PACKAGE LEAFLET

Package leaflet: information for the patient

Menec 2.5 mg tablets

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

Keep this leaflet. You may need to read it again.
If you have any questions, ask 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 adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

What Menec is and what it is used for
What you need to know before taking Menec
How to take Menec
Possible side effects
How to store Menec
Contents of the pack and other information

1. What Menec is and what it is used for

This medicinal product is a hormone replacement therapy (HRT). It contains tibolone, a substance that exerts
positive effects on various tissues in the body, such as brain, vaginal, and bone tissue.
This medicinal product is used in postmenopausal women after at least 12 months have passed since their last
natural menstrual period.
This medicinal product is used for:
Relief of symptoms occurring after menopause
During menopause, the amount of oestrogen 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"). Menec relieves these
symptoms after menopause. This medicinal product will be prescribed to you only if your symptoms severely
affect your daily life.
Prevention of osteoporosis
After menopause, some women may develop brittle bones (osteoporosis). Discuss with your doctor all available
treatment options.
If you are at increased risk of fractures due to osteoporosis and other medicinal products are not suitable for
you, you may use Menec to prevent osteoporosis after menopause.
There are three different types of hormone replacement therapies:

oestrogen-only hormone replacement therapy
combined hormone replacement therapy, containing two types of female hormones, an oestrogen and a progestogen
Menec, which contains a substance called tibolone.

Menec is different from other hormone replacement therapies: instead of containing actual hormones (such as oestrogen and progestogen),
it contains tibolone. The body breaks down tibolone to produce hormones.
The effects and benefits of Menec are similar to those of a combined hormone replacement therapy.

2. What you should know before taking Menec

Medical history and regular check-ups
Hormone replacement therapy involves certain risks that must be considered when deciding whether to start or continue taking the medicine.
Experience in treating women who have entered menopause prematurely (due to ovarian insufficiency or surgical intervention) is limited. If you have entered menopause prematurely, the risks associated with hormone replacement therapy may differ. Consult your doctor.
Before starting (or restarting) hormone replacement therapy, your doctor will ask you questions about your personal and family medical history. They may also decide to perform a physical examination, including a breast and/or pelvic examination, if necessary.
Inform your doctor if you have any medical problems or diseases.

Regular check-ups
Once you have started treatment with Menec, 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 associated with continuing therapy with Menec.
Have regular mammograms as recommended by your doctor.
Do not forget to:

have regular mammograms and cervical smear tests;
regularly check for any changes in your breasts, such as dimpling or indentations of the skin, changes in the nipple, or any lumps visible or palpable by touch.

Do not take Menec:

if you have or have previously had breast cancer, or if you suspect you may have it;
if you suffer from a form of estrogen-sensitive cancer, such as cancer of the uterine lining (endometrium), or if you suspect you may have it;
if you have abnormal vaginal bleeding;
if you have excessive thickening of the uterine lining (endometrial hyperplasia) that is untreated;
if you have or have previously 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 protein C, protein S or antithrombin deficiency);
if you suffer or have recently suffered from an arterial disease caused by blood clots, such as heart attack, stroke, or angina;
if you suffer or have previously suffered from liver disease and liver function test results are not within normal limits;
if you suffer from a rare inherited blood disorder called "porphyria";
if you are allergic to tibolone or to any of the other ingredients of Menec (listed in section 6).

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Menec.
In addition to benefits, hormone replacement therapy also involves certain risks that 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 recur or worsen during treatment with Menec. In such cases, your doctor may need to perform check-ups more frequently:

uterine fibroids;
growth of the uterine lining 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 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);
epilepsy;
asthma;
a disease affecting the eardrum and impairing hearing (otosclerosis);
very high levels of fats (triglycerides) in the blood;
fluid retention due to heart or kidney problems.

For athletes: using the medicine without therapeutic need constitutes doping and may lead to a positive result in anti-doping tests.
Stop taking Menec and consult a doctor immediately
if, during hormone replacement therapy, you notice any of the following conditions:

any of the conditions listed in the section "DO NOT take Menec";
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);
headaches similar to migraines occurring for the first time;
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 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)
An 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 Menec, 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 Menec for more than 6 months;
persists even after stopping Menec ➔ 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 studies on hormone replacement therapy, after stopping such therapy, the additional risk decreased over time, but could persist for 10 years or longer if hormone replacement therapy was 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
Among women aged 50 to 79 years not using hormone replacement therapy, on average, breast cancer will be diagnosed in 9–17 out of 1,000 women over a 5-year period. Among women aged 50 to 79 years using combined estrogen-progestin hormone replacement therapy 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 those on combined hormone replacement therapy, while their risk is similar to those taking estrogen-only hormone replacement therapy.

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

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

In addition, participation in mammographic screening programs is recommended when offered. For mammographic screening, it is important to inform the nurse/healthcare professional performing the X-ray that you are undergoing hormone replacement therapy, as this therapy can increase breast density, which affects the mammogram result. If breast density increases, mammography may not be able to detect all lumps.

Ovarian cancer
Ovarian cancer is rare, much rarer than breast cancer. The use of estrogen-only or combined estrogen-progestin hormone replacement therapy has been associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer varies with age. For example, among women aged 50 to 54 years not using hormone replacement therapy, 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 of ovarian cancer per 2,000 women (i.e. up to 1 additional case).
With the use of Menec, the increase in ovarian cancer risk is similar to that of other types of hormone replacement therapy.

