Qlaira

Package leaflet: Information for the user

Qlaira, coated tablets
Estradiol valerate + Dienogest
Please read all of this leaflet carefully before you start 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 harm them, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. Important information about combined hormonal contraceptives
• When used correctly, they are one of the most reliable reversible methods of contraception.
• They slightly increase the risk of blood clots in veins and arteries, especially in the first year of use or after restarting following a break of 4 weeks or more.
• Be alert and consult your doctor if you suspect symptoms of blood clots (see section 2 “Blood clots”).

Contents of the leaflet
Important information about combined hormonal contraceptives ....................................................................................... 1

1. What Qlaira is and what it is used for ........................................................ 2

2. Before you take Qlaira .............................................................................. 2
When not to take Qlaira ................................................................................ 2
Do not take Qlaira: ........................................................................................ 2
Additional information for specific patient groups ........................................ 4
BLOOD CLOTS .............................................................................................. 4
VENOUS BLOOD CLOTS ........................................................................... 6
Factors increasing the risk of venous blood clots ........................................ 7
ARTERIAL BLOOD CLOTS ........................................................................ 7
Qlaira and cancer ............................................................................................ 8
Psychiatric disorders ...................................................................................... 8
Breakthrough bleeding .................................................................................. 9
What to do if no bleeding occurs on day 26 or during several consecutive days ........................................................................................................ 9
Qlaira and other medicines ............................................................................ 9
Laboratory tests ............................................................................................ 10
Pregnancy and breastfeeding ........................................................................ 10
Driving and using machines ....................................................................... 10
Qlaira contains lactose .................................................................................. 10

3. How to take Qlaira ................................................................................... 10
   Preparing the cardboard blister pack (wallet-type packaging) .................... 10
   When to start the first wallet-type pack ......................................................... 11

Taking more Qlaira than you should ................................................................ 12
If you forget to take Qlaira ............................................................................ 12
Do not take more than 2 tablets containing active substances in one day. ... 12
Use in children ............................................................................................... 15
What to do if you have vomiting or severe diarrhoea ................................... 15
Stopping Qlaira .............................................................................................. 15

4. Possible side effects ................................................................................ 15
5. How to store Qlaira .................................................................................. 17
6. Contents of the pack and other information ........................................... 18

1. What Qlaira is and what it is used for

• Qlaira is a contraceptive tablet used to prevent pregnancy.
• Qlaira is used to treat heavy menstrual bleeding (not caused by any disease of the uterus) in women who wish to use oral contraception.
• Each coloured tablet contains a small amount of female hormones, namely: estradiol valerate or estradiol valerate in combination with dienogest.
• The two white tablets do not contain active substances and are referred to as "placebo".
• Contraceptive tablets containing two hormones are called "combined tablets".

2. Before you take Qlaira
General remarks
Before starting Qlaira, you should read the information about blood clots in section 2. It is especially important to be aware of the symptoms of blood clots (see section 2 “Blood clots”).
Before you can start taking Qlaira, your doctor will ask you several questions about your health and that of your close relatives. Your doctor will also measure your blood pressure and, depending on your condition, may carry out other examinations.
This leaflet describes several situations in which you should stop taking Qlaira or when its effectiveness may be reduced. In such cases, you should avoid sexual intercourse or use additional non-hormonal contraceptive methods, such as condoms or other mechanical methods. Do not use the calendar method or temperature measurement method. These methods may be unreliable because Qlaira alters the monthly changes in body temperature and cervical mucus.
Qlaira, like other hormonal contraceptives, does not protect against HIV (AIDS) infection or other sexually transmitted diseases.
When not to take Qlaira
Do not take Qlaira if you have any of the conditions listed below. If you have any of the conditions listed below, inform your doctor. Your doctor will discuss with you which other contraceptive method would be more suitable.
Do not take Qlaira:

