Lerna - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Ethinylestradiol, Drospirenone

LERNA 0.02 mg / 3 mg film-coated tablets

Why is Lerna used? What is it for?

• LERNA is a contraceptive pill and is used to prevent pregnancy.
• Each of the 24 pink colored tablets contains a small amount of two different female hormones, namely 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 Lerna should not be used

General notes

Before you start using LERNA 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 you can start taking LERNA, your doctor asks a few questions about your personal health history and that of your close relatives. Your doctor will measure your blood pressure and, depending on your personal situation, may also carry out other tests. In this leaflet, several situations are described where treatment with LERNA should be discontinued, or where the safety of LERNA may be decreased. In such situations, one must not have sexual intercourse or take extra non-hormonal contraceptive precautions, for example, using a condom or other barrier method. You don't use the rhythm or temperature method. These methods can be unreliable as LERNA alters the monthly changes in body temperature and cervical mucus.

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

Do not use LERNA

Do not use Lerna 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.

• 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 are going to lie down for a long time (see section 2" 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 blood clots in the arteries:
  • severe diabetes with blood vessel damage,
  • very high blood pressure, or very high level of fat (cholesterol or triglycerides) in the blood,
  • a disease known as hyperhomocysteinemia;
• if you have (or have ever had) a type of migraine called 'migraine with aura';
• if you suffer (or have suffered in the past) from liver disease and your liver function is not yet normalized;
• if your kidneys are not working well (kidney failure);
• if you have (or have ever had) liver cancer;
• if you have (or have had in the past) or if you are suspected of having breast cancer or cancer of the genital organs;
• if vaginal bleeding of unknown origin occurs;
• if you are allergic to ethinyl estradiol or drospirenone or any of the other ingredients of this medicine. This can be recognized by itching, rash or swelling.

Precautions for use What you need to know before you take Lerna

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"

In some situations, you need to be especially cautious while taking LERNA or any other combined hormonal contraceptive, and regular medical checks may be needed.

Tell your doctor if any of the following conditions appear or worsen while you are using LERNA

Talk to your doctor or pharmacist before taking LERNA:

• If a close relative suffers (or has suffered) from breast cancer;
• if you have cancer;
• if you suffer from a disease affecting the liver (such as a 'bile duct obstruction which can cause jaundice and symptoms such as itching and tingling) or gallbladder (such as gallstones);
• if you have other kidney problems (other than those described in the section "Do not take LERNA") and are taking medicines that increase the levels of potassium in your blood. Your doctor may check your blood potassium levels;
• 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 LERNA;
• if you have "inflammation of the veins under the skin (superficial thrombophlebitis);
• if you have varicose veins;
• if you suffer from epilepsy (see also "Other medicines and Lerna");
• if you have a disease that first appeared during pregnancy or during previous use of sex hormones, such as hearing loss, a blood disorder called porphyria, skin rash with blisters that occurred during pregnancy (herpes gestational), a nerve disease characterized by sudden body movements (Sydenham's chorea);
• if you have high blood pressure during therapy, which is not controlled by treatment with medicines;
• if you have or have had brown patches of pigmentation (chloasma), the so-called "pregnancy spots" especially of the face. If this applies to you, avoid direct exposure to sunlight or ultraviolet light while taking this medicine;
• if you suffer from hereditary angioedema, products containing estrogen can induce or worsen the symptoms. If you experience symptoms of angioedema such as swelling of the face, tongue and / or pharynx and / or difficulty in swallowing or hives together with difficulty in breathing, contact your doctor immediately.

BLOOD CLOTS

Using a combined hormonal contraceptive such as LERNA 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 LERNA 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 that 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

• sudden and unexplained shortness of breath or 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 shortness 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 were not using a combined hormonal contraceptive.

When you stop taking LERNA, your 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 LERNA 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 LERNA, 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 / patch / ring 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 LERNA 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 LERNA 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 LERNA a few weeks before the surgery or in the period in which you are less mobile. If you have to stop taking LERNA, ask your doctor when you can start taking it again;
• as you get older (especially over the age of 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 LERNA needs to be stopped.

If any of the above conditions change while you are using LERNA, 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 LERNA is very low but can increase:

• with increasing age (over 35 years);
• if you smoke. When using a combined hormonal contraceptive such as LERNA 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 LERNA, 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.

LERNA and cancer

Breast cancer occurs slightly more often in women using combination pills, but it is not known whether this is caused by the treatment. For example, it is possible that more tumors are detected in women who use combination pills because they undergo medical checks more often. The occurrence of breast tumors gradually becomes less after stopping combined hormonal contraceptives. It is important to check your breasts regularly and you should contact your doctor if you feel any lumps.

In rare cases, benign liver tumors and, in even rarer cases, malignant liver tumors have been reported in women using pills. Talk to your doctor if you have unusual severe abdominal pain, bloating (which may be due to an enlarged liver) or if you vomit blood, notice blood in your stools or very dark stools as these may be signs of bleeding from your stomach.

Intermenstrual bleeding

During the first few months of taking LERNA, unexpected bleeding (bleeding outside the placebo days) may occur. If bleeding occurs for more than a few months, or if it starts after a few months, your doctor should investigate the cause.

