Velbienne mini

Package leaflet: Information for the user

Velbienne mini, 1 mg + 2 mg, film-coated tablets
Estradiol valerate and dienogest
Please read all of this leaflet carefully before 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 further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

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

1. What Velbienne mini is and what it is used for

Velbienne mini is a medicine used in hormone replacement therapy (HRT).
It contains two types of female hormones, an estrogen and a progestagen. Velbienne mini is indicated for use in postmenopausal women who have had at least 12 months since their last natural menstrual period.
Velbienne mini is used to:
Relieve symptoms occurring after menopause
During menopause, the amount of estrogen produced by a woman's body decreases.
This may result in symptoms such as hot flushes affecting the face, neck, and chest (also known as hot flashes). Velbienne mini relieves these postmenopausal symptoms. Velbienne mini is prescribed only when symptoms significantly impair the patient's daily life.

2. Important information before using Velbienne mini

Medical history and regular check-ups
Hormone replacement therapy (HRT) carries risks that should be considered when deciding whether to start or continue treatment.
Experience with HRT use in women with premature menopause (due to ovarian failure or surgical procedures) is limited. In women with premature menopause, the risks of HRT may differ. Consult your doctor.
Before starting (or restarting) HRT, your doctor will take a detailed medical history of you and your family. Your doctor may perform a physical examination, including breast and (or) pelvic examination, if necessary.

• After starting Velbienne mini, you should attend regular check-up visits (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing Velbienne mini.
• You should undergo regular breast examinations as recommended by your doctor.

When not to use Velbienne mini
If any of the following apply to you, or if you have any doubts about any of the points listed below, you should consult your doctor before using Velbienne mini.
Do not use Velbienne mini:

• if you currently have or have had breast cancer, or if breast cancer is suspected;
• if you have or have had an estrogen-dependent malignant tumor, such as endometrial (lining of the uterus) cancer, or if such a tumor is suspected;
• if you have vaginal bleeding of unknown cause;
• if you have untreated excessive thickening of the endometrium (endometrial hyperplasia);
• if you currently have or have had venous thromboembolic disease (deep vein thrombosis, e.g., in the legs, or pulmonary embolism);
• if you have blood clotting disorders (such as protein C, protein S, or antithrombin deficiency);
• if you currently have or have recently had an arterial thrombotic disease, such as myocardial infarction, stroke, or angina pectoris;
• if you have or have had liver disease and liver function tests have not returned to normal;
• if you have a rare inherited blood disorder called porphyria;
• if you are allergic to estradiol valerate, dienogest, or any of the other ingredients of this medicine (listed in section 6).

➢ If any of the above conditions occur for the first time while taking Velbienne mini, stop taking the medicine immediately and contact your doctor without delay.
Warnings and precautions
Inform your doctor if you currently have or have previously had any of the following conditions, as they may recur or worsen during treatment with Velbienne mini. In such cases, more frequent monitoring may be required:

• uterine fibroids;
• endometriosis (endometrial tissue growing outside the uterus) or previous history of excessive endometrial growth (endometrial hyperplasia);
• increased risk of venous thromboembolic disorders or personal history thereof (see "Blood clots in veins (thrombosis)");
• increased risk of estrogen-dependent cancer (e.g., if your mother, sister, or grandmother had breast cancer);
• high blood pressure;
• liver function disorders, such as benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headaches;
• autoimmune disease affecting multiple organs (systemic lupus erythematosus, SLE);
• epilepsy;
• asthma;
• a disease affecting the middle ear and hearing (otosclerosis);
• very high levels of fats (triglycerides) in the blood;
• fluid retention due to heart or kidney dysfunction;
• hereditary or acquired angioedema.

Stop taking Velbienne mini and contact your doctor immediately
if you experience any of the following symptoms while taking HRT:

• any of the conditions listed under When not to use Velbienne mini;
• yellowing of the skin or whites of the eyes (jaundice). These may be signs of liver disease;
• swelling of the face, tongue, and (or) throat and (or) difficulty swallowing, or hives with breathing difficulties, suggesting angioedema;
• significantly increased blood pressure (possible symptoms include headache, fatigue, dizziness);
• new-onset migraine-type headaches;
• pregnancy;
• signs of blood clot formation, such as:
  • painful swelling and redness in the legs
  • sudden chest pain
  • difficulty breathing. More information is available in the section "Blood clots in veins (thrombosis)".