• if you are allergic (hypersensitive) to estradiol valerate or dienogest, or to any of the other ingredients of this medicine (listed in section 6). This may cause itching, rash or swelling.
• if you currently have (or have ever had) blood clots in the veins of the legs (deep vein thrombosis), in the lungs (pulmonary embolism), or in other organs;
• if you know you have disorders affecting blood clotting – for example, protein C deficiency, protein S deficiency, antithrombin III deficiency, factor V Leiden mutation, or antiphospholipid antibodies;
• if you are undergoing surgery or will not be walking for a long time (see section “Blood clots”).
• if you have had a heart attack or stroke;
• if you suffer from (or have suffered in the past) angina pectoris (a condition causing severe chest pain and may be the first sign of a heart attack) or transient ischaemic attack (temporary stroke-like symptoms);
• if you suffer from any of the following conditions, which may increase the risk of arterial blood clots:
• severe diabetes with blood vessel damage
• very high blood pressure;
• very high levels of fats in the blood (cholesterol or triglycerides).
• a condition called hyperhomocysteinemia
• if you currently have (or have had in the past) a type of migraine called “migraine with aura”;
• if you currently have or have had liver disease and liver function remains abnormal;
• if you currently have or have had liver tumour;
• if you currently have or have had diagnosed or suspected breast cancer or genital organ cancer;
• if you have any unexplained vaginal bleeding.

Warnings and precautions
When to contact your doctor
Seek immediate medical advice

• if you notice possible symptoms of blood clots, which may indicate that you have blood clots in the leg (deep vein thrombosis), in the lungs (pulmonary embolism), heart attack or stroke (see section below “Blood clots”). For a description of symptoms of these serious side effects, see “How to recognise blood clots”.

Tell your doctor if you have any of the following conditions.
Special caution may be needed when taking Qlaira or any combined contraceptive tablet; regular check-ups by your doctor may also be necessary. If any of these conditions appear or worsen during treatment with Qlaira, inform your doctor:

• family history of breast cancer;
• liver or gallbladder disease;
• jaundice;
• diabetes;
• depression;
• Crohn’s disease or ulcerative colitis (chronic inflammatory bowel diseases);
• systemic lupus erythematosus (a disease affecting the body’s natural defence system);
• haemolytic uraemic syndrome (a blood clotting disorder causing kidney failure);
• sickle cell anaemia (an inherited red blood cell disorder);
• hypertriglyceridaemia (high blood fat levels) or a positive family history of this condition. Hypertriglyceridaemia is associated with an increased risk of pancreatitis;
• need for surgery or inability to walk for a long time (see section 2 “Blood clots”).
• are immediately postpartum, as you are at increased risk of blood clots. Consult your doctor for advice on how soon you can start taking Qlaira after childbirth.
• have phlebitis (inflammation of superficial veins).
• have varicose veins.
• have epilepsy (see “Qlaira and other medicines”);
• have a condition that first occurred during pregnancy or previous use of sex hormones, such as hearing loss, porphyria (a blood disorder), herpes gestationis (skin rash with blisters during pregnancy), Sydenham’s chorea (a nervous system disorder with involuntary body movements);
• have melasma (brownish pigmentation patches, so-called pregnancy mask, especially on the face). In this case, avoid direct exposure to sunlight or ultraviolet radiation;
• have hereditary or acquired angioedema. Stop taking Qlaira and seek immediate medical attention if you experience symptoms such as: swelling of the face, tongue and/or throat and/or difficulty swallowing or hives combined with breathing difficulties, which suggest angioedema. Products containing estrogens may trigger or worsen angioedema symptoms.
• have heart or kidney failure. Consult your doctor before taking Qlaira. Additional information for specific patient groups Use in children Qlaira is not intended for use in girls before the onset of menstruation. BLOOD CLOTS The use of combined hormonal contraceptives such as Qlaira is associated with an increased risk of blood clots compared to not using hormonal contraception. In rare cases, a blood clot may block a blood vessel and cause serious problems. Blood clots may occur
• in veins (referred to as “venous thrombosis” or “venous thromboembolic disease”)
• in arteries (referred to as “arterial thrombosis” or “arterial thromboembolic events”). Full recovery after a blood clot is not always possible. In rare cases, the consequences of a blood clot may be permanent or, very rarely, fatal.

Remember that the overall risk of harmful blood clots caused by taking Qlaira is small.
HOW TO RECOGNISE BLOOD CLOTS
Seek immediate medical advice if you notice any of the following symptoms.
Are you experiencing any of these symptoms? Likely reason
why you may
be suffering?

