Effiprev - Package Leaflet

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

Active ingredients: Dienogest, Ethinylestradiol

Effiprev 2 mg / 0.03 mg film-coated tablets

Why is Effiprev 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")

What is Effiprev and what is it for

Effiprev film-coated tablets (briefly called Effiprev) are an oral contraceptive containing a "combination of two hormones.

Effiprev contains two types of female sex hormones in small quantities, namely ethinylestradiol (with similar effects similar to those of estrogen) and dienogest (which produces similar effects to the natural luteal hormone, progesterone). In view of the low hormone content, this drug belongs to the family of "micropills", combined hormonal contraceptives, consisting of two types of hormones, monophasic, ie containing the same quantities in all tablets

Contraindications When Effiprev should not be used

Oral contraceptive pills and cancer risk

Breast cancer has been found slightly more frequently in women who use the pill than in women who do not, although there is no certainty whether this is due to taking the pill. more frequent medical check-ups, so any breast cancer is noticed at an earlier stage than in other women with the same cancer.

10 years after stopping the pill, this small difference disappears.

In rare cases, benign liver tumors - and even more rarely malignant liver tumors - have been reported in women using the pill. These tumors can cause internal (abdominal) bleeding. If you experience severe pain in the upper abdomen, you should contact your doctor immediately.

Some studies have shown higher numbers of cervical cancers in women who use the pill over a long period of time. However, it is not entirely certain that this is caused by the Pill, because the incidence of cervical cancer is influenced by many other factors, such as sexual behavior (eg frequent partner changes).

Do not use Effiprev:

Do not use Effiprev 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 or a 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 are allergic to ethinylestradiol, dienogest or any of the other ingredients of this medicine (listed in section 6);
• severe active liver disease, jaundice in progress or present in your family history; jaundice or itching throughout the body could be the first signs of liver disease;
• liver tumor in active phase (benign or malignant) or present in its family history;
• known or suspected cancers of the genital organs or breasts;
• vaginal bleeding of unknown origin;
• pancreatitis or a history of pancreatitis if associated with severe hypertriglyceridaemia;
• severe kidney failure or acute kidney failure;

If you have any of the conditions listed above, tell your doctor before you start taking Effiprev. Your doctor will possibly suggest another type of oral contraceptive pill or another non-hormonal method of contraception.

Precautions for use What you need to know before taking Effiprev

Before you start using Effiprev you should read the information on blood clots. It is particularly important to read the symptoms of a blood clot (see section "Blood clots").

In this Patient Information Leaflet there are different scenarios as to when to stop taking Effiprev or in which situations the contraceptive action may be reduced. In these cases, you must refrain from sexual intercourse or use non-hormonal contraceptive measures (e.g. condoms) or another non-barrier method of contraception. Do not use methods based on biological rhythms or on the detection of body temperature, as these methods can be unreliable.

As with other combined oral contraceptives, taking Effiprev does not protect against HIV infection (AIDS) or other sexually transmitted diseases.

Interactions Which drugs or foods can modify the effect of Effiprev

Other medicines and Effiprev

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Some medicines can affect the effectiveness of COCs. One of the first signs of this could be abnormal genital bleeding. These medicines include the following:

• carbamazepine, oxycarbamazepine, topiramate and felbamate);
• medicines used to treat tuberculosis (e.g. rifampicin);
• antibiotics used to treat some infections (e.g. ampicillin, tetracycline, griseofulvin);
• ritonavir, rifabutin, efavirenz, nevirapin, nelvinafir);
• the herbal preparation called St. John's wort (Hypericum perforatum).

Certain drugs and grapefruit juice can affect the plasma levels of dienogest (eg azole antifungals, cimetidine, verapamil, diltiazem, macrolides, antidepressants).

COCs may also impair the efficacy of some medicines, eg medicines containing cyclosporine or lamotrigine. The progestogen compound may affect the effect of some antihypertensive medicines (medicines that lower blood pressure) and non-steroidal anti-inflammatory medicines.

Tell the doctor who is prescribing other medicines and also the dentist that you are taking Effiprev. Your doctor will tell you if you need to use other non-hormonal methods of contraception and how long you need to use them for.

Women on short-term treatment (maximum duration of one week) with the above medicines should take additional contraceptive measures, eg. barrier method (condom) during concomitant administration of the concomitant drug and in the 7 days following its discontinuation.

Concomitant treatment with rifampicin requires the adoption of additional contraceptive measures (eg a barrier method) while taking the concomitant medicinal product and for 28 days following its discontinuation. If concomitant administration of the medicinal product continues even after the end of a combined hormonal contraceptive pack, the next pack of the combined hormonal contraceptive should be started without observing the usual tablet-free interval.

Tell your doctor if you have been taking hepatic enzyme system inducing medicines for a long time (also read the package leaflets of the other products). In some cases it may be necessary to choose a non-hormonal method of contraception.

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".

Tell your doctor if any of the following apply to you.If this condition appears or worsens while you are using Effiprev you should tell your doctor.

• 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 Effiprev;
• if you have "inflammation of the veins under the skin (superficial thrombophlebitis);
• if you have varicose veins.
• if you have diabetes mellitus;
• if you suffer from obesity (body mass index above 30 kg / m2);
• if he has not reached his final adult height;
• if you suffer from hypertension;
• if you suffer from heart valve disease or heart rhythm disturbances;
• if any of your close relatives have had thrombosis, heart attack or stroke;
• if you suffer from migraines;
• if you suffer from seizures (epilepsy, Sydenham's chorea);
• if you suffer from liver disease or bile disorders;
• if you suffer from jaundice and / or itching all over your body;
• if you suffer from a rare disturbance of the hemoglobin metabolism (porphyria);
• if you suffer from hereditary angioedema;
• if you suffer from endogenous depression;
• if you have ever had a "blistering rash" in the late stage of pregnancy (gestational herpes);
• if you have a hearing difficulty known as otosclerosis;
• if you have or have ever had brownish-yellow spots on the skin, especially on the face (chloasma); if this problem affects you, you must avoid exposure to direct sunlight or ultraviolet light;
• if you smoke. Cigarette smoking increases the risk of serious side effects associated with the use of oral contraceptives, such as heart attack and stroke. The risk further increases if you are heavy smokers and as you age.

