Bijuvea 1 mg/100 mg soft capsules

Patient Information Leaflet

Introduction

Patient Information Leaflet

Bijuva 1 mg/100 mg soft capsules Estradiol/Progesterone

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

Always use this medicine exactly as described in this leaflet or as your pharmacist has instructed you.

Keep this leaflet, as you may need to read it again.

If you need advice or more information, consult your pharmacist.

If you experience any adverse effects, consult your pharmacist, even if they are effects not listed in this leaflet. See section 4. You should consult a doctor if you get worse or do not improve.

Leaflet Contents

1. What Bijuva is and what it is used for
2. What you need to know 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 Bijuva is and what it is used for

Bijuva is indicated as hormone replacement therapy (HRT).

It contains two types of female hormones, an oestrogen and a progestogen. Bijuva is used in postmenopausal women who have had their last natural menstrual period more than 1 year ago.

Relief of symptoms occurring after menopause

During menopause, the amount of oestrogen produced by a woman's body decreases. This may cause symptoms such as hot flushes (a feeling of warmth in the face, neck, and chest). Bijuva relieves these symptoms after menopause.

Bijuva will be prescribed to you only if your symptoms are seriously affecting your daily life.

2. What you need to know before starting Bijuva

Medical history and regular check-ups

The use of HRT carries risks that must be considered when deciding whether to start or continue treatment.

Experience with treating women who have premature menopause (due to ovarian insufficiency or surgical intervention) is limited. If you have premature menopause, the risks of using HRT may differ. Consult your doctor.

Before starting (or restarting) HRT, your doctor will ask about your personal and family medical history. Your doctor may decide to perform a physical examination. This may include a breast examination and/or an internal examination, if necessary.

Once you have started treatment with Bijuva, 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 Bijuva.

Regular breast examinations should be performed as recommended by your doctor.

Do not take Bijuva

if any of the following apply to you or if you are unsure about any of the following points, consult your doctor before taking Bijuva.

Do not take Bijuva

• If you are allergic to estradiol hemihydrate or progesterone or to any of the other components of this medicine (listed in section 6).
• If you have or have had breast cancer or suspect you may have it.
• If you have a cancer sensitive to estrogens, such as cancer of the inner lining of the uterus (endometrium), or if you suspect you may have it.
• If you have abnormal vaginal bleeding.
• If you have excessive thickening of the inner lining of the uterus (endometrial hyperplasia) that is not being treated.
• If you have or have had formation of a blood clot in a vein (venous thrombosis), e.g., in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).
• If you have a blood clotting disorder (such as protein C deficiency, protein S deficiency, or antithrombin deficiency).
• If you have or have recently had an arterial disease caused by blood clots, such as heart attack, stroke, or angina pectoris.
• If you have a liver disease and your liver function tests have not returned to normal.
• If you have a rare inherited blood disorder called "porphyria" passed from parents to children.

If any of these conditions occur for the first time while you are taking Bijuva, stop treatment immediately and consult your doctor.

When to take special care with Bijuva

Inform your doctor if you have ever had any of the following conditions before starting treatment, as they may recur or worsen during treatment with Bijuva. If so, you should consult your doctor more frequently for check-ups:

• fibroids within the uterus
• growth of the inner lining of the uterus outside the uterus (endometriosis) or history of excessive growth of the inner lining of the uterus (endometrial hyperplasia)
• increased risk of developing blood clots (see "Blood clots in a vein (thrombosis)")
• increased risk of developing an estrogen-sensitive cancer (e.g., having a mother, sister, or grandmother with breast cancer)
• high blood pressure
• a liver disorder, such as a benign liver tumor
• diabetes
• gallstones
• migraines or severe headaches
• an autoimmune disease affecting multiple organs of the body (systemic lupus erythematosus, SLE)
• epilepsy
• asthma
• a condition affecting the eardrum and ear (otosclerosis)
• very high levels of fat in the blood (triglycerides)
• fluid retention due to heart or kidney problems
• hereditary and acquired angioedema

Stop taking Bijuva and seek immediate medical attention

If you experience any of the following conditions while taking HRT:

• any of the conditions listed in the section "Do not take Bijuva"
• yellowing of the skin or whites of the eyes (jaundice). This may be a sign of liver disease
• swelling of the face, tongue, or throat and difficulty swallowing or hives accompanied by difficulty breathing, suggesting angioedema
• a significant increase in blood pressure (symptoms may include headache, fatigue, dizziness)
• new-onset migraine-type headaches
• if you become pregnant
• if you notice signs of a blood clot, such as:
  • painful swelling and redness in the legs;
  • sudden chest pain;
  • difficulty breathing;

for more information, see: "Blood clots in a vein (thrombosis)"

• very high levels of fat in the blood (triglycerides)
• fluid retention due to heart or kidney problems

Note: Bijuva is not a contraceptive. If less than 12 months have passed since your last menstrual period or if you are under 50 years of age, you may still need to use an additional contraceptive method to prevent pregnancy. Seek advice from your doctor.