What should be done if menstruation does not occur during the placebo days

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

If your period does not appear twice in a row, you 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 modify the effect of Lerna

Tell your doctor what medicines or herbal products you are using, have recently used or might use. Also tell any other doctor or dentist who prescribes another medicine (or pharmacist) that you use LERNA. They can tell you if you need to take extra contraceptive precautions (condoms for example) and for how long.

Some medicines can affect the blood levels of LERNA and can make it less effective in preventing pregnancy, or can cause unexpected bleeding. These include medicines used to treat:

• epilepsy (for example, primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, felbamate, topiramate)
• tuberculosis (for example, rifampicin)
• HIV and hepatitis C infections (medicines called protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine, efavirenz) or other infections (griseofulvin or ketoconazole)
• arthritis, osteoarthritis (etoricoxib)
• high blood pressure in the arteries of the lungs (bosentan)
• the remedy based on St. John's wort

LERNA 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)
• eophylline (used to treat breathing problems)
• tizanidine (used to treat muscle pain or muscle cramps)

Your doctor may monitor your blood potassium levels if you are taking certain medicines to treat heart problems (such as diuretics).

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.

Warnings It is important to know that:

Pregnancy and breastfeeding

Pregnancy

If you are pregnant, you must not take LERNA. If you become pregnant while taking LERNA you should stop immediately and contact your doctor. If you want to get pregnant, you can stop taking LERNA at any time (see also "If you want to stop taking LERNA").

Feeding time

The use of LERNA is generally not recommended during breastfeeding. If you want to take the pill while you are breastfeeding, you should contact your doctor.

Driving and using machines

There is no information that the use of LERNA affects the ability to drive or use machines.

LERNA contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking LERNA.

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

Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.

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

The two types of different colored tablets of LERNA are arranged in order. One blister contains 28 tablets.

Take one LERNA tablet every day, if needed with a small amount of water. You can take the tablet with or without food, but you should take the tablet at approximately the same time each day.

Do not confuse the tablets: take a pink tablet for the first 24 days and then a white tablet for the last 4 days. You must then start a new strip right away (24 pink and then 4 white tablets). There is therefore no gap between two blisters.

Due to the different composition of the tablets it is necessary to start with the first tablet on the top left and take the tablets every day. For the 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, there are 7 stickers each with 7 days of the week for each blister of LERNA. Choose the label that starts with the day of the week you start taking your tablets. For example, if it starts on Wednesday, you use the sticker that starts with "WED".

Apply the sticker of the week along the top of the blister that reads "Put label here", so that the first day is on top of the tablet marked "1". Now there is a day indicated above each tablet and you can check if you have taken a certain pill. The arrows indicate the order of taking the pills.

During the 4 days that you are taking the white placebo tablets (the placebo days), you must start your period (so-called withdrawal bleeding). This usually starts on day 2 or 3 after the last active pink tablet of LERNA. After taking the last white tablet, you should start the next strip, regardless of when your period ends. This means that each strip should start on the same day of the week, and that withdrawal bleeding should occur on the same days each month.

If you use LERNA in this way, you are protected against pregnancy even during the 4 days you are taking a placebo tablet.

When can I start with the first blister?

If you have never used a hormonal contraceptive in the previous month

You start LERNA on the first day of your usual period (ie, the first day of your period). If you start LERNA on the first day of your period you are immediately protected from pregnancy. It can also start between the 2nd-5th day of the cycle, but then it is necessary to use extra protective measures (for example, a condom) for the first 7 days.

Changing from a combined hormonal contraceptive, or from a vaginal combined contraceptive ring or patch

You should start taking LERNA preferably the day after the last active tablet (the last tablet containing the active ingredients) of the previous pill, but at the latest on the day after the end of the pill-free break (or after the last tablet. inactive 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 IUD)

It can change at any time from the progestogen-only pill (from an implant or an IUD you must change the day of its removal, from an injectable when the next injection should have been made), but in all these cases it is necessary to use additional protective measures (for example, a condom) for the first 7 days of taking the tablets.

After a miscarriage or at the end of pregnancy

Follow your doctor's advice.

After giving birth

You can start LERNA between the 21st and 28th day after delivery. If you start later than day 28, you must use the so-called barrier method of contraception (eg a condom) during the first 7 days of using LERNA. If, after having a baby, you have had sexual intercourse before starting (or restarting) LERNA, you must first make sure that you are not pregnant or wait until your next period.

If you are breastfeeding and want to start (or restart) LERNA after having a baby

Read the "Breastfeeding" paragraph.

Ask your doctor what to do if you are not sure when to start.

If you forget to take LERNA

The last 4 tablets in the 4th row of the blister are placebo tablets. If you forget to take one of these tablets, it will have no effect on the reliability of LERNA. Throw away the forgotten placebo tablet.

If you forget a pink, active tablet (tablets 1-24 of the blister strip) you need to do the following:

• If you are less than 24 hours late in taking a tablet, the protection against pregnancy is not reduced. Take the tablet as soon as you remember and then take the following tablets again at the usual time.
• If you are more than 24 hours late in taking a tablet, the protection against pregnancy may be reduced. The more tablets you have forgotten, the greater the risk of getting pregnant.