If you use the pill, stop smoking, especially if you are over 35. If you do not intend to stop smoking, you should use other methods of contraception, especially if other risk factors are also present.

When it is appropriate to carry out medical checks

Your doctor may recommend that you have regular medical checks while taking the pill. Based on your state of health and condition, the doctor will decide the frequency of these checks and the type of tests to be performed.

Contact your doctor as soon as possible if any of the following occur:

• if you notice any change in your state of health (check in particular the symptoms described in this leaflet), or if the disorders mentioned in the leaflet occur in a member of your family;
• if you notice a lump on palpation of the breast;
• if you need to take other medicines;
• before scheduled surgery or in case of immobilization (contact your doctor at least 4 weeks before);
• if you experience unusually intense and irregular vaginal bleeding;
• if you have forgotten to take one or more pills during the first week of treatment or if you have had sexual intercourse in the previous 7 days;
• if no withdrawal bleeding has occurred twice in a row, or if you suspect that you are pregnant (COC use may be resumed if your doctor considers it appropriate)

BLOOD CLOTS

Using a combined hormonal contraceptive such as Effiprev 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 the use of Effiprev 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
• 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 Effiprev your risk of developing a blood clot returns to normal within a few weeks.

What is the risk of developing a blood clot?

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

The overall risk of developing a blood clot in the leg or lung (DVT or PE) with Effiprev 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. -
• It is not yet known how the risk of developing a blood clot with Effiprev compares with the risk associated with a combined hormonal contraceptive containing levonorgestrel.
• The risk of a blood clot forming depends on your medical history (see under "Factors that increase the risk of a blood clot forming").

Risk of developing a blood clot in one year Women who are not using a combined hormone pill / patch / ring and who are not pregnant About 2 out of 10,000 women Women using a combined hormonal contraceptive pill containing levonorgestrel, norethisterone or norgestimate About 5-7 out of 10,000 women Women using Effiprev Not yet known.

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

The risk of developing a blood clot with Effiprev 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 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. You may need to stop taking Effiprev a few weeks before the surgery or in the period where you are less mobile. If you have to stop taking Effiprev 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 you stop taking Effiprev. If any of the above conditions change while you are using Effiprev, 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 Effiprev is very low but can increase:

• with increasing age (over 35 years);
• if you smoke. When using a combined hormonal contraceptive such as [invented name] 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 Effiprev, 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.

Pregnancy, breastfeeding and fertility

If you are pregnant or think you may be, do not take Effiprev. If pregnancy occurs while taking Effiprev, the pill should be discontinued immediately. The use of Effiprev while breastfeeding may reduce the volume and alter the composition of breast milk. Minimal amounts of active substances and / or excipients are excreted in breast milk, with potential effects on the infant. Breastfeeding mothers are therefore advised not to take Effiprev. Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Effiprev does not influence the driving of vehicles and the use of machines.

Effiprev contains lactose

This medicine contains lactose, glucose and (soy) lecithin. If you know that you are hypersensitive to certain sugars, peanuts or soya, talk to your doctor before taking Effiprev.

Dosage and method of use How to use Effiprev: Dosage

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

Each pack of Effiprev contains 21, 3x21.6x21, 13 x 21 film-coated tablets. The days of the week on which the film-coated tablets should be taken are indicated on the packaging.

You should try to take the pill at the same time every day, with liquid if necessary. Take one pill a day, following the direction of the arrows, until you have finished the pack. This is followed by 7 days during which no pills are taken. During this 7-day drug-free interval, withdrawal bleeding should occur, usually 2-3 days after taking the last pill.

Start the next pack of Effiprev on the 8th day after taking the last pill. You should start taking the tablets from the next pack of Effiprev even if the bleeding is still going on. Each new pack will be started on the same day of the week as the earlier, so that it will be easier for you to remember when to resume the tablets, and also your cycle will always occur on the same days of the month.

If you follow the instructions exactly, the pill will be able to protect you from unwanted pregnancy from the first day of treatment.

Taking the first pack of Effiprev

No hormonal contraceptive treatment in the last month:

One film-coated tablet, starting on the first day of your period (the first day of your period, defined as Day 1), taking the pill marked with the correct day of the week out of the blister.

Switching to Effiprev from a combined contraceptive (COC, vaginal ring, transdermal patch):

The first film-coated tablet of Effiprev should be taken at the usual tablet-free interval or on the first day immediately after taking the last tablet of the previous contraceptive (without the "tablet-free" interval).
If the previously taken product contained inactive (hormone-free) tablets, taking Effiprev should start with the usual placebo tablet-free interval or after taking the last active (hormone-containing) tablet of the previous contraceptive. if you are not sure which tablets are active, ask your doctor or pharmacist.
If the vaginal ring or transdermal patch has been used previously, Effiprev should be started on the day of removal of the vaginal ring or transdermal patch, or at the latest on the day that the new application is scheduled.

Changing from a progestogen-only method of contraception (minipill):

Women taking progestogen-only minipills can switch at any time to Effiprev, which can be taken the day after taking the previous contraceptive (at the usual time). An additional method of contraception, eg methods, is required. barrier (prophylactic) in the 7 days after taking the tablets.

If you previously used contraceptive injections or contraceptive implants or a progestogen-releasing intrauterine device (IUS):

Those using implants or IUS can start on the day the implant or IUS is removed. Women receiving injections can start taking the film-coated tablets on the day the next injection should be given. It is necessary to resort to an additional contraceptive method eg. barrier methods (prophylactic) within 7 days after taking the tablets.

After having a baby:

If you have just had a baby, your doctor may advise you to take Effiprev after the first menstrual cycle resumes. However, in some cases, hormonal contraception can start earlier: ask your doctor for information. If you take Effiprev you should not breast-feed your baby unless your doctor tells you that you can.

After a miscarriage or miscarriage: Follow your doctor's instructions.

If you forget to take Effiprev

If the forgotten tablet is taken within 12 hours, no further precautions are necessary; the tablet should be taken as soon as one remembers, and subsequent tablets should be taken at the usual time. The contraceptive protection of Effiprev is not impaired.

