Package Insert: Information for the User

Boltin 2.5 mg Tablets

Tibolone

Read this package insert carefully before you start taking this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others who have the same symptoms as you, as it may harm them.
• If you experience any side effects,consult your doctor or pharmacist, evenifthey are not listed in this package insert. See section 4.

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

Boltin is used for:

To alleviate symptoms that occur after menopause

During menopause, the amount of estrogens produced by the woman's body decreases. This can cause symptoms such as a sensation of heat in the face, neck, and chest (“hot flashes”). Boltin alleviates these symptoms after menopause. Boltin will only be prescribed if your symptoms seriously hinder your daily activities.

Follow carefully all the instructions given by your doctor.

Medical history and medical reviews

The use of hormone replacement therapy or Boltin is associated with risks that must be taken into account when deciding whether to start treatment or continue taking it.

The experience of 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 starting (or restarting) hormone replacement therapy or Boltin, your doctor will ask you 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 internal examination, if necessary.

Once you have started taking Boltin, you should visit your doctor for regular check-ups (at least once a year). In these check-ups, talk to your doctor about the benefits and risks of continuing with Boltin.

Get regular mammograms, as recommended by your doctor.

Do not take Boltin

If you meet any of the following conditions. If you have any doubts about any of them, consult your doctor before taking Boltin.

Do not take Boltin

• if you are allergic to tibolone or any of the other components of this medication (including those listed in section 6).
• if you have or have had any time breast cancer or if you suspect you may have it
• if you have a cancer sensitive to estrogens, such as endometrial cancer, or if you suspect you may have it.
• if you have any unexplained vaginal bleeding.
• if you have any 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 bleeding disorder (such as protein C deficiency, protein S deficiency or antithrombin deficiency).
• if you have or have had a disease caused by blood clots in the arteries, such as myocardial infarction, stroke or angina pectoris.
• if you have or have had liver disease and your liver function tests have not returned to normal.
• if you have a rare blood disorder called "porphyria" that is inherited.
• if you are pregnant or suspect you may be.
• 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 recur or worsen during treatment with Boltin. If so, you should visit your doctor more frequently for medical check-ups:

• fibroids inside the uterus,
• growth of the tissue that covers the inside of the uterus outside of it (endometriosis) or history of excessive growth of the tissue that covers the inside of the uterus (endometrial hyperplasia),
• increased risk of developing blood clots (see "blood clots in a vein (thrombosis)"),
• increased risk of having a cancer sensitive to estrogens (for example, if your mother, sister or grandmother have had breast cancer),
• high blood pressure,
• liver disease, such as a benign liver tumor,
• diabetes
• gallstones,
• migraines or intense headaches,
• systemic lupus erythematosus (LES),
• epilepsy,
• asthma,
• disease affecting 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 visit your 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 white of the eyes (jaundice), which may be a sign of liver disease,
• severe increase in blood pressure (symptoms may include headache, fatigue, dizziness),
• migraine-like headaches that appear for the first time,
• if you become pregnant,
• if you experience signs of a blood clot, such as:
• swollen and painful legs,
• sudden chest pain,
• difficulty breathing.

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

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

Hormone Replacement Therapy and Cancer

Endometrial hyperplasia and endometrial cancer

There have been reports and studies that have registered an increase in the growth of endometrial cells or endometrial cancer (the layer of tissue that covers the inside of the uterus) in women treated with Boltin. This risk of endometrial cancer is greater the longer the treatment.

Irregular bleeding

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

However, if the irregular bleeding:

• continues beyond the first 6 months
• starts after taking Boltin for more than 6 months
• continues after stopping taking Boltin

Visit your doctor as soon as possible

Breast cancer

The available data show that the use of tibolone increases the risk of breast cancer. The additional risk depends on the time during which you use 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 it cannot be ruled out that a similar pattern may occur.

Comparison

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

• sunken or dimpled skin,

• changes in the nipple,

• visible or palpable lumps.

Ovarian cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with estrogens alone or with a combination of estrogens-progestagens has been associated with a slightly higher risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women between 50 and 54 years of age who have not been treated with HRT, there are approximately 2 cases of ovarian cancer per 2,000 women in a 5-year period. In women who have taken HRT for 5 years, there are approximately 3 cases per 2,000 patients (i.e., approximately 1 additional case).

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

Effect of Hormone Replacement Therapy on the Heart and Circulation

Thrombosis

The risk of thrombosis is approximately 1.3 to 3 times higher in women taking hormone replacement therapy than in those who do not take it, especially during the first year of treatment.

