Boltin 2.5 mg tablets

Patient Information Leaflet

Introduction

Patient Information Leaflet

Boltin 2.5 mg tablets

Tibolone

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

• Keep this leaflet, 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, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet Contents

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

1. What Boltin is and what it is used for

Boltin is a hormone replacement therapy (HRT). Boltin contains tibolone, a substance that has beneficial effects on various tissues in the body, such as the brain, the vagina, and the bone. Boltin is used in postmenopausal women who have been naturally without menstruation for at least 12 months.

Boltin is used for:

Relieving symptoms that occur after menopause

During menopause, the amount of estrogen produced by a woman's body decreases. This may cause symptoms such as a feeling of warmth in the face, neck, and chest ("hot flushes"). Boltin relieves these postmenopausal symptoms. Boltin will only be prescribed to you if your symptoms seriously interfere with your daily activities.

2. What you need to know before starting to take Boltin

Carefully follow all instructions given by your doctor.

Medical history and medical check-ups

The use of hormone replacement therapy (HRT) or Boltin carries risks that must 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 differ.

Before starting (or restarting) hormone replacement therapy or Boltin, your doctor will ask about your personal and family medical history. Your doctor may decide to perform a physical examination, which may include a breast examination and a pelvic exam, if necessary.

Once you have started taking Boltin, you should visit your doctor regularly for check-ups (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing Boltin.

Have regular mammograms as recommended by your doctor.

Do not take Boltin

If any of the following conditions apply to you. 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 to any of the other components of this medicine (listed in section 6).
• if you have or have ever had breast cancer or suspect you may have it.
• if you have a cancer sensitive to estrogens, such as cancer of the tissue lining the inside of the uterus (endometrial cancer), or if such cancer is suspected.
• if you have any unexplained vaginal bleeding.
• if you have excessive growth of the tissue lining the inside of the uterus (endometrial hyperplasia) that is not being treated.
• if you currently 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 currently have or have recently had a disease caused by blood clots in the arteries, such as myocardial infarction, stroke, or angina pectoris.
• if you have or have had a liver disease and your liver function tests have not returned to normal.
• if you have a rare inherited blood disorder called "porphyria".
• if you are pregnant or suspect you may be pregnant.
• if you are breastfeeding.

If any of the above conditions appear for the first time while you are taking Boltin, stop taking it immediately and consult your doctor without delay.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Boltin.

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

• fibroids in the uterus,
• growth of the tissue lining the inside of the uterus outside the uterus (endometriosis) or history of excessive growth of the tissue lining the inside 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 (for example, if your mother, sister, or grandmother had breast cancer),
• high blood pressure,
• a liver disorder, such as a benign liver tumor,
• diabetes,
• gallstones,
• migraine headaches or severe headaches,
• an immune system disorder affecting multiple organs of the body (systemic lupus erythematosus, SLE),
• epilepsy,
• asthma,
• a condition affecting the eardrum and hearing (otosclerosis),
• very high levels of fat in the blood (triglycerides),
• fluid retention due to heart or kidney problems.

Stop taking Boltin and seek medical advice immediately

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

• any of the conditions listed in the section “Do not take Boltin”,
• yellowing of the skin or whites of the eyes (jaundice), which may be a sign of liver disease,
• a significant increase in blood pressure (symptoms may include headache, fatigue, dizziness),
• new-onset migraine-type headaches,
• if you become pregnant,
• if you develop 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)".

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

Hormone Replacement Therapy and Cancer

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

Reports and studies have documented an increased growth of endometrial cells or endometrial cancer (the tissue layer lining the inside of the uterus) in women treated with Boltin. The risk of endometrial cancer increases 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 after you have been taking Boltin for more than 6 months,
• continues after you have stopped taking Boltin,

contact your doctor as soon as possible.

Breast cancer

Available data show that the use of tibolone increases the risk of breast cancer. The additional risk depends on how long you use tibolone. In HRT studies, 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. Data on the persistence of risk after stopping tibolone are not available, 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.

• Examine your breasts regularly. Contact your doctor if you notice any changes such as:

• skin dimpling or pitting,

• changes in the nipple,

• presence of visible or palpable lumps.

Ovarian cancer

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

With the use of Boltin, the increase in 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 veins is approximately 1.3 to 3 times higher in women taking hormone replacement therapy than in those who do not, especially during the first year of treatment.

Venous blood clots can be serious, and if one travels to the lungs, it can cause chest pain, dyspnea (shortness of breath or difficulty breathing), fainting, or even death.

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

• you are pregnant or have recently given birth,
• you are using estrogens,
• you are unable to walk for long periods due to major surgery, injury, or illness (see also section 3 “If you need to undergo surgery”),
• you are significantly overweight (BMI > 30 kg/m²),
• you have a blood clotting disorder requiring long-term treatment with anticoagulant medication,
• if a close relative has had a blood clot in the leg, lung, or another organ,
• you have systemic lupus erythematosus (SLE),
• you have cancer.