If the forgotten tablet lasts beyond 12 hours, contraceptive protection will be reduced. The risk of unwanted pregnancy is extremely high if you forget to take the pill at the beginning or at the end of the pack. In this case, the following rules must be followed

If you forgot to take a tablet in the first week:

She must take the last forgotten tablet, even if this means that she has to take two tablets at once on the same day, and then continue taking the tablets according to the usual schedule. Additional contraceptive measures (eg condom) must be used in the following days. However, if you have had sexual intercourse in the previous seven days, pregnancy cannot be ruled out, in which case please inform your doctor without hesitation.

If you forgot to take a tablet during the second week:

You must take the last missed tablet, even if this means that you have to take two tablets at once on the same day, and then continue taking the tablets according to the usual schedule. If you have taken the tablets regularly for the previous 7 days, there is no need to take additional contraceptive measures.

If you forgot to take a tablet in week 3:

By using the following procedures, it is not necessary to resort to additional contraceptive measures, as long as the tablets have been taken regularly for the previous 7 days.

There are two possible options:

1. She must take the last missed tablet, even if this means that she has to take two tablets at once on the same day, and then continue to take the tablets according to the usual schedule. he must observe the usual time interval between one pack and the next. Withdrawal bleeding is likely not to appear until the end of the second pack, and you may notice spotting or withdrawal bleeding on tablet-taking days.
2. The second option is that you stop taking the tablets from the current pack, but observe a no-tablet interval for a maximum period of seven days (the days on which the tablet has been skipped must be counted), and then continue with a new pack If you wish to start the pack on the usual day of the week, the "pill-free" interval can be shorter than 7 days!

If you have forgotten to take more than one tablet:

Talk to your doctor. Don't forget that effective contraception is not guaranteed in this case. If several tablets have been missed from the current pack and no withdrawal bleeding occurs in the first tablet-free interval, the possibility of pregnancy is high. It is therefore recommended that you contact your doctor before starting a new pack of Effiprev.

Gastrointestinal disorders

If vomiting or intense diarrhea occurs within 3-4 hours of taking the tablet, the tablet may not have been fully absorbed from the gastrointestinal tract. This situation appears similar to when you forgot to take a tablet. In this case, one tablet should be taken as soon as possible, possibly within 12 hours.

If more than 12 hours have passed, follow the advice given in the section "If you forget to take Effiprev" regarding taking the missed tablets.

Delay the period of menstruation

It may delay the time of onset of menstruation if, after finishing the previous pack, you continue to take Effiprev without observing the tablet-free interval. Menstruation can be delayed until the end of the second pack, or if necessary, for a longer period. shorter period. While taking tablets from the second pack you may experience spotting or withdrawal bleeding on tablet-taking days. After finishing the second pack of tablets, taking Effiprev can be resumed regularly after a tablet-free period of 7 days.

If you want your period to occur on a different day

If you have always followed the tablet-taking instructions correctly, your period will occur on approximately the same day every four weeks. If you want your period to start on a different day of the week, the length of the tablet-free interval should be reduced as needed. Never extend the tablet-free period! For example, let's say that your period usually occurs on Friday, but you want it to appear on Tuesday (so three days earlier). To achieve this, start taking the tablets from the next pack three days earlier. However, if the no-tablet interval is greatly shortened (3 days or less), there is no stop of bleeding, but spotting or withdrawal bleeding while taking the second pack.

What to do if bleeding occurs between periods

In some cases, women taking COCs may experience small withdrawal bleeds or spotting, especially during the first few months of using the product. It may therefore be necessary to use tampons or sanitary towels; however, you must continue to take the pills. Once your body has adapted to the effects of the film-coated tablets, the irregular bleeding will stop: it usually takes three courses for this to happen. If the bleeding persists, appears more intense, or returns, contact your doctor.

What to do if withdrawal bleeding does not occur

If the tablets have been taken correctly, according to the instructions, and if no vomiting or diarrhea has occurred, pregnancy appears very unlikely. You should continue taking Effiprev as usual. If your period does not occur twice in a row, you may be pregnant. Contact your doctor without hesitation. You can continue to take Effiprev after having a pregnancy test on the advice of your doctor.

If you stop taking Effiprev

You can stop taking Effiprev at any time you wish. If you still want to avoid becoming pregnant, consult your doctor for other reliable methods of contraception. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Overdose What to do if you have taken an overdose of Effiprev

If you take more Effiprev than you should

There are no data on Effiprev overdose. According to information from the use of other combined oral contraceptives, toxicity following overdose is very low in both adults and children. Overdose can cause nausea, vomiting and, in girls, vaginal bleeding. If you have taken multiple tablets. of Effiprev as necessary, ask your doctor for advice.

If you have noticed that a child has probably swallowed several tablets, contact your doctor without hesitation.

Side Effects What are the side effects of Effiprev

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you get any side effects, especially if they are severe or persistent, or if there is any change in your health that you think might be due to Effiprev, 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 of taking combined hormonal contraceptives, see section 2 "What you need to know before you use Effiprev.

The frequency of undesirable effects was classified as follows:

Very common it occurs in more than 1 case in every 10 women treated Common: it occurs from 1 to 10 cases in every 100 women treated Uncommon: it occurs from 1 to 10 cases in every 1,000 women treated Rare: it occurs from 1 to 10 cases in every 10,000 women treated Very rare: occurs in less than 1 case in every 10,000 women treated, including sporadic cases and those with unknown frequency

Women taking hormonal contraceptives have an increased risk of thromboembolism. Certain factors may further increase this risk (see Section 2).

Serious side effects

For more serious side effects in women taking combined oral contraceptives see section "Warnings and precautions". If necessary, get medical help immediately.

Other possible side effects

In the table below, the undesirable effects of Effiprev are listed in decreasing order of frequency. Frequencies indicated relate to undesirable effects possibly related to Effiprev observed in clinical trials. None of the side effects occurred with a "very common" frequency.

