Data from FDA - Curated by EPG Health - Last updated 12 April 2018

Indication(s)

1 INDICATIONS AND USAGE Climara is an estrogen indicated for: • Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause ( 1.1 ) • Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause ( 1.2 ) • Treatment of Hypoestrogenism due to Hypogonadism, Castration or Primary Ovarian Failure ( 1.3 ) • Prevention of Postmenopausal Osteoporosis ( 1.4 ) 1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause 1.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Limitation of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, topical vaginal products should be considered. 1.3 Treatment of Hypoestrogenism due to Hypogonadism, Castration, or Primary Ovarian Failure 1.4 Prevention of Postmenopausal Osteoporosis Limitation of Use When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medication should be carefully considered.

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Advisory information

contraindications
4 CONTRAINDICATIONS Climara is contraindicated in women with any of the following conditions: •Undiagnosed abnormal genital bleeding •Known, suspected, or history of breast cancer •Known or suspected estrogen-dependent neoplasia •Active DVT, PE, or a history of these conditions •high risk of venous thrombosis (VTE) or arterial thrombosis (ATE) •Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions •Known anaphylactic reaction or angioedema with Climara •Known liver impairment or disease •Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders •Known or suspected pregnancy • Undiagnosed abnormal genital bleeding ( 4 ) • Known, suspected, or history of breast cancer ( 4 , 5.2 ) • Known or suspected estrogen-dependent neoplasia ( 4 , 5.2 ) • Active DVT, PE or a history of these conditions ( 4 , 5.1 ) • A high risk of VTE or arterial thrombosis (ATE) • Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions ( 4 , 5.1 ) • Known anaphylactic reaction or angioedema with Climara ( 4 ) • Known liver impairment or disease ( 4 , 5.10 ) • Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 ) • Known or suspected pregnancy ( 4 , 8.1 )
Adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: •Cardiovascular Disorders [see Boxed Warning, and Warnings and Precautions (5.1)] •Malignant Neoplasms [see Boxed Warning, and Warnings and Precautions (5.2)] In a prospective, randomized, placebo-controlled, double-blind study, the most common adverse reactions (≥10 percent) are breast pain, upper respiratory tract infections, headaches, abdominal pain, pain, and edema. (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. 6.1 Clinical 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 reflect pooled data from 5 clinical trials of Climara. A total of 614 women were exposed to Climara for 3 months (193 women at 0.025 mg per day, 201 women at 0.05 mg per day, 194 women at 0.1 mg per day) in randomized, double-blind trials of clinical efficacy versus placebo and versus active comparator. All women were postmenopausal, had a serum estradiol level of less than 20 pg/mL, and a minimum of five moderate to severe hot flushes per week or a minimum of 15 hot flushes per week of any severity at baseline. Included in this table are an additional 25 postmenopausal hysterectomized women exposed to Climara 0.025 mg per day for 6 to 24 months (N=16 at 24 months) in a randomized, double-blind, placebo-controlled study of Climara for the prevention of osteoporosis. Table 1: Treatment-Emergent Adverse Reactions Reported at a Frequency of ≥5 Percent and More Frequent in Women Receiving Climara Climara Body System Adverse Reactions 0.025 mg/day Adverse reactions occurring at rate of ≥5 percent in Climara trials of clinical efficacy versus placebo and versus active comparator; and trial of Climara versus placebo for the prevention of osteoporosis (N=219) 0.05 mg/day Adverse reactions occurring at rate of ≥5 percent in Climara trials of clinical efficacy versus placebo and versus active comparator (N=201) 0.1 mg/day (N=194) Placebo Adverse reactions occurring in placebo group in Climara trial of clinical efficacy versus placebo. (N=72) Body as a Whole Headache Pain Back Pain Edema 21% 5% 1% 4% 0.5% 39% 18% 8% 8% 13% 37% 13% 11% 9% 10% 29% 10% 7% 6% 6% Digestive System Abdominal Pain Nausea Flatulence 9% 0% 1% 1% 21% 11% 5% 3% 29% 16% 6% 7% 18% 8% 3% 1% Musculoskeletal System Arthralgia 7% 1% 9% 5% 11% 5% 4% 3% Nervous System Depression 13% 1% 10% 5% 11% 8% 1% 0% Urogenital System Breast Pain Leukorrhea 12% 5% 1% 18% 8% 6% 41% 29% 7% 11% 4% 1% Respiratory System URTI Pharyngitis Sinusitis Rhinitis 15% 6% 0.5% 4% 2% 26% 17% 3% 4% 4% 29% 17% 7% 5% 6% 14% 8% 3% 3% 1% Skin and Appendages Pruritus 19% 0.5% 12% 6% 12% 3% 15% 6% 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of the Climara transdermal system. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Genitourinary System Changes in bleeding pattern, pelvic pain Breast Breast cancer, breast pain, breast tenderness Cardiovascular Changes in blood pressure, palpitations, hot flashes Gastrointestinal Vomiting, abdominal pain, abdominal distension, nausea Skin Alopecia, hyperhidrosis, night sweats, urticaria, rash Eyes Visual disturbances, contact lens intolerance, Central Nervous System Depression, migraine, paresthesia, dizziness, anxiety, irritability, mood swings, nervousness, insomnia, headache Miscellaneous Fatigue, menopausal symptoms, weight increase, application site reaction, anaphylactic reactions

