Drospil - Package Leaflet

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

Active ingredients: Ethinylestradiol, Drospirenone

Drospil 0.02 mg / 3 mg film-coated tablets

Why is Drospil used? What is it for?

• Drospil is a contraceptive pill and is used to prevent pregnancy.
• Each of the 24 pink tablets contains a small amount of two different female hormones, namely drospirenone and ethinyl estradiol.
• The 4 white tablets do not contain active ingredients and are also called placebo tablets.
• Contraceptive pills that contain two hormones are called "combination" pills.

Contraindications When Drospil should not be used

General notes

Before you start using Drospil you should read the information on blood clots in section 2. It is especially important to read the symptoms of a blood clot - see section 2 "Blood clots".

Before you can start taking Drospil, your doctor will ask you questions about your personal medical history and that of your close relatives. Your doctor will also measure your blood pressure and, depending on your personal situation, may decide to have other tests done.

This leaflet describes several situations where you will need to stop using Drospil or where the reliability of Drospil may be reduced. In these situations you will have to avoid sexual intercourse or take additional non-hormonal contraceptive precautions, eg. a condom or other barrier method. Do not use methods based on biological rhythms or body temperature, as these methods can be unreliable as Drospil alters the changes in body temperature and cervical mucus that normally occur during the menstrual cycle.

Drospil, like other hormonal contraceptives, does not protect against HIV infection (AIDS) or other sexually transmitted diseases.

Do not use Drospil

Do not use drospil 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 due to have an "operation or if you are going to lie 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 blood clots in the arteries:
  • severe diabetes with blood vessel injury
  • very high blood pressure
  • 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 "inflammation of the pancreas (pancreatitis)
• if you have (or have had in the past) liver disease and your liver is still not functioning as it should
• if you have kidney problems (kidney failure)
• if you have (or have ever had) liver cancer
• if you have (or have had in the past) or are suspected of having breast or genital cancer
• if you have unexplained bleeding from the vagina
• if you are allergic to ethinylestradiol or drospirenone, or any of the other ingredients of this medicine (listed in section 6). In this case you may experience itching, rash or swelling.

Precautions for use What you need to know before taking Drospil

When to take special care with Drospil

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 clot (thrombosis) ").

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 careful when using Drospil or any other combination pill, and your doctor may need to see you regularly.

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

If this condition appears or worsens while you are using Drospil you should tell your doctor.

• if a close relative has or has ever had breast cancer
• if you suffer from 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 soon after having a baby you can start taking Drospil;
• if you have "inflammation of the veins under the skin (superficial thrombophlebitis);
• if you have varicose veins;
• if you suffer from epilepsy (see section "Other medicines and Drospil")
• if you have a condition that first appeared during pregnancy or with previous use of sex hormones (for example, hearing loss, a blood disorder called porphyria, blistering rash during pregnancy (gestational herpes) , a nerve disease causing sudden body movements (Sydenham's chorea)
• if you have or have ever had golden-brown spots (chloasma) known as "pregnancy spots" especially on the face. In this case, exposure to direct sunlight or ultraviolet light should be avoided.
• if you have hereditary angioedema, products containing estrogen can cause or worsen symptoms. You should therefore seek immediate medical attention if you experience symptoms of angioedema such as swelling of the face, tongue and / or pharynx, and / or difficulty in swallowing or hives with breathing difficulties.

Interactions Which drugs or foods may change the effect of Drospil

Always tell your doctor what medicines or herbal products you are already using. Also tell the other doctors or dentist who prescribes you medicines (or the pharmacist who gives you them) that you are using Drospil. Doctors will tell you if you need to take additional contraceptive measures (e.g. condoms) and if so, for how long.

• Some medicines can make Drospil less effective in preventing pregnancy, or can cause unexpected bleeding. These include medicines used to treat:
  • epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine)
  • tuberculosis (e.g. rifampicin)
  • HIV infections (ritonavir, nevirapine)
  • other infections (antibiotics such as griseofulvin, penicillin, tetracycline)
  • high pressure in the blood vessels of the lungs (bosentan)
  • and the herbal preparation St. John's Wort
• Drospil may influence the effect of other medicines, for example:
• medicines containing cyclosporine or the antiepileptic lamotrigine (this can cause an increase in the frequency of seizures)

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

Drospil with food, drink and alcohol

Drospil can be taken with or without food, with a small amount of water as needed.

Laboratory examination

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

Warnings It is important to know that:

Drospil and blood clots

Using a combined hormonal contraceptive such as Drospil 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 Drospil 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

• 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)

• pain, discomfort, feeling of pressure or heaviness in the chest, 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 Drospil 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 Drospil 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 Drospil, 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 using Drospil 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 Drospil is low but some conditions increase the risk. Its risk is greater:

• if you are 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 Drospil a few weeks before the surgery or in the period where you are less mobile. If you have to stop taking Drospil, 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 Drospil needs to be stopped.
• If any of the above conditions change while you are using Drospil, 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 Drospil is very low but may increase:

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

Drospil and the tumor

Breast cancer has been observed slightly more often in women using the combined pill than in those not using it, but it is not known whether this is attributable to the treatment. For example, the higher number of breast cancer diagnoses in women using the Pill may be due to a higher frequency of medical checks they undergo. The occurrence of breast cancers gradually decreases after discontinuation of the use of combined hormonal contraceptives. It is important to check your breasts regularly and contact your doctor if you notice any lumps.

