CARMENELLE 0.02/3 Milligram Film Coated Tablet

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
DROSPIRENONE, ETHINYLESTRADIOL
Available from:
Clonmel Healthcare Ltd
ATC code:
G03AA12
INN (International Name):
DROSPIRENONE, ETHINYLESTRADIOL
Dosage:
0.02/3 Milligram
Pharmaceutical form:
Film Coated Tablet
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
Progestogens and estrogens, fixed combinations
Authorization status:
Authorised
Authorization number:
PA0126/253/001
Authorization date:
2013-08-23

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Package leaflet: Information for the user

Carmenelle 0.02 mg/3 mg film-coated tablets

Ethinylestradiol/Drospirenone

Read all of this leaflet carefully before you start taking this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor, pharmacist or nurse.

This medicine has been prescribed for you only. Do no pass it on to others. It may harm them

even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4

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

They are one of the most reliable reversible methods of contraception if used correctly

They slightly increase the risk of having a blood clot in the veins and arteries, especially in

the first year or when restarting a combined hormonal contraceptive following a break of 4

or more weeks

Please be alert and see your doctor if you think you may have symptoms of a blood clot

(see section 2 “Blood clots”)

What is in this leaflet:

1.

What Carmenelle is and what it is used for

2.

What you need to know before you take Carmenelle

When you should not use Carmenelle

Warnings and precautions

Carmenelle and venous and arterial blood clots

Carmenelle and cancer

Bleeding between periods

What to do if no bleeding occurs during the gap week

Other medicines and Carmenelle

Taking Carmenelle with food, drink and alcohol

Laboratory tests

Pregnancy, breast-feeding and fertility

Driving and using machines

Carmenelle contains lactose

3.

How to take Carmenelle

When can you start with the first strip?

If you take more Carmenelle than you should

If you forget to take Carmenelle

What to do in the case of vomiting or severe diarrhoea

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Delaying your period: what you need to know

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

If you want to stop taking Carmenelle

4.

Possible side effects

5.

How to store Carmenelle

6.

Contents of the pack and other information

1.

What Carmenelle is and what it is used for

Carmenelle is a contraceptive pill and is used to prevent pregnancy.

Each tablet contains a small amount of two different female hormones, namely drospirenonen

and ethinylestradiol.

Contraceptive pills that contain two hormones are called “combination” pills.

2.

What you need to know before you take Carmenelle

General notes

Before you start using Carmenelle you should read the information on blood clots 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 Carmenelle, your doctor will ask you some questions about your

personal health history and that of your close relatives. The doctor will also measure your blood

pressure, and, depending upon your personal situation, may also carry out some other tests.

In this leaflet, several situations are described where you should stop using Carmenelle, or where

the reliability of Carmenelle may be decreased. In such situations you should either 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 can be unreliable

because Carmenelle alters the monthly changes of body temperature and of the cervical mucus.

Carmenelle, like other hormonal contraceptives, does not protect against HIV infection

(AIDS) or any other sexually transmitted disease.

When you should not use Carmenelle

You should not use Carmenelle 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 embolus, PE) or other organs

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

deficiency,

protein

deficiency,

antithrombin-III

deficiency,

Factor

Leiden

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 stroke

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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 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 fat in the blood (cholesterol or triglycerides)

a condition known as hyperhomocysteinaemia

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

if you have (or have ever had) an inflammation of the pancreas (pancreatitis)

if you have (or have ever had) a liver disease and your liver function is still not normal

if your kidneys are not working well (renal failure)

if you have (or have ever had) a tumour in the liver

if you have (or have ever had) or if you are suspected of having breast cancer or cancer of the

genital organs

if you have any unexplained bleeding from the vagina

if you are allergic to ethinylestradiol or drospirenone, or any of the other ingredients of this

medicine (listed in section 6). This may cause itching, rash or swelling.

When to take special care with Carmenelle

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 clot’ (thrombosis) section below.

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

blood clot”.

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

In some situations you need to take special care while using Carmenelle or any other combination

pill, and your doctor may need to examine you regularly.

If the condition develops, or gets worse while you are using Carmenelle, you should also 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 affecting your natural defence

system);

if you have haemolytic uraemic syndrome (HUS - a disorder of blood clotting causing failure of

the kidneys);

if you have sickle cell anaemia (an inherited disease of the red blood cells);

if you have 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);

if you need an operation, or you are off your feet for a long time (see in section 2 ‘Blood clots’);

if 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 Carmenelle;

If you have an inflammation in the veins under the skin (superficial thrombophlebitis);

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If you have varicose veins.

if a close relative has or has ever had breast cancer

if you have a disease of the liver or the gallbladder

if you have diabetes

if you have depression

if you have epilepsy (see page 9 "Carmenelle and using other medicines")

if you have a disease that first appeared during pregnancy or earlier use of sex hormones (for

example,

hearing

loss,

blood

disease

called

porphyria,

skin

rash

with

blisters

during

pregnancy

(gestational herpes),

nerve

disease

causing

sudden

movements

body

(Sydenham's chorea))

if you have or have ever had chloasma (a discoloration of the skin especially of the face or neck

known as “pregnancy patches”). If so, avoid direct sunlight or ultraviolet light.

if you have hereditary angioedema, products containing oestrogens may cause or worsen

symptoms.

should

your

doctor

immediately

experience

symptoms

angioedema such as swollen face, tongue and/or throat and/or difficulty swallowing or hives

together with difficulty breathing.

BLOOD CLOTS

Using a combined hormonal contraceptive such as Carmenelle 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 a ‘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 Carmenelle 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

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Are you experiencing any of these signs?

What are you possibly

suffering from?

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?

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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 Carmenelle 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 Carmenelle 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.

Out of 10,000 women who are using a combined hormonal contraceptive that contains

drospirenone, such as Carmenelle, between about 9 and 12 women will develop a blood clot

in a year.

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).

Risk of developing a blood clot

in a year

Women who are not using a combined hormonal

pill/patch/ring and 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 Carmenelle

About 9-12 out of 10,000 women

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

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

risk is higher:

if you are very overweight (body mass index or BMI over 30kg/m

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). In this case you could have a hereditary blood clotting

disorder;

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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 Carmenelle may need to be stopped several

weeks before surgery or while you are less mobile. If you need to stop Carmenelle 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 (>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 Carmenelle needs to be stopped.

If any of the above conditions change while you are using Carmenelle, for example a close family

member experiences 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 Carmenelle is very small

but can increase:

with increasing age (beyond about 35 years);

if you smoke. When using a combined hormonal contraceptive like Carmenelle you are

advised to stop smoking. If you are unable to stop smoking and are older than 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

then about 50). 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.

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If any of the above conditions change while you are using Carmenelle, 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.

Carmenelle and cancer

Breast cancer has been observed slightly more often in women using combination pills, but it is not

known whether this is caused by the treatment. For example, it may be that more tumours are

detected in women on combination pills because they are examined by their doctor more often. The

occurrence of breast tumours becomes gradually less after stopping the combination hormonal

contraceptives. It is important to regularly check your breasts and you should contact your doctor if

you feel any lump.

