Yaz - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Ethinylestradiol, Drospirenone

YAZ 0.02 mg / 3 mg film-coated tablets

Why is Yaz used? What is it for?

YAZ is a contraceptive pill and is used to prevent pregnancy.

Each of the 24 light pink tablets contains a small amount of two different female hormones, drospirenone and ethinyl estradiol.

The 4 white tablets contain no active ingredients and are also called placebo tablets.

Contraceptive pills that contain two hormones are called combination pills.

Contraindications When Yaz should not be used

Before you start using YAZ you should read the information on blood clots in section 2. It is especially important that you read the symptoms of a blood clot (see section 2 "Blood clots").

Before taking YAZ, your doctor will ask you a few questions about your personal health history and that of your family members. The doctor will also measure your blood pressure and, depending on your personal situation, may also carry out other tests.

This leaflet describes various situations in which you must stop YAZ or in which the safety of YAZ may be decreased. In such situations it is necessary to refrain from sexual intercourse or to take additional non-hormonal contraceptive measures, such as a condom or other barrier method. Do not use the rhythm or basal temperature method. In fact, such methods can be unreliable, as YAZ alters the monthly changes in body temperature and cervical mucus.

YAZ, like all hormonal contraceptives, offers no protection against HIV infection (AIDS) or other sexually transmitted diseases.

Precautions for use What you need to know before taking Yaz

Do not use YAZ if you have any of the conditions listed below. If you have any of the conditions listed below, please contact your doctor. Your doctor will discuss with you other birth control methods that may be more suitable for you.

Do not take YAZ:

• 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 that affects blood clotting, such as protein C deficiency, protein S deficiency, antithrombin-III deficiency, factor V Leiden or antiphospholipid antibodies
• if you are going to have an "operation or if you will be lying down for a long time (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 that causes severe chest pain and may be a first sign of a heart attack) or transient ischemic attack (TIA - temporary stroke symptoms);
• if you have any of the following diseases, which could increase the risk of clots in the arteries: o severe diabetes with blood vessel damage o very high blood pressure o very high level of fat (cholesterol or triglycerides) in the blood o a disease known as hyperhomocysteinemia
• if you have (or have ever had) a type of migraine called 'migraine with aura';
• if you have (or have ever had) liver disease and your liver function is still abnormal
• if your kidneys are not working well (kidney failure)
• if you have (or have ever had) liver cancer
• if you have (or have ever had) or if you are suspected of having cancer of the breast or genital organs;
• if you have unexplained vaginal bleeding
• if you are allergic to ethinylestradiol or drospirenone or any of the other ingredients of this medicine (listed in section 6). This condition can manifest itself as itching, rash or swelling.

When you need to be especially careful with YAZ

When should you see a doctor? Contact a doctor urgently

• if you notice possible signs of a blood clot which may indicate that you are suffering from a blood clot in the leg (deep vein thrombosis), a blood clot in the lung (pulmonary embolism), a heart attack or a stroke (see section below " Blood clots ").

For a description of the symptoms of these serious side effects go to the section "How to recognize a blood clot".

Tell your doctor if any of the following apply to you.

In some situations you need to be especially careful while using YAZ or any other combination pill, and your doctor may need to see you regularly. If this condition appears or worsens while you are using YAZ, you should tell your doctor.

• if a close relative has or has ever had breast cancer
• if you have liver or gallbladder disease
• 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 that affects the natural defense system);
• if you have haemolytic uremic syndrome (HUS, a blood clotting disorder causing kidney failure);
• if you have sickle cell anemia (an inherited disease of the red blood cells);
• if you have high levels of fat in the blood (hypertriglyceridaemia) or a "positive family history of this condition." Hypertriglyceridaemia has been associated with an increased risk of developing pancreatitis (inflammation of the pancreas);
• if you are going to have an "operation or if you are going to lie down for a long time (see section 2" Blood clots ");
• if you have just given birth, your risk of developing blood clots is higher. Ask your doctor how long after having a baby you can start taking YAZ;
• if you have "inflammation of the veins under the skin (superficial thrombophlebitis);
• if you have varicose veins;
• if you have epilepsy (see "Other medicines and YAZ")
• if you have a disease that first appeared during pregnancy or previous use of sex steroids (for example, hearing loss, a blood disorder called porphyria, rash with blisters during pregnancy (herpes gravidarum) ), a nerve disease that occurs with sudden movements of the body (Sydenham's chorea))
• if you have or have ever had brown patchy pigmentation (chloasma), known as "pregnancy spots", especially on the face. In this case, avoid direct exposure to sunlight or ultraviolet rays
• if you suffer from hereditary angioedema, medicines containing estrogen can cause or worsen the symptoms of angioedema. If you experience symptoms of angioedema such as swelling of the face, tongue and / or pharynx and / or difficulty in swallowing or hives with difficulty in breathing, contact your doctor immediately

Talk to your doctor before taking YAZ

Blood clots

Using a combined hormonal contraceptive such as YAZ increases your risk of developing a blood clot compared with not using one. In rare cases, a blood clot can block blood vessels and cause serious problems.

Blood clots can develop

• in veins (called "venous thrombosis", "venous thromboembolism" or VTE)
• in the arteries (referred to as 'arterial thrombosis', 'arterial thromboembolism' or ATE).

Recovery from blood clots is not always complete. Rarely, long-lasting severe effects can occur or, very rarely, they can be fatal.

It is important to remember that the overall risk of a harmful blood clot associated with YAZ is low.

HOW TO RECOGNIZE A BLOOD CLOT

See a doctor immediately if you notice any of the following signs or symptoms.

Do you have any of these signs? What are you probably suffering from?

• swelling of one leg or along a vein in the leg or foot, especially when accompanied by:
• pain or tenderness in the leg which may only be felt when standing or walking
• increased sensation of heat in the affected leg
• change in color of the skin on the leg, such as turning pale, red or blue

Deep vein thrombosis

• shortness of breath or sudden, unexplained rapid breathing;
• sudden cough with no obvious cause, possibly causing blood to be emitted;
• sharp chest pain which may increase with deep breathing;
• severe light headedness or dizziness;
• rapid or irregular heartbeat;
• severe pain in the stomach

If you are unsure, tell your doctor as some of these symptoms such as coughing or shortness of breath may be mistaken for a milder condition such as a "respiratory infection (eg a" common cold ").

Pulmonary embolism Symptoms that occur most frequently in one eye:

• immediate loss of vision or
• painless blurring of vision which can progress to loss of vision

Retinal vein thrombosis (blood clot in the eye)

• chest pain, discomfort, feeling of pressure or heaviness
• sensation of squeezing or fullness in the chest, arm or below the breastbone;
• feeling of fullness, indigestion or choking;
• upper body discomfort radiating to the back, jaw, throat, arms and stomach;
• sweating, nausea, vomiting or dizziness;
• extreme weakness, anxiety or lack of
• breath;
• rapid or irregular heartbeats

Heart attack

• sudden numbness or weakness of the face, arm or leg, especially on one side of the body;
• sudden confusion, difficulty speaking or understanding;
• sudden difficulty seeing in one or both eyes;
• sudden difficulty walking, dizziness, loss of balance or coordination;
• sudden, severe or prolonged migraine with no known cause;
• loss of consciousness or fainting with or without seizures.

Stroke symptoms can sometimes be brief, with almost immediate and complete recovery, but you still need to see a doctor urgently as you may be at risk for another stroke. Stroke

• swelling and pale blue discoloration of one "extremity;
• severe stomach pain (acute abdomen)

Blood clots that block 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 linked to an increased risk of blood clots forming in the veins (venous thrombosis). However, these side effects are rare. In most cases they occur in the first year of using a combined hormonal contraceptive.
• If a blood clot forms in a vein in the leg or foot, it can cause a 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 can 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 be even higher if you restart taking a combined hormonal contraceptive (the same drug or a different drug) after a break of 4 or more weeks.After the first year, the risk is reduced but is always slightly higher than if you do not were using a combined hormonal contraceptive.

When you stop taking YAZ, the risk of developing a blood clot returns to normal within a few weeks.

What is the risk of developing a blood clot?

The risk depends on your natural risk of 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 YAZ is low.

