Biiuva

Package Leaflet: Information for the Patient

Bijuva, 1 mg + 100 mg, Soft Capsules

estradiol + progesterone

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient. This medicine should always be taken exactly as described in the package leaflet for the patient or as directed by the pharmacist. Keep this leaflet, so you can read it again if needed.

In case of need, you may need to read it again. If you have any doubts, you should consult
your pharmacist. If you experience any side effects, including any not listed in this leaflet, you should tell your pharmacist. See section 4.

If there is no improvement or the patient feels worse, they should contact their doctor or pharmacist.

Table of Contents of the Leaflet

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

1. What is Bijuva and what is it used for

Bijuva is a hormone replacement therapy (HRT).
It contains two types of female hormones – estrogen and progestogen. Bijuva is used in postmenopausal women, at least 12 months (1 year) after their last natural menstrual period.

Relief of symptoms occurring after menopause

During menopause, the amount of estrogen produced in a woman's body decreases. This can cause symptoms such as a feeling of heat on the face, neck, and chest ("hot flashes"). Bijuva alleviates these menopausal symptoms.
Bijuva should only be prescribed to a patient if the symptoms seriously interfere with her daily life.

2. Important information before taking Bijuva

Medical history and regular check-ups

Taking HRT involves risks that need to be considered when deciding to start or continue treatment.
Experience in treating women with premature menopause (following ovarian failure or surgical removal) is limited. In the case of premature menopause, the risk associated with HRT may be different. You should consult your doctor.
Before starting or resuming HRT, your doctor will take your medical history, including your family history.
Your doctor may decide to perform a physical examination, including a breast and/or gynecological examination, if necessary.
After starting Bijuva, you should regularly visit your doctor for check-ups (at least once a year). During these check-ups, you should discuss the benefits and risks of continuing to take Bijuva with your doctor.
You should have regular breast examinations as recommended by your doctor.

When not to take Bijuva:

In the event of any of the following situations. If you are unsure about any of the following points, you should consult your doctorbefore taking Bijuva.
When not to take Bijuva:

• if you are allergic to estradiol hemihydrate or progesterone, or any of the other ingredients of this medicine (listed in section 6);
• if you have or have had breast cancer;
• if you have or are suspected to have estrogen-dependent cancer, such as endometrial cancer (cancer of the lining of the uterus);
• if you have vaginal bleeding of unknown cause;
• if you have untreated endometrial hyperplasia (overgrowth of the lining of the uterus);
• if you have or have had blood clots in the veins (thrombosis), such as deep vein thrombosis or pulmonary embolism;
• if you have blood clotting disorders (such as protein C, protein S, or antithrombin deficiency);
• if you have or have recently had a disease caused by blood clots in the arteries, such as a heart attack, stroke, or angina;
• if you have or have had liver disease, and liver function tests have not returned to normal;
• if you have a rare, inherited blood disorder - porphyria. If any of the above conditions occur for the first time while taking Bijuva, you should stop taking it and consult your doctor immediately.

When to be cautious when taking Bijuva

Before starting treatment, you should inform your doctor if you have had any of the following conditions in the past, as they may recur or worsen during treatment with Bijuva. In such cases, you should be monitored more closely:

• uterine fibroids;
• endometriosis or a history of endometrial hyperplasia;
• increased risk of blood clots (see "Blood clots in the veins (thrombosis)");
• increased risk of estrogen-dependent cancer (e.g., breast cancer in your mother, sister, or grandmother);
• high blood pressure;
• liver disease, such as liver tumors;
• diabetes;
• gallstones;
• migraine or severe headaches;
• systemic lupus erythematosus (SLE), a disease affecting many organs;
• epilepsy;
• asthma;
• otosclerosis (a disease affecting the eardrum and hearing);
• very high triglyceride levels in the blood;
• fluid retention due to heart or kidney problems;
• hereditary or acquired angioedema

When to stop taking Bijuva and consult your doctor immediately

In the event of any of the following situations while taking HRT:

• if any of the conditions listed in "When not to take Bijuva" occur;
• if your skin or the whites of your eyes turn yellow (jaundice), which may be a sign of liver disease;
• swelling of the face, tongue, and/or throat, and/or difficulty swallowing or breathing, which may indicate angioedema;
• in case of a significant increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• if you experience a migraine-type headache for the first time;
• if you become pregnant;
• if you experience symptoms of a blood clot, such as:
• painful swelling and redness of the legs,
• sudden chest pain,
• difficulty breathing; More information on this can be found in the section "Blood clots in the veins (thrombosis)".
• in case of very high triglyceride levels in the blood;
• in case of fluid retention due to heart or kidney problems.

