SHYLA

PACKAGE LEAFLET

Package leaflet: information for the user

Shyla 2.5 mg tablets

tibolone
Generic Medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Shyla is and what it is used for

This medicinal product is a hormone replacement therapy (HRT). It contains tibolone, a substance that exerts beneficial effects on various tissues in the body, such as brain, vaginal and bone tissue.
This medicine is used in postmenopausal women after at least 12 months have passed since the last natural menstrual period.
This medicine is used for:
Relief of symptoms occurring after menopause
During menopause, the amount of estrogens produced by a woman's body decreases. This can cause symptoms such as a feeling of warmth in the face, neck and chest ("hot flushes"). Shyla relieves these symptoms after menopause. Your doctor will prescribe this medicine only if your symptoms severely affect your daily life.
Prevention of osteoporosis
After menopause, some women may develop bone fragility (osteoporosis). Discuss all available treatment options with your doctor.
If you are at increased risk of fractures due to osteoporosis and other medicines are not suitable for you, you may use Shyla to prevent osteoporosis after menopause.
There are three different types of HRT:

• Estrogen-only HRT.
• Combined HRT, containing two types of female hormones, an estrogen and a progestogen.
• Shyla, which contains a substance called tibolone.

Shyla is different from other HRTs. Instead of containing actual hormones (such as estrogen and progestogen), it contains tibolone. Your body metabolizes tibolone to produce hormones.
Its effects and benefits are similar to those of a combined HRT.

2. What you should know before taking Shyla

Medical history and regular check-ups
Hormone replacement therapy (HRT) involves certain risks, which must be considered when deciding whether to start or continue taking this medicine.
Experience with treatment in women who have entered menopause prematurely (due to ovarian failure or surgical intervention) is limited. If you have experienced premature menopause, the risks associated with HRT may differ. Please consult your doctor.
Before starting (or restarting) HRT, your doctor will ask you questions about your personal and family medical history. They may also decide to perform a physical examination, which could include a breast examination and/or an internal examination, if necessary.
Inform your doctor if you have any medical problems or diseases.

Regular check-ups
Once you have started treatment with Shyla, you must 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 Shyla therapy.
Undergo regular mammographic screening as recommended by your doctor.
Do not forget to:

• undergo regular mammographic screening and cervical smear tests;
• regularly check for changes in the breasts such as dimpling or indentations of the skin, nipple changes, or any lumps visible or palpable.

Do not take Shyla:

• If you have or have ever had breast cancer, or if you suspect you might have it;
• If you have a form of cancer sensitive to estrogens, such as cancer of the uterine lining (endometrium), or if you suspect you might have it;
• If you have unexplained vaginal bleeding;
• If you have excessive thickening of the uterine lining (endometrial hyperplasia) that has not been treated;
• If you have or have ever had a blood clot in a vein (thrombosis), for example in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism);
• If you suffer from a blood clotting disorder (such as deficiency of protein C, protein S, or antithrombin);
• If you currently suffer or have recently suffered from an arterial disease caused by blood clots, such as heart attack, stroke, or angina;
• If you suffer from a liver disease and liver function test results have not returned to normal;
• If you have a rare inherited blood disease called "porphyria";
• If you are allergic to tibolone or to any of the other ingredients of Shyla (listed in section 6);

If you are unsure about any of the above points, consult your doctor before taking Shyla.
If any of the above conditions appear for the first time during treatment with Shyla, stop taking the medicine immediately and consult your doctor without delay.

Warnings and precautions
Talk to your doctor or pharmacist before taking Shyla.
In addition to its benefits, HRT also involves certain risks, which must be considered when deciding whether to start or continue taking the medicine.
Before starting treatment, inform your doctor if you have ever suffered from any of the following conditions, as they may reappear or worsen during treatment with Shyla. In such cases, your doctor may need to perform more frequent check-ups:

• uterine fibroids;
• growth of uterine lining tissue outside the uterus (endometriosis), or history of excessive growth of the uterine lining (endometrial hyperplasia);
• increased risk of developing blood clots (see “Blood clots in a vein (thrombosis)”);
• increased risk of developing an estrogen-sensitive tumor (e.g., if your mother, sister, or grandmother had breast cancer);
• high blood pressure;
• liver disease, such as benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headache;
• an autoimmune disease affecting multiple organs (systemic lupus erythematosus, SLE);
• epilepsy;
• asthma;
• a disease affecting the eardrum and hearing (otosclerosis);
• very high levels of fats (triglycerides) in the blood;
• fluid retention due to heart or kidney problems.

