Duavive

Patient Information Leaflet

DUAVIVE 0.45 mg/20 mg modified-release tablets

conjugated estrogens/bazedoxifene
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What DUAVIVE is and what it is used for

DUAVIVE is a medicine containing two active substances called conjugated estrogens and bazedoxifene. Conjugated estrogens are medicines belonging to a group of drugs known as hormone replacement therapy. Bazedoxifene belongs to a group of non-hormonal medicines called selective estrogen receptor modulators (SERMs, selective oestrogen receptor modulator).
DUAVIVE is used in postmenopausal women who still have their uterus and who have not had a spontaneous menstrual period in the past 12 months.
DUAVIVE is used for:
Relief of symptoms occurring after menopause
During menopause, the amount of estrogen produced by the female body decreases. This may cause symptoms such as warmth in the face, neck, and chest ("hot flushes"). DUAVIVE relieves these symptoms after menopause. This medicine will be prescribed to you only if your symptoms severely affect your daily life and if your doctor determines that other types of hormone replacement therapy are not suitable for you.

2. What you need to know before taking DUAVIVE

Medical history and regular check-ups
The use of DUAVIVE involves certain risks, which should be considered when deciding whether to start or continue taking it.
There is no experience with treating women with premature menopause (due to ovarian insufficiency or surgical intervention) using DUAVIVE.
Before you start taking this medicine, your doctor will ask about your personal and family medical history. Your doctor may decide to perform a physical examination, which might include a breast examination and/or a pelvic examination, if necessary or if there are specific concerns. Inform your doctor if you have any medical problems or illnesses.
Once you have started taking this medicine, you should visit your doctor for regular check-ups (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing DUAVIVE. You are advised to:

• have regular breast examinations and cervical smears, as recommended by your doctor.
• regularly check for changes in your breasts, such as skin retraction, nipple changes, 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, have had, or suspect you have breast cancer.
• if you have, have had, or suspect you have an estrogen-sensitive tumour, such as a tumour of the uterine lining (endometrium).
• if you have recently experienced unexplained vaginal bleeding.
• if you have excessive thickening of the uterine lining (endometrial hyperplasia) that is untreated.
• if you have or have previously had a blood clot in a vein (thrombosis), for example in the legs (deep vein thrombosis), in the lungs (pulmonary embolism), or in the eyes (retinal vein thrombosis).
• if you suffer from a blood clotting disorder (such as protein C, protein S, or antithrombin deficiency).
• if you have or have recently had an arterial disease caused by blood clots, such as heart attack, stroke, or angina.
• if you have or have had liver disease and liver function tests have not returned to normal.
• if you are pregnant or could become pregnant, or if you are breastfeeding.
• if you suffer from a rare blood disorder called porphyria, which is inherited from parents to children (hereditary).

If you are unsure whether any of these conditions apply to you, consult your doctor before taking this medicine.
If any of the above conditions develops for the first time while taking this medicine, stop taking it immediately and consult your doctor without delay.
Warnings and precautions
Consult your doctor before taking this medicine if you have ever suffered from any of the following conditions, as they may recur or worsen during treatment with DUAVIVE. In such cases, you may need to have more frequent medical check-ups:
uterine fibroids
endometriosis (growth of uterine lining tissue outside the uterus) or history of excessive growth of the uterine lining (endometrial hyperplasia)
increased risk of developing blood clots [see “Blood clots in a vein (thrombosis)”]
increased risk of estrogen-sensitive cancer (e.g. having a mother, sister, or grandmother who had breast cancer)
high blood pressure
liver disorder, such as benign liver tumour
diabetes
gallstones
migraine or severe headaches
a rare autoimmune disease affecting multiple organs (systemic lupus erythematosus, SLE)
seizures (epilepsy)
asthma
a disease affecting the ear drum and hearing (otosclerosis)
elevated levels of fats in the blood (triglycerides)
fluid retention due to heart or kidney problems

Stop taking DUAVIVE and contact a doctor immediately
If you notice any of the following:

• any of the conditions listed under ‘Do not take DUAVIVE’
• yellowing of the skin or whites of the eyes (jaundice). These could be signs of liver disease
• severe increase in blood pressure (symptoms may include headache, fatigue, dizziness)
• new-onset migraine-type headaches
• onset of pregnancy
• signs of a blood clot, such as painful swelling or redness in the legs, sudden chest pain, or difficulty breathing. For further information, see ‘Blood clots in a vein (thrombosis)’