In rare cases, benign liver tumours, and in even fewer cases malignant liver tumours have been

reported in pill users. Contact your doctor if you have unusually severe abdominal pain.

Bleeding between periods

During the first few months that you are taking Carmenelle you may have unexpected bleeding

(bleeding outside the gap week). If this bleeding occurs for more than a few months, or if it begins

after some months, your doctor must find out what is wrong.

What to do if no bleeding occurs during the gap week

If you have taken all the tablets correctly, have not had vomiting or severe diarrhoea and you have

not taken any other medicines, it is highly unlikely that you are pregnant.

If the expected bleeding does not happen twice in succession, you may be pregnant. Contact your

doctor immediately. Do not start the next strip until you are sure that you are not pregnant.

Other medicines and Carmenelle

Always tell your doctor which medicines or herbal products you are already using. Also tell any

other

doctor

dentist

prescribes

another

medicine

pharmacist)

that

Carmenelle. They can tell you if you need to take additional contraceptive precautions (for

example condoms) and if so, for how long.

Some medicines can have an influence on the blood levels of Carmenelle and can make it less

effective in preventing pregnancy, or can cause unexpected bleeding. These include:

medicines used for the treatment of

epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine)

tuberculosis (e.g.; rifampicin)

HIV and hepatitis C Virus so-called protease inhibitors and non-nucleoside reverse

transcriptase inhibitors such as ritonavir, nevirapine, efavirenz or other infections

(griseofulvin)

high blood pressure in the blood vessels in the lungs (bosentan)

the herbal remedy St John's wort

Carmenelle may influence the effect of other medicines, e.g.

medicines containing ciclosporin

the anti-epileptic lamotrigine (this could lead to an increased frequency of seizures)

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

Taking Carmenelle with food and drink and alcohol

Carmenelle may be taken with or without food, if necessary with a small amount of water.

Laboratory tests

If you need a blood test, tell your doctor or the laboratory staff that you are taking the pill, because

hormone contraceptives can affect the results of some tests.

Pregnancy, breast-feeding and fertility

Pregnancy

If you are pregnant, do not take Carmenelle. If you become pregnant while taking Carmenelle stop

immediately and contact your doctor. If you want to become pregnant, you can stop taking

Carmenelle at any time (see also “If you want to stop taking Carmenelle”).

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

Breast-feeding

Use of Carmenelle is generally not advisable when a woman is breast-feeding. If you want to take

the pill while you are breast-feeding you should contact your doctor.

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

Driving and using machines

There is no information suggesting that use of Carmenelle affects driving or use of machines.

Carmenelle contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your

doctor before taking this medicinal product.

3.

How to take Carmenelle

Always take this medicine exactly as your doctor has told you. You should check with your doctor

or pharmacist if you are not sure.

Take one tablet of Carmenelle every day, if necessary with a small amount of water. You may take

the tablets with or without food, but you should take the tablets every day around the same time.

The strip contains 21 tablets. Next to each tablet is printed the day of the week that it should be

taken. If, for example, you start on a Wednesday, take a tablet with "WED" next to it. Follow the

direction of the arrow on the strip until all 21 tablets have been taken.

Then take no tablets for 7 days. In the course of these 7 tablet-free days (otherwise called a stop or

gap week) bleeding should begin. This so-called “withdrawal bleeding” usually starts on the 2nd or

3rd day of the gap week.

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On the 8th day after the last Carmenelle tablet (that is, after the 7-day gap week), you should start

with the following strip, whether your bleeding has stopped or not. This means that you should start

every strip on the same day of the week and that the withdrawal bleed should occur on the same

days each month.

If you use Carmenelle in this manner, you are also protected against pregnancy also during the 7

days when you are not taking a tablet.

When can you start with the first strip?

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

Begin with Carmenelle on the first day of the cycle (that is the first day of your period). If you

start Carmenelle on the first day of your

period you are immediately protected against

pregnancy. You may also begin on day 2-5 of the cycle, but then you must use extra protective

measures (for example, a condom) for the first 7 days.

Changing from a combination hormonal contraceptive, or combination contraceptive vaginal

ring or patch

You can start Carmenelle preferably on the day after the last active tablet (the last tablet

containing active substances) of your previous pill, but at the latest on the day after the tablet-

free days of your previous pill (or after the last inactive tablet of your previous pill). When

changing from a combination contraceptive vaginal ring or patch, follow the advice of your

doctor.

Changing from a progestogen-only-method (progestogen-only pill, injection, implant or a

progestogen-releasing IUD).

You may switch any day from the progestogen-only pill (from an implant or an IUD on the day

of its removal, from an injectable when the next injection would be due) but in all of these cases

use extra protective measures (for example, a condom) for the first 7 days of tablet-taking.

After a miscarriage

Follow the advice of your doctor.

After having a baby

You can start Carmenelle between 21 and 28 days after having a baby. If you start later than

day 28, use a so-called barrier method (for example, a condom) during the first seven days of

Carmenelle use.

If, after having a baby, you have had sex before starting Carmenelle (again), be sure that you

are not pregnant or wait until your next period.

If you are breast-feeding and want to start Carmenelle (again) after having a baby

Read the section on "Breast-feeding", page 6.

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

If you take more Carmenelle than you should

There are no reports of serious harmful results of taking too many Carmenelle tablets.

If you take several tablets at once then you may have symptoms of nausea or vomiting. Young girls

may have bleeding from the vagina.

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If you have taken too many Carmenelle tablets, or you discover that a child has taken some, ask

your doctor or pharmacist for advice.

If you forget to take Carmenelle

If you are less than 12 hours late taking a tablet, the protection against pregnancy is not

reduced. Take the tablet as soon as you remember and then take the following tablets again at

the usual time.

If you are more than 12 hours late taking a tablet, the protection against pregnancy may be

reduced. The greater the number of tablets that you have forgotten, the greater is the risk of

becoming pregnant.

The risk of incomplete protection against pregnancy is greatest if you forget a tablet at the

beginning or at the end of the strip. Therefore, you should keep to the following rules (see the

diagram on page 9):

More than one tablet forgotten in this strip

Contact your doctor.

One tablet forgotten in week 1

Take the forgotten tablet as soon as you remember, even if that means that you have to take two

tablets at the same time. Continue taking the tablets at the usual time and use extra precautions

for the next 7 days, for example, a condom. If you have had sex in the week before forgetting

the tablet you may be pregnant. In that case, contact your doctor.

One tablet forgotten in week 2

Take the forgotten tablet as soon as you remember, even if that means that you have to take two

tablets at the same time. Continue taking the tablets at the usual time. The protection against

pregnancy is not reduced, and you do not need to take extra precautions.

One tablet forgotten in week 3

You can choose between two possibilities:

Take the forgotten tablet as soon as you remember, even if that means that you have to take

two tablets at the same time. Continue taking the tablets at the usual time. Instead of taking

the tablet-free period start the next strip .

Most likely, you will have a period at the end of the second strip but you may have light or

menstruation-like bleeding during the second strip.

You can also stop the strip and go directly to the tablet-free period of 7 days (record the

day on which you forgot your tablet). If you want to start a new strip on the day you

always start, make the tablet-free period less than 7 days.