• Out of 10,000 women who are not using any combined hormonal contraceptive and who are not pregnant, about 2 will develop a blood clot in a year.
• Out of 10,000 women who are using a combined hormonal contraceptive that contains levonorgestrel, norethisterone or norgestimate, about 5-7 will develop a blood clot in a year.
• Out of 10,000 women who are using a combined hormonal contraceptive containing drospirenone, such as YAZ, about 9-12 will develop a blood clot in a year.
• The risk of a blood clot forming depends on your medical history (see under "Factors that increase the risk of a blood clot forming").

Risk of developing a blood clot in one year Women who are not using a combined hormone pill and who are not pregnant About 2 out of 10,000 women Women using a combined hormonal contraceptive pill containing levonorgestrel, norethisterone or norgestimate About 5-7 out of 10,000 women Women who use YAZ About 9-12 out of 10,000 women

Factors that increase the risk of developing a blood clot in a vein

The risk of developing a blood clot with YAZ is low but some conditions cause it to increase. Its risk is greater:

• if you are severely overweight (body mass index or BMI over 30 kg / m2);
• if a close relative has had a blood clot in the leg, lung or other organ at a young age (less than about 50 years). In this case you could have an inherited blood clotting disorder;
• if you are going to have an operation or if you have to lie down for a long time because of an injury or illness or if you have a leg in a cast. You may need to stop taking YAZ a few weeks before the surgery or during the period where it is less mobile.

If you have to stop taking YAZ, ask your doctor when you can start taking it again;

• as you get older (especially over 35)
• if you gave birth less than a few weeks ago.

The risk of developing a blood clot increases the more conditions you have of this type.

Air travel (lasting> 4 hours) may temporarily increase the risk of a blood clot, especially if you have some of the other risk factors listed.

It is important that you tell your doctor if any of these apply to you, even if you are not sure. Your doctor may decide that YAZ needs to be stopped.

If any of the above conditions change while you are using YAZ, for example if a close relative has a thrombosis for no known reason or if you gain a lot of 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 can cause 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 YAZ is very low but can increase:

• with increasing age (over 35 years);
• if you smoke. When using a combined hormonal contraceptive such as YAZ you are advised to stop smoking. If you are unable to stop smoking and are over the age of 35, your doctor may advise you to use a different type of contraceptive;
• if you are overweight;
• if you have high blood pressure;
• if a member of your immediate family has had a heart attack or stroke at a young age (less than about 50 years). In this case, you may also be at high risk of having a heart attack or stroke;
• if you or a close relative have a high level of fat in the blood (cholesterol or triglycerides);
• if you suffer from migraines, especially migraines with aura;
• if you have any heart problems (valve defect, a heart rhythm disorder called atrial fibrillation);
• if you have diabetes.

If you have more than one of these conditions or if any of them are particularly severe, the risk of developing a blood clot may be even higher.

If any of the above conditions change while you are using YAZ, for example if you start smoking, if a close relative has a thrombosis for no known reason, or if you gain a lot of weight, contact your doctor.

YAZ and cancer

Breast cancer occurs slightly more often in women using the combined pill, but it is not known whether this is due to the treatment. For example, women on the Pill may be diagnosed with more cancers because they undergo more frequent medical checks.

The occurrence 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.

Rare cases of benign liver tumors and, even more rarely, malignant liver tumors have been observed in women using the Pill. Contact your doctor if you experience unusual and severe abdominal pain.

Intermenstrual bleeding

During the first few months of taking YAZ, unexpected bleeding (bleeding outside the placebo days) may occur. If this bleeding continues for more than a few months, or if it starts after a few months, your doctor should check what is wrong.

What to do if menstruation does not appear during the placebo days

If you have taken all the light pink active tablets correctly, have not had vomiting or severe diarrhea and have not taken any other medicines, it is highly unlikely that you are pregnant.

If the period does not appear twice in a row, she may be pregnant. Contact your doctor immediately. Only start the next strip if you are sure you are not pregnant.

Interactions Which drugs or foods can change the effect of Yaz

Always tell your doctor if you are taking any medicines or herbal products. Tell any other doctor or dentist who prescribes another medicine (or pharmacist) that you are taking YAZ. They will be able to tell you if you need to take additional contraceptive measures (e.g. condoms) and for how long.

Some medicines can make YAZ less effective in preventing pregnancy or can cause unexpected bleeding. These include medicines to treat:

• epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine),
• tuberculosis (e.g. rifampicin),
• HIV infection (ritonavir, nevirapine) or other infections (antibiotics such as griseofulvin, penicillin, tetracyclines),
• high blood pressure in the arteries of the lungs (bosentan) and St. John's wort (Hypericum perforatum), a herbal remedy.

YAZ may influence the effect of other medicines, for example:

• medicines containing cyclosporine,
• the antiepileptic lamotrigine (this can lead to an increase in the frequency of seizures). Ask your doctor or pharmacist for advice before taking any medicine.

YAZ with food and drink

YAZ can be taken with or without food, with a little water if needed.

Warnings It is important to know that:

Laboratory analysis

If you need to have a blood test, tell your doctor or laboratory staff that you are taking the pill, as hormonal contraceptives can affect the results of some tests.

Pregnancy

If you are pregnant you should not use YAZ. If you become pregnant while taking YAZ, you must stop taking the pill immediately and contact your doctor. If you wish to become pregnant, you can stop taking YAZ at any time (see also "If you stop taking YAZ").

Ask your doctor or pharmacist for advice before taking any medicine.

Feeding time

The use of YAZ is generally not recommended during breastfeeding. If you want to take the pill while breastfeeding, you should contact your doctor. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

There is no evidence that YAZ affects the ability to drive or use machines.

YAZ contains lactose

If you cannot tolerate some sugars, contact your doctor before taking YAZ.

Dose, Method and Time of Administration How to use Yaz: Posology

Each blister contains 24 light pink active tablets and 4 white placebo tablets.

The two types of different colored tablets of YAZ are arranged in succession. One blister contains 28 tablets.

Take one YAZ tablet every day, with a little water if needed. You can take the tablets with or without food, but you must take them around the same time each day.

Do not confuse the tablets: take a light pink tablet for the first 24 days and then a white tablet for the last 4 days. You must then start a new blister immediately (24 light pink tablets and 4 white tablets). So there is no gap between the two blisters.

As the composition of the tablets is different, you must start with the first tablet on the top left, and take the tablets every day. For a correct order, follow the direction of the arrows on the blister.

Preparation of the blister

To help you keep track of your daily pill intake, each blister of YAZ contains 7 self-adhesive labels with the 7 days of the week, each starting with a different day of the week. Choose the label that starts with the day it starts to take the tablets. For example, if it starts on a Wednesday, you use the sticker that starts with "WED".

Apply the adhesive label of the week to the entire length of the top of the YAZ blister, where it says "Put the adhesive label here", so that the first day is on top of the tablet marked with the number "1" .

Now there is a day indicated above each tablet and you can visually check if you have taken a certain pill. The arrows show the order of taking the pills.

During the 4 days that you are taking the white placebo tablets (the placebo days), menstruation should occur (so-called withdrawal bleeding). This usually starts on the 2nd or 3rd day after the last light pink active tablet of YAZ. Once you have taken the last white tablet, you should start the next strip, even if you are still menstruating. This means that you must start each strip on the same day of the week, and that your period will occur on the same days each month.

By taking YAZ as indicated above, you are protected from pregnancy even during the 4 days you are taking the placebo tablet.

When can the first blister start?

