DROSURELLE - PACKAGE LEAFLET - LEAFLETS

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Drosurelle - Package Leaflet

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

Active ingredients: Ethinylestradiol, Drospirenone

DROSURELLE 0.02 mg / 3 mg film-coated tablets

Why is Drosurelle used? What is it for?

Important things to know about combined hormonal contraceptives (COCs):

They are one of the most reliable reversible methods of contraception when used correctly
They slightly increase the risk of having blood clots in the veins and arteries, especially during the first year of taking or when restarting a combined hormonal contraceptive after a break of 4 or more weeks
Take care and see your doctor if you think you have symptoms of a blood clot (see section 2 "Blood clots")

DROSURELLE is a contraceptive pill, used to prevent pregnancy.

Each tablet contains a small amount of two different female hormones, drospirenone and ethinyl estradiol.

Contraceptive pills that contain two hormones are called "combination" pills.

General notes

Before you start using DROSURELLE 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 start taking DROSURELLE, your doctor will ask you a few questions about your personal health and that of your closest family members. Your doctor will also measure your blood pressure and, depending on your personal situation, may also perform some other tests.

In this leaflet, several situations are described where you should stop taking Drosurelle or where the reliability of Drosurelle may be reduced. In these situations you should not have sex or you should take extra non-hormonal contraceptive precautions, such as using a condom or other barrier method. Do not use the rhythm or basal temperature method. These methods can be unreliable as DROSURELLE alters the monthly changes in body temperature and cervical mucus.

Like other hormonal contraceptives, DROSURELLE does not protect against HIV infections (AIDS) or other sexually transmitted diseases.

Contraindications When Drosurelle should not be used

Do not use DROSURELLE 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 have (or have ever had) liver disease and your liver function is still not normal
if your kidneys are not working well (kidney failure)
if you have (or have ever had) liver cancer
if you have (or have ever had) or if you suspect that you have breast or genital cancer
if you have any unexplained vaginal bleeding
if you are allergic to ethinylestradiol or drospirenone or any of the other ingredients of this medicine (listed in section 6). This may include itching, rash or swelling.

Precautions for use What you need to know before taking Drosurelle

Talk to your doctor or pharmacist before taking DROSURELLE.

When to be especially careful with DROSURELLE

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".

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

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

if a close relative has or has ever had breast cancer
if you have liver or gallbladder disease
if you have diabetes
if she is depressed
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 DROSURELLE;
if you have "inflammation of the veins under the skin (superficial thrombophlebitis);
if you have varicose veins;
if you are epileptic (see "Using DROSURELLE with other medicines")
if you have a disease that first appeared during pregnancy or previous use of sex hormones (for example, hearing loss, a blood disorder called porphyria, rash with blisters during pregnancy (gestational herpes), a disease of the nerves that cause sudden body movements (Sydenham's chorea))
if you have or have ever had chloasma (discolouration of the skin, especially of the face or neck known as "pregnancy spots"). In this case, he must avoid direct sunlight and ultraviolet light.
if you have hereditary angioedema, products that contain estrogen can cause or worsen symptoms. You should see your doctor immediately if you experience symptoms of angioedema such as swelling of the face, tongue and / or throat and / or difficulty in swallowing or hives associated with breathing difficulties.

Blood clots

Using a combined hormonal contraceptive such as DROSURELLE 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 DROSURELLE 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 in 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, reddish or bluish;

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 Drosurelle, the risk of developing a blood clot returns to normal within a few weeks.

What is the risk of developing a blood clot?

The risk depends on your natural risk of VTE and the type of combined hormonal contraceptive you are taking.

The overall risk of developing a blood clot in the leg or lung (DVT or PE) with DROSURELLE 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 DROSURELLE, 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").

Women who are not using a combined hormone pill / patch / ring and who are not pregnant Risk of developing a blood clot in a year 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 DROSURELLE 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 DROSURELLE is low but some conditions will increase the risk. Its risk is greater:

if you are severely overweight (body mass index or BMI over 30 kg / m2);
if a member of your immediate family 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.It may be necessary to stop taking Drosurelle a few weeks before surgery or while you are less mobile. If you need to stop taking DROSURELLE, 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 DROSURELLE should be stopped.