Note: Bijuva is not a contraceptive. If it has been less than 12 months since your last menstrual period or you are under 50 years old, you may need to use an additional method of contraception. You should discuss this with your doctor.

Hormone Replacement Therapy (HRT) and Cancer

Endometrial Hyperplasia (Overgrowth of the Lining of the Uterus) and Endometrial Cancer

Taking HRT that only contains estrogen increases the risk of endometrial hyperplasia and endometrial cancer.
The progestogen in Bijuva prevents this additional increased risk.

Irregular Bleeding

During the first 3-6 months of taking Bijuva, you may experience irregular bleeding or spotting. However, if you experience irregular bleeding that:

• lasts longer than the first 6 months,
• starts after you have been taking Bijuva for more than 6 months,
• continues after you stop taking Bijuva, you should consult your doctor as soon as possible.

Breast Cancer

Data confirms that taking HRT in the form of a combination of estrogen and progestogen or estrogen alone increases the risk of breast cancer. The additional risk depends on the duration of HRT. This additional risk becomes apparent after 3 years of HRT. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or more if HRT lasted more than 5 years.
Comparison
In women aged 50-54 who do not take HRT, breast cancer will be diagnosed in approximately 13-17 out of 1000 women over a 5-year period.
In women aged 50 who start a 5-year estrogen-only HRT, the number of cases will be 16-17 out of 1000 women (i.e., 0 to 3 additional cases).
In women aged 50 who start a 5-year estrogen-progestogen HRT, the number of cases will be 13-21 out of 1000 women (i.e., 4 to 8 additional cases).
In women aged 50-59 who do not take HRT, breast cancer will be diagnosed in approximately 27 out of 1000 women over a 10-year period.
In women aged 50 who start a 10-year estrogen-only HRT, the number of cases will be 34 out of 1000 women (i.e., 7 additional cases).
In women aged 50 who start a 10-year estrogen-progestogen HRT, the number of cases will be 48 out of 1000 women (i.e., 21 additional cases).

• You should have regular breast examinations. You should consult your doctor if you notice any changes, such as skin dimpling, changes in the nipple area, or any noticeable or palpable lumps.

In addition, it is recommended to participate in proposed breast cancer screening programs.
When undergoing screening mammography, it is essential to inform the nurse or medical staff performing the X-ray examination that you are taking HRT, as this medication may increase breast density, which can affect the mammography result. Mammography may not detect all lumps in areas of increased breast density.

Ovarian Cancer

Ovarian cancer occurs much less frequently than breast cancer. Taking HRT that only contains estrogen or a combination of estrogen and progestogen causes a slight increase in the risk of ovarian cancer. The risk of ovarian cancer varies with age. For example, in women aged 50-54 who do not take HRT, ovarian cancer will be diagnosed in approximately 2 out of 2000 women over a 5-year period. In women who have taken HRT for 5 years, the number of cases will be approximately 3 out of 2000 women (i.e., about 1 additional case).

HRT and Its Effect on the Heart and Circulation

Blood Clots in the Veins (Thrombosis)

The risk of blood clots in the veins is about 1.3 to 3 times higher in women taking HRT compared to those not taking HRT. The occurrence of this complication is most likely in the first year of HRT. Blood clots can be life-threatening. If they move to the lungs, they can cause chest pain, shortness of breath, loss of consciousness, or even death.
The risk of blood clots in the veins is higher if you are older, and if you have any of the following conditions. You should inform your doctor if:

• you are unable to walk for a long time due to a serious surgical procedure, severe injury, or illness (see also section 3 "If surgery is planned");
• you are obese (BMI > 30 kg/m2);
• you have a history of blood clotting disorders requiring long-term use of blood-thinning medications;
• anyone in your close family has had blood clots in the legs, lungs, or other organs;
• you have systemic lupus erythematosus (SLE);
• you have cancer.

Symptoms of blood clots are listed in the section "When to stop taking Bijuva and consult your doctor immediately".
Comparison
In women aged 50-60 who do not take HRT, blood clots in the veins are likely to occur in 4 to 7 out of 1000 women over a 5-year period. In women aged 50-60 who have taken estrogen-progestogen HRT for more than 5 years, the number of cases will be 9 to 12 out of 1000 women (i.e., 5 additional cases).

