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CombiPatch

Last reviewed on RxList: 5/27/2015
CombiPatch Side Effects Center

Last reviewed on RxList 02/03/2017

CombiPatch (estradiol, norethindrone acetate transdermal system) is a combination of female hormones used to treat the symptoms of menopause such as feelings of warmth in the face, neck and chest, or sudden intense spells of heat and sweating ("hot flashes" or "hot flushes"); to treat vulvar and vaginal changes (itching, burning, dryness in or around the vagina, difficulty or burning with urination) caused by menopause; and to replace estrogen in conditions such as hypogonadism, removal of the ovaries, or primary ovarian failure that result in a lack of estrogen. Common side effects of CombiPatch include:

  • skin redness/irritation/rash at the application site,
  • abdominal pain,
  • nausea,
  • vomiting,
  • bloating,
  • breast tenderness or enlargement,
  • weakness,
  • swelling of the hands or feet,
  • spotty darkening of the skin (particularly on the face),
  • difficulty wearing contact lenses,
  • vaginal irritation or discomfort,
  • changes in menstrual cycle,
  • painful menstruation,
  • breakthrough bleeding,
  • headache, or
  • weight changes.

Tell your doctor if you have serious side effects of CombiPatch including:

Two CombiPatch transdermal delivery systems are available: 0.05 mg estradiol with 0.14 mg NETA per day (9 sq cm) and 0.05 mg estradiol with 0.25 mg NETA per day (16 sq cm). The lowest effective dose should be used. CombiPatch may interact with anticoagulants (blood thinners). Tell your doctor all medications you use. CombiPatch must not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor. This medication passes into breast milk. It may reduce the quality and amount of breast milk produced. Consult your doctor before breastfeeding.

Our CombiPatch (estradiol, norethindrone acetate transdermal system) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

CombiPatch Consumer Information

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 and seek emergency medical attention or notify your doctor immediately:

  • an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);
  • sharp chest pain, coughing of blood or shortness of breath (possible blood clot in the lung );
  • pain in the calf (possible blood clot in the leg);
  • crushing chest pain or heaviness in the chest (possible heart attack);
  • sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg (possible stroke);
  • partial or complete loss of vision (possible clot in the eye);
  • stomach pain or tenderness, yellowing of the skin or eyes, fever, fatigue, loss of appetite, dark-colored urine, or light-colored stools (possible liver problems); or
  • new or changing breast lumps.

Other, less serious side effects may be more likely to occur. Continue to use estradiol and norethindrone and talk to your doctor if you experience

  • nausea and vomiting;
  • tenderness or enlargement of the breasts;
  • weakness;
  • swelling of the hands or feet;
  • spotty darkening of the skin, particularly on the face;
  • difficulty in wearing contact lenses;
  • vaginal irritation or discomfort;
  • a rash or reaction at the patch application site; or
  • changes in menstrual cycle, painful menstruation, or breakthrough bleeding.

Estradiol increases the risk of developing endometrial hyperplasia, a condition that may lead to cancer of the lining of the uterus. Using a progestin, such as norethindrone, with estradiol lowers the risk of developing this condition. Visit your doctor regularly and report any unusual vaginal bleeding right away.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for CombiPatch (Estradiol, Norethindrone Acetate Transdermal System)

CombiPatch Professional Information

SIDE EFFECTS

See BOXED WARNING, WARNINGS and PRECAUTIONS.

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.

Table 9: All Adverse Reactions Regardless of Relationship Reported at a Frequency of Greater than or Equal to 5 Percent with CombiPatch

  VASOMOTOR SYMPTOM STUDIES Placebo
n=107
CombiPatch 0.05/0.14 mg per day†
n=113
CombiPatch 0.05/0.25 mg per day†
n=112
Body as a Whole 46% 48% 41%
  Abdominal Pain 7% 6% 4%
  Accidental Injury 4% 5% 8%
  Asthenia 8% 12% 4%
  Back Pain 11% 9% 5%
  Flu Syndrome 9% 5% 7%
  Headache 18% 20% 20%
  Pain 6% 4% 9%
Digestive 19% 23% 24%
  Diarrhea 4% 5% 7%
  Dyspepsia 1% 5% 5%
  Flatulence 4% 5% 4%
Nausea 11% 8% 7%
  Nervous 16% 28% 28%
  Depression 3% 5% 9%
  Insomnia 3% 6% 7%
  Nervousness 3% 5% 1%
Respiratory 24% 38% 26%
  Pharyngitis 4% 10% 2%
  Respiratory Disorder 7% 12% 7%
  Rhinitis 7% 13% 9%
  Sinusitis 4% 9% 9%
Skin and Appendages 8% 17% 16%
  Application Site Reaction* 2% 6% 4%
Urogenital 54% 63% 28%
  Breast Pain 25% 31% 7%
  Dysmenorrhea 20% 21% 5%
 Leukorrhea 5% 5% 3%
  Menstrual Disorder 6% 12% 2%
  Papanicolaou Smear Suspicious 8% 4% 5%
  Vaginitis 6% 13% 5%
†Represents milligrams of estradiol/NETA delivered daily by each system.
*Application site reactions includes localized bleeding, bruising, burning, discomfort, dryness, eczema, edema, erythema, inflammation, irritation, pain, papules, paresthesia, pruritus, rash, skin discoloration, skin pigmentation, swelling, urticaria, and vesicles.

Table 10: All Adverse Reactions Regardless of Relationship Reported at a Frequency of Greater than or Equal to 5 Percent with CombiPatch

  ENDOMETRIAL HYPERPLASIA STUDIES Vivelle 0.05 mg per day
n=318
CombiPatch 0.05/0.14 mg per day†
n=325
CombiPatch 0.05/0.25 mg per day†
n=312
Body as a Whole 61% 60% 59%
  Abdominal Pain 12% 14% 16%
  Accidental Injury 10% 11% 8%
  Asthenia 10% 13% 11%
  Back Pain 15% 14% 13%
  Flu Syndrome 14% 10% 7%
  Headache 25% 17% 21%
  Infection 5% 3% 3%
  Pain 19% 15% 13%
Digestive 42% 32% 31%
  Constipation 2% 5% 3%
  Diarrhea 14% 9% 7%
  Dyspepsia  8% 6% 5%
  Flatulence 7% 5% 6%
  Nausea 8% 12% 11%
  Tooth Disorder 6% 4% 1%
Metabolic and Nutritional Disorders 12% 13% 11%
  Peripheral Edema 6% 6% 5%
Musculoskeletal 17% 17% 15%
  Arthralgia 6% 6% 5%
Nervous 33% 30% 28%
  Depression 8% 9% 8%
  Dizziness 6% 7% 5%
  Insomnia 8% 6% 4%
  Nervousness 5% 6% 3%
Respiratory 45% 43% 40%
  Bronchitis 5% 3% 4%
  Pharyngitis 9% 9% 8%
  Respiratory Disorder 13% 9% 13%
  Rhinitis 19% 22% 17%
  Sinusitis 10% 12% 12%
Skin and Appendages 38% 37% 31%
  Acne 4% 5% 4%
  Application Site Reaction* 20% 23% 17%
  Rash 6% 5% 3%
Urogenital 71% 79% 74%
  Breast Enlargement 2% 7% 2%
  Breast Pain 34% 48% 40%
  Dysmenorrhea 30% 31% 19%
  Leukorrhea 10% 8% 9%
  Menorrhagia 2% 5% 9%
  Menstrual Disorder 17% 19% 14%
  Vaginal Hemorrhage 3% 6% 12%
  Vaginitis 9% 13% 13%
†Represents milligrams of estradiol/NETA delivered daily by each system.
*Application site reactions includes localized bleeding, bruising, burning, discomfort, dryness, eczema, edema, erythema, inflammation, irritation, pain, papules, paresthesia, pruritus, rash, skin discoloration, skin pigmentation, swelling, urticaria, and vesicles.

Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of CombiPatch. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Genitourinary System

Endometrial hyperplasia, endocervical polyp, uterine leiomyomata, fallopian tube cyst, uterine spasms.

Breast

Breast cancer.

Cardiovascular

Hypertension, varicose veins.

Gastrointestinal

Jaundice cholestatic, cholelithiasis, gall bladder disorder, transaminases increased.

Skin

Skin discoloration.

Central Nervous System

Affect lability, libido disorder, migraine, vertigo, paresthesia.

Miscellaneous

Angioedema, hypersensitivity, weight increased.

Read the entire FDA prescribing information for CombiPatch (Estradiol, Norethindrone Acetate Transdermal System)

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© CombiPatch Patient Information is supplied by Cerner Multum, Inc. and CombiPatch Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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