In rare cases, benign liver tumors and, in even fewer cases, malignant liver tumors have been reported in pill users. Contact your doctor if you experience unusual severe abdominal pain.

Intermenstrual bleeding

During the first few months of taking Drospil you may notice unexpected bleeding (outside the days of taking the placebo tablets). If this bleeding occurs for more than a few months, or if it appears after a few months, your doctor will need to evaluate the cause.

What to do if menstruation does not occur during the days of taking the placebo tablets

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

If the expected bleeding does not occur twice in a row, a pregnancy may have begun. Contact your doctor immediately. Do not start the new medicine strip until you are sure that you are not pregnant.

Pregnancy

If you are pregnant, you should not take Drospil. If you become pregnant while taking Drospil stop taking the tablets immediately and contact your doctor. If you find out you are pregnant you can stop taking Drospil at any time (see also "If you stop taking Drospil. ").

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

Breastfeeding

Generally, the use of Drospil is not recommended while breastfeeding. If you want to take the pill while you are breastfeeding you should contact your doctor.

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

Driving and using machines

There is no information indicating that the use of Drospil may affect the ability to drive or use machines.

Drospil contains lactose

If you have an intolerance to some sugars, contact your doctor before taking Drospil.

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

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

The tablets with the two different colors are arranged in order. One strip contains 28 tablets.

Take one Drospil tablet each day with a small amount of water as needed. You can take the tablets with or without food, but the tablets should be taken at approximately the same time each day.

Do not confuse the tablets: take one pink tablet for the first 24 days and then one white tablet for the last 4 days. Then you must immediately start taking a new strip of tablets (24 pink tablets and then 4 white tablets). There is therefore no interval between taking two strips.

Given the different composition of the tablets, it is necessary to start with the first tablet in the upper left part of the strip, then continue in the order to take the other tablets every day. To be sure that the order is correct, follow the direction of the arrows on the strip.

Preparation of the strip

To help you memorize, each Drospil strip comes with 7 adhesive labels showing the 7 days of the week. Choose the adhesive label that shows the day of the week on which you start taking your tablets. For example, if you start taking your tablets on Wednesday, use the "WED" sticker.

Paste the label with the day of the week along the top of the blister, marked with the "inscription". Paste the "adhesive label" here so that the first day is on top of the tablet marked with the number "1". Above each tablet is indicated on a day, so that you can check if you have taken a certain pill. The arrows indicate the order in which you take the pills.

During the 4 days that you take the white placebo tablets (the placebo days), you should experience some blood loss (so-called withdrawal bleeding). This usually occurs on the 2nd or 3rd day after taking the last pink active tablet of Drospil. After taking the last white tablet, you should start a new strip, regardless of whether the bleeding is still ongoing or not. This means that each strip of tablets should be started on the same day of the week, and that withdrawal bleeding should occur on the same days each month.

If you use Drospil following this procedure, you will be protected against pregnancy even during the 4 days of taking the placebo tablets.

When can the first strip begin

• If you have not used a hormonal contraceptive in the previous month

Start taking Drospil on the first day of your period (i.e. the first day of your natural period). If you start taking Drospil on the first day of your period, you will be immediately protected against unwanted pregnancy.You can also start taking the tablets between the 2nd and 5th day of your cycle, but in this case you will need to use additional contraceptive measures (e.g. condoms) for the first 7 days.

• Changing from another combined hormonal contraceptive, combination pill, vaginal ring or transdermal patch

You can start taking Drospil preferably the day after taking the last active tablet (the last tablet containing active substances) of your previous contraceptive, at the latest on the day following the tablet-free interval of your previous contraceptive (or after the "last inactive tablet of the previous contraceptive). As for switching from the vaginal ring or transdermal patch, follow the advice of your doctor.

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

If you have previously used the progestogen-only pill you can switch to Drospil at any time (if you have previously used an implant or an IUD you can start on the day of their removal, if you have used an injectable on the day it should be given the next injection), but in all these cases you must use additional contraceptive protection (e.g. condoms) for the first 7 days of taking the tablets.

• After an abortion

Follow your doctor's advice.

• After giving birth

You can start Drospil between 21 and 28 days after having a baby. If you start after day 28, you must also use a so-called barrier method of birth control (for example a condom) during the first seven days of using Drospil. If, after having a baby, you have had sex before starting Drospil (again), make sure you are not pregnant or wait until your next period.

• If you are breast-feeding and want to start Drospil (again) after having a baby

Read the section on "Breastfeeding".

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

If you forget to take Drospil

The last 4 tablets of the 4th row of the strip are placebo tablets. If you forget to take one of these tablets, there will be no effect on the reliability of Drospil. Throw away the forgotten placebo tablet.

If you forget to take a pink active tablet (the tablets numbered 1 to 24 on the blister strip) you should do the following:

• If you are less than 12 hours late in taking the tablet, contraceptive protection is not reduced. Then take the tablet as soon as you remember and then continue with the next tablet-taking at the usual time.
• If you are more than 12 hours late in taking a tablet, contraceptive protection may be reduced. The more tablets you have forgotten, the greater the risk of becoming pregnant.

