heart attacks, strokes, or dementia (declines of brain function). Using estrogens with progestogens may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots.
Using estrogens with progestogens may increase your chance of getting dementia, based on a study of women 65 years of age and older. Using estrogen-alone may increase your chance of getting cancer of the uterus (womb). Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia.
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 and older. Only one estrogen with progestogen product and dose have been shown to increase your chances of getting heart attacks, strokes, breast cancer, blood clots, and dementia.
Only one estrogen-alone product and dose have been shown to increase your chances of getting strokes, blood clots, and dementia. Because other products and doses have not been studied in the same way, it is not known how the use of Climara Pro will affect your chances of these conditions. 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 progestogen. 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 intense feelings of heat and sweating ("hot flashes" or "hot flushes"). In some women, the symptoms are mild, and they will not need to use estrogens.
In other women, symptoms can be more severe. Help reduce your chances of getting osteoporosis (thin weak bones) Osteoporosis from menopause is a thinning of the bones that makes them weaker and easier to break. If you use Climara Pro to prevent osteoporosis from 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 progestogen to decrease the chance of getting cancer of the uterus. If you do not have a uterus, you do not need a progestogen and you should not use Climara Pro. Do not start using Climara Pro 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 been diagnosed with a bleeding disorder currently have or have had certain cancers Estrogens may increase the chance of getting certain typ… [Excerpted — this section continues on DailyMed.]
📖 Instructions for Use ▾
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 Figure C Figure D 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 E and Figure F Do not touch the sticky side of the patch with your fingers. Figure E Figure F 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 G Figure G 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 E and F ) 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. Do not flush used patches in the toilet. This Patient Information and Instructions for Use have been approved by the U.S Food and Drug Administration.
Revised: 3/2023 © 2013, Bayer HealthCare Pharmaceuticals Inc. All rights reserved. Manufactured for: Bayer HealthCare Pharmaceuticals Inc.
Whippany, NJ 07981 Manufactured by: Kindeva Drug Delivery L.P. Northridge CA, 91324 Figure A Figure B Figure C Figure D Figure E Figure F Figure G
📄 Recent Major Changes ▾
Warnings and Precautions ( 5.2 ) 12/2023
📄 Package Label / Principal Display Panel ▾
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Climara Pro Carton