HRT and cancer

Excessive thickening of the inner lining of the uterus (endometrial hyperplasia) and cancer of the inner lining of the uterus (endometrial cancer)

Taking HRT with estrogens alone increases the risk of excessive thickening of the inner lining of the uterus (endometrial hyperplasia) and cancer of the inner lining of the uterus (endometrial cancer).

The progestogen in Bijuva protects against this additional risk.

Irregular bleeding

You may experience irregular bleeding or spotting during the first 3–6 months of taking Bijuva. However, if irregular bleeding:

• continues beyond the first 6 months
• starts after having taken Bijuva for more than 6 months
• continues after stopping treatment with Bijuva

consult your doctor as soon as possible.

Breast cancer

Available data show that the use of hormone replacement therapy (HRT) with combined estrogen-progestogen or with estrogen alone increases the risk of breast cancer. The additional risk depends on how long you use HRT. The additional risk becomes apparent within 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 you have used HRT for more than 5 years.

Comparison

In women aged 50 to 54 years who are not using HRT, an average of 13 to 17 out of 1,000 will be diagnosed with breast cancer over a 5-year period.

In women aged 50 who start estrogen-only HRT for 5 years, there will be 16 to 17 cases per 1,000 women (i.e., 0 to 3 additional cases).

In women aged 50 who start combined estrogen-progestogen HRT for 5 years, there will be 13 to 21 cases per 1,000 women (i.e., 4–8 additional cases).

In women aged 50 to 59 who are not taking HRT, an average of 27 cases of breast cancer per 1,000 women will be diagnosed over a 10-year period.

In women aged 50 who start estrogen-only HRT for 10 years, there will be 34 cases per 1,000 women (i.e., 7 additional cases).

In women aged 50 who start combined estrogen-progestogen HRT for 10 years, there will be 48 cases per 1,000 women (i.e., 21 additional cases).

• You should have regular breast examinations. Consult your doctor if you notice any changes such as:

• skin dimpling

• changes in the nipple

• any lump you can see or feel

In addition, it is recommended that you join mammography screening programs when offered. For screening mammograms, it is important that you inform the nurse/healthcare professional performing the X-ray that you are using HRT, as these medicines can increase breast density, which may affect the mammogram result. When breast density is increased, the mammogram may not detect all lumps.

Ovarian cancer

Ovarian cancer is less common than breast cancer. The use of HRT with estrogen alone or with combined estrogen-progestogen has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50 to 54 who are not on HRT, about 2 cases of ovarian cancer per 2,000 women are observed over a 5-year period. In women on HRT for 5 years, about 3 cases per 2,000 women are observed (i.e., about 1 additional case).

Effects of HRT on the heart and circulation. Blood clots in a vein (thrombosis)

The risk of blood clots in veins is approximately 1.3 to 3 times higher in HRT users compared to non-users, especially during the first year of use. Blood clots can be serious, and if one travels to the lungs, it can cause chest pain, difficulty breathing, fainting, or even death.

Your risk of developing a blood clot in the veins increases with age and if any of the following apply to you. Inform your doctor if any of these situations affect you:

• you cannot walk for a prolonged period due to major surgery, injury, or illness (see also section 3, If you need to undergo surgery)
• you have severe obesity (BMI > 30 kg/m²)
• you have a blood clotting disorder requiring long-term treatment with a medication used to prevent blood clots
• a close relative has ever had a blood clot in the leg, lung, or another organ
• you have systemic lupus erythematosus (SLE)
• you have cancer.

For symptoms of a blood clot, see "Stop taking Bijuva and seek immediate medical attention."

Comparison

In women in their fifties who are not taking HRT, an average of 4 to 7 out of 1,000 are expected to have a blood clot in a vein over a 5-year period.

In women in their fifties who have been taking estrogen-progestogen HRT, there will be 9 to 12 cases per 1,000 users (i.e., 5 additional cases) over a 5-year period.

Coronary heart disease (heart attack)

There is no evidence that HRT prevents heart attacks. Women over 60 years of age using estrogen-progestogen HRT are slightly more likely to develop heart disease than those not taking any HRT.

Stroke

The risk of stroke is approximately 1.5 times higher in HRT users compared to non-users. The number of additional stroke cases due to HRT use will increase with age.