For athletes: Using this medicine without therapeutic need constitutes doping and may lead to a positive result in anti-doping tests.

Stop taking Shyla and consult a doctor immediately
If, during HRT, you notice any of the following conditions:

• any of the conditions listed under “DO NOT take Shyla”;
• yellowing of the skin or whites of the eyes (jaundice). These may be signs of liver disease;
• a marked increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• new-onset migraine-like 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 further information, see “Blood clots in a vein (thrombosis)”.

Note: Tibolone 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. Ask your doctor for advice.

Hormone replacement therapy and cancer

Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer)
Increased cell growth or cancer of the uterine lining has been reported in women using tibolone. The risk of endometrial cancer increases the longer the medicine is taken.

Irregular bleeding
During the first 3–6 months of treatment with Shyla, you may experience irregular bleeding or small blood spots (spotting). However, if irregular bleeding:

• persists beyond the first 6 months;
• starts after you have been taking Shyla for more than 6 months;
• persists even after you have stopped taking Shyla; ➔ consult your doctor as soon as possible.

Breast cancer
Evidence shows that taking tibolone increases the risk of breast cancer. The additional risk depends on the duration of tibolone use. In HRT studies, after stopping HRT, the additional risk decreased over time, but this risk may persist for 10 years or more if HRT has been used for more than 5 years. Regarding tibolone, data on the persistence of risk after discontinuation are not available, but a similar pattern cannot be excluded.

Comparison
In women aged 50 to 79 years not using HRT, on average, breast cancer will be diagnosed in 9–17 out of 1,000 women over a 5-year period. In women aged 50 to 79 years using combined estrogen-progestin HRT for 5 years, there will be 13 to 23 cases per 1,000 users (i.e., 4 to 6 additional cases).
Women taking tibolone have a lower risk compared to women using combined HRT and a similar risk to those using estrogen-only HRT.

Check your breasts regularly. Consult your doctor as soon as possible if you notice any changes, such as:

• dimpling or indentations of the skin;
• changes in the nipple;
• any lumps visible or palpable.

Additionally, you are advised to participate in mammographic screening programs when offered.
For mammographic screening, it is important that you inform the nurse/healthcare professional performing the X-ray that you are using HRT, as this medicine can increase breast density, which affects the mammogram result. If breast density increases, mammography may not detect all lumps.

Ovarian cancer
Ovarian cancer is rare, much rarer than breast cancer. The use of estrogen-only and combined estrogen-progestin 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 using HRT, ovarian cancer will be diagnosed in about 2 out of 2,000 women over a 5-year period. For women using hormone replacement therapy for 5 years, there will be about 3 cases per 2,000 (i.e., up to 1 additional case).
The risk increase with Shyla use is similar to that of other types of HRT.

Effect of HRT on the heart and circulation

Blood clots in a vein (thrombosis)
The risk of blood clots in veins is approximately 1.3–3 times higher in women using HRT than in women not using HRT, especially during the first year of treatment.
Venous blood clots can be serious; if they travel to the lungs, they can cause chest pain, shortness of breath, fainting, or even death.
The likelihood of developing a venous blood clot increases with age and in the following situations. If any of these apply to you, inform your doctor:

• if you are unable to walk for long periods due to major surgery, trauma, or illness (see also section 3, “In case of surgery”);
• if you are severely overweight (BMI >30 kg/m²);
• if you have any clotting disorder requiring long-term anticoagulant treatment;
• if any of your close relatives have ever had blood clots in the legs, lungs, or other organs;
• if you have systemic lupus erythematosus (SLE);
• if you have cancer.