Signs of a blood clot are listed in the section “Stop taking Boltin and seek medical advice immediately”.

Comparison

On average, over a 5-year period, it is expected that between 4 and 7 out of 1,000 women in their 50s who do not take HRT will develop a venous blood clot.

In contrast, among 1,000 women of this age who have been taking estrogen-progestogen HRT for more than 5 years, there will be between 9 and 12 cases (i.e., 5 additional cases).

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

Heart disease (myocardial infarction)

There is no evidence that hormone replacement therapy or Boltin prevent myocardial infarction.

Women over 60 years of age who use estrogen-progestogen hormone replacement therapy are somewhat more likely to develop heart disease than those who do not. Since the risk of heart disease depends strongly on age, the number of additional cases of heart disease due to estrogen-progestogen HRT is very low in healthy women close to menopause, but increases with advancing age.

There is no evidence to suggest that the risk of myocardial infarction with Boltin differs 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 primarily in older postmenopausal women over the age of 60.

Comparison

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

On average, over a 5-year period, it is expected that 11 out of 1,000 women in their 60s who do not take Boltin will have a stroke, while among women of this age who take Boltin, the number 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 an increased risk of memory loss in women who start using hormone replacement therapy after age 65. Seek advice from your doctor.

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: drugs for 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 together with other hormone replacement therapy products.

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

Taking Boltin with food and drinks

You may eat and drink normally while taking Boltin.

Pregnancy, breastfeeding, and fertility

Boltin is intended for use only in postmenopausal women. If you become pregnant, stop taking Boltin and contact your doctor immediately.

Driving and using machines

No adverse effects of Boltin on the ability to drive or operate machinery have been reported.

Boltin contains lactose

This medicine contains lactose. If your doctor has informed you that you have an intolerance to certain sugars, consult with him before taking this medicine.

3. How to take Boltin

Follow exactly the instructions for administering this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

Boltin should not be taken until twelve months have passed since your last natural menstrual period. If Boltin is taken earlier, the likelihood of experiencing irregular vaginal bleeding may increase.

First dose of Boltin

• If you have not previously taken any other hormone replacement therapy (HRT) medicines, you may start immediately.
• If switching from another hormone replacement therapy preparation:

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

• If you were taking a sequential-type preparation, you should start taking Boltin immediately after your bleeding ends.
• If you were taking a continuous regimen (without bleeding), you may start taking Boltin at any time.

Boltin must be taken orally. Take one tablet daily, swallowing it with a little water or another drink.

Take the tablet at the same time each day. Boltin blister packs are marked with the days of the week. Begin by taking the tablet marked with the day of the week on which 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 following day. Do not leave any gap between blisters or packs.

Your doctor will aim to prescribe the lowest effective dose to treat your symptoms for the shortest possible duration. 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 recommended, consult a doctor or pharmacist immediately. If someone takes too many tablets, there is no need to panic. However, you should contact your doctor as soon as possible. Signs of overdose may include feeling unwell, nausea, or vaginal bleeding.

If you forget to take Boltin

If you forget to take a tablet, take it as soon as you remember, provided that less than 12 hours have passed since the missed dose. If more than 12 hours have passed, simply skip that dose. Do not take a double dose to make up for forgotten doses.

If you need to undergo surgery

If you are scheduled for surgery, inform your 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 clots (see section 2 Blood clots in a vein). Ask your doctor when you can restart taking Boltin.

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 age 65.

See section 2 for more information about these adverse effects.

Like all medicines, this medicine may cause adverse effects, although not everyone gets 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
• abnormal hair growth
• vaginal discomfort such as discharge, itching, and irritation.

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

• acne

Other adverse effects observed with general use include:

• dizziness, headache, migraine, depression
• skin rash or itching
• visual disturbances
• gastrointestinal discomfort
• fluid retention (swelling in the legs)
• joint or muscle pain
• changes in liver function laboratory tests

Cases of breast cancer and increased growth of endometrial cells or endometrial cancer have been reported 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 disease,
• various skin disorders:
  • skin discoloration, especially on the face or neck, known as "pregnancy mask" (chloasma),
  • painful red nodules on the skin (erythema nodosum),
  • skin rash with lesions or red target-shaped papules (erythema multiforme).

Reporting of adverse effects:

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

5. Storage of Boltin

Keep in the original packaging. Do not store above 25°C.

Check the packaging for any special storage conditions.

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

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.

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

6. Contents of the pack and other information

Composition of Boltin

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

Appearance of the product and contents of the pack

Boltin 2.5 mg tablets are white and marked “MK2” on one side and “Organon?” on the other. They are supplied in cardboard boxes containing 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

P.O. Box 20

5340 BH Oss

The Netherlands

Date of the latest revision of this leaflet: August 2020

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/