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 using hormone replacement therapy compared to those not using it, especially during the first year of treatment.
Venous blood clots can be serious and, if they travel to the lungs, 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, "If you need to undergo surgery");
if you are severely overweight (BMI >30 kg/m²);
if you suffer from 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 suffer from systemic lupus erythematosus;
if you have cancer.

For signs of a blood clot, see the section "Stop taking Menec and consult a doctor immediately."

Comparison
Among women aged 50 to 60 years not using hormone replacement therapy, 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 years using estrogen-progestin hormone replacement therapy for over 5 years, the number will be 9 to 12 out of 1,000 (i.e. 5 additional cases).
With the use of tibolone, the increase in the risk of developing a venous blood clot is lower than with other types of hormone replacement therapy.

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

Stroke
The risk of stroke is approximately 1.5 times higher in women using hormone replacement therapy compared to those not using it. The number of additional stroke cases due to hormone replacement therapy increases with age.

Comparison
Among women aged 50 to 60 years not using hormone replacement therapy, 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 years using hormone replacement therapy, there will be 11 cases per 1,000 users over 5 years (i.e. 3 additional cases).

Other conditions
Hormone replacement therapy 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. Ask your doctor for advice.
Menec 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 monitored during estrogen replacement therapy or hormone replacement therapy, as rare cases of marked increases in plasma triglycerides and subsequent pancreatitis have been reported with estrogen therapy.

Other medicines and Menec
Some medicines may interfere with the effect of Menec, which could cause irregular bleeding. This applies to the following medicines:

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 for blood clotting (such as warfarin);
herbal remedies containing St. John's wort (Hypericum perforatum).

Hormone replacement therapy may affect how some other medicines work:

an epilepsy medicine (lamotrigine), as it could increase the frequency of seizures.

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

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

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

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

Menec 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 Menec

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 with a glass of water, without chewing the tablet.
Tablets should be taken at the same time each day.
The tablet strips indicate the days of the week. Start by taking the tablet marked with today's date. For example,
if treatment begins on a Monday, take the tablet marked "Mon" 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 necessary to treat your symptoms for the shortest possible
duration.
If you think this dose is too strong or too weak, consult your doctor.
You must not start taking tibolone until at least 12 months have passed since your last spontaneous menstrual
period.
However, if you have had surgical removal of the uterus and ovaries, or if you have been treated with drugs such
as gonadotropin-releasing hormone analogues ( GnRH ), for conditions such as endometriosis, you may start
taking tibolone immediately.
If you have never previously taken hormone replacement therapy , you may start taking tibolone immediately.
If switching from another type of hormone replacement therapy
There are different types of hormone replacement therapies, including tablets, patches, and gels. Most contain
an oestrogen and a progestogen. With some of these types, menstrual bleeding occurs, while with others it does
not (non-cyclical hormone replacement therapy).
If you are switching from a hormone replacement therapy that causes menstrual bleeding, start taking tibolone
immediately after the end of your bleeding.
If you are switching from a hormone replacement therapy that does not cause menstrual bleeding, 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 Menec than you should
Taking more than one tablet is unlikely to cause toxicity. However, you may experience nausea, vomiting, or
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 missed tablet and take the next tablet at your usual time.
Do not take a double dose.
If you are due to have surgery
If you are about to undergo surgery, inform your surgeon that you are taking Menec. You may need to stop
taking Menec approximately 4–6 weeks before the procedure to reduce the risk of a blood clot (see section 2,
“Blood clots in a vein”). Ask your doctor when you can restart taking Menec.
If you stop taking tibolone
Do not stop taking tibolone 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 questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

The following conditions are reported more frequently in women receiving hormone replacement therapy (HRT) compared to women not receiving this therapy:

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 memory loss if hormone replacement therapy is started after the age of 65.

For further information on these side effects, see section 2.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most side effects are mild.
Other side effects
Common (may affect up to 1 in 10 women):

breast tenderness
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 hormone replacement therapy. If bleeding continues or starts after you have been on therapy for some time, see section 2 “Irregular bleeding”
vaginal problems, such as increased discharge, itching, irritation
inflammation of the vulva and vagina (vulvovaginitis)
fungal infection (candidiasis)
thickening of the uterine lining or cervical lining
tissue changes in the cervix
abnormal cervical smear
weight gain

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

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

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

skin itching

Some women taking Menec 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

In women using Menec, breast cancer and increased cell growth or tumour of the uterine lining have been reported. ➔ If any of the side effects listed above persist or worsen, inform your doctor.

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

gallbladder disease (cholelithiasis or cholecystitis)
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 target-shaped redness or ulcerations (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 Menec

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage temperature.
Store in the original blister and outer carton to protect the medicine from light and moisture.
Do not use this medicine after the expiry date stated on the blister and on the box after "Exp.".
The expiry date refers to the last day of that month.
Do not dispose of medicines 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 Menec contains

The active substance is tibolone.
The other components are: monohydrate lactose (see section 2, “Menec contains lactose”), mannitol (E421), potato starch, ascorbyl palmitate (E304), and magnesium stearate (E470).

Description of the appearance of Menec and package contents
Menec is presented as round, white to off-white tablets, 6 mm in diameter, with bevelled edges and no markings. It is available in packs containing 1 or 3 blisters of 30 tablets each.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Farmitalia S.r.l.
Via Pinciana 25
00198 Rome
Italy

Manufacturer
Cenexi - Osny Plant
17, Pontoise Street
95520 Osny
France

This medicinal product is authorised in the European Economic Area Member States under the following names:
Italy: Menec
Sweden: Menec 2.5 mg tablets