Heart Disease (Myocardial Infarction)

There is no evidence that HRT prevents myocardial infarction. Women over 60 years old taking estrogen-progestogen HRT are slightly more likely to develop heart disease than those not taking HRT.

Stroke

The risk of stroke is about 1.5 times higher in women taking HRT compared to those not taking it. The number of additional stroke cases due to HRT will increase with age.
Comparison
In women aged 50-60 who do not take HRT, stroke is likely to occur in 8 out of 1000 women over a 5-year period. In women aged 50-60 who take HRT, the number of cases will be 11 out of 1000 women over a 5-year period (i.e., 3 additional cases).

Other Conditions

HRT does not prevent memory loss. There is some evidence of an increased risk of memory loss in women who start HRT after the age of 65. You should discuss this with your doctor.

Children

Bijuva should not be taken by children.

Bijuva and Other Medicines

Bijuva may affect the action of some medicines. Some medicines may affect the action of Bijuva. This may lead to irregular bleeding. This applies to the following medicines:

• anti-epileptic medicines(such as phenobarbital, phenytoin, and carbamazepine);
• anti-tuberculosis medicines(such as rifampicin, rifabutin);
• HIV medicines(such as nevirapine, efavirenz, ritonavir, and nelfinavir);
• herbal preparations containing St. John's Wort(Hypericum perforatum);
• bromocriptine used for pituitary or Parkinson's disease disorders;
• ketokonazole, griseofulvin (used for fungal infections);
• cyclosporin (used to weaken the immune system);

Hormone replacement therapy may affect the action of other medicines:

• epilepsy medicine (lamotrigine), as it may increase the frequency of seizures;
• HCV medicines (such as combination schemes of ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir) (see section 4.4) may cause increased liver enzyme levels in the blood (increased ALT enzyme activity) in women taking combined hormonal products containing ethinyl estradiol. Bijuva contains estradiol instead of ethinyl estradiol. It is not known whether increased liver enzyme activity may occur when Bijuva is taken with these HCV treatment schemes.

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription, herbal preparations, or other products of natural origin. You should discuss this with your doctor.

Lab Tests

If a blood test is required, you should inform your doctor or laboratory staff that you are taking Bijuva, as it may affect the results of some tests.

Pregnancy and Breastfeeding

Bijuva is intended for use in postmenopausal women only.
If you become pregnant, you should stop taking Bijuva and consult your doctor.

Bijuva Contains Allura Red

Bijuva contains 0.042 mg of Allura Red (E 129)
It may cause allergic reactions.

3. How to Take Bijuva

This medicine should always be taken exactly as directed by your doctor or pharmacist. If you are unsure, you should consult your doctor or pharmacist. Your doctor should prescribe the lowest possible dose for the shortest possible time to alleviate your symptoms. If you think the dose of your medicine is too high or too low, you should consult your doctor.

Take one capsule daily, with food.

The medicine should be taken every day, without interruption.

Taking More Than the Recommended Dose of Bijuva

If you take more than the recommended dose of Bijuva, you should consult your doctor or go to the hospital. You should take the package leaflet with you.
You may experience: drowsiness, dizziness, fatigue.

Missing a Dose of Bijuva

If you miss a dose, you should take it as soon as possible. However, if more than 12 hours have passed, you should not take the missed dose.
You should not take a double dose to make up for the missed dose.
Missing a dose may increase the likelihood of irregular bleeding or spotting.

Stopping Bijuva

You should not stop taking Bijuva without first consulting your doctor. If you have any further doubts about taking this medicine, you should consult your doctor or pharmacist.

If Surgery is Planned

In the case of planned surgery, you should inform the surgeon that you are taking Bijuva. It may be necessary to stop taking Bijuva about 4 to 6 weeks before the operation to reduce the risk of blood clots (see section 2 "Blood clots in the veins"). Before restarting Bijuva, you should consult your doctor.

4. Possible Side Effects

Like all medicines, Bijuva can cause side effects, although not everybody gets them.
Women taking HRT are at increased risk of developing the following conditions compared to women not taking HRT:

• breast cancer;
• endometrial hyperplasia or cancer (cancer of the lining of the uterus);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• heart disease;
• stroke;
• possible memory loss, if HRT is started after the age of 65. More information on these side effects can be found in section 2.

You should inform your doctor about any of the following side effects that occur while taking Bijuva:
Very common side effects (may affect more than 1 in 10 women):

• breast tenderness.

