YAZ

Israel - English - Ministry of Health

Buy It Now

Active ingredient:
DROSPIRENONE; ETHINYLESTRADIOL
Available from:
BAYER ISRAEL LTD
ATC code:
G03AA12
Pharmaceutical form:
FILM COATED TABLETS
Composition:
DROSPIRENONE 3 MG; ETHINYLESTRADIOL 0.02 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
BAYER WEIMAR GMBH UND CO.KG, GERMANY
Therapeutic group:
DROSPIRENONE AND ESTROGEN
Therapeutic area:
DROSPIRENONE AND ESTROGEN
Therapeutic indications:
- Oral contraception. - Treatment of moderate acne vulgaris in women who seek oral contraception. - Treatment of symptoms of premenstrual dysphoric disorder (PMDD ) in women who have chosen oral contraceptives as their method of birth control. The efficacy of Yaz for PMDD was not assessed beyond 3 cycles. Yaz has not been evaluated for treatment of PMS ( premenstrual syndrome ).
Authorization number:
141 04 32023 00
Authorization date:
2014-07-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

25-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

23-07-2020

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PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE

PHARMACISTS’ REGULATIONS (PREPARATIONS) - 1986

The medicine is dispensed with a doctor’s prescription only

Yaz

Film-coated Tablets

Each pink tablet contains:

Drospirenone 3 mg

Ethinylestradiol (as betadex clathrate) 0.02 mg

The white tablets do not contain active ingredients.

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 for you. Do not pass it on to others. It may harm

them even if it seems to you that their medical condition is similar.

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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 have symptoms of a blood

clot (see “Blood clots” in section 2).

1)

WHAT IS THE MEDICINE INTENDED FOR?

intended

prevent

pregnancy

treat

moderate

acne

severe

premenstrual symptoms, in women who choose to use an oral contraceptive pill.

Therapeutic group: Yaz belongs to a group of medicines called combination pills

that contain 2 types of female hormones: estrogen (ethinylestradiol) and progestogen

(drospirenone).

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2)

BEFORE USING THE MEDICINE

Do not use the medicine if:

you are sensitive (allergic) to drospirenone or ethinylestradiol or to any of the other

ingredients contained in the medicine. An allergic reaction may cause itching, rash,

or swelling. For the list of inactive ingredients, see section 6 “Further Information”.

You are pregnant or suspect that you are pregnant.

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

vessels of your legs (deep vein thrombosis, DVT), in the lungs (pulmonary

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

know

have

blood

clotting

disorder

(for

instance,

protein

deficiency, protein S deficiency, antithrombin III deficiency, Factor V Leiden or

antiphospholipid antibodies).

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

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very high blood pressure

very high blood fat levels (cholesterol or triglycerides)

a medical condition characterized by high blood levels of homocysteine

(hyperhomocysteinemia)

you are suffering, or have suffered in the past, from a type of migraine called

“migraine with aura”.

you have, or have had, a liver disease, and your liver functions are not yet back

to normal.

you have impaired kidney function (kidney failure).

you have, or have ever had, a liver tumor.

you have, or have ever had, or there is suspicion for presence of breast cancer or

cancer of the reproductive organs.

you are suffering from unexplained vaginal bleeding.

suffering

from

hepatitis

taking

medicinal

products

containing

ombitasvir/paritaprevir/ritonavir and dasabuvir (see also section 2 “Drug interactions”).

If you are suffering from one of the above-mentioned conditions, you must not use

Yaz. If you have any of the above-mentioned conditions, you must inform your doctor.

The doctor will discuss with you other contraceptive methods that will better suit you.

Special warnings regarding use of the medicine

Before you start taking Yaz, read the information regarding blood clots further in

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this section. It is especially important that you read about the symptoms of a blood

clot detailed later in section 2 “Blood clots”.

This leaflet details a number of cases in which you must stop taking Yaz, or cases in

which the reliability of Yaz may be reduced. In such cases, avoid sexual intercourse

or use additional, non-hormonal contraceptive measures, such as use of a condom

or any other barrier method. Do not rely on the “safe days” or body temperature

measurement methods. These methods may be unreliable, since Yaz affects the

cyclic changes in body temperature and in cervical secretions.