The risk of incomplete contraceptive protection is greater if you forget to take a pink tablet at the beginning or at the end of the strip. Therefore, you must follow the following instructions (see also diagram below):

• More than 1 tablet forgotten in the strip in use

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 once on the same day. Then continue to take the following tablets at the usual time and use additional contraceptive measures for the next 7 days, for example a condom. If you had sex in the week before you forgot the tablet, there is a possibility of pregnancy. In this case, contact your doctor.

• 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 once on the same day. Then continue to take the following tablets at the usual time. The protection against pregnancy is not reduced and you do not need to take additional precautionary measures.

• One tablet forgotten between days 15 - 24 (third or 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 once on the same day. Then continue to take the following tablets at the usual time. Instead of taking the white placebo tablets from the current pack, discard them and start a new strip (the starting day does not matter). You are very likely to have a period at the end of the second pack - while taking the white placebo tablets - but you may notice light bleeding or menstruation-like discharge while taking the second pack.
2. You can also stop taking the pink active tablets and take the 4 white placebo tablets directly (before taking the placebo tablets, make a note of the day you forgot the tablet). If you want to start a new pack on the same day as the tablet. normal week, take the placebo tablets for less than 4 days and if you follow either of the two recommendations above, you will remain protected against pregnancy.

If you have forgotten several tablets from your current pack and no bleeding occurs during the days of taking the placebo tablets, you may be pregnant. Contact your doctor before starting a new pack.

What to do in case of vomiting or severe diarrhea

If you vomit within 3-4 hours of taking a pink active tablet or have severe diarrhea, there is a risk that the active ingredients contained in the pill have not been completely absorbed by the body. This situation is similar to forgetting a tablet. After vomiting or diarrhea you should take another pink tablet from a reserve pack as soon as possible. If possible, take it within 12 hours of the time you usually take your pill. If this is not possible or if 12 hours have already passed, you should follow the advice under "If you forget to take Drospil".

Delaying your period: what you need to know

Although not recommended, it is possible to delay menstruation by not taking the white placebo tablets from the 4th row and immediately switching to a new Drospil strip ending it. You may experience mild or menstruation-like bleeding while using the second strip. Finish the second strip by taking the 4 white tablets from the 4th row. Then start a new strip. You may ask your doctor for advice before deciding to delay your period .

Change 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 days of taking the placebo tablets. If you want to change the day you start your period, reduce the number of placebo days - when you take the white placebo tablets - (but never increase them - 4 days is the maximum!). For example, if the day you start taking the placebo tablets is Friday, and you want to move it to Tuesday (3 days earlier), start a new pack 3 days earlier than usual. During this time, no blood loss may occur. Later you may notice light or menstruation-like bleeding.

If you are unsure how to proceed, contact your doctor for advice.

If you stop taking Drospil

You can stop taking Drospil 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 Drospil and wait until you have a natural period before trying to conceive. This will make it easier to calculate the expected delivery date. 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 Drospil

There have been no reports of harmful outcomes from taking too many Drospil tablets.

If you have taken several tablets at once, you may experience symptoms such as nausea or vomiting. Younger girls can have vaginal bleeding.

If you have taken too many Drospil tablets, or if you have noticed that a child has taken some, ask your doctor or pharmacist for advice.

Side Effects What are the side effects of Drospil

Drospil 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 Drospil, 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 Drospil '.

The following list shows the side effects that have been associated with the use of Drospil:

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

• mood swings
• headache
• nausea
• breast pain, problems with your menstrual cycle, such as menstrual irregularities, absence of menstruation

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

• depression, nervousness, drowsiness
• dizziness, tingling
• migraine, varicose veins, increased blood pressure
• stomach pain, vomiting, indigestion, intestinal gas, stomach inflammation, diarrhea
• acne, itching, rash
• aches and pains, for example back pain, pain in limbs, muscle cramps
• vaginal fungal infections, 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 your period menstrual periods, painful periods, short periods of time, very heavy periods, vaginal dryness, abnormal cervical smear, decreased interest in sex
• lack of energy, increased sweating, fluid retention
• weight gain

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

• candida (a "fungal infection)
• anemia, increased number of blood platelets
• allergic reaction
• hormonal (endocrine) disorders
• increased appetite, loss of appetite, unusual high concentration of potassium in the blood, unusual low concentration of sodium in the blood
• failure to reach orgasm, insomnia
• dizziness, tremor
• eye disorders, for example inflammation of the eyelids, dry eyes
• unusually fast heartbeat
• inflammation of a vein, epistaxis (nosebleeds), fainting
• abdominal enlargement, intestinal upset, feeling full, stomach hernia, fungal infection of the mouth, constipation, dry mouth
• pain in the bile ducts or gallbladder, inflammation of the gallbladder
• yellow-brown spots on the skin, eczema, hair loss, acne-like skin inflammation, dry skin, skin inflammation with lumps, excessive hair growth, skin disorders, stretch marks on the skin, inflammation of the skin, inflammation of light-sensitive skin, skin nodules.
• sexual difficulties or pain during intercourse, inflammation of the vagina (vulvovaginitis), bleeding after intercourse, withdrawal bleeding, breast cyst, increased number of breast cells (hyperplasia), malignant breast lumps, abnormal surface growth mucosa of the cervix, thinning or deterioration of the lining of the uterus, ovarian cysts, enlargement of the uterus
• general feeling of being unwell
• weight loss
• harmful blood clots in a vein or artery, for example:
  • either in a leg or foot (DVT)
  • or in a lung (PE)
  • or heart attack
  • or stroke
  • or mini-stroke
  • or temporary stroke-like symptoms, 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 undesirable effects have also been reported but their frequency cannot be estimated from the available data: hypersensitivity, erythema multiforme (skin rash with redness or target-shaped ulcers).

