Package leaflet: Information for the user

KLAIRA film-coated tablets

Estradiol valerate / Dienogest
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 further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not pass it on to others. It may be harmful to other people, even if their symptoms are the same as yours.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Important information about combined hormonal contraceptives (COCs):

They are one of the most reliable reversible methods of contraception, 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 may be experiencing symptoms of a blood clot (see section 2 “Blood clots”).

Contents of this leaflet

What Klaira is and what it is used for
What you need to know before taking Klaira
➢ When you must not take Klaira
➢ Warnings and precautions
➢ Blood clots
➢ Klaira and cancer
➢ Psychiatric disorders
➢ Intermenstrual bleeding
➢ What to do if menstruation does not occur on day 26 or in the following days
➢ Other medicines and Klaira
➢ Klaira with food and drink
➢ Laboratory tests
➢ Pregnancy and breastfeeding
➢ Driving and using machines
➢ Klaira contains lactose
How to take Klaira
➢ Preparing the pack
➢ When to start the first pack
➢ If you take more Klaira than you should
➢ If you forget to take Klaira
➢ Use in children
➢ What to do in case of vomiting or severe diarrhoea
➢ If you stop taking Klaira
Possible side effects
How to store Klaira
Contents of the pack and other information

1. What Klaira is and what it is used for

Klaira is a contraceptive pill and is used to prevent pregnancy.
Klaira is used for the treatment of heavy menstrual bleeding (not caused by diseases of the uterus) in women who wish to use oral contraception.
Each active coloured tablet contains a small amount of female hormones, estradiol valerate or estradiol valerate combined with dienogest.
The 2 white tablets contain no active ingredient and are called inactive tablets.
Contraceptive pills that contain two hormones are also called "combined pills".

2. What you need to know before taking Klaira

General notes
Before starting to use Klaira, 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 taking Klaira, your doctor will ask you some questions about your personal health history and that of your family members. Your doctor will also measure your blood pressure and, depending on your individual situation, may carry out additional examinations.
This patient leaflet describes various situations in which you must stop using Klaira or in which the reliability of Klaira may be reduced. In such cases, you should abstain from sexual intercourse or use additional non-hormonal contraceptive measures, such as condoms or other barrier methods.
Do not use the rhythm method or the basal body temperature method. These methods may be unreliable because Klaira alters the monthly changes in body temperature and cervical mucus.
Klaira, like all hormonal contraceptives, does not protect against HIV infection (AIDS) or other sexually transmitted diseases.

When you must not take Klaira
Do not use Klaira 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 for your situation.
Do not take Klaira:

if you have (or have ever had) a blood clot in a blood vessel in your leg (deep vein thrombosis, DVT), lung (pulmonary embolism, PE), or other organs;
if you know you have a blood clotting disorder, such as protein C deficiency, protein S deficiency, antithrombin-III deficiency, factor V Leiden, or antiphospholipid antibodies;
if you are about 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, which could increase the risk of blood clots forming 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 had) a liver disease and your liver function is still abnormal;
if you have (or have had) a liver tumour;
if you have (or have had) breast cancer or genital organ cancer, or suspect you may have such cancer;
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 signs suggestive of a blood clot, which may indicate 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, see the section “How to recognize a blood clot”.
Inform your doctor if any of the following conditions apply to you.
In certain situations, you need to be particularly careful when using Klaira or any other combined oral contraceptive, and your doctor may need to examine you regularly. If any of these conditions develop or worsen while you are using Klaira, inform your doctor:

if a close relative has or has 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 about 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 delivery you can start taking Klaira;
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 Klaira”);
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 rash during pregnancy), Sydenham’s chorea (a nerve disorder causing sudden, involuntary movements);
if you have (or have had) patchy yellow-brown skin pigmentation, known as “melasma”, especially on the face. In such cases, avoid direct exposure to sunlight or ultraviolet radiation;
if you have hereditary or acquired angioedema. Stop taking Klaira and consult your doctor immediately if you experience 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 estrogens may induce or worsen angioedema symptoms;
if you have heart or kidney failure.

Consult your doctor before taking Klaira.
Additional information for specific patient groups
Use in children:
Klaira is not indicated for use in women who have not yet had their first menstrual period (menarche).