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

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

• you are pregnant or have recently given birth,
• you are taking estrogens,
• you are unable to walk for a long time due to a major surgical intervention, injury or disease (see also section 3 “If you need to undergo surgery”),
• you have significant obesity (BMI > 30 kg/m2),
• you have a bleeding disorder that requires long-term treatment with a medication to prevent blood clots,
• if a close relative has had a blood clot in a vein, lung or other organ,
• you have systemic lupus erythematosus (LES),
• you have cancer.

The signs of a blood clot are listed in the section “Stop taking Boltin and visit your doctor immediately”.

Comparison

On average, in a 5-year period, you can expect 4 to 7 women per 1,000 in the 50-year-old age group who do not take hormone replacement therapy to develop a blood clot in a vein. In contrast, for women of the same age who have been taking hormone replacement therapy with estrogens and progestagens for more than 5 years, the number may be 9 to 12 per 1,000 (i.e., 5 additional cases).

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

Cardiovascular disease (myocardial infarction)

There is no indication that hormone replacement therapy or Boltin prevents myocardial infarction.

Women over 60 years old who use hormone replacement therapy with estrogens and progestagens are slightly more likely to develop cardiovascular disease than those who do not take it. Since the risk of cardiovascular disease depends heavily on age, the number of additional cases of cardiovascular disease due to the use of hormone replacement therapy with estrogens and progestagens is very low in healthy women approaching menopause, but increases with advancing age.

There is no indication that the risk of myocardial infarction 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 stroke. This increased risk has been observed mainly in postmenopausal women over 60 years old.

Comparison

On average, in a 5-year period, you can expect 3 women per 1,000 in the 50-year-old age group who do not take Boltin to develop a stroke, while for women of the same age who take Boltin, the number may be 7 per 1,000 (i.e., 4 additional cases).

On average, in a 5-year period, you can expect 11 women per 1,000 in the 60-year-old age group who do not take Boltin to develop a stroke, while for women of the same age who take Boltin, the number may be 24 per 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 medications

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

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

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medication.

Taking Boltin with food and drinks

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 operating machinery

There have been no reports of adverse effects of Boltin on driving or operating machinery.

Boltin contains lactose

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

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

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

First dose of Boltin

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

There are several types of preparations, in tablets, patches, gels. With some, there is bleeding between cycles (sequential preparations) and others are taken continuously.

• If you were taking a sequential type preparation, you should start taking Boltin immediately after the bleeding ends.
• If you were taking a continuous regimen preparation (no 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 beverage.

Take the tablet at the same time every day. Boltin tablets have the days of the week marked. Start taking the tablet marked with the day of the week that starts your treatment. 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 time possible. 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 panic. However, you should consult your doctor as soon as possible. Signs of overdose may include feeling unwell, vomiting, or vaginal bleeding.

If you forgot to take Boltin

If you forgot to take a tablet, take it as soon as you remember, unless more than 12 hours have passed since the last dose. In this case, simply do not take it that day. Do not take a double dose to compensate for the missed doses.

If you need to undergo surgery

If you are going to undergo 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 blood clot (see section 2 Blood clots in a vein). Ask your doctor when you can start taking Boltin again.

In comparison with women who do not use hormone replacement therapy, the following diseases have been reported more frequently in women who use hormone replacement therapy:

• breast cancer,
• abnormal growth or cancer of the tissue that covers the inside of the uterus (endometrial hyperplasia or endometrial cancer),
• ovarian cancer,
• blood clots in the veins of the legs or lungs (venous thromboembolism),
• cardiac diseases,
• stroke,
• probable 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 medications, this medication may produce adverse effects, although not all people will experience 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
• unwanted hair growth
• vaginal discomfort such as discharge, itching, and irritation.

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

• acne

Other adverse effects have also been observed with general use, including:

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

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

Inform your doctor if vaginal bleeding or spotting occurs, or if any of the above adverse effects are bothersome or persistent.

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

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

Reporting adverse effects:

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

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

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

Keepthis medicationout of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after “CAD”. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and unused medications at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications.This will help protect the environment.

Composition of Boltin

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

Appearance of the product and contents of the packaging

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

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

Organon Salud, S.L.

Paseo de la Castellana, 77

28046 Madrid

Spain

Phone:915911279

Responsible for manufacturing:

N.V. Organon, Oss

PO Box 20

5340 BH Oss

Netherlands

Last review date of this leaflet:August 2020

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/