ARIANNA - BIRTH CONTROL PILL - PACKAGE LEAFLET - LEAFLETS

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Arianna - Birth Control Pill - Package Leaflet

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

Active ingredients: Gestodene, Ethinylestradiol

ARIANNA 60 micrograms / 15 micrograms, film-coated tablets

Why is Arianna - Contraceptive Pill used? What is it for?

ARIANNA is an oral contraceptive pill, used to prevent pregnancy.
Each of the 24 pale yellow tablets contains a small amount of two different female hormones, gestodene and ethinyl estradiol.
The 4 white tablets do not contain active substances and are called "placebo tablets".
Contraceptive pills that contain two hormones are called "combination" pills.

Contraindications When Arianna - Contraceptive Pill should not be used

Do not use ARIANNA 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 an allergy (hypersensitivity) to one of the active substances (gestodene or ethinyl estradiol) or to any of the other ingredients of this medicine (the list of excipients is given in section 6).
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 a clot in the arteries:
- severe diabetes with blood vessel injury
- very high blood pressure
- very high level of fat (cholesterol or triglycerides) in the blood
If you have (or have ever had) a type of migraine called "migraine with aura";
If you have (or have ever had) heart or blood vessel disease, especially: - a heart rhythm or heart valve disorder; - disease of certain blood vessels of the heart (coronary).
If you have (or have ever had) a benign tumor (called focal nodular hyperplasia or hepatic adenoma) or liver malignancy or if you have recently had liver disease. In these cases, your doctor will ask you to stop taking the tablets until your liver functions normally.
If you have vaginal bleeding of unknown cause.
If you have breast cancer or cancer of the womb or cancer that is sensitive to female sex hormones, or if you suspect you have any of these cancers.

Precautions for use What you need to know before taking Arianna - Contraceptive Pill

General notes

You should read the information on blood clots in section 2 before you start using MIA. It is especially important that you read the symptoms of a blood clot (see section 2 "Blood clots"). Before starting to take ARIANNA, your doctor will ask you some questions about your personal and family medical history. Your doctor will also measure your blood pressure and, depending on your personal situation, may also carry out other tests. This leaflet describes various situations that require the suspension of ARIANNA or in which the reliability of ARIANNA can be reduced. In such situations it is necessary to abstain from sexual intercourse or to adopt other non-hormonal contraceptive measures, such as the use of condoms or others. barrier methods. Do not use the rhythm or basal temperature method. In fact, these methods can be unreliable, because ARIANNA alters the monthly changes in body temperature and cervical mucus.

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

Interactions Which drugs or foods can modify the effect of Arianna - Contraceptive Pill

Always tell your doctor what medicines or herbal products you are already taking, including medicines bought without a prescription.

Also tell any other doctor or dentist who prescribes medicine (or the pharmacist who sells it to you) that you are using ARIANNA.

They can tell you if you need to use extra contraceptive precautions (such as a condom) and, if so, for how long.

Some medicines can reduce the effectiveness of ARIANNA in preventing pregnancy or can cause unexpected bleeding. These include:

Medicines used to treat:
- HIV infections (ritonavir)
- epilepsy (e.g. phenobarbital, phenytoin, primidone, carbamazepine or topiramate)
- some infections (e.g. rifabutin, rifampicin, griseofulvin, ampicillin, or tetracycline)
- sleep disturbances (modafinil)
The remedy made from St. John's wort, which is used to treat some types of depression.

Troleandomycin, given concomitantly with COCs, may increase the risk of intrahepatic cholestasis (retention of bile in the liver).

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

Pregnancy

If you are pregnant, your doctor has no reason to prescribe contraception. If you discover that you are pregnant while taking ARIANNA, stop taking this pill and consult your doctor. If you are planning to become pregnant, tell your doctor. Ask your doctor or pharmacist for advice before taking any medicine.

Feeding time

It is not recommended to use ARIANNA if you are breastfeeding.

If you wish to breastfeed, your doctor will recommend a suitable form of contraception.

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

Important information about some of the ingredients of ARIANNA

ARIANNA contains lactose. If you suffer from intolerance to some sugars, consult your doctor before taking ARIANNA.

Warnings It is important to know that:

When should you see a doctor?

Contact a doctor urgently

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

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

In some situations it is necessary to pay particular attention to the use of ARIANNA or other combined hormonal contraceptives and it may be necessary to undergo regular medical examinations.