• swelling of the leg or swelling along a vein in the leg or foot, especially Deep vein thrombosis
• pain or tenderness in the leg, which may occur only when standing or walking,
• increased warmth in the affected leg
• change in skin colour of the leg, e.g. pallor, redness, blueness
• sudden onset of unexplained shortness of breath or rapid breathing; Pulmonary embolism
• sudden cough without obvious cause, possibly with coughing up blood;
• sharp chest pain, which may worsen with deep breathing;
• severe dizziness or vertigo;
• rapid or irregular heartbeat.
• severe stomach pain;

If you are unsure, consult your doctor, as some of these symptoms, such as cough or shortness of breath, may be mistaken for milder conditions such as respiratory tract infection (e.g. cold).
Symptoms usually occur in one eye: Retinal vein thrombosis (blood clot in the eye)

• sudden loss of vision or
• painless visual disturbances, which may progress to vision loss
• chest pain, discomfort, pressure, heaviness Myocardial infarction
• squeezing or fullness in the chest, arm or below the breastbone;
• feeling of fullness, indigestion or choking;
• discomfort in the lower body radiating to the back, jaw, throat, arm or stomach;
• sweating, nausea, vomiting or dizziness;
• extreme weakness, restlessness or shortness of breath;
• rapid or irregular heartbeat.
• sudden weakness or numbness of the face, arms or legs, especially on one Stroke side of the body;
• sudden confusion, speech or understanding problems;
• sudden vision problems in one or both eyes;
• sudden walking difficulties, dizziness, loss of balance or coordination;
• sudden, severe or prolonged headache without known cause;

BLOOD CLOTS IN VEINS
What can happen if blood clots form in veins

• The use of combined hormonal contraceptives is associated with an increased risk of venous blood clots (venous thromboembolism). Although these adverse events are rare, they most commonly occur during the first year of using combined hormonal contraceptives.
• If blood clots form in the veins of the leg or foot, this may lead to the development of deep vein thrombosis.
• If a blood clot travels from the leg and lodges in the lungs, it can cause pulmonary embolism.
• In very rare cases, a clot may form in another organ, such as the eye (retinal vein thrombosis).

When the risk of venous blood clots is highest
The risk of venous blood clots is greatest during the first year of first-time use of combined hormonal contraceptives. The risk may also be increased when restarting combined hormonal contraceptives (the same or another product) after a break of 4 weeks or more.

After the first year, the risk decreases, although it remains higher compared to not using combined hormonal contraceptives.
If a patient stops taking Qlaira, the risk of blood clots returns to normal within a few weeks.

What influences the risk of blood clots
The risk depends on the individual's natural risk of venous thromboembolic disease and the type of combined hormonal contraceptive product used. The overall risk of blood clots in the legs or lungs associated with the use of Qlaira is low.

• In one year, about 2 out of 10,000 women who do not use combined hormonal contraceptives and are not pregnant will develop blood clots.
• In one year, about 5–7 out of 10,000 women who use combined hormonal contraceptives containing levonorgestrel, norethisterone, or norgestimate will develop blood clots.
• The risk of blood clots associated with the use of Qlaira is approximately the same as the risk associated with other combined hormonal contraceptives, including those containing levonorgestrel.
• The risk of blood clots depends on the individual's medical history (see "Factors that increase the risk of blood clots" below).

Factors increasing the risk of blood clots in veins
The risk of blood clots associated with the use of Qlaira is small, but certain factors may increase this risk. The risk is higher:

• if the patient is very overweight (body mass index (BMI) above 30 kg/m²);
• if a close family member of the patient has had blood clots in the legs, lungs or other organs at a young age (e.g. under 50 years of age). In this case, the patient may have an inherited tendency to form blood clots;
• if the patient needs to undergo surgery, is immobilised for a prolonged period due to injury or illness, or has a leg in plaster. It may be necessary to stop taking Qlaira several weeks before surgery or during immobilisation. If the patient needs to stop taking Qlaira, ask the doctor when it is safe to restart taking the medicine.
• with increasing age (especially over 35 years);
• if the patient has recently given birth (within the last few weeks). The risk of blood clots increases with the number of risk factors present in the patient. Air travel (>4 hours) may temporarily increase the risk of blood clots, particularly if the patient has another risk factor listed above. Tell the doctor if any of the listed factors apply to the patient, even if uncertain. The doctor may decide to stop the use of Qlaira. Inform the doctor if any of the above conditions change during treatment with Qlaira, for example, if a close family member is diagnosed with unexplained thrombosis or if the patient gains significant weight.