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

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

DROSURELLE and cancer

Breast cancer has a slightly higher incidence in women using combination pills but it is not known whether this is caused by the treatment. For example, more tumors may be detected in women taking combination pills because they are examined more often by their The appearance of breast tumors gradually decreases after stopping the combined hormonal contraceptives It is important to check your breasts regularly and contact your doctor if you feel a lump.

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

Intermenstrual bleeding

During the first few months that you are taking DROSURELLE, you may have unexpected bleeding (bleeding outside the gap week). If this bleeding occurs for more than a few months or if it starts after a few months, the doctor needs to find out what's wrong.

What to do in case of missed menstruation during the gap week

If you have taken all the tablets correctly, have not had severe vomiting or diarrhea and have not taken any other medicines, it is very unlikely that you are pregnant. If your expected period does not appear twice, you may be pregnant.

Contact your doctor immediately. Do not start the next pack until you are sure that you are not pregnant.

Interactions Which drugs or foods can modify the effect of Drosurelle

Always tell your doctor about any medicines or herbal products you are already using. Also tell any other doctor or dentist who prescribes other medicines (or the pharmacist) that you are using DROSURELLE. They can tell you if you need to take other contraceptive precautions (e.g. condoms) and if so, for how long.

Some medicines can make DROSURELLE less effective in preventing pregnancy, or can cause unexpected bleeding. Among them are:

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 blood pressure in the blood vessels in the lungs (bosentan)
the herbal remedy St. John's wort

DROSURELLE may affect the effect of other medicines, such as

medicines containing cyclosporine
the antiepileptic lamotrigine (thus causing an increase in the frequency of seizures)

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

DROSURELLE with food and drink

DROSURELLE can be taken with or without food, if needed with a small amount of water.

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

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

Ask your doctor or pharmacist for advice before taking any medicine

Feeding time

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

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

Driving and using machines

There is no information to suggest that the use of DROSURELLE affects driving or use of machines.

Important information about some of the ingredients of DROSURELLE

DROSURELLE contains lactose.

If you have been told by your doctor that you have an "intolerance to some sugars, contact your doctor before taking this medicinal product.

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

Take one DROSURELLE tablet a day, if needed with a small amount of water. You can take the tablets with or without food but should take them at about the same time each day.

The pack contains 21 tablets. Next to each tablet is printed the day of the week on which it should be taken. For example, if you start on a Wednesday, take a tablet with "WED" next to it. Follow the direction of the arrow on the pack until you have taken all 21 tablets.

Then do not take any tablets for 7 days. During these 7 tablet-free days (also called a stop or gap week) your period should begin. This so-called "withdrawal bleed" usually begins on the 2nd or 3rd day of the gap week.

On the 8th day after the last DROSURELLE tablet (ie after the 7-day interval), you must start a new pack, even if your period is not over. This means that you must start each pack on the same day of the week and that your period must occur on the same days of the month.

If you use DROSURELLE in this way, you will be protected from pregnancy even during the 7 days that you are not taking any tablets.

When can the first blister pack start?

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

Start taking DROSURELLE on the first day of your period (which is the first day of your period). If you start taking DROSURELLE on the first day of your period, the protection against pregnancy is immediate. You can also start between the second and fifth day of your period but you must use additional protective measures (eg a condom) for the first 7 days.

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

You can start taking DROSURELLE preferably the day after the last active tablet (the last tablet containing active ingredients) of the previous pill and at the latest the day after the pill-free interval of the previous pill (or after the last inactive tablet. of the previous pill) If you previously used a vaginal ring or a combined contraceptive patch, follow your doctor's advice.

Changing from a progestogen-only preparation (progestogen-only minipill, injection, implant, or progestogen-releasing IUD).

You can switch from the progestogen-only pill on any day (from an implant or IUD on the day of its removal, from an injectable when the next injection is due) but in all these cases use additional protective measures ( e.g. a condom) for the first 7 days of taking the tablets.

After an abortion

Follow your doctor's advice.

After giving birth

You can start taking DROSURELLE between the 21st and 28th day after giving birth. If you start after the 28th day, use a so-called barrier method (for example a condom) during the first seven days of using DROSURELLE

If, after giving birth, you have had sexual intercourse before starting DROSURELLE, make sure you are not pregnant or wait until your next period.

If you are breast-feeding and want to (re) start taking DROSURELLE after having a baby.

Read the section on "Breastfeeding".

