Zoely - patient leaflet, side effects, dosage

Patient leaflet - Zoely

1. What Zoely is and what it is used for

Zoely is a contraceptive pill that is used to prevent pregnancy.

All 24 white film-coated tablets are active tablets that contain a small amount of two different female hormones. These are nomegestrol acetate (a progestogen) and estradiol (an oestrogen).
The 4 yellow film-coated tablets are inactive tablets that do not contain hormones and are called placebo tablets.
Contraceptive pills that contain two different hormones, like Zoely, are called ‘combined pills’.
Nomegestrol acetate (the progestogen in Zoely) and estradiol (the oestrogen in Zoley) work

together to prevent ovulation (release of an egg from the ovary) and to reduce the chance of any released egg being fertilised and making you pregnant.

2. What you need to know before you use Zoely

General notes

Before you start using Zoely you should read the information on blood clots (thrombosis) in section 2.

It is particularly important to read the symptoms of a blood clot – see section 2 “Blood clots”.

Before you can begin taking Zoely, your doctor will ask you about your personal health history and that of your close relatives in order to give you an individual advice on the treatment. The doctor will also measure your blood pressure and, depending upon your personal situation, may also carry out some other tests.

This leaflet describes situations where you should stop taking the pill, or where the pill protection against pregnancy may be decreased. In such situations you should not have sex or you should take extra non-hormonal contraceptive precautions, e.g., use a condom or another barrier method. Do not use rhythm or temperature methods. These methods may not protect against pregnancy because the pill alters the usual changes in temperature and cervical mucus that occur during the menstrual cycle.

Zoely, like other hormonal contraceptives, does not protect against human immunodeficiency virus (HIV) infection (which can cause acquired immunodeficiency syndrome, AIDS) or any other sexually transmitted disease.

Do not use Zoely

You must not use Zoely if you have any of the conditions listed below. If you do have any of the conditions listed below, you must tell your doctor. Your doctor will discuss with you what other form of birth control would be more appropriate.

if you have (or have ever had) a blood clot in a blood vessel of your legs (deep vein thrombosis, DVT), your lungs (pulmonary embolism, PE) or other organs;

if you have a disorder affecting your blood clotting – for instance, protein C deficiency, protein

S deficiency, antithrombin – III deficiency, Factor V Leiden or antiphospholipid antibodies;

if you need an operation or if you are off your feet for a long time (see section ‘Blood clots);

if you have ever had a heart attack or a stroke;

if you have ever had angina pectoris (a condition that causes severe chest pain and may be a first sign of blocked blood vessels around your heart, known as heart attack) or transient ischaemic attack (TIA, temporary stroke symptoms);

if you have any of the following diseases that may increase your risk of a clot in the arteries:

– severe diabetes with blood vessel damage;
– very high blood pressure;
– a very high level of certain fat in the blood (cholesterol or triglycerides);
– a condition known as hyperhomocysteinaemia;

if you have ever had a type of migraine called ‘migraine with aura’;

if you have ever had inflammation of the pancreas (pancreatitis) associated with high levels of fat in your blood;

if you have ever had a severe liver disease and your liver function is not yet working normally;

if you have ever had a benign or malignant tumour in the liver;

if you have ever had, or if you may have, cancer of the breast or the genital organs;

in case of presence or history of meningioma (generally benign tumour of the tissue located between the brain and the skull). In case of doubt, contact your doctor.

if you have any unexplained bleeding from the vagina;

if you are allergic to estradiol or nomegestrol acetate, or any of the other ingredients of this medicine (listed in section 6).

If any of these conditions appear for the first time while using Zoely, stop taking it at once and tell your doctor. In the meantime, use a non-hormonal contraceptive. See also ‘General Notes’ in section 2 above.

Warnings and precautions

Talk to your doctor or pharmacist before using Zoley.

When should you contact your doctor?

Seek urgent medical attention if you:

notice possible signs of a blood clot that may mean you are suffering from a blood clot in the leg (i.e., deep vein thrombosis), a blood clot in the lung (i.e., pulmonary embolism), a heart attack or a stroke (see “Blood clots” section below).