DUAVIVE and cancer
Excessive thickening of the uterine lining (endometrial hyperplasia) or cancer of the uterine lining (endometrial cancer)
This medicine contains conjugated estrogens and bazedoxifene and is used to treat women who still have their uterus.
When taking DUAVIVE, you must not take other estrogens, as this could increase the risk of endometrial hyperplasia.
If you experience unexpected vaginal bleeding, you must consult a doctor as soon as possible.
Breast cancer
Evidence shows that taking estrogen-only hormone replacement therapy (HRT) increases the risk of breast cancer. The increased risk depends on the duration of HRT use. The additional risk becomes apparent within 3 years of use.
After stopping HRT, the additional risk decreases over time, but this risk may persist for 10 years or more if HRT has been used for over 5 years.
The effect of DUAVIVE on the risk of breast cancer may fall within the same range as that observed with combined estrogen-progestogen HRT.
Check your breasts regularly. See your doctor promptly if you notice any changes, such as:

• skin retraction
• nipple changes
• visible or palpable lumps

Ovarian cancer
Ovarian cancer is rare, much rarer than breast cancer. The use of estrogen-only hormone replacement therapy has been associated with a slight increase in the risk of ovarian cancer.
The risk of ovarian cancer varies with age. For example, among women aged 50 to 54 who do not take hormone replacement therapy, about 2 in 2,000 will be diagnosed with ovarian cancer over a 5-year period. Among women who take hormone replacement therapy for 5 years, there will be about 3 cases per 2,000 users (i.e. about 1 additional case). If you have any doubts, consult your doctor.
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.
Estrogens and bazedoxifene, when taken individually, increase the risk of blood clots in veins (also known as deep vein thrombosis or DVT), particularly during the first year of use.
Blood clots can be serious, and if one travels to the lungs, it can cause chest pain, shortness of breath, collapse, or even death.
Since the likelihood of developing a blood clot in the veins increases with age and in the presence of any of the following conditions, consult your doctor promptly:

• if you are unable to walk for a prolonged period due to major surgery, injury, or illness (see also section 3, if you are undergoing surgery)
• if you are severely overweight (BMI >30 kg/m²)
• if you have a blood clotting disorder requiring long-term treatment with a medicine to prevent blood clots
• if any of your close relatives has ever had a blood clot in the leg, lung, or another organ
• if you have systemic lupus erythematosus (SLE)
• if you have cancer.

If any of these conditions apply to you, consult your doctor before taking this medicine.
Heart disease (heart attack)
There is no evidence that hormone replacement therapy prevents heart attacks. Randomized controlled data have not shown an increased risk of coronary heart disease in hysterectomized women on estrogen-only therapy.
Stroke
The risk of stroke is approximately 1.5 times higher in users of hormone replacement therapy compared to non-users. The number of additional stroke cases due to HRT use increases with age.
For women aged 50 to 59 who do not take HRT, it is expected that on average 8 out of 1,000 will have a stroke over a 5-year period. For women aged 50 to 59 who take HRT, there will be 11 cases per 1,000 users over 5 years (i.e. 3 additional cases).
The effect of DUAVIVE on the risk of stroke may fall within the same range as that observed with combined estrogen-progestogen HRT.
Other factors that may increase the risk of stroke include:

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

If you are undergoing surgery
If you are scheduled for surgery, inform your doctor that you are taking DUAVIVE. You may need to stop taking DUAVIVE approximately 4–6 weeks before surgery to reduce the risk of blood clot formation (see Blood clots in a vein). Ask your doctor when you can resume taking this medicine.
If you have any doubts, consult your doctor before taking this medicine.
Other conditions
If you have any of the following conditions, your doctor should monitor you:

• kidney problems
• pre-existing high levels of fats in the blood (triglycerides)
• liver problems
• asthma
• seizures (epilepsy)
• migraine
• systemic lupus erythematosus (SLE, a rare autoimmune disease affecting multiple organs)
• fluid retention

Estrogen-based therapy does not prevent memory loss. There is some evidence of an increased risk of memory loss in women who start estrogen therapy after age 65. Consult your doctor for advice.
Children and adolescents
This medicine is not intended for use in children and adolescents under 18 years of age.
Other medicines and DUAVIVE
Inform 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 could lead to irregular bleeding. This applies to the following medicines:

• medicines for epilepsy (such as phenobarbital, phenytoin, and carbamazepine);
• medicines for tuberculosis (such as rifampicin, rifabutin);
• medicines for HIV infection (such as nevirapine, efavirenz, ritonavir, and nelfinavir);
• herbal remedies containing St. John’s wort (Hypericum perforatum)

DUAVIVE may affect how some other medicines work:

• a medicine for epilepsy (lamotrigine), as it could increase the frequency of seizures

Pregnancy and breastfeeding
This medicine is intended exclusively for use in postmenopausal women. Do not take this medicine if you are pregnant or suspect you may be pregnant. Do not take this medicine if you are breastfeeding.
Driving and using machines
DUAVIVE has minimal effects on the ability to drive or operate machinery.
If you experience drowsiness after taking this medicine, you must avoid driving or operating machinery.
Blurred vision has been reported with the bazedoxifene component of this medicine. In such cases, you must avoid driving or operating machinery until your doctor confirms it is safe to do so.
DUAVIVE contains lactose, sucrose, liquid maltitol, glucose, and sorbitol
If you have been told by your doctor that you have an intolerance to certain sugars, consult your doctor before using this medicine.
This medicine contains 0.0088 mg of sorbitol in each tablet.

