Velbienne

Package leaflet: Information for the user

Velbienne film-coated tablets

Estradiol valerate/Dienogest
Equivalent medicine
Please read all of 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 only. Do not give it to other people. It may be harmful to them, even if their symptoms are the same as yours.
• If you experience any side effects, inform your doctor or pharmacist. This includes any possible side effects not listed in this leaflet (see section 4).

Important things to know about combined hormonal contraceptives (CHCs):

• They are one of the most reliable reversible contraceptive methods when used correctly.
• They slightly increase the risk of developing blood clots in veins and arteries, especially during the first year of use or when restarting a combined hormonal contraceptive after a break of 4 or more weeks.
• Be alert and contact your doctor if you think you have symptoms of a blood clot (see section 2 “Blood clots”).

Contents of this leaflet

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

1. What Velbienne is and what it is used for

• Velbienne is a contraceptive pill and is used to prevent pregnancy.
• Each coloured active tablet contains a small amount of female hormones, either valerate estradiol or valerate estradiol combined with dienogest.
• The 2 white tablets do not contain active substances and are called inactive tablets.
• Contraceptive pills that contain two hormones are called "combined pills".

2. What you should know before taking Velbienne

General information
Before starting to use Velbienne, you must read the information about blood clots in section 2.
It is particularly important that you read about the symptoms of a blood clot – see section 2
“Blood clots”.
Before starting to take Velbienne, your doctor will ask you some questions about your personal
medical history and that of your family members. Your doctor will also measure your blood
pressure and, depending on your individual circumstances, may carry out additional examinations.
This patient leaflet describes various situations in which you must stop using Velbienne or in which
the reliability of Velbienne may be reduced. In such situations, you must not have sexual intercourse
or must use additional non-hormonal contraceptive measures, such as using a condom or another
barrier method. Do not use the rhythm method or basal body temperature method. These methods
may be unreliable because Velbienne alters the monthly variations in body temperature and cervical
mucus.
Velbienne, like all hormonal contraceptives, provides no protection against HIV (AIDS) or other
sexually transmitted infections.
When not to take Velbienne
Do not use Velbienne if you have any of the conditions listed below. If you have any of the
conditions listed below, consult your doctor. Your doctor will discuss with you other methods of
birth control that might be more suitable.
Do not take Velbienne:

• if you have (or have ever had) a blood clot in a blood vessel of the leg (deep vein thrombosis, DVT), lung (pulmonary embolism, PE), or other organs;
• if you know you have a disorder affecting blood clotting – for example, protein C deficiency, protein S deficiency, antithrombin-III deficiency, factor V Leiden, or antiphospholipid antibodies;
• if you are due to undergo surgery or will be bedridden for a prolonged period (see section “Blood clots”);
• if you have ever had a heart attack or stroke;
• if you have (or have ever had) angina pectoris (a condition causing severe chest pain that may be an early sign of heart attack) or a transient ischaemic attack (TIA – temporary stroke-like symptoms);
• if you have any of the following conditions that could increase the risk of developing clots in the arteries:
• severe diabetes with blood vessel damage
• very high blood pressure
• very high levels of fats (cholesterol or triglycerides) in the blood
• a condition known as hyperhomocysteinaemia;
• if you have (or have ever had) a type of migraine called “migraine with aura”;
• if you have (or have ever had) a liver disease and your liver function is still abnormal;
• if you have (or have ever had) a liver tumour;
• if you have (or suspect you have) cancer of the breast or genital organs;
• if you have unexplained vaginal bleeding;
• if you are allergic (hypersensitive) to estradiol valerate or dienogest, or to any of the excipients of this medicine (listed in section 6). This may cause itching, rash or swelling.

Warnings and precautions
When should you contact a doctor?
Contact a doctor urgently

• if you notice possible signs of a blood clot which may indicate that you have a blood clot in the leg (deep vein thrombosis), in the lung (pulmonary embolism), a heart attack or a stroke (see the following section “Blood clots”).

For a description of the symptoms of these serious side effects, go to the section “How to recognize
a blood clot”.
Inform your doctor if any of the following conditions apply to you.
In certain situations, you must be particularly careful when using Velbienne or any other combined
pill, and your doctor may need to examine you regularly. If any of these conditions develop or
worsen while you are using Velbienne, you must inform your doctor.