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

If this condition appears or worsens while you are using ARIANNA you must inform your doctor.

if your blood tests have shown that you have a high level of sugar, a high level of cholesterol or a high level of prolactin (hormone that stimulates milk production);
if you are obese;
if you have benign breast cancer or a close relative who has had breast cancer;
if you have uterine disease (uterine dystrophy);
if you have Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease);
if you have systemic lupus erythematosus (SLE, a disease that affects the natural defense system);
if you have haemolytic uremic syndrome (HUS, a blood clotting disorder causing kidney failure);
if you have sickle cell anemia (an inherited disease of the red blood cells);
if you have high levels of fat in the blood (hypertriglyceridaemia) or a "positive family history of this condition." Hypertriglyceridaemia has been associated with an increased risk of developing pancreatitis (inflammation of the pancreas);
if you are going to have an "operation or if you are going to lie down for a long time (see section 2" Blood clots ");
if you have just given birth, your risk of developing blood clots is higher. Ask your doctor how long after having a baby you can start taking ARIANNA;
if you have "inflammation of the veins under the skin (superficial thrombophlebitis);
if you have varicose veins.
if you or a close relative (parents, grandparents, brothers, sisters) have ever suffered from a disease with a tendency to develop blood clots (in the legs, lungs or elsewhere; heart attack; stroke);
if you suffer from epilepsy (see also "Taking other medicines");
if you suffer from migraines;
if you have hearing loss due to a disease known as otosclerosis;
if you suffer from asthma;
if during pregnancy, or while using another contraceptive pill, you have had a skin disease which caused itching, red spots and blisters (herpes gestationis);
if you have ever had spots on your face (chloasma) during pregnancy or while using another contraceptive pill. In this case, avoid direct exposure to sunlight while using ARIANNA;
if you suffer from gallstones;
if you have heart, liver or kidney disease;
if you suffer from depression;
if you have high blood pressure;
if you suffer from a disease known as 'chorea' characterized by involuntary, irregular and sudden movements.

If you have hereditary angioedema, products containing estrogen can induce or worsen the symptoms of angioedema. You should see your doctor immediately if you experience symptoms of angioedema, such as swelling of the face, tongue and / or pharynx and / or difficulty in swallowing or hives accompanied by breathing difficulties.

Do not hesitate to ask your doctor or pharmacist for advice if you have any questions about the use of ARIANNA.

BLOOD CLOTS

Using a combined hormonal contraceptive such as ARIANNA 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 ARIANNA 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)

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 MIA, 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 ARIANNA 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 that contains gestodene, such as ARIANNA, about 9-12 will develop a blood clot in a year.
The risk of a blood clot forming depends on your medical history (see under "Factors that increase the risk of a blood clot forming").

Risk of developing a blood clot in one year Women who are not using a combined hormone pill / patch / ring and who are not pregnant About 2 out of 10,000 women Women using a combined hormonal contraceptive pill containing levonorgestrel, norethisterone or norgestimate About 5-7 out of 10,000 women Women who use ARIANNA 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 ARIANNA is low but some conditions cause it to increase. Its risk is greater:

if you are severely overweight (body mass index or BMI over 30 kg / m2);
if a close relative has had a blood clot in the leg, lung or other organ at a young age (less than about 50 years). In this case you could have an inherited blood clotting disorder;
if you are going to have an operation or if you have to lie down for a long time because of an injury or illness or if you have a leg in a cast. You may need to stop taking ARIANNA a few weeks before surgery or during in which you are less mobile. If you have to stop taking ARIANNA, 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 to have you stop taking ARIANNA. If any of the above conditions change while you are using ARIANNA, 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 ARIANNA is very low but can increase:

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

ARIANNA and cancer

Breast cancer has been observed slightly more frequently in women using combination pills, but it is not known whether this is caused by the pill. It may be that these women were simply seen more thoroughly and more often and that breast cancer was detected earlier. In women who use combination pills for a relatively long period of time, studies have reported cases of cervical cancer. It is currently unknown whether this is caused by the pill or is attributable to sexual behavior (eg more frequent changes in partner) and other factors.

In rare cases, benign liver tumors and, even more rarely, malignant liver tumors have been reported in women using the Pill. If you experience unusually severe abdominal pain, contact your doctor.

Intermenstrual bleeding

Unexpected bleeding (bleeding outside the days on which you are taking the placebo tablets) may occur during the first months of taking ARIANNA. If this bleeding occurs for more than a few months, or begins after a few months, the doctor must investigate the cause.

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

If you have taken all the active pale yellow tablets correctly, have not had severe vomiting or diarrhea, and have not taken any other medications, it is very unlikely that you are pregnant. If your period does not appear twice in a row, you may be pregnant. Contact your doctor immediately. Do not start the next strip until you are sure you are not pregnant.