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

Overdose What to do if you have taken too much Drosurelle

No serious harmful effects have been reported from taking too many DROSURELLE tablets

If you take several tablets at the same time, you may feel sick or vomit. Young girls may have vaginal bleeding.

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

If you forget to take DROSURELLE

If less than 12 hours have passed since the time of usual intake, the protection against pregnancy is not reduced. Take the tablet as soon as you remember and then carry on with the following tablets at the usual time.
If more than 12 hours have passed since the time of usual intake, the protection against pregnancy may be reduced. The greater the number of tablets forgotten, the greater the risk of becoming pregnant.

The risk that the protection against pregnancy is incomplete is greater if you forget to take a tablet at the beginning or at the end of the pack. You should therefore observe the following rules (see diagram below):

More than one tablet forgotten in one pack

Consult your doctor.

One tablet forgotten in the first week

Take the tablet as soon as you remember, even if that means taking two tablets at the same time. Continue to take the tablets at the usual time and use extra precautions for the next 7 days, such as a condom. If you had sex in the week before you forgot, you may have become pregnant. In this case, consult your doctor.

One tablet forgotten in the second week

Take the tablet as soon as you remember, even if that means taking two tablets at the same time. Continue to take the tablets at the usual time. The protection against pregnancy is not reduced and you do not need to take additional precautions.

One tablet forgotten in the third week

You can choose between two alternatives:

1. Take the tablet as soon as you remember, even if that means taking two tablets at the same time. Continue taking the tablets at the usual time. Instead of starting the tablet-free period, start the next pack.

Most likely a period will appear at the end of the second pack but there may be a "light or menstruation-like bleeding" during the second pack.

2. You can also stop taking your tablets and go straight to the 7-day tablet-free period (record the day you forgot to take your tablet). If you want to start a new pack on the day you usually start it, make it last the tablet-free period less than 7 days.

If you follow either of these two recommendations, the protection against pregnancy will not be reduced.

If you have forgotten any of the tablets in a pack and you do not have a period during the first tablet-free period, you may have become pregnant. Consult your doctor before starting a new pack.

What to do in case of vomiting or severe diarrhea

If you vomit or have severe diarrhea within 3-4 hours after taking a tablet, there is a risk that the active ingredients of the pill have not been completely absorbed into your body. It is as if you have forgotten to take a tablet. vomiting or diarrhea, take another tablet from a reserve strip as soon as possible. If possible, take it within 12 hours of when you usually take the pill. If this is not possible or if it has been more than 12 hours, follow the advice given in the section "If you forget to take DROSURELLE".

To delay menstruation: what you need to know

Although it is not recommended, you can delay your period by switching directly to a new pack of DROSURELLE instead of taking a tablet-free interval, and finishing that pack. You may experience light or menstruation-like bleeding while taking the second pack. After the usual 7-day tablet-free interval, start the new pack.

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

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

If you take the tablets according to the instructions, your period will start during the tablet-free week. If you need to change the day, reduce the number of tablet-free days (but never increase it, 7 is the maximum!). For example, if your tablet-free interval usually starts on a Friday and you want to move that day to Tuesday (3 days earlier), start a new pack 3 days earlier than usual. days or less) you may not have a period during these days. You may experience a "light or menstruation-like bleeding."

If you are not sure how to do this, consult your doctor.

If you want to stop treatment with DROSURELLE

You can stop treatment with DROSURELLE when you want. 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 Drosurelle and wait for a period before trying to get pregnant. You will be able to calculate your due date more easily.

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

Side Effects What are the side effects of Drosurelle

Like all medicines, DROSURELLE 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 Drosurelle, 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 DROSURELLE".

The following is a list of side effects that have been related to the use of DROSURELLE.