BLOOD CLOTS
Using a combined hormonal contraceptive such as Klaira 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, and very rarely, such events can be fatal.
It is important to remember that the overall risk of a harmful blood clot associated with Klaira is low.
HOW TO RECOGNIZE A BLOOD CLOT
Contact a doctor immediately if you notice any of the following signs or symptoms.

Does it present any of these signs?	What is it probably 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 while standing or walking • increased warmth in the affected leg • change in skin color of the leg, such as paleness, reddish or bluish discoloration	Deep vein thrombosis

sudden and 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, consult a doctor, as some of these symptoms, such as cough or shortness of breath, may be mistaken for a milder condition like a respiratory infection (e.g., a "common cold").	Pulmonary embolism
Symptoms occurring more frequently in one eye: • sudden loss of vision or • painless blurring of vision that may progress to vision loss	Retinal vein thrombosis (blood clot in the eye)
pain, discomfort, pressure, or heaviness in the chest • squeezing or fullness sensation in the chest, in one arm, or under the breastbone; • feeling of fullness, indigestion, or choking; • discomfort in the upper body spreading to the back, jaw, throat, arms, or stomach; • sweating, nausea, vomiting, or dizziness; • extreme weakness, anxiety, or shortness of breath; • rapid or irregular heartbeat	Heart attack
sudden numbness or weakness of the face, one arm, or one leg, especially on one side of the body; • sudden confusion, difficulty speaking or understanding; • sudden vision problems in one or both eyes; • sudden difficulty walking, dizziness, loss of balance or coordination;	Stroke
sudden, severe or prolonged headache without known cause; • loss of consciousness or fainting with or without seizures. Sometimes stroke symptoms may be brief, with almost immediate and complete recovery, but you should still seek urgent medical attention as you may be at risk of another stroke.
swelling and pale blue discoloration of a limb; • severe abdominal pain (acute abdomen)	Blood clots blocking other blood vessels

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 developing blood clots 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 of 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 or a different medicine) 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 Klaira, 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 venous thromboembolism (VTE) 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 Klaira 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 Klaira 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”).

	Risk of developing a blood clot in one year
Women who do not use a combined hormonal pill/patch/ring and who are not pregnant	About 2 women out of 10,000
Women who use a combined oral contraceptive pill containing levonorgestrel, norethisterone or norgestimate	About 5-7 women out of 10,000
Women who use Klaira	Approximately the same as other combined hormonal contraceptives, including contraceptives containing levonorgestrel.

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

if you are very overweight (body mass index or BMI over 30 kg/m²);
if a close relative has had a blood clot in the leg, lung, or another organ at a young age (under approximately 50 years). In this case, you might have an inherited blood clotting disorder;
if you are due to undergo surgery or need to remain bedridden for a prolonged period due to injury or illness, or if you have a leg in plaster. You may need to stop taking Klaira several weeks before surgery or during periods of reduced mobility. If you need to stop taking Klaira, ask your doctor when you can start taking it again;
as you get older (especially over 35 years of age);
if you have given birth within the last few weeks.

The risk of developing a blood clot increases if you have more than one of these conditions.
Air travel (lasting >4 hours) may temporarily increase the risk of blood clots, particularly if you have any 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 stop your use of Klaira.
If any of the conditions listed above change while you are using Klaira—for example, if a close relative develops a blood clot without an obvious 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 Klaira is very low, but it may increase:

with increasing age (over 35 years);
if you smoke. When using a combined hormonal contraceptive such as Klaira, it is advisable to stop smoking. If you cannot stop smoking and 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 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 Klaira—for example, if you start smoking, if a close relative develops a thrombosis without an obvious cause, or if you gain significant weight—contact your doctor.

Klaira 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, more tumours may be detected in users simply because they are examined more frequently. The risk of breast cancer gradually decreases after stopping combined hormonal contraception.
It is important that you regularly check your breasts and contact your doctor if you feel any lumps.
In rare cases, benign liver tumours and even more rarely malignant liver tumours have been observed in women using oral contraceptives. In isolated cases, these tumours 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 behaviour or other factors such as human papillomavirus (HPV) contribute to this risk.

