BOLTIN 2.5 mg TABLETS

Introduction

Package Leaflet: Information for the User

Boltin 2.5 mg tablets

Tibolone

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

1. What is Boltin and what is it used for

Boltin is a hormone replacement therapy (HRT). Boltin contains tibolone, a substance that has favorable effects on various tissues in the body, such as the brain, vagina, and bone. Boltin is used in postmenopausal women who have had their last natural menstrual period at least 12 months ago.

Boltin is used to:

Relieve symptoms that occur after menopause

During menopause, the amount of estrogen produced by the body decreases. This can cause symptoms such as a feeling of heat in the face, neck, and chest ("hot flashes"). Boltin relieves these symptoms after menopause. You will only be prescribed Boltin if your symptoms are seriously affecting your daily activities.

2. What you need to know before you take Boltin

Follow carefully all instructions given by your doctor.

Medical history and medical examinations

The use of hormone replacement therapy or Boltin involves risks that need to be considered when deciding whether to start treatment or continue taking it.

Experience with treatment in women with premature menopause (due to ovarian failure or surgical intervention) is limited. If you have premature menopause, consult your doctor, as the risks of using hormone replacement therapy or Boltin may be different.

Before you start (or restart) hormone replacement therapy or Boltin, your doctor will ask about your medical history and that of your family. Your doctor may decide to perform a physical examination, which may include a breast examination and an internal examination, if necessary.

Once you have started taking Boltin, 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 Boltin with your doctor.

Have regular mammograms, as recommended by your doctor.

Do not take Boltin

If you have any of the following conditions. If you are unsure about any of these, consult your doctorbefore taking Boltin.

Do not take Boltin

• if you are allergic to tibolone or any of the other ingredients of this medicine (listed in section 6).
• if you have or have ever had breast canceror if you suspect you may have it
• if you have an estrogen-sensitive cancer, such as cancer of the lining of the uterus (endometrial cancer), or if it is suspected that you may have it.
• if you have any unexplained vaginal bleeding.
• if you have excessive growth of the lining of the uterus(endometrial hyperplasia) that is not being treated.
• if you have or have had a blood clot in a vein(thrombosis), 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 a disease caused by blood clots in the arteries, such as heart attack, stroke, or angina.
• if you have or have had a liver diseaseand your liver function tests have not returned to normal.
• if you have a rare blood problem called "porphyria" that is inherited in families.
• if you are pregnant or think you may be pregnant
• if you are breastfeeding

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take Boltin.

Before starting treatment, inform your doctor if you have had any of the following problems, as they may reappear or worsen during treatment with Boltin. If so, you should see your doctor more frequently for medical check-ups:

• fibroids in the uterus,
• growth of the lining of the uterus outside the uterus (endometriosis) or a history of excessive growth of the lining of the uterus (endometrial hyperplasia),
• increased risk of developing blood clots (see "blood clots in a vein (thrombosis)"),
• increased risk of having an estrogen-sensitive cancer (e.g., if your mother, sister, or grandmother had breast cancer),
• high blood pressure,
• a liver disorder, such as a benign liver tumor,
• diabetes
• gallstones,
• migraines or severe headaches,
• a disease of the immune system that affects many organs in the body (systemic lupus erythematosus, SLE),
• epilepsy,
• asthma,
• a disease that affects the eardrum and hearing (otosclerosis),
• very high levels of fat in your blood (triglycerides),
• fluid retention due to heart or kidney problems.

Stop taking Boltin and see a doctor immediately

If you experience any of the following while taking hormone replacement therapy or Boltin:

• any of the conditions mentioned in the section "Do not take Boltin",
• yellowing of the skin or the whites of the eyes (jaundice), which can be a sign of liver disease,
• a large increase in blood pressure (symptoms can be headache, tiredness, dizziness),
• migraine-like headaches that appear for the first time,
• if you become pregnant,
• if you experience signs of having a blood clot, such as:
• painful swelling and redness of the legs,
• sudden chest pain,
• difficulty breathing.

For more information, see "blood clots in a vein (thrombosis)".

Note: Boltin is not a contraceptive. If it has been less than 12 months since your last menstrual period or if you are under 50, you may still need to use an additional contraceptive method to avoid becoming pregnant. Ask your doctor for advice.

Hormone Replacement Therapy and Cancer

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

There are reports and studies that have recorded an increased growth of endometrial cells or endometrial cancer (which is the layer of tissue that lines the inside of the uterus) in women treated with Boltin. This risk of endometrial cancer is greater the longer the treatment lasts.

Irregular bleeding

You may experience irregular bleeding or spotting during the first 3-6 months of treatment with Boltin.