Dose, Method and Time of Administration How to use Arianna - Contraceptive Pill: Dosage

Dosage

Start taking ARIANNA by taking tablet number 1 located next to the word "START".
To help you keep track of your daily pill intake, there are 7 self-adhesive strips with 7 days of the week. Choose the strip that starts with the day you start taking your tablets. For example, if you start on a Wednesday, use the adhesive strip starting with "MER" Apply the adhesive strip along the top of the ARIANNA blister, where it says "Apply the adhesive strip here".
Each blister contains 28 tablets. Take one pill at the same time every day, for 28 consecutive days, following the direction indicated by the arrows, without ever making a mistake, as follows: take one pale yellow active tablet a day, for the first 24 days; then a white placebo pill every day for the last 4 days.
After taking the last tablet, continue taking ARIANNA the next day starting another strip with no free interval between one strip and the next. You will always have to start a new strip on the same day of the week. As there are no intervals, it is important that you have already got yourself a new blister before you run out of one.
Your period usually starts two to three days after you take the last pale yellow tablet in the strip and may not have finished before you start the next strip.

Method and route of administration

Take each tablet with a large glass of water.

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

Take the first tablet on the first day of your period.

If he used "another contraceptive pill

Use up the blister pack you are taking (if the pack of pills you are taking also contains hormone-free (inactive) tablets, do not take them). Then start the ARIANNA blister the next day, leaving no pill-free interval.

If you were using a progestogen-only method (progestogen-only pill, injectable method, or implant)

Changing from a progestogen-only pill: You can start MIA at any time during your period, the day after you stopped the progestogen-only pill.
Transition from an implant: you start ARIANNA the day the implant is removed.
Switching from an injectable contraceptive: Start MIA on the day your next injection was scheduled.

In any case, you must use a barrier method of contraception (such as a condom) for the first 7 days of taking the pill.

If it starts ARIANNA after an abortion occurred in the first trimester

You can start taking MELIE immediately, but you must follow your doctor's advice before starting. If ARIANNA starts after delivery or after an abortion in the second trimester As with any other contraceptive pill, ARIANNA should not be started earlier than 21-28 days after delivery or abortion, as the risk of blood clots is higher. If you start later, we advise you to use a barrier method of contraception during the first 7 days of taking the pill.If you have had sex before starting ARIANNA make sure you are not pregnant or wait for the next cycle.

Always ask your doctor for advice.

Duration of use

Your doctor will tell you how long to take this pill.

If you forget to take ARIANNA

If you forget to take the pill, there is a risk of getting pregnant

If you realize that you have not taken a pale yellow tablet within 12 hours of the time you normally take your tablet, take the forgotten tablet immediately and continue as normal, taking the next tablet at the usual time until the blister is finished.

If you find that you have not taken a pale yellow tablet more than 12 hours after the time you normally take it, there is a risk that you will become pregnant. Then:

take the forgotten tablet immediately, even if that means taking 2 tablets on the same day;
continue to take the contraceptive until the end of the strip;
in addition, use a barrier method of contraception (condom, spermicide) for the next 7 days;
if this 7-day period goes beyond the last pale yellow tablet, throw away the remaining tablets and start the next blister.

If you have forgotten some pale yellow tablets in a blister and you do not have your expected period, which should start while taking the white tablets, you may be pregnant.

If you have forgotten one or more white tablets, you are still protected as long as there are no more than 4 days between the last pale yellow tablet in the current strip and the first pale yellow tablet in the next strip.

Ask your doctor for advice.

If you have severe vomiting or diarrhea within 4 hours of taking the pill, the situation is similar to when you forget a tablet. After vomiting or diarrhea, you should take another tablet from a reserve strip as soon as possible. . If possible, take it within 12 hours of the usual time to take the pill. If this is not possible, or if 12 hours have already passed, you should follow the instructions given in "If you forget to take MIA".

If these episodes of severe vomiting or diarrhea recur for several days, you must use a barrier method of contraception (condom, spermicide ...) until the next blister begins.

Ask your doctor for advice.

Overdose What to do if you have taken too much Arianna - Birth Control Pill

An overdose can cause gastrointestinal problems (e.g. nausea, vomiting, abdominal pain), breast tenderness, dizziness, sleepiness / fatigue and irregular menstruation (bleeding).

Ask your doctor for advice.

Side Effects What are the side effects of Arianna - Birth Control Pill

Like all medicines, ARIANNA 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 MERRY, 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 arising from "taking combined hormonal contraceptives, see section 2" What you need to know before you use MERRY ".

The most frequently reported side effects (more than 10%) in women using ARIANNA are rare or absent menstruation during the pill or when stopping it, bleeding between menstruation or headache, including migraine.

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

vaginal infection, including vaginal candidiasis
mood changes, including depression or altered sexual desire
nervousness or dizziness
nausea, vomiting or abdominal pain
breast acne problems, such as pain, tenderness, swelling or discharge
painful menstruation or change in menstrual flow
changes in vaginal discharge or a change in the cervix (ectropion)
fluid retention in tissues or edema (marked fluid retention)
weight loss or gain

Uncommon side effects (may affect 1 to 10 in 1000 women):

changes in appetite
abdominal cramps or flatulence
rash, excessive hair growth, hair loss or facial blemishes (chloasma)
changes in laboratory test results: increased cholesterol, triglyceride levels or increased blood pressure Rare side effects (may affect 1 to 10 in 10,000 women):
allergic reactions (very rare cases of hives, angioedema or severe respiratory or circulatory disorders)
glucose intolerance
intolerance to contact lenses
jaundice
a type of skin reaction called "erythema nodosum"
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).