• If you have not used a hormonal contraceptive in the previous month Start taking YAZ on the first day of your period (ie the first day of your period). If you start on the first day of your period the contraceptive effect is immediate. You can also start taking YAZ between the 2nd and 5th day of your cycle, but in this case you must take additional contraceptive measures (for example, a condom) for the first 7 days.
• Changing from a combined hormonal contraceptive or a combined contraceptive vaginal ring or patch Start taking YAZ preferably the day after the last active tablet (the last tablet containing the active ingredients) of the previous pill, or at the latest on the day after the end of the tablet-free interval (or after the last inactive tablet of the previous pill). When switching from a combined contraceptive vaginal ring or patch, follow your doctor's advice.
• Changing from a progestogen-only method (progestogen-only pill, injection, implant or progestogen-releasing intrauterine system (IUS)) You can switch any day from the progestogen-only pill (from an implant or IUS) on the day of its removal, from an injectable when you have the next injection), but in all these cases you must use additional contraceptive measures (eg condoms) for the first 7 days of taking the tablets.
• After an abortion Follow your doctor's advice.
• After giving birth You can start taking YAZ between the 21st and 28th day after giving birth. If you start later than the 28th day, you must use a so-called barrier method (eg condom) during the first 7 days. days of taking YAZ. If, after having a baby, you have had intercourse before starting (or restarting) YAZ, you must first make sure that you are not pregnant or wait for your period.
• If you are breastfeeding and want to start (or restart) taking YAZ Read the section "Breastfeeding".

Ask your doctor for advice if you are not sure when to start.

Overdose What to do if you have taken too much Yaz

If you take more YAZ than you should

There are no reports of serious harmful effects of taking too many YAZ tablets.

If you take several tablets at once, you may feel sick or vomit. Young girls can have vaginal bleeding.

If you have taken too many YAZ tablets, or find that a child has taken some tablets, talk to your doctor or pharmacist.

If you forget to take YAZ

The last 4 tablets in the 4th row of the blister are the placebo tablets. If you forget one of these tablets, this has no effect on the reliability of YAZ. You should throw away the forgotten placebo tablet.

If you forget a light pink active tablet (tablets 1 to 24 from the blister pack), you should follow these tips:

• If you are less than 24 hours late in taking a tablet, contraceptive protection is not reduced. Take the tablet as soon as you remember and then take the next tablets as planned.
• If you are more than 24 hours late in taking a tablet, contraceptive protection may be reduced. The more tablets you miss, the greater the risk of becoming pregnant.

This risk is greatest if you forget a light pink tablet at the beginning or at the end of the strip. You should therefore follow the instructions below (see also the diagram below):

• More than one tablet forgotten in this pack. Talk to your doctor.

• One tablet forgotten on days 1-7 (first row). Take the forgotten tablet as soon as you remember, even if that means that you have to take two tablets at the same time. Then continue taking the tablets at the usual time and take additional contraceptive measures for the next 7 days, for example a condom. If you have had sexual intercourse in the week preceding the forgetfulness, you may have become pregnant. In this case, please contact your doctor.

• One tablet forgotten on days 8-14 (second row). Take the forgotten tablet as soon as you remember, even if that means that you have to take two tablets at the same time. Then continue taking the tablets as planned. The contraceptive safety of the pill is maintained and it is therefore not necessary to take additional precautions.

• One tablet forgotten on days 15-24 (third or fourth row). It has two choices:
  • 1.You can take the forgotten tablet as soon as you remember, even if that means that you have to take two tablets at the same time. Take the next tablets as planned. Instead of taking the placebo tablets from the blister, throw them away and start taking the new strip (the starting day will be different). Most likely your period will occur at the end of the second strip, while taking the white placebo tablets. but during the second blister spotting or breakthrough bleeding may occur.
  • you can also stop taking the light pink active tablets from the current cycle and switch directly to the 4 white placebo tablets (before taking the placebo tablets, record the day you forgot the tablet). If you want to start the next strip on your day usually, take the placebo tablets for less than 4 days.

If you follow either of these two recommendations, you will stay protected against pregnancy.

• If you have forgotten any of the tablets in the strip and do not menstruate during the placebo days, you may be pregnant. Talk to your doctor before starting a new strip.

What to do in case of vomiting or severe diarrhea

If you vomit within 3-4 hours of taking a light pink active tablet or have severe diarrhea, the active substances in the pill may not be fully absorbed by your body. The situation is comparable to when you forget to take. one tablet. After vomiting or diarrhea you should take a new light pink active tablet from a reserve pack as soon as possible. If possible, take it within 24 hours of your usual pill-taking time. If this is not possible, or if 24 hours have already passed, you should follow the instructions in the section "If you forget to take YAZ".

Delayed menstruation: what you need to know

Although it is not recommended, it is possible to delay your period by not taking the white placebo tablets from the fourth row and continuing with a new strip of YAZ. You may experience low or menstrual bleeding while using this second strip. Finish this second strip, including the 4 white tablets from the fourth row. Start the next strip.

You can ask your doctor for advice before deciding to delay your menstrual period.

Changing the start day of your period: what you need to know

If you take the tablets according to the instructions, your period will start during the placebo days. If you have to change the starting day, you can decrease (never increase - 4 days is the maximum!) The placebo days when you take the white placebo tablets. For example, if the placebo tablet period starts on a Friday and you want to move it to Tuesday (3 days earlier), you must start the next strip 3 days early.You may not have a period during this period.You may have low or menstrual bleeding afterwards.

Ask your doctor for advice if you are not sure what to do.

If you stop taking YAZ

You can stop taking YAZ at any time.If you still want to avoid becoming pregnant, ask your doctor for advice on other safe birth control methods. If you want to have a baby, stop taking YAZ and wait for your period before trying to get pregnant. This will allow you to calculate the estimated due date more precisely. If you have any questions about the use of this medicine, ask your doctor. doctor or pharmacist.

Side Effects What are the side effects of Yaz

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you get any side effects, especially if they are severe or persistent, or if there is any change in your health that you think might be due to YAZ, please tell your doctor.

An increased risk of developing blood clots in the veins (venous thromboembolism (VTE)) or blood clots in the arteries (arterial thromboembolism (ATE)) is present in all women taking combined hormonal contraceptives. For more detailed information on the different risks from "taking combined hormonal contraceptives, see section 2" What you need to know before you use YAZ ".

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

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

mood swings headache nausea

breast pain, problems with menstruation, such as irregular menstruation, absence of menstruation

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

depression, nervousness, drowsiness

dizziness, pins and needles

migraine, varicose veins, increased blood pressure

stomach pain, vomiting, indigestion, wind, stomach inflammation, diarrhea

acne, itching, rashes

aches, such as back pain, pain in the limbs, muscle cramps

vaginal fungal infection, pelvic pain, breast enlargement, benign breast lumps, uterine / vaginal bleeding (usually

decrease with continued treatment), genital discharge, hot flashes, inflammation of the vagina (vaginitis), problems with

menstruation, painful menstruation, low menstruation, very heavy menstruation, vaginal dryness, abnormal PAP test, decreased

interest in sex

lack of energy, increased sweating, water retention, weight gain

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

candidiasis (fungal infection)

anemia, increased number of blood platelets, allergic reaction

hormonal (endocrine) disorders

increased appetite, loss of appetite, excessively high blood potassium concentration, excessively low blood sodium concentration

inability to reach orgasm, insomnia

dizziness, tremor

eye disorders, such as inflammation of the eyelid, dry eye, excessively fast heartbeat

inflammation of a vein, nosebleed, fainting

enlarged abdomen, intestinal disturbances, bloating, hiatal hernia, fungal infection of the mouth, constipation, dry mouth

pain in the bile ducts or gallbladder, inflammation of the gallbladder

yellowish-brown spots on the skin, eczema, hair loss, acne-like skin inflammation, dry skin, inflammation

grainy skin, excessive hair growth, disorders

skin, stretch marks, skin inflammation, skin inflammation due to sensitivity to light, skin nodules

Difficult or painful sexual intercourse, inflammation of the vagina (vulvovaginitis), bleeding after intercourse, withdrawal bleeding,

breast cyst, increased number of breast cells (hyperplasia), malignant breast lumps, abnormal growth of the lining of the uterus, reduction or narrowing of the lining of the uterus, ovarian cysts, enlargement of the uterus

feeling of general malaise

weight loss

harmful blood clots in a vein or artery, for example: o in a leg or foot (DVT) or lung (PE) or heart attack or stroke or mini-stroke or temporary symptoms similar to those of " stroke, known as a transient ischemic attack (TIA) or blood clots in the liver, stomach / intestines, kidneys or eye.

The chance of developing a blood clot may be higher if you have any other conditions that increase this risk (see section 2 for more information on conditions that increase the risk of blood clots and the symptoms of a blood clot).

The following side effects have also been reported, but their frequency cannot be estimated from the available data: hypersensitivity, erythema multiforme (rash with red and inflamed target-shaped lesions).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. 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.