The risk of incomplete protection against pregnancy is greater if you forget a pink tablet at the beginning or at the end of the strip. Therefore, the following rules should be followed:

• If you have forgotten more than one tablet from this strip

Contact your doctor.

• One tablet forgotten between 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. Continue to take the tablets at the usual time and use extra precautions for the next 7 days, for example, a condom. If you have had sexual intercourse in the week before you forgot the tablet you should contact your doctor as there is a possibility that you may be pregnant.

• One tablet forgotten between 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. Continue taking the tablets at the usual time. Protection against pregnancy is not reduced, and there is no need to take any additional precautions.

• If you forget a tablet between days 15 - 24 (third and fourth row)

You can choose between two possibilities:

1. Take the forgotten tablet as soon as you remember, even if that means that you have to take two tablets at the same time. Continue taking the tablets at the usual time. Instead of taking the white placebo tablets from this strip, you throw them away, and start the next strip (the starting day will be different).

Most likely, you will have your period at the end of the second strip - while taking the white placebo tablets - but you may experience light or menstruation-like bleeding during the second strip.

2. It is also possible to stop the active pink tablets and go straight to the 4 placebo tablets (including the days you forgot the tablets, before taking the white placebo tablets, record the day you forgot the tablet). If you want to start a new strip on the usual day, take the placebo tablets for less than 4 days.

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

If you have forgotten one of the tablets in a blister, and you do not menstruate during the placebo days, this may mean that you are pregnant. Contact your doctor before starting the next strip.

What to do in case of vomiting or severe diarrhea

If you vomit within 3-4 hours of taking the active pink tablet or have severe diarrhea, there is a risk that the active ingredients contained in the pill have not been completely absorbed by your body. The situation is almost the same as when you forget a tablet. After vomiting or diarrhea, you must take another pink tablet from a reserve strip as soon as possible. If possible, take it within 24 hours of when you usually take the pill. If this is not possible or it has been more than 24 hours, you must follow the advice given in "If you forget to take LERNA".

Delaying your period: what you need to know

Although it is not recommended, it is possible to delay menstruation by not taking the white placebo tablets from the 4th row and going straight to a new LERNA blister and finishing it. You may experience light or menstruation-like bleeding while using this second strip. Finish this second strip by taking the 4 white tablets from the 4th row. Then start the next strip.

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

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

If you take the tablets according to the instructions, your period will begin during the placebo days. If you want to change this day, you can reduce the number of placebo days - when taking the white placebo tablets - (but don't increase them - 4 is the maximum!). For example, if you start taking the placebo tablets on Friday, and want to change it on Tuesday (3 days earlier), you need to start a new strip 3 days earlier than usual. You may not have any bleeding during this time. Light bleeding or menstruation-like bleeding may occur afterwards.

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

If you stop taking LERNA

You can stop taking LERNA at any time. If you do not want to become pregnant, ask your doctor for advice on other reliable methods of birth control. If you want to become pregnant, stop taking LERNA and wait for a period before trying to get pregnant. You will be able to calculate your estimated due date more easily.

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

Overdose What to do if you have taken too much Lerna

There are no reports of serious harmful effects from taking too many LERNA tablets. If you take several tablets at the same time you may have overdose symptoms such as nausea or vomiting. Young girls may have vaginal bleeding.

have taken too many LERNA tablets, or find that some have been taken by a child, ask your doctor or pharmacist for advice.

Side Effects What are the side effects of Lerna

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 LERNA, 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 take LERNA ".

If any of the following occur, you may need urgent medical attention. Stop taking LERNA and contact your doctor or go to the nearest hospital immediately.

Rare (may affect up to 1 in 1000 people)

• Inflammation of the gallbladder
• Hypersensitivity (allergic reactions with symptoms such as swelling of the face, tongue and / or throat and / or difficulty in swallowing, or hives accompanied by difficulty in breathing)
• harmful blood clots in a vein or artery, for example:
  • in a leg or foot (i.e., deep vein thrombosis (DVT))
  • in a lung (i.e., pulmonary embolism (PE))
  • heart attack
  • stroke or mini-stroke or temporary stroke-like symptoms, known as a transient ischemic attack (TIA)
  • 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).

Other possible side effects

Municipalities (may affect up to 1 in 10 people):

• mood swings
• headache
• nausea
• breast pain, problems with menstruation e.g. irregular menstruation, absence of menstruation

Uncommon (may affect up to 1 in 100 people):

• depression, nervousness, drowsiness
• dizziness or "tingling"
• migraine, varicose veins, increased blood pressure (hypertension)
• stomach pain, vomiting, indigestion, intestinal gas, stomach inflammation, diarrhea
• acne, itching, rashes
• aches and pains, for example pain in the back, limbs, muscle cramps
• vaginal fungal infection, pelvic pain, breast enlargement, benign breast lumps, uterine / vaginal bleeding (which usually subsides during continued treatment), genital discharge, flushing, inflammation of the vagina (vaginitis), problems with menstruation , painful periods, low periods, very heavy periods, vaginal dryness, cervical smear abnormalities, loss of libido
• lack of energy, increased sweating, fluid retention (with symptoms such as swelling of the face and limbs)
• weight gain.