If you follow one of these two recommendations, you will remain protected against pregnancy.

If you have forgotten any of the tablets in a strip, and you do not have a bleeding during the first

tablet-free period, you may be pregnant. Contact your doctor before you start the next strip.

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What to do in the case of vomiting or severe diarrhoea

If you vomit within 3-4 hours after taking a tablet or you have severe diarrhoea, there is a risk that

the active substances in the pill will not be fully taken up by your body. The situation is almost the

same as forgetting a tablet. After vomiting or diarrhoea, take another tablet from a reserve strip as

soon as possible. If possible take it within 12 hours of when you normally take your pill. If that is

not possible or 12 hours have passed, you should follow the advice given under "If you forget to

take Carmenelle", page 8.

Despu

Ask your doctor for advice

Only 1 tablet forgotten

(taken more than 12

hours late)

In week 2

In week 3

Take the forgotten tablet

Use a barrier method (condom) for the following

7 days and

Finish the strip

In week 1

Had sex in the previous week before forgetting?

Take the forgotten tablet

Finish the strip

Instead of the gap week

Go straight on to the next strip

Stop the strip immediately

Begin the gap week (no longer than 7 days,

including the forgotten tablet)

Then start the next strip

More than 1 tablet

forgotten in 1 strip

Take the forgotten tablet

Finish the strip

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Delaying your period: what you need to know

Even though it is not recommended, you can delay your period by going straight to a new strip of

Carmenelle

instead

tablet-free

period

finishing

experience

light

menstruation-like bleeding while using this second strip. After the usual tablet-free period of 7 days,

start the next strip.

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

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

If you take the tablets according to the instructions, then your period will begin during the tablet-

free week. If you have to change this day, reduce the number of tablet-free days (but never increase

them – 7 is the maximum!). For example, if your tablet-free days normally begin on a Friday, and

you want to change this to a Tuesday (3 days earlier) start a new strip 3 days earlier than usual. If

you make the tablet-free interval very short (for example, 3 days or less) you may not have any

bleeding during these days. You may then experience light or menstruation-like bleeding.

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

If you want to stop taking Carmenelle

You can stop taking Carmenelle whenever you want. If you do not want to become pregnant, ask

your doctor for advice about other reliable methods of birth control. If you want to become

pregnant, stop taking Carmenelle and wait for a period before trying to become pregnant. You will

be able to calculate the expected delivery date more easily.

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

4.

Possible side effects

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

If you get any side effect, particularly if severe and persistent, or have any change to your health

that you think may be due to Carmenelle, 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 Carmenelle”.The

following

list

side

effects

that

have

been

linked

with

Drospirenone/Ethinylestradiol.

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

mood swings

headache

abdominal pain (stomach ache)

acne

breast pain, breast enlargement, breast tenderness, painful or irregular periods

weight gain

NL/H/2631/001/IB/003

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

Candida (fungal infection)

cold sores (herpes simplex)

allergic reactions

increased appetite

depression, nervousness, sleep disorder

feeling of “pins and needles”, giddiness (vertigo)

problems with vision

irregular heart beat or unusually fast heart rate

high blood pressure, low blood pressure, migraine, varicose veins

sore throat

nausea, vomiting, inflammation of stomach and/or intestine, diarrhoea, constipation

sudden swelling of the skin and/or mucous membranes (e.g. tongue or throat), and/or

difficulty swallowing or hives together with difficulty breathing (angioedema), hair loss

(alopecia), eczema, itching, rashes, dry skin, oily skin disorder (seborrheic dermatitis)

neck pain, limb pain, muscle cramps

bladder infection

breast lump

(benign

and cancer),

milk

production

while

not pregnant

(galactorrhea),

ovarian cysts, hot flushes, absence of periods, very heavy periods, vaginal discharge,

vaginal dryness, lower abdominal (pelvic) pain, abnormal cervical smear (Papanicolaou or

Pap smear), decreased interest in sex

fluid retention, lack of energy, excessive thirst, increased sweating

weight loss.

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

asthma

hearing impairment

erythema nodosum (characterized by painful reddish skin nodules)

erythema multiforme (rash with target-shaped reddening or sores)

harmful blood clots in a vein or artery for example:

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

in a lung (i.e. PE)

heart attack

stroke

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

attack (TIA)

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)

NL/H/2631/001/IB/003

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects

listed

this

leaflet.

also

report

side

effects

directly

HPRA

Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517.

Website: www.hpra.ie; E-mail: medsafety@hpra.ie. By reporting side effects you can help provide

more information on the safety of this medicine.

5.

How to store Carmenelle

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

Store below 30ºC.

Expiry date

Do not use this medicine after the expiry date which is stated on the blister and package after "Do

not use after:" or "EXP:" The expiry date refers to the last day of that month.

Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to throw

away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Carmenelle contains:

The active substances are ethinylestradiol and drospirenone.

Each tablet contains 0.20 milligram ethinylestradiol and 3 milligram drospirenone.

Other ingredients (excipients) are lactose monohydrate, pregelatinised starch (maize), povidone

(E1201), croscarmellose sodium, polysorbate 80 (E433), magnesium stearate (E470b), Poly

(vinyl alcohol), titanium dioxide (E171), macrogol, talc (E553b), yellow iron oxide (E172), red

iron oxide (E172), black iron oxide (E172).

What Carmenelle looks like and contents of the pack

Each blister of Carmenelle contains 21 pink, round film-coated tablets.

Carmenelle is available in boxes of 1, 2, 3, 6 and 13 blisters each with 21 tablets.

Not all pack sizes may be marketed

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Clonmel Healthcare Ltd, Waterford Road, Clonmel, Co. Tipperary, Ireland

Manufacturer

Laboratorios León Farma, S.A., C/ La Vallina s/n, Pol. Ind. Navatejera, 24008 - Navatejera, León.

Spain

This medicinal product is authorised in the Member States of the EEA under the following names:

The Netherlands:

Carmenelle 0,02 mg/3 mg filmomhulde tabletten

Austria:

Laurine 0,02 mg/3 mg Filmtabletten

Belgium:

Ethinylestradiol/Drospirenone ELC-Group 0,02 mg/3 mg filmomhulde

tabletten

Luxembourg:

Ethinylestradiol/Drospirenone ELC 0,02 mg/3 mg comprimés pelliculés

Germany:

Laurine STADA 0,02 mg/ 3 mg Filmtabletten

NL/H/2631/001/IB/003

Denmark:

Sironelle

France:

Ethinylestradiol/Drospirenone EG 0.02 mg/3 mg comprimé pelliculé

Ireland:

Carmenelle 0.02 mg/3 mg film-coated tablets

Italy:

Chrystelle

Sweden:

Sironelle

This leaflet was last approved in March 2016.

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Carmenelle 0.02mg/3mg Film-coated Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

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

Excipients with known effect:

Lactose monohydrate 44 mg

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet.

