DUAVIVE 0.45 mg/20 mg Modified-release tablets

Зміст інструкції

1. DUAVIVE 0.45 mg/20 mg modified-release tablets
   1. What is DUAVIVE and what it is used for
   2. Cosa deve sapere prima di prendere DUAVIVE
   3. How to take DUAVIVE
   4. Possible side effects
   5. How to store DUAVIVE
   6. Contents of the pack and other information

DUAVIVE 0.45 mg/20 mg modified-release tablets

conjugated estrogens/bazedoxifene

Read this leaflet carefully before taking this medicine as 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell 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 you take 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 is DUAVIVE and what it is used for

DUAVIVE is a medicine that contains two active ingredients called conjugated estrogens and
bazedoxifene. Conjugated estrogens are medicines that belong to a group of drugs
called hormone replacement therapy. Bazedoxifene belongs to a group of non-
hormonal drugs called selective estrogen receptor modulators (SERM, selective estrogen

receptor modulator).
DUAVIVE is used in postmenopausal women who still have a uterus and have not had a
spontaneous menstruation in the last 12 months.
DUAVIVE is used for:
Relief of symptoms that occur after menopause
During menopause, the amount of estrogen produced by the female body decreases. This can
cause symptoms such as heat in the face, neck and chest ("hot flashes"). DUAVIVE relieves
these symptoms after menopause. This medicine will be prescribed to you only if the symptoms
severely compromise your daily life and if your doctor determines that other types of hormone
replacement therapy are not suitable for you.

2. Cosa deve sapere prima di prendere DUAVIVE

Medical history and periodic check-ups
The use of DUAVIVE involves risks, which must be taken into account when deciding whether to start or
continue taking it.
There is no experience of treating women in premature menopause (due to ovarian insufficiency or surgery) with DUAVIVE.
Before you start taking this medicine, your doctor will ask about your personal and
family medical history. The doctor may decide to perform a physical examination, which may include a
breast exam and/or a pelvic exam, if necessary or if there are particular concerns. Tell your doctor if you suffer from any medical problem or illness.
Once you have started taking this medicine, you will need to see your doctor for periodic check-ups
(at least once a year). During these check-ups, discuss the benefits and risks of continuing DUAVIVE with your doctor. You are advised to:

• perform regular breast exams and cervical smears, as recommended by your doctor.
• periodically check for changes in your breasts, such as skin retraction, changes in the nipple, 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 a cancer that is sensitive to estrogen, such as a cancer of the uterine lining (endometrium).
• if you have recently had unexplained vaginal bleeding.
• if you have an excessive thickening of the uterine lining (endometrial hyperplasia) that is not being treated.
• if you have or have 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 had a recent illness caused by blood clots in the arteries, such as a heart attack, stroke, or angina.
• if you have or have had liver disease and your liver function tests have not returned to normal.
• if you are pregnant or may become pregnant, or if you are breastfeeding.
• if you suffer from a rare blood disorder called porphyria, which is passed on from parents to children (inherited).

If you are unsure whether any of these conditions apply to you, talk to your doctorbefore
taking this medicine.
If any of the above conditions appear for the first time while you are taking this
medicine, stop taking it immediately and contact your doctor immediately.

Warnings and precautions
Talk to your doctor before taking this medicine if you have ever suffered from any of the
following problems, as they may recur or worsen during treatment with DUAVIVE.
In such cases, you will need to see your doctor more often for check-ups:
fibroids inside the uterus
growth of the uterine lining outside the uterus (endometriosis) or a 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 has had breast cancer)
high blood pressure
liver disorder, such as a benign liver tumor
diabetes
gallstones
migraine or severe headaches
a rare autoimmune disease that affects many organs (systemic lupus
erythematosus, SLE)
seizures (epilepsy)
asthma
a disease that affects the eardrum and hearing (otosclerosis)
high levels of fats in the blood (triglycerides)
fluid retention due to heart or kidney problems

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

• one of the conditions indicated in ‘Do not take DUAVIVE’
• yellowing of the skin or whites of the eyes (jaundice). These may be signs of a liver disease
• a severe increase in blood pressure (symptoms may include headache, fatigue, dizziness)
• migraine-type headache that occurs for the first time
• the onset of pregnancy
• signs of a blood clot, such as painful swelling or 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) or cancer of the
uterine lining (endometrial cancer)
This medicine contains conjugated estrogens and bazedoxifene, and is used to treat women
who still have a uterus.
When you take DUAVIVE, you should not take other estrogens, as this could increase the
risk of endometrial hyperplasia.
If you have unexpected vaginal bleeding, you should see a doctor as soon as possible.

Breast cancer
Evidence shows that taking hormone replacement therapy (HRT) with estrogen alone increases the risk of breast cancer. The higher risk depends on the duration of HRT use. The additional risk appears within 3 years of use.
After stopping HRT, the additional risk will decrease over time, but this 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 fall within the same range as that
found when using combination HRT based on estrogens and progestogens.