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be considered to reduce the risk of endometrial cancer. A woman without a uterus does not need a progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin [see Warnings and Precautions (5.2, 5.14)]. Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. • Start therapy with Climara 0.025 mg per day applied to the skin once-weekly. Dosage adjustment should be guided by the clinical response ( 2.1 ) • Climara should be placed on a clean, dry area of the lower abdomen (below the umbilicus) or upper quadrant of the buttock. Climara should not be applied to the breasts ( 2.5 ) 2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Start therapy with 0.025 mg per day applied to the skin once weekly. Therapy should be started at the lowest effective dose and the shortest duration consistent with the treatment goals. Attempts to taper or discontinue the medication should be made at 3 to 6 month intervals. 2.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Start therapy with 0.025 mg per day applied to the skin once weekly. Therapy should be started at the lowest effective dose and the shortest duration consistent with the treatment goals. Attempts to taper or discontinue the medication should be made at 3 to 6 month intervals. 2.3 Treatment of Hypoestrogenism due to Hypogonadism, Castration, or Primary Ovarian Failure Start therapy with 0.025 mg per day applied to the skin once weekly. The dose should be adjusted as necessary to control symptoms. Clinical responses (relief of symptoms) at the lowest effective dose should be the guide for establishing administration of the Climara transdermal system, especially in women with an intact uterus. 2.4 Prevention of Postmenopausal Osteoporosis Start therapy with 0.025 mg per day applied to the skin once weekly. 2.5 Application of the Climara Transdermal System Site Selection •The adhesive side of Climara should be placed on a clean, dry area of the lower abdomen or the upper quadrant of the buttock. •Climara should not be applied to or near the breasts. •The sites of application must be rotated, with an interval of at least 1-week allowed between applications to the same site. •The area selected should not be oily, damaged, or irritated. The waistline should be avoided, since tight clothing may rub the transdermal system off. •Application to areas where sitting would dislodge Climara should also be avoided. Application •Climara should be applied immediately after opening the pouch and removing the protective liner. •Climara should be pressed 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 it to a different location. If the system cannot be reapplied, a new system should be applied for the remainder of the 7-day dosing interval. •Only one system should be worn at any one time during the 7-day dosing interval. •Swimming, bathing, or using a sauna while using Climara has not been studied, and these activities may decrease the adhesion of the system and the delivery of estradiol. 2.6 Removal of the Climara Transdermal System •Removal of Climara should be done carefully and slowly to avoid irritation of the skin. •Should any adhesive remain on the skin after removal of the Climara system, allow the area to dry for 15 minutes. Then gently rubbing the area with an oil-based cream or lotion should remove the adhesive residue. •Used patches still contain some active hormones. Each patch should be carefully folded in half so that it sticks to itself before throwing it away.
Use in special populations
8 USE IN SPECIFIC POPULATIONS • Nursing Mothers: Estrogen administration to nursing women has been shown to decrease the quantity and quality of breast milk ( 8.3 ) • Geriatric Use: An increased risk of probable dementia in women over 65 years of age was reported in the WHIMS ancillary studies of the WHI ( 5.3 , 8.5 , 14.4 ) 8.1 Pregnancy Climara should not be used during pregnancy [see Contraindications (4)]. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as oral contraceptives inadvertently during early pregnancy. 8.3 Nursing Mothers Climara should not be used during lactation. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogens have been identified in the breast milk of women receiving estrogen therapy. Caution should be exercised when the Climara transdermal system is administered to a nursing woman. 8.4 Pediatric Use Climara is not indicated in children. Clinical studies have not been conducted in the pediatric population. 8.5 Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing Climara to determine whether those over 65 years of age differ from younger subjects in their response to Climara. The Women’s Health Initiative Studies 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 (14.3)]. In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher RR of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Clinical Studies (14.3)]. 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-alone or estrogen plus progestin when compared to placebo [see Warnings and Precautions (5.3), and Clinical Studies (14.4)]. Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women8 [see Warnings and Precautions (5.3), and Clinical Studies (14.4)]. 8.6 Renal Impairment In postmenopausal women with end stage renal disease (ESRD) receiving maintenance hemodialysis, total estradiol serum levels are higher than in normal subjects at baseline and following oral doses of estradiol. Therefore, conventional transdermal estradiol doses used in individuals with normal renal function may be excessive for postmenopausal women with ESRD receiving maintenance hemodialysis. 8.7 Hepatic Impairment Estrogens may be poorly metabolized in patients with impaired liver function and should be administered with caution.
Pregnancy and lactation
8.3 Nursing Mothers Climara should not be used during lactation. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogens have been identified in the breast milk of women receiving estrogen therapy. Caution should be exercised when the Climara transdermal system is administered to a nursing woman.