Yaz, like other hormonal contraceptives, does not protect against AIDS or any

other sexually transmitted disease.

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

are taking an oral contraceptive pill, since hormonal contraceptives may affect the

results of certain tests.

When should you contact the doctor?

Urgently seek medical attention

if you notice possible signs of a blood clot that may indicate the formation in

your body of 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.

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Some situations may require special care while using Yaz or any other combination

pill, and you may have to be regularly checked by your doctor.

Before using Yaz, tell the doctor if any of the following conditions applies to

you, develops or worsens while taking Yaz.

if a close relative has or has ever had breast cancer

if you have a disease of the liver or the gallbladder

if you have diabetes

if you suffer from depression

if you have Crohn’s disease or ulcerative colitis (chronic inflammatory bowel disease)

if you have systemic lupus erythematosus (lupus – a disease that affects the

immune system)

if you have hemolytic uremic syndrome (HUS - a blood clotting disorder causing

kidney failure)

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

if you have elevated fat levels in the blood (hypertriglyceridemia) or a family history

of this condition. Hypertriglyceridemia has been associated with an increased risk

of developing pancreatitis

if you need to undergo surgery, or if you are immobile for a long time (see “Blood

clots” in section 2)

f you have recently given birth, you are at an increased risk of blood clots. Consult

your doctor regarding how soon after delivery you can start taking Yaz

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if you have

an inflammation in the veins under the skin (superficial thrombophlebitis)

if you have varicose veins

if you have epilepsy (see “Drug interactions” in section 2)

if you have a disease that first appeared during pregnancy or during earlier use of

sex hormones (for example, hearing loss, a blood disease called porphyria, skin rash

with blisters during pregnancy [gestational herpes], a nerve disease causing sudden

movements of the body [Sydenham’s chorea])

if you have or have ever had goldish-brown patches on the skin (chloasma), known

as “pregnancy patches”, especially on the face. If so, avoid exposure to direct

sunlight or ultraviolet light

if you have hereditary angioedema, estrogen-containing preparations may cause the

symptoms of the disease or make them worse. Refer to a doctor immediately if you

experience symptoms of angioedema such as swollen face, tongue and/or throat

and/or difficulty swallowing or hives (urticaria), together with breathing difficulties

Blood clots

Using

combined

hormonal

contraceptive,

such

Yaz,

increases

your

risk

developing a blood clot compared to the risk when not using one. In rare cases, a

blood clot can block vessels and cause serious problems.

The risk level of thrombosis may vary in accordance with the type of pill you are taking.

Consult the doctor regarding the various options.

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Blood clots may form:

in the 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 fatal;

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

use of Yaz is small.

How to recognize a blood clot

Urgently seek 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 of the legs or along a vein in the leg

or foot, especially when accompanied by:

pain or tenderness in the leg, which

may be felt

only when standing or walking

ncreased warmth in the affected leg

change in color of the skin of the leg, e.g.,

turning pale, red or blue

Deep vein thrombosis

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Are you experiencing any of these signs?

What are you possibly

suffering from?

sudden unexplained breathlessness or rapid

breathing

sudden cough without an obvious cause, which

may bring up blood

sharp chest pain which may increase with deep

breathing

severe light-headedness or dizziness

rapid or irregular heartbeat

severe stomach pain

If you are unsure, talk to the doctor, as some of these

symptoms, such as coughing or breathlessness,

may be mistaken for milder conditions such as a

respiratory tract infection (e.g., a common cold).

Pulmonary embolism

Symptoms, which usually 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)

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Are you experiencing any of these signs?

What are you possibly

suffering from?

chest pain, discomfort, pressure, or heaviness

sensation of squeezing or fullness in the chest, arm

or below the breastbone

fullness, indigestion or feeling of choking

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

Stroke

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Are you experiencing any of these signs?

What are you possibly

suffering from?

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 must

still urgently seek medical attention, as you may be

at risk of another stroke.

Stroke

swelling and slight blue discoloration of the

extremities

severe stomach pain (acute abdomen)

Blood clots blocking

other blood vessels

Blood clots in a vein

What can happen if a blood clot forms in a vein?