For signs of a blood clot, see the section “Stop taking Shyla and consult a doctor immediately”.

Comparison
Among women aged 50 to 60 not using HRT, it is expected that, on average, 4 to 7 out of 1,000 will develop a venous blood clot over a 5-year period.
Among women aged 50 to 60 using estrogen-progestin HRT for more than 5 years, the number will be 9 to 12 per 1,000 (i.e., 5 additional cases).
With tibolone use, the increase in risk of developing a venous blood clot is lower than with other types of HRT.

Heart disease (heart attack)
There is no evidence that HRT or tibolone prevent heart attacks.
Women over 60 years of age using estrogen-progestin HRT have a slightly higher probability of developing heart disease compared to those not using HRT.
There is no evidence suggesting that the risk of myocardial infarction with tibolone differs from the risk with other HRT.

Stroke
The risk of stroke is about 1.5 times higher in women using HRT than in those not using it.
The number of additional stroke cases caused by HRT therapy increases with age.
Other factors that may increase stroke risk include:

• High blood pressure
• Smoking
• Heavy alcohol consumption
• Irregular heartbeat
  If you are concerned about any of these factors, consult your doctor to determine whether HRT is suitable for you.

Comparison
Among women aged 50 to 60 not using HRT, it is expected that, on average, 8 out of 1,000 will suffer a stroke over a 5-year period. Among women aged 50 to 60 using HRT, there will be 11 cases per 1,000 users over 5 years (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 hormone replacement therapy after age 65. Consult your doctor.
Shyla is not indicated for contraceptive use.
Estrogens may cause fluid retention; therefore, patients with renal or cardiac dysfunction should be closely monitored.
Women with pre-existing hypertriglyceridemia should be closely followed during estrogen therapy or HRT, as rare cases of significant increases in plasma triglycerides and subsequent pancreatitis have been reported with estrogen therapy.

Other medicines and Shyla
Some medicines may interfere with the effect of Shyla. This could cause irregular bleeding. The following medicines are known to interact:

• 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);
• Medicines affecting blood clotting (such as warfarin);
• Herbal remedies containing St. John’s wort (Hypericum perforatum).

Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including over-the-counter medicines, herbal remedies, or other natural products.

Laboratory tests
If you need to have a blood test, inform your doctor or healthcare staff that you are taking Shyla, as this medicine may affect the results of certain tests.

Tibolone with food and drink
You may eat and drink normally while taking Shyla.

Pregnancy, breastfeeding, and fertility
Shyla is intended for use in postmenopausal women only. If you become pregnant, stop taking Shyla and consult your doctor.

Driving and using machines
Tibolone has no known effect on the ability to drive or operate machinery.

Shyla contains lactose:
One tablet contains 43.2 mg of monohydrate lactose. If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine.

3. How to take Shyla

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is one tablet daily.
Tibolone should be taken without chewing, with a little water.
Tablets should be taken at the same time each day.
The tablet strips show the days of the week. Start by taking a tablet marked with today's date. For example, if treatment begins on Monday, take a tablet marked "Mo" in the first row of the strip. Follow the arrows until the strip is empty. Start the next strip the following day. Do not leave any gap between strips or packs.
Your doctor will prescribe the lowest effective dose needed to treat your symptoms, for the shortest possible duration.
If you think this dose is too strong or too weak, consult your doctor.
You should start taking tibolone no earlier than 12 months after your last spontaneous menstrual period.
However, if you have had surgical removal of the uterus and ovaries, or have been treated with medications such as gonadotropin-releasing hormone analogues (GnRH), for conditions such as endometriosis, you may start taking tibolone immediately.
If you have never taken HRT before, you may start taking tibolone immediately.
If switching from another type of HRT
There are different types of HRT, such as tablets, patches and gels. Most contain an oestrogen and a progestogen. With some types, you have a monthly bleed; with others, you do not (continuous HRT).
If you are switching from another type of HRT and are currently having a monthly bleed, start taking tibolone as soon as your bleed ends.
If you are switching from a continuous HRT (without monthly bleeds), you may start taking tibolone immediately. You may also start immediately if you are being treated for endometriosis.
Use in children and adolescents
Tibolone must not be taken by children.
If you take more Shyla than you should
Toxic effects are unlikely, even if several tablets are taken, but you may feel unwell, be nauseous or experience vaginal bleeding.
If you forget to take tibolone
If you forget to take a tablet at your usual time, take it as soon as possible, unless more than 12 hours have passed since the missed dose. In that case, skip the forgotten tablet and take the next tablet at your usual time.
Do not take a double dose.
If you are undergoing surgery
If you are about to have surgery, inform your surgeon that you are taking Shyla. You may need to stop taking Shyla approximately 4–6 weeks before surgery to reduce the risk of blood clots (see section 2, “Blood clots in a vein”). Ask your doctor when you can restart taking Shyla.
If you stop taking tibolone
Do not stop taking tibolone just because you feel better without first consulting your doctor. It is important to take the medicine exactly as prescribed by your doctor. Otherwise, your symptoms may return.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