BLOOD CLOTS IN ARTERIES
What can happen if blood clots form in arteries

As with blood clots in veins, blood clots in arteries can lead to serious consequences such as heart attack or stroke.

Factors increasing the risk of blood clots in arteries
It should be noted that the risk of heart attack or stroke associated with the use of Qlaira is very small, but may increase:

• with age (over approximately 35 years);
• if the patient smokes. When using a hormonal contraceptive such as Qlaira, it is recommended to stop smoking. If the patient is unable to stop smoking and is over 35 years of age, the doctor may recommend using a different type of contraception;
• if the patient is overweight;
• if the patient has high blood pressure;
• if a close family member has had a heart attack or stroke at a young age (under 50 years). In this case, the patient may also be at increased risk of heart attack or stroke;
• if the patient or a close family member has high levels of blood lipids (cholesterol or triglycerides);
• if the patient suffers from migraines, particularly migraines with aura;
• if the patient has heart disease (valve disorder, heart rhythm disorder known as atrial fibrillation);
• if the patient has diabetes. If the patient has more than one of the above conditions or if any of them are particularly severe, the risk of blood clots may be further increased. Inform the doctor if any of the above conditions change during treatment with Qlaira, for example, if the patient starts smoking, a close family member is diagnosed with unexplained thrombosis, or if the patient gains significant weight.

Qlaira and cancer
In women using combined hormonal contraceptives, breast cancer is observed slightly more frequently, but it is not known whether this is caused by taking the pills. For example, the higher detection rate of tumours in women using combined oral contraceptives may be due to the fact that these women are examined more frequently by doctors. The risk of breast cancer decreases gradually after stopping combined hormonal contraceptives. It is important to regularly examine the breasts and contact the doctor if any lump is felt. Cases of:

• rarely - benign liver tumours, and
• very rarely - malignant liver tumours

have been reported in women using oral contraceptives. In isolated cases, these tumours have led to life-threatening internal bleeding. If unusual, severe abdominal pain occurs, contact the doctor. Some studies suggest that long-term use of oral contraceptives increases the risk of 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 Qlaira, have reported depression or low mood. Depression can be severe and may sometimes lead to suicidal thoughts. If mood changes or symptoms of depression occur, contact the doctor as soon as possible for further medical advice.

Intermenstrual bleeding
During the first few months of taking Qlaira, unexpected bleeding may occur. Bleeding usually starts on day 26, i.e. on the day of taking the second dark red tablet, or within the following few days. According to diaries kept by women participating in clinical trials of Qlaira, such bleeding occurred frequently in a given cycle (reported by 10–18% of women). If unexpected bleeding persists for more than three consecutive months or starts after several months, the doctor should determine its cause.

What to do if no bleeding occurs on day 26 or within the following few days
According to diaries kept by women participating in clinical trials of Qlaira, bleeding withdrawal frequently did not occur after day 26 (observed in 15% of cycles).
If all tablets were taken correctly, there were no episodes of vomiting or severe diarrhoea, and no other medicines were taken, the likelihood of pregnancy is low.
If expected withdrawal bleeding does not occur in two consecutive cycles or if tablets were taken incorrectly, this may indicate pregnancy. Contact the doctor immediately.
Do not start the next pack until it is confirmed that you are not pregnant.

Qlaira and other medicines
Always inform the doctor prescribing Qlaira about any medicines or herbal products currently being taken. Similarly, inform any other doctor, including a dentist, or pharmacist prescribing or dispensing another medicine that you are taking Qlaira. They will advise whether additional contraceptive methods (e.g. condoms) are needed and, if so, for how long.
Some medicines may:

• affect the blood concentration of Qlaira;
• cause it to be less effective in preventing pregnancy;
• cause unexpected bleeding. These include medicines used to treat:
• epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate, felbamate);
• tuberculosis (e.g. rifampicin);
• HIV and hepatitis C virus infections (protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine, efavirenz);
• viral hepatitis C (HCV) (e.g. treatment regimens with ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir (see section 4) may cause increased liver function parameters in blood laboratory tests (elevated liver enzyme AlAT activity) in women taking combined hormonal contraceptives containing ethinylestradiol. Qlaira contains estradiol instead of ethinylestradiol. It is not known whether elevated AlAT liver enzyme activity may occur when taking Qlaira simultaneously with such treatment regimens;
• fungal infections (griseofulvin, ketoconazole);
• herbal products containing St John's wort (Hypericum perforatum).