Comparison

In women in their fifties who are not taking HRT, an average of 8 out of 1,000 are expected to have a stroke over a 5-year period. For women in their fifties taking HRT, there will be 11 cases per 1,000 users over a 5-year period (i.e., 3 additional cases).

Other diseases

HRT does not prevent memory loss. There is some evidence of greater memory loss in women who start using HRT after age 65. Consult your doctor.

Children

Bijuva must not be used in children.

Use of Bijuva with other medicines

Bijuva may affect how other medicines work. Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. Some medicines may interfere with the effect of Bijuva, which may lead to irregular bleeding. These medicines include:

• 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 preparations containing St. John's wort (Hypericum perforatum);
• bromocriptine used for pituitary gland problems or Parkinson's disease;
• ketoconazole, griseofulvin (for treatment of fungal infections);
• cyclosporine (used to suppress the immune system);

HRT may affect how other medicines work:

• an epilepsy medicine (lamotrigine), as it may increase the frequency of seizures.
• Combined regimens for hepatitis C virus (HCV) ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin; glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir (see section 4.4.), may cause elevations in blood liver function tests (increase in liver enzyme ALT) in women using HRT containing ethinylestradiol. Bijuva contains estradiol instead of ethinylestradiol. It is unknown whether an increase in liver enzyme ALT may occur when Bijuva is used with this HCV combination regimen. Your doctor will advise you.

Inform your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription, herbal medicines, and other natural products.

Your doctor will advise you.

Laboratory tests

If you need a blood test, inform your doctor or laboratory staff that you are taking Bijuva, as this medicine may affect the results of certain tests.

Pregnancy and breastfeeding

Bijuva is indicated only in postmenopausal women. If you become pregnant while taking Bijuva, you must stop treatment and contact your doctor.

Excipients

Bijuva contains the red dye Allura. Bijuva contains 0.042 mg of Allura red (E129) per capsule. It may cause allergic reactions. It may cause asthma, especially in patients allergic to acetylsalicylic acid.

3. How to take Bijuva

Bijuva is a medication containing the active substance estradiol, a form of estrogen used in hormone replacement therapy (HRT) to treat moderate to severe menopausal symptoms in postmenopausal women.

General Instructions:

• Take exactly as prescribed by your healthcare provider.
• Swallow the capsule whole with water, with or without food.
• Try to take Bijuva at the same time each day to maintain consistent levels in your body and to help you remember your dose.

Dosage:

• The usual recommended dose is one 1 mg capsule taken orally once daily.
• Your doctor may adjust the dose based on your individual needs and response to treatment.
• Do not take more than prescribed.

Important:

• Do not stop taking Bijuva without consulting your doctor, even if you feel well.
• If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for a missed one.
• If you take more Bijuva than prescribed, contact your doctor or seek medical attention immediately.

Duration of Treatment:

• The duration of treatment should be as short as possible and regularly reassessed by your doctor, typically every 3 to 6 months, to determine whether continued therapy is still necessary.

For more information, refer to the full prescribing information provided with the medication.

Follow exactly the instructions given by your doctor for taking this medicine. If in doubt, consult your doctor or pharmacist again. Your doctor will prescribe the lowest dose to treat your symptoms for the shortest possible time. Talk to your doctor if you think this dose is too strong or not strong enough.

Take one capsule daily with food.

Take this medicine every day without any breaks in treatment.

If you take more Bijuva than you should

If you have taken more Bijuva than you should, you may feel drowsy, dizzy, numb, or tired.

If you have taken more Bijuva than you should, contact your doctor or pharmacist immediately, or call the Toxicology Information Service (Tel: 91 562 04 20), stating the medicine and the amount taken.

If you forget to take Bijuva

If you forget a dose, take it as soon as you remember. However, if more than 12 hours have passed, skip the missed dose.

Do not take a double dose to make up for a forgotten dose.

The likelihood of unexpected bleeding or spotting may increase.

If you stop taking Bijuva

Do not stop taking Bijuva without first talking to your doctor. If you have any doubts about using this product, consult your doctor or pharmacist.

If you need surgery

If you are scheduled for surgery, inform your surgeon that you are taking Bijuva. You may need to stop treatment with Bijuva for about 4 to 6 weeks before the procedure to reduce the risk of blood clots (see also section 2, "Blood clots in a vein"). Ask your doctor when you can resume treatment with Bijuva.

4. Possible adverse effects

Like all medicines, Bijuva can cause adverse effects, although not everyone experiences them.

The following conditions occur more frequently in women using hormone therapy for menopause (HT) compared to women who do not take HT:

• breast cancer
• abnormal growth or cancer of the inner lining of the uterus (endometrial hyperplasia or cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• coronary heart disease;
• stroke;
• possible memory loss if HT is initiated after the age of 65.