The use of combined hormonal contraceptives has been associated with an increase in

the risk of blood clots in the vein (venous thrombosis). However, these side effects are rare

and most frequently occur in the first year of use of a combined hormonal contraceptive.

If a blood clot forms in a vein in the leg or foot, it can cause a deep vein thrombosis (DVT).

If a blood clot travels from the leg and reaches the lung, it can cause a pulmonary embolism.

Very rarely, a blood clot may form in a vein in another organ such as the eye (retinal

vein thrombosis).

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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 Yaz, your risk of developing a blood clot returns to normal within

a few weeks.

What is the risk of developing a blood clot?

The risk depends on your natural risk of venous thromboembolism (VTE) and the type

of combined hormonal contraceptive you are taking.

The overall risk of a blood clot in the leg or lung (DVT or PE) with Yaz is small.

of 10,000 women who are not using any combined hormonal contraceptive and

are not pregnant, about 2 will develop a blood clot in a year.

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

levonorgestrel, norethisterone, or norgestimate, about 5-7 will develop a blood clot in a year.

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

contains drospirenone, such as Yaz, between about 9 to 12 women will develop a

blood clot in a year.

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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” and “Factors

that increase your risk of a blood clot in an artery” 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 Yaz

About 9-12 out of 10,000 women

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

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

Your risk is higher:

if you are significantly 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 could have a

hereditary blood clotting disorder.

if you need to undergo surgery, or if you are immobile for a long time because of an

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injury or illness, or you have your leg in a cast. The use of Yaz may need to be stopped

several weeks before surgery or during the period in which you are less mobile. If you

need to stop Yaz, ask your doctor when you can start using it again.

with increasing age (particularly above about the age of 35).

if you gave birth less than a few weeks ago.

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

Air travel (more than 4 hours) may temporarily increase your risk of a blood clot,

particularly if you have some of the other factors listed.

It is important to tell your doctor if any of these conditions applies to you, even if you

are unsure. The doctor may decide that you should stop taking Yaz.

If any of the above conditions changes while you are using Yaz, for example, if a close

family member experiences a thrombosis for no known reason, or if you gain a lot of

weight, tell your doctor.

Blood clots in an artery

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

Like a blood clot in a vein, a blood clot in an artery can cause serious problems. For

example, a blood clot in an artery can 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 Yaz is very

small but can increase:

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with increasing age (above the age of about 35)

if you smoke. When using a combined hormonal contraceptive such as Yaz, it is

advisable to stop smoking. If you are unable to stop smoking and are over 35 years

of age, your doctor may advise you to use a different type of contraceptive measure

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 (below the age of about 50). In this case, you may also carry an increased risk of

having a heart attack or stroke

if you, or someone in your immediate family, have high blood fat levels (cholesterol

or triglycerides)

if you suffer from migraines, especially “migraine with aura”

if you have a problem with your heart (valve disorder, disturbance of the rhythm

called atrial fibrillation)

if you have diabetes.

If you have more than one of these conditions or if one of them is particularly severe,

the risk of developing a blood clot may be increased even more.

If one of the above conditions changes while you are using Yaz, for example, you start

smoking, a close family member experiences a thrombosis for no known reason, or you

gain a lot of weight, tell your doctor.

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Yaz and cancer

Breast cancer has been observed slightly more often in women taking combination

pills, but it is not known whether this increase is caused by the treatment with the

pills. For example, it could be that more tumors are detected in women who take

combination pills because they are examined by their doctors more often.

The incidence of breast cancer tumors gradually declines after discontinuing combined

hormonal contraceptive. It is important to regularly check your breasts and to contact

your doctor if you feel any lump.

There are rare reports of benign liver tumors, and there are even fewer reports of

malignant liver tumors in patients who took contraceptive pills. Contact the doctor if

you have unusually severe abdominal pain.

Psychiatric disorders

Some women using hormonal contraceptives, including Yaz, have reported

depression

or depressed mood. Depression may be serious and may sometimes lead to suicidal

thoughts. If you experience mood changes and symptoms of depression, contact your

doctor for medical advice as soon as possible.