Very rare side effects (may affect less than 1 in 10,000 women):

benign liver tumor (called focal nodular hyperplasia or hepatic adenoma) or malignant liver tumor
worsening of an immune system disease (lupus), liver disease (porphyria) or a disease known as 'chorea' characterized by irregular, sudden and involuntary movements
certain types of eye diseases, such as inflammation of the optic nerve, which can lead to partial or total loss of vision, or a blood clot in the retina
pancreatic diseases increased risk of gallstones or obstruction of the flow of bile
liver or biliary disease (such as hepatitis or abnormal liver function)
blood and urinary tract disease (haemolytic and uremic syndrome)
a type of skin reaction called "erythema multiforme"

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

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 ARIANNA out of the reach and sight of children.

Do not use ARIANNA after the expiry date which is stated on the carton and blister.

No special storage conditions are required.

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.

Other_information "> Other information

What ARIANNA contains

Pale yellow tablet

The active ingredients are: 60 micrograms of gestodene and 15 micrograms of ethinylestradiol.

The other ingredients are: lactose monohydrate, microcrystalline cellulose, magnesium stearate, polacrilin potassium, Opadry yellow YS-1-6386-G [hypromellose, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172)], macrogol 1450, E wax (montanglycolic wax).

White tablet

It does not contain active ingredients. The other ingredients are: lactose monohydrate, microcrystalline cellulose, magnesium stearate, polacrylin potassium, Opadry Y-5-18024-A [hypromellose, hydroxypropylcellulose, titanium dioxide (E171), macrogol 400], macrogol 1500, wax E (montanglycol wax).

Description of the appearance of ARIANNA and contents of the pack

ARIANNA is available in the form of film-coated tablets.

Each pack contains 1, 3 or 6 blisters, each containing 28 tablets (24 pale yellow active tablets and 4 white placebo 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 Arianna - Birth Control Pill is available in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT - 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION - 03.0 PHARMACEUTICAL FORM - 04.0 CLINICAL PARTICULARS - 04.1 Therapeutic indications - 04.2 Posology and method of administration - 04.3 Contraindications - 04.4 Special warnings and appropriate precautions for use - 04.5 Interactions with other medicinal products and other forms of 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 -

ARIANNA 60 MCG / 15 MCG TABLETS COATED WITH FILM

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -

Gestodene: 60 mcg

Ethinylestradiol: 15 mcg

For a pale yellow film-coated tablet (active tablet).

Excipient with known effect: lactose

The white film-coated tablets do not contain any active ingredients (placebo).

Excipient with known effect: lactose.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM -

Film-coated tablet.

The active tablet is pale yellow, round with convex faces.

The placebo tablet is white, round with convex faces.

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

Oral hormonal contraception.

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

04.2 Posology and method of administration -

Dosage

Take one tablet regularly and without interruption a day, at the same time, for 28 consecutive days (one pale yellow tablet active in the first 24 days and one white inactive tablet in the following 4 days), with no interval between one pack and the next. Withdrawal bleeding normally begins 2-3 days after taking the last active tablet and may persist beyond the start of the new pack.

How to start Arianna

- No hormonal contraceptive treatment in the previous month:

Take the first tablet on the 1st day of menstruation.

- Changing from another combined oral contraceptive:

The woman should start Arianna the day after the last active tablet of her previous combined oral contraceptive.

- Changing from a progestogen-only method (minipill, injection, implant):

You can switch to Arianna at any time if you use the minipill, starting the next day. In the case of an implant, Arianna should be started on the day of removal of the implant or, in the case of an injectable product, on the day when the next injection should be given. In all these cases the woman should be warned. to also use a non-hormonal method of contraception for the first 7 days of taking the tablets.

- After a first trimester abortion:

The woman can start Ariadne immediately. No additional contraceptive measures are necessary.

- After childbirth or second trimester abortion:

Since the immediate postpartum period is associated with an increased risk of thromboembolism, the use of COCs should not commence before the 21st-28th day after delivery or after a second trimester abortion. The woman should be warned. to also use a non-hormonal method of contraception in the first 7 days of taking the tablets. However, if you have had sexual intercourse in the meantime, pregnancy must be ruled out or the onset of the first menstruation.

- For breastfeeding women, see section 4.6.

Missing of one or more tablets

Contraceptive safety may decrease if you forget to take the pale yellow tablets, particularly if the forgotten occurs during the first few days of the pack.