Qlaira may affect the action of other medicines, e.g.:

• those containing cyclosporine;
• antiepileptic lamotrigine (this may lead to increased frequency of seizures).

Before taking any medicine, consult a doctor or pharmacist. The doctor or pharmacist may recommend using additional protective measures while taking another medicine concurrently with Qlaira.

Qlaira with food and drink
Qlaira can be taken regardless of meals, if necessary with a small amount of water.

Laboratory tests
If blood tests or other laboratory tests are required, inform the doctor or laboratory staff that you are taking Qlaira, as oral contraceptives may affect the results of certain tests.

Pregnancy and breastfeeding
If the patient becomes pregnant while taking Qlaira, she should stop taking it immediately and contact her doctor. If the patient wishes to become pregnant, she may stop taking Qlaira at any time (see also "Discontinuation of Qlaira").
Qlaira is generally not recommended during breastfeeding. If the patient wishes to take Qlaira while breastfeeding, she should contact her doctor.
Before taking any medicine, consult a doctor or pharmacist if the patient is pregnant or breastfeeding.

Driving and operating machinery
There is no information suggesting that Qlaira affects the ability to drive or operate machinery.

Qlaira contains lactose
If the patient has previously been diagnosed with intolerance to certain sugars, she should contact her doctor before taking Qlaira.

3. How to take Qlaira
Each cardboard box with blister pack (wallet-type packaging) contains 26 coloured tablets containing active substances and 2 white placebo tablets.
Take one Qlaira tablet daily, if necessary with a small amount of water. Tablets may be taken regardless of meals, but should be taken at approximately the same time each day.

Preparation of the cardboard box with blister pack (wallet-type packaging)
To make it easier to check whether a tablet has been taken each day, the package contains 7 adhesive strips with abbreviated names of the days of the week.
Choose a strip where the first day of the week corresponds to the day the pack is started. For example, if the first day of use is Wednesday, apply the strip where "WED" is the first day.
Apply the adhesive strip to the top of the Qlaira blister pack box, in the area marked "Place weekly label here". In this way, the first day is positioned above the tablet marked "1".
Each tablet now has the corresponding day of the week above it, and it is possible to check whether the correct tablet was taken each day. Tablets should be taken in the direction of the arrow on the packaging until all 28 tablets are used.
The so-called withdrawal bleeding usually starts after taking the second dark red tablet or during the intake of the white tablets and may not end before starting the next pack. In some women, bleeding continues after taking the first tablets of a new pack.
Start the next pack without a break; in other words, the next day after finishing the current pack, even if bleeding has not yet stopped. This means that the next pack starts on the same day of the week as the previous one, and withdrawal bleeding will occur approximately on the same days of the week each month.
If Qlaira is taken as described above, protection against pregnancy continues during the 2 days when placebo tablets are taken.

When to start the first wallet-type pack

• If no hormonal contraceptive has been used in the previous month. Start taking Qlaira on the first day of the cycle (i.e. the first day of menstrual bleeding).
• Switching from another combined hormonal contraceptive or from a combined vaginal contraceptive system or transdermal system. Start taking Qlaira the day after taking the last active tablet of the previous contraceptive. When switching from a combined vaginal contraceptive system or transdermal system, start taking Qlaira on the day of removal or as directed by the doctor.
• Switching from a progestogen-only method (progestogen-only mini-pill, injection, implant or intrauterine system (IUS) releasing progestogen). Switching from a progestogen-only mini-pill can be done on any day (from an implant or intrauterine system on the day of removal, or from injectable form on the day of the next scheduled injection), but in each case, additional contraceptive methods (e.g. condoms) must be used for the first 9 days of taking Qlaira.
• After miscarriage. Follow the doctor's instructions.
• After childbirth. After childbirth, Qlaira can be started between day 21 and 28. If started later than day 28, use the so-called mechanical method (e.g. condoms) for the first 9 days of taking Qlaira. If the woman had sexual intercourse after childbirth before starting Qlaira, ensure that she is not pregnant or wait until the next menstrual bleeding occurs.