• if a close relative has or has ever had breast cancer;
• if you have liver or gallbladder disease;
• if you have jaundice;
• if you have diabetes;
• if you suffer from depression;
• if you have Crohn’s disease or ulcerative colitis (chronic inflammatory bowel disease);
• if you have systemic lupus erythematosus (SLE – a disease affecting the body’s natural defence system);
• if you have haemolytic uraemic syndrome (HUS – a blood clotting disorder causing kidney failure);
• if you have sickle cell anaemia (an inherited red blood cell disorder);
• if you have high levels of fats in the blood (hypertriglyceridaemia) or a family history of this condition. Hypertriglyceridaemia has been associated with an increased risk of developing pancreatitis (inflammation of the pancreas);
• if you are due to undergo surgery or will be bedridden for a prolonged period (see section 2 “Blood clots”);
• if you have recently given birth, your risk of developing blood clots is higher. Ask your doctor how long after childbirth you can start taking Velbienne;
• if you have inflammation of veins near the skin surface (superficial thrombophlebitis);
• if you have varicose veins;
• if you have epilepsy (see section “Other medicines and Velbienne”);
• if you have a condition that first appeared during pregnancy or during previous use of sex hormones, for example, hearing loss, porphyria (a blood disorder), herpes gestationis (blistering skin rash during pregnancy), Sydenham’s chorea (a nerve disorder causing sudden involuntary body movements);
• if you have (or have ever had) patchy yellow-brown pigmentation, known as “melasma”, especially on the face (chloasma). In this case, avoid direct exposure to sunlight or ultraviolet rays;
• if you have hereditary or acquired angioedema. Stop taking Velbienne and consult your doctor immediately if you notice symptoms such as swelling of the face, tongue and/or throat and/or difficulty swallowing, or hives with breathing difficulties, which are indicative of angioedema. Medicines containing oestrogens may induce or worsen symptoms of angioedema;
• if you have heart or kidney failure.

Consult your doctor before taking Velbienne.
Supplementary information for specific patient groups
Use in children
Velbienne is not indicated for use in women who have not yet had their first menstrual period.
BLOOD CLOTS
Using a combined hormonal contraceptive such as Velbienne increases the risk of developing a
blood clot compared to not using one. In rare cases, a blood clot can block blood vessels and cause
serious problems.
Blood clots can develop

• in veins (a condition called “venous thrombosis”, “venous thromboembolism” or VTE);
• in arteries (a condition called “arterial thrombosis”, “arterial thromboembolism” or ATE).

Recovery from blood clots is not always complete. Rarely, serious long-term effects may occur, or, very rarely, such effects may be fatal.
It is important to remember that the overall risk of a dangerous blood clot associated with
Velbienne is low.
HOW TO RECOGNIZE A BLOOD CLOT
Seek immediate medical attention if you notice any of the following signs or symptoms.
Do you have any of these signs? What might you
be suffering from?

• swelling in one leg or along a vein in the leg or foot, especially if accompanied by:
• pain or tenderness in the leg, which may only be felt when standing or walking;
• increased warmth in the affected leg;
• change in skin colour of the leg, such as paleness, redness or bluish discolouration;
• sudden unexplained shortness of breath or rapid breathing;
• sudden cough without an obvious cause, possibly with coughing up blood;
• sharp chest pain that may worsen when breathing deeply;
• severe dizziness or lightheadedness;
• rapid or irregular heartbeat;
• severe stomach pain.

If you are unsure, inform your doctor, as some of these symptoms
such as cough or shortness of breath may be mistaken
for a milder condition such as a respiratory tract infection
(e.g. a “common cold”).
Symptoms occurring more frequently in an eye: Retinal vein thrombosis (blood clot in the eye)

• sudden loss of vision
• painless blurring of vision that may progress to loss of vision;

BLOOD CLOTS IN A VEIN
What can happen if a blood clot forms in a vein?

• The use of combined hormonal contraceptives has been associated with an increased risk of blood clots forming in veins (venous thrombosis). However, these side effects are rare. In most cases, they occur during the first year of using a combined hormonal contraceptive.
• If a blood clot forms in a vein of the leg or foot, it can cause deep vein thrombosis (DVT).
• If a blood clot travels from the leg and lodges in the lung, it can cause a pulmonary embolism.
• Very rarely, a clot may form in another organ such as the eye (retinal vein thrombosis).