Expiry and Retention

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 which is stated on the package after "Do not use after:" or "EXP:". The expiry date refers to the last day of the month.

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Composition and pharmaceutical form

What YAZ contains

The active substances are ethinyl estradiol (as betadxtrin clathrate) and drospirenone. Each light pink film-coated active tablet contains 0.020 milligrams of ethinyl estradiol (as betadxtrin clathrate) and 3 milligrams of drospirenone.

The white film-coated tablets contain no ingredients

The excipients are:

• in the active light pink film-coated tablets:
• In the tablet core: lactose monohydrate, corn starch, magnesium stearate (E470b).
• In the film-coating of the tablet: hypromellose (E464), talc (E553b), titanium dioxide (E171) and red iron oxide (E172).
• in the non-active white film-coated tablets:
• In the tablet core: lactose monohydrate, corn starch, povidone K25, magnesium stearate (E470b).
• In the film-coating of the tablet: hypromellose (E464), talc (E553b), titanium dioxide (E171). active.

Description of the appearance of YAZ and contents of the package

• Each pack of YAZ contains 24 active, light pink film-coated tablets in the 1st, 2nd, 3rd and 4th row of the blister and 4 white placebo film-coated tablets in the 4th row.
• YAZ tablets, both light pink and white, are film-coated tablets; the tablet core is covered with a coating.
• The active tablet is light pink, round, with convex faces, on one of which the letters "DS" are imprinted in a regular hexagon.
• The placebo tablet is white, round, with convex faces, on one of which the letters "DP" are imprinted in a regular hexagon.
• YAZ is available in packs of 1, 3, 6, 13 blisters each with 28 tablets.

Not all pack sizes may be marketed.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
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More information about Yaz can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other Forms of interaction04.6 Pregnancy and lactation Pregnancy04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE DE THE FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIATION DRUGS, FURTHER DETAILED INSTRUCTIONS ON QUALITY PREPARATION

01.0 NAME OF THE MEDICINAL PRODUCT

YAZ 0.02 MG / 3 MG, FILM COATED TABLETS

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

24 light pink film-coated tablets:

Each film-coated tablet contains 0.020 mg of ethinylestradiol (as betdextrin clathrate) and 3 mg of drospirenone.

Excipient with known effect: lactose 46 mg.

4 placebo (inactive) white film-coated tablets:

The tablet does not contain active ingredients.

Excipient with known effect: 22 mg lactose.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Film-coated tablets

The active tablets are light pink, round, with convex faces, on one of which the letters "DS" are imprinted in a regular hexagon.

The placebo tablets are white, round, with convex faces, on one of which the letters "DP" are imprinted in a regular hexagon.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Oral contraception.

The decision to prescribe YAZ must take into account the individual woman's current risk factors, particularly those related to venous thromboembolism (VTE) and the comparison between the risk of VTE associated with YAZ and that associated with other combined hormonal contraceptives (COCs). (see sections 4.3 and 4.4).

04.2 Posology and method of administration

Method of administration: oral use.

Dosage

How to take YAZ

The tablets should be taken at about the same time each day, with a small amount of liquid if needed, and in the order indicated on the blister pack. Tablet-taking is continuous. The dosage is one tablet per day for 28 consecutive days. Each subsequent pack should be started the day after the last tablet of the previous pack. Generally, 2-3 days after starting the placebo tablets (last row) a withdrawal bleed occurs, which may not have finished yet before "start of the next pack.

How to start treatment with YAZ

• No previous use of hormonal contraceptives (in the previous month)

The first tablet should be taken on the first day of your natural menstrual cycle (i.e. the first day of your period).

• Changing from a combined hormonal contraceptive (combined oral contraceptive, vaginal ring or transdermal patch)

YAZ should preferably be started on the day after the last active tablet (the last tablet containing the active ingredients) of the previous COC, or at the latest on the day after the usual tablet-free break or after the last one. placebo tablet of the previous combined oral contraceptive. If a vaginal ring or transdermal patch has been used, YAZ should preferably be started on the day of removal, or at the latest when the next application is to be made.

• Changing from a progestogen-only contraceptive (progestogen-only pill, injection, implant) or from a progestogen-releasing intrauterine system (IUS)

The woman can switch to YAZ at any time if she is using the progestogen-only pill (in the case of an implant or IUS, on the day of its removal; in the case of an injectable, the day it is to be given. " injection); however, in all these cases, the woman should be advised to use an additional barrier method of contraception for the first 7 days of dosing.

• After an abortion in the first trimester of pregnancy

You can start immediately without the need for additional contraceptive measures.

• After a birth or abortion in the second trimester of pregnancy

Tablet-taking should begin between the 21st and 28th day after delivery or abortion in the second trimester of pregnancy. In case of later initiation, the woman should be advised to use an additional barrier contraceptive method for the first few months. 7 days However, if intercourse has occurred in the meantime, pregnancy must be ruled out, or the next menstruation must be waited before starting COC use.

For breastfeeding women see section 4.6.

Behavior in case of failure to take tablets

Placebo tablets from the last (fourth) row of the blister can be skipped. However, they must be discarded to avoid inadvertently prolonging the placebo phase.

The following tips refer only to forgetting active tablets:

If she is less than 24 hours late in taking a tablet, contraceptive protection is maintained. The woman should take the tablet as soon as she remembers and then take the following tablets at the usual time.

If you are more than 24 hours late in taking a tablet, contraceptive protection may be reduced. If you miss a tablet, the following rules apply:

1. The recommended tablet-free interval is 4 days, tablet-taking should never be discontinued for more than 7 days.

2. It takes 7 days of uninterrupted tablet-taking to achieve "adequate suppression of the hypothalamus-pituitary-ovarian axis."

As a result, the following advice can be given in daily practice:

• Days 1-7

The forgotten tablet should be taken as soon as the woman remembers, even if this involves taking two tablets at the same time. Then she should continue to take the tablets regularly as planned. In addition, contraception is required for the next 7 days. such as a condom. If intercourse occurred in the previous 7 days, the possibility of pregnancy should be considered. The greater the number of forgotten tablets, the closer to tablet days. placebo, the higher the risk of pregnancy.

• Days 8-14

The forgotten tablet should be taken as soon as the woman remembers it even if this means taking two tablets at the same time. Then she should continue to take the tablets regularly as planned. If the tablets have been taken correctly within the previous 7 days , no additional contraceptive methods are necessary. However, if more than one tablet has been missed, the use of additional precautions should be recommended for 7 days.

• Days 15-24

Given the imminence of the placebo phase, the risk of reduced contraceptive reliability is greater. However, by changing the tablet-taking schedule, the reduction in contraceptive protection can still be prevented. By adopting either of the following two options, it is therefore not necessary to take any measures Supplementary contraceptives, provided that all tablets have been taken correctly in the 7 days preceding the first missed tablet, if not, the first of the two options must be followed and additional contraceptive measures must also be taken within the following 7 days.

1. The forgotten tablet should be taken as soon as the woman remembers, even if this involves taking two tablets at the same time. Then, she should continue to take the tablets regularly as planned until the active tablets are finished. 4 placebo tablets from the last row must be discarded. You have to go directly to the next pack. Withdrawal bleeding is unlikely to occur until the active tablets in the second pack are finished, however, spotting or breakthrough bleeding may occur while taking the tablets.

2. You may also be advised to stop taking the active tablets from the current pack. In this case, you should take placebo tablets from the last row to cover a period of 4 days, including the days on which they were forgotten. the tablets, and then resume with a new pack.

If the woman has forgotten to take the tablets and does not experience withdrawal bleeding in the subsequent placebo tablet phase, the possibility of an ongoing pregnancy should be considered.

Recommendations in case of gastrointestinal disorders

In case of severe gastrointestinal disturbances (eg vomiting or diarrhea), absorption may be impaired and additional contraceptive measures must be taken. If vomiting occurs within 3-4 hours of taking an active tablet, it is necessary take a new (replacement) tablet as soon as possible.If possible, the new tablet should be taken within 24 hours of the usual tablet-taking time. If more than 24 hours elapse, the same instructions regarding forgetting tablets apply, as explained in section 4.2 "Behavior in case of missing tablets".