System and organ classification Frequency of undesirable effects common Uncommon Rare Nervous system disorders Headache Migraine, leg cramps Ischemic stroke cerebrovascular disorders Psychiatric disorders Depressed mood, nervousness Anorexia, decreased libido, aggressive reactions, apathy Ocular pathologies Ophthalmological disorders Visual disturbances, conjunctivitis, intolerability to contact lenses Auditory and labyrinthine disorders Hearing difficulties Cardiac pathologies Tachycardia, heart disease Vascular pathologies Venous disorders High or low blood pressure Thrombophlebitis, venous and arterial thromboembolism (VTE and ATE) / pulmonary embolism, hematoma, cerebrovascular disorders Disorders of the blood and lymphatic system Anemia Respiratory, thoracic and mediastinal disorders Sinusitis, asthma, upper respiratory infections Gastrointestinal disorders Abdominal pain Nausea, vomiting Diarrhea Skin and subcutaneous tissue disorders Acne / acneiform dermatitis, rash, eczema, skin disorders, chloasma, hair loss Erythema multiforme, itching Endocrine pathologies Hypertrichosis, hirsutism Renal and urinary disorders Urinary tract infections Diseases of the reproductive system and breast Breast tenderness or pain Irregular bleeding, amenorrhea, dysmenorrhea, breast enlargement, development of ovarian cysts, dyspareunia, vaginitis / vulvovaginitis, changes in vaginal discharge Hypomenorrhea, mastitis, fibrocystic mastopathy, breast secretions, leiomyoma, endometritis, salpingitis Infections and infestations Vaginal candidiasis or other fungal infections General disorders and administration site conditions Flushing, fatigue / weakness, indisposition, back pain, changes in body weight, increased appetite, edema Allergic reactions, flu-like symptoms

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

• The following side effects have been observed in women taking COCs (see section "Warnings and precautions")
• hypertension;
• liver tumors;
• yellowish-brown spots on the face and body (chloasma);
• development or worsening of diseases whose origin is not completely clear, but which are related to the use of combined oral contraceptives:
• inflammatory bowel disease (Crohn's disease or ulcerative colitis);
• disturbance of hemoglobin metabolism (porphyria);
• some diseases of the immune system (systemic lupus erythematosus);
• rash with blisters in the final stage of pregnancy (gestational herpes);
• convulsions, Sydenham's chorea;
• blood clotting disorder associated with kidney disease (haemolytic-uremic syndrome);
• hereditary angioedema;
• jaundice.

The pill and breast cancer

The risk of breast cancer is slightly higher in women taking COCs. However, because the risk of developing breast cancer in women under 40 is low, the number of extra cases is modest when compared to the overall risk of breast cancer. Sex hormones affect the mammary gland. Variations in the hormonal field (eg due to the use of hormonal contraceptives) can create situations in which the sensitivity of the mammary glands to other factors that favor tumor development is enhanced, with a consequent increase in the probability of developing cancer. Studies recognize that the development of breast cancer in middle-aged women is related to the early and extensive use of COCs.

If you get any of the side effects, talk to your doctor or pharmacist. This also applies to undesired effects not listed in this leaflet

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not described in the package leaflet. The reporting of these effects can also be made through the National Reporting Network. By reporting side effects you can help provide more information on the safety of this drug.

Expiry and Retention

Keep this medicine out of the sight and reach of children.

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

This medicinal product does not require any special storage conditions.

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

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 Effiprev is available in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

EFFIPREV TABLETS COATED WITH FILM

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 2 mg of dienogest and 0.03 mg of ethinylestradiol.

Excipients with known effects: lactose monohydrate (54.6 mg), glucose (0.085 mg) and soy lecithin (0.031 mg).

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Film-coated tablet.

White or ivory white, round shaped, biconvex film-coated tablets.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Hormonal contraception.

The decision to prescribe EFFIPREV 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 EFFIPREV and that associated with other Combined Hormonal Contraceptives - CHC ( see sections 4.3 and 4.4).

04.2 Posology and method of administration

Dosage

The film-coated tablets should be taken at the same time each day (with liquid if necessary), according to the sequence shown on the blister. One film-coated tablet should be taken daily for 21 consecutive days. Each subsequent pack should be started after a 7-day tablet-free period; withdrawal bleeding usually occurs during this period. Bleeding usually starts 2-3 days after taking the last tablet and may still be ongoing when taking the first tablet from the next pack.

Method of administration

For oral use

How to start taking Effiprev

No hormonal contraceptive treatment (in the last month)

The first film-coated tablet should be taken on the first day of your natural menstrual cycle (the first day of your period, defined as Day 1).

Changing from a combined contraceptive (combined oral contraceptive, vaginal ring, transdermal patch) to oral contraception

The woman should start taking Effiprev the day after the usual no-active tablet interval or the day after the last placebo tablet of the previous oral contraceptive, or the day after taking the last active tablet of the previous oral contraceptive. In case a vaginal ring or transdermal patch has been used, the woman should start taking Effiprev preferably on the day of removal of these devices, or at the latest when the next application should be made.

Changing from a progestogen-only method of contraception (minipill, injection, implant) or from a progestogen-releasing intrauterine device (IUS)

Women taking progestogen-only minipills can switch to COCs at any time. Those using implants or IUS can start on the day the implant or IUS is removed. Women receiving injections can start taking the film-coated tablets on the day the next injection should be given. However, in all these cases it is recommended to use an additional supportive method of contraception for the first 7 days of taking the tablets.

For lactation see section 4.6.

After a first trimester abortion

The tablets can be taken immediately; no additional contraceptive measures are necessary.

After childbirth or second-trimester abortion

The intake of the tablets can be started 21-28 days after delivery or after a second trimester abortion. If the intake of the product is delayed, it is necessary to resort to an additional contraceptive method (eg barrier methods) for the first ones. 7 days of taking the tablets. However, if the woman has already had sexual intercourse, a possible pregnancy must be ruled out or the first menstrual period must be waited before starting the film-coated tablets.

Behavior in case of forgotten tablet

If the forgotten tablet is taken within 12 hours, no further precautions are necessary; the tablet should be taken as soon as you remember that you have forgotten it and subsequent tablets should be taken at the usual time.

If you are more than 12 hours late in taking a tablet, contraceptive protection may be reduced. In this case, the following principles apply:

1. Tablet-taking must never be discontinued for more than 7 days.

2. To achieve "adequate suppression of the hypothalamic-pituitary-ovarian axis, it is necessary to take the tablets continuously for 7 days.

Based on the above, the following suggestions for daily practice can be proposed:

First week

The patient should take the last missed tablet as soon as she remembers, even if this involves taking two tablets at the same time, and should then continue taking the tablets at the usual time each day. Additional contraceptive measures (e.g. condom) should be used for the next 7 days. However, if the woman has had sexual intercourse in the previous 7 days, a pregnancy cannot be ruled out. The risk of pregnancy is proportional to the number of tablets forgotten and increases as the forgetting period approaches the monthly tablet-free interval.

