Eve

PATIENT INFORMATION LEAFLET

EVE 2 mg / 0,03 mg film-coated tablets

chlormadinone/ethinylestradiol
Equivalent medicine

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

• They are one of the most reliable reversible methods of contraception when used correctly.
• They slightly increase the risk of developing blood clots in veins and arteries, especially during the first year of use or when restarting a combined hormonal contraceptive after a break of 4 or more weeks.
• Be alert and contact your doctor if you think you have symptoms of a blood clot (see section 2 “Blood clots”).

Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What EVE is and what it is used for
2. What you need to know before taking EVE
3. How to take EVE
4. Possible side effects
5. How to store EVE
6. Contents of the pack and other information

1. WHAT EVE IS AND WHAT IT IS USED FOR

EVE is a hormonal contraceptive taken orally. When such contraceptives contain two hormones, as is the case with EVE, they are also called "combined hormonal contraceptives".
The 21 tablets in one cycle pack contain the same amount of both hormones; therefore, EVE is also referred to as a "monophasic preparation".
Hormonal contraceptives such as EVE do not protect against AIDS (HIV infection) or other sexually transmitted diseases. Only condoms can provide such protection.

2. WHAT YOU NEED TO KNOW BEFORE TAKING EVE

General notes
Before starting to use EVE, you must read the information about blood clots in section 2. It is particularly important that you read about the symptoms of a blood clot (see section 2 “Blood clots”).
Before starting treatment with EVE, your doctor will carry out a thorough general and gynecological examination, exclude pregnancy, and, after considering contraindications and precautions, decide whether EVE is suitable for you. While taking EVE, this examination should be repeated annually.

Do not use EVE
Do not use EVE if you have any of the conditions listed below. If you have any of the conditions listed below, consult your doctor. Your doctor will discuss with you other methods of birth control that might be more suitable for your case.

• if you are allergic to ethinylestradiol or chloromadinone acetate or to any of the other ingredients of this medicine (listed in section 6);
• if you have (or have ever had) a blood clot in a vein of the leg (deep vein thrombosis, DVT), lung (pulmonary embolism, PE), or other organs;
• if you notice early signs and symptoms of a blood clot, vein inflammation, or embolism, such as transient stabbing pain, chest pain, and sensation of chest tightness;
• if you know you have a disorder affecting blood clotting, such as protein C deficiency, protein S deficiency, antithrombin-III deficiency, factor V Leiden, or antiphospholipid antibodies;
• if you are due to undergo surgery or if you will be bedridden for a prolonged period (see section “Blood clots”);
• if you have diabetes or if your blood sugar levels are uncontrollably fluctuating;
• if you have high blood pressure that is difficult to control or if it increases significantly (values constantly above 140/90 mmHg);
• if you have ever had a heart attack or stroke;
• if you have (or have ever had) angina pectoris (a condition causing severe chest pain and which may be an early sign of heart attack) or transient ischemic attack (TIA – temporary stroke-like symptoms);
• if you have any of the following diseases, which may increase the risk of developing clots in the arteries:
  • severe diabetes with blood vessel damage
  • very high blood pressure
  • very high levels of fats (cholesterol or triglycerides) in the blood
  • a condition known as hyperhomocysteinemia
• if you have (or have ever had) a type of migraine called “migraine with aura”;
• if you have liver inflammation (e.g., due to a virus) or jaundice and your liver values have not yet returned to normal;
• if you have itching all over the body or suffer from a bile flow disorder, especially if this occurred during a previous pregnancy or during estrogen treatment;
• if your plasma bilirubin levels (a product of blood pigment breakdown) are elevated, for example due to a congenital excretion disorder (Dubin-Johnson or Rotor syndromes);
• if you have a meningioma or have ever been diagnosed with a meningioma (a usually benign tumor of the tissue layer between the brain and skull);
• if you have a liver tumor or have had one in the past;
• if you suffer from severe stomach pain or liver enlargement, or if you notice signs of gastric bleeding;
• if you have porphyria (a disorder of blood pigment metabolism) for the first time or if porphyria has recurred;
• if you suffer from, have suffered from, or suspect you may have a hormone-dependent malignant tumor, for example of the breast or uterus;
• if you have severe disorders of fat metabolism;
• if you suffer from or have suffered from pancreatitis associated with a marked increase in blood fats (triglycerides);
• if you suffer from unusually severe, frequent, or persistent headaches;
• if you experience sudden disturbances in perception (vision or hearing);
• if you suffer from motor disorders (particularly signs of paralysis);
• if you notice worsening of epileptic seizures;
• if you suffer from severe depression;
• if you suffer from a certain type of hearing loss (otosclerosis) that worsened during previous pregnancies;
• if you have missed your period for unknown reasons;
• in case of excessive growth of the inner layer of the uterus (endometrial hyperplasia);
• if vaginal bleeding occurs for unknown reasons.