However, if irregular bleeding:

• continues beyond the first 6 months
• starts when you have been taking Boltin for more than 6 months
• continues after you have stopped taking Boltin

See your doctor as soon as possible.

Breast cancer

Existing data show that the use of tibolone increases the risk of breast cancer. The additional risk depends on the duration of use of tibolone. In studies with HRT, after stopping HRT, the additional risk decreased over time, but the risk may persist for 10 years or more in women who have used HRT for more than 5 years. There is no data on the persistence of risk after stopping tibolone, but a similar pattern cannot be ruled out.

Comparison

Women taking Boltin have a lower risk than women using combined hormone replacement therapy and a similar risk to women using estrogen-only hormone replacement therapy.

• Check your breasts regularly. See your doctorif you notice any change such as:

• skin dimpling or puckering,

• changes in the nipple,

• presence of visible or palpable lumps.

Ovarian cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with estrogen alone or in combination with 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 old who are not treated with HRT, about 2 cases of ovarian cancer are observed per 2,000 women over a 5-year period. In women who have taken HRT for 5 years, about 3 cases are observed per 2,000 patients (i.e., about 1 additional case).

With the use of Boltin, the increased risk of ovarian cancer is similar to that of other types of HRT.

Effect of Hormone Replacement Therapy on the heart and circulation

Blood clots in a vein (thrombosis)

The risk of blood clots in the veinsis approximately 1.3 to 3 times higher in women taking hormone replacement therapy than in those not taking it, especially during the first year of treatment.

Blood clots can be serious and if one reaches the lungs can cause chest pain, shortness of breath, fainting, or even death.

The likelihood of a blood clot in the veins increases with age and if any of the following conditions are met. Inform your doctor if you meet any of these conditions:

• you are pregnant or have recently given birth,
• you use estrogens,
• you are unable to walk for a long time due to major surgery, injury, or illness (see also section 3 "If you need to have surgery"),
• you are significantly overweight (BMI > 30 kg/m2),
• you have a blood clotting disorder that requires long-term treatment with a medicine to prevent blood clots,
• if a close relative has had a blood clot in the leg, lung, or other organ
• you have systemic lupus erythematosus (SLE),
• you have cancer.

The signs of a blood clot are listed in the section "Stop taking Boltin and see a doctor immediately".

Comparison

On average, over a 5-year period, it can be expected that out of 1,000 women in their 50s who do not take hormone replacement therapy, 4 to 7 will have a blood clot in a vein.

While, out of 1,000 women of this age who have been taking hormone replacement therapy with estrogens and progestogens for more than 5 years, there will be 9 to 12 cases (i.e., 5 additional cases).

With the use of Boltin, the increased risk of developing a blood clot in a vein is lower than with other types of hormone replacement therapy.

Heart disease (heart attack)

There is no indication that hormone replacement therapy or Boltin prevents a heart attack.

Women over 60 who use hormone replacement therapy with estrogens and progestogens are slightly more likely to have heart disease than those who do not take it. As the risk of heart disease depends greatly on age, the number of additional cases of heart disease due to the use of hormone replacement therapy with estrogens and progestogens is very low in healthy women close to menopause, but increases with advancing age.

There is no indication to suggest that the risk of heart attack with Boltin is different from that of other types of hormone replacement therapy.

Stroke

Recent studies suggest that hormone replacement therapy and Boltin increase the risk of having a stroke. This increased risk has been observed mainly in postmenopausal women over 60 years old.

Comparison

On average, over a 5-year period, it can be expected that out of 1,000 women in their 50s who do not take Boltin, 3 will have a stroke, while for women of this age who take Boltin, the figure may be 7 out of 1,000 (i.e., 4 additional cases).

On average, over a 5-year period, it can be expected that out of 1,000 women in their 60s who do not take Boltin, 11 will have a stroke, while for women of this age who take Boltin, the figure may be 24 out of 1,000 (i.e., 13 additional cases).

Other diseases

Hormone replacement therapy does not prevent memory loss. There is evidence of a higher risk of memory loss in women who start using hormone replacement therapy after the age of 65. Ask your doctor for advice.

Taking Boltin with other medicines

• Some medicines may interfere with the effect of Boltin, which could lead to irregular bleeding. This occurs with the following medicines: medicines against blood clotting(such as warfarin)
• medicines for epilepsy(such as phenobarbital, phenytoin, and carbamazepine),
• medicines for tuberculosis(such as rifampicin),
• herbal remedies containing St. John's Wort(Hypericum perforatum),
• medicines for insomnia(midazolam).

Boltin should not be taken with other hormone replacement therapy products.

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

Taking Boltin with food and drink

You can eat and drink normally while taking Boltin

Pregnancy, breastfeeding, and fertility

Boltin should only be used by postmenopausal women. If you become pregnant, stop taking Boltin and contact your doctor.