Second week

The patient should take the last missed tablet as soon as she remembers, even if this involves taking two tablets at the same time, and should then continue taking the tablets at the usual time each day. If the woman has taken the tablets correctly in the 7 days preceding the forgotten tablet, no additional contraceptive measures are required. However, if more than one tablet has been forgotten or if tablet intake has not been regular, additional contraceptive measures should be used for the next 7 days.

Third week

During this period, the risk of reduced contraceptive reliability is extremely high, considering the approaching no-tablet interval. However, it is still possible to prevent reduced contraceptive protection by changing the tablet-taking schedule. By adopting one of the following protocols it is therefore not necessary to take additional contraceptive measures, provided that the woman has taken all the tablets regularly in the 7 days preceding the first missed tablet. If not, it is recommended to follow the first of the two options and also to use extra contraceptive measures for the next 7 days.

1. The patient should take the last missed tablet as soon as she remembers, even if this involves taking two tablets at the same time, and then she should continue taking the tablets at the usual time each day. The next pack should be started immediately after the current pack is finished, ie without leaving any gap between packs. The patient is unlikely to experience withdrawal bleeding before the end of the second pack, however when taking the tablets they may have spotting or break-trough bleeding.

2. The second possibility is to stop taking the tablets from the current pack, and to observe a tablet-free interval for up to seven days (including the days when the tablets have been forgotten), and then continue with a new package.

If many tablets have been missed from the current pack and withdrawal bleeding does not occur in the first regular tablet-free interval, the possibility of an ongoing pregnancy cannot be excluded.

Gastrointestinal disorders

If vomiting or diarrhea occurs within 3-4 hours of taking the tablet, the tablet may not have been fully absorbed by the body. In this case, a tablet should be taken as soon as possible.

If more than 12 hours have elapsed, follow the recommendations in section 4.2 regarding the omission of some tablets. If the patient does not wish to change the usual dosing schedule, the required tablet (or tablets) must be withdrawn from a new pack.

How to delay or change your withdrawal period

To delay menstruation, Effiprev must continue to be taken by switching from one pack to another after finishing the previous pack, without observing the tablet-free interval. During the use of the second pack the patient may notice spotting or withdrawal bleeding on the days of taking the tablets. Once the second pack of tablets is finished, taking Effiprev can be resumed regularly at the end of the usual 7-day break.

If the woman wishes to shift her period to another day of the week than it occurs with the current schedule, the length of the tablet-free interval can be shortened to the desired days. However, the shorter the period. tablet-free time interval, the greater the likelihood of spotting or withdrawal bleeding while taking the second pack (similar to when you want to delay your period).

04.3 Contraindications

In the presence of the following disorders and conditions, the use of combined oral contraceptives is contraindicated. In the event of the first occurrence of the disorders listed below while using the combined contraceptive tablets, the intake should be stopped immediately.

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

- 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

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

- current or previous cerebrovascular event;

- severe liver disease in active phase or in history, if the values ​​of liver function tests have not yet returned to normal;

- liver tumor in progress (benign or malignant) or in anamnesis;

- Known or suspected sex-steroid-dependent cancers (cancers of the genital organs or breasts);

- vaginal haemorrhage of unknown origin;

- current or previous pancreatitis if associated with severe hypertriglyceridemia;

- severe renal failure or acute renal failure.

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 EFFIPREV 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 EFFIPREV 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 containing levonorgestrel, norgestimate or norethisterone are associated with a lower risk of VTE. It is not yet known in how the risk associated with EFFIPREV compares with these lower risk products. The decision to use a product other than those associated with a lower risk of VTE should only be made after discussion with the woman to ensure that she understands the risk of VTE associated with CHCs, how its current risk factors affect 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 of a COC is resumed after a break of 4 or more weeks.

In consideration of the possibility of serious damage to health (see section 4.8), in case of persistence of risk factors (such as varicose veins, advanced phlebitis and thrombosis, presence of heart disease, obesity, blood clotting disorders) it is necessary to evaluate carefully about the possible risks and benefits of using combined oral contraceptives before starting therapy with Effiprev.

About 2 out of 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).

Epidemiological studies in women using low-dose combined oral contraceptives (

It is estimated that out of 10,000 women who use a levonorgestrel-containing CHC, about 61 will develop a VTE in a year.

Limited epidemiological data suggest that the risk of VTE associated with dienogest-containing COCs may be similar to the risk associated with levonorgestrel-containing COCs.

The number of VTEs per year is less than the number expected in pregnant or postpartum women.

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

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

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

Risk factors for VTE

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

EFFIPREV 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. Note: Temporary restraint, including air travel lasting> 4 hours, can also be a risk factor for VTE, especially in women with other risk factors In these situations it is advisable to stop using the patch / pill / ring (in case of elective surgery at least four weeks earlier) and not restart it until two weeks after complete resumption of mobility. To avoid unwanted pregnancy, another method of contraception must be used. If Effiprev 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, 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 in the 6-week period of the puerperium, must be considered (for information on "Fertility, pregnancy and lactation" see section 4.6.

Symptoms of VTE (deep vein thrombosis and pulmonary embolism)

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

Symptoms of deep vein thrombosis (DVT) can include:

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

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

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

Symptoms of pulmonary embolism (PE) can include:

- sudden and unexplained onset of shortness of breath 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). Effiprev 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 must 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 (BMI body mass index) above 30 kg / m2) The risk increases considerably as the BMI increases. Especially important in women with other risk factors. Positive family history (arterial thromboembolism in a sibling or parent, especially at a relatively young age, i.e. before age 50). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding to take any COCs. Migraine An increase in migraine frequency or severity during CHC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation. Other medical conditions associated with adverse vascular events Diabetes mellitus, hyperhomocysteinemia, atrial valvulopathy and fibrillation, dyslipoproteinemia and systemic lupus erythematosus.

Symptoms of ATE

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

Symptoms of cerebrovascular accident can include:

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

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

- sudden confusion, difficulty in elocution or understanding;

- sudden difficulty seeing in one or both eyes;

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

- loss of consciousness or fainting with or without convulsions.

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

Symptoms of myocardial infarction (MI) can include:

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

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

- feeling of fullness, indigestion or choking;

- sweating, nausea, vomiting or dizziness;

- extreme weakness, anxiety or shortness of breath;

- rapid or irregular heartbeats.