Do not use EVE if you have hepatitis C and are taking medicines containing ombitasvir/paritaprevir/ritonavir, dasabuvir, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir (see also section “Other medicines and EVE”).
If any of these situations occur while you are taking EVE, stop taking the medicine immediately.
You must not start taking EVE, or must stop taking it immediately, if you have a high risk or multiple risk factors for developing blood clotting disorders (see section 2.2).

Warnings and precautions
Talk to your doctor or pharmacist before taking EVE:

When should you contact a doctor?
Contact a doctor urgently:

• if you notice possible signs of a blood clot, which may indicate you have a blood clot in the leg (deep vein thrombosis), in the lung (pulmonary embolism), a heart attack, or a stroke (see the following section “Blood clot (thrombosis)”).

For a description of the symptoms of these serious side effects, refer to the section “How to recognize a blood clot”.

Inform your doctor if any of the following conditions apply to you:

• If you smoke. While using combined hormonal contraceptives, smoking increases the risk of serious side effects affecting the heart and blood vessels. This risk increases with age and with the number of cigarettes smoked. This is especially true for women over 35 years of age. Women over 35 who smoke should use alternative contraceptive methods.

If any of these conditions develop or worsen while you are using EVE, inform your doctor.

• If you experience symptoms of angioedema such as swelling of the face, tongue, and/or throat and/or difficulty swallowing, or hives potentially with breathing difficulties, contact your doctor immediately. Products containing estrogens may cause or worsen symptoms of hereditary or acquired angioedema.
• if you have high blood pressure, high levels of fats in the blood, if you are overweight, or if you have diabetes (see also section “Do not use EVE” and “Other medical conditions”). In these cases, the risk of serious side effects from combined hormonal contraceptives (such as heart attack, embolism, stroke, or liver tumors) increases;
• if you have Crohn’s disease or ulcerative colitis (chronic inflammatory bowel disease);
• if you have systemic lupus erythematosus (SLE, a disease affecting the body’s natural defense system);
• if you have hemolytic uremic syndrome (HUS, a blood clotting disorder causing kidney failure);
• if you have sickle cell anemia (an inherited red blood cell disorder);
• if you have high levels of fats in the blood (hypertriglyceridemia) or a family history of this condition. Hypertriglyceridemia has been associated with an increased risk of developing pancreatitis (inflammation of the pancreas);
• if you are due to undergo surgery or if you will be bedridden for a prolonged period (see section 2 “Blood clots”);
• if you have recently given birth, your risk of developing blood clots is higher. Ask your doctor how long after delivery you can start taking EVE;
• if you have inflammation of the veins under the skin (superficial thrombophlebitis);
• if you have varicose veins.

BLOOD CLOTS
Using a combined hormonal contraceptive like EVE increases the risk of developing a blood clot compared to not using one. In rare cases, a blood clot can block blood vessels and cause serious problems.
Blood clots can develop:

• in veins (a condition called “venous thrombosis”, “venous thromboembolism” or VTE)
• in arteries (a condition called “arterial thrombosis”, “arterial thromboembolism” or ATE). Recovery from blood clots is not always complete. Rarely, long-term serious effects may occur, and very rarely, such effects may be fatal. It is important to remember that the overall risk of a harmful blood clot associated with EVE is low.