Pink, round film-coated tablets of 5.7 mm diameter.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Oral contraception

The decision to prescribe Carmenelle should take into consideration the individual

woman’s current

risk factors,

particularly those for venous thromboembolism (VTE), and how the risk of VTE with Carmenelle compares with other

CHCs (see sections 4.3 and 4.4).

4.2 Posology and method of administration

Route of administration: oral use.

How to take Carmenelle

The tablets must be taken every day at about the same time, if necessary with a little liquid, in the order shown on the

blister pack. One tablet is to be taken daily for 21 consecutive days. Each subsequent pack is started after a 7-day

tablet-free interval, during which time a withdrawal bleed usually occurs. This usually starts on day 2-3 after the last

tablet and may not have finished before the next pack is started.

How to start Carmenelle

No preceding hormonal contraceptive use (in the past month)

Tablet-taking has to start on day 1 of the woman’s natural cycle (i.e. the first day of her menstrual bleeding).

Changing from a combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring, or

transdermal patch)

The woman should start with Carmenelle preferably on the day after the last active tablet (the last tablet containing the

active substances) of her previous COC, but at the latest on the day following the usual tablet-free or placebo tablet

interval of her previous COC. In case a vaginal ring or transdermal patch has been used the woman should start using

Carmenelle preferably on the day of removal, but at the latest when the next application would have been due.

Changing from a progestogen-only-method (progestogen-only pill, injection, implant) or from a progestogen-

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releasing intrauterine system (IUS)

The woman may switch any day from the progestogen-only pill (from an implant or the IUS on the day of its removal,

from an injectable when the next injection would be due) but should in all of these cases be advised to additionally use

a barrier method for the first 7 days of tablet-taking.

Following first-trimester abortion

The woman may start immediately. When doing so, she need not take additional contraceptive measures.

Following delivery or second-trimester abortion

Women should be advised to start at day 21 to 28 after delivery or second-trimester abortion. When starting later, the

woman should be advised to additionally use a barrier method for the first 7 days. However, if intercourse has already

occurred, pregnancy should be excluded before the actual start of COC use or the woman has to wait for her first

menstrual period.

For breast-feeding women see Section 4.6.

Management of missed tablets

If the user is less than 12 hours late in taking any tablet, contraceptive protection is not reduced. The woman should

take the tablet as soon as she remembers and should take further tablets at the usual time.

If she is more than 12 hours late in taking any tablet, contraceptive protection may be reduced. The management of

missed tablets can be guided by the following two basic rules:

tablet-taking must never be discontinued for longer than 7 days

7 days of uninterrupted tablet-taking are required to attain adequate suppression of the hypothalamic-pituitary-

ovarian-axis.

Accordingly the following advice can be given in daily practice:

Week 1

The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same

time. She then continues to take tablets at her usual time. In addition, a barrier method such as a condom should be

used for the next 7 days. If intercourse took place in the preceding 7 days, the possibility of a pregnancy should be

considered. The more tablets are missed and the closer they are to the regular tablet-free interval, the higher the risk of

a pregnancy.

Week 2

The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same

time. She then continues to take tablets at her usual time. Provided that the woman has taken her tablets correctly in the

7 days preceding the first missed tablet, there is no need to use extra contraceptive precautions. However, if she has

missed more than 1 tablet, the woman should be advised to use extra precautions for 7 days.

Week 3

The risk of reduced reliability is imminent because of the forthcoming 7-day tablet-free interval However, by adjusting

the tablet-intake schedule, reduced contraceptive protection can still be prevented. By adhering to either of the

following two options, there is therefore no need to use extra contraceptive precautions, provided that in the 7 days

preceding the first missed tablet the woman has taken all tablets correctly. If this is not the case, she should follow the

first of these two options and use extra precautions for the next 7 days as well.

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The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at

the same time. She then continues to take tablets at her usual time. The next blister pack must be started as soon

as the current blister pack is finished, i.e., no gap should be left between packs. The user is unlikely to have a

withdrawal bleed until the end of the second pack, but she may experience spotting or breakthrough bleeding on

tablet-taking days.

The woman may also be advised to discontinue tablet-taking from the current blister pack. She should then

have a tablet-free interval of up to 7 days, including the days she missed tablets, and subsequently continue with

the next blister pack.

If the woman missed tablets and subsequently has no withdrawal bleed in the first normal tablet –free interval, the

possibility of a pregnancy should be considered.

Advice in case of gastro-intestinal disturbances

In case of severe gastro-intestinal disturbances (e.g., vomiting or diarrhoea), absorption may not be complete and

additional contraceptive measures should be taken. If vomiting occurs within 3-4 hours after tablet taking, a new

(replacement) tablet should be taken as soon as possible. The new tablet should be taken within 12 hours of the usual

time of tablet-taking if possible. If more than 12 hours elapse, the advice concerning missed tablets, as given in section

4.2 “Management of missed tablets” is applicable. If the woman does not want to change her normal tablet-taking

schedule, she has to take the extra tablet(s) from another blister pack.

How to postpone a withdrawal bleed

To delay a period the woman should continue with another blister pack of Carmenelle

without a tablet-free interval. The extension can be carried on for as long as wished until the end of the second pack.

During the extension the woman may experience breakthrough-bleeding or spotting. Regular intake of Carmenelle is

then resumed after the usual 7-day tablet–free interval.

To shift her periods to another day of the week than the woman is used to with her current scheme, she can be advised

to shorten her forthcoming tablet-free interval by as many days as she likes. The shorter the interval, the higher the risk

that she does not have a withdrawal bleed and will experience breakthrough-bleeding and spotting during the

subsequent pack (just as when delaying a period).

4.3 Contraindications

Combined hormonal contraceptives (CHCs) should not be used in the following conditionsShould any of the conditions

appear for the first time during CHC use, the product should be stopped immediately.

Presence or risk of venous thromboembolism (VTE)

Venous thromboembolism – current VTE (on anticoagulants) or history of (e.g. deep venous thrombosis

[DVT] or pulmonary embolism [PE])

Known hereditary or

acquired predisposition for

venous thromboembolism,

such as APC-resistance,

(including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency

Major surgery with prolonged immobilisation (see section 4.4)

A 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 arterial thromboembolism, history of arterial thromboembolism (e.g.

myocardial infarction) or prodromal condition (e.g. angina pectoris)

Cerebrovascular

disease – current

stroke,

history of

stroke or

prodromal

condition (e.g.

transient

ischaemic attack, TIA)

Known

hereditary

acquired

predisposition

arterial

thromboembolism,

such

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hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant).

History of migraine with focal neurological symptoms.

A high risk of arterial thromboembolism due to multiple risk factors (see section 4.4) or to the presence

of one serious risk factor such as:

diabetes mellitus with vascular symptoms

severe hypertension

severe dyslipoproteinaemia

Presence or history of severe hepatic disease as long as liver function values have not returned to normal

Severe renal insufficiency or acute renal failure

Presence or history of liver tumours (benign or malignant)

Known or suspected sex-steroid influenced malignancies (e.g. of the genital organs or the breasts).

Undiagnosed vaginal bleeding

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Warnings

If any of the conditions or risk factors mentioned below is present,

the suitability of Carmenelle should be discussed

with the woman.