For a description of the symptoms of these serious side effects please go to “How to recognise a blood clot”.

notice any changes in your own health, especially involving any of the items mentioned in this leaflet (see also in section 2 ‘Do not use Zoely’; do not forget about the changes in the health of your immediate family);
feel a lump in your breast;
experience symptoms of angioedema such as swollen face, tongue and/or throat and/or difficulty swallowing or hives together with difficulty breathing;
are going to use other medicines (see also in section 2 ‘Other medicines and Zoely’);
are to be immobilised or are to have surgery (tell your doctor at least four weeks in advance);
have unusual, heavy vaginal bleeding;
forgot one or more tablets in the first week of the blister pack and had unprotected sex in the seven days before (see also in section 3 ‘If you forget to take Zoely’);
have severe diarrhoea or experience severe vomiting;
miss periods and suspect you may be pregnant (do not start the next blister pack until your doctor tells you, see also in section 3 ‘If you have missed one or more periods’).

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

If the condition develops, or gets worse while you are using Zoely, you should also tell your doctor if you have:

hereditary and acquired angioedema. Consult your doctor immediately if you experience symptoms of angioedema such as swollen face, tongue and/or throat and/or difficulty swallowing or hives, together with difficulty breathing. Medicines containing oestrogens may induce or worsen symptoms of angioedema;
epilepsy (see in section 2 ‘Other medicines and Zoely’);
liver disease (for instance jaundice) or gallbladder disease (for instance gallstones);
diabetes;
depression;
Crohn’s disease or ulcerative colitis (chronic inflammatory bowel disease);
systemic lupus erythematosus (SLE, a disease affecting your natural defence system);
haemolytic uraemic syndrome (HUS, a disorder of blood clotting causing failure of the

kidneys);

sickle cell anaemia (an inherited disease of the red blood cells);
elevated levels of fat in the blood (hypertriglyceridaemia) or a positive family history for this condition. Hypertriglyceridaemia has been associated with an increased risk of developing pancreatitis (inflammation of the pancreas);
an inflammation in the veins under the skin (superficial thrombophlebitis);
varicose veins.
a condition that occurred for the first time or worsened during pregnancy or previous use of female hormones (e.g. hearing loss, porphyria [a disease of the blood], herpes gestationis [skin rash with vesicles during pregnancy], Sydenham’s chorea [a disease of the nerves in which sudden movements of the body occur]);
or have ever had chloasma (a skin yellowish-brown pigment patches, so called ‘pregnancy patches’, particularly on the face). If so, avoid too much exposure to the sun or ultraviolet light;

Also tell your doctor if:

a close relative has or has ever had breast cancer;
you need an operation or if you are off your feet for a long time (see in section 2 ‘Blood clots);
you have just given birth you are at an increased risk of blood clots. You should ask your doctor

how soon after delivery you can start taking Zoely.

BLOOD CLOTS

Using a combined hormonal contraceptive such as Zoely 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 (referred to as ‘venous thrombosis’, ‘venous thromboembolism’ or VTE)
in the arteries (referred to as an ‘arterial thrombosis’, ‘arterial thromboembolism’ or ATE).

Recovery from blood clots is not always complete. Rarely, there may be serious lasting effects or, very rarely, they may be fatal.

It is important to remember that the overall risk of a harmful blood clot due to Zoely is small.

HOW TO RECOGNISE A BLOOD CLOT

Seek urgent medical attention if you notice any of the following signs or symptoms.