HOW TO RECOGNIZE A BLOOD CLOT
Seek immediate medical attention if you notice any of the following signs or symptoms.

BLOOD CLOTS IN A VEIN
What can happen if a blood clot forms in a vein?

• The use of combined hormonal contraceptives has been associated with an increased risk of developing blood clots in veins (venous thrombosis). However, these side effects are rare. In most cases, they occur during the first year of using a combined hormonal contraceptive.
• If a blood clot forms in a vein of the leg or foot, it may cause deep vein thrombosis (DVT).
• If a blood clot breaks loose from the leg and travels to the lung, it may cause a pulmonary embolism.
• Very rarely, a clot may 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 also
be higher if you restart taking a combined hormonal contraceptive (the same medication or
a different one) after a break of 4 or more weeks.
After the first year, the risk decreases but remains slightly higher than if you were not
using a combined hormonal contraceptive.
When you stop taking EVE, the risk of developing a blood clot returns to
normal levels 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
EVE is low.

• Among 10,000 women who do not use any combined hormonal contraceptive and who are not pregnant, about 2 will develop a blood clot over one year.
• Among 10,000 women who use a combined hormonal contraceptive containing levonorgestrel, norethisterone, or norgestimate, about 5–7 will develop a blood clot over one year.
• Among 10,000 women who use a combined hormonal contraceptive containing cyproterone acetate, such as EVE, about 6–9 women will develop a blood clot over one year.
• The risk of developing a blood clot depends on your medical history (see below “Factors that increase the risk of developing a blood clot”).

If you notice an increase in the frequency or intensity of migraine attacks during treatment with EVE (which may indicate a disturbance in blood supply to the brain), consult your doctor as soon as possible. Your doctor may advise you to stop taking EVE immediately.

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

The risk of developing a blood clot with EVE is low, but certain conditions can increase this risk. Your risk is higher:

• if you are significantly overweight (body mass index or BMI above 30 kg/m²);
• if a close relative has had a blood clot in the leg, lung, or another organ at a young age (under approximately 50 years). In this case, you may have an inherited blood clotting disorder;
• if you are scheduled for surgery or need to remain bedridden for a prolonged period due to injury or illness, or if you have a leg in a cast. You may need to stop taking EVE several weeks before surgery or during periods of reduced mobility. If you need to stop taking EVE, ask your doctor when you can restart it;
• as you get older (especially over 35 years of age);
• if you have given birth within the last few weeks.

The risk of developing a blood clot increases if you have more than one of these conditions.

Air travel (lasting >4 hours) may temporarily increase the risk of blood clot formation, particularly if you have other listed risk factors.

It is important that you inform your doctor if any of these conditions apply to you, even if you are uncertain. Your doctor may decide to stop your treatment with EVE.

If any of the above conditions change while you are using EVE—for example, if a close relative develops thrombosis without a known cause or if you gain significant 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 may lead to 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 EVE is very low, but it may increase:

• with increasing age (over 35 years);
• if you smoke. When using a combined hormonal contraceptive like EVE, it is advisable to stop smoking. If you are unable to stop smoking and are over 35 years old, your doctor may recommend using a different type of contraceptive;
• if you are overweight;
• if you have high blood pressure;
• if a close relative has had a heart attack or stroke at a young age (under approximately 50 years). In this case, you may also have an increased risk of heart attack or stroke;
• if you or a close relative have high levels of fat in the blood (cholesterol or triglycerides);
• if you suffer from migraine, especially migraine with aura;
• if you have heart problems (valvular defect, a heart rhythm disorder called atrial fibrillation);
• if you have diabetes.

If you have more than one of these conditions or if one is particularly severe, the risk of developing a blood clot may be even higher.

If any of the above conditions change while you are using EVE—for example, if you start smoking, if a close relative develops thrombosis without a known cause, or if you gain significant weight—contact your doctor.

• Tumors Some studies show that women whose cervix has been infected with a particular sexually transmitted virus (human papillomavirus) may have an increased risk of cervical cancer if they take the pill for a long time. However, it is unclear to what extent these results are influenced by other factors (e.g., differences in the number of sexual partners or use of mechanical contraceptive methods).