If the woman does not want to change her usual dosing schedule, she will have to take the required tablet (s) from another pack.

How to move a "withdrawal bleed."

To delay a menstruation one should continue with another pack of YAZ without taking the placebo tablets from the current pack. The intake can be continued for as long as desired until the end of the active tablets in the second pack. During this prolonged intake, breakthrough bleeding or spotting may occur. Taking YAZ should be resumed regularly after the days of the placebo tablets.

To shift menstruation to another day of the week than it occurs with the current schedule, it may be advisable to shorten the first placebo phase by the desired days. The shorter this phase, the greater the chance that there will be no withdrawal bleeding and breakthrough bleeding or spotting during the next pack (such as when you want to delay your period).

04.3 Contraindications

Combined hormonal contraceptives (COCs) should not be used in the following conditions. Should any of these conditions occur for the first time during COC use, the medicinal product should be discontinued immediately.

• Presence or risk of venous thromboembolism (VTE)

• Venous thromboembolism - current (with anticoagulant intake) or previous VTE (eg deep vein thrombosis [DVT] or pulmonary embolism [PE])

• Known hereditary or acquired predisposition to venous thromboembolism, such as resistance to activated protein C (including factor V Leiden), antithrombin III deficiency, protein C deficiency, protein S deficiency

• Major surgery with prolonged immobilization (see section 4.4)

• High risk of venous thromboembolism due to the presence of multiple risk factors (see section 4.4)

• Presence or risk of arterial thromboembolism (ATE)

• Arterial thromboembolism - current or previous arterial thromboembolism (eg myocardial infarction) or prodromal conditions (eg angina pectoris)

• Cerebrovascular disease - current or previous stroke or prodromal conditions (eg transient ischemic attack (TIA))

• Known hereditary or acquired predisposition to arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant)

• History of migraine with focal neurological symptoms

• A high risk of arterial thromboembolism due to the presence of multiple risk factors (see section 4.4) or the presence of a serious risk factor such as:

• diabetes mellitus with vascular symptoms

• severe hypertension

• severe dyslipoproteinemia

• current or previous severe liver disease, until liver function values ​​return to normal

• severe or acute renal failure

• existing or previous liver tumors (benign or malignant)

• Known or suspected sex hormone-dependent malignant diseases (e.g. of the genital organs or breast)

• undiagnosed vaginal bleeding

• hypersensitivity to the active substances or to any of the excipients listed in section 6.1

04.4 Special warnings and appropriate precautions for use

Warnings

In case any of the conditions or risk factors mentioned below is present, the suitability of YAZ should be discussed with the woman.

In the event of worsening or first appearance of any of these risk factors or conditions, the woman should contact her physician to determine whether the use of YAZ should be discontinued.

In the event of a suspected or confirmed VTE or ATE, the use of COCs should be discontinued. If anticoagulant therapy is initiated, an alternative method of contraception should be used due to the risk of teratogenicity associated with anticoagulant therapy (coumarins).

• Circulatory Disorders

Risk of venous thromboembolism (VTE)

The use of any combined hormonal contraceptive (COC) results in an increased risk of venous thromboembolism (VTE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with a lower risk of VTE. The risk associated with others. products such as YAZ can also be doubled. The decision to use a product other than those associated with a lower risk of VTE should only be made after discussions with the woman to ensure that she understands the risk of VTE associated with YAZ, the way where your current risk factors influence that risk and the fact that the risk of developing a VTE is highest in the first year of use. There is also some evidence that the risk increases when taking a COC is resumed after a break of 4 or more weeks.

About 2 in 10,000 women who do not use a CHC and who are not pregnant will develop a VTE over a period of one year. In a single woman, however, the risk can be much higher, depending on her underlying risk factors (see below).

It is estimated [1] that out of 10,000 women who use a CHC containing drospirenone, between 9 and 12 will develop a VTE in one year; this compares with approximately 6 [2] women using a COC containing levonorgestrel.

[1] These incidences were estimated from the totality of epidemiological study data, using the relative risks of the different products compared to COCs containing levonorgestrel

[2] Median value of the range 5-7 per 10,000 women-years, based on a relative risk of approximately 2.3-3.6 of levonorgestrel-containing COCs compared with non-use.

In both cases, the number of VTEs per year is less than the number expected in pregnancy or in the postpartum period.

VTE can be fatal in 1-2% of cases.

Very rarely, thrombosis has been reported in CHC users in other blood vessels, e.g. hepatic, mesenteric, renal or retinal veins and arteries.

Risk factors for VTE

The risk of venous thromboembolic complications in CHC users may increase substantially if additional risk factors are present, especially if there are more than one risk factors (see table).

YAZ is contraindicated if a woman has several risk factors that increase her risk of venous thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the increased risk is greater than the sum of the individual factors; in this case her total risk of VTE should be considered. If the benefit-risk ratio is considered to be negative, a COC should not be prescribed (see section 4.3).

Table: Risk factors for VTE

Risk factor Comment Obesity (body mass index (BMI) above 30 kg / m2) The risk increases considerably as the BMI increases. Particularly important to consider if other risk factors are also present. Prolonged immobilization, major surgery, any type of leg and pelvis surgery, neurosurgery or major trauma. Note: Temporary restraint, including air travel lasting> 4 hours, can also be a risk factor for VTE, especially in women with other risk factors In these situations it is advisable to stop using the patch / pill / ring (in case of elective surgery at least four weeks earlier) and not restart it until two weeks after complete resumption of mobility. To avoid unwanted pregnancy, another method of contraception must be used. If YAZ has not been discontinued earlier, antithrombotic treatment should be considered. Positive family history (venous thromboembolism in a sibling or parent, especially at a relatively young age, i.e. before age 50). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding to take any COCs. Other medical conditions associated with VTE Cancer, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia. Old age Particularly above the age of 35

There is no agreement on the possible role of varicose veins and superficial thrombophlebitis in the onset and progression of venous thrombosis.

The increased risk of thromboembolism in pregnancy, particularly the 6-week period of the puerperium, must be considered (for information on "Pregnancy and lactation" see section 4.6).

Symptoms of VTE (deep vein thrombosis and pulmonary embolism)

If symptoms of this type occur, women should seek immediate medical attention and inform them that they are taking a CHC.

Symptoms of deep vein thrombosis (DVT) can include:

• unilateral swelling of the leg and / or foot or along a vein in the leg;

• pain or tenderness in the leg which may only be felt when standing or walking;

• increased sensation of heat in the affected leg; skin on the leg that is red or discolored.

Symptoms of pulmonary embolism (PE) can include:

• sudden and unexplained onset of shortness of breath and rapid breathing;

• sudden cough which may be associated with hemoptysis;

• sharp chest pain;

• severe light headedness or dizziness;

• rapid or irregular heartbeat.

Some of these symptoms (such as "shortness of breath" and "cough") are non-specific and may be misinterpreted as more common or less serious events (eg respiratory tract infections).

Other signs of vascular occlusion may include: sudden pain, swelling or a pale blue discoloration of one "extremity.

If the occlusion takes place in the eye, symptoms can range from painless blurring of vision to loss of vision. Sometimes vision loss occurs almost immediately.

Risk of arterial thromboembolism (ATE)

Epidemiological studies have associated the use of CHCs with an increased risk of arterial thromboembolism (myocardial infarction) or cerebrovascular accidents (eg transient ischemic attack, stroke). Arterial thromboembolic events can be fatal.

Risk factors of ATE

The risk of arterial thromboembolic complications or a cerebrovascular accident in CHC users increases in the presence of risk factors (see table). YAZ is contraindicated if a woman has one serious risk factor or multiple risk factors for ATE that increase her risk of arterial thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors; in this case her total risk should be considered. If the benefit-risk balance is believed to be negative, a CHC should not be prescribed (see section 4.3).

Table: Risk factors of ATE

Risk factor Comment Old age Particularly above the age of 35 Smoke Women should be advised not to smoke if they wish to use a CHC. Women over the age of 35 who continue to smoke should be strongly advised to use a different method of contraception. Hypertension Obesity (body mass index (BMI) above 30 kg / m2) The risk increases considerably as the BMI increases. Especially important in women with other risk factors. Positive family history (arterial thromboembolism in a sibling or parent, especially at a relatively young age, i.e. before age 50). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding to take any COCs. Migraine An increase in migraine frequency or severity during CHC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation. Other medical conditions associated with adverse vascular events Diabetes mellitus, hyperhomocysteinemia, atrial valvulopathy and fibrillation, dyslipoproteinemia and systemic lupus erythematosus.