Are you experiencing any of these signs?	What are you possibly 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 be felt only when standing or walking increased warmth in the affected leg change in colour of the skin on the leg e.g. turning pale, red or blue	Deep vein thrombosis
sudden unexplained breathlessness or rapid breathing; sudden cough without an obvious cause, which may bring up blood; sharp chest pain which may increase with deep breathing; severe light headedness or dizziness; rapid or irregular heartbeat; severe pain in your stomach; If you are unsure, talk to a doctor as some of these symptoms such as coughing or being short of breath may be mistaken for a milder condition such as a respiratory tract infection (e.g., a ‘common cold’).	Pulmonary embolism
Symptoms most commonly occur in one eye: immediate loss of vision or painless blurring of vision which can progress to loss of vision	Retinal vein thrombosis (blood clot in the eye)
chest pain, discomfort, pressure, heaviness sensation of squeezing or fullness in the chest, arm or below the breastbone; fullness, indigestion or choking feeling; upper body discomfort radiating to the back, jaw, throat, arm and stomach; sweating, nausea, vomiting or dizziness; extreme weakness, anxiety, or shortness of breath; rapid or irregular heartbeats	Heart attack
sudden weakness or numbness of the face, arm or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes; sudden trouble walking, dizziness, loss of balance or coordination; sudden, severe or prolonged headache with no known cause; loss of consciousness or fainting with or without seizure. Sometimes the symptoms of stroke can be brief with an almost immediate and full recovery, but you should still seek urgent medical attention as you may be at risk of another stroke.	Stroke
swelling and slight blue discolouration of an extremity; severe pain in your stomach (acute abdomen).	Blood clots blocking 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 connected with an increase in the risk of blood clots in the vein (venous thrombosis). However, these side effects are rare. Most frequently, they occur in the first year of use of 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 may form in a vein 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 product or a different product) after a break of 4 weeks or more.

After the first year, the risk gets smaller but is always slightly higher than if you were not using a combined hormonal contraceptive.

When you stop Zoely your risk of 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 a blood clot in the leg or lung (DVT or PE) with Zoely is small.

Out of 10,000 women who are not using any combined hormonal contraceptive and 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.
The risk of a blood clot with Zoely compares to the risk with a combined hormonal

contraceptive that contains levonorgestrel.

The risk of having a blood clot will vary according to your personal medical history (see “Factors that increase your risk of a blood clot” below).

Factors that increase your risk of a blood clot in a vein

The risk of a blood clot with Zoely is small but some conditions will increase the risk. Your risk is higher:

if you are very overweight (body mass index or BMI over 30 kg/m2);
if one of your immediate family has had a blood clot in the leg, lung or other organ at a young age (e.g., below the age of about 50 years). In this case you could have a hereditary blood clotting disorder;
if you need to have an operation, or if you are off your feet for a long time because of an injury or illness, or you have your leg in a cast. The use of Zoely may need to be stopped several weeks before surgery or while you are less mobile. If you need to stop Zoely ask your doctor when you can start using it again.
as you get older (particularly above about 35 years);
if you gave birth less than a few weeks ago.

The risk of developing a blood clot increases the more conditions you have.

Air travel (for longer than 4 hours) may temporarily increase your risk of a blood clot, particularly if you have some of the other factors listed.

It is important to tell your doctor if any of these conditions apply to you, even if you are unsure. Your doctor may decide that Zoely needs to be stopped.

If any of the above conditions change while you are using Zoely, for example a close family member has a thrombosis for no known reason or you gain a lot of weight, tell your doctor.

BLOOD CLOTS IN AN ARTERY

What can happen if a blood clot forms in an artery?

Like a blood clot in a vein, a clot in an artery can cause serious problems. For example, it can cause a heart attack or a stroke.

Factors that increase your risk of a blood clot in an artery

It is important to note that the risk of a heart attack or stroke from using Zoely is very small but can increase:

with increasing age (beyond about 35 years);
if you smoke. When using a combined hormonal contraceptive like Zoely you are advised to stop smoking. If you are unable to stop smoking and are older than 35 years 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 could also have a higher risk of having a heart attack or stroke;
if you, or someone in your immediate family, have a high level of fat in the blood (cholesterol or triglycerides);
if you get migraines, especially migraines with aura;
if you have a problem with your heart (valve disorder, disturbance of the rhythm 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 increased even more.

If any of the above conditions change while you are using Zoely, for example, you start smoking, a close family member experiences a thrombosis for no known reason or you gain a lot of weight, tell your doctor.

