Climara Information
Climara (Estradiol) Description
Climara (Estradiol) , estradiol transdermal system, is designed to release estradiol continuously upon application to intact skin. Six (6.5, 9.375, 12.5, 15, 18.75 and 25 cm) systems are available to provide nominal delivery of 0.025, 0.0375, 0.05, 0.06, 0.075 or 0.1 mg respectively of estradiol per day. The period of use is 7 days. Each system has a contact surface area of either 6.5, 9.375, 12.5, 15, 18.75 or 25 cm, and contains 2, 2.85, 3.8, 4.55, 5.7 or 7.6 mg of estradiol USP respectively. The composition of the systems per unit area is identical. Estradiol USP is a white, crystalline powder, chemically described as estra-1,3,5(10)-triene-3, 17β-diol. It has an empirical formula of CH O and molecular weight of 272.39. The structural formula is:
The Climara (Estradiol) system comprises three layers. Proceeding from the visible surface toward the surface attached to the skin, these layers are (1) a translucent polyethylene film, and (2) an acrylate adhesive matrix containing estradiol USP. A protective liner (3) of siliconized or fluoropolymer-coated polyester film is attached to the adhesive surface and must be removed before the system can be used.
The active component of the system is estradiol. The remaining components of the system (acrylate copolymer adhesive, fatty acid esters, and polyethylene backing) are pharmacologically inactive.
Climara (Estradiol) Clinical Pharmacology
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, secreted by the adrenal cortex, to estrone by 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 follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.
Climara (Estradiol) Indications And Usage
Climara (Estradiol) is indicated in the:
Climara (Estradiol) Contraindications
Climara (Estradiol) should not be used in women with any of the following conditions:
Climara (Estradiol) Warnings
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Estrogen and estrogen/progestin therapy has been associated with an increased risk of cardiovascular events such as myocardial infarction and stroke, as well as venous thrombosis and pulmonary embolism (venous thromboembolism or VTE). Should any of these occur or be suspected, estrogens should be discontinued immediately.
Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.
Climara (Estradiol) Precautions
Long-term continuous administration of estrogen, with and without progestin, in women with and without a uterus, has shown an increased risk of endometrial cancer, breast cancer, and ovarian cancer. (See , and .)
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.
There have not been sufficient numbers of geriatric patients involved in clinical studies utilizing Climara (Estradiol) to determine whether those over 65 years of age differ from younger subjects in their response to Climara (Estradiol) .
In the Women's Health Initiative Memory Study, including 4,532 women 65 years of age and older, followed for an average of 4 years, 82% (n=3,729) were 65 to 74 while 18% (n=803) were 75 and over. Most women (80%) had no prior hormone therapy use. Women treated with conjugated estrogens plus medroxyprogesterone acetate were reported to have a two-fold increase in the risk of developing probable dementia. Alzheimer's disease was the most common classification of probable dementia in both the conjugated estrogens plus medroxyprogesterone acetate group and the placebo group. Ninety percent of the cases of probable dementia occurred in the 54% of women that were older than 70. (See and , .)
Climara (Estradiol) Adverse Reactions
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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 adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
The following adverse reactions have been identified during post approval use of Climara (Estradiol) : a few cases in which there were a combination of the symptoms of generalized hives or rash with swelling of the throat or eyelid edema. 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.
The following additional adverse reactions have been reported with estrogen and/or progestin therapy.
Climara (Estradiol) Overdosage
Serious ill effects have not been reported following acute ingestion of large doses of estrogen-containing oral contraceptives by young children. Overdosage of estrogen may cause nausea and vomiting, and withdrawal bleeding may occur in females.
Climara (Estradiol) Dosage And Administration
When estrogen is prescribed for a postmenopausal woman with a uterus, progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. 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. Patients should be reevaluated periodically as clinically appropriate (e.g., 3-month to 6-month intervals) to determine if treatment is still necessary (See and .) For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
Patients should be started at the lowest dose. Six (6.5, 9.375, 12.5, 15, 18.75 and 25 cm) Climara (Estradiol) systems are available. For the treatment of vasomotor symptoms, treatment should be initiated with the 6.5 cm (0.025 mg/day) Climara (Estradiol) system 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 (Estradiol) system, especially in women with an intact uterus. Attempts to taper or discontinue the medication should be made at 3- to 6-month intervals. In women who are not currently taking oral estrogens, treatment with the Climara (Estradiol) system can be initiated at once. In women who are currently taking oral estrogen, treatment with the Climara (Estradiol) system can be initiated 1-week after withdrawal of oral therapy or sooner if symptoms reappear in less than 1-week. For the prevention of postmenopausal osteoporosis, the minimum dose that has been shown to be effective is the 6.5 cm (0.025 mg/day) Climara (Estradiol) system. Response to therapy can be assessed by biochemical markers and measurement of bone mineral density.
Climara (Estradiol) How Supplied
Do not store above 86°F (30°C). Do not store unpouched. Apply immediately upon removal from the protective pouch.
The following are representative examples of Climara (Estradiol) labeling. See the "How Supplied" section for a complete listing of all components.
Climara (Estradiol) Climara . Mg Trade Carton
NDC 50419-454-04
4 transdermal systems
Contents: Each 6.5 cm2 system contains 2 mg estradiol USP to
provide 0.025 mg of estradiol per day. The inactive components
are acrylate copolymer adhesive, fatty acid esters, and
polyethylene backing.
Keep this and all drugs out of the reach of children.
Climara (Estradiol) Climara . Mg Trade Carton
NDC 50419-456-04
4 transdermal systems
Contents: Each 6.5 cm2 system contains 2.85 mg estradiol USP to
provide 0.0375 mg of estradiol per day. The inactive components
are acrylate copolymer adhesive, fatty acid esters, and
polyethylene backing.
Keep this and all drugs out of the reach of children.
Climara (Estradiol) Patient Information Updated June
(estradiol transdermal system)
Read this PATIENT INFORMATION before you start using Climara (Estradiol) and read what you get each time you refill Climara (Estradiol) . There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