Rare (may affect up to 1 in 1000 people):

• candida (a "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, for example inflammation of the eyelid, dry eyes
• excessively rapid heartbeat
• inflammation of a vein, nosebleed, fainting
• enlarged abdomen, bowel disease, bloating sensation, hiatal hernia, fungal infection of the mouth, constipation, dry mouth
• pain in the bile ducts or gallbladder
• eczema, hair loss, acne-like skin inflammation, dry skin, grainy skin inflammation, excessive hair growth, skin 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), abnormal growth of the mucous membrane of the cervix, reduction of the lining of the uterus uterus, ovarian cysts, uterine enlargement
• malaise
• weight loss

Not known (frequency cannot be estimated from the available data)

• erythema multiforme (rash with red target lesions or sores).

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: www.agenziafarmaco.gov.it/it/responsabili. 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.

Do not use this medicine after the expiry date which is stated on the blister / carton after "EXP". The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions. 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.

Other information

What LERNA contains

• The active ingredients are ethinylestradiol and drospirenone.
• Each pink active film-coated tablet contains 0.02 mg ethinylestradiol and 3 mg drospirenone.
• The white film-coated tablets do not contain active ingredients.
• The other ingredients are:
  • Active pink film-coated tablets:
    • Tablet core: lactose monohydrate, pregelatinised starch (maize), povidone K-30 (E1201), croscarmellose sodium, polysorbate 80, magnesium stearate (E572).
    • Film-coating of the tablet: Partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172).
  • White film-coated tablets:
    • Tablet core: anhydrous lactose, povidone K-30 (E1201), magnesium stearate (E572).
    • Film-coating of the tablet: Partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc.

Description of the appearance of LERNA and contents of the pack

• Each blister of LERNA contains 24 active pink film-coated tablets, in rows 1a, 2a, 3a and 4a of the blister, and 4 white placebo film-coated tablets in row 4.
• LERNA tablets, both pink and white, are film-coated tablets; the tablet core is coated.
• LERNA is available in packs of 1, 3, 6 and 13 blisters, each containing 28 (24 +4) 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.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Lerna is available 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 lactation04.7 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 OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, ADDITIONAL DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

LERNA 0.02 MG / 3MG TABLETS COATED WITH FILM

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

24 pink film-coated tablets (active tablets):

Each film-coated tablet contains 0.02 mg of ethinylestradiol and 3 mg of drospirenone.

Excipient with known effect: lactose monohydrate 44 mg.

4 white (inactive) placebo film-coated tablets:

The tablet does not contain active ingredients.

Excipient with known effect: anhydrous lactose 89.5 mg.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Film-coated tablets.

The active tablet is pink, round, film-coated, 5.7 mm in diameter.

The placebo tablet is white, round, film-coated, 5.7 mm in diameter.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Oral contraception.

The decision to prescribe LERNA should 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 LERNA and that associated with other CHCs (see sections 4.3 and 4.4).

04.2 Posology and method of administration

Route of administration: oral use.

How to take LERNA

The tablets should be taken at about the same time each day, with a small amount of liquid if needed, and in the order they come in the blister pack. Tablet-taking is continuous. One tablet must be taken daily for 28 consecutive days. Each subsequent blister should start the day after the last tablet from the previous blister. Withdrawal bleeding usually occurs 2-3 days after taking the placebo tablets (last row) and may not finish before the start of the blister. following.

How to start treatment with LERNA

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

Tablet-taking should start on day 1 of the woman's natural cycle (ie the first day of menstruation).

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

The woman should start taking LERNA preferably on the day after the last active tablet (the last tablet containing the active substances) of her previous COC, but at the latest on the day after the usual pill-free or placebo interval of her. previous combined oral contraceptive. In the case of using a vaginal ring or a trans dermal patch, the woman should start using LERNA preferably on the day of removal, or at the latest when the next application would have been scheduled.

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

The woman can switch from the progestogen-only pill at any time (if she changes from an implant or IUS from the day of its removal, from a product for injectable use by the time the next injection would have been scheduled), but in all these cases she should be advised to use an additional barrier method for the first 7 days of tablet-taking.

After a first trimester abortion.

The woman can start immediately. In doing so, you do not need to take additional contraceptive measures.

After giving birth or after an abortion in the second trimester.

Women should be advised to start between the 21st and 28th day after delivery or a second trimester abortion. In case of later initiation, the woman should be advised to use an additional barrier method for the first 7 days. However, if intercourse has already occurred, pregnancy must be ruled out before starting COC use or wait for the next menstrual cycle.

For breastfeeding women see section 4.6.

Management of forgotten tablets

Taking placebo tablets from the last (4th) row of the blister can be neglected. However, they must be eliminated to avoid inadvertently prolonging the placebo tablet phase. The following advice refers only to forgetting active tablets:

If the user is less than 12 hours late in taking a tablet, contraceptive protection is not reduced. 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 12 hours late in taking a tablet, contraceptive protection can be reduced. The management of missed tablets can be guided by the following two basic rules:

1. Tablet-taking must never be interrupted for more than 4 days

2. 7 days of uninterrupted tablet-taking are required to achieve "adequate suppression of the hypothalamus-pituitary-ovary axis".