Cancer

Breast cancer has been detected slightly more often in women using combined contraceptives, but it is not known if it is caused by the combined pills. For example, it may be that tumours are detected more in women on combined pills because they have breast examination by their doctor more often. After stopping the combined pill, the increased risk gradually reduces.

It is important to check your breasts regularly and you should contact your doctor if you feel any lump. You should also tell your doctor if a close relative has, or ever had breast cancer (see section 2 “Warnings and precautions”).

In rare cases, benign (noncancerous) liver tumours, and in even rarer cases malignant (cancerous) liver tumours have been occurred in pill users. Contact your doctor if you have unusual severe abdominal pain.

Cervical cancer is caused by an infection with the human papilloma virus (HPV). It has been reported to occur more often in women using the pill for more than 5 years. It is not known if this is due to the use of hormonal contraceptives or to other factors, such as difference in sexual behaviour.

Meningiomas

Cases of meningioma (generally benign tumours of the brain) have been reported with prolonged use (several years) of nomegestrol monotherapy (without estradiol) at higher doses of 3.75 and 5 mg and more (see section ‘Do not use Zoely’). If a meningioma is diagnosed, treatment with Zoely should be stopped.

Psychiatric disorders

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

Laboratory tests

If you are having any blood or urinary test, tell your doctor that you are using Zoely as it may affect the results of some tests.

Children and adolescents

No data on efficacy and safety are available in adolescents below 18 years.

Other medicines and Zoely

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

Also tell any other healthcare professional who prescribes or dispenses another medicine that you use Zoely.

There are medicines that can make Zoely less effective in preventing pregnancy, or can cause unexpected bleeding. These include medicines used to treat:
– epilepsy (e.g. primidone, phenytoin, phenobarbital, carbamazepine, oxcarbazepine, topiramate, felbamate);
– tuberculosis (e.g. rifampicin);
– HIV infection (e.g. rifabutin, ritonavir, efavirenz);
– Hepatitis C virus (HCV) infection (e.g. protease inhibitors);
– other infectious diseases (e.g. griseofulvin);
– high blood pressure in the blood vessels in the lungs, known as pulmonary arterial hypertension (bosentan).

The herbal product St. John’s wort (Hypericum perforatum) may also stop Zoely from working properly. If you want to use herbal products containing St. John’s wort while you are already using Zoely you should check with your doctor first.
If you are taking medicines or herbal products that might make Zoely less effective, a barrier contraceptive method should also be used. Since the effect of another medicine on Zoely may last up to 28 days after you stop the medicine, it is necessary to use the additional barrier contraceptive method for that long.
Some medicines can increase the levels of the active substances of Zoely in the blood. The effectiveness of the pill is maintained, but tell your doctor if you are using anti-fungal medicines containing ketoconazole.
Zoely may also interfere with the working of other medicines, such as the anti-epileptic lamotrigine.
The Hepatitis C virus (HCV) combination regimen ombitasvir/paritaprevir/ritonavir with or

without dasabuvir as well as regimen glecaprevir/pibrentasvir may cause increases in liver function blood test results (increase in ALT liver enzyme) in women using CHCs containing ethinylestradiol. Zoely contains estradiol instead of ethinylestradiol. It is not known whether an increase in ALT liver enzyme can occur when using Zoely with this HCV combination regimen. Your doctor will advise you.

Pregnancy and breast-feeding

Zoely must not be used by women who are pregnant, or who think they may be pregnant. If you get pregnant while using Zoely you should stop using Zoely immediately and contact your doctor.

If you want to stop Zoely because you want to get pregnant, see in section 3 ‘If you stop taking Zoely’.

Zoely is not usually recommended for use during breast-feeding. If you wish to use the pill while breast-feeding, you should check with your doctor.

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

Driving and using machines

Zoely has no or negligible effect on your ability to drive and use machines.