When is the risk of developing a blood clot in a vein highest?
The risk of developing a blood clot in a vein is highest during the first year in which you
start taking a combined hormonal contraceptive for the first time. The risk may also be higher
if you restart taking a combined hormonal contraceptive (the same drug or a different one)
after a break of 4 or more weeks.
After the first year, the risk decreases but remains slightly higher than if you were not using
a combined hormonal contraceptive.
When you stop taking Velbienne, the risk of developing a blood clot returns to normal levels
within a few weeks.

What is the risk of developing a blood clot?
The risk depends on your natural risk of VTE (venous thromboembolism) and the type of combined hormonal contraceptive you are taking.
The overall risk of developing a blood clot in the leg or lung (DVT or PE) with Velbienne is low.

• Among 10,000 women who do not use any combined hormonal contraceptive and who are not pregnant, about 2 will develop a blood clot in one year.
• Among 10,000 women who use a combined hormonal contraceptive containing levonorgestrel, norethisterone, or norgestimate, about 5–7 will develop a blood clot in one year.
• The risk of developing a blood clot with Velbienne is approximately the same as with other combined hormonal contraceptives, including those containing levonorgestrel.
• The likelihood of a blood clot forming depends on your medical history (see below “Factors that increase the risk of developing a blood clot”).

Factors that increase the risk of developing a blood clot in a vein
The risk of developing a blood clot with Velbienne is low, but certain conditions can increase it. Your risk is higher:

• if you are significantly overweight (body mass index or BMI above 30 kg/m²);
• if a close relative has had a blood clot in the leg, lung, or another organ at a young age (e.g., under approximately 50 years). In this case, you might have an inherited blood clotting disorder;
• if you are scheduled for surgery or need to remain bedridden for a prolonged period due to injury or illness, or if you have a leg in a cast. You may need to stop taking Velbienne several weeks before surgery or during periods of reduced mobility. If you need to stop taking Velbienne, ask your doctor when you can resume taking it;
• as you get older (especially over 35 years);
• if you gave birth less than a few weeks ago.

The risk of developing a blood clot increases when you have more than one of these conditions.
Air travel (lasting >4 hours) may temporarily increase the risk of blood clot formation, particularly if you have some of the other risk factors listed above.
It is important that you inform your doctor if any of these conditions apply to you, even if you are uncertain. Your doctor may decide to have you stop taking Velbienne.
If any of the conditions listed above change while you are using Velbienne—for example, if a close relative develops thrombosis without a known cause or if you gain significant weight—contact your doctor.

BLOOD CLOTS IN AN ARTERY
What can happen if a blood clot forms in an artery?
Like blood clots in a vein, clots in an artery can cause serious problems—for example, they may lead to a heart attack or stroke.

Factors that increase the risk of developing a blood clot in an artery
It is important to note that the risk of heart attack or stroke associated with the use of Velbienne is very low, but it may increase:

• with increasing age (over approximately 35 years);
• if you smoke. When using a combined hormonal contraceptive such as Velbienne, it is advisable to stop smoking. If you are unable to stop smoking and you are over 35 years old, your doctor may recommend using a different type of contraceptive;
• if you are overweight;
• if you have high blood pressure;
• if a close relative has had a heart attack or stroke at a young age (under approximately 50 years). In this case, you may also have an increased risk of heart attack or stroke;
• if you or a close relative have high levels of fat in the blood (cholesterol or triglycerides);
• if you suffer from migraine, especially migraine with aura;
• if you have heart problems (valvular defect, a heart rhythm disorder called atrial fibrillation);
• if you have diabetes.

If you have more than one of these conditions or if one of them is particularly severe, the risk of developing a blood clot may be even higher.
If any of the conditions listed above change while you are using Velbienne—for example, if you start smoking, if a close relative develops thrombosis without a known cause, or if you gain significant weight—contact your doctor.

Velbienne and cancer
Breast cancer has been observed slightly more frequently in women using combined oral contraceptives, but it is not known whether this is due to the treatment. For example, it is possible that more tumors are detected in women using combined oral contraceptives because they undergo more frequent medical check-ups. The risk of breast cancer gradually decreases after stopping combined hormonal contraception. It is important that you regularly examine your breasts and contact your doctor if you feel any lumps.