The following conditions are reported more frequently in women undergoing HRT compared to women not undergoing HRT:

• breast cancer;
• abnormal growth or tumour of the uterine lining (endometrial hyperplasia or endometrial cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• heart disease;
• stroke;
• possible loss of memory if HRT is started after the age of 65.

For further information on these side effects, see paragraph 2.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most side effects are mild.
Serious side effects – consult a doctor immediately
If you think you are experiencing signs of a serious side effect, consult a doctor immediately.
You may need to stop taking Shyla:

• If your blood pressure increases
• If your skin or the whites of your eyes turn yellowish ( jaundice )
• If you experience sudden headaches similar to migraines (see paragraph 2 above)
• If you experience signs of a blood clot (see paragraph 2 above)
• If any of the conditions listed in paragraph 2 (“Do not take Shyla”) occur

Other side effects
Common (affects up to 1 in 10 women):

• breast pain
• stomach or pelvic pain
• unusual hair growth
• vaginal bleeding or discharge. This is generally not a cause for concern during the first few months of HRT. If bleeding continues or starts after HRT has been ongoing for some time, see paragraph 2 “Irregular bleeding”.
• vaginal problems, such as increased discharge, itching, irritation
• inflammation of the vulva and vagina (vulvovaginitis)
• thrush (candidiasis)
• thickening of the uterine lining or cervical lining
• tissue changes in the cervix
• abnormal cervical smear
• weight gain

Uncommon (affects up to 1 in 100 women):

• swelling of hands, ankles or feet – a sign of fluid retention
• stomach discomfort
• acne
• sore nipples or breast discomfort
• vaginal infection (fungal)
• fungal infection

Rare (affects up to 1 in 1,000 women):

• skin itching

Some women taking Shyla have also reported:

• depression, dizziness, headache

• joint or muscle pain

• skin problems such as rash or itching

• loss of vision or blurred vision

• changes in liver function test parameters. Breast cancer and increased cell growth or tumour of the uterine lining have been reported in women using Shyla.

• If any of the above side effects persist or worsen, inform your doctor.

The following side effects have been reported with other HRTs:

• gallbladder disease (cholestatic gallbladder or biliary tract disorders)
• various skin disorders:
• skin discolouration, especially on the face or neck, known as "pregnancy mask" (chloasma)
• painful red nodules (erythema nodosum)
• skin rash with redness or inflammation (erythema multiforme)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Shyla

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage temperature.
Store in the original packaging to protect the medicine from light and moisture.
Do not use this medicine after the expiry date stated on the blister pack/box after EXP.
The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Shyla contains

• The active substance is tibolone.
• The other ingredients are: monohydrate lactose (see section 2, “Shyla contains lactose”), mannitol, potato starch, ascorbyl palmitate and magnesium stearate.

Description of the appearance of Shyla and pack sizes
Shyla is supplied as round, white to off-white tablets, 6 mm in diameter, with bevelled edges and no markings.
Available in packs containing 1, 3 or 6 blisters with either 28 or 30 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest, Hungary

Manufacturer
Cenexi
17, rue de Pontoise
95520 OSNY
FRANCE