In the event of aggravation, or first appearance of any of these conditions or risk factors, the woman should be advised

to contact her doctor to determine whether the use of Carmenelle should be discontinued.

In case of suspected or confirmed VTE or ATE,

CHC use should be discontinued.

In case anti-coagulant

therapy is

started,

adequate alternative contraception should be initiated because of

teratogenicity of

anti-coagulant

therapy

(coumarins).

Circulatory Disorders

Risk of venous thromboembolism (VTE)

The use of

any combined hormonal

contraceptive (CHC)

increases the risk of

venous thromboembolism (VTE)

compared with no use.

Products that contain levonorgestrel,

norgestimate or norethisterone are associated with

the lowest risk of VTE. Other products such as Carmenelle may have up to twice this level of risk. The decision

to use any product other than one with the lowest VTE risk should be taken only after a discussion with the

woman to ensure she understands the risk of VTE with [invented name], how her current risk factors influence

this risk, and that her VTE risk is highest in the first ever year of use.

There is also some evidence that the risk

is increased when a CHC is re-started after a break in use of 4 weeks or more.

In women who do not use a CHC and are not pregnant about 2 out of 10,000 will develop a VTE over the period of one

year.

However,

in any individual

woman the risk may be far higher,

depending on her underlying risk factors (see

below).

is estimated

that

of 10,000 women who use a CHC containing drospirenone,

between 9 and 12 women will

develop a VTE in one year; this compares with about 6

in women who use a levonorgestrel-containing CHC.

In both cases, the number of VTEs per year is fewer than the number expected during pregnancy or in the postpartum

period.

VTE may be fatal in 1-2% of cases

Number of VTE events per 10,000 women in one year

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Extremely rarely, thrombosis has been reported to occur in CHC users in other blood vessels, e.g. hepatic, mesenteric,

renal or retinal veins and arteries.

Risk factors for VTE

The risk for

venous

thromboembolic complications

in CHC users

may increase substantially in a woman with

additional risk factors, particularly if there are multiple risk factors (see table).

Carmenelle is contraindicated if a woman has multiple risk factors that put her at high risk of venous 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 of VTE should be considered. If the balance of benefits and risks is

considered to be negative a CHC should not be prescribed (see section 4.3).

Table: Risk factors for VTE

Risk factor

Comment

Obesity (body mass index over 30

kg/m²)

Risk increases substantially as BMI rises.

Particularly important to consider if other risk factors

also present.

Prolonged immobilisation, major

surgery, any surgery to the legs or

pelvis, neurosurgery, or major trauma

Note:

temporary immobilisation

including air travel >4 hours can also

be a risk factor for VTE, particularly

in women with other risk factors

In these situations it is advisable to discontinue use of

the patch/pill/ring (in the case of elective surgery at

least four weeks in advance) and not resume until

two weeks after complete remobilisation. Another

method of contraception should be used to avoid

unintentional pregnancy.

Antithrombotic treatment should be considered if

Carmenelle has not been discontinued in advance.

Positive family history (venous

thromboembolism ever in a sibling or

parent especially at a relatively early

age e.g. before 50).

If a hereditary predisposition is suspected, the woman

should be referred to a specialist for advice before

deciding about any CHC use

Cancer, systemic lupus erythematosus, haemolytic

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There is no consensus about

the possible role of

varicose veins and superficial

thrombophlebitis in the onset

progression of venous thrombosis.

The increased risk of thromboembolism in pregnancy,

and particularly the 6 week period of the puerperium, must be

considered (for information on “Pregnancy and lactation” see section 4.6).

Symptoms of VTE (deep vein thrombosis and pulmonary embolism)

In the event

of symptoms women should be advised to seek urgent

medical

attention and to inform the healthcare

professional that she is 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 be felt only when standing or walking,

- increased warmth in the affected leg; red or discoloured skin on the leg.

Symptoms of pulmonary embolism (PE) can include:

- sudden onset of unexplained shortness of breath or rapid breathing;

- sudden coughing which may be associated with haemoptysis;

- sharp chest pain;

- severe light headedness or dizziness;

- rapid or irregular heartbeat.

Some of these symptoms (e.g. “shortness of breath”, “coughing”) are non-specific and might be misinterpreted as more

common or less severe events (e.g. respiratory tract infections).

Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of an extremity.

If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can progress to loss of

vision. Sometimes loss of vision can occur almost immediately.

Risk of arterial thromboembolism (ATE)

Epidemiological

studies

have associated the use of

CHCs

with an increased risk for

arterial

thromboembolism

(myocardial

infarction)

cerebrovascular

accident

(e.g.

transient

ischaemic

attack,

stroke).

Arterial

thromboembolic events may be fatal.

Risk factors for ATE

The risk of arterial thromboembolic complications or of a cerebrovascular accident in CHC users increases in women

with risk factors (see table).

Carmenelle is contraindicated if a woman has one serious or multiple risk factors for ATE

that puts her at high risk of arterial thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible

that

the increase in risk is greater

than the sum of

the individual

factors -

in this case her

total

risk should be

considered.

If the balance of benefits and risks is considered to be negative a CHC should not

be prescribed (see

section 4.3).

Table: Risk factors for ATE

Other medical conditions associated

with VTE

uraemic syndrome, chronic inflammatory bowel

disease (Crohn’s disease or ulcerative colitis) and

sickle cell disease

Increasing age

Particularly above 35 years

Risk factor

Comment

Increasing age

Particularly above 35 years

Smoking

Women should be advised not to smoke if they wish

to use a CHC.

Women over 35 who continue to

smoke should be strongly advised to use a different

method of contraception.

Hypertension

Obesity (body mass index over 30

Risk increases substantially as BMI increases.

Particularly important in women with additional risk

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Symptoms of ATE

In the event

of symptoms women should be advised to seek urgent

medical

attention and to inform the healthcare

professional that she is taking a CHC.

Symptoms of a cerebrovascular accident can include:

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

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

- sudden confusion, trouble speaking or understanding;

- sudden trouble seeing in one or both eyes;

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

- loss of consciousness or fainting with or without seizure.

Temporary symptoms suggest the event is a transient ischaemic attack (TIA).

Symptoms of myocardial infarction (MI) can include:

pain,

discomfort,

pressure,

heaviness,

sensation of

squeezing or

fullness

in the chest,

arm,

below the

breastbone;

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

- feeling of being full, having indigestion or choking;

- sweating, nausea, vomiting or dizziness;

- extreme weakness, anxiety, or shortness of breath;

- rapid or irregular heartbeats.

Tumours

An increased risk of cervical cancer in long-term users of COCs (> 5 years) has been reported in some epidemiological

studies, but there continues to be controversy about the extent to which this finding is attributable to the confounding

effects of sexual behaviour and other factors such as human papilloma virus (HPV).

A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of

having breast cancer diagnosed in women who are currently using COCs. The excess risk gradually disappears during

the course of the 10 years after cessation of COC use. Because breast cancer is rare in women under 40 years of age,

the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of

breast cancer. These studies do not provide evidence for causation. The observed pattern of increased risk may be due

to an earlier diagnosis of breast cancer in COC users,

the biological effects of COCs or a combination of both.

breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users.