In rare cases, benign liver tumors have been observed in women using oral contraceptives, and even more rarely, malignant liver tumors. In isolated cases, these tumors have led to life-threatening internal bleeding. Contact your doctor if you experience severe abdominal pain.

Some studies suggest that long-term use of oral contraceptives may increase the risk of developing cervical cancer. However, it is unclear to what extent sexual behavior or other factors such as human papillomavirus (HPV) contribute to this risk.

Psychiatric disorders
Some women using hormonal contraceptives, including Estradiol valerate/Dienogest, have reported depression or depressed mood. Depression can be severe and sometimes may lead to suicidal thoughts. If you experience mood changes or depressive symptoms, consult your doctor as soon as possible for further medical advice.

Intermenstrual bleeding
During the first few months of taking Velbienne, unexpected bleeding may occur. Usually, bleeding starts on day 26, the day you take the second brown tablet, or in the following days. Data from diaries kept by women during a clinical study with Estradiol valerate/Dienogest show that unexpected bleeding in a given cycle is not uncommon (observed in 10–18% of users). If unexpected bleeding occurs for more than three consecutive months, or if it appears after several months, your doctor should investigate the cause.

What to do if menstruation does not occur on day 26 or in the following days
Data from diaries kept by women during a clinical study with Estradiol valerate/Dienogest show that it is not uncommon for menstruation not to occur on day 26 (observed in approximately 15% of cycles).
If you have taken all tablets correctly, have not vomited or had severe diarrhea, and have not taken other medications, it is highly unlikely that you are pregnant.
If menstruation does not occur for two consecutive cycles or if you have missed taking tablets correctly, you may be pregnant. Contact your doctor immediately. Do not start the next blister pack until you have confirmed that pregnancy has been ruled out.

Other medicines and Velbienne
Always inform your doctor about any medicines or herbal products you are currently taking. Also inform any other doctor or dentist who prescribes you medicines (or the pharmacist providing the medicine) that you are taking Velbienne. They can advise you whether you need to use additional contraceptive measures (e.g., condoms) and, if so, for how long.
Some medicines:

• can affect the levels of Velbienne in the blood;
• can make it less effective in preventing pregnancy;
• can cause unexpected bleeding.

These include:
o Medicines used to treat:

• epilepsy (e.g., primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate, felbamate);
• tuberculosis (e.g., rifampicin);
• HIV infection and hepatitis C virus (HCV) (ritonavir, nevirapine, efavirenz, known as protease inhibitors and non-nucleoside reverse transcriptase inhibitors);
• hepatitis C virus (HCV) (such as the combination regimen of ombitasvir/paritaprevir/ritonavir with or without dasabuvir, and the regimen of glecaprevir/pibrentasvir) may cause

increased liver function test results (elevated liver enzyme ALT) in women using COCs containing ethinylestradiol. Velbienne contains estradiol instead of ethinylestradiol. It is not known whether elevated ALT liver enzyme levels can occur when using Velbienne with these HCV combination regimens. Your doctor will provide you with necessary instructions;

• fungal infections (e.g., griseofulvin, ketoconazole); or the herbal product St. John’s wort.

Velbienne may affect the effect of other medicines, for example:
o medicines containing cyclosporine;
o the antiepileptic lamotrigine (this may lead to an increased frequency of epileptic seizures).
Consult your doctor or pharmacist before taking any medicine. Your doctor or pharmacist can advise you whether you need to take additional protective measures while taking Velbienne together with other medicines.

Velbienne with food
Velbienne can be taken with or without food.

Laboratory tests
If you need a blood test or other laboratory tests, inform your doctor or laboratory staff that you are taking the pill, as oral contraceptives may affect the results of certain tests.

Pregnancy and breastfeeding
During pregnancy, you must not use Velbienne. If you become pregnant while taking Velbienne, you must stop treatment immediately and contact your doctor. If you wish to become pregnant, you may stop taking Velbienne at any time (see also “If you stop treatment with Velbienne”).
Generally, you should not take Velbienne while breastfeeding. If you wish to take the pill during breastfeeding, you should consult your doctor.
Consult your doctor or pharmacist before taking any medicine during pregnancy or breastfeeding.

Driving and using machines
There are no reasons to believe that Velbienne affects the ability to drive or use machinery.