Note: Velbienne mini 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, additional contraceptive measures may be necessary. Consult your doctor.
HRT and malignant tumors
Excessive thickening of the endometrium (endometrial hyperplasia) and endometrial cancer
Estrogen-only HRT increases the risk of endometrial hyperplasia and endometrial cancer. The presence of progestogen (dienogest) in Velbienne mini protects against this additional risk.
Irregular bleeding
Irregular bleeding or spotting may occur during the first 3 to 6 months of taking Velbienne mini. However, if irregular bleeding:

• persists beyond the first 6 months;
• occurs after you have been taking Velbienne mini for more than 6 months;
• continues after stopping Velbienne mini;

you should see your doctor immediately.
Breast cancer
Evidence shows that taking hormone replacement therapy (HRT), either estrogen-progestogen combination or estrogen-only, increases the risk of developing breast cancer. This additional risk depends on how long HRT is used. The increased risk becomes apparent after 3 years of HRT use. After stopping HRT, the additional risk gradually decreases, but may persist for 10 years or longer if HRT was used for more than 5 years.
Comparison
Among women aged 50 to 54 who do not use HRT, breast cancer will be diagnosed in an average of 13 to 17 out of 1,000 women over a 5-year period.
Among women aged 50 who start a 5-year course of estrogen-only HRT, the number of cases will be 16–17 per 1,000 women (i.e., 0 to 3 additional cases).
Among women aged 50 who start a 5-year course of estrogen-progestogen HRT, the number of cases will be 21 per 1,000 women (i.e., 4 to 8 additional cases).
Among women aged 50 to 59 who do not use HRT, breast cancer will be diagnosed in an average of 27 out of 1,000 women over a 10-year period.
Among women aged 50 who start a 10-year course of estrogen-only HRT, the number of cases will be 34 per 1,000 women (i.e., 7 additional cases).
Among women aged 50 who start a 10-year course of estrogen-progestogen HRT, the number of cases will be 48 per 1,000 women (i.e., 21 additional cases).
➢ You should regularly examine your breasts. Contact your doctor if you notice any changes such as:

• skin dimpling;
• nipple changes;
• any visible or palpable lumps.

Regular mammograms are recommended. Before undergoing a mammogram, inform the healthcare staff or nurse that you are taking this medicine, as hormone replacement therapy may increase breast density, which can affect mammogram results. In areas of increased breast density, mammography may not detect all abnormalities.
Ovarian cancer
Ovarian cancer is rare—much less common than breast cancer. The use of estrogen-only or estrogen-progestogen HRT is associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer increases with age. For example, among women aged 50 to 54 who do not use HRT, ovarian cancer will be diagnosed in about 2 out of 2,000 women over a 5-year period. Among women who have used HRT for 5 years, it will occur in about 3 out of 2,000 women (i.e., about 1 additional case).
Effects of HRT on the heart and circulation
Blood clots in veins (thrombosis)
The risk of developing venous thromboembolic disease is approximately 1.3 to 3 times higher in women using HRT, especially during the first year of treatment, compared to women not using HRT.
Blood clots can be dangerous. If a clot travels to the lungs, it may cause chest pain, shortness of breath, fainting, or even death.
The likelihood of venous blood clots increases with age and with the presence of the following risk factors. Inform your doctor if any of the following apply to you:

• you are unable to walk for prolonged periods due to major surgery, injury, or illness (see also section 3 "If surgery is required");
• you are obese (body mass index BMI > 30 kg/m²);
• you have blood clotting disorders requiring long-term anticoagulant therapy;
• a close relative has had a blood clot in the leg, lung, or another organ;
• you have systemic lupus erythematosus (SLE);
• you have cancer.