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

mood changes
headache
abdominal pain (stomach pain)
acne
breast pain, breast enlargement, breast tenderness, painful or irregular periods
weight gain

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

Candida (fungal infection)
herpes simplex
allergic reactions
increased appetite
depression, nervousness, sleep disturbances
tingling sensation, dizziness
vision problems
irregular heartbeat or unusually high heart rate
high blood pressure, low blood pressure, migraine, varicose veins
sore throat
nausea, vomiting, inflammation of the stomach and / or intestines, diarrhea, constipation
sudden swelling of the skin and / or mucous membranes (e.g. tongue and throat) and / or difficulty in swallowing or hives associated with difficulty in breathing (angioedema), hair loss (alopecia), eczema, itching, rash, dryness of the skin, oily skin (seborrheic dermatitis)
neck pain, pain in limb, muscle cramps
bladder infection
breast lumps (benign and malignant), milk production in the absence of pregnancy (galactorrhea), ovarian cysts, hot flashes, no menstruation, very heavy periods, vaginal discharge, vaginal dryness, pain in the lower abdomen (pelvis), smear abnormal cervical (Papanicolaou test or Pap test), decreased sexual desire
fluid retention, lack of energy, excessive thirst, increased sweating
weight loss

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

asthma
impaired hearing
erythema nodosum (characterized by painful reddish skin nodules)
erythema multiforme (rash with redness or "target" blisters)
harmful blood clots in a vein or artery, for example:
in a leg or foot (DVT)
in one lung (PE)
heart attack
stroke
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).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse

By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

Keep DROSURELLE out of the reach and sight of children.

This medicine does not require any special storage conditions.

Expiration date

Do not use DROSURELLE after the expiry date which is stated on the package after "Use by:" or "EXP".

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

What DROSURELLE contains

The active ingredients are 0.02 mg ethinylestradiol and 3 mg drospirenone.

The excipients are:

Tablet core: lactose monohydrate, pregelatinised starch (maize), povidone, croscarmellose sodium, polysorbate 80, magnesium stearate.

Coating: partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172).

Description of what DROSURELLE looks like and contents of the pack

The tablets are pink, round, film-coated.

DROSURELLE is available in packs of 1, 2, 3, 6 and 13 blisters, each containing 21 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 Drosurelle can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on the ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical data of 06.0 PHARMACEUTICAL PARTICULARS 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 HOLDER OF THE ALL AUTHORIZATION "PLACING ON MARKETING 08.0 AUTHORIZATION NUMBER" PLACING ON MARKET09.0 DATE OF PR IMA 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 RADIOPharmaceuticals, ADDITIONAL DETAILED INSTRUCTIONS ON ESTEMPORAN PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

DROSURELLE 0.02 MG / 3MG

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

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

Excipient: lactose monohydrate 44 mg.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Film-coated tablet.

Pink, round, film-coated tablets.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Oral contraception

The decision to prescribe DROSURELLE should take into account the individual woman's current risk factors, particularly those relating to venous thromboembolism (VTE) and the comparison between the risk of VTE associated with Drosurelle 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 DROSURELLE

The tablets should be taken at approximately the same time each day, if needed with a small amount of liquid, in the order shown on the blister pack. One tablet must be taken daily for 21 consecutive days. Subsequent packs should be started after a 7-day tablet-free interval, during which a withdrawal bleed usually occurs. It usually starts 2-3 days after the last tablet and may not have finished at the start of the next pack.

How to start taking DROSURELLE

• No hormonal contraceptive used in the previous month

Taking the tablets should start on the 1st day of the woman's natural cycle, ie the first day of menstruation.

• Changing from a combined hormonal method of contraception (combined oral contraceptive vaginal ring or transdermal patch)

DROSURELLE should preferably be started on the day following the last active tablet (the last tablet containing the active ingredients) of the previous combined oral contraceptive, and at the latest on the day following the end of the usual tablet-free or tablet-free interval. placebo of the previous oral contraceptive. If a vaginal ring or transdermal patch has been used, DROSURELLE should preferably be started on the day of removal and at the latest when the next application would have been scheduled.

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

Switching from the progestogen-only pill can be done on any day (from an implant or IUS on the day of its removal, from an injectable product when the next injection would be expected) but in all these cases the woman must use in addition a barrier method for the first 7 days of tablet-taking.

• After a first trimester abortion

You can start taking it immediately. In this case you do not need to take any additional contraceptive measures.

• After childbirth or an abortion in the second trimester

Intake should begin between day 21 and 28 after delivery or after an abortion in the second trimester. If starting later, a barrier method should be used additionally for the first 7 days. If intercourse has occurred in the meantime, pregnancy must be ruled out or the first menstruation must be awaited before actually starting the COC.

For breastfeeding women, see section 4.6.

Management of forgotten tablets

If less than 12 hours have passed since the time of usual taking of any tablet, contraceptive protection is not reduced. The woman should take the tablet as soon as she remembers and should continue taking the other tablets at the usual time.