Studies have reported a slight increase in the risk of breast cancer in women using combined oral contraceptives (COCs). Over the 10 years following discontinuation of COC use, this increased risk gradually returns to the baseline levels associated with age. Since breast cancer is rare in women under 40 years of age, the number of additional breast cancer diagnoses in women who are currently using or have recently used COCs is limited compared to the overall risk of breast cancer.

In rare cases, benign liver tumors have developed after taking hormonal contraceptives, and even more rarely, malignant liver tumors. These can cause dangerous internal bleeding. If you experience severe stomach pain that does not resolve spontaneously, you should consult your doctor.

The use of chlormadinone acetate has been associated with the development of a generally benign tumor of the tissue layer between the brain and the skull (meningioma). The risk increases especially when used at high doses for prolonged periods (several years). If you are diagnosed with a meningioma, your doctor will stop treatment with EVE (see section 'Do not take EVE'). If you notice symptoms such as vision changes (e.g., double or blurred vision), hearing loss or ringing in the ears, loss of smell, headaches that worsen over time, memory loss, seizures, or weakness in the arms or legs, inform your doctor immediately.

• Other conditions

Psychiatric disorders

Some women using hormonal contraceptives, including EVE, have reported depression or depressed mood. Depression can be severe and sometimes may lead to suicidal thoughts. If you experience mood changes or symptoms of depression, consult your doctor as soon as possible for further medical advice.

During treatment with hormonal contraceptives, many women experience a slight increase in blood pressure. If your blood pressure increases significantly while taking EVE, your doctor may advise you to stop taking EVE and prescribe a medication to lower your blood pressure. Once your blood pressure returns to normal, you may resume taking EVE.

If you have previously suffered from herpes during pregnancy, this condition may recur during use of a hormonal contraceptive.

If you have a specific disorder affecting blood fat levels (hypertriglyceridemia) or if this condition runs in your family, there is an increased risk of pancreatitis. If you have acute or chronic liver function disorders, your doctor may advise you to stop taking EVE until liver values return to normal. If you previously developed jaundice during a pregnancy or while using a hormonal contraceptive and it reoccurs, your doctor will advise you to stop taking EVE.

If you are diabetic, and your blood glucose levels are under control while taking EVE, your doctor will monitor you closely throughout your treatment. It may also be necessary to adjust your diabetes treatment.

In uncommon cases, brown patches on the skin (chloasma) may appear, especially if they occurred during a previous pregnancy. If you know you are predisposed, avoid direct sunlight or UV rays during treatment with EVE.

Conditions that may be negatively affected

Specialist medical supervision is also necessary in the following cases:

• if you suffer from epilepsy
• if you suffer from multiple sclerosis
• if you suffer from severe muscle cramps (tetany)
• if you suffer from migraine (see also section 2)
• if you suffer from asthma
• if you suffer from impaired heart or kidney function (see also section 2)
• if you suffer from a disorder called "Sydenham's chorea" (chorea minor)
• if you are diabetic (see also section 2)
• if you suffer from a liver disorder (see also section 2)
• if you suffer from a fat metabolism disorder (see also section 2)
• if you suffer from an immune system disorder (including systemic lupus erythematosus)
• if you are significantly overweight
• if you suffer from high blood pressure (see also section 2)
• if you suffer from endometriosis (the tissue lining the uterine cavity, called endometrium, is found outside this lining layer – see also section 2)
• if you suffer from varicose veins or vein inflammation (see also section 2)
• if you have blood clotting disorders (see also section 2)
• if you suffer from a breast disorder (mastopathy)
• if you have had benign tumors (fibroids) in the uterus
• if you previously suffered from blisters (herpes gestationis) during pregnancy
• if you suffer from depression (see also section 2)
• if you suffer from chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis).

If you currently suffer from, have suffered from in the past, or develop any of the above conditions during treatment with EVE, consult your doctor.