Information on symptoms of blood clots is provided in the section "Stop taking Velbienne mini and contact your doctor immediately".
Comparison
Among women aged 50 to 59 who do not use HRT, approximately 4 to 7 out of 1,000 will develop a venous clot over 5 years.
Among women aged 50 to 59 who have used combined estrogen-progestogen HRT for more than 5 years, 9 to 12 out of 1,000 will develop a venous clot (i.e., 5 additional cases).
Heart disease (myocardial infarction)
There is no scientific evidence that HRT prevents heart attacks. Women over the age of 60 who use combined estrogen-progestogen HRT have a slightly higher risk of heart disease compared to women who do not use HRT.
Stroke
The risk of stroke is approximately 1.5 times higher in women using HRT than in those who do not. The number of additional stroke cases due to HRT use increases with age.
Comparison
Among women aged 50 to 59 who do not use HRT, approximately 8 out of 1,000 will have a stroke over 5 years. Among women aged 50–59 using HRT, 11 out of 1,000 will have a stroke over 5 years (i.e., 3 additional cases).
Other conditions

• HRT does not prevent memory loss. Evidence suggests an increased risk of memory loss in women who start HRT after age 65. Consult your doctor.

Velbienne mini and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take, including over-the-counter medicines, herbal remedies, or other natural products. Your doctor will advise you accordingly.
Some medicines may affect the action of Velbienne mini and may lead to irregular bleeding. These include:

• Medicines used to treat epilepsy (such as barbiturates, phenytoin, primidone, carbamazepine, and possibly oxcarbazepine, topiramate, and felbamate);
• Medicines used to treat tuberculosis (such as rifampicin and rifabutin);
• Medicines used to treat HIV and hepatitis C virus infection (so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors, such as nevirapine, efavirenz, ritonavir, and nelfinavir);
• Herbal preparations containing St. John's wort (Hypericum perforatum);
• Medicines used to treat fungal infections (such as griseofulvin, itraconazole, ketoconazole, voriconazole, fluconazole);
• Medicines used to treat bacterial infections (such as clarithromycin and erythromycin);
• Medicines used to treat certain heart conditions and high blood pressure (such as verapamil and diltiazem);
• Grapefruit juice.

HRT may affect the action of other medicines:

• Lamotrigine, used to treat epilepsy, as this may increase the frequency of seizures;
• Medicines used to treat hepatitis C virus infection (medicines containing ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, or glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir), as this may cause abnormalities in liver function tests (increased liver enzyme AlAT activity). Velbienne mini contains estradiol instead of ethinylestradiol. It is not known whether concomitant use of Velbienne mini with these hepatitis C treatments may also lead to increased AlAT activity.

Laboratory tests
If blood tests are required, inform the laboratory staff that you are taking Velbienne mini, as it may affect the results of certain tests.
Pregnancy and breastfeeding
Velbienne mini is intended for use only in postmenopausal women.
If pregnancy occurs, stop taking the medicine and contact your doctor.
Driving and operating machinery
No effects of Velbienne mini on the ability to drive or operate machinery have been observed.
Important information about certain ingredients of Velbienne mini
Velbienne mini contains lactose. If you have been previously diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to use Velbienne mini

Your doctor will prescribe the lowest possible dose needed to treat your symptoms for the shortest possible duration. If you feel that the effect of this medicine is too weak or too strong, you should inform your doctor.

This medicine should always be taken exactly as your doctor has instructed. If you are unsure, consult your doctor or pharmacist. Your doctor will decide how long you should continue taking Velbienne mini.

The recommended dose is one tablet daily, taken at approximately the same time each day. The tablet should be swallowed whole with water. Velbienne mini may be taken with or without food. A new calendar pack should be started the day after finishing the current pack.

Do not interrupt treatment between packs.

If you have previously been using other HRT preparations: Continue treatment until all tablets in the current pack have been taken. Start taking Velbienne mini the following day. Do not make a break between your previous HRT and starting Velbienne mini.

If you have previously used HRT with a weekly break: Begin the new pack the day after the break ends.

If starting HRT for the first time: Treatment with Velbienne mini may be started at any time.

Taking more Velbienne mini than recommended

If you take too much Velbienne mini, symptoms such as nausea, vomiting, or vaginal bleeding may occur. Specific treatment is not usually required, but if in doubt, contact your doctor or pharmacist.

If you forget to take a dose of Velbienne mini

If you forget to take a tablet and less than 24 hours have passed since it was due, take it as soon as possible. Then take the next tablet at your usual time.

If more than 24 hours have passed since the missed dose, leave the forgotten tablet in the pack and do not take it. Continue taking one tablet daily at your usual time. Do not take a double dose to make up for the missed tablet.

Missing tablets for several days may lead to vaginal bleeding.