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

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 carton and blister after "EXP". The expiry date refers to the last day of that month.

This medicinal product 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.

Deadline "> Other information

What Drospil 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 (E1201), croscarmellose sodium, polysorbate 80, magnesium stearate (E572).
  • Tablet coating: Polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172).
• Inactive white film-coated tablets:
  • Tablet core: anhydrous lactose, povidone (E1201), magnesium stearate (E572).
  • Tablet coating: Polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc.

What Drospil looks like and contents of the pack

• Each blister of Drospil contains 24 active pink film-coated tablets placed in the 1st, 2nd, 3rd and 4th row of the strip, and 4 placebo film-coated tablets placed in row 4.
• Both the pink and white tablets of Drospil are film-coated tablets, i.e. the core of the tablet is coated.
• Drospil is available in cartons 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 Drospil 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 interaction - 04.6 Pregnancy and lactation - 04.7 Effects on the ability to drive and use machines - 04.8 Undesirable effects - 04.9 Overdose - 05.0 PHARMACOLOGICAL PROPERTIES - 05.1 "Pharmacodynamic properties - 05.2 Pharmacokinetic properties" - 05.3 Preclinical safety data - 06.0 PHARMACEUTICAL PARTICULARS - 06.1 Excipients - 06.2 Incompatibility "- 06.3 Shelf life" - 06.4 Special precautions for storage - 06.5 Nature of the primary packaging and contents of the package - 06.6 Instructions for use and handling - 07.0 AUTHORIZATION HOLDER ALL "PLACING ON THE MARKET - 08.0 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 RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY - 12.0 INSTRUCTIONS FOR RADIOPHONES ON EXTEMPORARY PREPARATION AND QUALITY CONTROL -

01.0 NAME OF THE MEDICINAL PRODUCT -

DROSPIL 0.02 MG / 3 MG 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 (s) with known effect: Lactose monohydrate 44 mg

4 placebo (inactive) film-coated tablets:

The tablet does not contain active ingredients

Excipient (s) with known effect: Anhydrous lactose 89.5 mg

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM -

Film-coated tablet.

The active tablet is pink, round shaped, film-coated, with a diameter of 5.7 mm.

The placebo tablet is white, round shaped, film-coated, with a diameter of 5.7 mm.

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

Oral contraception.

The decision to prescribe DROSPIL should take into account the individual woman's current risk factors, in particular those related to venous thromboembolism (VTE) and the comparison between the risk of VTE associated with DROSPIL and that associated with other combined oral contraceptives - COCs ( see sections 4.3 and 4.4).

04.2 Posology and method of administration -

Route of administration: oral use.

How to take Drospil

The tablets should be taken at approximately the same time each day, with a little water if necessary, in the order indicated on the blister. The tablets should be taken continuously. Each tablet should be taken daily for 28 consecutive days. Each subsequent blister pack should be started the day after taking the last tablet from the previous blister. Withdrawal bleeding usually starts 2-3 days after taking the placebo tablets (last row) and may not have finished yet when starting a new pack.

How to start treatment with Drospil

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

Taking the tablets should start on the first day of the woman's natural menstrual cycle (ie the first day of her period).

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

The woman should start Drospil preferably on the day following the last active tablet (the last tablet containing the active substances) of the previous combined oral contraceptive, at the latest on the day following the usual tablet-free or tablet-taking interval. placebo from his previous combined oral contraceptive. In case of previous use of vaginal ring or transdermal patch, the woman should start taking Drospil preferably on the day of removal of the device, at the latest on the day scheduled for the next application.

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

Switching from the progestogen-only pill can occur at any time (from implantation or IUS on the day of their removal, from an injectable on the day the next injection was scheduled), but in all these cases to the woman an additional barrier method should be advised for the first 7 days of tablet-taking.

• After an abortion in the first trimester of pregnancy

The intake can be started immediately. In this case no additional contraceptive measures are necessary.

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

The woman should be advised to start taking 21 to 28 days after delivery or after an abortion in the second trimester of pregnancy. In cases of later onset, the woman should use supplemental barrier contraception for the first 7 days. However, if intercourse has already taken place, a possible pregnancy must be ruled out before starting COC use, or the woman must wait for the first subsequent menstrual cycle.

For use during breastfeeding, see section 4.6.

Behavior in case of missed tablets

Placebo tablets from the last (fourth) row of the blister can be skipped. However, they should be discarded to avoid an unintended prolongation of the placebo tablet phase. The following suggestions therefore only refer to the forgetting of active tablets:

If she is less than 12 hours late in taking the tablet, contraceptive protection is not reduced. The woman should take the forgotten 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 any tablet, contraceptive protection may be reduced. The behavior to be adopted in case of forgotten tablets is based on the following two fundamental 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".

