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Estradiol and norethindrone (Transdermal route)

Pronunciation:

es-tra-DYE-ol, nor-ETH-in-drone AS-e-tate

Brand Names:

  • Combipatch
  • Estalis
  • Estalis-Sequi

Dosage Forms:

  • Patch, Extended Release

Warnings:

Transdermal route(Patch, Extended Release)

Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia. An increased risk of DVT, pulmonary embolism, stroke, myocardial infarction, and invasive breast cancer have been reported. An increased risk of probable dementia in postmenopausal women 65 years of age or older has also been reported. There is an increased risk of endometrial cancer in women with a uterus who use unopposed 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 .

Classifications:

Therapeutic

Estrogen/Progestin Combination

Pharmacologic

Estrogen

Uses of This Medicine:

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.

Before Using This Medicine:

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.

Children

Use of CombiPatch® is not indicated in children.

Older adults

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

Pregnancy CategoryExplanation
All TrimestersXStudies 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.

Breast-feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Other medicines

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.

  • Bupropion
  • Carbamazepine
  • Ceritinib
  • Dabrafenib
  • Darunavir
  • Donepezil
  • Eliglustat
  • Idelalisib
  • Isotretinoin
  • Lesinurad
  • Lixisenatide
  • Lumacaftor
  • Pitolisant
  • Pixantrone
  • Sugammadex
  • Theophylline
  • Tizanidine
  • Ulipristal

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
  • Delavirdine
  • Efavirenz
  • Etravirine
  • Fosamprenavir
  • Fosaprepitant
  • Fosphenytoin
  • Ginseng
  • Griseofulvin
  • Ketoconazole
  • Lamotrigine
  • Levothyroxine
  • Licorice
  • Modafinil
  • Mycophenolate Mofetil
  • Mycophenolic Acid
  • Nelfinavir
  • Oxcarbazepine
  • Parecoxib
  • Phenobarbital
  • Phenytoin
  • 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 of This Medicine:

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 a 28-day 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-Dot®) two times a week (every 3 to 4 days) for the first 14 days of the 28-day cycle. Then, apply one CombiPatch® two times a week (every 3 to 4 days) for the next 14 days of the 28-day cycle. 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 While Using This Medicine:

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).

This medicine may cause serious types of allergic reactions, including anaphylaxis which can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, lightheadedness or dizziness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth with this medicine.

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 of This Medicine:

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
Bloating or swelling of the face, arms, hands, lower legs, or feet
heavy non-menstrual vaginal bleeding
itching of the vagina or genital area
pain during sexual intercourse
rapid weight gain
thick, white vaginal discharge with no odor or with a mild odor
tingling of the hands or feet
unusual weight gain or loss
Less common
Cough or hoarseness
fever or chills
lower back or side pain
painful or difficult urination
Incidence not known
Abdominal or stomach bloating or fullness
abdominal or stomach pain
blurred vision
change in vaginal discharge
clay-colored stools
clear or bloody discharge from the nipple
dark urine
diarrhea
dimpling of the breast skin
dizziness
gaseous abdominal or stomach pain
headache, severe and throbbing
hives
hoarseness
inverted nipple
irritation
itching
joint pain, stiffness or swelling
large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
loss of appetite
lump in the breast or under the arm
nausea and vomiting
nervousness
pain or feeling of pressure in the pelvis
persistent crusting or scaling of the nipple
pounding in the ears
rash
recurrent fever
redness of the skin
redness or swelling of the breast
severe cramping of the uterus
slow or fast heartbeat
sore on the skin of the breast that does not heal
swelling of the eyelids, face, lips, hands, or feet
tightness in the chest
troubled breathing or swallowing
unpleasant breath odor
unusual tiredness or weakness
vaginal bleeding
vomiting of blood
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
Acid or sour stomach
back pain
belching
body aches or pain
breast pain
burning, itching, redness, skin rash, swelling, or soreness at the application site
congestion
cramps
difficulty with moving
discouragement
dryness or soreness of the throat
excess air or gas in the stomach or intestines
feeling sad or empty
general feeling of discomfort or illness
headache
heartburn
heavy bleeding
increased clear or white vaginal discharge
indigestion
irritability
lack or loss of strength
loss of interest or pleasure
muscle aches and pains
muscle stiffness
pain during sexual intercourse
pain or tenderness around the eyes and cheekbones
passing gas
shivering
sneezing
stomach discomfort or upset
stuffy or runny nose
sweating
tender, swollen glands in the neck
thick, white vaginal discharge with no odor or with a mild odor
tiredness
trouble concentrating
trouble sleeping
Less common
Blemishes on the skin
difficulty having a bowel movement (stool)
longer or heavier menstrual periods
pimples
Incidence not known
Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
change in color of the treated skin
decreased interest in sexual intercourse
dizziness or lightheadedness
dull ache or feeling of pressure or heaviness in the legs
feeling of constant movement of self or surroundings
inability to have or keep an erection
increased in sexual ability, desire, drive, or performance
increased interest in sexual intercourse
itching skin near damaged veins
loss in sexual ability, desire, drive, or performance
sensation of spinning
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.


Last Updated: 9/15/2016
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