Bleeding between periods

During the first few months of treatment with Yaz, you may have unexpected bleeding

(bleeding outside of the days on which you take the white tablets). If this bleeding

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occurs for more than a few months, or if it begins after a few months of treatment, your

doctor should evaluate what is wrong.

What to do if no bleeding occurs while taking the white tablets

If you have taken all the pink tablets correctly, have not vomited or had severe diarrhea

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

If the expected bleeding does not happen over 2 consecutive cycles, you may be

pregnant. Contact the doctor immediately. Do not start a new strip until you are sure

that you are not pregnant.

Drug interactions

If

you

are

taking,

or

have

recently

taken,

other

medicines,

including

non-

prescription medicines and nutritional supplements, tell the doctor or pharmacist.

Also inform the dentist or any other doctor who prescribes another medicine for you,

that you are taking Yaz. They will be able to tell you if you need to use an additional

contraceptive (e.g., condom), and if so, for how long, or, whether the use of the other

medicine you need to take should be changed. It is especially important to inform the

doctor or pharmacist if you are taking:

Certain medicines that can

have an influence on the blood levels of Yaz

make Yaz less efficacious in pregnancy prevention

cause unexpected bleeding

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This includes medicines used for the treatment of:

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

tuberculosis (e.g., rifampicin)

AIDS (HIV) and Hepatitis C infections (so-called protease inhibitors and non-

nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine, efavirenz)

fungal infections (griseofulvin, ketoconazole)

arthritis, arthrosis (etoricoxib)

pulmonary hypertension (bosentan)

the herbal preparation Hypericum (St. John’s wort)

Other medicines which may be influenced by the use of Yaz, such as:

medicines containing ciclosporin

lamotrigine to treat epilepsy (may lead to an increase in the frequency of seizures)

theophylline to treat breathing problems

tizanidine to treat muscle pain and/or muscle cramps

Do not use Yaz if you are suffering from hepatitis C and taking medicinal products

containing ombitasvir/paritaprevir/ritonavir and dasabuvir as this may lead to

increase in the results of liver function blood tests (increase in the liver enzyme ALT). Your

doctor will prescribe for you another type of contraceptive prior to starting treatment

with these medicinal products. You can resume the use of Yaz about 2 weeks after

completing treatment with these products. See section 2 “Do not use the medicine if”.

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Use of the medicine and food

The medicine can be swallowed on an empty stomach or with food, if necessary, with

a small amount of water.

Pregnancy and breastfeeding

Pregnancy

If you are pregnant, you must not take Yaz. If you became pregnant, while using Yaz,

you must immediately stop taking Yaz and contact your doctor. If you would like to

become pregnant, you can stop taking Yaz at any time (also see “If you stop taking the

medicine” in section 3).

Consult with your doctor or pharmacist prior to taking any medicine.

Breastfeeding

It is usually not recommended to take Yaz when breastfeeding. Use of Yaz while

breastfeeding may lead to a reduction in the volume of milk produced and change its

composition. Tiny quantities of the active substances are secreted in breast milk. These

quantities may affect the baby.

If you want to take the pill while breastfeeding, contact your doctor.

Consult with your doctor or pharmacist prior to taking any medicine.

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Driving and use of machines

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

Smoking

recommended

that

stop

smoking

when

using

combined

hormonal

contraceptive such as Yaz. 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.

Important information regarding some of the ingredients of the medicine

Yaz contains lactose.

If you suffer from intolerance to certain sugars, refer to the doctor before you start

taking the medicine.

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.

Each strip contains 24 light pink tablets that contain active ingredients, and 4 white

tablets that do not contain active ingredients.

The 2 types of tablets are packaged in a specific, predetermined order. A strip contains

28 tablets.

The dosage and the treatment regimen will be determined by the doctor only. The

usual dosage is generally one tablet every day.

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Do not exceed the recommended dose

Mode of administration:

The medicine can be swallowed with a little water.

The medicine can be taken without regard to meal times, but make sure to take the

tablet at the same time every day.

Do not crush/halve/chew the tablet, so as not to damage the coating of the tablet.

Be careful not to get confused when taking the tablets: Take the pink tablets for

the first 24 days and afterwards, take the white tablets on the following 4 days. Start a

new strip immediately after that. Do not take a break between one strip and the next.