Velbienne contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take Velbienne

Each blister contains 26 coloured active tablets and 2 inactive white tablets.
Take one Velbienne tablet every day. You may take the tablets with or without food, but you should take them at approximately the same time each day.

Preparing the blister
To help you follow the correct sequence, the tablets are marked on the aluminium side with a number and an arrow indicating the order of intake. Start with tablet number 1 and follow the direction of the arrow on the blister until you have taken all 28 tablets.

Usually, the so-called withdrawal bleeding starts while you are taking the second brown tablet or the white tablets, and may not yet have finished before you start the next blister. Some women may still be menstruating even after starting the first tablets of the new blister.

Start the next blister without a break, i.e. the day after finishing the current blister, even if menstruation has not yet ended.

If you use Velbienne in this way, contraceptive protection is maintained throughout the 2 days during which you are taking the inactive tablets.

When can you start the first blister?

• If you have not used a hormonal contraceptive in the previous month: Start taking Velbienne on the first day of your cycle (i.e. the first day of menstruation).
• Switching from another combined oral contraceptive pill, or from a combined vaginal ring or contraceptive patch: Start taking Velbienne the day after the last active tablet (the last tablet containing active ingredients) of the previous pill. When switching from a combined vaginal ring or contraceptive patch, start using Velbienne on the day of removal, or follow your doctor’s advice.
• Switching from a progestogen-only method (progestogen-only pill, injection, implant, or progestogen-releasing IUS, intrauterine system): You may switch at any time from the progestogen-only pill (from an implant or IUS on the day of removal, from the injectable when the next injection would have been due), but in all these cases you must use additional contraceptive precautions (e.g. condom) for the first 9 days of taking Velbienne.
• After an abortion: Follow your doctor’s advice.
• After childbirth: You may start taking Velbienne between day 21 and day 28 after delivery. If you start later than day 28, use a barrier method (e.g. condom) during the first 9 days of taking Velbienne. If you have had sexual intercourse after childbirth and before restarting Velbienne, you must exclude pregnancy or wait for the next menstrual period. If you wish to start taking Velbienne after pregnancy and are breastfeeding, read the section “Pregnancy and breastfeeding”. Ask your doctor for advice if you are unsure about when to start.

If you take more Velbienne than you should
There have been no reports of serious harmful effects from taking too many Velbienne tablets.
If several tablets are taken at once, you may experience nausea or vomiting. Young girls may have vaginal bleeding.
If you have taken too many Velbienne tablets, or if you discover that a child has taken any of the tablets, contact your doctor or pharmacist immediately.

If you forget to take Velbienne

Inactive tablet: If you forget a white tablet (the 2 tablets at the end of the blister), you do not need to take it later, as they contain no active ingredient. However, it is important that you discard the forgotten white tablet(s) so that the number of days taking inactive tablets does not increase; doing so would increase the risk of pregnancy. Continue taking the next tablet at your usual time.

Active tablets: Depending on the day of the cycle when one active tablet is forgotten, you must use additional contraceptive precautions, such as a barrier method (e.g. condom).

Take the tablets according to the instructions below. For details, also see the ‘Missed tablet diagram’.

• If the delay in taking a tablet is less than 12 hours, contraceptive protection is not reduced. Take the tablet as soon as you remember, and then continue taking the following tablets at your usual time.
• If the delay in taking a tablet is more than 12 hours, contraceptive protection may be reduced. Depending on the day of the cycle when the tablet was forgotten, you must use additional contraceptive precautions, such as a barrier method (e.g. condom). For details, also see the ‘Missed tablet diagram’.
• More than one tablet forgotten in a blister: Consult your doctor.

Do not take more than 2 active tablets in one day.
If you forgot to start a new blister, or if you forgot one or more tablets during days 3–9 of the blister, there is a risk of pregnancy (if you had sexual intercourse in the 7 days before forgetting the tablet). In this case, consult your doctor. The greater the number of tablets forgotten (especially those during days 3–24) and the closer the missed tablets are to the inactive tablet phase, the higher the risk that contraceptive protection is reduced. For details, also see the ‘Missed tablet diagram’.
If you have forgotten any of the active tablets in a blister and do not have a withdrawal bleed at the end of the blister, you may be pregnant. Consult your doctor before starting the next blister.

Use in children
No data are available in adolescents under 18 years of age.