If the patient wishes to start taking Qlaira after childbirth and is breastfeeding, read the section "Pregnancy and breastfeeding".
If the woman is unsure when to start taking the medicine, she should consult her doctor.

Taking more than the recommended dose of Qlaira
There are no reports of serious harmful effects from taking too many Qlaira tablets. If several active tablets are taken at once, nausea or vomiting may occur. Young girls may experience vaginal bleeding.
If too many Qlaira tablets are taken or if a child accidentally swallows them, contact the doctor or pharmacist.

Missed dose of Qlaira
Tablets without active substance: If the patient forgets to take a white tablet (the 2 tablets at the end of the pack), she does not need to take it later, as these tablets do not contain any active substances. However, it is important to discard the missed white tablets to avoid unintentionally increasing the number of days on which inactive tablets are taken, which could increase the risk of pregnancy. Take the next tablet at the usual time.

Tablets containing active substance: Depending on the day of the cycle indicated on the current pack when one active tablet was missed, it may be necessary to use additional contraceptive methods, e.g. mechanical method such as a condom. Tablets should be taken according to the rules below.
Detailed information is also shown on the "missed tablet management chart".

• If less than 12 hours have passed since the usual time of taking the tablet, protection against pregnancy is not reduced. Take the tablet as soon as possible, then continue taking the following tablets at the usual time.
• If more than 12 hours have passed since the usual time of taking the tablet, protection against pregnancy may be reduced. Depending on the day of the cycle indicated on the current pack when one tablet was missed, use additional contraceptive methods, e.g. a mechanical method such as a condom. Detailed information is also shown on the "missed tablet management chart".
• More than one tablet in the pack has been missed. Contact the doctor. Do not take more than 2 tablets containing active substances in one day. If the patient forgot to start taking tablets from a new pack, or forgot to take one or more tablets on days 3 to 9, there is a risk of pregnancy (if sexual intercourse occurred during the seven days before the missed tablet). In such a case, contact the doctor. The more tablets are missed (especially on days 3 to 24) and the closer it is to the phase of taking tablets without active substances, the greater the risk of reduced protection against pregnancy. Detailed information is also shown on the "missed tablet management chart". If any active tablet was missed during use and no withdrawal bleeding occurred during the intake of the tablets at the end of the pack, this may indicate that the woman is pregnant. In this case, contact the doctor before starting the next pack.

YES
NO
Use in children
There are no data regarding use in individuals under 18 years of age.
What to do if vomiting or severe diarrhoea occurs
If vomiting occurs within 3 to 4 hours after taking a tablet containing the active substance, or if severe diarrhoea occurs, there is a risk that the active substances in the tablet have not been completely absorbed by the body.
This situation is very similar to having missed a tablet. After vomiting or diarrhoea, take the next tablet as soon as possible. Ideally, take it within 12 hours of the scheduled time for taking the tablet. If this is not possible, or if more than 12 hours have passed, follow the instructions given in the section "Missed dose of Qlaira". If a woman does not wish to change her established tablet-taking schedule, she should take the appropriate tablet from another pack.
Stopping treatment with Qlaira
Treatment with Qlaira can be stopped at any time. If pregnancy is not desired, consult a doctor about other effective methods of birth control. If pregnancy is desired, stop taking Qlaira and wait for a menstrual period before trying to conceive. This makes it easier to calculate the expected date of delivery.
If you have any doubts regarding the use of this medicine, consult your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody will experience them.
If any side effects occur, especially severe or persistent ones, or changes in health that the patient considers related to the use of Qlaira, consult a doctor.
All women taking combined hormonal contraceptives have an increased risk of blood clots in the veins (venous thromboembolic disease) or blood clots in the arteries (arterial thromboembolic disorders). For detailed information on various risk factors associated with the use of combined hormonal contraceptives, refer to section 2, "Important information before using Qlaira".
Serious side effects
Serious reactions related to the use of the medicine, as well as associated symptoms, are described in the following sections: "Blood clots" and "Qlaira and cancer". Please read these sections carefully and consult your doctor if necessary.
Other possible side effects
The following side effects have been reported with the use of Qlaira:
Common side effects (occur in 1 to 10 out of 100 people):

