Lopreeza (Oral)

Estradiol and norethindrone combination is used to treat moderate to severe symptoms of menopause (for example, feelings of warmth in the face, neck, and chest, sudden strong feelings of heat and sweating [hot flashes], and vaginal problems). This medicine is also used to prevent osteoporosis after 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 properly and not causing unwanted effects. These visits may be every 3 to 6 months. Blood or urine tests, 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. However, 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 if you 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 muscles, or an inability to speak.

Using this medicine for a long time may increase your risk of endometrial cancer, breast cancer, or uterine cancer. Talk with your doctor about this risk. Do not use this medicine if you have had your uterus (womb) removed (hysterectomy). Check with your doctor immediately if you experience abnormal vaginal bleeding.

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

This medicine may increase your risk of having gallbladder disease. Check with your doctor if you start to have stomach pains, nausea, and vomiting.

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

Tell your doctor or dentist treating you that you are using this medicine before any kind of surgery (for example, surgery that will require inactivity for a long time) or emergency treatment. Your doctor will decide whether you should continue using this medicine. This medicine may also affect the results of certain medical tests.

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 (for example, St. John's wort) or vitamin supplements.

In deciding to use a medicine, you and your doctor need to weigh the risks of taking it against the benefits it may provide. Consider the following points for this medicine:

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 other allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, carefully read the label or package ingredients.

Pediatric

There have not been appropriate studies on how estradiol and norethindrone combination affects children. This medicine is not meant for use in children.

Geriatric

Studies have not shown any specific problems in older adults that would limit the use of estradiol and norethindrone combination. However, older patients are more likely to have breast cancer, strokes, or dementia, which may require caution when using estradiol and norethindrone combination.

Breast Feeding

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

Interactions with Medicines

Some medicines should never be used together, while others may be used together even if an interaction could happen. In these cases, your doctor may adjust the dose or take other precautions. It is very important for your healthcare professional to know if you are taking any of the medicines listed below. The following interactions are based on their potential significance and are not a complete list.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medicine 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 it may be necessary in some cases. If both medicines are prescribed together, your doctor may adjust the dose or how often you use one or both.

• 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 increase the risk of certain side effects, but using both may be necessary for your treatment. If both medicines are prescribed together, your doctor may adjust the dose or how often you use one or both.

• 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 at or around mealtime, as certain food interactions may occur. Using alcohol or tobacco with some medicines may also cause interactions. The following interactions are based on their potential significance and are not a complete list.

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

• Caffeine

Other Medical Problems

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

• Abnormal or unusual vaginal bleeding or
• Bleeding problems or
• Blood clots (e.g., deep vein thrombosis, pulmonary embolism), either current or past or
• Breast cancer, known or suspected, or a history of or
• Dementia or
• Heart attack, history of or
• Heart or blood vessel disease or
• Liver disease or
• Protein C, protein S, or antithrombin deficiency, or other known blood clotting disorders or
• Stroke, history of or
• Tumors (estrogen-dependent, including cancer of the uterus), known or suspected—Should not be used in patients with these conditions.

• Asthma or
• Cancer, history of 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
• Hypercholesterolemia (high cholesterol or fats in the blood) or
• Hypertension (high blood pressure) or
• Hypertriglyceridemia (high triglycerides or fats in the blood) or
• Hypothyroidism (an underactive thyroid) or
• Jaundice during pregnancy or from previous hormonal therapy or
• Kidney disease or
• Liver tumors or
• Migraine headache or
• Obesity or
• Porphyria (an enzyme problem) or
• Systemic lupus erythematosus (SLE)—Use with caution. May worsen these conditions.

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

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

More common

• Body aches or pain
• chills or fever
• cold or flu-like symptoms
• difficulty breathing
• headache
• itching of the vagina or genital area
• non-menstrual vaginal bleeding
• pain during sexual intercourse
• thick, white vaginal discharge with no odor or with a mild odor
• unusual tiredness or weakness

Incidence not known

• Blistering, peeling, or loosening of the skin
• breast tenderness
• change in vaginal discharge
• change in vision
• chest pain, discomfort, or tightness
• clay-colored stools
• clear or bloody discharge from the nipple
• confusion
• dark urine
• difficulty speaking
• difficulty swallowing
• dizziness or lightheadedness
• double vision
• fainting
• fast heartbeat
• inability to move the arms, legs, or facial muscles
• inability to speak
• joint or muscle pain
• loss of appetite
• lump in the breast or under the arm
• nausea and vomiting
• noisy breathing
• pain in the ankles or knees
• pain or discomfort in the arms, jaw, back, or neck
• pain or feeling of pressure in the pelvis
• pain, redness, or swelling in the arm or leg
• painful, red lumps under the skin, mostly on the legs
• pains in the stomach, side, or abdomen, possibly radiating to the back
• problems with memory or speech
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red, irritated eyes
• redness or swelling of the breast
• skin rash, hives, or itching
• sores, ulcers, or white spots in the mouth or on the lips
• stomach pain
• sweating
• trouble breathing
• trouble recognizing objects
• trouble thinking and planning
• trouble walking
• unexpected or excess milk flow from the breasts

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

• Back pain
• cramps
• crying
• euphoria
• mental depression
• paranoia
• quick to react or overreact emotionally
• rapidly changing moods
• trouble sleeping
• weakness
• weight gain

Incidence not known

• Changes in appetite
• changes in sexual ability, desire, drive, or performance
• excess air or gas in the stomach or intestines
• increased hair growth, especially on the face
• patchy brown or dark brown discoloration of the skin
• trouble wearing contact lenses

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.

• Activella
• Lopreeza
• Mimvey

Available Dosage Forms:

• Tablet

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.

This medicine sometimes comes in a special dispenser pack with a calendar reminder dial.

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.

To use:

• To use this dispenser, first turn the inner disc so the current day of the week is lined up with the plastic tab. Pull the plastic tab up and break if off. Tip out the first tablet.
• To get the next tablet out (on the next day), turn the outer transparent dial one space clockwise as shown by the arrow.
• The transparent dial can be turned only after the tablet in the opening has been removed. This will help you to remember to take one tablet every day.

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 oral dosage form (tablets): For moderate to severe hot flashes: Adults—One tablet once a day. Each tablet contains 1 milligram (mg) of estradiol and 0.5 mg of norethindrone or 0.5 mg of estradiol and 0.1 mg of norethindrone. Children—Use is not recommended. For moderate to severe vaginal problems or dryness: Adults—One tablet once a day. Each tablet contains 1 milligram (mg) of estradiol and 0.5 mg of norethindrone. Children—Use is not recommended. For prevention of osteoporosis after menopause: Adults—One tablet once a day. Each tablet contains 1 milligram (mg) of estradiol and 0.5 mg of norethindrone, or 0.5 mg of estradiol and 0.1 mg of norethindrone. Children—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

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

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.