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

Intermenstrual bleeding
During the first few months of taking Klaira, unexpected bleeding may occur. Bleeding usually starts on day 26, the day you take the second dark red tablet, or in the following days. Data from diaries kept by women during a clinical study with Klaira show that unexpected bleeding in a given cycle is not uncommon (occurring in 10–18% of users). If unexpected bleeding occurs for more than three consecutive months, or if bleeding starts after several months of use, 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 Klaira show that it is not unusual for menstruation not to occur on day 26 (observed in about 15% of cycles).
If you have taken all tablets correctly, have not vomited or had severe diarrhoea, and have not taken any other medicines, it is highly unlikely that you are pregnant.
If you miss two consecutive periods or have not taken the tablets correctly, you may be pregnant. Contact your doctor immediately. Do not start the next pack until you have confirmed that you are not pregnant.

Other medicines and Klaira
Always inform your doctor or pharmacist if you are taking or have recently taken any other medicines or herbal remedies, including those obtained without a prescription. Also inform any other doctor or dentist who prescribes medicines (or your pharmacist) that you are taking Klaira. They can advise you whether you need to use additional contraceptive measures (e.g. condoms), and if so, for how long.
Some medicines:

affect Klaira levels in the blood;
may make it less effective in preventing pregnancy;
may cause unexpected bleeding.

These include:

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);
- combination regimens for hepatitis C virus (HCV) consisting of ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir may cause increases in blood test results related to liver function (elevated liver enzyme ALT) in women using COCs containing ethinylestradiol. Klaira contains estradiol instead of ethinylestradiol. It is not known whether elevated liver enzyme ALT may occur when using Klaira with these HCV combination regimens. Your doctor will provide you with necessary instructions.
- fungal infections (e.g. griseofulvin, ketoconazole);
- St John’s wort (Hypericum perforatum).
Klaira may affect the effect of other medicines, for example:
- medicines containing cyclosporine;
- the antiepileptic lamotrigine (this may lead to an increased frequency of epileptic seizures).
  Ask your doctor or pharmacist for advice before taking any medicine. Your doctor or pharmacist can advise you whether you need to use additional protective measures while taking Klaira together with other medicines.

Klaira with food and drinks
Klaira can be taken with or without food, if necessary with a small amount of water.

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

Pregnancy and breastfeeding
If you become pregnant while taking Klaira, you must stop treatment immediately and contact your doctor. If you wish to become pregnant, you may stop taking Klaira at any time (see also "If you stop taking Klaira").
The use of Klaira is generally not recommended during breastfeeding. If you wish to take the pill while breastfeeding, you should consult your doctor.
Ask your doctor or pharmacist for advice before taking any medicine during pregnancy or breastfeeding.

Driving and use of machines
There are no reasons to believe that Klaira affects the ability to drive or use machines.

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

3. How to take Klaira

Each pack contains 26 coloured active tablets and 2 white inactive tablets.
Take one tablet of Klaira every day, with a small amount of liquid if necessary. You may take the tablets with or without food, but you must take them at approximately the same time each day.

Preparing the pack
To help you follow the correct sequence, each pack of Klaira contains 7 self-adhesive labels with the 7 days of the week.
Choose the weekly label starting with the day on which you begin taking the tablets. For example, if you start on Wednesday, use the adhesive label beginning with "WED".
Attach the weekly adhesive label along the top edge of the Klaira pack where it says "Place label here", so that the first day is above the tablet marked with the number "1".
This way, each tablet will have a day marked above it, allowing you to check whether you have taken the tablet on any given day. Follow the direction of the arrow on the pack until all 28 tablets have been taken.

Usually, menstruation, also called withdrawal bleeding, begins while you are taking the second dark red tablet or the white tablets, and may not have finished before you start the next pack. Some women may still be bleeding even after they have already started taking the first tablets of the new pack.

Start the next pack the day after finishing the current one, without any break, even if menstruation has not yet ended. This means you should start the next pack on the same day of the week, and your period should occur on the same days every month.

If you use Klaira in this way, contraceptive protection is maintained even during the 2 days when you are taking the inactive tablets.