In rare cases,

benign liver tumours,

and even more rarely,

malignant

liver tumours have been reported in users of

COCs.

In isolated cases,

these tumours have led to life-threatening intra-abdominal haemorrhages.

A hepatic tumour

should be considered in the differential

diagnosis when severe upper abdominal

pain,

liver enlargement

or signs of

intra-abdominal haemorrhage occur in women taking COCs.

With the use of the higher-dosed COCs (50 µg ethinylestradiol) the risk of endometrial and ovarian cancer is reduced.

kg/m2)

factors

Positive family history (arterial

thromboembolism ever in a sibling or

parent especially at relatively early

age e.g. below 50).

If a hereditary predisposition is suspected, the woman

should be referred to a specialist for advice before

deciding about any CHC use

Migraine

An increase in frequency or severity of migraine

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, hyperhomocysteinaemia, valvular

heart disease and atrial fibrillation,

dyslipoproteinaemia and systemic lupus

erythematosus.

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Whether this also applies to lower-dosed COCs remains to be confirmed.

Other conditions

The progestogen component

in Carmenelle is an aldosterone antagonist

with potassium sparing properties.

In most

cases,

no increase of potassium levels is to be expected.

In a clinical

study,

however in some patients with mild or

moderate renal

impairment

and concomitant

use of

potassium-sparing medicinal

products serum potassium levels

slightly,

significantly,

increased during drospirenone intake.

Therefore,

is recommended to check serum

potassium during the first

treatment

cycle in patients presenting with renal

insufficiency and a pretreatment

serum

potassium in the upper

reference range,

and particularly during concomitant

use of

potassium sparing medicinal

products. See also section 4.5.

Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using

COCs.

Although small

increases in blood pressure have been reported in many women taking COCs,

clinically relevant

increases are rare. Only in these rare cases an immediate discontinuation of COC use is justified. If, during the use of a

COC in preexisting hypertension, constantly elevated blood pressure values or a significant increase in blood pressure

do not respond adequately to antihypertensive treatment, the COC must be withdrawn. Where considered appropriate,

COC use may be resumed if normotensive values can be achieved with antihypertensive therapy.

The following conditions have been reported to occur

deteriorate with both pregnancy and COC use,

evidence of an association with COC use is inconclusive:

jaundice and/or pruritus related to cholestasis;

gallstones;

porphyria;

systemic lupus

erythematosus;

haemolytic uremic syndrome;

Sydenham's

chorea;

herpes

gestationis;

otosclerosis-related hearing loss.

In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.

Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver

function return to normal.

Recurrence of

cholestatic jaundice and/or

cholestasis-related pruritus which previously

occurred during pregnancy or during previous use of sex steroids necessitates the discontinuation of COCs.

Although COCs may have an effect on peripheral insulin resistance and glucose tolerance,

there is no evidence for a

need to alter

the therapeutic regimen in diabetics using low-dose COCs (containing < 0.05 mg ethinylestradiol).

However, diabetic women should be carefully observed, particularly in the early stage of COC use.

Worsening of endogenous depression, of epilepsy, of Crohn's disease and of ulcerative colitis has been reported during

COC use.

Chloasma may occasionally occur,

especially in women with a history of

chloasma gravidarum.

Women with a

tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking COCs.

This

medicinal

product

contains

44 mg lactose per

tablet.

Patients

with rare hereditary problems

galactose

intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should take

this amount into consideration.

Medical examination/consultation

Prior to the initiation or reinstitution of Carmenelle a complete medical

history (including family history) should be

taken and pregnancy must

be ruled out.

Blood pressure should be measured and a physical

examination should be

performed, guided by the contra-indications (see section 4.3) and warnings (see section 4.4). It is important to draw a

woman’s attention to the information on venous and arterial

thrombosis,

including the risk of Carmenelle compared

with other CHCs, the symptoms of VTE and ATE,

the known risk factors and what to do in the event of a suspected

thrombosis.

The woman should also be instructed to carefully read the user leaflet and to adhere to the advice given. The frequency

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and nature of examinations should be based on established practice guidelines and 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.

Reduced efficacy

The efficacy of COCs may be reduced in the event of e.g. missed tablets (see section 4.2), gastro-intestinal disturbances

(see section 4.2) or concomitant medication (see section 4.5).

Reduced cycle control

With all COCs, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of

use.

Therefore,

the evaluation of any irregular bleeding is only meaningful after an adaptation interval of about three

cycles.

bleeding irregularities

persist

occur

after

previously regular

cycles,

then non-hormonal

causes

should be

considered and adequate diagnostic measures are indicated to exclude malignancy or pregnancy.

These may include

curettage.

In some women withdrawal

bleeding may not

occur

during the tablet-free interval.

the COC has been taken

according to the directions described in section 4.2, it is unlikely that the woman is pregnant. However, if the COC has

not been taken according to these directions prior to the first missed withdrawal bleed or if two withdrawal bleeds are

missed, pregnancy must be ruled out before COC use is continued.

_________________________________

These incidences were estimated from the totality of the epidemiological study data, using relative risks for the different products compared with

levonorgestrel-containing CHCs.

Mid-point of range of 5-7 per 10,000 WY, based on a relative risk for CHCs containing levonorgestrel versus non-use of approximately 2.3 to 3.6

4.5 Interaction with other medicinal products and other forms of interaction

Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.

Effects of other medicinal products on Carmenelle

Interactions can occur with drugs that induce microsomal enzymes which can result in increased clearance of sex

hormones and which may lead to breakthrough bleeding and/or contraceptive failure.

Management

Enzyme induction can already be observed after a few days of treatment. Maximal enzyme induction is generally seen

within a few weeks. After the cessation of drug therapy enzyme induction may be sustained for about 4 weeks.

Short-term treatment

Women on treatment with enzyme inducing drugs should temporarily use a barrier method or another method of

contraception in addition to the COC. The barrier method must be used during the whole time of the concomitant drug

therapy and for 28 days after its discontinuation.

If the drug therapy runs beyond the end of the tablets in the COC pack, the next COC pack should be started right after

the previous one without the usual tablet-free interval.

Long-term treatment

In women on long-term treatment with enzyme-inducing active substances, another reliable, nonhormonal, method of

contraception is recommended.

The following interactions have been reported in the literature.

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Substances increasing the clearance of COCs (diminished efficacy of COCs by enzyme-induction),

e.g.:.

Barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, and HIV medication ritonavir, nevirapine and

efavirenz and possibly also felbamate, griseofulvin, oxcarbazepine, topiramate and products containing the herbal

remedy St. John's Wort (hypericum perforatum).

Substances with variable effects on the clearance of COCs,

When co-administered with COCs, many combinations of HIV protease inhibitors and non-nucleoside reverse

transcriptase inhibitors, including combinations with HCV inhibitors can increase or decrease plasma concentrations of

estrogen or progestins. The net effect of these changes may be clinically relevant in some cases.

Therefore, the prescribing information of concomitant HIV/HCV medications should be consulted to identify potential

interactions and any related recommendations. In case of any doubt, an additional barrier contraceptive method should

be used by women on protease inhibitor or non-nucleoside reverse transcriptase inhibitor therapy.