As a result, the following tips can be applied in daily practice:

• Day 1-7

The woman should take the last missed tablet as soon as she remembers, even if this involves taking two tablets at the same time, and then she should continue taking the following tablets at the usual time each day. Also, a barrier method, such as a condom, should be used for the next 7 days. In case of sexual intercourse in the previous 7 days, the possibility of pregnancy should be considered. The more tablets you have forgotten and the closer you are to taking the placebo tablets, the greater the risk of pregnancy.

• Day 8-14

The woman should take the last missed tablet as soon as she remembers, even if this involves taking two tablets at the same time, and then she should continue taking the following tablets at the usual time each day. Provided that the woman has taken the tablets correctly in the 7 days preceding the first missed tablet, there is no need to use additional contraceptive measures. However, if more than one tablet is missed, the woman should take additional precautionary measures for the next 7 days.

• Day 15-24

The risk of reduced contraceptive reliability is extremely high as the placebo tablet phase approaches. However, reduced contraceptive protection can still be prevented by changing the tablet-taking schedule. By adopting either of the following two options, you will not it is therefore necessary to resort to additional contraceptive measures, provided that the woman has taken all the tablets regularly in the 7 days preceding the first missed tablet. If not, she must follow the first of the two options and also use additional contraceptive measures for the next 7 days .

1. The woman should take the last missed tablet as soon as she remembers, even if this involves taking two tablets at the same time, and then she should continue taking the following tablets at the usual time each day, until active tablets will be finished. The 4 placebo tablets from the last row should be discarded. The next pack should be started immediately after finishing the current one. The patient is unlikely to experience withdrawal bleeding before finishing the active tablets from the second blister pack, however it may experience spotting or breakthrough bleeding on tablet-taking days.

2. The woman may also be advised to stop taking the active tablets from the current pack. In this case she should take the placebo tablets from the last row for up to 4 days, including the days when they have been forgotten. the tablets, and then continue with a new pack.

If the woman has forgotten to take several tablets, resulting in no withdrawal bleeding in the placebo tablet-taking interval, the possibility of pregnancy should be considered.

Tips in case of gastrointestinal disorders

In the presence of severe gastrointestinal disturbances (eg vomiting or diarrhea), absorption may be incomplete and additional contraceptive measures must be used. If vomiting occurs within 3-4 hours after taking a tablet, it should be taken at the same time. a new tablet (as a replacement) as soon as possible. If possible, the new tablet should be taken within 12 hours of the usual time of taking. If more than 12 hours have passed, the instructions on forgetting tablets in section 4.2 "Behavior in case of missed tablets" apply. If the woman does not wish to change the usual dosage regimen, she will need to withdraw the required tablet (or more tablets) from a new blister pack.

How to delay a withdrawal period

To delay menstruation, the woman should continue to take the active tablets from another blister pack of Drospil without taking the placebo tablets from the current pack. The delay can be extended according to the woman's wishes until the end of the active tablets The woman may experience breakthrough bleeding or spotting during this prolonged use. The regular intake of Drospil should be resumed regularly after taking the placebo tablets.

To shift menstruation to another day of the week than expected according to the woman's schedule, the placebo days interval can be shortened to the desired days. The shorter the interval, the greater the risk of absence of withdrawal flow and breakthrough bleeding and spotting while taking the next pack (as occurs when menstruation is delayed).

04.3 Contraindications -

Combined Hormonal Contraceptives (COCs) should not be used in the following conditions. If any of the following conditions appear for the first time while using a combined hormonal contraceptive, taking the medicine 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

•

• Pancreatitis or a history of pancreatitis if associated with severe hypertriglyceridaemia

• Serious 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 malignancies (eg 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

If any of the conditions or risk factors mentioned below is present, the suitability of DROSPIL 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 consult her physician to determine whether the use of DROSPIL should be discontinued.

In the event of a suspected or confirmed VTE or ATE, the intake of the COC should be discontinued. In the event that anti-coagulation therapy is initiated, suitable alternative contraceptive methods should be used, as anticoagulant (coumarin) therapy is teratogenic.

• 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 DROSPIL can 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 DROSPIL, 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.

Number of VTE events per year per 10,000 women

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).

DROSPIL is contraindicated if a woman has several risk factors that increase the individual 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 immobilization, 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 DROSPIL 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 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 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). DROSPIL 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 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 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

In the event of suspected or confirmed VTE or ATE, the use of COCs should be discontinued. In the event that anti-coagulation therapy is initiated, an appropriate alternative method of contraception should be initiated as anticoagulant (coumarin) therapy is teratogenic.

Tumors

An increased risk of cervical cancer has been reported in some epidemiological studies in women on long-term treatment with COCs (> 5 years); however, it still remains controversial to what extent this result is to be attributed to the confounding effects for the interpretation of the outcome of sexual behavior and other factors such as human papillomavirus (HPV) infection.