When to start the first pack

If you have not used any hormonal contraceptive in the previous month: Start taking Klaira on the first day of your cycle (the first day of menstruation).
Switching from another combined oral contraceptive pill, vaginal ring, or combined contraceptive patch: Start taking Klaira the day after the last active tablet (the last tablet containing active ingredients) of your previous pill. When switching from a vaginal contraceptive ring or patch, start using Klaira 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): You may switch to Klaira at any time from the progestogen-only pill (from an implant or IUS on the day of removal, from an 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 Klaira.
After an abortion: Follow your doctor’s advice.
After childbirth: You may start taking Klaira between the 21st and 28th day after delivery. If you start later than the 28th day, use a barrier method (e.g. condom) during the first 9 days of taking Klaira. If you have had sexual intercourse after childbirth and before starting Klaira, you must exclude pregnancy or wait for the next menstrual period. If you wish to start taking Klaira 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 Klaira than you should
There have been no reports of serious harmful effects from taking too many Klaira 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 KLAIRA tablets, or find that a child has taken any tablets, contact your doctor or pharmacist immediately.

If you forget to take Klaira
Inactive tablets: If you forget one white tablet (the two tablets at the end of the pack), you do not need to take it later, as they contain no active ingredients. However, it is important that you discard the forgotten white tablet to ensure that the number of days during which inactive tablets are taken does not increase; doing so could increase the risk of pregnancy. Continue taking the next tablet at your usual time.

Active tablets: Depending on the day of the cycle, as indicated in your calendar pack, when one active tablet has been forgotten, you must use additional contraceptive precautions, such as a barrier method (e.g. condom). Take the tablets as described below. For details, see also the diagram below:

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, then continue taking the following tablets as scheduled.
If the delay in taking a tablet is more than 12 hours, contraceptive protection may be reduced. Depending on the day of the cycle (as indicated in your calendar pack) when the tablet was missed, you must use additional contraceptive precautions, such as a barrier method (e.g. condom). See also the diagram below.
More than one tablet missed in a pack: Consult your doctor.

Do not take more than two active tablets in one day.
If you forget to start a new pack, or if you forget one or more tablets during days 3–9 of the pack, 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 missed (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, see also the diagram below.

If you have missed any of the active tablets in a pack and do not have a withdrawal bleed at the end of the pack, you may be pregnant. Consult your doctor before starting the next pack.

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, the active ingredients of the tablet may not be 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, preferably within 12 hours of your usual time of taking the tablet. If this is not possible, or if more than 12 hours have passed, follow the instructions under “If you forget to take Klaira”. If you do not wish to change your usual dosing schedule, take the corresponding tablet from another pack.

If you stop taking Klaira
You may stop taking Klaira 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 Klaira 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 Klaira, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Klaira can cause side effects, although not everyone experiences them. If you experience any side effect, especially if severe or persistent, or if you notice any change in your health that you think could be due to Klaira, inform your doctor.

There is an increased risk of developing blood clots in veins (venous thromboembolism, VTE) or blood clots in arteries (arterial thromboembolism, ATE) 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 need to know before taking Klaira”.

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 “Klaira 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 Klaira:

Common side effects (may affect up to 1 in 10 users)

Headache
Abdominal pain, nausea
Acne
Absence of menstruation, breast discomfort, painful menstruation, irregular menstruation (with irregular heavy bleeding)
Weight gain

Uncommon side effects (may affect up to 1 in 100 users)

Fungal infection, fungal infection of the vulva and vagina, vaginal infection
Increased appetite
Depression, depressed mood, emotional disturbance, difficulty sleeping, decreased sexual desire, mental disorder, mood swings
Dizziness, migraine
Hot flushes, high blood pressure
Diarrhea, vomiting
Increased liver enzymes
Hair loss, excessive sweating (hyperhidrosis), itching, rash
Muscle cramps
Breast enlargement, breast lumps, 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 body parts, for example ankles (edema)
Weight loss, changes in blood pressure

Rare side effects (may affect up to 1 in 1,000 users)