Stopping Velbienne mini

Symptoms of menopause such as hot flushes, sleep disturbances, nervousness, dizziness, or vaginal dryness may return. After stopping Velbienne mini, the process of bone mass loss will resume. If you are considering stopping treatment with Velbienne mini, consult your doctor or pharmacist.

If surgery is required

Inform your surgeon that you are taking Velbienne mini. You may need to stop taking Velbienne mini approximately 4 to 6 weeks before surgery to reduce the risk of blood clots (see section 2 Venous thrombosis). Ask your doctor when it is safe to restart Velbienne mini after surgery.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following conditions occur more frequently in women using HRT than in women who do not use HRT:

• breast cancer;
• abnormal growth or cancer of the lining of the womb (endometrial hyperplasia or endometrial cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolic disorders);
• heart diseases;
• stroke;
• risk of memory loss if HRT is started after the age of 65.

Further information on the above adverse reactions is provided in section 2.
The following adverse reactions are associated with the use of Velbienne mini:
Irregular bleeding may occur during the first months of treatment with Velbienne mini.
This is usually temporary and resolves as treatment continues. If bleeding does not stop, you should contact your doctor.
Common (may affect fewer than 1 in 10 people):

• headache,
• nausea,
• breast tenderness, vaginal bleeding, hot flushes.

Uncommon (may affect fewer than 1 in 100 people):

• weight gain,
• drowsiness, nervousness, loss of appetite leading to weight loss, aggression, depression, insomnia, decreased libido, inability to achieve orgasm,
• dizziness, migraine, hyperactivity, tingling sensation,
• high blood pressure, venous thrombosis (leg pain) (see also section 2 "Venous thromboembolism (blood clots)"), phlebitis, nosebleeds,
• bloating, abdominal pain, constipation, diarrhoea, dry mouth, vomiting,
• gallbladder pain,
• excessive sweating, acne, itching of the skin, dry skin with red, scaly areas (psoriasis),
• muscle pain, leg cramps,
• disorders of the endometrium, painful menstruation, genital itching, vaginal candidiasis,
• fatigue, generalized fluid retention, facial swelling,
• oedema.

With other HRTs, the following adverse reactions have been reported:

• gallbladder disease
• skin disorders:
  • skin discolouration, especially on the face or neck (melasma);
  • painful red nodules on the skin (erythema nodosum);
  • rash with lesions or redness resembling a target (erythema multiforme).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl .
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Velbienne mini

Keep out of the sight and reach of children.
Do not use this medicinal product after the expiry date stated on the carton and blister after
"Expiry date". The expiry date refers to the last day of the stated month.
Velbienne mini should be stored in the original packaging to protect from light.
Velbienne mini does not require any special storage temperature.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Velbienne mini contains
The active substances in this medicine are estradiol valerate and dienogest. One tablet contains 1.0 mg of estradiol valerate (equivalent to 0.764 mg of estradiol) and 2.0 mg of dienogest.
Other ingredients are: monohydrate lactose, corn starch, pregelatinized corn starch, povidone K30, magnesium stearate, polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, iron oxide red (E172), iron oxide black (E172).

What Velbienne mini looks like and contents of the pack
Velbienne mini is a round, pink, film-coated tablet.
Velbienne mini is available in packs containing 28, 3x28 and 6x28 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Exeltis Poland Sp. z o.o.
Szamocka Street 8
01-748 Warsaw
email: [email protected]

Manufacturer
Laboratorios León Farma S.A.
La Vallina s/n, Pol. Ind. Navatejera,
Villaquilambre-24193 León
Spain

This medicinal product is authorised in the European Economic Area countries under the following names:
Netherlands: Estradiol Valeraat 1 mg / Dienogest 2 mg Laboratorios León Farma filmomhulde tabletten
Germany: Velbienne 1 mg / 2 mg Filmtabletten
Austria: Velbienne 1 mg / 2 mg Filmtabletten
Slovakia: VELBIENNE 2 mg/1 mg filmom obalené tablety
Estonia: VELBIENNE 2 mg + 1 mg ohukese polümeerikattega tablett
Lithuania: VELBIENNE 2 mg/1 mg plėvele dengtos tabletės
Poland: Velbienne mini
Latvia: Velbienne 2 mg/1 mg apvalkotās tabletes
France: CLIFEMME 1mg / 2mg, comprimé pelliculé
Portugal: Clifemme 2 mg + 1 mg, comprimidos revestidos por película