Tumors

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

A meta-analysis of 54 epidemiological studies found that there is a slightly increased relative risk (RR = 1.24) of breast cancer diagnosis in women currently using COCs. This excess risk decreases over 10 years after discontinuation of COC treatment. For more information see section 4.8.

Breast cancer belongs to the family of hormone-dependent malignant tumors. Some conditions such as early menarche, late menopause (after 52 years of age), the state of nulliparity, the presence of anovulatory cycles, etc., have long been recognized as risk factors for the development of breast cancer. These risk factors increase the possibility of hormonal effects in the pathogenesis of breast cancer. Hormone receptors play a central role in the biology of breast cancer. Some of these hormone receptors induce growth factors, such as transforming growth factor alpha (TGF-alpha).

Estrogen and progestogen affect the proliferation of breast cancer cells. Among others, this represents the biological rationale for the pharmacological treatment of postmenopausal hormone receptor positive breast cancer.

Numerous epidemiological studies on the connection between the use of combined oral contraceptives and breast cancer recognize that the development of breast cancer in middle-aged women is related to the early and extensive use of combined oral contraceptives. However this is only one factor among the possible factors involved.

On rare occasions, benign liver tumors and very rarely malignant liver tumors have been observed in women who have taken long-term oral contraceptives. In isolated cases, these tumors have resulted in life-threatening abdominal haemorrhage. The possibility of hepatic neoplasia should be considered as a differential diagnosis in the presence of severe pain in the upper abdomen, hepatomegaly or signs suggestive of intra-abdominal haemorrhage.

Other conditions

If hypertriglyceridaemia is present in the patient's personal or family history, the use of COCs may increase the risk of developing pancreatitis.

Although increased blood pressure is a common occurrence in women taking COCs, clinically relevant increases in blood pressure are a rare event. However, if hypertension develops while taking COCs, treatment should be stopped and Appropriate antihypertensive therapy should be instituted. Following successful resolution of the hypertensive state, it will be possible to resume treatment with combined oral contraceptives, if the doctor deems it clinically appropriate.

If, during the use of a COC in the presence of a pre-existing hypertensive state, consistently elevated blood pressure values ​​or a significant increase in blood pressure are observed not responding adequately to antihypertensive treatment, the COC should be discontinued.

Where deemed appropriate, COC use may be resumed if normotensive values ​​are recorded following antihypertensive therapy.

Although no causal relationship has been proven, the following diseases / conditions worsen both with COC use and during pregnancy: cholestatic jaundice and / or cholestatic pruritus, gallstones, porphyria, systemic lupus erythematosus, haemolytic uremic syndrome , Sydenham's chorea, gestational herpes, hearing impairment caused by otosclerosis of the middle ear.

If active or chronic liver disease is present, the use of COCs should be suspended until liver function tests have returned to normal.

The reappearance of cholestatic jaundice and / or itching already manifested during pregnancy or during previous treatment with sex steroids requires the discontinuation of hormonal contraceptives.

COCs can reduce glucose tolerance and increase the demand for insulin in peripheral tissues; however, it is not usually necessary to change the antidiabetic regimen in women taking COCs. However, diabetic women should be closely monitored, especially at the start of taking the tablets.

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

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

Worsening of endogenous depression or epilepsy has been reported during COC use.

The use of estrogen in girls can cause premature closure of the epiphysis with consequent reduction of final height in adulthood.

Compounds containing progestogens may exhibit the antagonistic properties of aldosterone, which can have a major impact on the potassium level.

Medical examinations / visits

Before initiating or resuming use of Effiprev, 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 Effiprev 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.

Regular periodic medical check-ups are important, as some contraindications or risk factors may first occur during the use of COCs.

Reduced effectiveness

The efficacy of COCs may be reduced in the following circumstances: if the patient fails to take the tablets regularly, in the presence of vomiting or severe diarrhea (see section 4.2) or due to interactions with other medicinal products (see section 4.5).

Cycle control anomalies

Taking oral contraceptives can cause irregular vaginal bleeding (spotting or withdrawal bleeding), especially in the first months of use. Therefore, it is advisable to evaluate any irregular blood loss only after a hormonal balance has been reached, which is usually occurs after three treatment cycles.

If irregular bleeding persists or occurs after previously regular cycles, possible non-hormonal causes must be excluded, and appropriate diagnostic measures, including possibly diagnostic curettage, must be implemented to rule out malignancy or pregnancy.

Occasionally, withdrawal bleeding may not occur at all during the off days. If the tablets have been taken correctly (according to the instructions in section 4.2), it is very unlikely that you are pregnant. If withdrawal bleeding does not appear at the end of the second pack of tablets, or if the woman has not followed the advice above, pregnancy must be ruled out before starting a new pack.

Metabolic interactions resulting in increased clearance of sex hormones may induce withdrawal bleeding or reduce contraceptive action (see section 4.5).

Herbal preparations containing St. John's wort (Hypericum perforatum) should not be taken concomitantly with Effiprev, as they may lead to a potential reduction in contraceptive efficacy (see section 4.5).

Effiprev contains lactose, glucose and lecithin (from soy). Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or peanut and soy allergy should not take this medicine.

04.5 Interactions with other medicinal products and other forms of interaction

Interactions with other medicines

Several drugs that increase the clearance of sex hormones can induce withdrawal bleeding or reduce contraceptive action. These interactions have been demonstrated in the case of hydantoin, barbiturates, primidone, carbamazepine and rifampicin.An interaction is also suspected in the case of rifabutin, efavirenz, nevirapin, oxycarbazepine, topiramate, felbamate, ritonavir, nelvinafir, griseofulvin and herbal preparations containing St. John's wort (Hypericum perforatum). These drugs increase the induction of liver enzymes.

A reduction in the efficacy of COCs is also possible with some antibiotics (such as ampicillin or tetracycline), although the mechanism of this effect has not yet been elucidated.

Women on short-term therapy (up to one week) with any of the above classes of medicines, must use additional contraceptive measures (eg a barrier method) while taking the concomitant medicine and for 7 days after stopping the drug. therapy.

Concomitant treatment with rifampicin requires the adoption of additional contraceptive measures (eg a barrier method) while taking the concomitant medicinal product and for 4 weeks following its discontinuation. If concomitant administration of the medicinal product continues even after the end of a pack, the next pack of the same should be started without observing the usual no-intake interval.