Consequently, the following advice can be given in daily practice:

• Day 1-7

The user should take the last missed tablet as soon as she remembers, even if that means taking two tablets at the same time. She then needs to continue taking the tablets at the usual time. In addition, a barrier method such as a condom should be used for the next 7 days. If intercourse took place in the previous 7 days, the possibility of pregnancy should be considered. The greater the number of tablets forgotten and the closer this is to the placebo tablet phase, the higher the risk of pregnancy.

• Day 8-14

The user should take the last missed tablet as soon as she remembers, even if that means taking two tablets at the same time. She then needs to continue taking the tablets at the usual time. If the tablets have been taken correctly in the 7 days preceding the forgotten tablet, there is no need to use any other supplementary contraceptive methods. However, if you have forgotten to take more than 1 tablet, you need to take extra contraceptive measures for 7 days.

• Day 15-24

The risk of reduced safety is greater, due to the approaching days of placebo tablets. However, by adjusting the tablet-taking schedule, the reduction in contraceptive protection may be prevented. By following one of the following two options, it is not necessary to adopt additional contraceptive measures, 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 user should take the last missed tablet as soon as she remembers, even if that means taking two tablets at the same time. Then you should continue taking the tablets at the usual time until the active tablets are used up. The 4 placebo tablets from the last row should be discarded. The next blister should be started immediately. Withdrawal periods are unlikely until the active tablets in the second blister are finished, but the user may experience spotting or bleeding from break during tablet-taking days.

2. The user may also be advised to stop taking active tablets from the current blister. Then she must take the placebo tablets from the last row for a maximum of 4 days, including the days she missed the tablets, and then continue with the next strip.

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

Advice in the case of gastro-intestinal disorders

In case of severe gastro-intestinal disturbances (eg vomiting or diarrhea), absorption may not be complete and additional contraceptive measures must be taken. If vomiting occurs within 3-4 hours after taking the active tablets, you should be taken a new (replacement) tablet as soon as possible. The new tablet should be taken, if possible, within 12 hours of the usual tablet-taking time. If more than 12 hours have elapsed, the instructions on forgetting tablets apply, as detailed in section 4.2 "Management of forgotten tablets". If the woman does not wish to change her normal tablet-taking schedule, she should take the extra tablet (s) from another strip.

How to postpone a withdrawal period

To delay a period, the user must continue with another blister pack of LERNA, without taking the placebo tablets from her current blister. The delay can be extended according to the wishes of the user until the end of the second blister of active tablets. During the prolonged intake the user may experience breakthrough bleeding or spotting. The intake of LERNA must resume regularly after the intake phase of placebo.

To shift her period to another day of the week than the expected day according to her current schedule, the user may be advised to shorten the placebo day interval by the desired days. The shorter the interval, the greater the risk that you will not have a withdrawal bleed and experience withdrawal bleeding and spotting during the next blister (as if you want to delay your period).

04.3 Contraindications

COCs should not be used under the conditions listed below. If any of the conditions occurs for the first time during the use of COCs, treatment should be stopped 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 (transient ischaemic 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 pancreatitis if associated with severe hypertriglyceridaemia;

• severe hepatic pathologies in progress or in the past, until the values ​​of liver function return to normal;

• severe renal failure or acute renal failure;

• current or previous liver tumors (benign or malignant);

• known or suspected hormone-dependent neoplasms (for example, of the genital organs or breasts);

• 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

If any of the conditions or risk factors mentioned below are present, the suitability of LERNA 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 LERNA should be discontinued.

If VTE or ATE is suspected or confirmed, the use of COCs should be discontinued.

If anticoagulant therapy is initiated, an adequate alternative method of contraception must be used, due to the teratogenicity of anticoagulant therapy (coumarins).

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 LERNA can also be twofold. 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 LERNA, 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 estimated1 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 62 women using a levonorgestrel-containing CHC.

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.

1 These incidences were estimated from the totality of epidemiological study data, using the relative risks for the different products compared with levonorgestrel-containing COCs.

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

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).

LERNA 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 In these situations it is advisable to stop using the patch / pill / ring (in the case of elective interventions at least four weeks earlier) and not re-use it until two weeks after complete resumption of mobility. To avoid unwanted pregnancy, another method of contraception must be used. If LERNA has not been discontinued earlier, antithrombotic treatment should be considered. Note: Temporary restraint, including air travel lasting> 4 hours, can also be a risk factor for VTE, especially in women with other risk factors 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 in the 6-week period of the puerperium, must be considered (for information on "Fertility, 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 or rapid breathing;

- sudden cough which may be associated with hemoptysis;

- sharp pain in the chest;

- 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 accident (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). LERNA 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 should contact a healthcare professional immediately and inform them that they are taking a CHC.

Symptoms of 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 in elocution 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 long-term users of COCs (> 5 years) has been reported in some epidemiological studies, but the extent to which this finding is attributable to the confounding effects of sexual behavior and other factors such as human papilloma virus (HPV).

A meta-analysis of 54 epidemiological studies reported that there is a slightly higher relative risk (RR = 1.24) of having breast cancer diagnosed in women currently using COCs. The excess risk gradually disappears over 10 years after cessation of COC use. Because breast cancer is rare in women under 40 years of age, the higher number of breast cancer diagnoses in women using or who have recently used COCs is small in relation to the overall risk of breast cancer. These studies do not provide evidence of causation. The observed pattern of increased risk may be due to an early diagnosis of breast cancer in COC users, the biological effects of COCs, or a combination of both. Breast cancers diagnosed in users tend to be less clinically advanced than cancers diagnosed in women who have never used them.

In rare cases, benign liver tumors and, even more rarely, malignant liver tumors have been reported in COC users. In isolated cases, these tumors have resulted in life-threatening intra-abdominal haemorrhages. In COC users who present with severe upper abdominal pain, liver enlargement or signs suggestive of intra-abdominal haemorrhage, the possibility of liver cancer should be considered in the differential diagnosis.

With the use of the higher dosage of combined oral contraceptives (50 micrograms ethinyl estradiol) the risk of endometrial and ovarian cancer is reduced. Whether this is also applicable at the lower dosage remains to be confirmed.

Other conditions

The progestogen component of LERNA 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. or moderate and concomitant use of potassium-sparing medicinal products, potassium levels were increased slightly but not significantly during administration of drospirenone. Therefore, in patients with renal insufficiency and baseline serum potassium values ​​below the maximum limit, yes recommends that serum potassium be monitored in the first treatment cycle, particularly in the case of concomitant intake of potassium-sparing medicinal products See also section 4.5.

Women with hypertriglyceridaemia, or a family history of the disease, may be at increased risk of pancreatitis when using COCs.

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

The onset or worsening of the conditions listed below has been reported both during pregnancy and while taking COCs, but the evidence of an association with COC use is not conclusive: jaundice and / or itching due to cholestasis, gallstone formation, porphyria, systemic lupus erythematosus, uraemic-haemolytic syndrome, Sydenham's chorea, herpes gestationis, 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 markers of liver function return to normal. The return of cholestatic jaundice and / or itching associated with cholestasis 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 the use of COCs.

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 taking COCs.

Each pink tablet of this medicine contains 44 mg of lactose monohydrate, each white tablet contains 89.5 mg of anhydrous lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption who follow a lactose-free diet should consider this intake.

Medical examination / consultation

A complete medical history (including family history) must be taken and pregnancy excluded before initiating or re-starting LERNA. Blood pressure should be measured and physical examination performed in light of contraindications (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 LERNA compared to other CHCs, symptoms of VTE and ATE, known risk factors and what to do in the event of a suspected thrombosis.

The woman should also be advised of the need to read the package leaflet carefully and to follow its advice. The frequency and type of examinations 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 infections (AIDS) and other sexually transmitted diseases.

Reduced effectiveness

The efficacy of COCs may be reduced in case of, for example, not taking the active tablets (see section 4.2), or in case of gastrointestinal disturbances while taking the active tablets (see section 4.2) or concomitant therapy. (see section 4.5).

Reduced cycle control

Irregular bleeding (spotting or breakthrough bleeding) may occur with the use of COCs, especially during the first months of use. Therefore, the evaluation of possible irregular bleeding is only meaningful after an adjustment period of approximately three cycles.

If irregular bleeding persists or occurs after previously regular cycles, non-hormonal causes should be evaluated and appropriate diagnostic measures taken to rule out malignancy or pregnancy. These can include scraping.

In some women, withdrawal bleeding during the days of taking the placebo tablets may not occur. If the COC has been taken according to the directions described in section 4.2, it is unlikely that the user is pregnant. However, if the COC has not been taken according to these directions before the first missed period from suspension, or if two withdrawal periods have been missed, pregnancy must be ruled out before continuing the use of the COC.

04.5 Interactions with other medicinal products and other forms of interaction

Note: Consult information on concomitant medications to identify potential interactions.

Influence of other medicinal products on LERNA

Interactions between oral contraceptives and other medicinal products can lead to blood loss and / or contraceptive failure. The following interactions have been reported in the literature:

Hepatic metabolism

Interactions may occur with drugs that induce liver enzymes that can lead to increased clearance of sex hormones (eg phenytoin, barbiturates, primidone, carbamazepine, rifampicin, bosentan and drugs for the treatment of HIV (eg ritonavir, nevirapine) and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing the remedy based on St. John's wort (Hypericum perforatum)). Generally, maximum enzyme induction is seen in approximately 10 days but can be maintained for at least 4 weeks after cessation of drug therapy.

Interference with the enterohepatic circulation

Failures of contraceptive efficacy have also been reported with antibiotics, such as penicillins and tetracyclines. The mechanism of this effect has not been elucidated.

Behavior to follow

Women on short-term treatment with any of the above classes of medicines or single active substances (liver enzyme-inducing medicines), including those taking rifampicin-containing medicines, should temporarily use a barrier method in addition to the combined oral contraceptive, i.e. during concomitant administration of the other medicines and for 7 days after the end of treatment.

Women taking rifampicin must use contraception in addition to the combined oral contraceptive for the period of rifampicin administration and for 28 days after the end of treatment.

In women on long-term treatment with active substances that induce liver enzymes, another reliable non-hormonal method of contraception is recommended.

Women being treated with antibiotics (including rifampicin, see above) should use a barrier method for up to 7 days after stopping.

If concomitant medication continues beyond the end of the active tablets in the COC blister, the placebo tablets should be discarded and the next blister started immediately.

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.

Influence of LERNA on other medicinal products

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

Based on inhibition studies in vitro and on interaction studies in vivo in volunteer patients 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 interactions

In patients without renal insufficiency, concomitant use of drospirenone and ACE inhibitors or NSAIDs did not show a significant effect on serum potassium. However, concomitant use of LERNA with aldosterone antagonists or potassium-sparing diuretics was not In this case, serum potassium should be tested during the first treatment cycle See also section 4.4.

Laboratory tests

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

04.6 Pregnancy and breastfeeding

Pregnancy

LERNA is not indicated in pregnancy.

If pregnancy occurs during the use of LERNA, the product should be discontinued immediately. Extensive epidemiological studies have not revealed any increased risk of birth defects in children born to women who used COCs prior to pregnancy, nor an effect. teratogenic in case of accidental use 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 components cannot be excluded. However, general experience with COCs during pregnancy did not provide any evidence of adverse effects in humans.

The available data regarding the use of LERNA during pregnancy are too limited to allow conclusions regarding the adverse effects of LERNA on pregnancy, fetal or newborn health. To date, no relevant epidemiological data are available.

The increased risk of thromboembolism in the postpartum period should be taken into account when LERNA is restarted (see sections 4.2. And 4.4).

Feeding time

Breastfeeding may be affected by COCs as they can reduce the quantity and change the composition of breast milk. Therefore, the use of COCs should not be recommended until the nursing mother has completed weaning. of child. Small amounts of contraceptive steroids and / or their metabolites may be excreted with milk during COC use. Such amounts may affect the baby.

04.7 Effects on ability to drive and use machines

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

04.8 Undesirable effects

The following side effects have been reported during the use of LERNA:

The table below lists undesirable effects by MedDRA System Organ Class (MedDRA SOC). Frequencies are based on clinical data. The more appropriate MedDRA term was used to describe a particular reaction, its synonyms and related conditions.

Undesirable effects that have been associated with the use of LERNA as an oral contraceptive according to the MedDRA system organ class and MedDRA terms

System and organ classification common Uncommon Rare Not known (MedDRA version 9.1) (≥1 / 100 up to (≥1 / 1000 up to (≥1 / 10000 up to (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 reactions, k hypersensitivity Endocrine pathologies endocrine disorder Metabolism and nutrition disorders increased appetite, anorexia, hyperkalemia, hyponatremia Psychiatric disorders emotional lability depression, nervousness, drowsiness, anorgasmia, insomnia Nervous system disorders headache dizziness, paraesthesia dizziness, tremor Eye disorders conjunctivitis, dry eye, eye disorder Cardiac pathologies tachycardia Vascular pathologies migraine, varicose veins, hypertension phlebitis, vascular disorder, epistaxis, syncope, venous thromboembolism (VTE), arterial thromboembolism Gastrointestinal disorders nausea abdominal pain, vomiting, dyspepsia, flatulence, gastritis, diarrhea enlarged abdomen, gastrointestinal disorder, 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, skin striae, contact dermatitis, photosensitive dermatitis, skin nodules 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 breasts, uterine / vaginal bleeding *, genital discharge, hot flashes, vaginitis, menstrual disorder, dysmenorrhea, hypomenorrhea, menorrhagia, vaginal dryness, suspected PAP test, decreased libido dyspareunia, vulvovaginitis, post-coital bleeding, withdrawal bleeding, breast cyst, breast hyperplasia, breast neoplasm, cervical polyp, endometrial atrophy, ovarian cysts, enlarged uterus General disorders and administration site conditions asthenia, increased sweating, edema (generalized, peripheral, facial) malaise Diagnostic tests weight gain weight decrease

* irregular bleeding usually decreases with continued treatment.

Description of selected 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 undesirable effects have been reported in COC users, which are discussed in section 4.4

• thromboembolic venous disorders;

• thromboembolic arterial disorders;

• hypertension;

• liver tumors;

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

• chloasma;

• acute or chronic disturbances of liver function may require the interruption of oral contraceptives until liver markers return to normal;

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

The frequency of breast cancer diagnoses is slightly increased among COC users. Since breast cancer is rare in women under 40 years of age, the increase is small in relation to the overall risk of breast cancer. The correlation with COCs is unknown. For further information, see sections 4.3. and 4.4.

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: www.agenziafarmaco.gov.it/it/responsabili.

04.9 Overdose

To date, there is no experience of overdose with LERNA. Based on general experience with COCs, the symptoms that may occur in case of overdose of active tablets are: nausea, vomiting and, in young girls, mild vaginal bleeding. There are no antidotes and treatment. it must be symptomatic.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group (ATC): progestogens and estrogens, fixed combinations. ATC code: G03AA12.

Pearl Index for method failure: 0.41 (upper value of the bilateral 95% confidence interval: 0.85). Overall Pearl Index (method failure + patient error): 0.80 (upper value of the interval 95% bilateral confidence: 1.30).

