Description and Brand Names

Drug information provided by: Micromedex

US Brand Name

  1. Combipatch

Canadian Brand Name

  1. Estalis
  2. Estalis-Sequi

Descriptions


Estradiol and norethindrone skin patch is used to treat moderate to severe hot flashes and other symptoms of menopause. It is also used to treat changes in and around the vagina (such as vaginal dryness, itching, and burning) caused by low estrogen levels or menopause. This medicine is also used to treat certain conditions in women before menopause if their ovaries do not make enough estrogens naturally.

This medicine is a combination of two hormones: an estrogen hormone (estradiol) and a progestin hormone (norethindrone). These hormones are absorbed through your skin into your body. It works by preventing symptoms, such as feelings of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating (hot flashes) in women during menopause.

This medicine is available only with your doctor's prescription.

This product is available in the following dosage forms:

  • Patch, Extended Release

Before Using

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Use of CombiPatch® is not indicated in children.

Geriatric

Although appropriate studies on the relationship of age to the effects of CombiPatch® have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have breast cancer, strokes, or dementia, which may require caution in patients receiving this medicine.

Pregnancy

Information about this estradiol-and-norethindrone-transdermal-route
Pregnancy Category Explanation
All Trimesters X Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

Breastfeeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Tranexamic Acid

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Carbamazepine
  • Ceritinib
  • Crizotinib
  • Dabrafenib
  • Eslicarbazepine Acetate
  • Fentanyl
  • Isotretinoin
  • Mitotane
  • Piperaquine
  • Pixantrone
  • Primidone
  • Siltuximab
  • Theophylline
  • Tizanidine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Alprazolam
  • Amprenavir
  • Aprepitant
  • Atazanavir
  • Bacampicillin
  • Betamethasone
  • Bexarotene
  • Bosentan
  • Clarithromycin
  • Colesevelam
  • Cyclosporine
  • Darunavir
  • Delavirdine
  • Efavirenz
  • Etravirine
  • Fosamprenavir
  • Fosaprepitant
  • Fosphenytoin
  • Ginseng
  • Griseofulvin
  • Itraconazole
  • Ketoconazole
  • Lamotrigine
  • Levothyroxine
  • Licorice
  • Modafinil
  • Mycophenolate Mofetil
  • Mycophenolic Acid
  • Nelfinavir
  • Oxcarbazepine
  • Phenobarbital
  • Phenytoin
  • Pioglitazone
  • Prednisolone
  • Primidone
  • Rifabutin
  • Rifampin
  • Rifapentine
  • Ritonavir
  • Rosuvastatin
  • Rufinamide
  • Selegiline
  • St John's Wort
  • Tacrine
  • Telaprevir
  • Tipranavir
  • Topiramate
  • Troglitazone
  • Troleandomycin
  • Valdecoxib
  • Voriconazole
  • Warfarin

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Caffeine

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Abnormal or unusual vaginal bleeding or
  • Blood clots (eg, deep vein thrombosis, pulmonary embolism), active or history of or
  • Breast cancer, known or suspected, or a history of or
  • Heart attack, history of or
  • Liver disease or
  • Protein C, protein S, or other known blood clotting disorders or
  • Stroke, history of or
  • Tumors (estrogen-dependent), known or suspected—Should not be used in patients with these conditions.
  • Asthma or
  • Bone problems or
  • Diabetes or
  • Edema (fluid retention or body swelling) or
  • Endometriosis or
  • Epilepsy (seizures) or
  • Gallbladder disease or
  • Hereditary angioedema (swelling of the face, lips, tongue, or throat) or
  • Hypercalcemia (high calcium in the blood) or
  • Hypocalcemia (low calcium in the blood) or
  • Hypothyroidism (an underactive thyroid) or
  • Jaundice during pregnancy or from using hormonal therapy in the past or
  • Liver tumors or
  • Migraine headache or
  • Porphyria (an enzyme problem) or
  • Systemic lupus erythematosus (SLE)—Use with caution. May make these conditions worse.
  • Heart disease or
  • Hypercholesterolemia (high cholesterol or fats in the blood) or
  • Hypertension (high blood pressure) or
  • Hypertriglyceridemia (high triglycerides or fats in the blood) or
  • Obesity, or history of or
  • Prolonged periods of immobilization—Use with caution. These conditions may increase risk for more serious side effects.

Proper Use

It is very important that you use this medicine exactly as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects.

This medicine comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Before starting CombiPatch® therapy, you may need to tell your doctor if you are currently using continuous estrogen or combination estrogen plus progestin therapy. This will allow your doctor to determine when to start your treatment.

You may have monthly bleeding or spotting at the completion of each cycle.

This transdermal patch system is to be applied on the skin of the lower abdomen (lower stomach area) two times a week, depending on your dosing regimen (either continuous combined regimen or continuous sequential regimen), as advised by your doctor.

To use the skin patch:

  • Wash your hands with soap and water before and after you use this medicine.
  • Carefully tear open the pouch when you are ready to put the patch on your skin. Do not cut it.
  • Peel off the backing from the patch and apply the patch to a clean, dry, and hair-free area of the lower stomach. This area must be free of powder, oil, or lotion for the patch to stick on to your skin.
  • Press the patch firmly in place with your hand for about 10 seconds.
  • Do not apply the patch on the breast or over any skin folds. Do not apply the patch on oily, broken, burned, or irritated skin, or areas with skin conditions (such as birth marks, tattoos). Avoid applying the patch on the waistline or other places where tight clothing may rub it off.
  • Wear the patch at all times until it is time to put on a new patch. Do not expose it to the sun for long periods of time.
  • When replacing your patch, make sure to apply the new patch to a different area of your lower abdomen. Wait at least 1 week before applying a patch to the same area.
  • When changing a patch, slowly peel it off from your skin. If you have any patch adhesive left on your skin, allow it to dry for 15 minutes and gently rub the sticky area with oil or lotion to remove it. It is best to change your patch on the same days of each week to help you remember.
  • You may take a bath, shower, or swim while using this medicine. Doing so will not affect the patch.
  • If a patch falls off, just put it back on a different area. If the patch does not stick completely, put on a new patch but continue to follow your original schedule for changing your patch.
  • To throw away a used patch: Fold the patch in half with the sticky side together and place it in a sturdy child-proof container. Throw this container in the trash away from children and pets. Do not flush the patch down the toilet.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For transdermal dosage form (patch):
    • For treatment of hot flashes, atrophic vaginitis caused by menopause:
      • Continuous combined regimen:
        • Adults—Apply 1 CombiPatch® two times a week (every 3 to 4 days) for 28-days cycle. One CombiPatch® contains 0.05 milligrams (mg) of estradiol and 0.14 or 0.25 mg of norethindrone).
        • Children—Use is not recommended.
      • Continuous sequential regimen:
        • Adults—Apply 0.05 milligram (mg) estradiol patch (Vivelle®) two times a week for the first 14 days of the 28-days cycle. Then, apply one CombiPatch® two times a week (every 3 to 4 days) for the next 14 days. One CombiPatch® contains 0.05 milligrams (mg) of estradiol and 0.14 or 0.25 mg of norethindrone).
        • Children—Use is not recommended.

Missed Dose

If you forget to wear or change a patch, put one on as soon as you can. If it is almost time to put on your next patch, wait until then to apply a new patch and skip the one you missed. Do not apply extra patches to make up for a missed dose.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the patches at room temperature in a closed container, away from heat, moisture, and direct light.

Store the unopened pouches at room temperature for up to 6 months. Do not store the patch outside of its pouch.

Precautions

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and does not cause unwanted effects. Pelvic exam, breast exam, and mammogram (breast x-ray) may be needed to check for unwanted effects, unless your doctor tells you otherwise. Be sure to keep all appointments.

It is unlikely that a postmenopausal woman may become pregnant. But, you should know that using this medicine while you are pregnant could harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.

Using this medicine may increase your risk for having blood clots, strokes, or heart attacks. This risk may continue even after you stop using the medicine. Your risk for these serious problems is even greater if you have high blood pressure, high cholesterol in your blood, diabetes or are overweight or smoke cigarettes. Contact your doctor immediately if you experience chest pain, confusion, difficulty speaking, double vision, headaches, an inability to move arms, legs or facial muscle, or an inability to speak.

Using this medicine may increase your risk of endometrial cancer, breast cancer, or uterine cancer. Talk with your doctor about this risk. Check with your doctor immediately if your experience abnormal vaginal bleeding.

Do not use this medicine if you have had your uterus (womb) removed (hysterectomy).

Using this medicine may increase your risk of dementia, especially in women 65 years of age and older.

Check with your doctor immediately if severe headache or sudden loss of vision or any other change in vision occurs while you are using this medicine. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine before you have surgery or if you need to stay in bed for an extended time. This medicine may affect the results of certain medical tests.

Do not eat grapefruit or drink grapefruit juice while you are using this medicine. Grapefruit and grapefruit juice may change the amount of this medicine that is absorbed in the body.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

  1. Bloating or swelling of the face, arms, hands, lower legs, or feet
  2. heavy non-menstrual vaginal bleeding
  3. itching of the vagina or genital area
  4. pain during sexual intercourse
  5. rapid weight gain
  6. thick, white vaginal discharge with no odor or with a mild odor
  7. tingling of the hands or feet
  8. unusual weight gain or loss

Less common

  1. Cough or hoarseness
  2. fever or chills
  3. lower back or side pain
  4. painful or difficult urination

Incidence not known

  1. Abdominal or stomach bloating or fullness
  2. abdominal or stomach pain
  3. blurred vision
  4. change in vaginal discharge
  5. clay-colored stools
  6. clear or bloody discharge from the nipple
  7. dark urine
  8. diarrhea
  9. dimpling of the breast skin
  10. dizziness
  11. gaseous abdominal or stomach pain
  12. headache, severe and throbbing
  13. hives
  14. hoarseness
  15. inverted nipple
  16. irritation
  17. itching
  18. joint pain, stiffness or swelling
  19. large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  20. loss of appetite
  21. lump in the breast or under the arm
  22. nausea and vomiting
  23. nervousness
  24. pain or feeling of pressure in the pelvis
  25. persistent crusting or scaling of the nipple
  26. pounding in the ears
  27. rash
  28. recurrent fever
  29. redness of the skin
  30. redness or swelling of the breast
  31. severe cramping of the uterus
  32. slow or fast heartbeat
  33. sore on the skin of the breast that does not heal
  34. swelling of the eyelids, face, lips, hands, or feet
  35. tightness in the chest
  36. troubled breathing or swallowing
  37. unpleasant breath odor
  38. unusual tiredness or weakness
  39. vaginal bleeding
  40. vomiting of blood
  41. yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  1. Acid or sour stomach
  2. back pain
  3. belching
  4. body aches or pain
  5. breast pain
  6. burning, itching, redness, skin rash, swelling, or soreness at the application site
  7. congestion
  8. cramps
  9. difficulty with moving
  10. discouragement
  11. dryness or soreness of the throat
  12. excess air or gas in the stomach or intestines
  13. feeling sad or empty
  14. general feeling of discomfort or illness
  15. headache
  16. heartburn
  17. heavy bleeding
  18. increased clear or white vaginal discharge
  19. indigestion
  20. irritability
  21. lack or loss of strength
  22. loss of interest or pleasure
  23. muscle aches and pains
  24. muscle stiffness
  25. pain during sexual intercourse
  26. pain or tenderness around the eyes and cheekbones
  27. passing gas
  28. shivering
  29. sneezing
  30. stomach discomfort or upset
  31. stuffy or runny nose
  32. sweating
  33. tender, swollen glands in the neck
  34. thick, white vaginal discharge with no odor or with a mild odor
  35. tiredness
  36. trouble concentrating
  37. trouble sleeping

Less common

  1. Blemishes on the skin
  2. difficulty having a bowel movement (stool)
  3. longer or heavier menstrual periods
  4. pimples

Incidence not known

  1. Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  2. change in color of the treated skin
  3. decreased interest in sexual intercourse
  4. dizziness or lightheadedness
  5. dull ache or feeling of pressure or heaviness in the legs
  6. feeling of constant movement of self or surroundings
  7. inability to have or keep an erection
  8. increased in sexual ability, desire, drive, or performance
  9. increased interest in sexual intercourse
  10. itching skin near damaged veins
  11. loss in sexual ability, desire, drive, or performance
  12. sensation of spinning
  13. weight gain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.