A meta-analysis of 54 epidemiological studies found that there is a slightly increased relative risk (RR = 1.24) of breast cancer diagnosis in women currently using COCs. This excess risk decreases over the 10 years following discontinuation of COC treatment. Since breast cancer is rare in women under 40 years of age, the increased number of breast cancer diagnoses in users current and recent COCs is low in relation to the overall risk of breast cancer. These studies do not provide any evidence of a possible 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 these two factors. Breast cancer diagnosed in COC users it generally tends to be at a less clinically advanced stage than cancer diagnosed in women who have never used COCs.

Benign liver tumors and even more rarely malignant liver tumors have been observed on rare occasions in women taking COCs. In isolated cases, these tumors have resulted in life-threatening intra-abdominal haemorrhage. The possibility of hepatic neoplasia should be considered as a differential diagnosis in the presence of severe pain in the upper abdomen, liver enlargement or signs suggestive of intra-abdominal haemorrhage in women taking COCs.

the use of higher-dose combined oral contraceptives (50 mcg ethinylestradiol) reduces the risk of endometrial and ovarian cancer. It remains to be confirmed whether this data is also valid for lower-dose combined oral contraceptives.

Other conditions

The progestogen component of Drospil is an aldosterone antagonist with potassium sparing properties. In the majority of cases no increases in potassium levels are expected. However, in a clinical study conducted in some patients with mild or moderate renal impairment treated In conjunction with potassium-sparing medicinal products, serum potassium levels appeared slightly, but not significantly, increased during administration of drospirenone. Therefore, it is recommended that serum potassium be monitored during the first course of treatment in patients with renal insufficiency and values basal serum potassium levels in the upper normal range, particularly during concomitant use of potassium-sparing medicinal products. See also section 4.5.

Women with hypertriglyceridaemia or a positive family history of hypertriglyceridaemia may be more at risk of pancreatitis when using COCs.

Although small increases in blood pressure have been reported in women taking COCs, clinically relevant increases in blood pressure are a rare event. Only in these rare cases does the immediate suspension of the use of the combined oral contraceptive appear justified. If, during the use of a COC in the presence of a pre-existing hypertensive state, consistently elevated blood pressure values ​​or a significant increase in blood pressure are observed not responding adequately to antihypertensive treatment, the COC should be discontinued. Where deemed appropriate. , COC use can be resumed if normotensive values ​​are recorded following antihypertensive therapy.

The onset or worsening of the following conditions has been reported both during pregnancy and during the use of COCs, but the evidence of a correlation with COC use is not conclusive: jaundice and / or pruritus related to cholestasis; gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; sydenham's chorea; gestational herpes; hearing loss related to otosclerosis.

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

The presence of acute or chronic liver dysfunction may make it necessary to discontinue use of COCs until markers of liver function return to normal. A recurrence of cholestatic jaundice and / or cholestasis-related pruritus, previously occurring during pregnancy or previous use of sex steroids, necessitates discontinuation of COC use.

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

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

Chloasma may occasionally occur, particularly in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking COCs.

Each pink tablet of this medicine contains 44 mg of lactose monohydrate, and each white tablet contains 89.5 mg of anhydrous lactose. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption who follow a lactose-free diet should take into account this rate introduced by taking the tablet.

Medical examination / consultation

Before initiating or restarting treatment with Drospil, a detailed personal (and family) medical history of the woman should be obtained and an ongoing pregnancy ruled out. Blood pressure should be measured and a complete physical examination should then be undertaken taking into account the contraindications (see section 4.3) and warnings (see section 4.4). & EGRAVE; It is important to draw the woman's attention to information relating to venous or arterial thrombosis, including the risk associated with DROSPIL compared to other CHCs, the symptoms of VTE and ATE, the known risk factors and what to do in the event of a suspected thrombosis. The woman she should be asked to read the package leaflet carefully and follow the suggestions given therein The frequency and type of checks should be based on specific guidelines and adapted to the individual patient.

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 be reduced, for example, in case of forgotten active tablets (see section 4.2), gastrointestinal disturbances while taking active tablets (see section 4.2) or concomitant treatments with other medicinal products ( see section 4.5).

Reduced cycle control

With all COCs, irregular bleeding (spotting or breakthrough bleeding) may occur, particularly in the first months of use. Therefore, the assessment of any irregular blood loss is only meaningful after an adaptation interval of approximately three cycles.

If irregularities persist or occur after previously regular cycles, possible non-hormonal causes should be considered and appropriate diagnostic procedures applied to rule out the presence of malignancy or pregnancy, including curettage.

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

04.5 Interactions with other medicinal products and other forms of interaction -

Note: Information regarding concomitant medications should be consulted to identify potential interactions.

• Influence of other medicines on Drospil

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

Hepatic metabolism

Interactions may occur with drugs that induce liver enzymes, resulting in possible increased clearance of sex hormones (eg phenytoin, barbiturates, primidone, carbamazepine, rifampicin, bosentan) and anti-HIV drugs (eg ritonavir, nevirapine) and possibly also with oxcarbazepine, topiramate, felbamato, griseofulvin and preparations containing St. John's wort (hypericum perforatum). Maximal enzyme induction is generally observed in approximately 10 days but may persist for at least 4 weeks after cessation of drug therapy.

