Combipatch (Transdermal)

Estradiol and norethindrone skin patch is used to treat moderate to severe hot flashes and other menopause symptoms. It is also used to address changes in and around the vagina (such as dryness, itching, and burning) due to low estrogen levels or menopause. Additionally, this medicine can be used to treat certain conditions in women before menopause if their ovaries do not produce enough estrogens naturally.

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

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

It is very important for your doctor to check your progress at regular visits to ensure this medicine is working correctly and does not cause unwanted effects. You may need a pelvic exam, breast exam, and mammogram (breast x-ray) to check for unwanted effects, unless your doctor advises otherwise. Be sure to keep all appointments.

It is unlikely for a postmenopausal woman to become pregnant. However, using this medicine while you are pregnant could harm your unborn baby. If you think you may be pregnant while using the medicine, tell your doctor immediately.

Using this medicine may increase your risk of blood clots, strokes, or heart attacks. This risk may continue even after you stop using the medicine. Your risk for these serious issues is higher if you have high blood pressure, high cholesterol, diabetes, are overweight, or smoke cigarettes. Contact your doctor right away if you have chest pain, confusion, trouble speaking, double vision, headaches, or difficulty moving your arms, legs, or facial muscles, or if you cannot speak.

Using this medicine may raise your risk of endometrial cancer, breast cancer, or uterine cancer. Discuss this risk with your doctor. Check with your doctor immediately if you experience abnormal vaginal bleeding.

Do not use this medicine if you have had a hysterectomy (removal of the uterus).

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

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

This medicine may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and needs 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 while using this medicine.

Make sure any doctor or dentist treating you knows that you are using this medicine. You may need to stop using this medicine before having surgery or if you need to stay in bed for a long time. This medicine may affect the results of some medical tests.

Do not eat grapefruit or drink grapefruit juice while using this medicine. Grapefruit and grapefruit juice may change how much of this medicine is absorbed in your body.

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

In deciding to use a medicine, you need to consider the risks of taking the medicine against the benefits it will provide. This is a choice you and your doctor will make together. For this medicine, you should think about the following:

Allergies

Inform your doctor if you have ever had any unusual or allergic reactions to this medicine or any other medicines. Also, let your healthcare professional know 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

CombiPatch® is not intended for use in children.

Geriatric

While appropriate studies on the effects of CombiPatch® in older adults have not been conducted, no specific problems for elderly patients have been noted so far. However, older patients are more likely to have breast cancer, strokes, or dementia, which may require caution when using this medicine.

Breast Feeding

There are no adequate studies in women to determine the risk to infants when using this medication while breastfeeding. Consider the potential benefits and risks before taking this medication during breastfeeding.

Interactions with Medicines

Some medicines should never be used together. In other cases, two different medicines can be used together even if there might be an interaction. In these situations, your doctor may adjust the dose, or take other precautions. It is very important that your healthcare professional knows if you are taking any of the medicines listed below. The following interactions have been chosen based on their potential importance and may not include all possible interactions.

Using this medicine with any of the following medicines is not recommended. Your doctor may choose not to prescribe this medication or change some of your other medicines.

• Tranexamic Acid

Using this medicine with any of the following medicines is usually not recommended, but may be necessary in some cases. If both medicines are prescribed, your doctor may adjust the dose or frequency for one or both medicines.