In case of long-term treatment with hepatic enzyme inducers, the dose of contraceptive steroids should be increased. If the high dosage induces undesirable effects (e.g. irregular bleeding), or if it appears ineffective, another non-hormonal method of contraception should be used.

Known inhibitors of the CYP3A4 enzyme such as azole antifungals, cimetidine, verapamil, macrolides, diltiazem, antidepressants and grapefruit juice may increase the plasma levels of dienogest.

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

The progestogen compound may interact with ACE inhibitors, angiotensin II receptor antagonists, potassium-sparing diuretics, aldosterone antagonists, and non-steroidal anti-inflammatory drugs.

In studies in vitro dienogest did not inhibit the function of the cytochrome P450 enzyme system at the dose used, therefore interactions with regard to this enzyme system are not conceivable.

Laboratory tests

The use of contraceptive steroids may affect the results of some laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma protein levels (such as corticosteroid-binding globulin) and lipid fractions / lipoprotein, glucose metabolism parameters and those of coagulation and fibrinolysis However, these variations remain within normal limits.

Note: Information on the SmPC of concomitant medications used should be consulted to identify potential interactions.

04.6 Pregnancy and lactation

Pregnancy

Effiprev is not indicated during pregnancy.

If pregnancy occurs while taking the oral contraceptive, treatment should be stopped immediately. Extensive epidemiological studies have not shown an increased risk of congenital malformations in children born to women who had taken oral contraceptives before pregnancy, nor were they found teratogenic effects on the offspring when the drug was taken in the early stages of gestation These studies have not been conducted with Effiprev.

As only limited data are available on the use of Effiprev during pregnancy, no conclusions can be drawn regarding adverse effects on pregnancy or the health of the fetus or neonate. To date no epidemiological data are available.

Animal studies have shown reproductive toxicity during pregnancy and lactation (see section 5.3). Effects on humans are unknown. Based on the available studies on oral contraceptive use during pregnancy, there are no indications of possible teratogenic effects.

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

Feeding time

The use of COCs while breastfeeding can reduce the amount and change the composition of breast milk. Minimal amounts of active substances and / or excipients are excreted in breast milk, with potential effects on the newborn. Breastfeeding mothers are therefore advised not to take Effiprev.

04.7 Effects on ability to drive and use machines

No effects on the ability to drive and use machines have been observed.

04.8 Undesirable effects

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 table below lists the undesirable effects of tablets containing dienogest 2 mg / ethinyl estradiol 0.03 mg in decreasing order of frequency. These frequencies are related to undesirable effects observed during clinical trials with dienogest 2 mg / ethinyl estradiol 0.03 mg tablets (a total of 3590 women participated in these studies); the onset of these undesirable effects may be related to the use of Effiprev. As all side effects occurred less than 1/10 in frequency, none of them were classified as "very common".

Undesirable effects have been classified according to the following frequency convention:

Very common (≥ 1/10)

Common (≥ 1/100 to

Uncommon (≥ 1 / 1,000 to

Rare (≥ 1 / 10,000a

Very rare (

The following side effects were reported during studies with Effiprev containing dienogest 2 mg / ethinyl estradiol 0.03 mg:

System and organ classification Frequency of undesirable effects common Uncommon Rare Nervous system disorders Headache Migraine, leg cramps Ischemic stroke cerebrovascular disorders Psychiatric disorders Depressed mood, nervousness Anorexia, decreased libido, aggressive reactions, apathy Ocular pathologies Ophthalmological disorders Visual disturbances, conjunctivitis, intolerability to contact lenses Auditory and labyrinthine disorders Hearing difficulties Cardiac pathologies Tachycardia, heart disease Vascular pathologies Venous disorders High or low blood pressure Thrombophlebitis, venous and arterial thromboembolism (VTE and ATE) / pulmonary embolism, hematoma, cerebrovascular disorders Disorders of the blood and lymphatic system Anemia Respiratory, thoracic and mediastinal disorders Sinusitis, asthma, upper respiratory infections Gastrointestinal disorders Abdominal pain Nausea, vomiting Diarrhea Skin and subcutaneous tissue disorders Acne / acneiform dermatitis, rash, eczema, skin disorders, chloasma, hair loss Erythema multiforme, itching Endocrine pathologies Hypertrichosis, hirsutism Renal and urinary disorders Urinary tract infections Diseases of the reproductive system and breast Breast tenderness or pain Irregular bleeding, amenorrhea, dysmenorrhea, breast enlargement, development of ovarian cysts, dyspareunia, vaginitis / vulvovaginitis, changes in vaginal discharge Hypomenorrhea, mastitis, fibrocystic mastopathy, breast secretions, leiomyoma, endometritis, salpingitis Infections and infestations Vaginal candidiasis or other fungal infections General disorders and administration site conditions Flushing, fatigue / weakness, indisposition, back pain, changes in body weight, increased appetite, edema Allergic reactions, flu-like symptoms

The following side effects have been reported in women taking COCs:

- venous or arterial thromboembolism

- cerebrovascular events;

- hypertension;

- liver tumors;

- development or aggravation of pre-existing diseases after the use of combined oral contraceptives, such as Crohn's disease, ulcerative colitis, porphyria, systemic lupus erythematosus, gestational herpes, Sydenham's chorea, haemolytic-uremic syndrome, cholestatic jaundice;

- chloasma.

There is a slightly increased risk of breast cancer in women taking COCs. However, as the risk of developing breast cancer is low in women under the age of 40, the number of extra cases is modest when compared to the overall risk of breast cancer. For more information see sections 4.3 and 4.4.

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

For more information see sections 4.3 and 4.4.

Reporting of Suspected Adverse Reactions

It is important to report suspected adverse reactions after authorization of the medicinal product. This allows continuous monitoring of the benefit / risk ratio of the product. Healthcare professionals should report any suspected adverse reactions through the National Reporting Network.

04.9 Overdose

The acute oral toxicity of dienogest and ethinylestradiol is low. If a considerable amount of Effiprev is taken by a small child, the possibility of developing toxic symptoms is reduced. Symptoms that may occur in the event of an overdose are nausea, vomiting and, in young girls, withdrawal bleeding. No special treatment is required. If necessary, symptomatic treatment can be used.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: progestogens and estrogens, fixed combination.