• Efficacy If you do not take the contraceptive regularly, or if you experience vomiting or diarrhea after taking the medicine (see section 3), or if you take certain medications concomitantly (see section 2), the contraceptive effect may be reduced. In very rare cases, metabolic disorders may impair contraceptive efficacy.

Even if you take hormonal contraceptives correctly, absolute control of contraception cannot be guaranteed.

• Irregular bleeding Irregular vaginal bleeding (intermenstrual bleeding/spotting) may occur, especially during the first few months of taking hormonal contraceptives. If this irregular bleeding continues for 3 months or reappears after previously regular cycles, consult your doctor.

Spotting may also indicate a reduced contraceptive effect. In some cases, the withdrawal bleed may be absent after taking EVE for 21 days. If you have taken EVE according to the instructions in section 3 (below), pregnancy is unlikely. If EVE was not taken according to the instructions before the first absence of withdrawal bleeding, a pregnancy must be definitively ruled out before continuing to use the medicinal product.

Children and adolescents

EVE is indicated only after the first menstrual period. The safety and efficacy of EVE in adolescents under 16 years of age have not been established.

Elderly

EVE is not indicated after menopause.

Other medicines and EVE

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

Do not use EVE if you have hepatitis C and are taking medications containing ombitasvir/paritaprevir/ritonavir, dasabuvir, or glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir, as these medications can cause increases in liver function test results (elevated liver enzymes ALT). Your doctor will prescribe a different type of contraceptive before starting treatment with these medications.

EVE can be resumed approximately 2 weeks after completing this treatment. See section “How to take EVE”.

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

• epilepsy (e.g., barbiturates, carbamazepine, phenytoin, topiramate, felbamate, oxcarbazepine, barbital, primidone),
• tuberculosis (e.g., rifampicin, rifabutin),
• sleep disorders (modafinil),
• HIV and hepatitis C (so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors, e.g., ritonavir, nevirapine, efavirenz),
• fungal infections (griseofulvin),
• high blood pressure in the pulmonary blood vessels (bosentan),
• herbal preparations containing St. John’s wort (Hypericum perforatum). If you wish to use herbal products containing St. John’s wort while using EVE, you must first consult your doctor.
• medicines that stimulate intestinal motility (e.g., metoclopramide) and activated charcoal may interfere with the absorption of the active ingredients in EVE.

If you are taking a medicine containing any of the above active substances (except St. John’s wort) or start taking one, you may continue taking EVE. During treatment with these medicines, you must use additional mechanical contraceptive methods (such as condoms). If you take these medicines, you must use additional mechanical contraceptive methods for 28 days after the end of treatment. If long-term treatment with the above medicines is required, you must use non-hormonal contraceptive methods. Ask your doctor or pharmacist for advice.

Interactions between EVE and other medicines may increase or intensify the adverse effects of EVE. The following medicines may negatively affect the tolerability of EVE:

• ascorbic acid (a preservative, also known as vitamin C),
• paracetamol (for pain relief and fever control),
• atorvastatin (lowers blood cholesterol),
• troleandomycin (an antibiotic),
• imidazole antifungals – e.g., fluconazole (for treating fungal infections),
• indinavir (a preparation for treating HIV infection).

EVE may affect the action of other medicines. The efficacy or tolerability of the following medicines may be reduced by EVE:

• certain benzodiazepines, e.g., diazepam (for treating sleep disorders),
• cyclosporine (an immunosuppressive medicine),
• theophylline (for treating asthma symptoms),
• corticosteroids, e.g., prednisolone (known as steroids, anti-inflammatory medicines, e.g., for lupus, arthritis, psoriasis),
• lamotrigine (for treating epilepsy),
• clofibrate (reduces elevated cholesterol levels),
• paracetamol (for pain relief and fever control),
• morphine (a potent specific analgesic – pain relief),
• lorazepam (used to treat anxiety disorders).

If concomitant administration of another medicine extends beyond the end of the tablets in a blister pack, you should start the next pack of COCs without observing the usual tablet-free interval.

Also read the package leaflets of other prescribed medications.