If more than 12 hours have passed since the time of usual taking of any tablet, contraceptive protection may 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 7 days

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

In daily practice we can therefore recommend the following:

• Week 1

Take the last forgotten tablet as soon as you remember, even if that means taking two tablets at the same time. Continue taking your tablets at the usual time. Use an additional barrier method such as a condom for the next 7 days. If you have had sexual intercourse in the previous 7 days, there is a possibility that you have become pregnant. The greater the number of tablets forgotten and the closer this is to the usual tablet-free range, the higher the risk of pregnancy.

• Week 2

Take the last forgotten tablet as soon as you remember, even if that means taking two tablets at the same time. Continue taking your tablets at the usual time. If the tablets have been taken correctly in the 7 days preceding the first missed tablet, no additional contraceptive precautions need to be used. If 2 or more tablets have been missed, additional precautions should be taken for 7 days.

• Week 3

The risk of reduced reliability is greater as the 7-day tablet-free interval approaches. By changing your tablet intake, you can still prevent the reduction of contraceptive protection. If you adhere to one of the following two options, it is therefore not necessary to use additional contraceptive precautions provided that in the 7 days preceding the first missed tablet, all tablets have been taken correctly. If not, the first of these two options should be followed and additional precautions should be used for the next 7 days.

1. Take the last forgotten tablet as soon as you remember, even if that means taking two tablets at the same time. Continue taking your tablets at the usual time. The next pack should start as soon as the current pack is finished, ie there should be no gap between the two packs. A withdrawal bleed is unlikely until the second pack is finished but spotting or breakthrough bleeding may occur in days taking the tablets.

2. You can also stop taking the tablets from the current blister. You should then practice a tablet-free interval of 7 days, including the days on which tablets have been missed, and continue with the next pack thereafter.

If you forget to take one or more tablets and subsequently do not experience a withdrawal bleed during the first normal tablet-free interval, it is possible that you are pregnant.

Advice in case of gastrointestinal disorders

In case of severe gastrointestinal disturbances (eg vomiting or diarrhea), absorption may not be complete and additional contraceptive measures should be taken. If vomiting occurs within 3-4 hours after taking a tablet, a new (replacement) tablet as soon as possible. The new tablet should be taken, if possible, within 12 hours of the usual time of intake. If more than 12 hours have elapsed, the advice on forgotten tablets provided in section 4.2 "Management of missed tablets" applies. if you wish to change your normal tablet-taking schedule, you must / must take the additional tablet (s) from another pack.

How to postpone a "withdrawal bleed."

To delay menstruation, a new pack of DROSURELLE should be started and the tablet-free interval should not be used. The delay can be extended as long as desired until the second pack is finished. During this prolongation, breakthrough bleeding or spotting may occur. L Regular intake of DROSURELLE is then resumed at the end of the normal 7-day tablet-free interval.

To shift your period to another day of the week than expected with your schedule, you can shorten your next tablet-free interval by as many days as you like. The shorter the interval, the greater the risk that you will not have a withdrawal bleed and instead experience breakthrough bleeding and spotting during the next pack (such as when you delay your period).

04.3 Contraindications

Combined hormonal contraceptives (COCs) should not be used in the following conditions. If any of these conditions appear for the first time while using a COC, you should stop taking them 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

• Present or previous severe liver disease up to normalization of liver function values

• Severe renal failure or acute renal failure

• Past or present liver tumors (benign or malignant)

• Known or suspected malignancies sensitive to sex steroids (such as those of the genital organs or breasts)

• Vaginal bleeding of unknown origin

• Hypersensitivity to the active substances or to any of the excipients listed in sections 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 DROSURELLE 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 Drosurelle should be discontinued.

• 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 Drosurelle 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 Drug. 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.

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).

DROSURELLE 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. Especially 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 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 DROSURELLE 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, haemolytic 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 of 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). DROSURELLE 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

In case of anticoagulant therapy, an adequate alternative method of contraception should be started due to the teratogenicity of the therapy (coumarins).

• Tumors

An increased risk of cervical cancer in long-term users of COCs (> 5 years) has been reported in some epidemiological studies, but there continues to be controversy over the extent to which this is attributable to the confounding effects of sexual behavior and other factors such as the human papilloma virus (HPV).