ATC code: G03AA.

Effiprev is a combined oral contraceptive with anti-androgenic effect that contains ethinylestradiol as estrogen and dienogest as progestin.

Mechanism of action

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

Ethinylestradiol is a powerful, orally active synthetic estrogen. Like natural estradiol, ethinylestradiol has a proliferative effect in the epithelia of female genital organs. It stimulates the production of cervical mucus, reduces its viscosity and increases its fibrousness. L "Ethinylestradiol promotes the growth of milk ducts and inhibits breastfeeding." Ethinylestradiol stimulates extracellular water retention. Ethinylestradiol influences the parameters of lipid and carbohydrate metabolism, haemostasis, the renin-angiotensin-aldosterone system, and protein binding.

Dienogest is a derivative of nortestosterone, which has a 10-30 times lower affinity to progesterone receptors in vitro than other synthetic progestogens. In vivo dienogest did not show significant androgenic, mineralocorticoid or glucocorticoid effects.

Administered as monotherapy, dienogest inhibits ovulation at a dose of 1 mg / day.

05.2 Pharmacokinetic properties

Ethinylestradiol

Absorption

Orally taken ethinylestradiol is rapidly and completely absorbed. After taking Effiprev, maximum serum concentrations of about 67 pg / ml are reached in 1.5-4 hours. After "absorption and" first pass effect "ethinylestradiol is extensively metabolised, with a mean oral bioavailability of approximately 44%.

Distribution

Ethinylestradiol binds strongly but not specifically to serum albumin (approximately 98%) and raises serum levels of steroid hormone binding globulin (SHBG). Ethinylestradiol has an apparent volume of distribution of approximately 2.8-8.6 L / kg.

Biotransformation

Ethinylestradiol is conjugated both in the mucosa of the small intestine and in the liver. Ethinylestradiol is metabolised by aromatic hydroxylation, however different types of hydroxylated and methylated metabolites are generated which are present as free metabolites or as glucuronide or sulfate conjugates. The metabolic clearance rate is approximately 2.3-7 ml / min / kg.

Elimination

Serum levels of ethinylestradiol are reduced following two different kinetic phases characterized by half-lives of 1 hour and 10-20 hours. Unchanged drug is not subject to excretion. The metabolites of ethinylestradiol are excreted in the urine and bile with a ratio of 4: 6 and a half-life of approximately 1 day.

Steady state

Steady state is reached in the second half of the treatment period, when the serum level is twice the value of a single dose.

Dienogest

Absorption

Dienogest taken orally is absorbed quickly and completely. After taking Effiprev, maximum serum concentrations of about 51 pg / ml are reached in 2.5 hours. In association with ethinylestradiol the average bioavailability is about 96%.

Distribution

Dienogest binds to serum albumin but not to SHBG or corticosteroid-binding globulin (CBG). 10% of the amount of dienogest present in serum is free steroid, while 90% is non-specifically bound to albumin.

Dienogest has an apparent volume of distribution of approximately 37-45 l.

Biotransformation Dienogest is mainly metabolized via hydroxylation; however, conjugation also plays an important role in creating endocrinologically inactive metabolites. These metabolites are rapidly cleared from the plasma, so apart from the unchanged portion of dienogest, no significant amounts of its metabolites are detectable in human plasma. Total clearance (Cl / F) after single dose administration is 3.6 l / hour.

Elimination

Dienogest has a "half-life of 8.5-10.8 hours. Only negligible amounts of dienogest are excreted unchanged via the kidney. After administration of a dose of 0.1 mg / kg, the ratio of renal to faecal excretion is equal to 3: 1. After oral administration, 86% of the dose is eliminated within 6 days; a considerable portion is excreted in the first 24 hours, mainly in the urine.

Steady state

The pharmacokinetic profile of dienogest is not affected by serum SHBG levels. With the daily intake, the serum levels of dienogest are increased by one and a half times, and the steady state is reached after 4 days.

05.3 Preclinical safety data

In animal studies it was observed that the effect of ethinylestradiol and dienogest is limited to the pharmacological properties of the active ingredients.

Reproductive toxicity studies performed with dienogest have shown the typical effects of progestogens: increased pre- and post-implantation abnormalities, prolongation of the gestational period, increased neonatal mortality of puppies. Administration of a high dose of dienogest to animals in late pregnancy and lactation may result in impaired fertility in offspring.

Ethinylestradiol is the estrogenic component present in most COCs. Embryotoxicity has been demonstrated at high doses, and harmful effects have been observed on the differentiation of urogenital organs.

There are no preclinical toxicity data obtained on the basis of conventional studies that reveal particular risks of genotoxicity and carcinogenic potential following repeated administration of the preparation, other than those reported above related to the use of combined oral contraceptives.

However, it should be emphasized that sex hormones can promote the growth of specific hormone-dependent tissues and tumors.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Core of the tablet

Lactose monohydrate

Magnesium stearate

Cornstarch

Povidone 30

Talc

Coating

Opaglos 2 clear, containing:

Croscarmellose sodium

Glucose

Maltodextrin

Sodium citrate dihydrate

Soy lecithin

06.2 Incompatibility

Not relevant.

06.3 Period of validity

3 years.

06.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

06.5 Nature of the immediate packaging and contents of the package

PVC / PVDC / Aluminum blisters, pack sizes: 21 and 3x21 and 6x21 and 13 X21 film-coated tablets.

Not all pack sizes may be marketed.

06.6 Instructions for use and handling

No special instructions for disposal.

07.0 MARKETING AUTHORIZATION HOLDER

EFFIK ITALIA SpA

Via Lincoln 7 / A

20092 Cinisello Balsamo, Milan

08.0 MARKETING AUTHORIZATION NUMBER

042101016 - 2 mg / 0.03 mg film-coated tablets "1 x 21 tablets in PVC / PVDC / AL blister

042101028- 2 mg / 0.03 mg film-coated tablets "3 x 21 tablets in PVC / PVDC / AL blister packs

042101030 - 2 mg / 0.03 mg film-coated tablets "6 x 21 tablets in PVC / PVDC / AL blister

042101042- 2 mg / 0.03 mg film-coated tablets "13 x 21 tablets in PVC / PVDC / AL blister

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

January 2013

10.0 DATE OF REVISION OF THE TEXT

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

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