Prospecto:information for the patient

DUAVIVE 0.45mg/20mg modified-release tablets

conjugated estrogens/bazedoxifene

Read this prospectus carefully before starting to take this medication, as it contains important information for you.

• Keep this prospectus,as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed to you alone,and you should not give it to otherswho may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist,even if they are not listed in this prospectus.See section4.

DUAVIVE is a medication that contains two active ingredients called conjugated estrogens and bazedoxifene.Conjugated estrogens are a medication that belongs to a group called hormone replacement therapy (HRT).Bazedoxifene belongs to a group of non-hormonal medications called selective estrogen receptor modulators (SERMs).

DUAVIVE is used in postmenopausal women who still have a uterus (womb) and have not had a period in the last 12 months.

DUAVIVE is used for:

Relief of symptoms that appear after menopause

During menopause, there is a decrease in the amount of estrogens produced by the woman's body.This decrease can cause symptoms such as hot flashes in the face, neck, and chest («hot flashes»).DUAVIVE relieves these symptoms after menopause.Only your doctor will prescribe this medication if the symptoms are a significant obstacle in your daily life and if the doctor determines that other types of HRT are not suitable for you.

Medical History and Regular Check-Ups

The use of DUAVIVE involves risks that should be taken into account when deciding whether to start taking it or continue its administration.

There is no experience in the treatment of DUAVIVE in women with premature menopause (caused by ovarian insufficiency or surgical intervention).

Before starting to take this medication, your doctor will ask you about your personal and family medical history.It may be decided to perform a physical examination.In case necessary or if you have a specific concern, it may include a mammography and/or internal examination.Inform your doctor if you have any disease or medical problem.

Once the treatment with this medication is initiated, you must visit your doctor for regular check-ups (at least once a year).During these check-ups, discuss with your doctor the benefits and risks of continuing with DUAVIVE.It is recommended:

• to undergo regular diagnostic tests for breast diseases and cervical smears, as recommended by your doctor,
• to perform frequent breast examinations to detect possible changes, such as dimples in the skin, changes in the nipples, or visible or palpable nodules.

Do Not Take DUAVIVE

• If you are allergic to conjugated estrogens, bazedoxifene, or any of the other components of this medication (including those in section 6).
• If you have or have had breast cancer or if there are suspicions that you have it.
• If you have or have had any type of cancer sensitive to estrogens, such as endometrial cancer or if there are suspicions that you have it.
• If you have recently experienced vaginal bleeding of unknown cause.
• If you have an excessive thickening of the uterine mucosa (endometrial hyperplasia) that is not being treated.
• If you have or have had any type of blood clot in a vein (thrombosis), for example, in the legs (deep vein thrombosis), lungs (pulmonary embolism), or eyes (retinal vein thrombosis).
• If you have any coagulation disorder of the blood (such as protein C deficiency, protein S deficiency, or antithrombin deficiency).
• If you have or have had any disease caused by the presence of blood clots in the arteries, such as heart attack, stroke, or angina.
• If you have or have had any liver disease and your liver function tests have not returned to normal values.
• If you are pregnant or could still be pregnant, or are breastfeeding.
• If you have a rare blood disorder called porphyria, which is inherited.

If you have doubts about any of the above points,consult your doctorbefore taking this medication.

If any of the above diseases appear for the first time while taking this medication, stop taking it immediately and consult your doctor immediately.

Warnings and Precautions

Consult your doctor before starting to take this medication if you have ever had any of the following problems, as they may recur or worsen during treatment with DUAVIVE.In case affirmative, you must visit your doctor more frequently for check-ups:

• uterine fibroids
• growth of the uterine mucosa outside the uterus (endometriosis) or history of excessive growth of the uterine mucosa (endometrial hyperplasia)
• an increased risk of blood clots (see "Blood clots in a vein [thrombosis]")
• an increased risk of developing estrogen-sensitive cancer (such as having a mother, sister, or grandmother who has had breast cancer)
• high blood pressure
• liver alteration, such as a benign liver tumor
• diabetes
• gallstones
• migraine or severe headaches
• a rare autoimmune disease that affects numerous organs in the body (systemic lupus erythematosus, SLE)
• seizures (epilepsy)
• asthma
• a disease that affects the eardrum and hearing (otosclerosis)
• high levels of fat in the blood (triglycerides)
• fluid retention caused by cardiac or renal problems

Stop Taking DUAVIVE and Consult a Doctor Immediately

If you notice any of the following conditions:

• any of the diseases mentioned in the "Do Not Take DUAVIVE" section
• yellowing of the skin or white part of the eyes (jaundice),which may be signs of liver disease
• a significant increase in blood pressure (symptoms may include headache, fatigue, dizziness)
• pseudomigraine headaches that appear for the first time
• if you become pregnant
• if you notice signs of a blood clot, such as painful and swollen legs, sudden chest pain, or difficulty breathing.For more information, see "Blood clots in a vein (thrombosis)"

DUAVIVE and Cancer

Endometrial Hyperplasia and Endometrial Cancer

This medication contains two active principles, conjugated estrogens, and bazedoxifene, and is used to treat women with a uterus.