Since the tablets have a different composition, it is important to start by taking the tablet

in the upper left corner, and to take one tablet every day. To maintain the correct order

of administration, follow the direction of the arrows that appear on the back of the strip.

Preparation of the strip before taking the tablets

To help you properly keep track of tablet administration, there are 7 stickers each with

the 7 days of the week. Choose the week sticker that starts with the day you begin

taking Yaz tablets. For example, if you start taking the tablets on a Wednesday, use the

week sticker that starts with “WED”.

Stick the week sticker along the top of the back of the Yaz strip, where it reads “Place

week sticker here”, so that the first day is above the tablet marked “1”.

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There is now a day indicated above every tablet, so you can see whether you have taken

a certain tablet that month. The arrows show the order you are to take the tablets.

During the 4 days when you are taking the white tablets, bleeding, resembling

menstrual bleeding, should begin. The bleeding usually starts on the 2nd or 3rd day

after the last pink tablet of Yaz is taken. On the day after you have taken the last white

tablet, you should start a new strip, whether your bleeding has stopped or not. This

means that you will start each strip on the same day of the week, and bleeding will

occur on the same days each month.

Taking Yaz in this manner will also provide protection against pregnancy during the 4

days when you are taking the white tablets.

When can you start using the first strip?

If you did not use a hormonal contraceptive in the previous month

Start taking Yaz tablets on the first day of the menstrual bleeding. In this case, you

are immediately protected from pregnancy. You can also begin between days 2-5 of

menstrual bleeding, but in this case, an additional contraceptive (e.g., a condom)

must be used during the first 7 days of taking Yaz.

Switching from another combined oral contraceptive pill, combined (vaginal) ring or patch

You can start taking Yaz on the day after taking the last active tablet of the previous

pills (the last tablet that includes active ingredients), but no later than the day after

you finish taking the inactive tablets of the previous pills (or after taking the last

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inactive tablet of the previous pills).

When switching from a combined (vaginal) ring or patch, consult the doctor.

Switching from a progestogen-only contraceptive (pills, contraceptive injections or

intrauterine device)

You may switch from the progestogen-only pill to Yaz on any day you wish (start

taking Yaz at the time of the next scheduled injection or on the day the intrauterine

device is removed), but in all of these cases, you must use an additional contraceptive

(e.g., a condom) during the first 7 days of taking Yaz.

After a miscarriage

Consult the doctor.

After having a baby

You can start taking Yaz between days 21 and 28 after having a baby. If you start

later than day 28, use a barrier contraceptive (e.g., a condom) during the first 7 days

of using Yaz.

If, after having a baby, you have had sex before you started taking Yaz, you must be

sure that you are not pregnant or wait until your next period.

If you are breastfeeding and want to start taking Yaz

Read “Pregnancy and breastfeeding” in section 2.

First consult with the doctor. Consult with the doctor if you are not sure when to start

taking Yaz.

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Tests and follow-up

Before commencing use of Yaz, your doctor will ask you questions regarding your and

your close family’s medical history. The doctor will measure your blood pressure and

may perform other tests, in accordance with your medical condition.

If you need to have blood tests done, tell the doctor or laboratory staff that you are taking

a combination pill, as hormonal contraceptives can affect the results of certain tests.

If you accidentally take too high a dosage

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

If you accidentally took several Yaz tablets at once, you may suffer from nausea,

vomiting or vaginal bleeding. Such bleeding may also appear in girls who have not yet

had their first menstrual period and have accidentally taken the medicine.

If you took an overdose, or if a child has 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

The last 4 tablets in the 4th row of the strip are inactive tablets. If you forget one of these

tablets, this has no effect on the reliability of Yaz. Throw away the forgotten tablet.

If you forget a pink, active tablet (tablets 1-24 of the strip), you must act according to

the following instructions:

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If the delay in taking a tablet is less than 24 hours, the protection against pregnancy

is not reduced. Take the tablet as soon as you can and then continue taking the rest

of the tablets as usual.

If the delay in taking a tablet is more than 24 hours, the protection against pregnancy

may be reduced. The greater the number of tablets you have forgotten, the greater is

the risk of becoming pregnant.