Check your breasts regularly. See your doctor as soon as possible if you notice any
changes,such as:

• skin retraction
• changes in the nipple
• 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 depending on age. For example, among women aged 50 to 54 who
do not take hormone replacement therapy, about 2 out of 1,000 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 1,000 users (i.e. about 1 extra case). If you have any concerns, talk to your doctor.
The effect of DUAVIVE on the risk of ovarian cancer is not known.

DUAVIVE and the heart or circulation
Blood clots in a vein (thrombosis)
DUAVIVE may increase the risk of blood clots
Estrogens and bazedoxifene taken alone increase the risk of blood clots in the
veins (also called deep vein thrombosis or DVT), especially during the first year of
use.
Blood clots can be serious and if one of these moves to the lungs it can cause chest pain, shortness of breath, collapse or even death.
As the likelihood of a blood clot forming in the veins increases with age and in
the presence of any of the following situations, contact 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 going to have surgery)
• if you are severely overweight (BMI >30 kg/m )
• if you have a blood clotting problem that needs to be treated long-term with a medicine used to prevent blood clots
• if any of your close relatives have 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,talk to your doctor before taking this
medicine.

Heart disease (heart attack)
There is no evidence that hormone replacement therapy prevents heart attack. Randomized controlled
trials have not found an increased risk of coronary heart disease in women who have had a hysterectomy
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 extra stroke cases due to the use of hormone replacement therapy
increases with age.
For women aged 50 to 59 who do not take hormone replacement therapy, an average of 8 out of 1,000 will have a stroke over a 5-year period. For women aged 50 to 59 who
take hormone replacement therapy, there will be 11 cases per 1,000 users over 5 years (i.e. 3
extra cases).
The effect of DUAVIVE on the risk of stroke may fall within the same range
found when using combination HRT based on estrogens and progestogens.
Other factors that may increase the risk of stroke include:

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

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

Other conditions
If you have any of the following conditions, your doctor needs to 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 that affects many organs)
• fluid retention

Estrogen therapy does not prevent memory loss. There is some evidence of an
increased risk of memory loss in women who start using estrogen therapy at an age over 65. Ask your doctor for advice.

Children and adolescents
This medicine is not intended for use in children and adolescents under the age of 18.

Other medicines and DUAVIVE
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 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 can affect how some other medicines work:

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

Pregnancy and breastfeeding
This medicine is intended for use only in postmenopausal women. If you are pregnant or suspect you are pregnant, do not take this medicine. Do not take this medicine
if you are breastfeeding.

Driving and using machines
DUAVIVE has minimal effects on the ability to drive and operate machines.
If you feel drowsy after taking this medicine, you should avoid driving or operating
machines.
The bazedoxifene component of this medicine has been reported to cause vision problems,
such as blurred vision. In this case, you should avoid driving or operating machinery until
your doctor has told you 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 some sugars, contact your
doctor before using this medicine.
This medicine contains 0.0088 mg of sorbitol in each tablet.

3. How to take DUAVIVE

To treat the symptoms, the doctor will aim to prescribe the lowest dose for the shortest possible time.
Contact your doctor if you think the dose is too high or too low.
Take this medicine following exactly the instructions of your doctor. If you have any doubts, consult
your doctor or pharmacist.
The recommended dose is one tablet once a day.
Swallow the tablet whole with a glass of water.
You can take the tablet at any time of the day, with or without food; however, it is advisable to
take the tablet at the same time each day as this will help you to remember.
You must continue to take this medicine for the entire period prescribed by your doctor. To be effective, the
medicine must be taken every day as prescribed.

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 feel breast tenderness, dizziness, abdominal pain, drowsiness/fatigue, or experience a short
period 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
to take your next tablet, skip the forgotten one and take only the next scheduled tablet.
Do not take a double dose to make up for a missed tablet.

If you stop taking DUAVIVE
If you decide to stop taking this medicine before completing the prescribed course of
treatment, you should first consult your doctor.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Stop taking DUAVIVE and contact your doctor immediately if you notice any of the following serious side effects:
Uncommon:may affect 1 in 100 people

• If you start to experience migraine-like 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 of 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, pain or swelling of the eye, especially if sudden
• Severe allergic reaction, the 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, skin rash (symptoms of angioedema)
• Symptoms of pancreatitis, which may include severe pain in the upper part of the abdomen, which may spread to the back, accompanied by abdominal bloating, fever, nausea and vomiting
• Sudden abdominal pain and passage of bright red blood in the stool, with or without diarrhea, due to a sudden blockage of an artery that carries blood to the intestine (ischemic colitis)
• A heart attack, the symptoms of which generally include pain, including chest pain that spreads 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 serious increase in blood pressure (symptoms may include headache, fatigue, dizziness)
• Erythema multiforme: symptoms may include a skin rash with pink-red patches, especially on the palms of the hands or soles of the feet, with possible blister formation. Ulcers may also be present in the mouth, eyes or genitals, and fever.