A meta-analysis of 54 epidemiological studies reported that the relative risk of being diagnosed with breast cancer is slightly higher (RR = 1.24) in women using COCs. This increased risk gradually disappears during the 10 years following discontinuation of their use. Breast cancer is rare in women under the age of 40 so the greatest number of cases diagnosed in women who use or have recently used oral contraceptives COCs is low compared to the overall risk of this cancer. These studies do not provide evidence of causality. The increased risk observed in COC users may be due to earlier diagnosis, biological effects of COCs or a combination of the two Breast cancers diagnosed in COC users tend to be less clinically advanced than those diagnosed in COC users.

In rare cases in COC users. benign liver tumors and in even rarer cases malignant liver tumors have been reported. In isolated cases, these tumors have resulted in life-threatening intra-abdominal haemorrhages. In women taking COCs. liver tumors should be considered in the differential diagnosis of severe upper abdominal pain, liver enlargement, or signs of intra-abdominal haemorrhage.

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

• Other conditions

The progestogen component of DROSURELLE 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 or moderate renal impairment and concomitant use of potassium-sparing medicinal products, serum potassium levels increased slightly, but not significantly, while taking drospirenone. It is therefore recommended to verify the serum potassium level during the first treatment course in patients with renal insufficiency and pretreatment serum potassium values in the upper reference range, particularly during concomitant use of potassium-sparing medicinal products. See also section 4.5.

Women with hypertriglyceridaemia or a family history of this disease may have an 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 hypertensive treatment, the COC should be discontinued. If appropriate, use of the COC should be discontinued. COC may be resumed if normal values can be achieved with antihypertensive therapy.

Occurrence or worsening of the following conditions has been reported during pregnancy and during COC use, but there is no conclusive evidence of an association with COC use: jaundice and / or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea; gestational herpes; hearing loss due to 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 use until markers of liver function return to normal. with sex steroids, requires discontinuation of combined oral contraceptives.

Although COCs may affect peripheral insulin resistance and glucose tolerance, there is no evidence for the need to change the treatment regimen in diabetic women using low-dose COCs (containing COCs).

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

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

This medicinal product contains 44 mg of lactose per tablet. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should take this amount into consideration.

Medical examinations / visits

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

Reduction of effectiveness

The efficacy of COCs may be reduced, for example, in the case of forgotten tablets (see section 4.2), in case of gastrointestinal disturbances (see section 4.2) or concomitant use of other medicinal products (see section 4.5).

Reduction of cycle control

With all COCs, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. The evaluation of any irregular bleeding therefore only has significance after an adaptation period of approximately three cycles.

If irregularities persist or occur after previously normal cycles, non-hormonal causes should be considered and adequate diagnostic measures are needed to rule out malignancy or pregnancy. Such measures may include a curettage.

In some women, "withdrawal bleeding" may not occur during the tablet-free interval. If the COC has been taken according to the directions described in section 4.2, it is unlikely that the woman is pregnant. However, if the COC has not been taken according to these indications before the first missed withdrawal bleed or if two withdrawal bleeds are 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: The prescribing information for concomitant medications should always be consulted to identify potential interactions.

• Influence of other medicines on DROSURELLE

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, which can cause increased elimination of sex hormones (eg phenytoin, barbiturates, primidone, carbamazepine, rifampicin, bosentan, HIV drugs (eg ritonavir, nevirapine ), possibly also oxcarbazepine, topiramate, felbamato, griseofulvin and products containing the herbal remedy St. John's wort (hypericum perforatum).

Maximal enzyme induction is usually seen after approximately 10 days but can be maintained for at least 4 weeks after discontinuation of drug therapy.

Interference with the enterohepatic circulation

Cases of contraceptive failure have been reported with some antibiotics, such as penicillins and tetracyclines. The mechanism of this effect has not been elucidated.

Management

Women who are taking a medicine belonging to the above mentioned classes for short periods or single active substances (medicines that induce liver enzymes) other than rifampicin must temporarily use a barrier method in addition to the combined oral contraceptive, i.e. during the period of concomitant administration. of the medicine and for 7 days after its discontinuation.

Women taking rifampicin must use a barrier method in addition to the combined oral contraceptive during the rifampicin administration period and for 28 days after its discontinuation.