Interactions

7 DRUG INTERACTIONS • Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism ( 7.1 ) 7.1 Metabolic 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 side effects.

More information

Category Value
Authorisation number NDA020375
Agency product number 4TI98Z838E
Orphan designation No
Product NDC 50419-459,50419-452,50419-453,50419-451,50419-456,50419-454
Date Last Revised 01-11-2017
Type HUMAN PRESCRIPTION DRUG
RXCUI 404657
Marketing authorisation holder Bayer HealthCare Pharmaceuticals Inc.
Warnings WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER AND PROBABLE DEMENTIA 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 progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed, persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2)]. Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1, 5.3), and Clinical Studies (14.3, 14.4)]. The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo [see Warnings and Precautions (5.1), and Clinical Studies (14.3)]. The WHI Memory Study (WHIMS) estrogen-alone ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or 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 (14.4)]. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other forms of estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1, 5.3), and Clinical Studies (14.3, 14.4)]. The WHI estrogen plus progestin substudy reported increased risks of 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 CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo [see Warnings and Precautions (5.1), and Clinical Studies (14.3)]. The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or 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 (14.4)]. Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.2), and Clinical Studies (14.3)]. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER AND PROBABLE DEMENTIA See full prescribing information for complete boxed warning. Estrogen-Alone Therapy •There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens (5.2) •Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia (5.1, 5.3) •The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) (5.1) •The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older (5.3) Estrogen Plus Progestin Therapy • Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia ( 5.1 , 5.3 ) • The WHI estrogen plus progestin substudy reported increased risks of stroke, DVT, pulmonary embolism (PE), and myocardial infarction (MI) ( 5.1 ) • The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer ( 5.2 ) • The WHIMS estrogen plus progestin ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older ( 5.3 )