The risk of incomplete protection against pregnancy is greater if you forget a pink

tablet at the beginning or at the end of the strip. Therefore, keep to the following rules

(see the “I forgot to take” diagram below and on the back of the

package):

You forgot more than one tablet in a strip

Consult the doctor.

You forgot to take one tablet between days 1-7 (1st row)

Take the forgotten tablet as soon as possible, even if it means that you have

to take 2 tablets at the same time. Continue taking the rest of the tablets as

usual and use additional contraceptives (e.g., a condom) for the next 7 days. If

you have had sex in the week before the day you forgot the tablet, you may be

pregnant. In that case, consult the doctor.

You forgot to take one tablet between days 8-14 (2nd row)

Take the forgotten tablet as soon as possible, even if it means that you have to

take 2 tablets at the same time. Continue taking the rest of the tablets as usual.

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The protection against pregnancy is not reduced, and there is no need for use of

additional contraceptives.

You forgot to take one tablet between days 15-24 (3rd or 4th row)

You can choose between 2 possibilities:

Take the forgotten tablet as soon as possible, even if it means that you have

to take 2 tablets at the same time. Continue taking the rest of the tablets as

usual. Instead of taking the 4 white inactive tablets in the strip, discard them

and start the next strip (the start day will change). You will most likely have

a period at the end of the 2nd strip – when taking the white inactive tablets –

but you may have bleeding or spotting while using the 2nd strip.

u can also stop taking the pink active tablets and immediately start taking

the 4 white inactive tablets (before taking the inactive tablets, record the day

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

normally start, take the inactive tablets for less than 4 days.

If you follow one of these 2 recommendations, you will remain protected against

pregnancy.

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

during the days on which you are taking the inactive tablets, you may be pregnant.

Refer to the doctor before you start the next strip.

Adhere to the treatment regimen recommended by the doctor.

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“I forgot to take” Flowchart

You forgot

to take

more than

one pink

tablet in

a strip

Consult with the attending doctor

You had sexual intercourse in the week preceding

the day you forgot to take the tablet?

Take the forgotten tablet

Use a condom for 7 days

Finish the strip of pills

Take the forgotten tablet

Finish the strip of pills

Take the forgotten tablet

Finish taking the pink tablets in the strip

Discard the 4 white tablets

Start a new strip of pills

Immediately stop taking the pink tablets

Go on to taking the 4 white tablets

Afterwards, start a new strip of pills

You forgot

to take

only one

pink tablet

(a delay of

more than

24 hours

in taking)

Days

Days

8-14

Days

15-24

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What to do in the case of vomiting or severe diarrhea

If you vomit within 3-4 hours of taking a pink active tablet or if you have severe

diarrhea, there is a risk that the active ingredients in the tablet will not be fully taken

up by your body. The situation is similar to a case in which you forget a tablet. After

vomiting or diarrhea, take another pink tablet from another strip as soon as possible.

If possible, take it within 24 hours of when you normally take the tablet. If that is not

possible or more than 24 hours have passed, follow the instructions given under “If you

forget to take the medicine”.

Delaying your period: what you should do

Although it is not recommended, you can delay your period by skipping the white

tablets in the 4th row, and immediately starting a new strip of Yaz until finishing it.

You may experience spotting or menstruation-like bleeding while taking the 2nd strip.

Finish taking the 2nd strip by taking the 4 white tablets in the 4th row. After that, start

the next strip.

Consult the doctor before deciding to delay your period.

Changing the first day of your period: what you should do

If you take the tablets according to the instructions, your period will begin while taking

the white tablets. If you have to change this day, shorten the period during which you

take the placebo tablets – the days you take the white tablets – (but never make this

period longer – 4 days is the maximum!). For example, if you start taking the white

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tablets on a Friday, and you want to change this to a Tuesday (3 days earlier), start a

new strip 3 days earlier than usual. You may not have any bleeding during this time.

You may experience light or menstruation-like bleeding.

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

If you stop taking the medicine

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

ask the doctor for advice about other reliable methods of contraception. If you want

to become pregnant, stop taking Yaz and wait for a natural menstrual period before

trying to become pregnant. You will be able to calculate the expected delivery date

more easily.