• headache;

• abdominal pain, vomiting;

• acne;

• absence of menstruation, breast pain, painful menstruation, irregular bleeding (increased irregular bleeding);

• weight gain. Uncommon side effects (occur in 1 to 10 out of 1,000 people):

• fungal infections, fungal infection of the vulva and vagina, vaginal infection;

• increased appetite;

• depression, low mood, emotional disorders, difficulty sleeping, decreased interest in sex, psychiatric disorders, mood swings;

• dizziness, migraine;

• hot flushes, high blood pressure;

• diarrhoea, vomiting;

• increased liver enzyme activity;

• excessive hair loss, excessive sweating, itching, rash;

• muscle cramps;

• breast enlargement, breast nodules, abnormal cervical cell growth (cervical dysplasia), menstrual disorders, painful sexual intercourse, fibrocystic breast disease, heavy menstruation, abnormal menstruation, ovarian cyst, pelvic pain, premenstrual syndrome, endometrial hyperplasia, uterine cramps, vaginal bleeding including spotting, vaginal discharge, dryness of the vulva and vagina;

• fatigue, irritability, swelling of certain body areas, e.g. ankles;

• weight loss, changes in blood pressure. Rare side effects (occur in 1 to 10 out of 10,000 people):

• candidiasis, cold sores, pelvic inflammatory disease, eye vessel disease resembling fungal infection (presumed ocular histoplasmosis syndrome), fungal skin infections (tinea versicolor), urinary tract infection, bacterial vaginosis;

• fluid retention, increased blood triglyceride levels;

• aggression, anxiety, feeling of unhappiness, increased interest in sexual activity, nightmares, nervousness, psychomotor agitation, sleep disorders, tension;

• difficulty concentrating, tingling sensation, dizziness;

• intolerance to contact lenses, dry eye syndrome, eye swelling;

• heart attack, palpitations;

• bleeding from varicose veins, decreased blood pressure, superficial thrombophlebitis, vein pain;

• harmful blood clots in a vein or artery, for example:

• in the leg or foot (e.g. deep vein thrombosis)

• in the lungs (e.g. pulmonary embolism)

• heart attack

• stroke

• mini-stroke or transient stroke-like symptoms, known as transient ischaemic attack

• blood clots in the liver, stomach and (or) intestine, kidneys or eye
  The likelihood of developing blood clots may be higher if the patient has any other risk factors increasing this risk (see section 2 for further information on risk factors for blood clots and symptoms of blood clots).

• constipation, dry mouth, indigestion, heartburn;

• liver nodules (focal nodular hyperplasia), chronic cholecystitis;

• skin allergic reactions, brownish pigmentation (chloasma) and other pigment disorders, male-pattern hair growth, excessive hair growth, skin inflammation and eczema (neurodermatitis), dandruff and oily skin (seborrhoea) and other skin changes;

• back pain (lumbar), jaw pain, feeling of heaviness;

• urinary tract pain;

• breakthrough bleeding, benign breast tumours, early-stage breast cancer, breast cysts, nipple discharge, cervical polyp, cervical redness, bleeding during intercourse, unexpected milk secretion, vaginal discharge, lighter periods, delayed menstruation, ovarian cyst rupture, burning sensation in the vagina, unpleasant vaginal odour, vulvar and vaginal discomfort;

• enlarged lymph nodes;

• asthma, breathing difficulties, nosebleeds;

• chest pain, feeling of fatigue and general malaise, fever;

• abnormal cervical smear.
  Additional information (from diaries kept by women participating in the clinical trial with Qlaira) on possible side effects such as irregular bleeding (increased irregular bleeding) and absence of menstruation are described in the sections: "Intermenstrual bleeding" and "What to do if no bleeding occurs on day 26 or over several consecutive days".
  Description of selected side effects
  Side effects occurring very rarely or with delayed onset, which may be related to the use of combined oral contraceptives and may occur during treatment with Qlaira, are listed below (see also sections "When not to use Qlaira" and "Warnings and precautions"):

• liver tumour (benign and malignant),

• nodular erythema (tender red nodules under the skin), erythema multiforme (skin rash with red spots or sores),