If you are taking insulin or other medicines to lower blood glucose levels, inform your doctor. The dosage of these medicines may need to be adjusted.

The above also applies if you have taken any of these active substances shortly before starting EVE.

Administration of EVE may alter certain laboratory tests assessing liver, kidney, adrenal gland, and thyroid function, certain blood proteins, carbohydrate metabolism, and blood coagulation. Changes generally remain within the normal laboratory range. Before undergoing blood tests, inform your doctor that you are taking EVE.

Pregnancy and breastfeeding

Pregnancy

EVE is not indicated during pregnancy. If you become pregnant while taking EVE, you must stop taking the medicine immediately. However, previous use of EVE does not justify termination of pregnancy.

Breastfeeding

If you take EVE, be aware that milk production may be reduced and milk quality compromised. Very small amounts of active ingredients pass into breast milk. Hormonal contraceptives such as EVE should only be taken after breastfeeding has been discontinued.

Driving and use of machines

Combined hormonal contraceptives are not known to have negative effects on the ability to drive or use machinery.

EVE contains lactose

If your doctor has diagnosed you with an intolerance to certain sugars, consult him before taking this medicine.

3. HOW TO TAKE EVE

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
Method of administration
For oral use.
How and when to take EVE
Take the first tablet from the position in the pack marked with the corresponding day of the week (e.g., “Sun” for Sunday) and swallow it without chewing. Then take one tablet daily, following the direction of the arrow, preferably at the same time each day and ideally in the evening. The interval between taking two tablets should ideally always be 24 hours. The days printed on the pack will help you check daily whether you have already taken the tablet for that particular day.
Take one tablet daily for 21 consecutive days, followed by a 7-day interval. Usually, 2–4 days after taking the last tablet, you will experience a withdrawal bleed similar to your menstrual period. After the 7-day interval, continue taking tablets from the next pack of EVE, regardless of whether bleeding has stopped or not.

When to start taking EVE
If you have not previously used any hormonal contraceptive (during the last menstrual cycle):
Take the first tablet of EVE on the first day of your next menstrual cycle.
Contraceptive protection starts on the first day of tablet intake and continues throughout the 7-day tablet-free interval.
If your period has already started, take the first tablet on day 2–5 of the cycle, regardless of whether bleeding has stopped. However, in this case, you must use additional mechanical contraceptive methods (e.g., condoms) during the first 7 days of tablet intake (seven-day rule).
If your period has already lasted more than five days, wait until your next cycle to start taking EVE.

If you have previously used another combined hormonal contraceptive:
Take all tablets from the old pack as usual. Start taking EVE the day after the usual tablet-free interval (during which no tablets or placebo tablets are taken) of the previous combined hormonal contraceptive.

If you have previously used a progestogen-only hormonal contraceptive (minipill or “POP”):
When using a progestogen-only hormonal contraceptive, a withdrawal bleed similar to menstruation may not occur. Take the first tablet of EVE the day after taking the last progestogen-only pill (minipill). In this case, you must use additional mechanical contraceptive methods for the first 7 days.

If you have previously used hormonal contraceptive injections or a contraceptive implant:
Take the first tablet of EVE on the day the implant is removed or on the day the next injection was due. In this case, you must use additional contraceptive methods for the first 7 days.

If you have had a spontaneous or induced abortion in the first three months of pregnancy:
After a spontaneous or induced abortion, you may start taking EVE immediately. In this case, no additional contraceptive method is required.

If you have given birth or had a spontaneous abortion between the 3rd and 6th month of pregnancy:
If you are not breastfeeding, you may start taking EVE 21–28 days after delivery. No additional mechanical contraceptive method is required.
However, if more than 28 days have passed since delivery, you must use additional mechanical contraceptive methods for the first 7 days.
If you have already had sexual intercourse, you must either exclude pregnancy before starting EVE or wait until your next menstrual cycle.
Do not use EVE if you are breastfeeding (see section “Pregnancy and breastfeeding”).

How long can you take EVE
You may take EVE for as long as desired, provided no health risks arise (see section “Do not use” and “Other diseases”). After stopping EVE, the onset of the next menstrual cycle may be delayed by about one week.