• Abametapir
• Amifampridine
• Amobarbital
• Amoxicillin
• Ampicillin
• Amprenavir
• Apalutamide
• Aprepitant
• Armodafinil
• Artemether
• Bacampicillin
• Belzutifan
• Betamethasone
• Bexarotene
• Boceprevir
• Bosentan
• Bupropion
• Butabarbital
• Butalbital
• Carbamazepine
• Carbenicillin
• Cefaclor
• Cefadroxil
• Cefdinir
• Cefditoren
• Cefixime
• Cefpodoxime
• Cefprozil
• Ceftazidime
• Ceftibuten
• Cefuroxime
• Cenobamate
• Ceritinib
• Clobazam
• Cloxacillin
• Colesevelam
• Conivaptan
• Cyclacillin
• Cyclosporine
• Dabrafenib
• Darunavir
• Dexamethasone
• Dicloxacillin
• Dipyrone
• Donepezil
• Doxycycline
• Efavirenz
• Elagolix
• Elvitegravir
• Encorafenib
• Enzalutamide
• Eslicarbazepine Acetate
• Etravirine
• Fedratinib
• Felbamate
• Fexinidazole
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Grazoprevir
• Griseofulvin
• Guar Gum
• Indinavir
• Isotretinoin
• Itraconazole
• Ivosidenib
• Lesinurad
• Lixisenatide
• Lopinavir
• Lorlatinib
• Lumacaftor
• Mavacamten
• Mephobarbital
• Meropenem
• Methohexital
• Minocycline
• Mitapivat
• Mitotane
• Mobocertinib
• Modafinil
• Mycophenolate Mofetil
• Mycophenolic Acid
• Nafcillin
• Nelfinavir
• Netupitant
• Nevirapine
• Octreotide
• Oxacillin
• Oxcarbazepine
• Oxytetracycline
• Penicillin G
• Penicillin G Procaine
• Penicillin V
• Pentobarbital
• Phenobarbital
• Phenylbutazone
• Phenytoin
• Pitolisant
• Pixantrone
• Prednisolone
• Prednisone
• Primidone
• Red Clover
• Rifabutin
• Rifampin
• Rifapentine
• Rilpivirine
• Ritonavir
• Rufinamide
• Saquinavir
• Secobarbital
• Simeprevir
• Somatrogon-ghla
• St John's Wort
• Sugammadex
• Sultamicillin
• Tazemetostat
• Telaprevir
• Telotristat Ethyl
• Tetracycline
• Theophylline
• Thiopental
• Thioridazine
• Ticarcillin
• Tigecycline
• Tipranavir
• Tirzepatide
• Tizanidine
• Topiramate
• Troglitazone
• Ulipristal
• Valproic Acid
• Voxilaprevir

Using this medicine with any of the following medicines may result in a higher risk of certain side effects, but using both might be the best treatment for you. If both medicines are prescribed, your doctor may adjust the dose or frequency for one or both medicines.

• Amitriptyline
• Atazanavir
• Atorvastatin
• Clomipramine
• Diazepam
• Doxepin
• Ginseng
• Imipramine
• Lamotrigine
• Levothyroxine
• Licorice
• Lorazepam
• Parecoxib
• Selegiline
• Tacrine
• Temazepam
• Tipranavir
• Triazolam
• Troleandomycin
• Valdecoxib
• Voriconazole
• Warfarin

Interactions with Food/Tobacco/Alcohol

Some medicines should not be taken around the time of eating food or specific foods due to potential interactions. Using alcohol or tobacco with certain medicines may also lead to interactions. The following interactions have been selected based on their potential significance and may not include all possible interactions.

Using this medicine with any of the following may increase the risk of certain side effects, but it may be unavoidable in some cases. If used together, your doctor may adjust the dose or frequency for this medicine or provide special instructions about using food, alcohol, or tobacco.

• Caffeine

Other Medical Problems

Having other medical issues may affect how this medicine works. Be sure to inform your doctor if you have any other medical problems, especially:

• Abnormal or unusual vaginal bleeding or
• Blood clots (e.g., deep vein thrombosis, pulmonary embolism), active or a 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 worsen these conditions.

• 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 the risk for more serious side effects.

Along with its needed effects, a medicine may cause some unwanted effects. Not all of these side effects may happen, but if they do, they might require medical attention.

Check with your doctor right away 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
• Severe and throbbing headache
• 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. Your health care professional may also tell you how to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue, 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 sexual ability, desire, drive, or performance
• Increased interest in sexual intercourse
• Itching skin near damaged veins
• Loss of 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.

In the U.S.

• Combipatch

In Canada

• Estalis
• Estalis-Sequi

Available Dosage Forms:

• Patch, Extended Release

Therapeutic Class: Estrogen/Progestin Combination

Pharmacologic Class: Estrogen

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.