Interference with the enterohepatic circulation

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

Treatment

Women on short-term therapy with any of the above classes of medicines or single active substances (liver enzyme inducing substances) in addition to rifampicin, must temporarily use a barrier method in addition to the combined oral contraceptive, both while taking of the concomitant medicinal product and within 7 days after discontinuation of therapy.

Concomitant treatment with rifampicin requires the adoption of a barrier method in addition to the combined oral contraceptive during the period of taking rifampicin and for 28 days after its discontinuation.

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

Women on concomitant treatment with antibiotics (in addition to rifampicin, see above) should adopt a barrier method within 7 days of stopping treatment.

If concomitant administration of other medicinal products extends beyond the term of the active tablets contained in the COC blister pack, the placebo tablets should be discarded and the next COC blister pack started immediately.

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

• Influence of Drospil on other medicines

Oral contraceptives can interfere with the metabolism of some active ingredients. Consequently, plasma and tissue concentrations may be increased (e.g. cyclosporine) or decreased (e.g. lamotrigine).

Based on in vitro inhibition studies and in vivo interaction studies 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 appears 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 Drospil with aldosterone antagonists or potassium-sparing diuretics did not In this case, serum potassium should be evaluated during the first treatment cycle See also section 4.4.

• Laboratory tests

The use of contraceptive steroids may affect the results of some laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of (transporter) proteins, eg corticosteroid-binding globulin and the lipid / lipoprotein fractions, parameters of glucose metabolism and parameters of coagulation and fibrinolysis. However, these changes generally remain within normal limits. Drospirenone causes an increase in plasma renin and plasma aldosterone activity, induced by its mild antimineralocorticoid activity.

04.6 Pregnancy and breastfeeding -

Pregnancy

Drospil is not indicated during pregnancy.

If pregnancy occurs while taking Drospil, treatment should be stopped immediately. Extensive epidemiological studies have not revealed an increased risk of birth defects in children of women who used COCs prior to pregnancy. nor a teratogenic effect 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 clinical experience with the use of COCs during pregnancy has not provided any evidence of actual adverse effects in humans.

The available data on the use of Drospil during pregnancy are too limited to allow any conclusions to be drawn regarding the adverse effects of Drospil 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 taken into account when DROSPIL is restarted (see sections 4.2. And 4.4).

Breastfeeding

Lactation may be affected by COCs, as they can reduce the quantity and change the composition of breast milk. Therefore, the use of COCs should generally not be recommended until complete weaning. minimal amounts of contraceptive steroids and / or their metabolites may be excreted in breast milk during COC use, with potential effects on the infant.

04.7 Effects on ability to drive and use machines -

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

04.8 Undesirable effects -

The following adverse drug reactions have been reported during use of Drospil.

The table below lists adverse reactions by MedDRA System Organ Class (MedDRA SOC). Frequencies are based on data from clinical studies. The most appropriate MedDRA term was used to describe a specific reaction, its synonyms and related conditions.

Adverse drug reactions that have been associated with the use of Drospil as an oral contraceptive or in the treatment of moderate acne vulgaris according to the MedDRA system organ class and MedDRA terms.

System and organ classification Common (≥1 / 100, Uncommon (≥1 / 1,000 to Rare (≥1 / 10,000, Not known (frequency cannot be estimated from the available data) (MedDRA version 9.1) Infections and infestations Candidiasis Disorders of the blood and lymphatic system Anemia, thrombocytopenia 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, sleepiness Anorgasmia, insomnia Nervous system disorders Headache Dizziness, paraesthesia Vertigo, tremor Eye disorders Conjunctivitis, eye weariness, eye disorders Cardiac pathologies Tachycardia Vascular pathologies Migraine, varicose veins, hypertension Phlebitis, vascular disorders, epistaxis, syncope, venous (VTE) and arterial (ATE) thrombebolism Gastrointestinal disorders Nausea Abdominal pain, vomiting, dyspepsia, flatulence, gastritis, diarrhea Enlarged abdomen, gastrointestinal upset, repletion, gastrointestinal, 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 disturbances, 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 loss

* irregular bleeding usually decreases 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 events have been reported in women taking COCs, and were addressed in chapter 4.4:

• Venous thromboembolic disorders;

• Arterial thromboembolic disorders;

• Hypertension;

• Liver tumors;

• Onset or aggravation of conditions for which the causal relationship with the use of COCs is not definitive: Crohn's disease, ulcerative colitis, epilepsy, uterine myoma, porphyria, systemic lupus erythematosus, gestational herpes, Sydenham's chorea, hemolytic-uremic syndrome, cholestatic jaundice;

• Chloasma;

• Acute or chronic disturbances of liver function may require discontinuation of COC use until liver markers return to normal range;

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

In women taking combined hormonal contraceptives, the frequency of breast cancer diagnosis is only slightly higher. However, since breast cancer is rare in women under 40 years of age, the number of extra cases is modest when compared to the overall risk of breast cancer. The causal relationship 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 -

There is to date no experience of overdose with Drospil. Based on general experience with COCs, symptoms that may occur with overdose of active tablets are: nausea, vomiting and, in young girls, slight vaginal bleeding. No antidotes are available and treatment should 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 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 Drospil is based on the interaction of numerous factors, the most important of which are the inhibition of ovulation and changes in the endometrium.