What to do in case of vomiting or severe diarrhoea
If you vomit within 3–4 hours after taking an active tablet, or if you have severe diarrhoea, there is a risk that the active ingredients of the tablet are not completely absorbed by your body.
This situation is therefore similar to that which occurs when you forget to take a tablet. After vomiting or severe diarrhoea, you should take the next tablet as soon as possible, ideally within 12 hours of your usual time of taking the pill. If this is not possible, or if more than 12 hours have passed, follow the instructions under “If you forget to take Velbienne”. If you do not wish to change your normal dosing schedule, take the corresponding tablet from another blister.

If you stop taking Velbienne
You may stop taking Velbienne at any time. If you still wish to avoid pregnancy, consult your doctor for advice on other reliable contraceptive methods. If you wish to become pregnant, stop taking Velbienne and wait for one menstrual cycle before trying to conceive. This will allow you to calculate the expected date of delivery more accurately.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Velbienne can cause side effects, although not everybody gets them. If you experience any side effect, especially if it is severe or persistent, or if you notice any change in your health that you think may be due to Velbienne, inform your doctor.

An increased risk of developing blood clots in veins (venous thromboembolism, VTE) or blood clots in arteries (arterial thromboembolism, ATE) exists in all women taking combined hormonal contraceptives. For more detailed information on the different risks associated with taking combined hormonal contraceptives, see section 2, “What you should know before taking Velbienne”.

Serious side effects

Serious reactions associated with the use of the pill, along with related symptoms, are described in the following sections: “Blood clots” and “Velbienne and cancer”. Please read these sections carefully and consult your doctor immediately if necessary.

Other possible side effects

The following side effects have been associated with the use of Velbienne:

Common side effects (may affect between 1 and 10 users in 100):

• headache
• abdominal pain, nausea
• acne
• absence of menstruation, breast tenderness, painful menstruation, irregular menstruation (with irregular heavy bleeding)
• weight gain

Uncommon side effects (may affect between 1 and 10 users in 1,000):

• fungal infection, fungal infection of the vulva and vagina, vaginal infection
• increased appetite
• depression, depressed mood, emotional disorder, difficulty sleeping, decreased sexual desire, mental disorder, mood swings
• dizziness, migraine
• hot flushes, high blood pressure
• diarrhoea, vomiting
• increased liver enzymes
• hair loss, excessive sweating (hyperhidrosis), itching, rash
• muscle cramps
• breast enlargement, breast nodules, abnormal cell growth in the cervix (cervical dysplasia), genital dysfunctional bleeding, pain during intercourse, fibrocystic mastopathy, heavy menstruation, menstrual disorders, ovarian cyst, pelvic pain, premenstrual syndrome, benign uterine tumour, uterine contractions, uterine/vaginal bleeding including spotting, vaginal discharge, vulvovaginal dryness
• fatigue, irritability, swelling of certain parts of the body, for example the ankles (oedema)
• weight loss, changes in blood pressure

Rare side effects (may affect between 1 and 10 users in 10,000):

• candidiasis, oral herpes, pelvic inflammatory disease, an eye vascular disorder resembling a fungal infection (presumed ocular histoplasmosis syndrome), a fungal skin infection (tinea versicolor), urinary tract infection, bacterial inflammation of the vagina

• fluid retention, increase in certain blood fats (triglycerides)

• aggression, anxiety, feeling of unhappiness, increased sexual desire, nervousness, nightmares, restlessness, sleep disorders, stress

• reduced attention, sensation of “pins and needles”, vertigo

• intolerance to contact lenses, dry eyes, swollen eyes

• heart attack (myocardial infarction), palpitations

• bleeding from a varicose vein, low blood pressure, inflammation of superficial veins, vein pain

• dangerous blood clots in a vein or an artery, for example: in a leg or foot (DVT), or in a lung (PE), or heart attack, or stroke, or mini-stroke, or temporary symptoms similar to stroke known as transient ischaemic attack (TIA), or blood clots in the liver, stomach/intestine, kidneys or eye. The likelihood of developing a blood clot may be higher if you have any other condition that increases this risk (see section 2 for more information on conditions that increase the risk of blood clots and symptoms of a blood clot)

• constipation, dry mouth, indigestion, heartburn

• liver nodules (focal nodular hyperplasia), chronic inflammation of the gallbladder