Zoely contains lactose

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

3. How to use Zoely

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

When and how to take the tablets

The Zoely blister contains 28 film-coated tablets: 24 white tablets with the active substances (number 1–24) and 4 yellow tablets without active substances (number 25–28).

Each time you start a new blister of Zoely, take the number 1 white active tablet in the left-hand top corner (see ‘Start’). Choose from the 7 stickers with day indicators the one in the grey column that begins with your starting day. For example, if you start on a Wednesday, use the day label sticker that starts with ‘WED’. Place it on the blister, just above the row of white active tablets where it reads ‘Place day label here’. This allows you to check whether you took your daily tablet.

Take one tablet each day at about the same time, with some water if necessary.

Follow the direction of the arrows on the blister, so use the white active tablets first and then the yellow placebo tablets.

Your period will start during the 4 days that you use the yellow placebo tablets (so-called withdrawal bleeding). Usually it will start 2–3 days after you use the last white active tablet and may not have finished before you start the next blister.

Start taking the next blister immediately after you use the last yellow placebo tablet, even if your period hasn’t finished. This means that you will always start a new blister on the same day of the week, and also that you have your period on roughly the same days each month.

Some women may not have their period every month when they are using the yellow placebo tablets. If you have taken Zoely every day according to these directions, it is unlikely that you are pregnant (see also section 3 ‘If you have missed one or more periods’).

Starting your first pack of Zoely

If you have not used a contraceptive with hormones in the previous month

Begin with Zoely on the first day of the cycle (that is the first day of your period). If you start Zoely on the first day of your period you are immediately protected against pregnancy. You do not need to use an additional contraceptive method.

Changing from another combined hormonal contraceptive (combined pill, vaginal ring, or transdermal patch)

You can start Zoely preferably on the day after you have taken the last active tablet (the last tablet containing the active substances) of your present pill blister (this means no tablet-free break). If your present pill blister also contains inactive (placebo) tablets you can start Zoely on the day after taking the last active tablet (if you are not sure which this is, ask your doctor or pharmacist). You can also start Zoely later, but never later than the day following the tablet-free break of your present pill (or the day after the last inactive tablet of your present pill). In case you change from a vaginal ring or transdermal patch, it is best to start Zoely on the day you remove the ring or patch. You can also start, at the latest, on the day you would have started using the next ring or patch.

If you follow these instructions, it is not necessary to use an additional contraceptive method. If you have any concerns about whether you are protected please seek the advice of your doctor.

Changing from a progestogen-only pill (minipill)

You can switch any day from the progestogen-only pill to start Zoely on the next day, but you must use a barrier method of contraception (for example, a condom) during the first 7 days that you are taking Zoely.

When changing from a progestogen-only injectable, implant or a hormone-medicated intrauterine system (IUS)

Start using Zoely when your next injection is due or on the day that your implant or IUS is removed. But if you are having intercourse, make sure you also use a barrier method of contraception for the first 7 days that you are taking Zoely.

After having a baby

You can start Zoely between 21 and 28 days after having a baby. If you start later than day 28, you must use a barrier method of contraception (for example, a condom) during the first 7 days that you are taking Zoely. If, after having a baby, you have had sex before starting Zoely, you must first be sure that you are not pregnant or you must wait until your next period.

If you are breast-feeding and want to start Zoely after having a baby, see section 2 ‘Pregnancy and Breast-feeding’.

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

After a miscarriage or an abortion Follow the advice of your doctor.

If you take more Zoely than you should

There have been no reports of serious harm from taking too many Zoely tablets. If you have taken several tablets at once, then you may feel sick (nausea), vomit or bleed from the vagina. If you have taken too many Zoely tablets, or you discover that a child has taken some, ask your doctor or pharmacist for advice.

If you forget to take Zoely ____________________________________________________________________

The following advice only refers to missed white active tablets.

if you are less than 24 hours late taking a tablet, the pill protection against pregnancy is maintained. Take the tablet as soon as possible and then take the next tablets at the usual time.
if you are 24 or more hours late taking a tablet, the pill protection against pregnancy may be reduced. The more tablets you have forgotten, the higher your risk of becoming pregnant. There is a particularly high risk of becoming pregnant if you miss white active tablets at the beginning or at the end of the blister. Therefore you should follow the rules given below.

Day 1–7 of white active tablet intake (see picture and schedule)

Take the forgotten white active tablet as soon as possible, even if this means that you have to take two tablets at the same time, and continue to take the next tablet at the usual time. However, use a barrier method of contraception (for example, a condom) as an extra precaution until you have taken your tablets correctly for 7 days in a row.

If you had sex in the week before missing the tablets, there is a possibility of you becoming or being pregnant. In that case, contact your doctor immediately.

Day 8–17 of white active tablet intake (see picture and schedule)

Take the last missed tablet as soon as you remember (even if this means taking two tablets at the same time) and take the next tablets at the usual time. If you have taken your tablets correctly in the 7 days prior to the missed tablet, the protection against pregnancy is not reduced, and you do not need to use extra precautions. However, if you have missed more than 1 tablet, use a barrier method such as a condom as an extra precaution until you have taken your tablets correctly for 7 days in a row.

Day 18–24 of white active tablet intake (see picture and schedule)

There is a particularly high risk of you becoming pregnant if you miss white active tablets close to the yellow placebo tablet interval. By adjusting your intake schedule this higher risk can be prevented.

The following two options can be followed. You do not need to use extra precautions if you have taken your tablets correctly in the 7 days prior to the missed tablet. If this is not the case, you should follow the first of these two options and use a barrier method of contraception (for example, a condom) as an extra precaution until you have taken your tablets correctly for 7 days in a row.

Option 1 : Take the last missed white active tablet as soon as possible, even if this means that you have to take two tablets at the same time, and continue to take the next tablets at the usual time. Start the next blister as soon as the white active tablets in the current blister are finished, so skip the yellow placebo tablets. You may not have your period until you take the yellow placebo tablets at the end of the second blister, but you may have light or menstruation-like bleeding while taking the white active tablets.

Option 2 : Stop taking the white active tablets and start taking the yellow placebo tablets for a maximum of 3 days so that the total number of placebo plus missed white active tablets is not more than 4. At the end of the yellow placebo tablets intake, start the next blister.

If you cannot remember how many white active tablets you have missed, follow the first option, use a barrier method such as a condom as an extra precaution until you have taken your tablets correctly for 7 days in a row, and contact your doctor (as you may not have been protected from being pregnant). If you have forgotten to take white active tablets in a blister, and you do not have the expected monthly period while taking the yellow placebo tablets from the same blister, you may be pregnant. You must contact your doctor before you start with the next blister.

The following advice only refers to forgotten yellow placebo tablets

The last 4 yellow tablets of the fourth row are placebo tablets which do not contain active substances. If you forgot to take one of these tablets, the Zoely protection against pregnancy is maintained. Throw away the yellow placebo tablet(s) you missed and start taking the tablets of the next blister at the usual time.

Picture

Schedule if you are 24 or more hours late taking white active tablets

If you vomit or have severe diarrhoea

If you vomit within 3–4 hours of taking a white active tablet, or you have severe diarrhoea, there is a risk that the active substance in Zoely tablets may not have been completely absorbed into your body. The situation is similar to if you forget a white active tablet. After vomiting or diarrhoea, you must take another white active tablet from a reserve blister as soon as possible. If possible, take it within 24 hours of when you normally take your pill. Take the next tablet at the usual time. If this is not possible or 24 or more hours have passed, you should follow the advice given under „If you forget to take Zoely“. If you have severe diarrhoea, please tell your doctor.

The yellow tablets are placebo tablets which do not contain active substances. If you vomit or have severe diarrhoea within 3–4 hours of taking a yellow placebo tablet, the Zoely protection against pregnancy is maintained.

If you want to delay your period

Even if it is not recommended, you can delay your period by missing out taking the yellow placebo tablets from the fourth row and going straight to a new blister of Zoely. You may have light or menstruation-like bleeding while using this second blister. When you wish your period to begin during the second blister, stop taking the white active tablets and start taking the yellow placebo tablets. Finish this second blister by taking the 4 yellow placebo tablets, and then start with the next (third) blister. If you are not sure what to do, ask your doctor or pharmacist for advice .

If you want to change the starting day of your period

If you take the tablets according to the instructions, then your period will begin during the placebo days. If you have to change this day, reduce the number of placebo days – when you take the yellow placebo tablets – but never increase them (4 is the maximum). For example, if you start taking the yellow placebo tablets on Friday, and you want to change this to a Tuesday (3 days earlier) you must start a new blister 3 days earlier than usual. You may not have any bleeding during the shortened period of yellow placebo tablet intake. While using the next blister you may have light or menstruation-like bleeding on white active tablet-taking days. If you are not sure what to do, ask your doctor or pharmacist for advice.

If you have unexpected bleeding

With all combined pills, for the first few months, you can have some irregular vaginal bleeding (spotting or breakthrough bleeding) between your periods. You may need to use sanitary protection, but keep taking your tablets as usual. Irregular vaginal bleeding usually stops once your body has adjusted to the pill (usually after about 3 months). If bleeding continues, becomes heavy or starts again, contact your doctor.

If you have missed one or more periods

Clinical trials with Zoely have shown that you may occasionally miss your regular monthly period after Day 24.

If you have taken all the tablets correctly, and you have not vomited or had severe diarrhoea, or used other medicines, then it is very unlikely that you are pregnant. Keep taking Zoely as usual. See also in section 3 ‘If you vomit or have severe diarrhoea’ or in section 2 ‘Other medicines and Zoely’.
If you have not taken all the tablets correctly, or if your expected period does not happen twice in a row, you may be pregnant. Contact your doctor immediately. Do not start the next blister of Zoely until your doctor has checked that you are not pregnant.

If you stop taking Zoely

You can stop taking Zoely at any time. If you do not want to become pregnant, first ask your doctor about other methods of birth control.

If you stop taking Zoely because you want to get pregnant, it is best to wait until you have had a natural period before trying to become pregnant. This will help you to determine when the baby will be due.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you get any side effect, particularly if severe or persistent, or have any change to your health that you think may be due to Zoely, please talk to your doctor.

An increased risk of blood clots in your veins (venous thromboembolism (VTE)) or blood clots in your arteries (arterial thromboembolism (ATE)) is present for all women taking combined hormonal contraceptives. For more detailed information on the different risks from taking combined hormonal contraceptives, please see section 2, “What you need to know before you use Zoely”.

The following side effects have been linked with the use of Zoely:

Very common (may affect more than 1 in 10 people):

acne
changes to menstrual periods (e.g. absence or irregularity)

Common (may affect up to 1 in 10 people):

decreased interest in sex; depression/depressed mood; mood changes
headache or migraine
feeling sick (nausea)
heavy menstrual periods, breast pain, pelvic pain
weight gain

Uncommon (may affect up to 1 in 100 people):

increased appetite, fluid retention (oedema)
hot flush
swollen abdomen (belly)
increased sweating, hair loss, itching, dry skin, oily skin
heaviness in limbs
regular but scanty periods, larger breasts, breast lump, milk production while not pregnant,

premenstrual syndrome, pain during sex, dryness in the vagina or vulva, spasm of the uterus

irritability
increased liver enzymes

Rare (may affect up to 1 in 1,000 people):

harmful blood clots in a vein or artery, for example:

o in a leg or foot (i.e., DVT)

o in a lung (i.e., PE)

o heart attack

o stroke

o mini-stroke or temporary stroke-like symptoms known as a transient ischaemic attack

(TIA)

o blood clots in the liver, stomach/intestine, kidneys or eye.

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

decreased appetite
increased interest in sex
disturbance in attention
dry eye, contact lens intolerance
dry mouth
golden brown pigment patches, mostly in the face, excessive hair growth
vaginal smell, discomfort in the vagina or vulva
hunger
disease of the gallbladder

Allergic (hypersensitive) reactions have been reported in users of Zoely, but the frequency cannot be estimated from the available data.

Further information on the possible side effect changes to menstrual periods (e.g. absence or irregular) during the use of Zoely is described in section 3 ‘When and how to take the tablets’, ‘If you have unexpected bleeding’ and ‘If you have missed one or more periods’).

Reporting of side effects

If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed inBy reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zoely

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

This medicine does not require any special storage conditions.

Combined pills (including Zoely tablets) no longer required should not be disposed via wastewater or the municipal sewage system. The hormonal active substances in the tablet may have harmful effects if they reach the aquatic environment. Return them to a pharmacy or dispose them in another safe way according to local requirements. These measures will help to protect the environment.

6. Contents of the pack and other information

What Zoely contains

– The active substances are: nomegestrol acetate and estradiol

White active film-coated tablets: Each tablet contains 2.5 mg nomegestrol acetate and 1.5 mg estradiol (as hemihydrate).

Yellow placebo film-coated tablets: The tablet does not contain active substances.

– The other ingredients are:

What Zoely looks like and contents of the pack

The active film-coated tablets (tablets) are white and round. They are coded ‘ne’ on both sides.

The placebo film-coated tablets are yellow and round. They are coded ‘p’ on both sides.

Zoely comes in blisters of 28 film-coated tablets (24 white active film-coated tablets and 4 yellow placebo film-coated tablets) packed in a ply carton. Pack sizes: 28, 84, 168 and 364 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Theramex Ireland Limited

3rd Floor, Kilmore House,

Park Lane, Spencer Dock,

Dublin 1

D01 YE64

Ireland

Manufacturer

Delpharm Lille S.A.S.

Parc d’Activites Roubaix-Est

22 Rue de Toufflers

CS 50070

59452 LYS-LEZ-LANNOY

France

Teva Operations Poland Sp. z o.o.

ul. Mogilska 80

31–546 Krakow

Poland

N.V. Organon

Kloosterstraat 6

5349 AB Oss

The Netherlands

Merck Sharp & Dohme B.V.

Waarderweg 39 2031 BN Haarlem The Netherlands

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:.

Annex IV

Scientific conclusions and grounds for the variation to the terms of the marketing authorisation(s)

Scientific conclusions

Taking into account the PRAC Assessment Report on the PSUR(s) for estradiol / nomegestrol acetate, the scientific conclusions of CHMP are as follows:

In view of available data on the risks from clinical trials, the literature and in view of a plausible mechanism of action, as well as previous PSUSA outcomes, the PRAC considers a causal relationship for the drug-drug interaction between estradiol / nomegestrol acetate and glecaprevir/pibrentasvir is at least a reasonable possibility. The PRAC concluded that the sections 4.4. and 4.5 of the SmPC of product information of products containing estradiol / nomegestrol acetate should be amended accordingly.

In addition, in view of a literature data, a plausible mechanism of actions and previous PSUSA outcomes, the PRAC considers a causal relationship between estradiol / nomegestrol acetate and the exacerbation of symptoms of hereditary and acquired angioedema is at least a reasonable possibility.

The PRAC concluded that the product information of products containing estradiol / nomegestrol acetate should be amended accordingly.

Update of section 4.4 of the SmPC to add warnings on the drug-drug interaction with glecaprevir/pibrentasvir in the case of patients suffering from hepatitis C, as well as on the exacerbation of symptoms of hereditary and acquired angioedema.

Update of section 4.5 of the SmPC with details on the drug-drug interaction with glecaprevir/pibrentasvir.

The Package leaflet is updated accordingly.

The CHMP agrees with the scientific conclusions made by the PRAC.

Grounds for the variation to the terms of the marketing authorisation(s)

On the basis of the scientific conclusions for estradiol / nomegestrol acetate the CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing estradiol / nomegestrol acetate is unchanged subject to the proposed changes to the product information.

The CHMP recommends that the terms of the marketing authorisation(s) should be varied.