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

LERNA is a combined oral contraceptive with ethinylestradiol and the progestin drospirenone. In a therapeutic dosage, drospirenone also possesses antiandrogenic properties and mild antimineralocorticoid properties. It is devoid of estrogenic, glucocorticoid and antiglucocorticoid activity. This gives drospirenone a similar pharmacological profile to natural progesterone.

There is evidence from clinical studies that indicates that the mild antimineralocorticoid properties of LERNA translate into a mild antimineralocorticoid activity.

Two multicentre, double-blind, randomized, placebo-controlled studies were conducted to evaluate the efficacy and safety of LERNA in patients with moderate acne vulgaris.

After six months of treatment, compared to placebo, LERNA showed a statistically significant greater than 15.6% (49.3% versus 33.7%) reduction in inflammatory lesions, 18.5% (40.6% versus 22). , 1%) in non-inflammatory lesions, and 16.5% (44.6% versus 28.1%) of the total lesion count. In addition, a higher percentage of subjects, 11.8% (18.6% versus 6.8%), showed an ISGA (Investigator "sStatic Global Assessment) score of" clear "or" nearly clear ".

05.2 Pharmacokinetic properties

Drospirenone

Absorption

Drospirenone administered orally is rapidly and almost completely absorbed. Maximum concentrations of the active substance in serum of approximately 38 ng / ml are reached within 1-2 hours after a single administration. Bioavailability is between 76% and 85%. Simultaneous food intake has no influence on the bioavailability of drospirenone.

Distribution

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

Biotransformation

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

Elimination

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

Steady state conditions

During a course of treatment, the maximum steady-state concentrations of drospirenone in serum of approximately 70 ng / ml are reached after approximately 8 days of treatment. Serum drospirenone levels accumulate by a factor of approximately 3 as a result of the ratio of the half-life to the dose interval.

Special populations

Effect of renal impairment

Steady state serum levels of drospirenone 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 well tolerated even by women with mild to moderate renal impairment. Treatment with drospirenone did not show any clinically significant effect on serum potassium concentration.

Effect of hepatic impairment

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

Ethnic groups

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

Ethinylestradiol

Absorption

Orally administered ethinylestradiol is rapidly and completely absorbed. Peak serum concentrations of approximately 33 pg / ml are achieved within 1 - 2 hours after single oral administration. Absolute bioavailability as a result of presystemic conjugation and first pass metabolism is about 60%. Concomitant food intake reduces the bioavailability of ethinylestradiol in about 25% of the subjects studied while no changes were observed in the others.

Distribution

Serum levels of ethinylestradiol decrease in two phases, the terminal disposition phase is characterized by a half-life of approximately 24 hours. Ethinylestradiol is highly, but not specifically, bound to serum albumin (approximately 98.5%), and induces an increase in serum concentrations of SHBG and corticoid-binding globulin (CBG). An apparent volume of distribution was determined to be approximately 5 L / kg.

Biotransformation

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

Elimination

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

Steady state conditions

Steady state conditions are reached during the second half of a treatment cycle and serum levels of ethinylestradiol accumulate to approximately 2.0 to 2.3.

05.3 Preclinical safety data

In laboratory animals the effects of drospirenone and ethinylestradiol were limited to those associated with recognized pharmacological activity. In particular, in animals, reproductive toxicity studies revealed embryotoxic and foetotoxic effects which were considered species specific. At doses higher than those used in LERNA users, effects on sexual differentiation were observed in rat fetuses, but not in monkeys.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Active film-coated tablets (pink):

Core of the tablet:

Lactose monohydrate; pregelatinised starch (maize); povidone K-30 (E1201); croscarmellose sodium; polysorbate 80; magnesium stearate (E572).

Tablet coating film:

Polyvinyl alcohol; titanium dioxide (E171); macrogol 3350; talc; yellow iron oxide (E172); red iron oxide (E172); black iron oxide (E172).

Placebo (white) film-coated tablets:

Core of the tablet:

Anhydrous lactose; povidone (E1201); magnesium stearate (E572).

Tablet coating film:

Polyvinyl alcohol; titanium dioxide (E171); macrogol 3350; talc.

06.2 Incompatibility

Not relevant.

06.3 Period of validity

3 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, clear to slightly opaque PVC / PVDC-Al blister. Each blister contains 24 pink film-coated tablets (active tablets) and 4 white placebo film-coated tablets.

Packs:

1 x 28 film-coated tablets

3 x 28 film-coated tablets

6 x 28 film-coated tablets

13 x 28 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

FARMITALIA s.r.l. - Viale A. De Gasperi 165 / B - 95127 CATANIA

08.0 MARKETING AUTHORIZATION NUMBER

0.02 mg / 3 mg film-coated tablets 1x28 tablets in PVC / PVDC / Al blister - AIC: 041345012

0.02 mg / 3 mg film-coated tablets 3x28 tablets in PVC / PVDC / Al blister - AIC: 041345024

0.02 mg / 3 mg film-coated tablets 6x28 tablets in PVC / PVDC / Al blister - AIC: 041345036

0.02 mg / 3 mg film-coated tablets 13x28 tablets in PVC / PVDC / Al blister - AIC: 041345048

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

January 2013

10.0 DATE OF REVISION OF THE TEXT

September 2014

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