What to do in case of vomiting or diarrhoea during EVE intake
If you experience vomiting or diarrhoea within 4 hours of taking a tablet, the active ingredients of EVE may not be completely absorbed. This situation is similar to missing a tablet. Immediately take another tablet from a new pack. If possible, take the new tablet within 12 hours of taking the last tablet and continue taking EVE at your usual time. If this is not possible, or if more than 12 hours have passed, follow the instructions in section 3.4 (“If you forget to take EVE”) or consult your doctor.

If you take more EVE than you should
There is no evidence of serious signs of poisoning after taking an excessive number of tablets in a single dose. Symptoms such as nausea, vomiting, and slight vaginal bleeding, particularly in young women, may occur. In such cases, consult a doctor, who may, if necessary, monitor your fluid and electrolyte balance and liver function.

If you forget to take EVE
If you forget to take a tablet at your usual time, take it as soon as possible, but no later than 12 hours after the usual time. In this case, no additional contraceptive methods are needed, and you may continue taking tablets as usual.
If the interval exceeds 12 hours, the contraceptive effect of EVE is no longer assured. In this case, take the missed tablet immediately and continue taking EVE at your usual time. This may mean taking two tablets in one day. During the following 7 days, you must use additional mechanical contraceptive methods (e.g., condoms). If during these 7 days you finish the current pack of EVE, immediately start taking tablets from the next pack: there must be no break between packs (seven-day rule). A normal withdrawal bleed will probably not occur until after the entire new pack has been used. While using the new pack, breakthrough bleeding or spotting may occur.
The greater the number of missed tablets, the higher the risk of reduced pregnancy protection. If you missed one or more tablets in the first week and had sexual intercourse in the week before the missed dose, there is a risk of pregnancy. The same applies if you miss one or more tablets and do not experience any bleeding during the subsequent tablet-free interval. In such cases, consult your doctor.

If you wish to delay your menstrual period
Although not recommended, it is possible to delay your menstrual period (withdrawal bleeding) by starting a new EVE blister pack immediately, without observing the usual tablet-free interval, and continuing until the end of the second blister pack. During use of the second blister pack, spotting (light bleeding) or intermenstrual bleeding may occur. After the usual 7-day tablet-free interval, continue with the next blister pack.
Before deciding to delay your menstrual period, it is advisable to consult your doctor.

If you wish to shift the first day of your menstruation
If you take the tablets as instructed, your menstrual period/withdrawal bleeding will begin during the tablet-free week. To shift this day, shorten the tablet-free interval (never extend it!). For example, if the tablet-free week starts on Friday and you wish to shift the bleeding to Tuesday (3 days earlier), start the new blister pack 3 days earlier than usual. If you significantly shorten the interval (e.g., to 3 days or less), you may not experience any bleeding during this shortened interval. Spotting (light bleeding or blood spots) or intermenstrual bleeding may also occur.
If you are unsure how to proceed, consult your doctor.

If you stop treatment with EVE
When you stop taking EVE, your ovaries quickly resume full activity, and you may become pregnant.