• If you notice that you have forgotten to take a pale yellow tablet within 12 hours of the usual time, you should take it immediately and continue treatment as normal, taking the next tablet at the usual time.

• If you notice that you have forgotten to take a pale yellow tablet when more than 12 hours have passed since the usual time, contraceptive protection is no longer ensured. The last missed tablet should be taken immediately, even if this may mean take two tablets on the same day, and the oral contraceptive treatment continued until the end of the calendar pack, using at the same time also a non-hormonal method of contraception (condoms, spermicides, etc.) for the next 7 days.If the 7-day period in which an additional contraceptive method is required goes beyond the last active tablet in the current pack, the new pack must be started on the day following that of taking the last active tablet in the current pack. discarding all inactive tablets. Withdrawal bleeding is unlikely before you start taking the second pack, but spotting or breakthrough bleeding may occur. If no withdrawal bleeding occurs at the end of the second pack. contraceptive, the possibility of pregnancy must be ruled out before resuming taking tablets.

Errors in taking one or more white tablets have no consequences, as long as the interval between the last pale yellow tablet in the current pack and the first pale yellow tablet in the next pack is no more than 4 days.

In case of onset of gastrointestinal disorders:

The onset of intercurrent digestive disturbances, such as vomiting within four hours of taking the tablet or severe diarrhea, can temporarily render the method ineffective due to impaired hormonal absorption. Such occurrences should be dealt with in the same way as forgetting the tablet for less than 12 hours. Supplemental tablets must be taken from a reserve pack. If these episodes recur for several days, an additional non-hormonal method of contraception (condom, spermicide, etc.) should be used until the next pack is started.

Pediatric population

There is limited data available on use in adolescents below 18 years

Elderly population

Arianna is not indicated after menopause.

Patients with hepatic impairment

Arianna is contraindicated in women with severe liver disease. See section "Contraindications".

Patients with renal impairment

Arianna has not been specifically studied in patients with impaired renal function

Method of administration

Oral use

04.3 Contraindications -

Combined hormonal contraceptives (COCs) should not be used in the following conditions.

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

- coronary artery disease

- valvulopathy

- thrombogenic rhythm disturbances

- Presence or risk of venous thromboembolism (VTE)

o Venous thromboembolism - current VTE (with anticoagulant intake) or history (e.g. deep vein thrombosis [DVT] or pulmonary embolism [PE])

o 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

o Major surgery with prolonged immobilization (see section 4.4)

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

- Presence or risk of arterial thromboembolism (ATE)

o Arterial thromboembolism - current or past arterial thromboembolism (e.g. myocardial infarction) or prodromal conditions (e.g. angina pectoris)

o Cerebrovascular disease - current or previous stroke or prodromal conditions (e.g. transient ischaemic attack (TIA))

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

o History of migraine with focal neurological symptoms

o 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

- Known or suspected breast cancer

- carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasm

- liver adenomas or carcinoma, or active liver disease, until liver function tests have returned to normal

- genital bleeding of an undetermined nature

04.4 Special warnings and appropriate precautions for use -

Warnings

If any of the conditions or risk factors mentioned below are present, Arianna's suitability should be discussed with the woman.

In the event of worsening or first appearance of any of these risk factors or conditions, the woman should contact her doctor to determine whether the use of Arianna 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 Arianna 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 Arianna, the way where your current risk factors influence that risk and the fact that the risk of developing a VTE is highest in the first year of use. There is also some evidence that the risk increases when taking a COC is resumed after a break of 4 or more weeks.

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

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

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

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

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).

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

Table: Risk factors for VTE Risk factor Comment Obesity (body mass index (BMI) above 30 kg / m² The risk increases considerably as the BMI increases. Particularly important to consider if other risk factors are also present Prolonged immobilization, major surgery, any type of leg and pelvis surgery, neurosurgery or major trauma Note: Temporary 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 Arianna 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). Arianna 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.

GYNECOLOGICAL CANCERS

A meta-analysis of data from 54 international studies found a slightly higher risk of being diagnosed with breast cancer among oral contraceptive users. This increased risk does not appear to depend on the duration of treatment. The influence of risk factors such as nulliparity or family history of breast cancer is not proven.

This increased risk is temporary and disappears 10 years after the oral contraceptive is stopped.

More breast cancers may be diagnosed in women taking oral contraceptives due to the more regular clinical monitoring they undergo, which increases the likelihood of early detection.

Because breast cancer is rare in women under 40 years of age, the excess number of breast cancer diagnoses in women taking or who have recently taken COCs is small when compared to the risk of breast cancer during that period. Whole life span Breast cancers diagnosed in COC users tend to be less advanced clinically than those diagnosed in non-users.

Some epidemiological studies report an increased risk of cervical cancer in long-term users of COCs. However, the extent to which such data can be attributed to differences in sexual behavior or to other factors such as human papilloma virus (HPV) continues to be controversial.