In women who take active substances that induce liver enzymes for long periods, the use of another reliable non-hormonal method of contraception is recommended.

Women being treated with antibiotics (in addition to rifampicin, see above) should use the barrier method for up to 7 days after stopping treatment.

If concomitant administration of other medicinal products extends beyond the term of the tablets in the COC blister pack, the next COC blister pack should be started and the normal tablet-free interval should not be practiced.

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

• Influence of DROSURELLE on other medicines

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

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

• Other interactions

In patients with renal insufficiency, concomitant use of drospirenone and ACE inhibitors or NSAIDs did not show significant effects on serum potassium. The concomitant use of DROSURELLE and aldosterone antagonists or potassium-sparing diuretics has not been studied. in this case, serum potassium should be evaluated during the first treatment cycle See also section 4.4.

• Laboratory analysis

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 (transport) proteins, such as corticosteroid-binding globulin and lipid fractions / lipoprotein, carbohydrate metabolism parameters, and coagulation and fibrinolysis parameters. Variations are usually within the normal laboratory range. Drospirenone causes an increase in plasma renin and plasma aldosterone activity, induced by its mild antimineralocorticoid action.

04.6 Pregnancy and lactation

Pregnancy

DROSURELLE is not indicated during pregnancy.

If pregnancy occurs during use of DROSURELLE the medicinal product must be discontinued immediately. Extensive epidemiological studies have not revealed either an increased risk of birth defects in children born to women who used COCs prior to pregnancy or an effect. teratogenic when COCs were taken involuntarily during pregnancy.

Animal studies have shown undesirable effects during pregnancy and lactation (see section 5.3). Based on these animal data, undesirable effects due to the hormonal action of the active substances cannot be excluded. General experience with COCs during pregnancy, however, did not provide evidence of any actual undesirable effects in humans.

The available data regarding the use of DROSURELLE during pregnancy are too limited to allow conclusions on the adverse effects of DROSURELLE on pregnancy, fetal or newborn health. No relevant epidemiological data are currently available.

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

Feeding time

Lactation may be influenced by COCs as they can reduce the quantity and change the composition of breast milk. The use of COCs is therefore generally not recommended until the mother has weaned the baby completely. Small amounts of the contraceptive steroids and / or their metabolites may be excreted in the 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 ability to drive and use machines have been observed in COC users.

04.8 Undesirable effects

For serious undesirable effects in COC users see section 4.4.

The following undesirable effects have been reported during use of DROSURELLE.

The table below lists undesirable effects by MedDRA System Organ Class (MedDRA SOC). Frequencies are based on clinical trial data.

System and organ classification Frequency of undesirable effects Common ≥1 / 100 y Uncommon ≥1 / 1,000 to Rare ≥10,000 y Infections and infestations Candidiasis, Herpes simplex Disorders of the immune system Allergic reaction Asthma Metabolism and nutrition disorders Increased appetite Psychiatric disorders Emotional instability Depression, nervousness, sleep disturbances Nervous system disorders Headache Paresthesia, dizziness Ear and labyrinth disorders Hypoacusis Eye disorders Visual disturbance Cardiac pathologies Extrasystole, tachycardia Vascular pathologies Hypertension, hypotension, migraine, varicose veins Venous and arterial thromboembolism Respiratory, thoracic and mediastinal disorders Pharyngitis Gastrointestinal disorders Abdominal pain Nausea, vomiting, gastroenteritis, diarrhea, gastrointestinal disturbances stipsim Skin and subcutaneous tissue disorders Acne Angioedema, alopecia, eczema, pruritus, rash, dry skin, seborrhea, skin disorders Erythema nodosum, erythema multiforme Musculoskeletal and connective tissue disorders Neck pain, pain in extremities, muscle cramps Renal and urinary disorders Cystitis Diseases of the reproductive system and breast Breast pain, breast enlargement, breast tenderness, dysmenorrhea, metrorrhagia Breast cancer, fibrocystic breast, galactorrhea, ovarian cysts, hot flashes, menstrual disturbances, amenorrhea, menorrhagia, vaginal candidiasis, vaginitis, vaginal discharge, vulvovaginal disorders, vaginal dryness, pelvic pain, suspected pap test, decreased libido General disorders and administration site conditions Edema, asthenia, pain, excessive thirst, increased sweating Diagnostic tests Weight gain Weight reduction

The most appropriate MedDRA term is used to describe a particular reaction, its synonyms and related conditions.