• skin allergic reactions, yellow-brown patches (chloasma) and other pigmentary disorders, growth of hair in a male pattern, excessive hair growth, skin disorders such as dermatitis and neurodermatitis, dandruff and oily skin (seborrhoea) and other skin disorders

• back pain, jaw pain, feeling of heaviness

• urinary tract pain

• abnormal bleeding after discontinuation, benign breast nodules, early-stage breast cancer, breast cysts, breast discharge, cervical polyp, cervical redness, bleeding during intercourse, spontaneous milk secretion from the breast, genital discharge, scanty menstruation, delayed menstruation, rupture of ovarian cyst, foul-smelling vaginal discharge, burning sensation in the vulva and vagina, vulvovaginal discomfort

• swollen lymph nodes

• asthma, breathing difficulties, nosebleeds

• chest pain, tiredness and general feeling of malaise, fever

• abnormal Pap test (cervical smear)

Additional information (taken from diaries kept by women during a clinical study with dienogest/estradiol valerate) on the possible side effects “irregular menstruation (irregular heavy bleeding)” and “absence of menstruation” is reported in the sections “Intermenstrual bleeding” and “What to do if menstruation does not occur on day 26 or in the following days”.

Description of selected adverse reactions

Adverse reactions with very low frequency or delayed manifestation, which are considered to be related to those of combined oral contraceptives, may also occur during the use of Velbienne and are listed below (see also sections “When not to take Velbienne” and “Warnings and precautions”):

• liver tumours (benign and malignant)
• erythema nodosum (soft red lumps under the skin), erythema multiforme (skin rash with red spots or lesions)
• hypersensitivity (including symptoms such as rash, urticaria)
• in women with hereditary angioedema (characterised by sudden swelling, for example of the eyes, mouth, throat, etc.), the oestrogens contained in combined oral contraceptive pills may trigger or worsen symptoms of angioedema.

If liver function is impaired, temporary discontinuation of combined oral contraceptive pills may be necessary.

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 the following website:
http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Velbienne

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the blister 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 Velbienne contains
The active substances are estradiol valerate, or estradiol valerate combined with dienogest.
One blister (28 film-coated tablets) of Velbienne contains 26 active tablets of 4 different colours in the 1st, 2nd, 3rd and 4th rows, and 2 white inactive tablets in the 4th row.
Composition of the coloured tablets containing one or two active substances:

• 2 dark yellow tablets, each containing 3 mg of estradiol valerate
• 5 pink tablets, each containing 2 mg of estradiol valerate and 2 mg of dienogest
• 17 light yellow tablets, each containing 2 mg of estradiol valerate and 3 mg of dienogest
• 2 brown tablets, each containing 1 mg of estradiol valerate

Composition of the white inactive tablets:
These tablets do not contain any active substance.

Other excipients in the coloured active tablets:
Tablet core: monohydrate lactose, maize starch, pregelatinized maize starch, povidone (E1201), anhydrous colloidal silica, magnesium stearate (E572).
Tablet coating: hypromellose (E464), macrogol 6000, iron oxide red (E172), titanium dioxide (E171), talc (E553b), iron oxide yellow (E172).

Excipients in the white inactive tablets:
Tablet core: monohydrate lactose, microcrystalline cellulose, magnesium stearate (E572).
Tablet coating: partially hydrolysed polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc (E553b).

Description of the appearance of Velbienne and package contents
Velbienne tablets are film-coated tablets; the tablet core is covered with a coating.
Each blister (28 film-coated tablets) contains 2 dark yellow tablets in the 1st row, 5 pink tablets in the 1st row, 17 light yellow tablets in the 2nd, 3rd and 4th rows, 2 brown tablets in the 4th row, and 2 white tablets in the 4th row.
The dark yellow active tablet is round, biconvex, film-coated, with "L" marked on one side.
The pink active tablet is round, biconvex, film-coated, with "L" marked on one side.
The light yellow active tablet is round, biconvex, film-coated, with "L" marked on one side.
The brown active tablet is round, biconvex, film-coated, with "L" marked on one side.
The white inactive tablet is round, biconvex, film-coated, with "PL" marked on one side.
Velbienne is available in packages containing 1, 3 or 6 blisters, each with 28 tablets.

Not all pack sizes may be marketed.