Symptoms of ATE

If symptoms of this type occur, women must contact a healthcare professional immediately and inform them that they are taking a CHC.

Symptoms of a cerebrovascular accident can include:

• sudden numbness or weakness of the face, arm or leg, especially on one side of the body;

• sudden difficulty walking, dizziness, loss of balance or coordination;

• sudden confusion, difficulty speaking or understanding;

• sudden difficulty seeing in one or both eyes;

• sudden, severe or prolonged migraine with no known cause;

• loss of consciousness or fainting with or without convulsions.

Temporary symptoms suggest it is a transient ischemic attack (TIA).

Symptoms of myocardial infarction (MI) can include:

• pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm or below the breastbone;

• discomfort radiating to the back, jaw, throat, arms, stomach;

• feeling of fullness, indigestion or choking;

• sweating, nausea, vomiting or dizziness;

• extreme weakness, anxiety or shortness of breath;

• rapid or irregular heartbeats.

• Tumors

An increased risk of cervical cancer in COC users for long periods (> 5 years) has been reported in some epidemiological studies, but it is still controversial to what extent this finding is attributable to confounding effects of sexual and other behavior. factors such as human papilloma virus (HPV).

A meta-analysis of 54 epidemiological studies found that women currently using COCs have a slightly higher relative risk (RR = 1.24) of having breast cancer diagnosed. The excess risk gradually disappears over the 10 years following discontinuation of COCs. Because breast cancer is rare in women under the age of 40, the extra number of breast cancers diagnosed in women using or who have recently used COCs is small in relation to the overall risk of breast cancer. . Such studies provide no evidence of a causal relationship. The observed increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs, or a combination of both. Breast cancer diagnosed in COC users combined tends to be less clinically advanced than that diagnosed in women who have never used them.

Benign liver tumors and, even more rarely, malignant liver tumors have been reported rarely in women taking COCs. In isolated cases, these tumors have resulted in life-threatening intra-abdominal haemorrhage. If a woman taking a combined oral contraceptive develops severe pain in the upper abdomen, enlarged liver, or signs suggestive of intra-abdominal haemorrhage, the possibility of liver cancer should be considered in the diagnosis.

With the use of the higher-dosed COCs (50 mcg ethinylestradiol), the risk of endometrial and ovarian cancer is reduced. Whether this also applies to lower-dose COCs remains to be confirmed.

• Other conditions

The progestogen component of YAZ is an aldosterone antagonist with potassium sparing properties. In most cases, no increases in potassium levels are to be expected. In a clinical study, however, in some patients with mild renal impairment. taking concomitant potassium-sparing medicinal products, serum potassium levels increased slightly, but not significantly, during administration of drospirenone. Therefore, it is recommended that serum potassium be monitored during the first course of treatment in patients presenting renal insufficiency and have a pre-treatment serum potassium value in the upper part of the reference range, particularly if they are taking potassium-sparing medicines at the same time. See also section 4.5.

Women with hypertriglyceridaemia, or a family history of the condition, may have an increased risk of pancreatitis when using COCs.

Although a small increase in blood pressure has been reported in many women taking COCs, a clinically relevant increase is rare. Only in these rare cases is an immediate discontinuation of COCs justified. If, during the use of a COC in a patient with pre-existing hypertension, blood pressure values ​​are consistently high or a significant increase in blood pressure is not responds adequately to antihypertensive therapy, the COC should be discontinued. If deemed appropriate, COC use can be resumed if blood pressure has normalized following antihypertensive therapy.

Both during pregnancy and while taking COCs, the onset or worsening of the conditions listed below has been reported, however there is no conclusive evidence of a correlation between these conditions and the use of COCs: jaundice and / or itching due to cholestasis, gallstone formation, porphyria, systemic lupus erythematosus, haemolytic uremic syndrome, Sydenham's chorea, herpes gravidarum, hearing loss from otosclerosis.

In women with hereditary angioedema, exogenous estrogens can induce or aggravate the symptoms of angioedema.

Acute or chronic disturbances of liver function may require discontinuation of COC treatment until liver function indices have returned to normal. Return of cholestatic jaundice and / or cholestatic pruritus already occurring in pregnancy or during a previous Sex steroid treatment requires discontinuation of the combined oral contraceptive.

Although COCs may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for the need to change the treatment regimen in diabetic patients using low-dose combined oral contraceptives (containing

Worsening of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis has been reported during COC use.

Occasionally chloasma may occur especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet rays while using COCs.

Each light pink tablet of YAZ contains 46 mg of lactose and each white tablet contains 22 mg of lactose. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should take this rate into account.

Medical examination / visits

Before initiating or resuming use of YAZ, a complete medical history (including family history) should be taken and pregnancy should be ruled out. Blood pressure should be measured and a clinical examination, guided by contraindications, should be performed (see section 4.3) and warnings (see section 4.4). It is important to draw a woman's attention to information relating to venous or arterial thrombosis, including the risk associated with YAZ compared to other CHCs, symptoms of VTE and ATE, known risk and what to do in case of suspected thrombosis.

The woman should also be advised of the need to read the package leaflet carefully and follow its advice. The frequency and type of checkups should be based on established guidelines and should be adapted to the individual woman.

Women should be advised that hormonal contraceptives do not protect against HIV infection (AIDS) or other sexually transmitted diseases.

Reduced effectiveness

The efficacy of COCs may decrease in case of missed active tablet intake (see section 4.2), gastro-intestinal disturbances during the period of active tablet-taking (see section 4.2) or concomitant administration of other medicinal products (see section 4.5).

Reduced cycle control

Irregular vaginal bleeding (spotting or breakthrough bleeding) may occur with all COCs, especially in the first months of use. Therefore, evaluation of any irregular bleeding is meaningful only after a settling period of approximately three treatment cycles.

If irregular bleeding persists or occurs after previously regular cycles, a non-hormonal etiology should be considered and adequate diagnostic measures should be implemented to rule out malignancy or pregnancy. Such measures may include scraping.

In some women, withdrawal bleeding may not occur during the placebo days. If the COC has been taken according to the directions given in section 4.2, it is unlikely that the woman is pregnant. However, if the COC has not been taken according to directions prior to the first missed withdrawal bleed, or if two withdrawal bleeds have not occurred, pregnancy must be ruled out before COC use is continued.

04.5 Interactions with other medicinal products and other forms of interaction

Note: The information in the Summary of Product Characteristics of concomitant medicinal products should be consulted to identify possible interactions.

• Effects of other medicines on YAZ

Interactions may occur with drugs that induce microsomal enzymes resulting in increased clearance of sex hormones and which can cause breakthrough bleeding and / or contraceptive failure.

Management

Enzyme induction can already be observed after a few days of treatment. Maximal enzyme induction is generally observed within a few weeks. After discontinuation of therapy, enzyme induction may persist for approximately 4 weeks.

Short-term treatment

Women undergoing enzyme inducer treatments should temporarily use a barrier method or another method of contraception in addition to the combined oral contraceptive. The barrier method should be used for the entire period of concomitant drug intake and for 28 days following discontinuation of therapy. If therapy continues after the end of the active tablets of the COC pack, the placebo tablets should be discarded and the next COC pack started.

Long-term treatment

For women undergoing long-term treatment with hepatic enzyme inducers, another reliable, non-hormonal method of contraception is recommended.

The following interactions have been reported in the literature.

Substances increasing the clearance of COCs (decreased efficacy of COCs by enzyme inducers)

Barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, the HIV drug ritonavir, nevirapine and efavirenz and possibly also felbamate, griseofulvin, oxycarbazepine, topiramate and products containing "St. John's wort" (Hypericum perforatum).

Substances with variable effect on the clearance of COCs

When co-administered with COCs, combinations of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, including combinations with HCV inhibitors, may increase or decrease plasma concentrations of estrogen or progestogen. The net effect of these changes in some cases may be clinically relevant.