Not known:the frequency cannot be estimated based on 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 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
• Diarrhea
• Nausea
• Candidiasis (vaginal yeast infection)
• 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 ingredients of this medicine) have been 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 edema)

Common:may affect 1 in 10 people

• Breast pain, breast tenderness, breast enlargement
• Nipple discharge
• Joint pain
• Alopecia (hair loss)
• Weight changes (increase or decrease)
• Increases in liver enzymes (detected with routine liver function tests)
• Dry mouth
• Sleepiness
• Urticaria
• Skin rash
• Itching

Uncommon:may affect up to 1 in 100 people

• Vaginal inflammation
• Vaginal discharge
• Cervical erosion detected during a medical examination
• Blood clot in the veins of the legs
• Blood clot in the lungs
• Blood clot in a vein in the back of the eye (retinal vein), which can cause loss of vision
• Nausea
• Headache
• Migraine
• Dizziness
• Mood changes
• Nervousness
• Depression
• Memory loss (dementia)
• Changes in sex drive (increased or decreased libido)
• Changes in skin color of the face or other parts of the body
• Increased hair/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 how 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 tumor of the membranes surrounding the brain or spinal cord

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

• Painful and reddened bumps on the skin
• Worsening of chorea (a neurological disorder characterized by spasmodic and involuntary body movements)
• Enlargement of hepatic angiomas, benign (non-cancerous) liver tumors
• Low levels of calcium in the blood (hypocalcemia); often there are no symptoms to suggest a low level of calcium in the blood, but when hypocalcemia is severe, you may feel tired, unwell, depressed, and may become dehydrated. Bone pain and abdominal pain may also develop. 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:the frequency cannot be estimated based on 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, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system detailed 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 which is stated on the package and on the blister after
Exp. The expiry date refers to the last day of that month.
Do not store at a temperature above 25 ºC.
Store in the original package to protect the medicine from moisture.
After opening the blister, use within 60 days.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What DUAVIVE contains
The active ingredients 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 ingredients are: lactose monohydrate, 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 contents of the pack
The modified-release tablet of DUAVIVE 0.45 mg/20 mg is a pink, oval-shaped tablet, bearing “0.45/20” imprinted on one side.
The modified-release tablets are supplied in PVC/Aclar/PVC blisters containing 28 tablets.
Each blister is sealed to an aluminium foil with an oxygen absorber.

Marketing Authorisation 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 on this medicinal product, contact the local representative of the Marketing
Authorisation Holder:

België / Belgique / Belgien
Luxembourg / Luxemburg
Pfizer NV/SA
Tél/Tel: +32 (0)2 554 62 11

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. + 370 52 51 4000

България
Пфайзер Люксембург САРЛ,
Клон България
Ten: +359 2 970 4333

Latvijā
Pfizer Luxembourg SARL filiāle Latvijā
Tel.: + 371 670 35 775

Česká Republika
Pfizer, spol. s r.o.
Tel: +420-283-004-111

Magyarország
Pfizer Kft
Tel: +36 1 488 3700

Danmark
Pfizer ApS
Tlf.: +45 44 201 100

Malta
Vivian Corporation Ltd.
Tel: +35621 344610

Deutschland
PFIZER PHARMA GmbH
Tel: +49 (0) 30 550055-51000

Nederland
Pfizer BV
Tel: +31 (0)10 406 43 01

Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel.: +372 666 7500

Norge
Pfizer AS
Tlf: +47 67 526 100

Ελλάδα
Pfizer Hellas A.E.
Τηλ.: +30 210 6785 800

Österreich
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

España
Organon Salud, S.L.
Tel.: +34 91 591 12 79

Polska
Pfizer Polska Sp. z o.o.
Tel: +48 22 335 61 00

France
Pfizer
Tel +33 (0)1 58 07 34 40

Portugal
Laboratórios Pfizer, Lda.
Tel: + 351 21 423 5500

România
Pfizer Romania S.R.L
Tel: +40 (0) 21 207 28 00

Hrvatska
Pfizer Croatia d.o.o.
Tel: + 385 1 3908 777

Ireland
Pfizer Healthcare Ireland
Tel: 1800 633 363 (toll free)
+44 (0)1304 616161

Slovenija
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel.: + 386 (0) 1 52 11 400

Ísland
Icepharma hf
Simi: +354 540 8000

Slovenská Republika
Pfizer Luxembourg SARL,
organizačná zložka
Tel: + 421 2 3355 5500

Italia
Organon Italia S.r.l.
Tel: +39 06 90259059

Suomi/Finland
Pfizer Oy
Puh/Tel: +358 (0)9 430 040

Kύπρος
Pfizer Hellas (Cyprus Branch) A.E.
Τηλ: +357 22 817690

Sverige
Pfizer AB
Tel: +46 (0)8 550 520 00

Altre fonti d’informazioni
More detailed information on this medicinal product is available on the website of the European
Medicines Agency, https://www.ema.europa.eu .