Driving and using machines

No adverse effects of Boltin on the ability to drive or use machines have been reported.

Boltin contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Boltin

Follow exactly the instructions for administration of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

Boltin should not be taken until 12 months after your last natural menstrual period. If Boltin is taken before, the possibility of irregular vaginal bleeding may increase.

First intake of Boltin

• If you have not taken other hormone replacement therapy medicines before, you can start immediately.
• If you are switching from another hormone replacement therapy preparation:

There are several types of preparations, in tablets, patches, gels. Some have bleeding between cycles (sequential preparations) and others are taken continuously.

• If you were taking a sequential preparation, you should start taking Boltin immediately after the bleeding has finished.
• If you were taking a continuous regimen (without bleeding) you can start taking Boltin at any time.

Boltin should be taken orally. Take one tablet every day. You can swallow it with a little water or other drink.

Take the tablet at the same time every day. The Boltin blisters are marked with the days of the week. Start by taking the tablet marked with the day of the week that your treatment starts. For example, if it is Monday, take the tablet marked Monday in the top row of the blister. Follow the arrows until the blister is empty. Start the next blister the next day. Do not leave any days between blisters or boxes.

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

If you take more Boltin than you should

If you have taken more Boltin than you should, consult a doctor or pharmacist immediately. If someone takes too many tablets, there is no need to be alarmed. However, you should consult your doctor as soon as possible. The signs of overdose may be feeling unwell, being sick, or vaginal bleeding.

If you forget to take Boltin

If you forget to take a tablet, take it as soon as you remember, unless more than 12 hours have passed since the last intake. In this case, simply skip that day's dose. Do not take a double dose to make up for forgotten doses.

If you need to have surgery

If you are going to have surgery, inform the surgeon that you are taking Boltin. You may need to stop taking Boltin 4 to 6 weeks before the operation to reduce the risk of a blood clot (see section 2 Blood clots in a vein). Ask your doctor when you can start taking Boltin again.

4. Possible Adverse Effects

Compared to women who do not use hormone replacement therapy, the following diseases have been reported more frequently in women using hormone replacement therapy:

• breast cancer,
• abnormal growth or cancer of the tissue lining the inside of the uterus (endometrial hyperplasia or endometrial cancer),
• ovarian cancer,
• blood clots in the veins of the legs or lungs (venous thromboembolism),
• heart disease,
• stroke,
• possible memory loss if hormone replacement therapy is started after the age of 65.

See section 2 for more information on these adverse effects.

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

Most of these effects are mild.

The adverse effects observed in clinical studies are:

Frequent (may affect up to 1 in 100 women):

• vaginal bleeding or spotting
• abdominal pain
• weight gain
• breast pain
• unnatural hair growth
• vaginal discomfort such as discharge, itching, and irritation.

Infrequent (may affect up to 1 in 1,000 women):

• acne

Additionally, other adverse effects have been observed with general use, such as:

• dizziness, headache, migraine, depression
• skin rash or itching
• vision changes
• digestive disorders
• fluid retention (swelling in the legs)
• joint or muscle pain
• changes in liver function laboratory tests

There have been reports of breast cancer and an increased growth of endometrial cells or endometrial cancer in women treated with Boltin.

Tell your doctor if you experience vaginal bleeding or spotting, or if any of the above adverse effects are bothersome or continuous.

The following adverse effects have been reported with other hormone replacement therapies:

• bile duct disease,
• various skin disorders:
• • skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma),
  • painful and reddish nodules on the skin (erythema nodosum),
  • skin rash with reddish lesions or papules in a target shape (erythema multiforme).

Reporting of Adverse Effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Boltin

Store in the original packaging. Do not store at a temperature above 25°C.

Check if there are special storage conditions listed on the packaging.

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

Do not use this medicine after the expiration date shown on the packaging after "CAD". The expiration date is the last day of the month indicated.

Medicines should not be thrown away through drains or into the trash. Deposit the packaging and medicines you no longer need at the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Packaging Contents and Additional Information

Composition of Boltin

• The active ingredient is tibolone.
• The other components are potato starch, lactose, ascorbyl palmitate, and magnesium stearate.

Appearance of the Product and Packaging Contents

Boltin 2.5 mg tablets are white and marked "MK2" on one side and "Organon?" on the other. They are presented in cardboard boxes with 1 calendar blister pack of 28 tablets.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Organon Salud, S.L.

Paseo de la Castellana, 77

28046 Madrid

Spain

Tel.: 915911279

Manufacturer:

N.V. Organon, Oss

PO Box 20

5340 BH Oss

Netherlands

Date of the Last Revision of this Prospectus:August 2020

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