If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE EFFECTS

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them. If you experience any adverse effect, especially if severe or persistent, or if you notice any change in your health that you think could be due to EVE, inform your doctor.
Contact your doctor immediately if you experience any of the following symptoms of angioedema: swelling of the face, tongue and/or throat and/or difficulty swallowing, or hives with potential breathing difficulties (see also section “Warnings and precautions”).
An increased risk of developing blood clots in the veins (venous thromboembolism (VTE)) or blood clots in the arteries (arterial thromboembolism (ATE)) exists in all women taking combined hormonal contraceptives. For more detailed information on the different risks associated with taking combined hormonal contraceptives, see section 2 “What you need to know before taking EVE”.
The frequencies with which adverse effects have been reported are defined as follows:
Very common: may affect more than 1 in 10 people
Nausea, vaginal spotting, menstrual pain, absence of menstruation.
Common: may affect up to 1 in 10 people
Depression, nervousness, irritability, dizziness, migraine (and/or worsening), visual disturbances, vomiting, acne, stomach ache, fatigue, feeling of heaviness in the legs, fluid retention, weight gain, increased blood pressure.
Uncommon: may affect up to 1 in 100 people
Fungal vaginal infections, onset of changes in breast connective tissue, drug hypersensitivity, including skin allergic reactions, changes in blood lipid values including increased triglycerides, decreased libido, stomach discomfort, intestinal rumbling, diarrhoea, pigmentation disorders, brown spots on the face, hair loss, dry skin, tendency to sweat, back pain, muscle problems, breast secretion.
Rare: may affect up to 1 in 1,000 people
Inflammation of the vagina, increased appetite, conjunctivitis, discomfort when wearing contact lenses, deafness, tinnitus, high blood pressure, low blood pressure, circulatory collapse, varicose veins, urticaria, eczema, inflamed skin, pruritus, worsening of psoriasis, excessive body or facial hair, breast enlargement, longer and/or heavier menstrual periods, premenstrual syndrome (physical and emotional problems before the onset of menstruation).

• Harmful blood clots in a vein or artery, for example:
• in a leg or foot (DVT)
• in a lung (PE)
• heart attack
• stroke
• mini-stroke or temporary stroke-like symptoms, known as transient ischaemic attack (TIA)
• blood clots in the liver, stomach/intestine, kidneys or eye. The likelihood of developing a blood clot may be higher if you have any other condition that increases this risk (see section 2 for more information on conditions that increase the risk of blood clots and symptoms of a blood clot).

Very rare: may affect up to 1 in 10,000 people
Erythema nodosum.
Additionally, the following adverse reactions have been reported with the active substances ethinylestradiol and chlormadinone acetate during post-marketing use: weakness and allergic reactions including swelling of the deeper layers of the skin (angioedema).
Serious adverse effects:
Combined hormonal contraceptives have been associated with an increased risk of serious disorders and adverse effects:

• risk of obstruction of veins and arteries ( see section 2 )
• risk of biliary tract disorders ( see section 2 )
• risk of tumours (e.g. liver tumours, which in isolated cases may cause potentially fatal bleeding into the abdominal cavity, cervical or breast cancer - see section 2 )
• worsening of chronic intestinal inflammation (Crohn’s disease, ulcerative colitis - see section 2 ).

Please read the information contained in section 2 carefully and, if necessary, seek immediate advice from your doctor.
Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report adverse effects directly via the national reporting system at the website https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. HOW TO STORE EVE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging and on the blister
(cycle pack), after the word "Exp". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. PACKAGING CONTENTS AND OTHER INFORMATION

What EVE contains

• The active substances are ethinylestradiol and chloromadinone acetate. Each film-coated tablet contains 0.03 mg of ethinylestradiol and 2.0 mg of chloromadinone acetate.

The other components are:
monohydrate lactose, magnesium stearate (Ph.Eur.), maize starch, pregelatinized starch,
hydrogenated cottonseed oil, hydroxypropylcellulose, hypromellose, talc, titanium dioxide (E171), iron oxide red (E172)
Description of the appearance of EVE and packaging contents
Film-coated tablets, round, pink-red in colour.
The film-coated tablets are packaged in aluminum PVC/COC/PVDC
or aluminum PVC/PVDC blisters/cards, placed in a cardboard box.
Pack sizes:
Blister: 21 film-coated tablets.
Calendar packs: 1x21, 3x21, 4x21 and 6x21 film-coated tablets.
Not all pack sizes may be marketed.
Marketing Authorization Holder
Sandoz S.p.A.
Viale Luigi Sturzo 43
20154 Milan
Italy
Manufacturer
Haupt Pharma Münster GmbH Schleebruggenkamp 15, 48159 Münster, Germany
Salutas Pharma GmbH Otto von Guericke Allee 1, 39179 Barleben, Germany
Lek Pharmaceuticals d.d. Verovškova ulica 57, SI - 1526 Ljubljana, Slovenia
This medicinal product is authorized in the European Economic Area countries under the
following names:
IT: EVE