Published data do not compromise the use of oral contraceptives, as the benefits outweigh the potential risks.

In addition, oral contraception reduces the risk of ovarian and endometrial cancer.

NEOPLASIA / LIVER DISEASE

Benign liver tumors (e.g. focal nodular hyperplasia, hepatic adenomas) and, even more rarely, malignant liver tumors have been reported rarely in women taking COCs. In isolated cases, these tumors have resulted in life-threatening intra-abdominal haemorrhages.

Both during pregnancy and during the use of COCs, the occurrence of cholestasis or its worsening has been reported, but there is no conclusive evidence of an association with COCs.

Hepatic and hepatobiliary disorders have been reported with the use of COCs. Acute or chronic disturbances of liver function may require discontinuation of the COC until parameters of liver function have returned to normal values.

HEADACHE

The onset or exacerbation of migraine or the development of headache with unusual features, ie recurrent, persistent, or intense, requires discontinuation of the COC and evaluation of the cause.

HYPERTENSION

Although uncommonly, increases in blood pressure have been reported in women taking COCs.

In women with hypertension, a history of hypertension or conditions related to hypertension (including some kidney conditions), another method of contraception may be preferable.

If COCs are used in these cases, careful monitoring and discontinuation of the COC is recommended in the event of a significant increase in blood pressure.

OTHER

- Caution should be exercised in women with:

- Metabolic disorders such as uncomplicated diabetes.

- Hyperlipidemia (hypertriglyceridemia, hypercholesterolemia). Women being treated for hyperlipidaemia should be monitored constantly if they choose to take COCs. Persistent hypertriglyceridaemia may occur in a small percentage of COC users.

- In patients with elevated triglycerides, the use of estrogen-containing preparations may be associated with rare but marked increases in plasma triglycerides, which can lead to pancreatitis.

- Obesity (body mass index = weight / height² ≥ 30).

- Benign breast tumors and uterine dystrophy (hyperplasia; fibroid).

- Hyperprolactinemia with or without galactorea.

- Close surveillance is also necessary in the presence of conditions that may occur or worsen during pregnancy or with the use of combined oral contraceptives and in patients with a history or presence of: epilepsy, migraine, otosclerosis, asthma, family history of vascular disease, varicose veins, herpes gestationis, gallstones, systemic lupus erythematosus, cardiac, renal or hepatic dysfunction, depression, hypertension, chorea, haemolytic uremic syndrome.

- Exogenous estrogens can induce or aggravate the symptoms of angioedema, particularly in women with hereditary angioedema.

- In clinical studies, non-pregnancy related amenorrhea was observed in 7% of cycles (in 24% of women throughout the duration of clinical studies) and 3.6% of women had consecutive amenorrhoeic cycles. In clinical studies, only 1% of women discontinued treatment due to amenorrhea.

- When Arianna is taken according to the instructions, in the event of an amenorrhoeic cycle there is no reason to stop treatment and perform a pregnancy test. If Arianna is not taken according to the instructions or if amenorrhea occurs after a long period of menstruation regular, pregnancy must be excluded.

- Some women may experience post-therapeutic amenorrhea (which may be accompanied by anovulation) or oligomenorrhea, particularly if the condition was pre-existing. These conditions usually resolve spontaneously. If protracted, investigations into the possibility of pituitary disorders should be conducted before further prescriptions.

- With all COCs, irregular bleeding (spotting and bleeding from stopping the contraceptive) may occur, particularly during the first months of treatment. Thus, the assessment of any irregular bleeding is only meaningful after an adaptation interval of approximately three cycles. If these irregularities persist or appear after previously regular cycles, the possibility of an organic cause should be examined and adequate diagnostic measures are indicated to rule out malignancy or pregnancy. Diagnostic measures may include curettage.

- There have been reports of depression while using COCs. Women with a history of depression using COCs should be closely monitored.

- If melasma / chloasma has developed during a previous pregnancy or previous use of COCs, avoid exposure to sunlight to minimize exacerbation of this condition.

- Diarrhea and / or vomiting may reduce hormone absorption from COCs (see section 4.2).

This medicine is not recommended in women with lactose intolerance, as it contains lactose.

Medical examinations / visits

Before initiating or resuming use of Arianna, a complete medical history (including family history) should be taken and pregnancy should be ruled out. Blood pressure should be measured and a clinical examination, guided by contraindications, should be performed (see section 4.3 ) and warnings (see section 4.4). It is important to draw a woman's attention to information relating to venous or arterial thrombosis, including the risk associated with Arianna 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.

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

Interactions between ethinyl estradiol or gestodene and other substances may lead to a decrease or increase in plasma and tissue concentrations of ethinyl estradiol or gestodene.

Decreased serum concentrations of ethinylestradiol may cause an increased incidence of breakthrough bleeding, menstrual irregularities and may reduce the effectiveness of the COC.

