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CombiPatch

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CombiPatch

CombiPatch®
(estradiol/norethindrone acetate) transdermal system




WARNING

CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER, AND PROBABLE DEMENTIA

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 Clinical Studies and WARNINGS, 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 Clinical Studies and WARNINGS, Cardiovascular Disorders).

The WHI Memory Study (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 Clinical Studies and WARNINGS, Probable Dementia and PRECAUTIONS, Geriatric Use).

Breast Cancer

The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer. (See Clinical Studies and WARNINGS, Malignant Neoplasms, Breast Cancer).

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.

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, Malignant Neoplasms, Endometrial Cancer).

Cardiovascular Disorders and Probable Dementia

Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia. (See Clinical Studies and WARNINGS, 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 Clinical Studies and WARNINGS, Cardiovascular Disorders).

The 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 Clinical Studies and WARNINGS, Probable Dementia and PRECAUTIONS, Geriatric Use).

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage 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.

DRUG DESCRIPTION

CombiPatch® (estradiol/norethindrone acetate transdermal system) is an adhesive-based matrix transdermal patch designed to release both estradiol, an estrogen, and norethindrone acetate (NETA), a progestational agent, continuously upon application to intact skin.

Two systems are available, providing the following in vivo delivery rates of estradiol and NETA.

System Size Estradiol (mg) NETA1 (mg) Nominal Delivery Rate2 (mg per day) Estradiol / NETA
9 cm² round 0.62 2.7 0.05/0.14
16 cm² round 0.51 4.8 0.05/0.25
1NETA=norethindrone acetate.
2Based on in vivo/in vitro flux data, delivery of both components per day via skin of average permeability (interindividual variation in skin permeability is approximately 20 percent).

Estradiol USP (estradiol) is a white to creamy white, odorless, crystalline powder, chemically described as estra-1,3,5(10)-triene-3,17β-diol. The molecular weight of estradiol is 272.39 and the molecular formula is C18H24O2.

NETA USP is a white to creamy white, odorless, crystalline powder, chemically described as 17hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one acetate. The molecular weight of NETA is 340.47 and the molecular formula is C22H28O3.

The structural formulas for estradiol and NETA are:

CombiPatch® (estradiol/norethindrone acetate) Structural Formula Illustration

CombiPatch is comprised of 3 layers. Proceeding from the visible surface toward the surface attached to the skin, these layers are (1) a translucent polyolefin film backing, (2) an adhesive layer containing estradiol, NETA, acrylic adhesive, silicone adhesive, oleic acid NF, povidone USP and dipropylene glycol, and (3) a polyester release protective liner, which is attached to the adhesive surface and must be removed before the system can be used.

3 layers of CombiPatch - Illustration

The active components of the system are estradiol USP and NETA USP. The remaining components of the system are pharmacologically inactive.

What are the possible side effects of estradiol and norethindrone (Combipatch)?

Treatment with estrogens long-term may increase the risk of heart attack, stroke, breast cancer, and blood clots in the lungs or legs. Because of these risks, you should contact your doctor or healthcare provider to discuss your individual risks and benefits before using estradiol and norethindrone long-term. You should also talk to your doctor or healthcare provider on a regular basis (for example, every 3-6 months) about whether you should continue this treatment.

If you experience any of the following serious side effects, stop using estradiol and norethindrone...

Read All Potential Side Effects and See Pictures of CombiPatch »

What are the precautions when taking estradiol, norethindrone acetate transdermal system (CombiPatch)?

Before using this medication, tell your doctor or pharmacist if you are allergic to estradiol or norethindrone; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: vaginal bleeding of unknown cause, certain cancers (such as breast cancer, cancer of the uterus/ovaries), blood clots, stroke, heart disease (such as heart attack), liver disease, kidney disease, family medical history (especially breast lumps, cancer, blood clots, angioedema), blood clotting disorders (such as protein C or protein S deficiency), high blood pressure, diabetes, high blood...

Read All Potential Precautions of CombiPatch »

Last reviewed on RxList: 5/27/2015
This monograph has been modified to include the generic and brand name in many instances.

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CombiPatch - User Reviews

CombiPatch User Reviews

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Here is a collection of user reviews for the medication CombiPatch sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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