Estradiol and norethindrone (oral)

Estradiol and norethindrone (oral)

Estradiol and norethindrone (oral) Oral (tablet)

Estrogen plus progestogen therapy

Cardiovascular disease and probable dementia

The Women's Health Initiative (WHI) estrogen-progestin substudy reported an increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years) during 5.6 years of treatment with daily oral conjugated estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg), compared to placebo.

The WHI Memory Study (WHIMS) estrogen-progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women aged 65 years or older during 4 years of treatment with daily conjugated estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) compared to placebo. It is not known whether this finding applies to younger postmenopausal women.

Do not use estrogen-progestin therapy to prevent cardiovascular disease or dementia.

Breast cancer

The WHI estrogen plus progestogen substudy also showed an increased risk of invasive breast cancer.

In the estrogen plus progestin substudy of the WHI, only 0.625 mg CE and 2.5 mg MPA daily were examined. Therefore, the relevance of the WHI results regarding adverse cardiovascular events, dementia, and breast cancer to reducing CE plus other MPA doses, other routes of administration, or other estrogen plus progestin products is unknown. Without this data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss the benefits and risks of estrogen-progestogen therapy with your patient, taking her individual risk profile into account.

Prescribe estrogens with or without progestins at the lowest effective doses and for the shortest duration according to the treatment goals and risks for the individual woman.

Estrogen alone therapy

Endometrial cancer

A woman whose uterus freely takes estrogens is at increased risk of uterine cancer.

Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which can be a precursor to endometrial cancer.

To rule out malignancy in postmenopausal women with undiagnosed persistent or recurrent abnormal genital bleeding, appropriate diagnostic measures, including targeted or random endometrial sampling, should be undertaken when indicated. Cardiovascular disease and probable dementia

The WHI estrogen-alone substudy reported an increased risk of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogen (0.625 mg) alone compared to placebo.

The WHIMS ancillary study of estrogen alone reported an increased risk of developing probable dementia in postmenopausal women aged 65 years or older during 5.2 years of treatment with daily conjugated estrogen (0.625 mg) alone compared to placebo. It is not known whether this finding applies to younger postmenopausal women.

Do not use estrogen monotherapy to prevent cardiovascular disease or dementia.

In the estrogen-only substudy of the WHI, only 0.625 mg CE daily were examined. Therefore, the relevance of the WHI results on adverse cardiovascular events and dementia for lower doses of CE, other routes of administration, or other estrogen-only products is unknown. Without this data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss the benefits and risks of estrogen monotherapy with your patient, taking her individual risk profile into account.

Prescribe estrogens with or without progestins at the lowest effective doses and for the shortest duration according to the treatment goals and risks for the individual woman.

Used for estradiol and norethindrone

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

Before using estradiol and norethindrone

When deciding whether to use a medicine, the risks of taking the medicine must be weighed against the benefits it produces. This is a decision that you and your doctor will make. The following should be noted with this medicine:

Allergies

Tell your doctor if you have ever had an unusual or allergic reaction to this medicine or any other medicines. Also tell your doctor if you have other allergies, such as to foods, dyes, preservatives or animals. For over-the-counter products, read the label or package ingredients carefully.

Pediatrics

No appropriate studies have been conducted on the relationship between age and the effects of the combination of estradiol and norethindrone in children and adolescents. The use of a combination of estradiol and norethindrone is not indicated for use in children.

geriatrics

Related studies conducted to date have not demonstrated any geriatric-specific problems that would limit the benefit of the combination of estradiol and norethindrone in the geriatric population. However, older patients are at higher risk of breast cancer, stroke, or dementia and therefore caution may be warranted in patients receiving a combination of estradiol and norethindrone.

Breastfeeding

There are insufficient studies in women to determine the risk to infants when using this drug while breast-feeding. 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 can be used together, although interactions may occur. In these cases, your doctor may want to change the dose or other precautions may be necessary. If you are taking this medicine, it is particularly important that your doctor knows whether you are taking any of the medicines listed below. The following interactions were selected for their potential significance and are not necessarily exhaustive.

The use of this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or to change some of the other medications you are taking.