The concomitant use of:

- Enzyme inducers such as: anticonvulsants (phenobarbital, phenytoin, primidone, carbamazepine, topiramate); rifabutin; rifampicin; griseofulvin and possibly St. John's wort (Hypericum perforatum). Decreased contraceptive efficacy due to increased hepatic metabolism during treatment and for the cycle following treatment discontinuation. A non-hormonal method of contraception should be preferred.

When co-administered with COCs, many HIV / HCV1 protease inhibitors and non-nucleoside reverse transcriptase inhibitors may increase or decrease plasma concentrations of estrogen or progestogen. The net effect of these changes in some cases may be clinically relevant.

See the corresponding sections of the SmPCs of each of the protease inhibitors and non-nucleoside reverse transcriptase inhibitors, HIV and HCV, for specific recommendations.

Plasma concentrations of estrogen, progestogen or both may be increased by strong or moderate inhibitors of CYP3A4 such as azole antifungals (e.g. itraconazole, voriconazole, fluconazole), macrolides (e.g. clarithromycin, erythromycin), verapamil, diltiazem and grapefruit juice .

- Etoricoxib doses of 60 to 120 mg / day have been shown to increase plasma concentrations of ethinylestradiol 1.4 to 1.6-fold, respectively when taken concomitantly with a combined hormonal contraceptive containing 0.035 mg ethinylesteradiol.

The clinical relevance of the potential interactions with enzyme inhibitors is unknown.

- Modafinil: risk of reduced contraceptive efficacy during treatment and for the cycle following discontinuation of treatment.

- Flunarizine: risk of galactorrhea due to the increased sensitivity of the breast tissue to prolactin, due to the action of flunarizine.

- Troleandomycin may increase the risk of intrahepatic cholestasis during concomitant administration with COCs.

Effects of Arianna on other medicinal products

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

Clinical data suggest that ethinylestradiol inhibits the clearance of CYP1A2 substrates leading to a weak (eg theophylline) or moderate (eg tizanidine) increase in their plasma concentration.

Package leaflets of concomitant medications should be consulted in order to identify potential interactions.

04.6 Pregnancy and breastfeeding -

Pregnancy

The product is not indicated during pregnancy.

So far, in clinical use, and unlike diethylstilbestrol, the results of numerous epidemiological studies allow us to consider reduced the risk of malformations with estrogens administered at early pregnancy, alone or in combination.

Furthermore, the risks related to the sexual differentiation of the fetus (especially female), which have been described with the first highly androgenomimetic progestogens, cannot be extrapolated to the more recent progestogens (such as that used in this medicinal product), which are much less, or not at all, androgenomimetics.

Consequently, the discovery of a pregnancy in a patient taking an "estrogen-progestogen combination" does not justify the abortion.

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

Feeding time

The use of the product in breastfeeding mothers is not recommended, as estrogens and progestogens pass into breast milk.

During breastfeeding, a different contraceptive method should be offered.

04.7 Effects on ability to drive and use machines -

Not relevant.

04.8 Undesirable effects -

The following undesirable effects have been reported in COC users:

For serious adverse events in COC users see section 4.4.

Occurrence of amenorrhea was reported in 15% of women during the clinical trial, see section 4.4.

Among the most frequently reported adverse events (greater than 10%) during phase III studies and post-marketing surveillance in Arianna users are headache, including migraine, and breakthrough bleeding / spotting.

Other adverse reactions seen in women taking COCs:

Common ≥ 1%, Uncommon ≥ 0.1%, Rare ≥ 0.01%, Very rare Neoplasms benign, malignant and unspecified (including cysts and polyps) Hepatocellular carcinoma and benign liver tumors (e.g. focal nodular hyperplasia, hepatic adenoma) Infections and infestations Vaginitis, including candidiasis Disorders of the immune system Anaphylactic / anaphylactoid reactions, including very rare cases of urticaria, angioedema and severe reactions with respiratory and circulatory symptoms Exacerbation of systemic lupus erythematosus Metabolism and nutrition disorders Change in appetite (increase or decrease) Glucose intolerance Exacerbation of porphyria Psychiatric disorders Changes in mood including depression, changes in libido Nervous system disorders Nervousness, dizziness Exacerbation of chorea Eye disorders Contact lens intolerance Optic neuritis, retinal vascular thrombosis Vascular pathologies Venous thromboembolism (VTE), arterial thromboembolism (ATE) Gastrointestinal disorders Nausea, vomiting, abdominal pain Abdominal cramps, bloating Pancreatitis Hepatobiliary disorders Cholestatic jaundice Biliary lithiasis and cholestasis¹, hepatic and hepatobiliary disorders (e.g. hepatitis, abnormal liver function) Skin and subcutaneous tissue disorders Acne Rash, sometimes persistent chloasma (melasma), hirsutism, alopecia Erythema nodosum Erythema multiforme Renal and urinary disorders Hemolytic-uremic syndrome Diseases of the reproductive system and breast Breast pain, breast tenderness, breast enlargement, breast discharge, dysmenorrhea, altered menstrual flow, changes in ectropion and cervical discharge. General disorders and administration site conditions Water retention / edema Diagnostic tests Weight changes (increase or decrease) Increase in blood pressure, changes in serum lipid levels, including hypertriglyceride-my

¹ COCs can worsen biliary lithiasis and ongoing cholestasis.