• hypersensitivity reactions (including symptoms such as rash, urticaria),

• in women with hereditary angioedema (characterised by sudden swelling, e.g. of eyes, face, throat, etc.), estrogens in combined oral contraceptive tablets may trigger or worsen symptoms of this disease. In case of liver function disorders, it may be necessary to discontinue combined oral contraceptive tablets.
  Reporting of side effects
  If any adverse reactions occur, including those not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181PC, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
  Side effects can also be reported to the Marketing Authorisation Holder. Reporting side effects helps to provide more information on the safety of the medicine.
  5. How to store Qlaira
  Keep the medicine out of the sight and reach of children.
  No special storage conditions apply.
  Do not use this medicine after the expiry date stated on the blister pack after "Expiry date (EXP):". The expiry date refers to the last day of the stated month.
  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 Qlaira contains
  The active substances in Qlaira are: estradiol valerate or estradiol valerate in combination with dienogest.
  Each blister pack (wallet-type pack) contains 26 active tablets (in 4 different colours) arranged in rows 1, 2, 3 and 4, and 2 white inactive tablets (placebo) in row 4.
  Composition of the coloured tablets containing one or two active substances:
  2 dark yellow tablets, each containing 3 mg of estradiol valerate;
  5 light red tablets, each containing 2 mg of estradi 2 mg of dienogest;
  17 light yellow tablets, each containing 2 mg of estradiol valerate and 3 mg of dienogest;
  2 dark red tablets, each containing 1 mg of estradiol valerate.
  Composition of the white tablets (placebo):
  The white tablets (placebo) do not contain any active substance.
  Other ingredients in the coloured active tablets:
  Tablet core:
  Monohydrate lactose
  Corn starch
  Pregelatinized corn starch
  Povidone K25 (E1201)
  Magnesium stearate (E572)
  Coating:
  Hypromellose 2910 (E464)
  Macrogol 6000
  Talc (E553b)
  Titanium dioxide (E171)
  Red iron oxide (E172)
  and (or) Yellow iron oxide (E172)
  Other ingredients in the white inactive tablets:
  Tablet core:
  Monohydrate lactose
  Corn starch
  Povidone K25 (E1201)
  Magnesium stearate (E572)
  Coating:
  Hypromellose 2910 (E464)
  Talc (E553b)
  Titanium dioxide (E171)
  What Qlaira looks like and contents of the pack
  Qlaira tablets are film-coated tablets; the tablet core is covered with a coating.
  Each cardboard box with an attached blister (wallet-type pack) contains 28 film-coated tablets, including: 2 dark yellow and 5 light red tablets in the first row, 17 light yellow tablets in the second, third and fourth rows, 2 dark red tablets and 2 white tablets (placebo) in the fourth row.
  The dark yellow active tablets are round, biconvex; on one side marked with the letters "DD" in a regular hexagon.
  The light red active tablets are round, biconvex; on one side marked with the letters "DJ" in a regular hexagon.
  The light yellow active tablets are round, biconvex; on one side marked with the letters "DH" in a regular hexagon.
  The dark red active tablets are round, biconvex; on one side marked with the letters "DN" in a regular hexagon.
  The white inactive tablets are round, biconvex; on one side marked with the letters "DT" in a regular hexagon.
  Qlaira is available in packs containing 1, 3 or 6 cardboard boxes with attached blisters (wallet-type packs), each containing 28 tablets.
  Not all pack sizes may be available on the market.
  Marketing Authorisation Holder and Manufacturer
  Marketing Authorisation Holder
  Bayer AG
  Kaiser-Wilhelm-Allee 1
  51373 Leverkusen
  Germany
  Manufacturers:
  Bayer Weimar GmbH und Co. KG
  99427 Weimar
  Germany
  Bayer Pharma AG
  13353 Berlin
  Germany
  This medicinal product is authorised for sale in the European Economic Area member states under the following names:

• Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden: QLAIRA / Qlaira

• Italy: KLAIRA

For more detailed information on this medicine, contact your doctor or the representative of the Marketing Authorisation Holder.
Bayer Sp. z o.o.
Al. Jerozolimskie 158
02-326 Warsaw, Poland
tel. (0 22) 572 35 00