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 undesirable effects have been reported in women using COCs and are discussed in section 4.4 Special warnings and precautions for use:

• Venous thromboembolic disorders

• Arterial thromboembolic disorders

• Hypertension

• Liver tumors

• Presence or aggravation of conditions whose correlation with the use of COCs is not proven: Crohn's disease, ulcerative colitis, epilepsy, migraine, uterine myoma, porphyria, systemic lupus erythematosus, gestational herpes, Sydenham's chorea, haemolytic syndrome uremic, cholestatic jaundice

• Chloasma

• Acute or chronic disturbances of liver function may require discontinuation of COC use until markers of liver function normalize

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

The frequency of breast cancer diagnosis is slightly higher among oral contraceptive users. Breast cancer is rare in women under the age of 40 so the increase is small compared to the overall risk of breast cancer. The correlation with the use of COCs is unknown. For more 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 https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

04.9 Overdose

To date, there is no experience of overdose with DROSURELLE. Based on general experience with COCs, the symptoms that may occur in this case are: nausea, vomiting and, in young girls, slight vaginal bleeding. There is no antidote 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: 0.11 (two-tailed upper 95% confidence limit: 0.60).

Overall Pearl Index (method failure + patient error): 0.31 (two-sided upper 95% confidence limit: 0.91)

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

DROSURELLE is a combined oral contraceptive with ethinylestradiol and the progestin drospirenone. At the therapeutic dose, drospirenone also possesses antiandrogenic properties and mild antimineralocorticoid properties. It has no estrogenic, glucocorticoid and antiglucocorticoid activity. This gives drospirenone a pharmacological profile that closely resembles that of natural progesterone.

There are indications from clinical studies that the mild antimineralocorticoid properties of DROSURELLE would result in a mild antimineralocorticoid effect.

05.2 "Pharmacokinetic properties

Drospirenone

Absorption

Drospirenone administered orally is absorbed rapidly and almost completely. The maximum concentrations of the active principle in the serum, equal to about 38 ng / ml, are reached 1-2 hours after ingestion. The bioavailability is between 76 and 85%. Concomitant ingestion of food has no effect on the bioavailability of drospirenone.

Distribution

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

Drospirenone is bound 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 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.

Metabolism

Drospirenone is extensively metabolised after oral administration. The major metabolites in plasma are the acid form of drospirenone, generated by the lactone ring opening, and 4,5-dihydro-drospirenone-3-sulfate, both 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 metabolic clearance rate of drospirenone in serum is 1.5 ± 0.2 ml / min / kg. Drospirenone is excreted in trace amounts in unchanged form. The metabolites of drospirenone are excreted in the faeces and urine at a ratio of approximately 1.2 to 1.4. The half-life of metabolite excretion with urine and faeces is approximately 40 hours.

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 levels of drospirenone accumulate by a factor of approximately 3 as a consequence of the relationship between terminal half-life and dose range.

Special populations

Effect of impaired renal function

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

Effect of impaired liver function

In a single dose study, oral clearance (CL / F) was reduced by approximately 50% in volunteers with moderate hepatic impairment compared to those with normal hepatic function. The reduction in drospirenone clearance observed in volunteers with moderate hepatic impairment does not translate into apparent differences 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 the normal range was observed. It can be concluded that drospirenone it is well tolerated in patients with mild to 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 administered ethinylestradiol is rapidly and completely absorbed. Peak serum concentrations of 33 pg / ml are achieved within 1-2 hours of a single oral administration. Absolute bioavailability, resulting from presystemic conjugation and metabolism of first pass, it is about 60%. Concomitant food intake reduced the bioavailability of ethinylestradiol in about 25% of the subjects studied while in the others no change was observed.

Distribution

Serum ethinylestradiol levels decrease in two phases and 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 of approximately 5 L / kg was determined.

Metabolism

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

Elimination

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

Steady state conditions

Steady-state conditions are achieved during the second half of a treatment cycle and serum levels of ethinylestradiol accumulate by 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 known pharmacological action. In particular, reproductive toxicity studies revealed embryotoxic and foetotoxic effects in animals, considered to be species specific. Effects on sexual differentiation were observed in rat but not monkey fetuses at exposure levels above those of Drosurelle users.