• Tranexamsäure

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

• Abametapir
• Amifampridin
• Amobarbital
• Amoxicillin
• Ampicillin
• Amprenavir
• Apalutamid
• Aprepitant
• Armodafinil
• Artemether
• Bacampicillin
• Belzutifan
• Betamethason
• Bexaroten
• Boceprevir
• Bosentan
• Bupropion
• Butabarbital
• Butalbital
• Carbamazepin
• Carbenicillin
• Cefaclor
• Cefadroxil
• Cefdinir
• Cefditoren
• Cefixim
• Cefpodoxim
• Cefprozil
• Ceftazidim
• Ceftibuten
• Cefuroxim
• Cenobamat
• Ceritinib
• Clobazam
• Cloxacillin
• Colesevelam
• Conivaptan
• Cyclacillin
• Cyclosporin
• Dabrafenib
• Darunavir
• Dexamethason
• Dicloxacillin
• Dipyron
• Donepezil
• Doxycyclin
• Efavirenz
• Elagolix
• Elvitegravir
• Encorafenib
• Enzalutamid
• Eslicarbazepinacetat
• Etravirin
• Fedratinib
• Felbamat
• Fexinidazol
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Grazoprevir
• Griseofulvin
• Guarkernmehl
• Indinavir
• Isotretinoin
• Itraconazol
• Ivosidenib
• Lesinurad
• Lixisenatid
• Lopinavir
• Lorlatinib
• Lumacaftor
• Mavacamten
• Mephobarbital
• Meropenem
• Methohexital
• Minocyclin
• Mitapivat
• Mitotan
• Mobocertinib
• Modafinil
• Mycophenolatmofetil
• Mycophenolsäure
• Nafcillin
• Nelfinavir
• Netupitant
• Nevirapin
• Octreotid
• Oxacillin
• Oxcarbazepin
• Oxytetracyclin
• Penicillin G
• Penicillin G Procain
• Penicillin V
• Pentobarbital
• Phenobarbital
• Phenylbutazon
• Phenytoin
• Pitolisant
• Pixantrone
• Prednisolon
• Prednison
• Primidon
• Rotklee
• Rifabutin
• Rifampin
• Rifapentin
• Rilpivirin
• Ritonavir
• Rufinamid
• Saquinavir
• Secobarbital
• Simeprevir
• Somatrogon-ghla
• Johanniskraut
• Sugammadex
• Sultamicillin
• Tazemetostat
• Telaprevir
• Telotristat Ethyl
• Tetracyclin
• Theophyllin
• Thiopental
• Thioridazin
• Ticarcillin
• Tigecyclin
• Tipranavir
• Tirzepatid
• Tizanidin
• Topiramat
• Troglitazon
• Ulipristal
• Valproinsäure
• Voxilaprevir

Using this medicine with any of the following medicines may result in an increased risk of certain side effects, but using both medicines 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 medicines.

• Amitriptylin
• Atazanavir
• Atorvastatin
• Clomipramin
• Diazepam
• Doxepin
• Ginseng
• Imipramin
• Lamotrigin
• Levothyroxin
• Lakritze
• Lorazepam
• Parecoxib
• Selegilin
• Tacrin
• Temazepam
• Tipranavir
• Triazolam
• Troleandomycin
• Valdecoxib
• Voriconazol
• Warfarin

Interactions with food/tobacco/alcohol

Certain medicines should not be taken during or near food or consumption of certain foods because interactions may occur. Consuming alcohol or tobacco with certain medications can also lead to interactions. The following interactions were selected for their potential significance and are not necessarily exhaustive.

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

• Koffein

Other medical problems

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

• Abnormale oder ungewöhnliche Vaginalblutungen oder
• Blutungsprobleme bzw
• Blutgerinnsel (z. B. tiefe Venenthrombose, Lungenembolie), aktiv oder in der Vorgeschichte oder
• Brustkrebs, bekannt oder vermutet, oder eine Vorgeschichte von oder
• Demenz bzw
• Herzinfarkt, Geschichte von oder
• Herz- oder Blutgefäßerkrankung oder
• Lebererkrankung bzw
• Protein C-, Protein S- oder Antithrombinmangel oder andere bekannte Blutgerinnungsstörungen oder
• Schlaganfall, Geschichte von oder
• Bekannte oder vermutete Tumoren (östrogenabhängig, einschließlich Gebärmutterkrebs): Sollte bei Patienten mit diesen Erkrankungen nicht angewendet werden.