3. How to take DUAVIVE

To treat symptoms, your doctor will aim to prescribe the lowest effective dose for the shortest possible duration.
If you think the dose is too high or too low, consult your doctor.
Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
The recommended dose is one tablet once daily.
Swallow the tablet whole with a glass of water.
You may take the tablet at any time of day, with or without food; however, it is advisable to take the tablet at the same time each day, as this will help you remember to take it.
You must continue taking this medicine for the entire duration prescribed by your doctor. For the medicine to work, it must be taken every day as directed.

If you take more DUAVIVE than you should
Contact your doctor or pharmacist.
If you take too many tablets, you may experience nausea or vomiting. You may also have breast tenderness, dizziness, abdominal pain, drowsiness/fatigue, or have a short episode of vaginal bleeding.

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 dose, skip the missed dose and take only the next scheduled tablet. Do not take a double dose to make up for the forgotten tablet.

If you stop taking DUAVIVE
If you decide to stop taking this medicine before completing the prescribed treatment course, you must first consult your doctor.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking DUAVIVE and contact a doctor immediately if you experience any of the following serious side effects:

Uncommon: may affect up to 1 in 100 people

• If you start getting migraine-type headaches or severe headaches

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

• Signs of a blood clot, such as painful swelling or redness in the legs, sudden chest pain or difficulty breathing
• Signs of a blood clot in the eye (retinal vein), such as vision problems in one eye, including loss of vision, eye pain or swelling, particularly if sudden
• Severe allergic reaction, symptoms of which may include sudden wheezing and chest pain or tightness, swelling of the eyelids, face, lips, mouth, tongue or throat, difficulty breathing, collapse
• Swelling of the eyes, nose, lips, mouth, tongue or throat, difficulty breathing, severe dizziness or fainting, rash (symptoms of angioedema)
• Symptoms of pancreatitis, which may include severe pain in the upper abdomen spreading to the back, accompanied by abdominal swelling, fever, nausea and vomiting
• Sudden onset of abdominal pain and passage of bright red blood in the stool, with or without diarrhoea, due to sudden blockage of an artery supplying blood to the intestine (ischemic colitis)
• A heart attack, symptoms of which usually include pain, including chest pain spreading to the jaw, neck and upper arm. The pain may be accompanied by sweating, shortness of breath, fatigue, nausea and fainting

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

• A severe increase in blood pressure (symptoms may include headache, fatigue, dizziness)
• Erythema multiforme: symptoms may include a rash with pink-red patches, particularly on the palms of the hands or soles of the feet, possibly with blister formation. Mouth ulcers, eye or genital ulcers, and fever may also be present.

Not known: frequency cannot be determined from the available data

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

Other side effects
Very common: may affect more than 1 in 10 people

• Abdominal pain (stomach ache)

Common: may affect 1 in 10 people

• Muscle spasms (including leg cramps)
• Constipation
• Diarrhoea
• Nausea
• Vaginal candidiasis (yeast infection of the vagina)
• Increases in triglyceride levels (fatty substances in the blood)

Uncommon: may affect 1 in 100 people

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

The following side effects have been observed when conjugated estrogens and/or bazedoxifene (the active substances of this medicine) were taken individually and may also occur with this medicine:
Very common: may affect more than 1 in 10 people

• Hot flushes
• Muscle cramps
• Visible swelling of the face, hands, legs, feet or ankles (peripheral oedema)

Common: may affect 1 in 10 people

• Breast pain, breast tenderness, breast swelling
• Nipple discharge
• Joint pain
• Alopecia (hair loss)
• Changes in weight (increase or decrease)
• Increases in liver enzymes (detected by routine liver function tests)
• Dry mouth
• Drowsiness
• Hives
• Rash
• Itching

Uncommon: may affect up to 1 in 100 people

• Inflammation of the vagina
• Vaginal discharge
• Cervical erosion detected during medical examination
• Blood clot in the veins of the legs
• Blood clot in the lungs
• Blood clot in a vein at the back of the eye (retinal vein), which may cause loss of vision
• Nausea
• Headache
• Migraine
• Dizziness
• Mood changes
• Nervousness
• Depression
• Memory loss (dementia)
• Changes in sexual interest (increased or decreased libido)
• Changes in skin colour of the face or other parts of the body
• Increased hair growth
• Difficulty wearing contact lenses