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.

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 -

Symptoms of oral contraceptive overdose in adults and children may include nausea, vomiting, breast tenderness, dizziness, abdominal pain, sleepiness / fatigue; withdrawal bleeding may occur in women. There are no antidotes and treatment should be symptomatic.

05.0 PHARMACOLOGICAL PROPERTIES -

05.1 "Pharmacodynamic properties -

PROGESTINICS AND ESTROGENS IN FIXED ASSOCIATION

ATC code G03AA10 (genitourinary system and sex hormones).

Monophasic estrogen-progestogen association. Incorrect Pearl Index 0.24 (21,521 cycles).

Arianna's contraceptive efficacy arises from three complementary action mechanisms:

- inhibit ovulation at the level of the hypothalamic-pituitary axis;

- make cervical secretions impermeable to the migration of spermatozoa;

- make the endometrium unsuitable for implantation.

05.2 "Pharmacokinetic properties -

Ethinylestradiol

Absorption:

Ethinylestradiol is rapidly and completely absorbed after oral administration. After administration of 15 micrograms, peak plasma concentrations of 30 pg / ml are reached after 1-1.5 hours. Ethinylestradiol undergoes a marked first pass effect, with great inter-individual variations. Absolute bioavailability is approximately 45%.

Distribution:

Ethinylestradiol has an apparent volume of distribution of 15 l / kg and plasma protein binding is approximately 98%.

Ethinylestradiol induces hepatic synthesis of sex hormone binding globulin (SHBG) and corticosteroid (CBG). During treatment with ethinylestradiol 15 mcg, the plasma concentration of SHBG increases from 86 to approximately 200 nmol / l.

Biotransformation

Ethinylestradiol is completely metabolised (metabolic plasma clearance approximately 10 ml / min / kg). The metabolites that are formed are excreted in the urine (40%) and faeces (60%). In vitro, ethinylestradiol is a reversible inhibitor of CYP2C19, CYP1A1 and CYP1A2 as well as an irreversible inhibitor of CYP3A4 / 5, CYP2C8 and CYP2J2.

Elimination

The elimination half-life of ethinylestradiol is approximately 15 hours. Ethinylestradiol is not significantly excreted in the unchanged form. The metabolites of ethinylestradiol are excreted in a urine / bile ratio of 4: 6.

Steady state conditions:

Steady state conditions are achieved in the second half of the treatment cycle. There is an accumulation of ethinylestradiol of a factor ranging from about 1.4 to 2.1.

Gestodene:

Absorption

Gestodene is rapidly and completely absorbed after oral administration. Absolute bioavailability is approximately 100%. After a single oral dose of 60 micrograms of gestodene, peak plasma concentrations of 2 ng / ml are reached in approximately 60 minutes. Plasma concentrations are strongly dependent on SHBG concentration.

Distribution:

Gestodene has an apparent volume of distribution of 1.4 L / kg after a single dose of 60 micrograms. It is 30% bound to plasma albumin and 50-70% to SHBG.

Biotransformation:

Gestodene is extensively metabolised via the steroid pathway. Metabolic clearance is approximately 0.8 ml / min / kg after a single dose of 60 micrograms. The inactive metabolites that are formed are excreted in the urine (60%) and faeces (40%).

Elimination:

The apparent elimination half-life of gestodene is approximately 13 hours. The half-life is prolonged to 20 hours following concomitant administration with ethinylestradiol.

Steady state conditions:

After repeated doses in combination with ethinylestradiol the plasma concentration increases by approximately a factor of 2-4.

05.3 Preclinical safety data -

Toxicological studies have been performed on all components both individually and in combination.

Acute toxicity studies in animals revealed no risk of acute symptoms due to accidental overdose.

General safety studies with repeated administration have revealed no unforeseen risks in humans.

Long-term and repeated dose carcinogenicity studies did not show carcinogenic properties. However, it is important to remember that sex steroids can promote the development of certain tissues in hormone-dependent tumors.

Teratogenicity studies did not reveal any particular risk if the estrogen-progestagen combinations are used correctly. However, it is essential to stop treatment immediately if taken by mistake at the beginning of pregnancy.

Mutagenicity studies did not reveal any mutagenic potential of ethinylestradiol or gestodene.