Consequently, prescribing information regarding HIV / HCV concomitant medications should be consulted to identify potential interactions and any related recommendations. If in doubt, the woman undergoing therapy with protease inhibitors or non-nucleoside reverse transcriptase inhibitors should use a barrier method of contraception.

The major metabolites of drospirenone in human plasma are produced without the involvement of the cytochrome P450 system. Inhibitors of this enzyme system are therefore unlikely to affect the metabolism of drospirenone.

• Effects of YAZ on other medicines

Oral contraceptives can affect the metabolism of some active ingredients. Consequently, plasma and tissue concentrations of these may increase (e.g. cyclosporine) or decrease (e.g. lamotrigine).

Based on inhibition studies in vitro and interaction studies in vivo performed in female volunteers using omeprazole, simvastatin and midazolam as marker substrates, an interaction of drospirenone at a dose of 3 mg with the metabolism of other active substances is unlikely.

• Other forms of interaction

In patients without renal insufficiency, concomitant use of drospirenone and ACE inhibitors or NSAIDs has not been shown to exert a significant effect on serum potassium. However, concomitant use of YAZ with aldosterone antagonists or potassium-sparing diuretics It has not been studied. In this case, serum potassium should be monitored during the first treatment cycle. See also section 4.4.

• Laboratory tests

The use of contraceptive steroids can affect the results of some laboratory tests, including biochemical parameters relating to liver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins, such as, for example, blood-binding globulin corticosteroids and lipid / lipoprotein fractions, the parameters of glucose metabolism and the parameters of coagulation and fibrinolysis. Generally, the changes remain within normal limits. Drospirenone causes an increase in plasma renin activity and plasma aldosterone, a due to its weak antimineralocorticoid activity.

04.6 Pregnancy and breastfeeding

Pregnancy

YAZ is not indicated during pregnancy.

In the event of pregnancy occurring while using YAZ, the medicinal product must be discontinued immediately. Large epidemiological studies have shown neither increased risk of congenital malformations in children born to women who have used COCs before. of pregnancy, nor teratogenic effects in case of accidental intake of COCs during pregnancy.

Animal studies have shown undesirable effects during pregnancy and lactation (see section 5.3). Based on these animal data, undesirable effects due to the hormonal action of the active substances cannot be excluded. However, general clinical experience with COCs during pregnancy did not provide any evidence of a real adverse effect in man.

The available data on the use of YAZ in pregnancy are too limited to draw any conclusions about the adverse effects of YAZ on pregnancy or on the health of the fetus or newborn. To date, no relevant epidemiological data are available.

The increased risk of thromboembolism in the postpartum period should be considered when YAZ is restarted (see sections 4.2. And 4.4).

Pregnancy

Breastfeeding can be affected by COCs, as they can decrease the quantity and change the composition of breast milk. Therefore, the use of COCs should not normally be recommended until weaning is done. been completed. Small amounts of contraceptive steroids and / or their metabolites may be excreted in breast milk during COC use. Such amounts may affect the baby.

Fertility

YAZ is indicated for the prevention of pregnancy. For information on restoring fertility, see section 5.1

04.7 Effects on ability to drive and use machines

No studies on the ability to drive and use machines have been performed. No effect on the ability to drive or use machines has been observed in COC users.

04.8 Undesirable effects

For serious undesirable effects in COC users see also section 4.4.

The following adverse reactions have been reported during the use of YAZ.

The table below shows adverse reactions by system organ according to MedDRA (MedDRA SOC). Frequencies are derived from clinical trial data. The more appropriate MedDRA term was used to describe a specific reaction, its synonyms and related conditions.

Undesirable effects that have been associated with the use of YAZ as an oral contraceptive or in the treatment of moderate acne vulgaris according to the MedDRA system organ class and MedDRA terms.

System Organ Class (MedDRA Version 9.1) Common (≥1 / 100, Uncommon (≥1 / 1,000 to Rare (≥1 / 10,000, Not known (frequency cannot be estimated from the available data) Infections and infestations candidiasis Disorders of the blood and lymphatic system anemia, thrombocythemia Disorders of the immune system allergic reaction hypersensitivity Endocrine pathologies Endocrine Disorders Metabolism and nutrition disorders increased appetite, anorexia, hyperkalaemia, hyponatremia Psychiatric disorders emotional lability depression, nervousness, drowsiness anorgasmia, insomnia Nervous system disorders headache dizziness, paraesthesia dizziness, tremor Eye disorders conjunctivitis, dry eye, eye disorders Cardiac pathologies tachycardia Vascular pathologies migraine, varicose vein, hypertension phlebitis, vascular disorders, epistaxis, syncope, venous thromboembolism (VTE) arterial thromboembolism (ATE) Gastrointestinal disorders nausea abdominal pain, vomiting, dyspepsia, flatulence, gastritis, diarrhea enlarged abdomen, gastrointestinal complaints, gastrointestinal fullness, hiatus hernia, oral candidiasis, constipation, dry mouth Hepatobiliary disorders biliary pain, cholecystitis Skin and subcutaneous tissue disorders acne, itching, rash chloasma, eczema, alopecia, acneiform dermatitis, dry skin, erythema nodosum, hypertrichosis, skin disorders, stretch marks, contact dermatitis, photosensitivity dermatitis, skin nodule Erythema multiforme Musculoskeletal and connective tissue disorders back pain, pain in extremities, muscle cramps Diseases of the reproductive system and breast breast pain, metrorrhagia *, amenorrhea vaginal candidiasis, pelvic pain, breast enlargement, fibrocystic mastopathy, uterine / vaginal bleeding *, genital discharge, hot flashes, vaginitis, menstrual disturbances, dysmenorrhea, hypomenorrhea, menorrhagia, vaginal dryness, suspected PAP test, decreased libido dyspareunia, vulvovaginitis, post-coital bleeding, withdrawal bleeding, breast cyst, breast hyperplasia, breast neoplasia, cervical polyp, endometrial atrophy, ovarian cyst, enlargement of the uterus General disorders and administration site conditions asthenia, increased sweating, edema (generalized, peripheral, facial) malaise Diagnostic tests weight gain weight decrease

* menstrual irregularities generally tend to disappear with continued treatment.

Description of some adverse reactions

An increased risk of arterial and venous thrombotic and thromboembolic events, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism has been observed in CHC users, and this risk is discussed in more detail in section 4.4.

The following serious adverse reactions were observed in women using COCs, discussed in section 4.4"Special warnings and precautions for use":

• venous thromboembolic disorders

• arterial thromboembolic disorders

• hypertension

• liver tumors

• onset or aggravation of conditions for which the association with the use of combined oral contraceptives is not definitively demonstrated: Crohn's disease, ulcerative colitis, epilepsy, uterine myoma, porphyria, systemic lupus erythematosus, herpes gravidarum, Sydenham's chorea, hemolytic-uremic syndrome, cholestatic jaundice

• chloasma

• chronic or acute disturbances of liver function may require the discontinuation of oral contraceptives until liver function indices have returned to normal

• in women with hereditary angioedema, exogenous estrogens can induce or aggravate the symptoms of angioedema

The frequency of breast cancer diagnoses among COC users increased very slightly. Because breast cancer is rare in women under the age of 40, the extra number of cases is small compared to the overall risk of breast cancer. It is not known whether there is a causal link with COCs. For further information see sections 4.3 and 4.4.

Interactions

Interaction between oral contraceptives and other drugs (enzyme inducers) may cause breakthrough bleeding and / or contraception failure (see section 4.5).

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

04.9 Overdose

There is no experience of overdose with YAZ. Based on general experience with COCs, symptoms that may occur with excessive intake of active tablets are: nausea, vomiting and, in young girls, mild vaginal bleeding. There are no antidotes and treatment should be symptomatic. .

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: progestogens and estrogens, fixed combinations.

ATC code: G03AA12.

Pearl Index for method failure: 0.41 (upper limit of the bilateral 95% confidence interval: 0.85).

Overall Pearl Index (method failure + patient error): 0.80 (upper limit of the bilateral 95% confidence interval: 1.30).

The contraceptive effect of YAZ is based on the interaction of various factors, the most important of which are the inhibition of ovulation and the changes occurring in the endometrium.