When you take DUAVIVE, do not take other estrogens, as this may increase the risk of endometrial hyperplasia.

If you experience unexpected vaginal bleeding,contact your doctor as soon as possible.

Breast Cancer

The data show that the risk of breast cancer increases with the administration of hormone replacement therapy (HRT) based solely on estrogens. The increase in risk depends on the duration of HRT and becomes apparent after 3 years of use. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or more if HRT has been used for more than 5 years.

The effect of DUAVIVE on the risk of breast cancer may be in the same range as with combined HRT.

Perform Regular MammogramsConsult your doctor as soon as possibleif you notice any changes, such as:

• dimples in the skin
• changes in the nipples
• visible or palpable nodules

Ovarian Cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with estrogens alone or in combination with progestogens has been associated with a slightly higher risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women between 50 and 54 years of age who do not follow HRT, there are approximately 2 cases of ovarian cancer per 2000 women over a 5-year period. In women treated with HRT for 5 years, there are approximately 3 cases per 2000 patients (i.e., approximately 1 additional case). Consult your doctor if you have any doubts.

The effect of DUAVIVE on the risk of ovarian cancer is unknown.

DUAVIVE and the Heart or Circulation

Blood Clots in a Vein (Thrombosis)

DUAVIVE may increase the risk of blood clots.

Monotherapy (treatment with a single medication) with estrogens or bazedoxifene increases the risk of blood clots in veins (also known as deep vein thrombosis or DVT), especially during the first year of treatment with these medications.

Blood clots can be serious, and if one dislodges and travels to the lungs, it can cause chest pain, difficulty breathing, collapse, or even death.

Since the likelihood of a blood clot forming in a vein increases with age and in the following cases, inform your doctor immediately:

• if you are unable to walk for a long time due to a major surgery, injury, or illness (see also section 3 if you need to undergo surgery)
• if you have severe obesity (BMI > 30 kg/m2)
• if you have any coagulation disorder of the blood that requires long-term treatment with medications used to prevent blood clots
• if a close relative has or has had a blood clot in the leg, lung, or other organ
• if you have systemic lupus erythematosus (SLE)
• if you have cancer

If you are in any of the above cases, consult your doctor before starting to take this medication.

Cardiac Disease (Heart Attack)

There is no indication that HRT prevents heart attacks.The data from controlled randomized trials showed that there was no increase in the risk of coronary artery disease in women who had undergone hysterectomy (women who had their uterus removed) and were taking estrogens as monotherapy.

Stroke

The risk of stroke is approximately 1.5 times higher in women treated with HRT than in women who do not take HRT. The number of additional stroke cases resulting from HRT will increase with age.

For women in their fifth decade of life who do not take HRT, approximately 8 out of 1,000 are expected to experience a stroke over a 5-year period. In women in their fifth decade of life who take HRT, there will be approximately 11 cases per 1,000 women treated (i.e., approximately 3 additional cases).

The effect of DUAVIVE on the risk of stroke may be in the same range as with combined HRT.

Other factors that may increase the risk of stroke include:

• age
• high blood pressure
• smoking
• excessive alcohol consumption
• irregular heartbeat

If you are undergoing surgery

If you are undergoing surgery, inform your doctor that you are taking DUAVIVE.You may need to stop taking DUAVIVE approximately 4 to 6 weeks before surgery to reduce the risk of blood clots (see "Blood clots in a vein").Ask your doctor when you can start taking this medication again.

In case of doubt, consult your doctor before taking this medication.

Other Diseases

If you have any of the following diseases, your doctor should monitor you:

• kidney problems
• high levels of fat in the blood (triglycerides)
• liver problems
• asthma
• seizures (epilepsy)
• migraine
• systemic lupus erythematosus (SLE - a rare autoimmune disease that can affect numerous organs in the body)
• fluid retention

Hormone replacement therapy does not prevent memory loss.Some data show an increased risk of memory loss in women who start hormone replacement therapy after the age of 65. Consult your doctor.

Children and Adolescents

This medication should not be used in children and adolescents under 18 years of age.

DUAVIVE with Other Medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Some medications may interfere with the effect of DUAVIVE, causing irregular bleeding. This applies to the following medications:

• Medications for the treatment of epilepsy (such as phenobarbital, phenytoin, and carbamazepine)
• Medications for the treatment of tuberculosis (such as rifampicin and rifabutin)
• Medications for the treatment of HIV infection (such as nevirapine, efavirenz, ritonavir, and nelfinavir)
• Herbal remedies containing St. John's Wort (Hypericum perforatum)

DUAVIVE may affect the way other medications work:

• A medication for the treatment of epilepsy (lamotrigine),which may increase the frequency of seizures

Pregnancy and Breastfeeding

This medication is only intended for postmenopausal women.Do not take this medication if you are pregnant or think you may be pregnant.Do not take this medication if you are breastfeeding.

Driving and Using Machines

DUAVIVE has a mild effect on the ability to drive or use machines.

If you experience drowsiness after taking this medication, you should avoid driving and operating machines.

There have been reports of vision problems, such as blurred vision, associated with the use of bazedoxifene, one of the components of this medication.If this occurs, you should avoid driving and operating machines until your doctor tells you it is safe to do so.

DUAVIVE contains lactose, sucrose, liquid maltitol, glucose, and sorbitol

If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

This medication contains 0.0088 mg of sorbitol in each tablet.

Your doctor will try to prescribe the lowest dose necessary to treat your symptom, for the shortest period possible. Consult your doctor if you think the prescribed dose is excessive or insufficient.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

The recommended dose is one tablet once a day.

The tablet should be swallowed whole with a glass of water.

You can take the tablet at any time of the day, with or without food; however, it is recommended to take the tablet at the same time every day, as this will help you remember to take your medication.

You should continue taking this medication for the time your doctor indicates. For it to be effective, this medication must be taken every day as prescribed.

If you take more DUAVIVE than you should

Call your doctor or pharmacist.

If you take too many tablets, you may experience nausea or vomiting. You may feel breast tenderness upon palpation, dizziness, abdominal pain, numbness/fatigue or experience vaginal bleeding for a short period.

If you forget to take DUAVIVE

If you forget to take a tablet, take it as soon as you remember. However, if it is almost time to take the next tablet, skip the missed tablet and take only the next one due. Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with DUAVIVE

If you decide to stop taking this medication before completing the prescribed treatment cycle, speak with your doctor first.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Stop treatment with DUAVIVE and consult a doctor immediately if you experience any of the following serious side effects:

Rare:may affect 1 person in every 100

• If you start experiencing pseudomigraine headaches or intense headaches.

Uncommon:may affect up to 1 person in every 1,000

• Signs of blood clots, such as painful and swollen legs, sudden chest pain or difficulty breathing.
• Signs of blood clots in the eye (retinal vein), such as vision loss in one eye, including loss of vision, eye pain, and swelling, especially if sudden.
• Severe allergic reaction - symptoms may include sudden hissing sound while breathing, chest pain or tightness, swollen eyelids, face, lips, mouth, tongue, or throat, difficulty breathing, and collapse.
• Swelling of the eyes, nose, lips, mouth, tongue, or throat, difficulty breathing, intense dizziness or fainting, skin rash (symptoms of angioedema).
• Symptoms of pancreatitis, which may include severe upper abdominal pain that can extend to the back, accompanied by abdominal swelling, fever, nausea, and vomiting.
• Sudden onset of abdominal pain and bright red and shiny stools with or without diarrhea, due to a sudden blockage of an artery that supplies the intestines (ischemic colitis).
• Heart attack - symptoms usually include pain, including chest pain that extends to the jaw, neck, and upper arm.In addition to pain, you may feel sweaty, tired, nauseous, and experience difficulty breathing and loss of consciousness.

Very rare:may affect up to 1 person in every 10,000

• Severe elevation of blood pressure (symptoms may include headache, fatigue, dizziness).
• Erythema multiforme:symptoms may include skin rash with red and pink spots, especially on the palms of the hands or soles of the feet, which may blister.You may also have ulcers in the mouth, eyes, or genitals, and fever.

Frequency not known:cannot be estimated from available data

• Other eye problems (seeing flashes or sparks of light, narrowing of the visual field, and swelling of the eye or eyelid).

Other side effects

Very common:may affect more than 1 person in every 10

• Abdominal pain (stomach pain).

Common:may affect up to 1 person in every 10

• Muscle spasms (including leg cramps).
• Constipation.
• Dyspepsia.
• Nausea.
• Candidiasis (vaginal infection by fungi).
• Increased triglyceride levels (fatty substances in the blood).

Uncommon:may affect up to 1 person in every 100

• Gallbladder disease (e.g., gallstones, inflammation of the gallbladder (cholecystitis)).

The following side effects have been observed with the use of conjugated estrogens and/or bazedoxifene (the active ingredients of this medicine) in monotherapy, and may also occur with this medicine.

Very common:may affect more than 1 person in every 10

• Hot flashes.
• Muscle cramps.
• Visible swelling of the face, hands, legs, feet, or ankles (peripheral edema).

Common:may affect up to 1 person in every 10

• Mammary pain, breast tenderness to palpation, breast inflammation.
• Nipple discharge.
• Joint pain.
• Hair loss.
• Weight changes (increase or decrease).
• Increased liver enzymes (detected in routine liver function tests).
• Dry mouth.
• Numbness.
• Hives (urticaria).
• Rash.
• Itching.

Uncommon:may affect up to 1 person in every 100

• Vaginal inflammation.
• Vaginal discharge.
• Cervical erosion detected in a medical examination.
• Deep vein thrombosis.
• Pulmonary embolism.
• Retinal vein thrombosis in the back of the eye, which may cause vision loss.
• Nausea (feeling unwell).
• Headache.
• Migraine.
• Dizziness.
• Mood changes.
• Nervousness.
• Depression.
• Memory loss (dementia).
• Changes in sexual appetite (increase or decrease).
• Change in skin color of the face or other parts of the body.
• Increased hair growth.
• Difficulty wearing contact lenses.

Rare:may affect up to 1 person in every 1,000

• Pelvic pain.
• Changes in breast tissue.
• Vomiting.
• Irritability.
• Effects on the way blood sugar levels are controlled, including increased blood glucose levels.
• Worsening of asthma.
• Worsening of epilepsy (seizures).
• Benign meningioma growth, a non-cancerous tumor of the membranes surrounding the brain or spinal cord.

Very rare:may affect up to 1 person in every 10,000

• Red and painful skin nodules.
• Worsening of chorea (a neurological disorder characterized by involuntary spasmodic movements of the body).
• Increased size of liver hemangiomas, a benign (non-cancerous) liver tumor.
• Low calcium levels in the blood (hypocalcemia); often there will be no symptoms indicating low calcium, but in severe hypocalcemia you may feel tired, usually unwell, depressed, and experience dehydration.These symptoms may be accompanied by bone pain and abdominal pain.You may also form kidney stones and experience severe pain in the middle back region (renal colic).

• Worsening of porphyria, a rare blood disorder that is inherited (hereditary).

Frequency not known:cannot be estimated from available data

• Palpitations (perception of heartbeats).

• Dry eye, eye pain, decreased visual acuity, visual disturbances, blepharospasm (abnormal and involuntary blinking of the eyelids).

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist,even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and on the blister pack after CAD.The expiration date is the last day of the month indicated.

Do not store above 25°C.

Store in the original packaging to protect it from moisture.

Once the blister pack bag is opened, use within 60days.

Medicines should not be disposed of through drains or in the trash.Ask your pharmacist how to dispose of the packaging and medications that you no longer need.This will help protect the environment.

Composition of DUAVIVE

The active principles are conjugated estrogens and bazedoxifene.Each tablet contains 0.45mg of conjugated estrogens and acetate of bazedoxifene equivalent to 20mg of bazedoxifene.

The other components are:lactosemonohydrate, sucrose, monopalmitate of sucrose, polydextrose (E1200, which contains glucose and sorbitol) and liquid maltitol (see section2), microcrystalline cellulose, powdered cellulose, hydroxypropylcellulose, hydroxyethylcellulose, magnesium stearate, ascorbic acid, hypromellose(E464), povidone(E1201), poloxamer188, calcium phosphate, titanium dioxide (E171), macrogol(400), red iron oxide(E172), black iron oxide (E172) and propylene glycol(E1520).

Appearance of the product and content of the container

The modified-release tablet of DUAVIVE 0.45mg/20mg is a pink, oval-shaped tablet with the imprint «0.45/20» on one face.

The modified-release tablets are supplied in PVC/Aclar/PVC blisters that contain 28units.Each blister is sealed in an aluminum overwrap with an oxygen absorber.

Marketing Authorization Holder

Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Brussels, Belgium.

Responsible for manufacturing

Pfizer Ireland Pharmaceuticals, Little Connell, Newbridge, County Kildare, Ireland

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Spain

Organon Health, S.L.

Tel.: +34 91 591 12 79

Last review date of this leaflet:05/2024

Other sources of information

The detailed information about this medication is available on the website of the European Medicines Agency:https://www.ema.europa.eu.