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

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

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

• Painful, red lumps on the skin
• Worsening of chorea (a neurological disorder characterised by spasmodic, involuntary body movements)
• Enlargement of hepatic haemangiomas, benign (non-cancerous) liver tumours
• Low levels of calcium in the blood (hypocalcaemia); symptoms suggesting low calcium levels are often absent, but when hypocalcaemia is severe, fatigue, general malaise, depression and dehydration may occur. Bone pain and abdominal pain may also be present. Kidney stones may develop, causing severe pain in the middle of the back (renal colic)
• Worsening of porphyria, a rare inherited blood disorder

Not known: frequency cannot be determined from the available data

• Palpitations (awareness of heartbeat)
• Dry eyes, eye pain, reduced visual acuity, decreased vision, blepharospasm (abnormal and involuntary blinking or eyelid spasm).

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store DUAVIVE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after
Exp. The expiry date refers to the last day of that month.
Do not store above 25 °C.
Store in the original packaging to protect the medicine from moisture.
After opening the blister, use within 60 days.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What DUAVIVE contains
The active substances are conjugated estrogens and bazedoxifene. Each tablet contains 0.45 mg of
conjugated estrogens and bazedoxifene acetate equivalent to 20 mg of bazedoxifene.
The other components are: monohydrate lactose, sucrose, sucrose monopalmitate, polydextrose
(E1200, containing glucose and sorbitol), and liquid maltitol (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).
Description of the appearance of DUAVIVE and package contents
The modified-release tablet of DUAVIVE 0.45 mg/20 mg is a pink, oval-shaped tablet, imprinted with “0.45/20” on one side.
The modified-release tablets are supplied in PVC/Aclar/PVC blisters containing 28 tablets.
Each blister is sealed in an aluminum foil sheet with an oxygen absorber.
Marketing Authorization Holder
Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Brussels, Belgium.
Manufacturer
Pfizer Ireland Pharmaceuticals, Little Connell Newbridge, County Kildare, Ireland.
For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:
België / Belgique / Belgien Lietuva
Luxembourg / Luxemburg Pfizer Luxembourg SARL filialas Lietuvoje
Pfizer NV/SA Tel. + 370 52 51 4000
Tél/Tel: +32 (0)2 554 62 11
България Latvijā
Пфайзер Люксембург САРЛ, Pfizer Luxembourg SARL filiāle Latvijā
Клон България Tel.: + 371 670 35 775
Ten: +359 2 970 4333
Česká Republika Magyarország
Pfizer, spol. s r.o. Pfizer Kft
Tel: +420-283-004-111 Tel: +36 1 488 3700
Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf.: +45 44 201 100 Tel: +35621 344610
Deutschland Nederland
PFIZER PHARMA GmbH Pfizer BV
Tel: +49 (0) 30 550055-51000 Tel: +31 (0)10 406 43 01
Eesti Norge
Pfizer Luxembourg SARL Eesti filiaal Pfizer AS
Tel.: +372 666 7500 Tlf: +47 67 526 100
Ελλάδα Österreich
Pfizer Hellas A.E. Pfizer Corporation Austria Ges.m.b.H.
Τηλ.: +30 210 6785 800 Tel: +43 (0)1 521 15-0
España Polska
Organon Salud, S.L. Pfizer Polska Sp. z o.o.
Tel.: +34 91 591 12 79 Tel: +48 22 335 61 00
France Portugal
Pfizer Laboratórios Pfizer, Lda.
Tel +33 (0)1 58 07 34 40 Tel: + 351 21 423 5500
Hrvatska România
Pfizer Croatia d.o.o. Pfizer Romania S.R.L
Tel: + 385 1 3908 777 Tel: +40 (0) 21 207 28 00
Ireland Slovenija
Pfizer Healthcare Ireland Pfizer Luxembourg SARL
Tel: 1800 633 363 (toll free) Pfizer, podružnica za svetovanje s področja
+44 (0)1304 616161 farmacevtske dejavnosti, Ljubljana
Tel.: + 386 (0) 1 52 11 400
Ísland Slovenská Republika
Icepharma hf Pfizer Luxembourg SARL,
Simi: +354 540 8000 organizačná zložka
Tel: + 421 2 3355 5500
Italia Suomi/Finland
Organon Italia S.r.l. Pfizer Oy
Tel: +39 06 90259059 Puh/Tel: +358 (0)9 430 040
Kύπρος Sverige
Pfizer Hellas (Cyprus Branch) A.E. Pfizer AB
Τηλ: +357 22 817690 Tel: +46 (0)8 550 520 00
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu .