MELIANE

Packaging Technology Berlin SGQCL

page 2

Bayer AG

client: 0021,GV15

material-no.: 87038688

PZ: 2773C-3

code-no.:

name: LF-INS-Meliane SCT 21

country: IL/-/BPH

colors: Black

version: 14.05.2020/01

Restricted Document

dimension: 398 x 798 mm

87038688

Meliane

Meliane

®

Coated Tablets

PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE

PHARMACISTS’ REGULATIONS (PREPARATIONS) – 1986

The medicine is dispensed with a

doctor’s prescription only

Each tablet contains:

Gestodene 0.075 mg

Ethinylestradiol 0.02 mg

Inactive ingredients and allergens: See section 6 “Further

Information”.

Read this leaflet carefully in its entirety before using

the medicine. This leaflet contains concise information

about the medicine. If you have further questions, refer to

the doctor or pharmacist.

This medicine has been prescribed to treat you. Do not pass

it on to others. It may harm them even if it seems to you

that their medical condition is similar.

ESSENTIAL INFORMATION ABOUT COMBINED HORMONAL

CONTRACEPTIVES AND ABOUT THE MEDICINE

When used properly, combined hormonal contraceptives

are considered one of the most reliable reversible methods

of contraception.

They slightly increase the risk of a blood clot in the veins

and arteries, especially in the first year or when resuming

treatment with a combined hormonal contraceptive

following a break of 4 or more weeks.

You must be alert and refer to the doctor if you think you

may have symptoms of a blood clot (see “Blood clots” in

section 2).

If taken for prolonged periods, oral contraceptive pills

may reduce your risk of cancer of the ovaries and womb.

Contraceptive pills do not protect against sexually

transmitted diseases, such as AIDS or chlamydia. Only a

condom can help with this.

This medicine can increase your risk of effects such as

blood clots and breast cancer.

Oral contraceptive pills are not suitable for some women

due to their medical condition. Please read this leaflet to

make sure Meliane is suitable for you.

To prevent pregnancy, it is important to take Meliane as

instructed and start each new strip on time. Please make

sure that you understand what to do if you miss a pill or

if you think you are pregnant.

1) WHAT IS THE MEDICINE INTENDED FOR?

Meliane is intended to prevent pregnancy.

Therapeutic group: Meliane belongs to a group of medicines

called combined pills (oral contraceptive pills) that contain

2 types of female hormones: estrogen and progestogen.

These hormones prevent pregnancy in 3 ways: by preventing

release of an egg from the ovaries, thickening the secretions

from the cervix, which makes it more difficult for sperm to

enter the womb, and preventing thickening of the lining of

the womb required for implantation of the egg.

When used properly, oral contraceptive pills are

considered one of the most reliable reversible methods

of contraception.

Oral contraceptive pills do not interrupt sexual intercourse.

Oral contraceptive pills usually make regular, lighter and

less painful periods.

Oral contraceptive pills may relieve premenstrual

symptoms.

2) BEFORE USING THE MEDICINE

Do not use the medicine if:

you are sensitive (allergic) to gestodene or to

ethinylestradiol or to any of the additional ingredients

contained in the medicine. For the list of inactive

ingredients, see section 6 “Further Information”.

you are pregnant or breastfeeding.

you have, or have ever had, a blood clot in your

legs (deep vein thrombosis, DVT), lungs (pulmonary

embolism, PE), or in other parts of the body.

you know you have a blood clotting disorder (for

instance, protein C deficiency, protein S deficiency,

antithrombin-III deficiency, Factor V Leiden or

antiphospholipid syndrome).

you have to undergo surgery or if you are immobile for

a long time (see “Blood clots” in section 2).

you have had a heart attack or stroke in the past.

you have, or have ever had, angina pectoris (a condition

that causes severe chest pain and may be a first

sign of a heart attack) or transient ischemic attack

(TIA – temporary stroke symptoms).

you have any of the following diseases that may

increase your risk of a blood clot in the arteries:

∘ severe diabetes with blood vessel damage

∘ very high blood pressure

∘ very high blood fat levels (cholesterol or triglycerides)

∘ a medical condition characterized by high blood

homocysteine levels (hyperhomocysteinemia)

you are suffering, or have suffered in the past, from a

type of migraine called “migraine with aura”.

you have, or have ever had, breast cancer.

you have had a severe liver disease in the past, and you

have been told by the doctor that your liver functions

are not yet back to normal.

you have, or have ever had, liver tumors.

you have hepatitis C and are taking medicinal

preparations containing ombitasvir/paritaprevir/

ritonavir and dasabuvir (also see in section “If you are

taking, or have recently taken, other medicines”).

If you are suffering from one of the above-mentioned

conditions, or if you develop any of them for the first time,

stop treatment and tell the doctor. The doctor will discuss

with you other contraceptive methods that may suit you

better.

Special warnings regarding use of the medicine:

Before you start taking Meliane, read the information

regarding blood clots later in this section. It is especially

important that you read about the symptoms of blood

clots detailed in section 2 “Blood clots”.

Before starting treatment, or in order to make a decision

about continuing treatment, it is important that you

understand the advantages and disadvantages of oral

contraceptive pills. Although oral contraceptive pills suit

most healthy women, they do not suit everyone.

Tell the doctor if you are suffering from the medical

conditions or risk factors mentioned in this leaflet.

If you need to have a blood test, inform the doctor that you

are taking an oral contraceptive pill, since combined oral

contraceptive pills can affect the results of certain tests.

When should you contact the doctor?

Seek urgent medical attention

- if you notice possible signs of a blood clot that may

indicate that you are suffering from a blood clot in the

leg (i.e., deep vein thrombosis), a blood clot in the lungs

(i.e., pulmonary embolism), a heart attack or a stroke

(see “Blood clots” in section 2).

For a description of the symptoms of these serious side

effects, please see “How to recognize a blood clot” in

section 2.

Some of the conditions listed below may worsen when

taking oral contraceptive pills, or they may indicate that

Meliane is not suitable for you. You may still be able to

take Meliane but it will require closer monitoring by your

doctor.

Before using Meliane, tell the doctor if any of the

following conditions apply to you, develop or worsen

while taking Meliane:

∘ If you have Crohn’s disease or ulcerative colitis (chronic

inflammatory bowel disease)

∘ If you have systemic lupus erythematosus (SLE – a

disease affecting your immune system)

∘ If you have hemolytic uremic syndrome (a blood

clotting disorder causing kidney failure)

∘ If you have sickle cell anemia (an inherited disease of

the red blood cells)

∘ If you are suffering from an inflammation of the

pancreas (pancreatitis)

∘ If you suffer from elevated levels of fat in the blood

(hypertriglyceridemia) or if you have a family history

of this condition. Hypertriglyceridemia has been

associated with an increased risk of developing

pancreatitis

∘ If you need to undergo surgery, or you are immobile

for a long time (see “Blood clots” in section 2)

∘ If you have recently given birth, you are at an increased

risk of blood clots. Consult your doctor as to how soon

after delivery can you start taking Meliane

∘ If you are suffering from an inflammation in the veins

under the skin (superficial thrombophlebitis)

∘ If you suffer from varicose veins

∘ If you have diabetes

∘ If you or a close relative has ever had heart or circulation

problems such as high blood pressure

∘ If you or a close relative has ever had blood clotting

problems

∘ If you suffer from an inherited disease called porphyria

∘ If you are obese

∘ If you suffer from migraines

∘ If you have any illness that worsened during pregnancy

or during previous use of oral contraceptive pills (see

section 4 “Side Effects”)

Blood clots

Using a combined hormonal contraceptive such as Meliane

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 (a condition called “venous thrombosis”, “venous

thromboembolism” or VTE)

in the arteries (a condition called “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 life-threatening.

It is important to remember that the overall risk of

having a harmful blood clot due to use of Meliane is

small.

How to recognize 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

∘ pain or tenderness in the leg which may

be felt only when standing or walking

∘ increased warmth in the affected leg

∘ change in color 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 increases with

deep breathing

Severe light-headedness or dizziness

Rapid or irregular heartbeat

Severe stomach pain

If you are unsure, talk to the 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., the common cold).

Pulmonary

embolism

Symptoms which most commonly occur

in one eye:

Sudden 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 or

heaviness

Sensation of squeezing or fullness in the

chest, arm or below the breastbone

Fullness, choking feeling or indigestion

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 heartbeat

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 still must seek urgent

medical attention, as you may be at risk

of another stroke.

Stroke

Swelling and slight blue discoloration of

the extremities

Severe stomach pain

Blood clots

blocking

other blood

vessels

If you are suffering from any of these conditions, refer to

the doctor immediately. Stop taking Meliane until being

instructed otherwise by the doctor. In the meantime, use

another method of contraception, such as a condom.

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 and occur most frequently 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 could

cause a deep vein thrombosis (DVT).

If a blood clot travels from the leg and reaches the lung,

a pulmonary embolism could form.

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 resume taking a combined hormonal contraceptive

(the same medicine or a different medicine) after a break

of 4 weeks or more.

After the first year, the risk declines, but will always be

slightly higher than if you were not using a combined

hormonal contraceptive.

When you stop using Meliane, your risk of developing a

blood clot returns to a normal degree within a few weeks.

What is the risk of developing a blood clot?

The risk depends on your natural risk of developing venous

thromboembolism (VTE) and on the type of combined

hormonal contraceptive you are taking.

The overall risk of developing a blood clot in the leg or

lungs (DVT or PE) with Meliane 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 gestodene, such

as Meliane, between about 9 to 12 women will develop

a blood clot in a year.

The risk of developing a blood clot will vary according

to your personal medical history (see “Factors that

increase your risk of developing a blood clot in a vein” in

section 2).

Risk of developing a blood

clot in a year

Women who are not

using a combined

hormonal pill 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 Meliane

About 9-12 out of 10,000

women

Factors that increase your risk of developing a blood

clot in a vein

The risk of developing a blood clot with Meliane is small,

but some conditions will increase the risk. Your risk is

higher:

if you are very overweight (BMI over 30 kg/m

if a member 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 50). In such a case, you may have a

hereditary blood clotting disorder

if you need to undergo surgery, or if you are immobile for

a long time because of an injury or illness, or if your leg

is in a cast. The use of Meliane may need to be stopped

several weeks before surgery or while you are less mobile.

If you need to stop Meliane, ask your doctor when you

can start using the medicine again.

with age (particularly above the age of about 35)

if you gave birth within the past few weeks

The risk of developing a blood clot increases the more of

these conditions you have.

Air travel (over 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 the doctor if any of these conditions

apply to you, even if you are unsure. The doctor may decide

that Meliane needs to be stopped.

If any of the above-mentioned conditions change while you

are using Meliane, for example, if a close family member

experiences a thrombosis for no known reason, or if you

gain a lot of weight, tell the doctor.

Blood clots in an artery

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

Like a blood clot in a vein, a blood clot in an artery could

cause serious problems. For example, it may cause a heart

attack or a stroke.

Factors that increase your risk of developing a blood

clot in an artery

It is important to note that the risk of a heart attack or

stroke from using Meliane is very low but can increase:

with age (over the age of about 35)

if you smoke. When using a combined hormonal

contraceptive like Meliane, it is recommended that you

stop smoking. If you are unable to stop smoking and are

more than 35 years old, 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 the age

of 50). In this case, you may also have a higher risk of

having a heart attack or stroke

if you, or a member of your immediate family, have high

blood fat levels (cholesterol or triglycerides)

if you suffer from migraines, especially “migraine with

aura”

if you have a heart function problem (a heart valve

disorder, a disturbance of heart rhythm called atrial

fibrillation)

if you have diabetes

If you have more than one of these conditions or if any of

them is particularly severe, the risk of developing a blood

clot may be even higher.

If any of the above-mentioned conditions change while

you are using Meliane, for example, if you start smoking,

a close family member experiences a thrombosis for no

known reason, or you gain a lot of weight, tell your doctor.

Oral contraceptive pills and cancer

While high-dosage oral contraceptive pills reduce the risk

of developing cancer of the ovaries and womb in long-term

use, it is not clear whether low-dosage oral contraceptive

pills like Meliane also provide the same protective effect.

However, it also seems that taking oral contraceptive pills

slightly increases the risk of developing cancer of the cervix –

although this may be due to having sex without a condom

more than due to the use of oral contraceptive pills. All

women should have regular Pap smear tests.

If you have breast cancer, or have had it in the past, use

of oral contraceptive pills is not recommended. Oral

contraceptive pills slightly increase your risk of breast

cancer. This risk continues to rise for as long as you are

taking oral contraceptive pills, but returns to normal within

about 10 years of stopping it. Because breast cancer is rare

in women under the age of 40, the extra cases of breast

cancer diagnosed in current and recent oral contraceptive

pill users is small. For example:

Out of 10,000 women who have never taken pills, about

16 will have breast cancer by the time they are 35 years

old.

Out of 10,000 women who took pills for 5 years in their

early twenties, about 17-18 will have breast cancer by

the time they are 35 years old.

Out of 10,000 women who have never taken pills, about

100 will have breast cancer by the time they are 45 years

old.

Out of 10,000 women who took pills for 5 years in their

early thirties, about 110 will have breast cancer by the

time they are 45 years old.

Your risk of breast cancer is higher:

if you have a close relative (mother, sister or grandmother)

who has had breast cancer.

if you are seriously overweight.

Refer to the doctor immediately if you notice changes in

your breasts, such as dimpling of the skin, changes in the

nipple or any lumps you can see or feel.

Taking oral contraceptive pills has also been linked to liver

diseases, such as jaundice and non-cancerous liver tumors,

but these cases are rare. In rarer cases, oral contraceptive

pills have been linked with some forms of liver cancer in

women who have taken the medicine for a long time.

Refer to a doctor immediately if you experience severe

stomach pain or yellowing of the whites of the eye

(jaundice). You may need to stop taking Meliane.

Psychiatric disorders

Some women using hormonal contraceptives including

Meliane have reported depression or depressed mood.

Depression may 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.

Smoking

The risk of arterial thrombosis and serious cardiovascular

side effects associated with oral contraceptive pills

increases with age. This risk is higher in women who smoke

large numbers of cigarettes, especially if they are over the

age of 35. Therefore, smoking is not recommended when

using the medicine. If you cannot stop smoking and you

are over the age of 35, your doctor may recommend that

you use a different type of contraceptive method.

Tests and follow-up

Before beginning use of an oral contraceptive pill, the

doctor will ask you about your and your family’s medical

history, will check your blood pressure and will rule out

any possibility of pregnancy. Additional tests, such as a

breast examination, may be necessary, but only if you

need to have these tests performed or if you have specific

concerns.

During the course of treatment, you should have regular

check-ups with the doctor, including a Pap smear test.

Check every month if there have been changes in your

breasts and nipples; inform the doctor if you notice or

feel any change, such as lumps or dimples.

If you need to undergo surgery, verify that the doctor knows

you are taking Meliane. You may be asked to stop taking

the pill 4-6 weeks before the surgery. This is to lower the

risk of a blood clot (see “Blood clots” in section 2). The

doctor will tell you when you can resume taking pills.

Drug interactions:

If you are taking, or have recently taken, other

medicines, including non-prescription medicines and

nutritional supplements, tell the doctor or pharmacist. It

is particularly important to inform the doctor or pharmacist

if you are taking any of the following medicines that may

impact Meliane levels in the blood, thereby impairing its

effectiveness:

medicines to treat epilepsy, such as barbiturates,

primidone, phenytoin, carbamazepine, oxcarbazepine,

topiramate

certain medicines used to treat AIDS and hepatitis C

(called protease inhibitors and non-nucleoside reverse

transcriptase inhibitors) such as ritonavir, nelfinavir,

nevirapine

griseofulvin to treat fungal infections

CYP3A4 enzyme inhibitors, such as itraconazole,

voriconazole and fluconazole (used to treat fungal

infections) and antibiotics of the macrolide group (such

as erythromycin) that may increase the level of estrogen

and/or progestogen in the blood

certain antibiotics to treat infectious diseases, such as

rifampicin

St. John’s wort (

Hypericum

) to treat depressed moods

etoricoxib (anti-inflammatory and painkiller)

medicines whose blood concentrations may be increased

when used with Meliane – cyclosporine, tizanidine,

theophylline

medicines whose blood concentrations may be reduced

when used with Meliane – lamotrigine

If you are taking one of the above-mentioned medicines,

Meliane may not be suitable for you and you will need to

use an extra contraceptive method for a while. The doctor

will instruct you if this is necessary and for how long.

In addition, it is recommended that you check the leaflets

of the medicines you are taking to see if they can be used

concomitantly with hormonal contraceptives.

Moreover, Meliane may also affect the activity of other

medicines. Your doctor may adjust the dosage of the

medicines you are taking concomitantly with Meliane.

Do not use Meliane if you have hepatitis C and are

taking medicinal preparations containing ombitasvir/

paritaprevir/ritonavir and dasabuvir, as this may cause

an increase in liver function blood test results (increase

in ALT liver enzyme). Your doctor will prescribe another

type of contraceptive before starting treatment with

these medicinal products. Meliane use can be resumed

approximately 2 weeks after completion of treatment. See

“Do not use the medicine if” section.

Use of the medicine and food

The medicine can be taken on an empty stomach or with

food.

Pregnancy, breastfeeding and fertility

Do not use Meliane if you are pregnant.

If you think you might be pregnant, perform a pregnancy

test before you stop taking the medicine.

Meliane use while breastfeeding may lead to a reduced

volume of produced milk and to a change in its composition.

Small amounts of active ingredients are secreted in the

breast milk. These amounts may affect the baby, especially

during the first 6 weeks after delivery.

If you are breastfeeding, your doctor may advise you not

to take Meliane. He will be able to help you choose an

alternative contraceptive method. Breastfeeding does not

prevent you from becoming pregnant.

Driving and use of machines

Meliane has no effect on the ability to drive or use machines.

Important information regarding some of the

components of the medicine

The medicine contains lactose and sucrose. If you have

been told by the doctor that you have intolerance to some

sugars, consult the doctor before using Meliane.

3) HOW SHOULD YOU USE THE MEDICINE?

Always use according to the doctor’s instructions. Check

with the doctor or pharmacist if you are uncertain.

The dosage and treatment regimen will be determined

by the doctor only. The usual dosage is generally one

tablet, once a day, at a set time, for 21 days. After taking

the tablet for 21 days, take a 7-day break.

Do not exceed the recommended dose.

Mode of administration

Swallow the tablet whole, with water if necessary.

Do not crush/halve/chew so as not to damage the tablet

coating.

Duration of treatment

Take Meliane every day for 21 days

Each Meliane strip has 21 tablets. The day of the week

and an arrow pointing you in the direction of progression

are marked on the back of the strip, on the back of each

tablet. Start by taking the tablet marked with the correct

day of the week; continue taking the tablets in the direction

of the arrows. Take one tablet each day, until you have

finished the strip.

Take a 7-day break

After 21 days of taking tablets, take a 7-day break. So, if

you took the last tablet of the strip on a Friday, take the

first tablet of the next strip on the Saturday of the following

week. Within a few days of taking the last tablet from the

strip, you will have menstrual bleeding. The bleeding may

still not have stopped when you start a new strip of pills.

There is no need for an extra contraception during the 7-day

break – as long as you have taken the tablets as per the

instructions and started a new strip on time.

Start a new strip

Start a new strip – even if the menstrual bleeding has not

stopped yet. Always start the new strip on time.

As long as you take Meliane as per the instructions, you

will always start a new strip on the same day of the week.

Starting use of Meliane

Starting Meliane for the first time or after discontinued

use

It is recommended to take the first tablet on the first day

of your period. In this way, you will have contraceptive

protection starting from the first tablet.

Switching to Meliane from another oral contraceptive pill

∘ If you are currently taking a 21-day Pill: Start Meliane

the day after you finish the other oral contraceptive pill.

This way, you will have contraceptive protection from

the first tablet. Menstrual bleeding will only occur after

finishing the strip of Meliane.

∘ If you are taking a 28-day Pill: Start taking Meliane the

day after taking the last active tablet from the previous

strip. This way, you will have contraceptive protection

from the first tablet. Menstrual bleeding will only occur

after you finish taking the strip of Meliane.

∘ If you are taking a progestogen-only Pill (POP): Start

taking Meliane on the first day of menstrual bleeding,

even if you have already taken the progestogen-only

pill for that day. This way, you will have contraceptive

protection immediately.

Starting Meliane after a miscarriage or abortion

If you have had a miscarriage or an abortion during the

first three months of pregnancy, your doctor may tell

you to start taking Meliane immediately. In this case you

will have contraceptive protection from the first tablet.

If you have had a miscarriage or an abortion after the

third month of pregnancy, consult the doctor. You may

need to use an extra method of contraception, such as a

condom, for a short time.

Using contraceptives after having a baby

If you have recently had a baby, the doctor will advise you

to take Meliane 21 days after delivery, provided that you

are fully mobile. There is no need to wait for a period. You

will need to use another method of contraception, such as

a condom, until you start using Meliane and for the first

7 days of use.

If you accidentally take too high a dosage

It is unlikely that taking more than one tablet will cause

harm, but you may feel nauseous, vomit or have vaginal

bleeding. Such bleeding may also occur in girls who have

never menstruated and accidentally took the medicine.

Consult the doctor if you experience any of these symptoms.

If you took an overdose, or if a child accidentally swallowed

the medicine, immediately refer to a doctor or proceed to

a hospital emergency room and bring the package of the

medicine with you.

If you forget to take the medicine

If the delay in taking the tablet is less than 12 hours,

take the tablet as soon as possible and continue taking the

rest of the tablets as usual. This may mean taking 2 tablets

in one day. Do not worry – your contraceptive protection

was not reduced.

If the delay in taking the tablet is more than 12 hours, or

you have missed more than one tablet, your contraceptive

protection may be reduced.

Take the most recently missed tablet as soon as possible,

even if it means taking 2 tablets at once. Leave any earlier

missed tablets in the strip.

Continue to take one tablet a day for the next 7 days at

the usual time.

If you finish a strip during these 7 days, start a new strip

without taking a 7-day break. You probably won’t have

menstrual bleeding until after you finish the second strip,

but there is no need to worry. If you have finished the

second strip and menstrual bleeding has not yet occurred,

perform a pregnancy test before starting another strip.

Use an additional contraceptive method, such as a

condom, for the 7 days after missing a tablet.

If you have missed one or more tablets from the first week

of your strip (days 1-7) and you had sex in that week,

you might be pregnant. Consult the doctor as soon as

possible. The doctor will advise you regarding emergency

contraception.

If you have missed any of the tablets in a strip, and

menstrual bleeding does not occur in the pill-free break,

you may be pregnant. Contact the doctor as soon as

possible, or take a home pregnancy test.

If you started a new strip late, or you extended the break

beyond 7 days, you may not be protected from pregnancy.

If you had sex in the last 7 days, consult the doctor. You

may need emergency contraception. You should also use

extra contraception, such as a condom, for the next 7 days.

If you lost a tablet

Choose one of these two options:

Take the last tablet of the strip in place of the lost tablet.

Continue taking all the other tablets on their proper days.

Your cycle will be one day shorter than normal, but your

contraceptive protection won’t be impaired. After the 7-day

break, you will have a new starting day, one day earlier

than the previous strip.

Or, if you have an extra strip and you do not want to

change the starting day of your cycle, take a tablet from

that extra strip. Continue taking all the other tablets from

your current strip as usual. You can then keep the opened

strip as a spare strip, in case you lose any more tablets.

In the event of vomiting or diarrhea

If you are suffering from vomiting or severe diarrhea within

4 hours of taking a tablet, there is no guarantee that the

daily tablet will be fully absorbed from the digestive system.

If you get better within 12 hours of taking Meliane, follow

the instructions in this section “If you lost a tablet”, which

describes how to take another tablet.

If you are suffering from vomiting or diarrhea more than

12 hours after taking the tablet, follow the instructions in

this section “If you forget to take the medicine”.

Tell the doctor if the digestive disturbances carry on

or get worse. He may recommend another method of

contraception.

A missed a period – could you be pregnant?

Occasionally, you may not have menstrual bleeding. This

could mean that you are pregnant, but it is very unlikely

if you have taken your tablets as per the instructions. Start

the next strip at the normal time. If you think there is a

chance you are pregnant (for example, if you missed a

tablet or you took other medicines concomitantly), or if you

miss a second menstrual bleed, you should take a home

pregnancy test. If you are pregnant, stop taking Meliane

and refer to the doctor.

When you want to get pregnant

If you are planning a baby, it is recommended to use

another method of contraception after stopping Meliane

until you have a period. Your doctor will rely on the date of

your last natural period to predict when your baby is due.

However, it will not cause you or your baby any harm if

you get pregnant straight away.

Do not take medicines in the dark! Check the label and

dose each time you take medicine. Wear glasses if you

need them.

If you have further questions regarding use of the

medicine, consult the doctor or pharmacist.

4) SIDE EFFECTS

As with any medicine, use of Meliane may cause side effects

in some users. Do not be alarmed when reading the list of

side effects. You may not suffer from any of them.

If you have one or more of the following side effects,

especially if it is severe or prolonged, or if there is a change

in your health status that you think could be related to

Meliane, inform your doctor.

An increased risk of blood clots in the veins (venous

thromboembolism [VTE]) or blood clots in the arteries

(arterial thromboembolism [ATE]) exists in all women using

combined hormonal contraceptives. For more detailed

information on the different risks from taking combined

hormonal contraceptives, see section 2 “Before using the

medicine”.

Serious side effects – refer to a doctor immediately

Rare side effects – effects that occur in 1-10 out of 10,000

users

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

n a leg or foot (DVT)

- in a lung (PE)

- heart attack

- stroke

- mini-stroke or temporary stroke-like symptoms, known

as a transient ischemic attack (TIA)

- blood clots in the liver, stomach/intestine, kidneys or

eyes

The risk of developing a blood clot may be higher if you

have any other conditions that increase this risk (see

section 2 for more information on the risk factors and

signs for blood clots).

Signs of a blood clot (see “Blood clots” in section 2)

Signs of a severe allergic reaction or worsening of hereditary

angioedema:

swelling of the hands, face, lips, mouth, tongue or throat.

Swelling of the tongue or throat may lead to difficulty

swallowing and breathing

a red bumpy rash (hives) and itching

Signs of breast cancer include:

- dimpling of the skin

- changes in the nipple

- lumps you see or feel

Signs of cancer of the cervix include:

- vaginal discharge that smells and/or contains blood

- unusual vaginal bleeding

- pelvic pain

- painful sex

Signs of severe liver problems include:

- severe pain in the upper abdomen

- yellowing of the skin or eyes (jaundice)

- viral inflammation of the liver (hepatitis)

- itching all over the body

If you have any of the above-mentioned effects, refer to a

doctor immediately. The doctor may instruct you to stop

taking Meliane.

Additional side effects, less serious

Common side effects – effects that occur in 1-10 out of

100 users

- nausea

- stomachache

- putting on weight

- headache

- mood swings or depressive moods

- sore or painful breasts

Uncommon side effects – effects that occur in 1-10 out

of 1,000 users

- vomiting and stomach upset

- fluid retention

- migraine

- decreased libido

- breast enlargement

- rash, which may be itchy

Rare side effects – effects that occur in 1-10 out of 10,000

users

- intolerance of contact lenses

- losing weight

- increased libido

- vaginal or breast discharge

Other side effects reported

- Breakthrough bleeding (spotting and light bleeding) may

occur for the first few months. This breakthrough bleeding

will usually stop once your body has adjusted to Meliane.

If the bleeding is heavy, prolonged or resumes, refer to

the doctor (see in section 4 “Breakthrough bleeding”).

- Chloasma (yellow-brown patches on the skin). These

patches can appear even after use of Meliane for a

number of months. The incidence of chloasma can be

reduced by avoiding sunlight or UV radiation.

- Medical conditions that may worsen during pregnancy

or previous use of the medicine:

∘ yellowing of the skin (jaundice)

∘ persistent itching (pruritus)

∘ kidney or liver function problems

∘ gallstones

∘ rare medical conditions such as systemic lupus

erythematosus

∘ occurrence or deterioration of the movement disorder

called chorea

∘ blister-like rash (herpes gestationis) whilst pregnant

∘ inherited deafness of the otosclerosis type

∘ Crohn’s disease

∘ ulcerative colitis

∘ if you, or someone in your family, have a history of sickle

cell anemia

∘ swelling of body parts (hereditary angioedema)

∘ an inherited disease called porphyria

∘ cancer of the cervix

Breakthrough bleeding

Some women taking Meliane have light bleeding or

spotting between periods, especially during the first few

months of treatment. Normally, this bleeding will stop after

a day or two and is nothing to worry about. Keep taking

Meliane as usual. The effect will most likely disappear after

using a few strips.

Breakthrough bleeding can also occur due to irregular use

of Meliane; therefore, be sure to take the pill at the same

time every day. Also, breakthrough bleeding can be due to

use of other medicines.

Consult the doctor if you get breakthrough bleeding or

spotting that:

carries on for more than a few months

started after you have been taking Meliane for a while

carries on even after you have stopped taking Meliane

If you experience a side effect, if one of the side effects

worsens, or if you experience a side effect not mentioned

in the leaflet, consult the doctor.

Side effects can be reported to the Ministry of Health

by clicking on the link “Reporting Side Effects of Drug

Treatment” found on the Ministry of Health homepage

(www.health.gov.il) that directs you to the online form for

reporting side effects, or by entering the link:

https://sideeffects.health.gov.il

5) HOW SHOULD THE MEDICINE BE STORED?

Avoid poisoning! This medicine and any other medicine

must be kept in a safe place out of the reach and sight

of children and/or infants to avoid poisoning. Do not

induce vomiting unless explicitly instructed to do so by

the doctor.

Do not use the medicine after the expiry date (exp. date)

that appears on the package. The expiry date refers to the

last day of that month.

Do not store at a temperature that exceeds 25°C. Protect

from light.

Do not discard medicines in the waste bin. Ask the

pharmacist what to do with medicines you no longer

use; this way, you will help protect the environment.

6) FURTHER INFORMATION

In addition to the active ingredients, the medicine also

contains:

Lactose monohydrate, sucrose, maize starch, calcium

carbonate, talc, polyethylene glycol 6000, povidone

25000, magnesium stearate, povidone 700000,

montanglycol wax (wax E).

Each tablet contains 37.155 mg lactose monohydrate,

and 19.66 mg sucrose.

What the medicine looks like and the contents of the

package

Round, white, coated tablets.

The tablets are provided in trays (blisters) in strips of 21

tablets. Each package contains 1 or 3 strips.

A day of the week is marked on the back of each tablet

in the blister.

Not all package sizes may be marketed.

Registration holder and address: Bayer Israel Ltd., 36

Hacharash St., Hod Hasharon 45240.

Manufacturer and address: Delpharm Lille S.A.S, Lys Lez

Lannoy, France, or Bayer Pharma AG, Germany.

This leaflet was checked and approved by the Ministry of

Health in December 2015 and was updated in accordance

with the Ministry of Health guidelines in March 2020.

Registration number of the medicine in the National Drug

Registry of the Ministry of Health: 109 12 29094 00

MELI CTAB PL SH 070520

MELI CTAB PL SH 070520

ءاودلا لوانت تيسن اذإ عرسأب صرقلا يلوانت ،ةعاس 12 نم لقأ دحاو صرق لوانتب رخأتلا ناك اذإ لوانت رملأا ينعي نأ زئاجلا نم .داتعملاك صارقلأا يقاب لوانتب يرمتسإو نكمي ام .ررضتت مل لمحلا نم ةيامحلا نإف ـ يقلقت لا .مويلا سفنب نيصرق صرق نم رثكأ تيسن وأ ،ةعاس 12 نم رثكأ دحاو صرق لوانتب رخأتلا ناك اذإ .تررضت لمحلا نم ةيامحلا نأ زئاجلا نمف ،دحاو نيصرق لوانت ينعي كلذ نأ ولو ىتح ،نكمي ام عرسأب ريخلأا يسنملا صرقلا يلوانت .ةبلعلا يف اهيقبأ ،ةقباس صارقأ تيسن لاح يف .ةيوس .يدايتعلإا تقولا يف ،ةيلاتلا 7 ـلا مايلأا ةدمل مويلا يف صرق لوانت يلصاو هردق لصاف نود نم ةديدج ةبلعب يئدباف ،كلت 7 ـلا مايلأا للاخ ةبلعلا تيهنأ اذإ نكلو ،طقف ةيناثلا ةبلعلا ءاهتنإ دعب لاإ يثمط فزن رهظي لاأ ضرتفملا نم .مايأ 7 صحف ءارجإب يموق ،دعب فزن رهظي ملو ةيناثلا ةبلعلا تيهنأ اذإ .قلقلل ةجاح لا .ةيفاضإ ةبلع يئدبت نأ لبق لمحلا يتلا ةمداقلا 7 ـلا مايلأا للاخ مودنوكلا لثم لمحلا عنمل ةيفاضإ ةليسو يلمعتسإ .صرقلل كنايسن يلت (1-7 مايلأا( ةبلعلا نم لولأا عوبسلأا نم رثكأ وأ دحاو صرق لوانت تيسن اذإ .لماح ينوكت نأب لامتحإ كانهف ،عوبسلأا اذه للاخ ةيسنج تاقلاع تسرامو تاقولأل لمحلا عنم لئاسو صوصخب كيصويس .نكمي ام عرسأب بيبطلا يريشتسإ .ةئراطلا كانهف ،فقوتلا مايأ للاخ يثمط فزن رهظي ملو ،ةبلعلا نم صرق يأ لوانت تيسن اذإ صحف ءارجإب يموق وأ ،نكمي ام عرسأب بيبطلاب يلصتإ .لماح ينوكت نأب لامتحإ .لمحلل يتيب لامتحإ كانهف ،مايأ 7 نم رثكلأ فقوتلا مايأ ةلاطإب تمق وأ ،رخأتب ةديدج ةبلع تأدب اذإ ،ةريخلأا 7 ـلا مايلأا للاخ ةيسنج تاقلاع تسرام اذإ .لمحلا نم ةيمحم ريغ كنأب ةفاضإ .ةئراطلا تاقولأل لمح عنم ةليسول يجاتحت نأ زئاجلا نم .بيبطلا يريشتسإ .ةمداقلا 7 ـلا مايلأا يف مودنوكلا لثم لمحلا عنمل ةليسو يلمعتسإ ،كلذل صرق تدقف اذإ :نيتيلاتلا نيتيناكملإا ىدحإ بسحب يفرصت يقاب لوانت يلصاو .دوقفملا صرقلا نع

اضوع ةبلعلا نم ريخلأا صرقلا يلوانت نع دحاو مويب ةيرهشلا كترود رصقتس .داتعملاك اهل صصخملا مايلأا يف صارقلأا ءدب موي ريغتيس ،فقوتلا مايأ 7 دعب .ررضتت مل لمحلا نم ةيامحلا نكلو ،داتعملا .ةقباسلا ةبلعلا نم موي لبق أدبيسو ةبلعلا يلوانت ،ةيرهشلا كترود ءدب موي رييغتب نيبغرت لا تنكو ةيفاضإ ةبلع كتزوحب ناك اذإ وأ كنكمي .داتعملاك ةيلاحلا ةبلعلا نم صارقلأا يقاب لوانت يلصاو .ةيفاضلإا ةبلعلا نم صرق .ةيفاضإ صارقأ كنادقف ةلاحل كلذو ،)ةيطايتحإ( ةيفاضإ ةبلعك ةحوتفملا ةبلعلا ظفح لاهسلإا وأ ؤيقتلا لاح يف ،صرق لوانت ةظحل نم تاعاس 4 للاخ ةديدش تلااهسإ وأ تاؤيقت نم كتاناعم لاح يف لاح يف .مضهلا زاهج نم هلمكأب يمويلا صرقلا صتمي نأب مات نامض كانه سيلف تدقف اذإ" ةرقفلا هذه يف تاداشرلإا يعبات ،نايلم لوانت نم ةعاس 12 للاخ كئافش .يفاضإ صرق لوانت كيلع بجوتي فيك حرشت يتلا ،"صرق ،صرقلا لوانت ذنم ةعاس 12 نم رثكأ ةدمل تلااهسإ وأ تاؤيقت نم كتاناعم لاح يف ."ءاودلا لوانت تيسن اذإ" ةرقفلا هذه يف تاداشرلإا يعبات كيصوي نأ زئاجلا نم .ةيمضهلا تابارطضلإا مقافت وأ رارمتسإ لاح يف بيبطلا يغلب .لمحلا عنمل ةليدب ةليسو لامعتسإب ؟لماح كنأب لامتحإ كانه له ـ ةيرهشلا ةرودلا بايغ نكلو ،لماح كنأ ىلع لدت نأ نكمي ةلاحلا هذه .يثمط فزن رهظي لاأ زئاجلا نم ،

انايحأ .تاداشرلإا بسح صارقلأا تلوانت اذإ كلذو رملأا اذه ثودح لامتحإ

ادج دعبتسم نأب لامتحإ كانه نأب نيدقتعت تنك اذإ .اهل صصخملا دعوملا يف ةيلاتلا ةبلعلا يئدبإ رهظي مل اذإ وأ ،)نمازتلاب ىرخأ ةيودأ تلوانت وأ صرق تيسن اذإ ،

لاثم( لماح ينوكت نع يفقوت ،

لاماح تنك اذإ .لمحلل يتيب صحف ءارجإ كيلعف ،ةيفاضإ ةرم يثمط فزن .بيبطلل يهجوتو نايلم لوانت لمحلاب نيبغرت تنك اذإ نع فقوتلا دعب لمحلا عنمل ىرخأ ةليسو لامعتسإب ىصوي ،لمحلل نيططخت تنك اذإ ضرغل كيدل يعيبطلا ثمطلا يقلت خيرات ىلع كبيبط دمتعي .ثمطلا يقلت ىتحو نايلم ببسي نلف ،لاحلا يف لمحلا ثودح لاح يف ،كلذ عم .عقوتملا ةدلاولا خيراتب نهكتلا .كعيضرل وأ كل

اررض رملأا اذه رادقملا نم دكأتلاو ءاودلا عباط صيخشت بجي !ةمتعلا يف ةيودلأا لوانت زوجي لا .كلذ رملأا مزل اذإ ةيبطلا تاراظنلا يعض .ءاود اهيف نيلوانتت ةرم لك يف يئاودلا بيبطلا يريشتسإ ،ءاودلا اذه لامعتسإ لوح ةيفاضإ ةلئسأ كيدل ترفوت اذإ .يلديصلا وأ ةيبناجلا ضارعلأا

)4

.تلامعتسملا ضعب دنع ةيبناج

اضارعأ ببسي دق نايلم لامعتسإ نإ ،ءاود لكب امك .اهنم

ايأ يناعت لاأ زئاجلا نم .ةيبناجلا ضارعلأا ةمئاق نم يشهدنت لا اذإ وأ ،

لاصاوتم وأ

اديدش ناك اذإ ةصاخ ،ةيبناجلا ضارعلأا نم رثكأ وأ دحاو كيدل رهظ اذإ .كلذ نع كبيبط يغلب ،نايلم ـب ةلص هل نأب نيدقتعت يذلا ةيحصلا كتلاح ىلع ريغت أرط وأ )]VTE[ ةيديرو ةطلج( ةدرولأا يف ةيومد تارثخ ثودحل ةدئاز ةروطخ كانه نلوانتت يتاوللا ءاسنلا ةفاك ىدل )]ATE[ ةينايرش ةطلج( نييارشلا يف ةيومد تارثخ نع ةجتانلا ةفلتخملا رطاخملا لوح ةيفاضإ ليصافتل .ةبكرم ةينومروه لمح عنم لئاسو ."ءاودلا لامعتسإ لبق" 2 ةرقفلا يرظنأ ،ةبكرملا ةينومروهلا لمحلا عنم لئاسو لوانت بيبطلا ىلإ

ً

لااح هجوتلا بجي ـ ةريطخ ةيبناج ضارعأ 10٫000 نيب نم تلامعتسم 1-10 ىدل رهظت ضارعأ ـ ةردان ةيبناج ضارعأ

لاثم نايرشلا يف وأ ديرولا يف ةراض ةيومد تارثخ )ةقيمعلا ةدرولأا ةطلج( مدقلا ةحار يف وأ لجرلا يف - )يوئر مامصنإ( ةئرلا يف - ةيبلق ةبون - ةيغامد ةتكس - ةيرافقإ ةبونك فرعت يتلا ةتكسلا هبشت ةرباع ضارعأ وأ ةفيفخ ةيغامد ةتكس

(TIA( ةرباع نينيعلا يف وأ ىلكلا يف ،ءاعملأا/ةدعملا يف ،دبكلا يف ةيومد تارثخ - ديزي يذلا رخآ لماع يأ كيدل دجو اذإ ربكأ نوكت دق ةيومد ةرثخ ريوطت ةروطخ نإ ،ةيومدلا ةرثخلا ضارعأو ةروطخلا لماوع نع ةيفاضإ تامولعمل( ةروطخلا هذه نم .(2 ةرقفلا يرظنأ .)”ةيومدلا تارثخلا“ 2 ةرقفلا يرظنأ( ةيومد ةرثخ دجاوتل تاملاع :ةيثارو ةيئاعو ةمذو مقافتل وأ ديدش يسسحت لعف درل تاملاع ةرجنحلا وأ ناسللا خافتنإ .ةرجنحلا وأ ناسللا ،مفلا ،نيتفشلا ،هجولا ،نيديلا خافتنإ

سفنتلاو علبلا يف تابوعصل يدؤي دق ةكحو )ىرش( زراب رمحأ حفط - :لمشت يدثلا ناطرسل تاملاع دلجلا يف ةرفح روهظ - ةملحلا يف تاريغت - اهب نيرعشت وأ اهيرت يتلا لتك - :لمشت محرلا قنع ناطرسل تاملاع مد يوحي وأ/و ةحئار وذ يلبهم زارفإ

يداع ريغ يلبهم فزن - ضوحلا يف ملاآ

ةيسنج تاقلاع ةسرامم ءانثأ ملأ

:لمشت دبكلا يف ةريطخ لكاشمل تاملاع نطبلا ىلعأ يف ديدش ملأ

)ناقري( نينيعلا وأ دلجلا رارفصإ

hepatitis

( يسوريﭭلا دبكلا باهتلإ

مسجلا لماكب ةكح - زئاجلا نم .بيبطلا ىلإ

لااح يهجوت ،

افنآ تركذ يتلا ضارعلأا ىدحإ كيدل ترهظ اذإ .نايلم لوانت نع فقوتلاب كيصوي نأ ةروطخ لقأ ،ةيفاضإ ةيبناج ضارعأ 100 نيب نم تلامعتسم 1-10 ىدل رهظت ضارعأ ـ ةعئاش ةيبناج ضارعأ نايثغ - نطبلا يف ملأ

مسجلا نزو ةدايز - عادص - يبائتكإ جازم وأ ةيسفنلا ةلاحلا يف تاريغت - نييدثلا يف ةيساسح وأ ملأ

1٫000 نيب نم تلامعتسم 1-10 ىدل رهظت ضارعأ ـ ةعئاش ريغ ةيبناج ضارعأ ةدعملا داسفو تاؤيقت - لئاوسلا سابتحإ

ةقيقش - ةيسنجلا ةبغرلا صقانت - نييدثلا مخضت - ةكح ببسي دق يذلا حفط - 10٫000 نيب نم تلامعتسم 1-10 ىدل رهظت ضارعأ ـ ةردان ةيبناج ضارعأ ةقصلالا تاسدعلا لمحت مدع - نزولا صقانت - ةيسنجلا ةبغرلا ةدايز - نييدثلا نم تازارفإ وأ ةيلبهم تازارفإ

اهنع غلب يتلا ىرخأ ةيبناج ضارعأ فقوتي .)فيفخ فزن وأ عقب روهظ( نيثمط نيب ةفزنأ رهظت دق ىلولأا رهشلأا للاخ - ناك لاح يف .لامعتسلإا ىلع كمسج دوعتي نأ دعب ةداع نيثمطلا نيب فزنلا اذه روهظ" 4 ةرقفلا يف يرظنأ( بيبطلا يعجار ،

اددجتم وأ

ارمتسم ،

اديدش فزنلا .)"نيثمط نيب فزن رهشأ ةدع دعب

اضيأ رهظت نأ نكمي عقبلا هذه .)دلجلا ىلع ءارفص ـ ةينب عقب( فلك - ةعشلأل وأ سمشلل ضرعتلا بنجتب عقبلا ثودح ليلقت ناكملإاب .نايلم لامعتسإ نم .(UV( ةيجسفنبلا قوف :ءاودلل قباس لامعتسإب وأ لمحلا للاخ مقافتت دق يتلا ةيبط تلااح - )ناقري( دلجلا رارفصإ ○

pruritus

( ةلصاوتم ةكح ○ ىلكلا وأ دبكلل يفيظولا ءادلأا يف لكاشم ○ ةرارملا يف ىصح ○ ةيزاهج ةيمامح ةبئذ لثم ةردان ةيبط تلااح ○

chorea

( صقرلا ىمسملا يكرحلا بارطضلإا مقافت وأ روهظ ○ لمحلا للاخ )herpes gestationis( تلاصيوحلا هبشي حفط ○

otosclerosis

( نذلأا بلصت عون نم يثارو ممص ○ نورك ءاد ○ يحرقتلا نولوقلا باهتلإ ○ يلجنملا مدلا رقف نم نوناعت كتلئاع دارفأ دحأ وأ تنأ تنك اذإ ○ )ةيثارو ةيئاعو ةمذو( مسجلا نم ءازجأ خافتنإ ○ ايريفروﭘ مسإب يثارو ضرم ○ محرلا قنع ناطرس ○ نيثمط نيب فزن روهظ ةصاخ ،نايلم نلوانتت يتاوللا ءاسنلا ضعب ىدل عقب وأ فيفخ نيثمط نيب فزن رهظي ةجاح لاو نيموي ـ موي للاخ فزنلا اذه لوزي ام ،ةداع .جلاعلل ىلولأا رهشلأا للاخ هذه لوزت نأ تلاامتحلإا بلغأ .داتعملاك نايلم لوانتب يرمتسإ .هروهظ ببسب قلقلل .بلع ةدع لامعتسإ دعب ةرهاظلا ,كلذل ،مظتنم ريغ لكشب نايلم لوانت ببسب

اضيأ رهظي نأ نكمي نيثمط نيب فزنلا رهظي نأ نكمي ،كلذل ةفاضإ .موي لك نم ةعاسلا سفنب صرقلا لوانت ىلع يصرحإ .ىرخأ ةيودأ لامعتسإ ةجيتن نيثمط نيب فزنلا :يذلا عقب وأ نيثمط نيب فزن رهظ اذإ بيبطلا يريشتسإ رهشأ ةدع نم رثكأ رمتسإ نمزلا نم ةرتفل نايلم تلوانت نأ دعب أدب نايلم لوانت نع تفقوت نأ دعب ىتح رمتسإ نيناعت امدنع وأ ،ةيبناجلا ضارعلأا ىدحإ تمقافت اذإ ،يبناج ضرع رهظ اذإ .بيبطلا ةراشتسإ كيلع ،ةرشنلا هذه يف ركذي مل يبناج ضرع نم غيلبت« طبارلا ىلع طغضلا ةطساوب ةحصلا ةرازول ةيبناج ضارعأ نع غيلبتلا ناكملإاب ةرازو عقومل ةيسيئرلا ةحفصلا ىلع دوجوملا »يئاود جلاع بقع ةيبناج ضارعأ نع ضارعأ نع غيلبتلل رشابملا جذومنلل كهجوي يذلا )www.health.gov.il( ةحصلا :طبارلا حفصت قيرط نع وأ ،ةيبناج

https://sideeffects.health.gov.il

؟ءاودلا نيزخت ةيفيك )5 لوانتم نع

اديعب قلغم ناكم يف رخآ ءاود لكو ءاودلا اذه ظفح بجي !ممستلا يبنجت يببست لا .ممستلاب مهتباصإ يدافتل كلذو ،عضرلا وأ/و لافطلأا ةيؤر لاجمو يديأ .بيبطلا نم ةحيرص تاميلعت نودب ؤيقتلا رهظي يذلا )exp. date( ةيحلاصلا خيرات ءاضقنإ دعب ءاودلا لامعتسإ زوجي لا .رهشلا سفن نم ريخلأا مويلا ىلإ ةيحلاصلا ءاضقنإ خيرات ريشي .ةبلعلا رهظ ىلع .ءوضلا نم ةيامحلا بجي .ةيوئم ةجرد 25 نع ديزت ةرارح ةجردب نيزختلا زوجي لا ةيودأ عم فرصتلا ةيفيك نع يلديصلا يلأسإ .ةمامقلا ةلس ىلإ ةيودلأا يمر زوجي لا .ةئيبلا ىلع ظافحلا يف يدعاست كلذب ،لامعتسلإا ديق دعت مل ةيفاضإ تامولعم )6

اضيأ ةلاعفلا داوملل ةفاضلإاب ءاودلا يوتحي

Lactose monohydrate, sucrose, maize starch, calcium

carbonate, talc, polyethylene glycol 6000, povidone 25000,

magnesium stearate, povidone 700000, montanglycol wax

.(wax E)

.زوركس غلم 19.66 -و ،تارديهونوم زوتكل غلم 37.155 ىلع صرق لك يوتحي ةبلعلا ىوتحم وه امو ءاودلا ودبي فيك .ةيلطم ،ءاضيب ،ةريدتسم صارقأ

ةبلع لك يوتحت .

اصرق 21 تاذ بلعب )رتسيلب( تاحيول نمض ةرفوتم صارقلأا

.تاوبع 3 وأ 1 ىلع .عوبسلأا مايأ نم مويب ملعم صرق لك ،ةحيوللا رهظ ىلع

.بلعلا ماجحأ ةفاك قوست لاأ زئاجلا نم

نوراشه دوه ،36 شاراحاه عراش ،.ض.م ليئارسا رياب :هناونعو زايتملإا بحاص

.45240

رياب وأ ،اسنرف ،Lys Lez Lannoy ،.سإ.يأ.سإ ليل مرافليد :هناونعو جتنملا مسإ .ايناملأ ،.يج.يآ امراف نوناك خيرات يف صخ

رو صح

ف اهاوتحمو ةرشنلا هذه ةغيص ةحصلا ةرازو ترقأ .2020 راذآ خيراتب ةحصلا ةرازو تاميلعت بجومب اهثيدحت متو 2015 لولأا :ةحصلا ةرازو يف يموكحلا ةيودلأا لجس يف ءاودلا لجس مقر

109 12 29094 00

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Prescribing Information

1.

NAME OF THE MEDICINAL PRODUCT

Meliane

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 0.075mg gestodene and 0.02mg ethinylestradiol

3.

PHARMACEUTICAL FORM

Sugar - coated tablets

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications.

Oral contraception.

The decision to prescribe Meliane should take into consideration the individual

woman’s current risk factors, particularly those for venous thromboembolism (VTE),

and how the risk of VTE with Meliane compares with other combined hormonal

contraceptives (CHCs) (see sections 4.3 and 4.4).

4.2

Posology and method of administration.

First treatment cycle:

1 tablet for 21 days, starting on the first day of the menstrual

cycle. Contraceptive protection begins immediately.

Subsequent cycles:

Tablet taking from the next pack of Meliane is continued after a

7-day interval, beginning on the same day of the week as the first pack.

Changing from 21 day combined oral contraceptives:

The first tablet of Meliane

should be taken on the first day immediately after the end of the previous oral

contraceptive course. Additional contraceptive precautions are not required.

Changing from a combined Every Day pill (28 day tablets):

Meliane should be started after taking the last active tablet from the Every Day Pill

pack. The first Meliane tablet is taken the next day. Additional contraceptive

precautions are not then required.

Changing from a progestogen-only pill (POP):

The first tablet of Meliane should be taken on the first day of bleeding, even if a POP

has already been taken on that day. Additional contraceptive precautions are not then

required. The remaining progestogen-only pills should be discarded.

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Post-partum and post-abortum use:

After pregnancy, oral contraception can be

started 21 days after a vaginal delivery, provided that the patient is fully ambulant

and there are no puerperal complications. Additional contraceptive precautions will

be required for the first 7 days of pill taking. Since the first post-partum ovulation

may precede the first bleeding, another method of contraception should be used in

the interval between childbirth and the first course of tablets. After a first-trimester

abortion, oral contraception may be started immediately in which case no additional

contraceptive precautions are required.

Special circumstances requiring additional contraception

Incorrect administration:

A single delayed tablet should be taken as soon as possible,

and if this can be done within 12 hours of the correct time, contraceptive protection

is maintained. With longer delays, additional contraception is needed. Only the most

recently delayed tablet should be taken, earlier missed tablets being omitted, and

additional non-hormonal methods of contraception (except the rhythm and

temperature methods) should be used for the next 7 days, while the next 7 tablets are

being taken. Additionally, therefore, if tablet(s) have been missed during the last 7

days of a pack, there should be no break before the next pack is started. In this

situation, a withdrawal bleed should not be expected until the end of the second pack.

Some breakthrough bleeding may occur on pill taking days but this is not clinically

significant. If the patient does not have a withdrawal bleed during the tablet-free

interval following the end of the second pack, the possibility of pregnancy must be

ruled out before starting the next pack.

Gastro-intestinal upset:

Vomiting or diarrhoea may reduce the efficacy of oral

contraceptives by preventing full absorption. If vomiting or diarrhoea occurs within 4

hours of taking Meliane tablet-taking from the current pack should be continued.

Additional non-hormonal methods of contraception (except the rhythm or

temperature methods) should be used during the gastro-intestinal upset and for 7 days

following the upset. If these 7 days overrun the end of a pack, the next pack should

be started without a break. In this situation, a withdrawal bleed should not be

expected until the end of the second pack. If the patient does not have a withdrawal

bleed during the tablet-free interval following the end of the second pack, the

possibility of pregnancy must be ruled out before starting the next pack. Other

methods of contraception should be considered if the gastro-intestinal disorder is

likely to be prolonged.

Children: Not applicable.

Elderly: Not applicable.

4.3

Contraindications.

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

Should any of the conditions appear for the first time during CHC use,

the product should

be stopped immediately.

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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 or acquired predisposition for arterial thromboembolism, such as

hyperhomocysteinaemia and anti-phospholipid 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, e.g. active viral hepatitis and severe

cirrhosis, as long as liver function values have not returned to normal.

Presence or history of liver tumours (benign or malignant).

Current or history of breast cancer.

Pregnancy and Breastfeeding

Hypersensitivity to the active substance(s) or to any of the excipients.

Meliane is contraindicated for concomitant use with the medicinal products containing

ombitasvir / paritaprevir / ritonavir or dasabuvir (see sections 4.4 and 4.5).

4.4

Special warnings and precautions for use.

Warnings

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

Meliane 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

Meliane should be discontinued.

Risk of venous thromboembolism (VTE)

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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 Meliane 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 Meliane, 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).

It is estimated

that out of 10,000 women who use a CHC containing gestodene 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.

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.

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, cerebral 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).

Meliane 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 pill (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

Meliane has not been discontinued in advance.

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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.

Other medical conditions associated

with VTE

Cancer, systemic lupus erythematosus, haemolytic

uraemic syndrome, chronic inflammatory bowel

disease (Crohn’s disease or ulcerative colitis) and

sickle cell disease.

Increasing age

Particularly above 35 years.

There is no consensus about the possible role of varicose veins and superficial

thrombophlebitis in the onset or 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)

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Epidemiological studies have associated the use of CHCs with an increased risk for arterial

thromboembolism (myocardial infarction) or for 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). Meliane 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

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 kg/m²)

Risk increases substantially as BMI increases.

Particularly important in women with additional

risk

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.

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;

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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, or 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.

Medical Examination/Consultation

Prior to the initiation or reinstitution of Meliane 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 Meliane

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 and nature of examinations should be based on established

practice guidelines and be adapted to the individual woman.

Women

should

advised

that

hormonal

contraceptives

protect

against

infections (AIDS) and other sexually transmitted diseases.

Undiagnosed vaginal bleeding that is suspicious for underlying conditions should be

investigated.

Conditions which require strict medical supervision

The decision to prescribe the COC must be made using clinical judgement and in

consultation with the woman. Exacerbation or first appearance of any of these conditions

may indicate that use of the oral contraceptive should be discontinued:

Diabetes mellitus with mild vascular disease or mild nephropathy, retinopathy or

neuropathy

Hypertension that is adequately controlled, i.e. systolic >140 to159 mm Hg or

diastolic > 90 to 94mmHg (see also Section 4.4 ‘Reasons for stopping oral

contraception immediately’)

porphyria

obesity

migraine

cardiovascular diseases

Reasons for stopping oral contraception immediately:

When stopping oral contraception non-hormonal contraception should be used to ensure

contraceptive protection is maintained.

Occurrence for the first time, or exacerbation, of migrainous headaches or unusually

frequent or unusually severe headaches

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Sudden disturbances of vision, of hearing or other perceptual disorders

First signs of thrombosis or blood clots (e.g. unusual pains in or swelling of the

leg(s), stabbing pains on breathing or coughing for no apparent reason). Feeling of

pain and tightness in the chest

Six weeks before an elective major operation (e.g. abdominal, orthopaedic), any

surgery to the legs, medical treatment for varicose veins or prolonged

immobilisation, e.g. after accidents or surgery. Do not restart until 2 weeks after full

ambulation. In case of emergency surgery, thrombotic prophylaxis is usually

indicated e.g. subcutaneous heparin

Onset of jaundice, hepatitis, itching of the whole body

Significant rise in blood pressure

Severe upper abdominal pain or liver enlargement

Clear exacerbation of conditions known to be capable of deteriorating during oral

contraception or pregnancy (see section 4.4 ‘Conditions which deteriorate in

pregnancy or during previous COC use’ under 'Other conditions')

Tumours

Numerous epidemiological studies have been reported on the risks of ovarian, endometrial,

cervical and breast cancer in women using combined oral contraceptives. The evidence is

clear that high dose combined oral contraceptives offer substantial protection against both

ovarian and endometrial cancer. However, it is not clear whether low dose COCs confer

protective effects to the same level.

Breast cancer

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 combined oral contraceptives (COCs). 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. The additional breast cancers diagnosed in current users of COCs or

in women who have used COCs in the last ten years are more likely to be localised to the

breast than those in women who never used COCs.

Breast cancer is rare among women under 40 years of age whether or not they take COCs.

Whilst this background risk increases with 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 (see bar chart).

The most important risk factor for breast cancer in COC users is the age women discontinue

the COC; the older the age at stopping, the more breast cancers are diagnosed. Duration of

use is less important and the excess risk gradually disappears during the course of the 10

years after stopping COC use such that by 10 years there appears to be no excess.

The possible increase in risk of breast cancer should be discussed with the user and

weighed against the benefits of COCs taking into account the evidence that they offer

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substantial protection against the risk of developing certain other cancers (e.g. ovarian and

endometrial cancer).

Estimated cumulative numbers of breast cancers per 10,000

women diagnosed in 5 years of use and up to 10 years after

stopping COCs, compared with numbers of breast cancers

diagnosed in 10,000 women who had never used COCs

17.5

48.7

Under 20

20-24

25-29

30-34

35-39

40-44

Took the Pill at these ages:

Number of breast

cancers

Never took COCs

Used COCs for 5 years

Cancers found up to the age of:

Cervical Cancer

The most important risk factor for cervical cancer is persistent HPV infection. Some

epidemiological studies have indicated that long-term use of COCs may further contribute

to this increased risk but there continues to be controversy about the extent to which this

finding is attributable to confounding effects, e.g., cervical screening and sexual behaviour

including use of barrier contraceptives.

Liver Cancer

In rare cases, benign and, in even rarer cases, malignant liver tumours leading in isolated

cases to life-threatening intraabdominal haemorrhage have been observed after the use of

hormonal substances such as those contained in Meliane. If severe upper abdominal

complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, the

possibility of a liver tumour should be included in the differential diagnosis.

Other conditions

possibility

cannot

ruled

that

certain

chronic

diseases

occasionally

deteriorate during the use of combined oral contraceptives.

Known hyperlipidaemias

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Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk

of pancreatitis when using COCs.

Women with hyperlipidaemias are at an increased risk of arterial disease (see section 4.4

‘Circulatory disorders’). However routine screening of women on COCs is not appropriate.

Blood pressure

Hypertension is a risk factor for stroke and myocardial infarction (see section 4.4 ‘Arterial

thromboembolic-related conditions’). Although small increases in blood pressure have been

reported in many women taking COCs, clinically relevant increases are rare. However, if

sustained hypertension develops during the use of a COC, antihypertensive treatment

should normally be instigated at a level of 160/100 mm Hg in uncomplicated patients or at

140/90 mm Hg in those with target organ damage, established cardiovascular disease,

diabetes or with increased cardiovascular risk factors. Decisions about the continued use of

the COC should be made at lower BP levels, and alternative contraception may be advised.

Conditions which deteriorate in pregnancy or during previous COC use

The following conditions have been reported to occur or deteriorate with both pregnancy

and COC use. Consideration should be given to stopping Meliane if any of the following

occur during use:

jaundice and/or pruritus related to cholestasis

COCs may increase the risk of gallstone formation and may worsen existing disease

systemic lupus erythematosus

herpes gestationis

otosclerosis-related hearing loss

sickle cell anaemia

renal dysfunction

hereditary angioedema

any other condition an individual woman has experienced worsening of during

pregnancy or previous use of COCs.

Disturbances of liver function

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

use until markers of liver function return to normal.

Diabetes (without vascular involvement)

Insulin-dependent diabetics without vascular disease can use COCs. However it should be

remembered that all diabetics are at an increased risk of arterial disease and this should be

considered when prescribing COCs. Diabetics with existing vascular disease are

contraindicated from using COCs (see section 4.3 Contraindications).

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

ethinylestradiol).

However,

diabetic

women

should

carefully observed while taking COCs.

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Psychiatric Disorders

Depressed mood and depression are well-known undesirable effects of hormonal

contraceptive use (see section 4.8). Depression can be serious and is a well-known risk factor

for suicidal behaviour and suicide. Women should be advised to contact their physician in

case of mood changes and depressive symptoms, including shortly after initiating the

treatment."

Chloasma

Chloasma

occasionally

occur,

especially

women

with

history

chloasma

gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or

ultraviolet radiation whilst taking COCs.

Menstrual Changes

Reduction of menstrual flow:

This is not abnormal and it is to be expected in some patients.

Indeed, it may be beneficial where heavy periods were previously experienced.

Missed menstruation:

Occasionally, withdrawal bleeding may not occur at all. If the tablets

have been taken correctly, pregnancy is very unlikely. If withdrawal bleeding fails to occur

at the end of a second pack, the possibility of pregnancy must be ruled out before resuming

with the next pack.

Intermenstrual bleeding

: 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. If bleeding

irregularities persist or occur after previously regular cycles, then non-hormonal causes

should be considered and adequate diagnostic measures are indicated to exclude

malignancy or pregnancy. This may include curettage.

Some women may experience amenorrhoea or oligomenorrhoea after discontinuation of

oral contraceptives, especially when these conditions existed prior to use. Women should be

informed of this possibility.

Lactose and Sucrose Intolerance

Each tablet of this medicinal product contains 37.155 mg lactose and 19.660 mg sucrose per

tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase

deficiency, fructose intolerance or glucose-galactose malabsorption or sucrase-isomaltase

should not take this medicine.

ALT elevations

During clinical trials with patients treated for hepatitis C virus infections (HCV) with the

medicinal products containing ombitasvir / paritaprevir / ritonavir and dasabuvir with or

without ribavirin, transaminase (ALT) elevations higher than 5 times the upper limit of

normal (ULN) occurred significantly more frequently in women using ethinylestradiol-

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containing medications such as combined hormonal contraceptives (CHCs) (see section 4.3

and 4.5).

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.

Enzyme inducers

Interactions can occur with drugs that induce microsomal enzymes (especially cytochrome

P450 3A4) which can result in increased clearance of sex hormones and which may lead to

breakthrough bleeding and/or contraceptive failure.

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.

Women on short term treatment with any of these drugs should temporarily use a barrier

method in addition to the COC or choose another method of contraception. The barrier

method should be used during the time of concomitant drug administration and for 28 days

after their discontinuation. If the period during which the barrier method is used runs

beyond the end of a pack, the next pack should be started without a break. In this situation,

a withdrawal bleed should not be expected until the end of the second pack. If the patient

does not have a withdrawal bleed during the tablet-free interval following the end of the

second pack, the possibility of pregnancy must be ruled out before resuming with the next

pack.

For women receiving long-term therapy with enzyme inducers, another method of

contraception should be used.

The following have been shown to have clinically important interactions with COCs:

Anticonvulsants:

barbiturates (including phenobarbitone), primidone, phenytoin,

carbamazepine, oxcarbazepine, topiramate.

Antibiotics/antifungals:

griseofulvin , rifampicin.

Herbal remedies:

St. John’s wort (

Hypericum perforatum

Antiretroviral agents

: ritonavir, nelfinavir, nevirapine.

Note: There are other antiretroviral agents that may increase plasma concentration of sex

hormones.

Substances decreasing the clearance of COCs

enzyme inhibitors

Strong and moderate CYP3A4 inhibitors such as azole antifungals (e.g. itraconazole,

voriconazole, fluconazole) and macrolides (e.g. erythromycin) can increase plasma

concentrations of the estrogen or the progestin or both.

Etoricoxib doses of 60 to 120 mg/day have been shown to increase plasma concentrations

of ethinylestradiol 1.4 to 1.6-fold, respectively when taken concomitantly with a combined

hormonal contraceptive containing 0.035 mg ethinylestradiol.

Effects on other drugs

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Oral contraceptives may affect the metabolism of certain other drugs. Accordingly, plasma

and tissue concentrations may either increase (e.g. cyclosporin, tizanidine, theophylline) or

decrease (e.g. lamotrigine).

Pharmacodynamic interactions

Concomitant use with the medicinal products containing ombitasvir / paritaprevir / ritonavir

and dasabuvir, with or without ribavirin may increase the risk of ALT elevations (see

sections 4.3 and 4.4).

Therefore, Meliane-users must switch to an alternative method of contraception (e.g.,

progestagen-only contraception or non-hormonal methods) prior to starting therapy with this

combination drug regimen. Meliane can be restarted 2 weeks following completion of

treatment with this combination drug regimen.

Other forms of interactions

Laboratory tests

The use of oral contraceptives may influence the results of certain laboratory tests,

including biochemical parameters of liver, thyroid, adrenal and renal function, plasma

levels of carrier proteins, and lipid/lipoprotein fractions, parameters of carbohydrate

metabolism and parameters of coagulation and fibrinolysis. Laboratory staff should

therefore be informed about oral contraceptive use when laboratory tests are requested.

4.6 Pregnancy and lactation.

Meliane is not indicated during pregnancy. If pregnancy occurs during treatment with

Meliane, further intake must be stopped. However, 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 early pregnancy.

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

starting Meliane (see section 4.2 and 4.4).

The use of Meliane during lactation may lead to a reduction in the volume of milk produced

and to a change in its composition. Minute amounts of the active substances are excreted

with the milk. These amounts may affect the child particularly in the first 6 weeks post-

partum. Mothers who are breast-feeding may be advised instead to use another method of

contraception.

4.7 Effects on ability to drive and use machines.

None known.

4.8 Undesirable effects.

Summary of the safety profile

The most commonly reported adverse reactions with Meliane are nausea, abdominal

pain, increased weight, headache, depressed mood, altered mood, breast pain, breast

tenderness. They occur in ≥1% of users.

Serious adverse reactions are arterial and venous thromboembolism.

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System Organ

Class

Adverse events reported in clinical trials

Adverse events

reported post

marketing

Common

(≥ 1/100)

Uncommon

(≥ 1/1000,

< 1/100)

Rare

(<1/1000)

Eye disorders

contact lens

intolerance

Gastrointestinal

disorders

nausea,

abdominal

pain

vomiting,

diarrhea

Immune system

disorders

hypersensitivity

exacerbation of

hereditary angioedema

Investigations

weight

increased

weight decreased

Metabolism and

nutrition

disorders

fluid

retention

Hypertriglyceridemia,

changes in glucose

tolerance or effect on

peripheral insulin

resistance

Nervous system

disorders

headache

migraine

Vascular system

Venous

thromboembolism

(VTE), Arterial

thromboembolism

(ATE)

Hepatobiliary

disorders

liver function

disturbances

Psychiatric

disorders

depressed

mood,

mood

altered

libido

decreased

libido increased

Reproductive

system and

breast disorders

breast

pain,

breast

tenderness

breast

hypertrophy

vaginal discharge,

breast discharge

reduced menstrual

flow, spotting,

breakthrough bleeding

and missed withdrawal

bleeding, post pill

amenorrhoea

Skin and

subcutaneous

tissue disorders

rash,

urticaria

erythema nodosum,

erythema

multiforme

chloasma

Description of selected adverse reactions

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’:

Venous thromboembolic disorders

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Arterial thromboembolic disorders

Strokes (e.g. transient ischemic attack, ischemic stroke, haemorrhagic stroke

Hypertension

Liver tumours (benign and malignant)

The frequency of diagnosis of breast cancer is very slightly increased among COC 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 ‘Contraindications’ and 4.4 ‘Special warnings and precautions

for use’.

Conditions reported to deteriorate with pregnancy or previous COC use

Jaundice and/or pruritus related to cholestasis; gallstone formation; systemic lupus

erythematosus; exacerbation of chorea, herpes gestationis; otosclerosis-related hearing

loss; Crohn’s disease, ulcerative colitis, sickle cell anaemia; renal dysfunction; hereditary

angioedema; porphyria; cervical cancer.

Reporting of suspected adverse reactions

Reporting

suspected

adverse

reactions

after

authorisation

medicinal

product

important. It allows continued monitoring of the benefit/risk balance of the medicinal

product.

Any suspected adverse events should be reported to the Ministry of Health according to the

National Regulation by using an online form

https://sideeffects.health.gov.il

4.9 Overdose

Overdosage may cause nausea, vomiting and, in females, withdrawal bleeding. Withdrawal

bleeding may even occur in girls before their menarche, if they accidentally take the

medicinal product.

There are no specific antidotes and treatment should be symptomatic

5. PHARMACOLOGICAL PARTICULARS

5.1 Pharmacodynamic properties

The contraceptive effect of Meliane 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 cervical

secretion. Furthermore, the endometrium is rendered unreceptive to implantation.

5.2 Pharmacokinetic properties

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Gestodene

Orally administered gestodene is rapidly and completely absorbed. Following ingestion of a

single Meliane tablet, maximum drug serum levels of about 3.5 ng/ml are reached at about

1.0 hour. Thereafter, gestodene serum levels decrease in two phases. The terminal

disposition phase is characterised by a half-life of about 12 hours. For gestodene, an

apparent volume of distribution of 0.7 l/kg and a metabolic clearance rate from serum of

about 0.8 ml/min/kg were determined.

Gestodene is not excreted in unchanged form, but as metabolites, which are eliminated with

a half-life of about 1 day. Gestodene metabolites are excreted at a urinary to biliary ratio of

about 6:4. The biotransformation follows the known pathways of steroid metabolism. No

pharmacologically active metabolites are known.

Gestodene is bound to serum albumin and to sex hormone binding globulin (SHBG). Only

about 1.3% of the total serum drug levels are present as free steroid, but about 69% are

specifically bound to SHBG. The relative distribution (free, albumin-bound, SHBG-bound)

depends on the SHBG concentrations in the serum. Following induction of the binding

protein, the SHBG bound fraction increases to ca. 80 % while the unbound and the

albumin-bound fraction decrease.

Following daily repeated administration of Meliane, an accumulation of gestodene

concentration in the serum is observed. Mean serum levels are about fivefold higher at a

steady-state, which is generally reached during the second half of a treatment cycle. The

pharmacokinetics of gestodene are influenced by SHBG serum levels. Under treatment with

Meliane a twofold increase in the serum SHBG levels has been observed for the first

treatment cycle. Due to the specific binding of gestodene to SHBG, the increase in SHBG

levels is accompanied by an almost parallel increase in gestodene serum levels. After three

treatment cycles, the extent of SHBG induction per cycle does not seem to change further.

The absolute bioavailability of gestodene was determined to be 99 % of the dose

administered.

Ethinylestradiol

Orally administered ethinylestradiol is rapidly and completely absorbed. Following

ingestion of a single Meliane tablet, maximum drug serum levels of about 65 pg/ml are

reached at 1.7 hours.

Thereafter, ethinylestradiol serum levels decrease in two disposition phases, characterised

by half-lives of about 2 hours and 21 hours, respectively. The terminal half-life of

ethinylestradiol is subject to a large interindividual variation and a range of 5 to 30h has

been reported in the literature. Due to analytical reasons, these parameters can only be

calculated following the administration of higher doses. For ethinylestradiol, an apparent

volume of distribution of about 5 l/kg and a metabolic clearance rate from plasma of about

5 ml/min/kg were determined. Ethinylestradiol is highly but non-specifically bound to

albumin. About 2 % of drug levels are present unbound.

During absorption and first-liver passage, ethinylestradiol is metabolized extensively,

resulting in a mean oral bioavailability of about 45% with a large interindividual variation

of about 20-65%. Unchanged drug is not excreted. Ethinylestradiol metabolites are excreted

at a urinary to biliary ratio of 4:6 with a half-life of about 1 day.

According to the half-life of the terminal disposition phase from serum and the daily

ingestion, steady-state serum levels of ethinylestradiol can be expected to be reached after 5

– 6 days. At the end of a treatment cycle, they were found to be higher by about 40-60% as

compared to single dose administration.

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During established lactation, 0.02 % of the daily maternal dose could be transferred to the

newborn via milk.

The systemic availability of ethinylestradiol might be influenced in both directions by other

drugs. There is, however, no interaction with high doses of Vitamin C. Ethinylestradiol

induces the hepatic synthesis of SHBG and corticoid binding globulin (CBG) during

continuous use. The extent of SHBG induction, however, depends on the chemical structure

and the dose of the co-administered progestogen. During treatment with Meliane, SHBG

concentrations in the serum increased from 107 nmol/l to 216 nmol/l in the first and to 223

nmol/l in the third cycle. Serum concentrations of CBG were increased from 42 µg/ml to 77

µg/ml in the first cycle and remained constant thereafter.

5.3 Preclinical safety data

The combination of ethinylestradiol and gestodene, like other contraceptive steroids, is

associated with an increased incidence of neoplastic nodules in the rat liver, the relevance

of which to man is unknown. Malignant liver tumours have been reported on rare occasions

in long-term users of oral contraceptives.

There are no other preclinical safety data which could be of relevance to the prescriber and

which are not already included in other relevant sections of the leaflet.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose monohydrate

Sucrose

Maize starch

Calcium carbonate

Talc

polyethylene glycol 6000

Povidone 25 000

Magnesium stearate

Povidone 700 000

Montanglycol wax

6.2 Incompatibilities

None Known

6.3 Shelf life

The expiry date of the product is indicated on the packaging materials

6.4 Special precautions for storage

Do not store above 25°C, protect from light.

6.5 Nature and contents of container

Primary containers:

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The blister packs consist of hard tempered aluminium foil of thickness 20

m and

transparent PVC film of thickness 250

Presentation:

Blister memo-packs containing 21 tablets or 3x21 tablets.

6.6 Special precautions for disposal

No special requirements

Manufacturer

Delpharm Lille, SAS, France or

Bayer Pharma AG, Germany

Registration Holder

Bayer Israel Ltd 36 Hacharash St., Hod Hasharon 45240

The format of this leaflet was determined by the Ministry of Health and its content was

checked and approved by in December 2015 and updated according to the guidelines of

the Ministry of Health in March 2020.