Drospil is a combined oral contraceptive containing ethinylestradiol and the progestogen 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 pharmacological profile very similar to natural progesterone.

Some indications from clinical studies seem to attest that the weak antimineralocorticoid properties of Drospil result in a mild antimineralocorticoid effect.

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

After six months of treatment, Drospil compared to placebo showed more marked and statistically significant reductions of 15.6% (49.3% vs 33.7%) in inflammatory lesions, 18.5% (40.6% vs 22%). , 1%) of non-inflammatory lesions and 16.5% (44.6% versus 28.1%) of total lesions. In addition, a higher percentage of subjects, equal to 11.8% (18.6% versus 6.8%), reported "smooth" or "almost smooth" skin on the investigator's global static rating scale ( Investigator's Static Global Assessment (ISGA) scale).

05.2 "Pharmacokinetic properties -

Drospirenone

Absorption

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

Distribution

After oral administration, drospirenone serum levels decrease with a terminal half-life of 31 hours.

Drospirenone binds to serum albumin, but not to hormone-binding globulin (SHBG) or corticoid-binding globulin (CBG). Only 3 - 5% of total serum concentrations of the active substance are present in the free steroid form. 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 extensively metabolised. 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 produced without the 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 cytochromes P450 1A1, P450 2C9 and P450 2C19 in vitro.

Elimination

The metabolic clearance of drospirenone in serum is 1.5 ± 0.2 ml / min / kg. Drospirenone is excreted unchanged in trace amounts only. 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 in urine and faeces is approximately 40 hours.

Steady state conditions

During a course of treatment, maximum steady-state 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 terminal 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) appeared comparable to those in women with normal renal function. Serum levels of drospirenone were on average 37% higher in women with moderate renal impairment (CLcr, 30 - 50 mL / min) than in women with normal renal function. Drospirenone treatment was well tolerated by women with mild and moderate renal impairment. Drospirenone treatment did not show any clinically significant effect on serum potassium concentration.

Effect of impaired liver function

In a single dose study conducted in volunteers with moderate hepatic impairment, oral clearance (CL / F) was reduced by approximately 50% compared to that of patients with normal hepatic function. The decline in drospirenone clearance observed in volunteers with moderate hepatic impairment did not translate into an apparent difference in serum potassium concentrations. Even in the presence of diabetes and concomitant treatment with spironolactone (two factors that can predispose a patient to hyperkalaemia), no increase in serum potassium concentrations above the upper limit of normal has been observed. It can therefore be concluded that drospirenone is well tolerated in patients with mild or moderate hepatic impairment (Child-Pugh B).

Ethnic groups

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

Ethinylestradiol

Absorption

Orally taken ethinylestradiol is rapidly and completely absorbed. Maximum serum concentrations of approximately 33 pg / ml are reached within 1-2 hours after single oral administration. Absolute bioavailability is approximately 60%, as a result of a presystemic conjugation and first pass metabolism. Concomitant food intake reduced the bioavailability of ethinylestradiol in about 25% of the subjects tested, while no changes were reported in the others.

Distribution

Serum levels of ethinylestradiol decrease with a biphasic trend and the terminal elimination phase is characterized by a "half-life of about 24 hours." Ethinylestradiol binds strongly but not specifically to "serum albumin (about 98.5%), and induces an increase in serum concentrations of SHBG and corticoid-binding globulin (CBG) An apparent volume of distribution of approximately 5 L / kg was determined.

Biotransformation

Ethinylestradiol is subject to presystemic conjugation both in the mucosa of the small intestine and in the liver. Ethinylestradiol is metabolised primarily by aromatic hydroxylation, by which different types of hydroxylated and methylated metabolites are generated which are present as free metabolites or as serum conjugates of glucuronide or sulfate. The metabolic clearance rate of ethinylestradiol is approximately 5 ml / min / kg.

Elimination

Ethinylestradiol is not significantly eliminated in unchanged form. The metabolites of ethinylestradiol are excreted in the urine and bile at a 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 levels of ethinyl estradiol 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 were limited to those associated with their recognized pharmacological action. In particular, reproductive toxicity studies in animals revealed embryotoxic and foetotoxic effects considered as species-specific. Effects on sexual differentiation were observed in rat fetuses but not monkeys at exposures in excess of those observed in Drospil users.

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:

- 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:

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

Pack sizes:

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 HOLDER OF THE "MARKETING AUTHORIZATION" -

EFFIK ITALIA S.p.A

Via Lincoln 7 / A

20092 Cinisello Balsamo, Milan

08.0 MARKETING AUTHORIZATION NUMBER -

• 041315019 "0.02 MG / 3 MG film-coated tablets" 1 X 28 tablets in PVC / PVDC / AL blister

• 041315021 "0.02 MG / 3 MG film-coated tablets" 3 X 28 tablets in PVC / PVDC / AL blister

• 041315033 "0.02 MG / 3 MG film-coated tablets" 6 X 28 tablets in PVC / PVDC / AL blister

• 041315045 "0.02 MG / 3 MG film-coated tablets 13 X 28 tablets in PVC / PVDC / AL blister

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -

November 2012

10.0 DATE OF REVISION OF THE TEXT -

October 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 -