Candida infection, oral herpes, pelvic inflammatory disease, an eye vascular disease 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)
Aggressiveness, anxiety, feeling of unhappiness, increased sexual desire, nervousness, nightmares, restlessness, sleep disturbances, stress
Reduced attention, tingling sensation, vertigo
Intolerance to contact lenses, dry eyes, swollen eyes
Heart attack (myocardial infarction), palpitations
Bleeding from varicose veins, low blood pressure, inflammation of superficial veins, vein pain
Harmful blood clots in a vein or an artery, for example:
- In a leg or foot (DVT)
- In a lung (PE)
- Heart attack
- Stroke
- Mini-stroke or temporary stroke-like symptoms, known as transient ischaemic attack (TIA)
- 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, hirsutism, 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, nipple 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 vulva and vagina, vulvovaginal discomfort
Enlarged 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 Klaira) on the possible side effects “irregular menstruation (with irregular heavy bleeding)” and “absence of menstruation” is provided 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 onset, considered to be related to those of combined oral contraceptives, may also occur during the use of Klaira and are listed below (see also sections “When not to take Klaira” and “Warnings and precautions”):

Liver tumours (benign or malignant)
Erythema nodosum (red, soft subcutaneous nodules), erythema multiforme (skin rash with red spots or lesions)
Hypersensitivity (including symptoms such as rash, urticaria)
In women with hereditary angioedema (characterized by sudden swelling, for example of the eyes, mouth, throat, etc.), the oestrogens contained in combined oral contraceptives may trigger or worsen angioedema symptoms. If liver function is impaired, temporary discontinuation of combined oral contraceptives 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 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 Klaira

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 packaging after “EXP”. The expiry date refers to the last day of that month.
Medicines should not be disposed of 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 Klaira contains
The active substances are valerate estradiol, or valerate estradiol combined with dienogest.
One pack (28 film-coated tablets) of Klaira contains 26 active tablets in 4 different colours,
in the 1st, 2nd, 3rd and 4th rows, and 2 inactive white 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 valerate estradiol,
➢ 5 red tablets, each containing 2 mg of valerate estradiol and 2 mg of dienogest,
➢ 17 light yellow tablets, each containing 2 mg of valerate estradiol and 3 mg of dienogest,
➢ 2 dark red tablets, each containing 1 mg of valerate estradiol.
Composition of the inactive white tablets:
These tablets do not contain any active substance.
Excipients in the coloured tablets containing the active substances:
Tablet core: monohydrate lactose, maize starch, pregelatinized maize starch, povidone K25 (E1201), magnesium stearate (E572).
Tablet coating: hypromellose type 2910 (E464), macrogol 6000, talc (E553b), titanium dioxide (E171), iron oxide red (E172) and/or iron oxide yellow (E172).
Excipients in the inactive white tablets:
Tablet core: monohydrate lactose, maize starch, povidone K25 (E1201), magnesium stearate (E572).
Tablet coating: hypromellose type 2910 (E464), talc (E553b), titanium dioxide (E171).

Description of the appearance of Klaira and package contents
Klaira tablets are film-coated tablets; the tablet core is covered with a coating.
One pack (28 film-coated tablets) of Klaira contains 2 dark yellow tablets in the 1st row, 5 red tablets in the 1st row, 17 light yellow tablets in the 2nd, 3rd and 4th rows, 2 dark red tablets in the 4th row, and 2 inactive white tablets in the 4th row.
The dark yellow tablet is round, biconvex-faced, with the letters “DD” printed within a regular hexagon on one side.
The red tablet is round, biconvex-faced, with the letters “DJ” printed within a regular hexagon on one side.
The light yellow tablet is round, biconvex-faced, with the letters “DH” printed within a regular hexagon on one side.
The dark red tablet is round, biconvex-faced, with the letters “DN” printed within a regular hexagon on one side.
The white tablet (inactive) is round, biconvex-faced, with the letters “DT” printed within a regular hexagon on one side.
Klaira is available in packs of 1, 3 and 6 blisters, each containing 28 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Bayer S.p.A. - Viale Certosa, 130 - 20156, Milan (Italy)

Manufacturers
➢ Bayer Weimar GmbH und Co. KG, 99427 Weimar – Germany
➢ Bayer AG, 13342 Berlin – Germany

This medicinal product is authorized in the European Economic Area countries under the following names:
➢ Austria, Belgium, Croatia, Cyprus, Czech Republic, Germany, Denmark, Estonia, Greece, Spain, Finland, France, Ireland, Iceland, Latvia, Luxembourg, Lithuania, Malta, Netherlands, Norway, Poland, Portugal, Romania, Sweden, Slovenia, Slovakia, Hungary: QLAIRA/Qlaira.
➢ Italy: Klaira