The main metabolites of drospirenone in human plasma are generated without involvement of the cytochrome P450

system. Inhibitors of this enzyme system are therefore unlikely to influence the metabolism of drospirenone.

Effects of Carmenelle on other medicinal products

Oral

contraceptives may affect

the metabolism of

certain other

active substances.

Accordingly,

plasma and tissue

concentrations may either increase (e.g. ciclosporin) or decrease (e.g. lamotrigine).

Based on in vitro inhibition studies and in vivo interaction studies in female volunteers using omeprazole, simvastatin

and midazolam as marker substrate, an interaction of drospirenone at doses of 3 mg with the metabolism of other active

substances is unlikely.

Other forms of interactions

In patients without

renal

insufficiency,

the concomitant

use of drospirenone and ACE-inhibitors or NSAIDs did not

show a

significant

effect

on serum potassium.

Nevertheless,

concomitant

Carmenelle

with aldosterone

antagonists or potassium-sparing diuretics has not been studied. In this case, serum potassium should be tested during

the first treatment cycle. See also section 4.4.

Laboratory tests

The use of contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters

of liver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins, e.g. corticosteroid-binding globulin and

lipid/lipoprotein fractions,

parameters of

carbohydrate metabolism and parameters of

coagulation and fibrinolysis.

Changes generally remain within the normal laboratory range. Drospirenone causes an increase in plasma renin activity

and plasma aldosterone induced by its mild antimineralocorticoid activity.

4.6 Fertility, pregnancy and lactation

Pregnancy

Carmenelle is not indicated during pregnancy.

pregnancy occurs

during use

Carmenelle,

preparation should be

withdrawn immediately.

Extensive

epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used

COCs prior to pregnancy, nor a teratogenic effect when COCs were taken inadvertently during pregnancy.

Animal studies have shown undesirable effects during pregnancy and lactation (see section 5.3). Based on these animal

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0

data,

undesirable effects due to hormonal

action of

the active compounds cannot

be excluded.

However,

general

experience with COCs during pregnancy did not provide evidence for an actual undesirable effect in humans.

The available data regarding the use of Carmenelle during pregnancy are too limited to permit conclusions concerning

negative effects of Carmenelle on pregnancy, health of the foetus or neonate. To date, no relevant epidemiological data

are available.

The increased risk of VTE during the postpartum period should be considered when re-starting CarmenelleCarmenelle

(see section 4.2 and 4.4).

Breast-feeding

Lactation may be influenced by COCs as they may reduce the quantity and change the composition of breast

milk.

Therefore,

the use of COCs should generally not

be recommended until

the breast-feeding mother has completely

weaned her child. Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the milk

during COC use. These amounts may affect the child.

4.7 Effects on ability to drive and use machines

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

and use machines have been observed in users of COCs.

4.8 Undesirable effects

Description of selected adverse reactions

The following adverse drug reactions have been reported during use of Carmenelle:

The table below reports adverse reactions by MedDRA system organ classes (MedDRA SOCs). The frequencies

are based on clinical trial data.

System Organ Class

Frequency of adverse reactions

Common

1/100 to <1/10

Uncommon

1/1,000 to <1/100

Rare

10,000 to <1/1,000

Infections and

infestations

Candidiasis

Herpes simplex

Immune system

disorders

Allergic reaction

Asthma

Metabolism and

nutrition disorders

Increased appetite

Psychiatric disorders

Emotional lability

Depression

Nervousness

Sleep disorder

Nervous system

disorders

Headache

Paresthesia

Vertigo

Ear and labyrinth

disorders

Hypacusis

Eye disorders

Visual disturbance

Cardiac disorders

Extrasystoles

Tachycardia

Vascular disorders

Hypertension

Hypotension

Migraine

Varicose vein

Venous

thromboembolism

(VTE)

Arterial

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

An increased risk of

arterial

and venous thrombotic and thrombo-embolic events,

including myocardial

infarction,

stroke,

transient

ischemic attacks,

venous thrombosis and pulmonary embolism has been observed in women using

CHCs, which are discussed in more detail in section 4.4.

The following serious adverse events have been reported in women using COCs,

which are discussed in section 4.4

Special warnings and precautions for use:

Hypertension;

thromboembolism

(ATE)

Respiratory, thoracic

and mediastinal

disorders

Pharyngitis

Gastrointestinal

disorders

Abdominal pain

Nausea

Vomiting

Gastroenteritis

Diarrhea

Constipation

Gastrointestinal disorder

Skin and subcutaneous

tissue disorders

Acne

Angioedema

Alopecia

Eczema

Pruritus

Rash

Dry skin

Seborrhea

Skin disorder

Erythema nodosum

Erythema

multiforme

Musculoskeletal and

connective tissue

disorders

Neck pain

Pain in extremity

Muscle cramps

Renal and urinary

disorders

Cystitis

Reproductive system

and breast disorders

Breast pain

Breast enlargement

Breast tenderness

Dysmenorrhea

Metrorrhagia

Breast neoplasm

Fibrocystic breast

Galactorrhea

Ovarian cyst

Hot flushes

Menstrual disorder

Amenorrhea

Menorrhagia

Vaginal candidiasis

Vaginitis

Genital discharge

Vulvovaginal disorder

Vaginal dryness

Pelvic pain

Papanicolaou smear

suspicious

Libido decreased

General disorders and

administration site

conditions

Edema

Asthenia

Pain

Excessive thirst

Sweating increased

Investigations

Weight increase

Weight decrease

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Liver tumours;

Occurrence or deterioration of conditions for which association with COC use is not

conclusive:

Crohn's disease,

ulcerative colitis,

epilepsy,

uterine myoma,

porphyria,

systemic lupus erythematosus,

herpes gestationis,

Sydenham's

chorea, haemolytic uremic syndrome, cholestatic jaundice;

Chloasma;

Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver

function return to normal.

In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.

The frequency of diagnosis of breast

cancer is very slightly increased among OC users.

As breast

cancer is rare in

women under 40 years of age the excess number is small in relation to the overall risk of breast cancer. Causation with

COC use is unknown. For further information, see sections 4.3 and 4.4.

Interactions

Breakthrough bleeding and/or contraceptive failure may result from interactions of other drugs (enzyme

inducers) with oral contraceptives (see section 4.5).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal

product

is important.

allows continued

monitoring of

the benefit/risk balance of

the medicinal

product.

Healthcare professionals are asked to report

suspected adverse reactions via HPRA Pharmacovigilance,

Earlsfort

Terrace,

IRL - Dublin 2;

Tel:

+353 1 6764971;

Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9 Overdose

There has not yet been any experience of overdose with Carmenelle. On the basis of general experience with combined

oral contraceptives, symptoms that may possibly occur in this case are: nausea, vomiting and, in young girls, slight

vaginal bleeding. There are no antidotes and further treatment should be symptomatic.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group (ATC): Progestogens and estrogens, fixed combinations.