Common side effects (may affect up to 1 in 10 women):

• headache, dizziness,
• mood changes,
• fatigue,
• back pain,
• abdominal pain, nausea,
• pelvic pain,
• weight gain,
• acne, dry skin,
• breast pain,
• nausea,
• vaginal discharge (white or yellowish discharge from the vagina),
• vaginal bleeding or heavy menstrual cramps,
• hair loss,
• limb pain (e.g., back, arm, leg, wrist, ankle pain).

Uncommon side effects (may affect up to 1 in 100 women):

• low iron levels in the blood,
• high blood pressure,
• fluid retention in the legs,
• high cholesterol levels,
• increased appetite,
• urination and bowel problems
• muscle pain,
• breast cancer,
• short sleep,
• uterine or ovarian tumors,
• memory loss, severe headaches,
• tingling sensation,
• loss of smell,
• difficulty sleeping or unusual dreams,
• mood changes or irritability,
• vomiting,
• dry mouth,
• constipation,
• diarrhea,
• weight loss, dizziness,
• chills,
• acute pancreatitis,
• anxiety, depression,
• increased interest in sexual activity,
• hot flashes,
• vaginal irritation or burning,
• vaginal infections, such as thrush,
• blood clots,
• dryness and itching of the skin or skin discoloration,
• rash or appearance of red lines on the skin,
• vertigo of labyrinthine origin,
• excessive hair growth,
• vision disturbances,
• discomfort in the abdominal cavity, abdominal tenderness,
• nausea,
• increased appetite (hyperphagia),
• discomfort in the mouth,
• taste disturbances,
• bloating,
• hypersensitivity,
• gastritis,
• boils,
• acute otitis media,
• abnormal liver function test results,
• limb pain,
• ovarian cysts,
• attention disorders,
• paresthesia (abnormal sensation),
• olfactory hallucinations,
• excitement,
• breast diseases,
• breast dysplasia,
• nipple pain,
• benign breast tumor,
• endometrial hyperplasia (overgrowth of the lining of the uterus),
• abnormal biopsy result,
• postmenopausal bleeding,
• itching of the vulva and vagina, and telangiectasia.

Rare side effects (may affect up to 1 in 1000 women):

• muscle weakness,
• benign tumors derived from smooth muscle cells of the uterus,
• ovarian cysts.

Very rare side effects (may affect up to 1 in 10,000 women):

• itching, dark urine discoloration.

The following side effects have been reported with other HRTs:

• gallbladder disease,
• various skin diseases:
• skin discoloration, especially on the face or neck, known as "pregnancy patches" (chloasma),
• painful red lumps on the skin (erythema nodosum),
• rash with redness or ulcers in a ring shape (erythema multiforme).

Reporting Side Effects

If you experience any side effects, including any not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products,
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl.
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to Store Bijuva

The medicine should be stored out of sight and reach of children.
This medicinal product does not require storage at a specific temperature. To protect from light, the blister should be stored in the outer packaging.
Do not use this medicine after the expiry date stated on the packaging after "Expiry Date". The expiry date refers to the last day of the month stated.
Do not use this medicine if you notice visible signs of deterioration.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the Pack and Other Information

What Bijuva Contains

The active substances of Bijuva are estradiol (in the form of estradiol hemihydrate) and progesterone.
The other ingredients are: mono/diglycerides of medium-chain fatty acids, macrogol lauryl ether 32, gelatin, hydrolyzed gelatin, glycerol, Allura Red (E 129), titanium dioxide (E 171), propylene glycol, polyvinyl acetate phthalate, polyethylene glycol, and ammonium hydroxide.

What Bijuva Looks Like and Contents of the Pack

Bijuva capsules are oval, opaque, light pink on one side and dark pink on the other, with the imprint "1C1" in white ink.
They are packaged in PVC/PE/PCTFE/Aluminum blisters containing 28 or 84 soft gelatin capsules in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorization Holder

Theramex Ireland Limited
3rd Floor, Kilmore House
Spencer Dock, Park Lane
Dublin 1, D01 YE64
Ireland

Manufacturer

Millmount Healthcare Ltd
Block-7
City North Business Campus
Stamullen, Co. Meath
K32 YD60
Ireland
Pfizer Italia S.R.L.
Localita Marino Del Tronto
63100 Ascoli Piceno
Italy

This Medicinal Product is Authorized in the Member States of the European Economic Area Under the Following Names:

Belgium, France, Germany, Italy, Luxembourg, Netherlands, Poland, Spain: Bijuva
Date of Last Revision of the Leaflet:May 2025

Other Sources of Information