• Asthma bzw
• Krebs, Geschichte von oder
• Diabetes bzw
• Ödeme (Flüssigkeitsansammlung oder Körperschwellung) oder
• Endometriose bzw
• Epilepsie (Anfälle) oder
• Gallenblasenerkrankung bzw
• Hereditäres Angioödem (Schwellung von Gesicht, Lippen, Zunge oder Rachen) oder
• Hyperkalzämie (hoher Kalziumspiegel im Blut) oder
• Hypokalzämie (niedriger Kalziumspiegel im Blut) oder
• Hypercholesterinämie (hoher Cholesterin- oder Fettgehalt im Blut) oder
• Hypertonie (Bluthochdruck) bzw
• Hypertriglyceridämie (hohe Triglyceride oder Fette im Blut) oder
• Hypothyreose (eine Unterfunktion der Schilddrüse) oder
• Gelbsucht während der Schwangerschaft oder aufgrund einer Hormontherapie in der Vergangenheit oder
• Nierenerkrankung bzw
• Lebertumoren bzw
• Migränekopfschmerz oder
• Fettleibigkeit bzw
• Porphyrie (ein Enzymproblem) oder
• Systemischer Lupus erythematodes (SLE) – Mit Vorsicht anwenden. Kann diese Bedingungen verschlimmern.

Proper use of estradiol and norethindrone

It is very important that you use this medicine exactly as your doctor has told you. Do not use more of it, do not use it more often or for longer than prescribed by your doctor. This can lead to unwanted side effects.

This medicine comes with a package 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 wheel.

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

Use:

• Um diesen Spender zu verwenden, drehen Sie zunächst die innere Scheibe, sodass der aktuelle Wochentag mit der Kunststofflasche übereinstimmt. Ziehen Sie die Plastiklasche nach oben und brechen Sie sie ab, wenn sie abreißt. Geben Sie die erste Tablette aus.
• Um die nächste Tablette (am nächsten Tag) herauszunehmen, drehen Sie die äußere transparente Skala um eine Stelle im Uhrzeigersinn, wie durch den Pfeil angezeigt.
• Der transparente Drehknopf lässt sich erst drehen, nachdem das Tablet in der Öffnung entnommen wurde. Dies wird Ihnen helfen, daran zu denken, jeden Tag eine Tablette einzunehmen.

dosage

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

The amount of medicine you take depends on the strength of the medicine. In addition, the number of doses you take each day, the time between doses, and how long you take the medicine depend on the medical problem for which you are using the medicine.

• Für orale Darreichungsform (Tabletten):
  • Bei mittelschweren bis starken Hitzewallungen:
    • Erwachsene: Eine Tablette einmal täglich. Jede Tablette enthält 1 Milligramm (mg) Östradiol und 0,5 mg Norethindron oder 0,5 mg Östradiol und 0,1 mg Norethindron.
    • Kinder – Die Verwendung wird nicht empfohlen.
  • Bei mittelschweren bis schweren Vaginalproblemen oder Trockenheit:
    • Erwachsene: Eine Tablette einmal täglich. Jede Tablette enthält 1 Milligramm (mg) Östradiol und 0,5 mg Norethindron.
    • Kinder – Die Verwendung wird nicht empfohlen.
  • Zur Vorbeugung von Osteoporose nach den Wechseljahren:
    • Erwachsene: Eine Tablette einmal täglich. Jede Tablette enthält 1 Milligramm (mg) Östradiol und 0,5 mg Norethindron oder 0,5 mg Östradiol und 0,1 mg Norethindron.
    • Kinder – Die Verwendung wird nicht empfohlen.

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 return to your regular dosing schedule. Do not double the dose.

storage

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

Keep away from children.

Do not keep medications that are outdated or no longer needed.

Ask your doctor how to throw away medicines you don't use.

Precautions when using estradiol and norethindrone

It is very important that your doctor checks your progress at regular visits to make sure this medicine is working properly and is not causing any unwanted effects. These visits can occur every 3 to 6 months. Unless your doctor tells you otherwise, blood or urine tests, a pelvic exam, a breast exam, and a mammogram (chest x-ray) may be needed to check for adverse effects. Be sure to keep all appointments.

A woman is unlikely to become pregnant after menopause. However, you should know that taking this medicine during pregnancy may harm your unborn baby. If you think you have become pregnant while using this medicine, tell your doctor immediately.

Using this medicine may increase your risk of blood clots, stroke, or heart attack. This risk may remain even if you stop using the medicine. Your risk of these serious problems is even greater if you have high blood pressure, high blood cholesterol, diabetes, are overweight or smoke cigarettes. Contact your doctor immediately if you experience chest pain, confusion, difficulty speaking, double vision, headache, inability to move arms, legs, or facial muscles, or inability to speak.

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

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

This medicine may increase your risk of gallbladder disease. Consult your doctor if you experience stomach pain, nausea and vomiting.

Consult your doctor immediately if you experience a severe headache or sudden loss of vision or other vision change while using this medication. Your doctor may want you to have your eyes examined by an ophthalmologist.

Before you have surgery (such as surgery that requires prolonged inactivity) or emergency treatment, tell your doctor or dentist who is treating you that you are using this medicine. 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 any other medicines unless you have discussed this with your doctor. This includes both prescription and non-prescription (over-the-counter [OTC]) medicines and herbal (e.g. St. John's wort) or vitamin supplements.

Side effects of estradiol and norethindrone

In addition to the necessary effects, a medicine may also have some undesirable effects. Although not all of these side effects may occur, medical attention may be required if they occur.

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

More common

• Körperschmerzen oder Schmerzen
• Schüttelfrost oder Fieber
• Erkältungs- oder grippeähnliche Symptome
• Schwierigkeiten beim Atmen
• Kopfschmerzen
• Juckreiz der Vagina oder des Genitalbereichs
• Nicht-menstruelle vaginale Blutung
• Schmerzen beim Geschlechtsverkehr
• dicker, weißer Vaginalausfluss ohne Geruch oder mit mildem Geruch
• ungewöhnliche Müdigkeit oder Schwäche

Incident not known

• Blasenbildung, Abschälen oder Lockerung der Haut
• Brustspannen
• Veränderung des Vaginalausflusses
• Veränderung der Vision
• Brustschmerzen, Unwohlsein oder Engegefühl
• lehmfarbener Stuhlgang
• klarer oder blutiger Ausfluss aus der Brustwarze
• Verwirrung
• dunkler Urin
• Schwierigkeiten beim Sprechen
• Schluckbeschwerden
• Schwindel oder Benommenheit
• Doppeltsehen
• Ohnmacht
• schneller Herzschlag
• Unfähigkeit, Arme, Beine oder Gesichtsmuskeln zu bewegen
• Unfähigkeit zu sprechen
• Gelenk- oder Muskelschmerzen
• Appetitverlust
• Knoten in der Brust oder unter dem Arm
• Übelkeit und Erbrechen
• lautes Atmen
• Schmerzen in den Knöcheln oder Knien
• Schmerzen oder Beschwerden in Armen, Kiefer, Rücken oder Nacken
• Schmerzen oder Druckgefühl im Becken
• Schmerzen, Rötung oder Schwellung im Arm oder Bein
• schmerzhafte, rote Knoten unter der Haut, meist an den Beinen
• Schmerzen im Magen, in der Seite oder im Unterleib, die möglicherweise in den Rücken ausstrahlen
• Probleme mit dem Gedächtnis oder der Sprache
• Schwellungen oder Schwellungen der Augenlider oder um die Augen, das Gesicht, die Lippen oder die Zunge
• rote, gereizte Augen
• Rötung oder Schwellung der Brust
• Hautausschlag, Nesselsucht oder Juckreiz
• Wunden, Geschwüre oder weiße Flecken im Mund oder auf den Lippen
• Magenschmerzen
• Schwitzen
• Atembeschwerden
• Probleme beim Erkennen von Objekten
• Schwierigkeiten beim Denken und Planen
• Schwierigkeiten beim Gehen
• unerwarteter oder übermäßiger Milchfluss aus den Brüsten

Some side effects may occur that usually do not require medical attention. These side effects may disappear during treatment as your body gets used to the medicine. Your doctor may also be able to give you ways to prevent or reduce some of these side effects. If any of the following side effects persist or are bothersome, or if you have any questions, contact your doctor:

More common

• Rückenschmerzen
• Krämpfe
• Weinen
• Euphorie
• mentale Depression
• Paranoia
• schnell reagieren oder emotional überreagieren
• schnell wechselnde Stimmungen
• Schlafstörungen
• Schwäche
• Gewichtszunahme

Incident not known

• Appetitveränderungen
• Veränderungen der sexuellen Fähigkeiten, des Verlangens, des Antriebs oder der Leistung
• überschüssige Luft oder Gas im Magen oder Darm
• vermehrter Haarwuchs, insbesondere im Gesicht
• fleckige braune oder dunkelbraune Verfärbung der Haut
• Probleme beim Tragen von Kontaktlinsen

Some patients may also experience other side effects not listed. If you notice other side effects, contact your doctor.

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

Commonly used brand names

In the USA

• Activella
• Lopreeza
• Mimvey

Available dosage forms:

• Tablette

Therapeutic class: estrogen/progestogen combination

Pharmacological class: Estrogen

More information