ATC Code: G03AA12

Pearl Index for method failure: 0.11 (upper two-sided 95 % confidence limit: 0.60). Overall Pearl Index (method failure

+ patient failure): 0.31 (upper two-sided 95 % confidence limit: 0.91)

The contraceptive effect of Carmenelle is based on the interaction of various factors, the most important of which are

seen as the inhibition of ovulation and the changes in the endometrium.

Carmenelle is a combined oral contraceptive with ethinylestradiol and the progestogen drospirenone. In a therapeutic

dosage, drospirenone also possesses antiandrogenic and mild antimineralocorticoid properties. It has no estrogenic,

glucocorticoid and antiglucocorticoid activity. This gives drospirenone a pharmacological profile closely resembling

the natural hormone progesterone.

There are indications from clinical studies that the mild antimineralocorticoid properties of Carmenelle result in a mild

antimineralocorticoid effect.

5.2 Pharmacokinetic properties

Drospirenone

Absorption

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Orally administered drospirenone is rapidly and almost completely absorbed. Maximum concentrations of the active

substance in serum of about 38 ng/ml are reached at about 1 - 2 h after single ingestion. Bioavailability is between 76

and 85 %. Concomitant ingestion of food has no influence on the bioavailability of drospirenone.

Distribution

After oral administration, serum drospirenone levels decrease with a terminal half-life of 31 h. Drospirenone is bound

to serum albumin and does not bind to sex hormone binding globulin (SHBG) or corticoid binding globulin (CBG).

Only 3 - 5 % of the total serum concentrations of the active substance are present as free steroid. The ethinylestradiol-

induced increase in SHBG does not influence the serum protein binding of drospirenone. The mean apparent volume of

distribution of drospirenone is 3.7 ± 1.2 l/kg.

Biotransformation

Drospirenone is extensively metabolized after oral administration. The major metabolites in the plasma are the acid

form of drospirenone, generated by opening of the lactone ring, and the 4,5-dihydro-drospirenone-3-sulfate, both of

which are formed without involvement of the P450 system. Drospirenone is metabolized to a minor extent by

cytochrome P450 3A4 and has demonstrated a capacity to inhibit this enzyme and cytochrome P450 1A1, cytochrome

P450 2C9 and cytochrome P450 2C19 in vitro.

Elimination

The metabolic clearance rate of drospirenone in serum is 1.5 ± 0.2 ml/min/kg. Drospirenone is excreted only in trace

amounts in unchanged form. The metabolites of drospirenone are excreted with the faeces and urine at an excretion

ratio of about 1.2 to 1.4. The half-life of metabolite excretion with the urine and faeces is about 40 h.

Steady-State Conditions

During a treatment cycle, maximum steady-state concentrations of drospirenone in serum of about 70 ng/ml are

reached after about 8 days of treatment. Serum drospirenone levels accumulated by a factor of about 3 as a

consequence of the ratio of terminal half-life and dosing interval.

Special Populations

Effect of renal impairment

Steady-state serum drospirenone levels in women with mild renal impairment (creatinine clearance CLcr, 50-80

mL/min) were comparable to those of women with normal renal function. The serum drospirenone levels were on

average 37 % higher in women with moderate renal impairment (CLcr, 30 - 50 mL/min) compared to those in women

with normal renal function. Drospirenone treatment was also well tolerated by women with mild and moderate renal

impairment. Drospirenone treatment did not show any clinically significant effect on serum potassium concentration.

Effect of hepatic impairment

In a single dose study, oral clearance (CL/F) was decreased approximately 50 % in volunteers with moderate hepatic

impairment as compared to those with normal liver function. The observed decline in drospirenone clearance in

volunteers with moderate hepatic impairment did not translate into any apparent difference in terms of serum potassium

concentrations. Even in the presence of diabetes and concomitant treatment with spironolactone (two factors that can

predispose a patient to hyperkalemia) an increase in serum potassium concentrations above the upper limit of the

normal range was not observed. It can be concluded that drospirenone is well tolerated in patients with mild or

moderate hepatic impairment (Child-Pugh B).

Ethnic groups

No clinically relevant differences in the pharmacokinetics of drospirenone or ethinylestradiol between Japanese and

Caucasian women have been observed.

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Ethinylestradiol

Absorption

Orally administered ethinylestradiol is absorbed rapidly and completely. Peak serum concentrations of about 33 pg/ml

are reached within 1-2 hours after single oral administration. Absolute bioavailability as a result of presystemic

conjugation and first-pass metabolism is approximately 60 %. Concomitant intake of food reduced the bioavailability

of ethinylestradiol in about 25 % of the investigated subjects while no change was observed in the others.

Distribution

Serum ethinylestradiol levels decrease in two phases, the terminal disposition phase is characterized by a half-life of

approximately 24 hours. Ethinylestradiol is highly but non-specifically bound to serum albumin (approximately 98.5

%), and induces an increase in the serum concentrations of SHBG and corticoid binding globulin (CBG). An apparent

volume of distribution of about 5 l/kg was determined.

Biotransformation

Ethinylestradiol is subject to presystemic conjugation in both small bowel mucosa and the liver. Ethinylestradiol is

primarily metabolized by aromatic hydroxylation but a wide variety of hydroxylated and methylated metabolites are

formed, and these are present as free metabolites and as conjugates with glucuronides and sulfates. The metabolic

clearance rate of ethinylestradiol is about 5 ml/min/kg.

Elimination

Ethinylestradiol is not excreted in unchanged form to any significant extent. The metabolites of ethinylestradiol are

excreted at a urinary to biliary ratio of 4:6. The half-life of metabolite excretion is about 1 day.

Steady-state conditions

Steady-state conditions are reached during the second half of a treatment cycle and serum levels of ethinylestradiol

accumulate by a factor of about 2.0 to 2.3.

5.3 Preclinical safety data

In laboratory animals, the effects of drospirenone and ethinylestradiol were confined to those associated with the

recognised pharmacological action. In particular, reproduction toxicity studies revealed embryotoxic and fetotoxic

effects in animals which are considered as species specific. At exposures exceeding those in users of Carmenelle,

effects on sexual differentiation were observed in rat fetuses but not in monkeys.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:

Lactose monohydrate

Pregelatinised starch (maize)

Povidone (E1201)

Sodium croscarmellose

Polysorbate 80 (E433)

Magnesium stearate (E470b)

Coating:

Poly (vinyl alcohol)

Titanium dioxide (E171)

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Macrogol

Talc (E553b)

Yellow iron oxide (E172)

Red iron oxide (E172)

Black iron oxide (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Store below 30ºC.

6.5 Nature and contents of container

Clear to slightly opaque transparent PVC/PVDC-Al blister.

Pack sizes:

1 x 21 film-coated tablets

2 x 21 film-coated tablets

3 x 21 film-coated tablets

6 x 21 film-coated tablets

13 x 21 film-coated tablets

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Clonmel Healthcare Ltd

Waterford Road,

Clonmel,

Co. Tipperary,

Ireland

8 MARKETING AUTHORISATION NUMBER

PA0126/253/001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of First Authorisation: 23

August 2013

10 DATE OF REVISION OF THE TEXT

January 2017

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