In a 3-cycle ovulation inhibition study comparing drospirenone 3 mg / ethinylestradiol 0.020 mg over a 24-day and 21-day regimen, the 24-day regimen was associated with greater suppression of follicular development. intentionally errors of intake during the third treatment cycle, a higher percentage of women on the 21-day regimen exhibited ovarian activity including ovulation compared to women on the 24-day regimen. Ovarian activity returned to pre-treatment levels during the post-treatment cycle in 91.8% of women following the 24-day regimen.

YAZ is a combined oral contraceptive containing ethinylestradiol and the progestin drospirenone. At the therapeutic dose, drospirenone also possesses antiandrogenic properties and weak antimineralocorticoid properties. It is devoid of estrogenic, glucocorticoid and antiglucocorticoid activity. This gives drospirenone a similar pharmacological profile to that of natural progesterone.

Data from clinical studies indicate that the mild antimineralocorticoid properties of YAZ translate into a mild antimineralocorticoid activity.

The efficacy and safety of YAZ in women with moderate acne vulgaris were evaluated in two multicentre, double-blind, randomized, placebo-controlled studies.

After six months of treatment, YAZ produced a statistically significant greater reduction than placebo of 15.6% (49.3% vs 33.7%) in inflammatory lesions, 18.5% (40.6% vs 22.1%) in non-inflammatory lesions and 16.5% (44.6% vs 28.1%) in the total number of lesions. In addition, a higher percentage of subjects, 11.8% (18.6% vs 6.8%) had an ISGA score (Investigator's Stated Global Assessment) of "free" or "almost free".

05.2 Pharmacokinetic properties

• Drospirenone

Absorption

After oral administration drospirenone is rapidly and almost completely absorbed. Maximum concentrations of the active ingredient in serum of about 38 ng / ml are reached 1-2 hours after a single intake. Bioavailability is between 76 and 85%. Simultaneous ingestion of food has no influence on the bioavailability of drospirenone.

Distribution

After oral administration, serum drospirenone levels decrease with a terminal half-life of 31 hours. Drospirenone binds to serum albumin, but not to sex hormone-binding globulin (SHBG) or corticoid-binding globulin (CBG). Only 3-5% of the total concentrations of the active substance in serum are present in the form of free steroid. The ethinylestradiol-induced increase in SHBG does not affect the serum protein binding of drospirenone. The mean apparent volume of distribution of drospirenone is 3.7 ± 1.2 L / kg.

Biotransformation

After oral administration drospirenone is completely metabolised. The major metabolites in plasma are the acid form of drospirenone, produced by the opening of the lactone ring, and 4,5-dihydro-drospirenone-3-sulfate, both produced without involvement of the P450 system. Drospirenone is metabolised to a lesser extent by cytochrome P450 3A4 and has been shown to inhibit in vitro this enzyme and the cytochromes P450 1A1, P450 2C9 and P450 2C19.

Elimination

The metabolic clearance of drospirenone in serum is 1.5 ± 0.2 ml / min / kg. Drospirenone is eliminated in unchanged form only in trace amounts. The metabolites of drospirenone are excreted in the faeces and urine in a ratio of approximately 1.2 - 1.4. The half-life of metabolite excretion with urine and faeces is approximately 40 hours.

Steady-state conditions

During a course of treatment, steady-state maximum serum concentrations of drospirenone of approximately 70 ng / ml are reached after approximately 8 days of treatment. An accumulation of drospirenone serum levels by a factor of approximately 3 occurs as a consequence of the relationship between the half-life and the interval between doses.

Special patient populations

Effect of impaired renal function

Steady-state serum drospirenone levels in women with mild renal impairment (creatinine clearance CLcr, 50-80 ml / min) are comparable to those in women with normal renal function. Serum levels of drospirenone are on average 37% higher in women with moderate renal impairment (CLcr, 30-50 mL / min) than in women with normal renal function. Drospirenone treatment is also well tolerated by women with mildly and moderately impaired renal function. Treatment with drospirenone shows no clinically significant effect on serum potassium concentration.

Effect of impaired liver function

In a single dose study in volunteers with moderate hepatic impairment, oral clearance (CL / F) was decreased by approximately 50% compared to that of patients with normal hepatic function. The reduction in drospirenone clearance observed in volunteers with moderate hepatic impairment did not result in marked differences in serum potassium concentrations. Even in the presence of diabetes and concomitant treatment with spironolactone (two factors that can predispose to hyperkalemia), no increase in serum potassium above the upper limit of normal has been observed. It can be concluded that drospirenone is well tolerated in patients with mild or moderate hepatic impairment (Child-Pugh classification B).

Ethnic groups

No relevant differences in the pharmacokinetics of drospirenone or ethinylestradiol were observed between Japanese and Caucasian women.

• Ethinylestradiol

Absorption

After oral administration, ethinylestradiol is rapidly and completely absorbed. Maximum serum concentrations of approximately 33 pg / ml are reached within 1-2 hours after single intake. Absolute bioavailability is approximately 60%, as a consequence of presystemic conjugation and of first pass metabolism. The simultaneous ingestion of food reduced the bioavailability of ethinylestradiol by about 25% in the subjects studied, while no change was observed in the others.

Distribution

Serum levels of ethinylestradiol decrease with a biphasic trend and the terminal phase of elimination is characterized by a "half-life of approximately 24 hours." Ethinylestradiol is largely bound to "serum albumin (approximately 98.5%) but in a non-specific manner, and induces an increase in the serum concentration of SHBG and corticoid binding globulin (CBG) An apparent volume of distribution of approximately 5 l / kg has been calculated.

Biotransformation

Ethinylestradiol is subject to presystemic conjugation both in the mucosa of the small intestine and in the liver. Ethinylestradiol is metabolised mainly by aromatic hydroxylation, but a large variety of hydroxylated and methylated metabolites are formed, which are present both as free metabolites and as conjugates with glucuronides and sulphates. The rate of metabolic clearance of ethinylestradiol is approximately 5 ml / min / kg.

Elimination

Ethinylestradiol is not eliminated to a significant extent in unchanged form. The metabolites of ethinylestradiol are eliminated at a urine / bile ratio of 4: 6. The half-life of metabolite excretion is approximately 1 day.

Steady-state conditions

Steady-state conditions are achieved during the second half of a treatment cycle and serum ethinylestradiol levels show an accumulation of a factor of approximately 2.0 - 2.3.

05.3 Preclinical safety data

In laboratory animals the effects of drospirenone and ethinylestradiol are limited to those associated with their recognized pharmacological activity. In particular, reproductive toxicity studies have shown embryotoxic and foetotoxic effects in animals which are considered species-specific. At exposures above those occurring in users of YAZ, effects on sexual differentiation were observed in rat fetuses, but not in monkeys.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Active film-coated tablet (light pink) Placebo (white) film-coated tablet Core of the tablet Lactose monohydrate Lactose monohydrate Cornstarch Magnesium stearate (E470b) Microcrystalline cellulose Magnesium stearate (E470b) Film coating of the tablet hypromellose (E464) hypromellose (E464) talc (E553b) talc (E553b) titanium dioxide (E171) titanium dioxide (E171) red iron oxide (E172)

06.2 Incompatibility

Not relevant.

06.3 Period of validity

5 years.

06.4 Special precautions for storage

This medicine does not require any special storage conditions.

06.5 Nature of the immediate packaging and contents of the package

Transparent PVC / aluminum blister in a cardboard wallet.

Packs of:

1x28 tablets.

3x28 tablets.

6x28 tablets.

13x28 tablets.

Each blister contains 24 light pink active film-coated tablets and 4 placebo film-coated tablets.

Not all pack sizes may be marketed.

06.6 Instructions for use and handling

Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.

07.0 MARKETING AUTHORIZATION HOLDER

Bayer S.p.A. - Viale Certosa, 130 - 20156 Milan

08.0 MARKETING AUTHORIZATION NUMBER

1x28 film-coated tablets AIC n. 038542015

3x28 film-coated tablets AIC n. 038542027

6x28 film-coated tablets AIC n. 038542039

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

07 October 2008/29 June 2012

10.0 DATE OF REVISION OF THE TEXT

04/2015

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL