DUAVIVE 0.45 mg/20 mg EXTENDED-RELEASE TABLETS

Introduction

Package Leaflet:information for the patient

DUAVIVE 0.45mg/20mg modified-release tablets

conjugated estrogens/bazedoxifene

Read the package leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

1. What is DUAVIVE and what is it used for
2. What you need to know before you take DUAVIVE
3. How to take DUAVIVE
4. Possible side effects
5. Storing DUAVIVE
6. Contents of the pack and other information

1. What is DUAVIVE and what is it used for

DUAVIVE is a medicine that contains two active substances called conjugated estrogens and bazedoxifene. Conjugated estrogens are a medicine that belongs to a group called hormone replacement therapy (HRT). Bazedoxifene belongs to a group of non-hormonal medicines 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 occur after menopause

During menopause, there is a decrease in the amount of estrogen produced by the woman's body. This decrease can cause symptoms such as flushing of the face, neck, and chest ("hot flashes"). DUAVIVE relieves these symptoms after menopause. You will only be prescribed this medicine if your symptoms are a significant obstacle in your daily life and if your doctor determines that other types of HRT are not suitable for you.

2. What you need to know before you take DUAVIVE

Medical history and frequent check-ups

Using DUAVIVE involves risks that need to be considered when deciding whether to start taking it or to continue taking it.

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

Before you start taking this medicine, your doctor will ask you about your personal and family medical history. Your doctor may decide to perform a physical examination. If necessary or if you have any specific concerns, this may include a breast examination and/or an internal examination. Tell your doctor if you have any illness or medical problem.

Once you have started treatment with this medicine, you should see your doctor for regular check-ups (at least once a year). During these check-ups, discuss the benefits and risks of continuing with DUAVIVE with your doctor. It is recommended that you:

• have regular tests for breast diseases and cervical smears as recommended by your doctor,
• have regular breast examinations to detect any changes, such as dimpling of the skin, changes in the nipples, or visible or palpable lumps.

Do not take DUAVIVE

• If you are allergic to conjugated estrogens, bazedoxifene, or any of the other ingredients of this medicine (listed in section 6).
• If you have or have ever had breast cancer or if there is a suspicion that you have it.
• If you have or have ever had estrogen-sensitive cancer, such as cancer of the lining of the uterus (endometrium) or if there is a suspicion that you have it.
• If you have recently had a vaginal bleeding of unknown cause.
• If you have excessive thickening of the lining of the uterus (endometrial hyperplasia) that is not being treated.
• If you have or have ever had a 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 a blood clotting disorder (such as protein C, protein S, or antithrombin deficiency).
• If you have or have recently had a disease caused by the presence of blood clots in the arteries, such as a heart attack, stroke, or angina.
• If you have or have ever had liver disease and your liver function tests have not returned to normal.
• If you are pregnant or think you may be pregnant, or are breast-feeding.
• If you have a rare blood disorder called porphyria, which is inherited from your parents.

If you are unsure about any of the above points, consult your doctorbefore taking this medicine.

If any of the above conditions occur for the first time while taking this medicine, stop taking it immediately and consult your doctor immediately.

Warnings and precautions

Consult your doctor before starting to take this medicine if you have ever had any of the following problems, as they may come back or get worse during treatment with DUAVIVE. If so, you will need to see your doctor more often for check-ups:

• fibroids in the uterus
• growth of the uterine lining outside the uterus (endometriosis) or a history of excessive growth of the uterine lining (endometrial hyperplasia)
• a higher risk of blood clots (see "Blood clots in a vein (thrombosis)")
• a higher risk of estrogen-sensitive cancer (such as having a mother, sister, or grandmother who has had breast cancer)
• high blood pressure
• a liver disorder, such as a benign liver tumor
• diabetes
• gallstones
• migraine or severe headaches
• a rare disease of the immune system that affects many parts of 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 heart or kidney problems

Stop taking DUAVIVE and consult a doctor immediately

If you notice any of the following:

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

DUAVIVE and cancer

Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer)

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

When taking 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

Data show that the risk of breast cancer increases with the use of hormone replacement therapy (HRT) with estrogens only. The increased 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 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 with estrogens and progestogens.

Have regular breast examinations.Consult your doctor as soon as possibleif you notice any changes, such as:

• dimpling of the skin
• changes in the nipple
• visible or palpable lumps

Ovarian cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with estrogens alone or in combination with estrogens and progestogens has been associated with a slightly increased 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 take HRT, about 2 cases of ovarian cancer are observed per 2,000 women over a 5-year period. In women treated with HRT for 5 years, about 3 cases are observed per 2,000 patients (i.e., about 1 additional case). Consult your doctor if you have any questions.

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 medicine) with estrogens or bazedoxifene increases the risk of blood clots in the veins (also called deep vein thrombosis or DVT), especially during the first year of treatment with these medicines.

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

Since the likelihood of forming a blood clot in the veins 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 surgical procedure, injury, or illness (see also section 3 if you need to have surgery)
• if you are severely overweight (BMI >30 kg/m2)
• if you have a blood clotting disorder that requires long-term treatment with medicines used to prevent blood clots
• if a close relative 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 going to have surgery

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

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

Other diseases

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

• kidney problems
• a high level of fat in the blood (triglycerides) in the past
• liver problems
• asthma
• seizures (epilepsy)
• migraine
• systemic lupus erythematosus (SLE - a rare disease of the immune system that can affect many parts of 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. Ask your doctor for advice.

Children and adolescents

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

Taking DUAVIVE with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Some medicines may interfere with the effect of DUAVIVE. This may cause irregular bleeding. This applies to the following medicines:

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

DUAVIVE may affect the way other medicines work:

• A medicine for the treatment of epilepsy (lamotrigine), as it may increase the frequency of seizures

Pregnancy and breast-feeding

This medicine is only intended for postmenopausal women. Do not take this medicine if you are pregnant or think you may be pregnant. Do not take this medicine if you are breast-feeding.

Driving and using machines

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

If you feel drowsy after taking this medicine, you should avoid driving and using machines.

There have been reports of vision problems, such as blurred vision, associated with the use of bazedoxifene, one of the components of this medicine. If this happens, you should avoid driving and using 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 some sugars, consult your doctor before taking this medicine.

This medicine contains 0.0088 mg of sorbitol in each tablet.

3. How to take DUAVIVE

Your doctor will try to prescribe the lowest dose necessary to treat your symptoms for the shortest possible time. Consult your doctor if you think the dose is too high or too low.

Follow the instructions for taking this medicine exactly as your doctor has told you. If you are unsure, 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 that you take the tablet at the same time every day, as this will help you remember to take your medicine.

You should continue to take this medicine for as long as your doctor tells you. For this medicine to work, it should 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 feel sick or vomit. You may experience breast tenderness, dizziness, abdominal pain, numbness/fatigue, or 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 for your next tablet, skip the missed tablet and take only the next one. Do not take a double dose to make up for forgotten doses.

If you stop taking DUAVIVE

If you decide to stop taking this medicine before finishing the prescribed treatment cycle, talk to your doctor first.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people will suffer from them.

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

Uncommon:may affect 1 person in 100

• If you start to have pseudo-migraine headaches or intense headaches.

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

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

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

• A significant increase in blood pressure (symptoms may be headache, fatigue, dizziness).
• Erythema multiforme: symptoms may consist of a 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:frequency cannot be estimated from the available data

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

Other Adverse Effects

Very Common:may affect more than 1 person in 10

• Abdominal pain (stomach pain).

Common:may affect up to 1 person in 10

• Muscle spasms (including leg cramps).
• Constipation.
• Diarrhea.
• Nausea.
• Candidiasis (vaginal yeast infection).
• Increased levels of triglycerides (fatty substances in the blood).

Uncommon:may affect up to 1 person in 100

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

The following adverse effects have been observed with the use of estrogen conjugates 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 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 10

• Breast pain, breast tenderness, breast inflammation.
• Nipple discharge.
• Joint pain.
• Alopecia (hair loss).
• Weight changes (increase or decrease).
• Increased liver enzymes (detected in ordinary liver function tests).
• Dry mouth.
• Numbness.
• Hives (urticaria).
• Rash.
• Itching.

Uncommon:may affect up to 1 person in 100

• Vaginal inflammation.
• Vaginal discharge.
• Cervical erosion detected during a medical examination.
• Blood clots in the legs.
• Blood clots in the lungs.
• Blood clots in a vein in the back of the eye (retinal vein) that can cause vision loss.
• Nausea (feeling sick).
• Headache.
• Migraine.
• Dizziness.
• Mood changes.
• Nervousness.
• Depression.
• Memory loss (dementia).
• Changes in sexual desire (increased or decreased libido).
• Changes in skin color on the face or other parts of the body.
• Increased hair growth.
• Difficulty wearing contact lenses.

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

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

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

• Painful red lumps on the skin.
• Worsening of chorea (a neurological disorder characterized by involuntary muscle movements).
• Increased size of hepatic hemangiomas, a benign (non-cancerous) tumor of the liver.
• Low calcium levels in the blood (hypocalcemia); often there will be no symptoms indicating that you have low calcium levels, but in case of severe hypocalcemia, you may feel tired, usually unwell, depressed, and suffer from dehydration. These symptoms may be accompanied by bone pain and abdominal pain. Kidney stones may form and cause severe pain in the middle back (renal colic).

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

Frequency Not Known:cannot be estimated from the available data

• Palpitations (perception of heartbeat).

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

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of DUAVIVE

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

Do not use this medicine after the expiration date stated on the packaging and on the blister pack after EXP. The expiration date is the last day of the month indicated.

Do not store above 25°C.

Store in the original packaging to protect from moisture.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of DUAVIVE

The active ingredients are estrogen conjugates and bazedoxifene. Each tablet contains 0.45 mg of estrogen conjugates and bazedoxifene acetate equivalent to 20 mg of bazedoxifene.

The other ingredients are: lactose monohydrate, sucrose, sucrose monopalmitate, polydextrose (E1200, which contains glucose and sorbitol) and maltitol liquid (see section 2), microcrystalline cellulose, powdered cellulose, hydroxypropylcellulose, hydroxyethylcellulose, magnesium stearate, ascorbic acid, hypromellose (E464), povidone (E1201), poloxamer 188, calcium phosphate, titanium dioxide (E171), macrogol (400), red iron oxide (E172), black iron oxide (E172), and propylene glycol (E1520).

Appearance and Packaging of the Product

The DUAVIVE 0.45 mg/20 mg modified-release tablet is a pink, oval tablet with the imprint "0.45/20" on one side.

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

Marketing Authorization Holder

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

Manufacturer

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

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

Date of Last Revision of this Prospectus:

Other Sources of Information

Detailed information about this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.