For more information about these adverse effects, see section 2.

Inform your doctor if you experience any of the following adverse effects while using Bijuva:

Very common (affects more than 1 in 10 people)

• breast tenderness

Common (affects up to 1 in 10 people)

• headache, dizziness
• mood changes
• fatigue
• back pain
• abdominal pain, indigestion
• pelvic pain
• weight gain
• acne, dry skin
• breast pain
• feeling unwell (nausea)
• vaginal discharge (white or yellowish vaginal discharge)
• vaginal bleeding or severe uterine contractions
• hair loss
• pain in the limbs (e.g., back, arms, legs, wrists, ankles)

Uncommon (affects up to 1 in 100 people)

• low iron levels in the blood
• high blood pressure
• excessive fluid retention in the legs
• increased cholesterol levels
• increased appetite
• bowel problems
• muscle pain
• breast cancer
• sleep disorders
• tumors in the uterus or fallopian tubes
• memory loss, severe headaches
• tingling sensation
• loss of smell
• difficulty sleeping or abnormal dreams
• mood changes or feeling irritable
• vomiting
• dry mouth
• constipation
• diarrhea
• weight loss, dizziness
• chills
• acute pancreatitis
• anxiety, feeling depressed
• increased sexual desire
• hot flushes
• vaginal irritation or burning sensation
• vaginal infections such as candidiasis
• blood clots
• dry skin, skin itching, or skin discoloration
• skin rash or appearance of red lines on the skin
• dizziness
• hirsutism
• visual disturbances
• abdominal discomfort, abdominal tenderness
• dyspepsia
• hyperphagia
• oral discomfort
• dysgeusia
• flatulence
• hypersensitivity
• gastroenteritis
• boil
• acute otitis media
• abnormal liver function tests
• limb pain
• uterine adnexal cysts
• decreased attention capacity
• paresthesia
• parosmia
• restlessness
• breast disorders
• fibrocystic breast disease
• nipple pain
• benign breast neoplasm
• endometrial hypertrophy
• abnormal biopsy
• postmenopausal bleeding
• vulvovaginal pruritus and telangiectasia

Rare (affects up to 1 in 1,000 people)

• muscle weakness
• benign growths in the smooth muscle of the uterus (fibroids)
• cysts near the fallopian tubes

Very rare (affects up to 1 in 10,000 people)

• itching, dark-colored urine

The following adverse effects have been reported with other HTs:

• gallbladder disease
• various skin disorders:
  • skin discoloration, especially on the face or neck, known as "melasma" or "chloasma";
  • painful red nodules on the skin (erythema nodosum);
  • skin rash with target-like redness or sores (erythema multiforme).

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es/. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Bijuva

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

This medicine does not require special storage temperature conditions. Keep the blister pack in the outer packaging to protect it from light.

Do not use this medicine after the expiry date stated on the packaging after "EXP". The expiry date refers to the last day of the month indicated.

Do not use this medicine if you notice any visible signs of deterioration.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE Point at your pharmacy. If in doubt, ask your pharmacist how to properly dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

The active substances are estradiol (as estradiol hemihydrate) and progesterone.

The other components are: mono/diglycerides of medium-chain fatty acids, lauroyl macrogol glycerides 32, gelatin 200 Bloom, hydrolyzed gelatin, glycerol (E422), Allura red (E129), titanium dioxide (E171), propylene glycol (E1520), polyvinyl acetate phthalate, polyethylene glycol (E1521) and ammonium hydroxide (E527).

Appearance of the product and contents of the pack

Bijuva capsules are oval, opaque, light pink on one side and dark pink on the other, printed with "1C1" in white ink.

They are supplied in blisters containing 28 or 84 capsules.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

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

Manufacturer

Pfizer Italia S.R.L.,
Localita Marino Del Tronto
63100 Ascoli Piceno (AP)
Italy

Further information about this medicine is available from the local representative of the Marketing Authorization Holder:

Theramex Healthcare Spain, S.L.
Calle Martínez Villergas 52, Edificio C, 2nd floor, left side
28027 Madrid
Spain

This medicine is authorized in the EEA Member States under the following names:

Netherlands: Bijuva 1 mg/100mg zachte capsules
Belgium: Bijuva 1 mg/100mg zachte capsules
Luxembourg, Italy, France, Poland: Bijuva
Germany: Bijuva 1mg/100mg Weichkapseln
Spain: Bijuva 1 mg/100 mg cápsulas blandas

Date of the most recent review of this leaflet: May 2025

Detailed information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (https://www.aemps.gob.es/)