Do not take medicines in the dark! Check the label and the 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 Yaz 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 any side effect, especially if it is severe or prolonged, or if there is any

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change in your health that you think can be related to Yaz, please talk with your doctor

about it.

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 taking

combined hormonal contraceptives. For more detailed information on the different

risks arising from taking combined hormonal contraceptives, please see section 2

“Before Using the Medicine”.

The following side effects have been linked with use of Yaz:

Common side effects - effects occurring in 1-10 out of 100 users

mood swings

headache

nausea

breast pain, problems with your menstrual periods, such as irregular periods,

absence of periods

Uncommon side effects - effects occurring in 1-10 out of 1,000 users

depression, nervousness, sleepiness

dizziness, sensation of ‘pins and needles’

migraine, varicose veins, increased blood pressure

stomach ache, vomiting, indigestion, intestinal gas, inflammation of the stomach,

diarrhea

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acne, itching, rash

aches and pains, e.g., back pain, limb pain, muscle cramps

vaginal fungal infection, pelvic pain, breast enlargement, benign breast lumps,

uterine/vaginal bleeding (which usually subsides with continued treatment), genital

discharge, hot flushes, inflammation of the vagina (vaginitis), problems with your

menstrual periods, painful periods, light periods (with reduced menstrual bleeding),

very heavy periods (with heavy menstrual bleeding), vaginal dryness, abnormal

cervical smear tests result, decreased interest in sex

lack of energy, increased sweating, fluid retention

weight increase

Rare side effects - effects occurring in 1-10 out of 10,000 users

Candida (fungal infection)

anemia, increase in the number of platelets in the blood

allergic reaction

hormonal (endocrine) disorder

increased appetite, loss of appetite, abnormally high concentration of potassium in

the blood, abnormally low concentration of sodium in the blood

failure to experience an orgasm, insomnia

giddiness, tremor

eye disorders, e.g., inflammation of the eyelid, dry eyes

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abnormally rapid heartbeat

inflammation of a vein, nosebleed, fainting

enlarged abdomen, bowel disorder, feeling bloated, stomach hernia, fungal infection

of the mouth, constipation, dry mouth

pain of bile ducts or the gallbladder, inflammation of the gallbladder

yellow-brown patches on the skin, eczema, hair loss, acne-like inflammation of the

skin, dry skin, lumpy inflammation of the skin, excessive hair growth, skin disorder,

stretch marks on the skin, skin inflammation, light-sensitive skin inflammation, skin

nodules

difficult

painful

sex,

inflammation

vagina

(vulvovaginitis),

bleeding

following intercourse, vaginal bleeding, breast cysts, increase in the number of

breast cells (hyperplasia), malignant lumps in the breast, abnormal growth of

the mucosal surface of the cervix, shrinkage or wasting of the lining of the womb,

ovarian cysts, enlargement of the womb

feeling generally unwell

weight loss

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

in a leg or foot (i.e., DVT - deep vein thrombosis)

in a lung (i.e., PE - pulmonary embolism)

heart attack

stroke

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

attack (TIA)

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

The risk of having a blood clot may be higher if you have other conditions that increase

this risk (See section 2 “Before Using the Medicine” for more information on conditions

increasing the risk factors of blood clots and symptoms of a blood clot).

The following side effects have also been reported, but their incidence cannot be

evaluated from the available data: hypersensitivity, erythema multiforme (a rash with

red “target-like” lesions or sores).

If any side effect occurs, if any side effect worsens, or if you suffer from a side effect not

mentioned in the leaflet, consult with the doctor.

Side effects can be reported to the Ministry of Health by clicking on the “Reporting

side effects following drug treatment” link 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

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5)

HOW SHOULD THE MEDICINE BE STORED?

Avoid poisoning! This medicine and any other medicine must be kept in a closed

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.

There are no special storage conditions. It is recommended to store at room

temperature.

Do not store different medicines in the same package.

Do not discard the tablets in the toilet or waste bin. Consult a pharmacist regarding

how to discard of medicines you no longer need. These measures will help protect

the environment.

6(

FURTHER INFORMATION

In addition to the active ingredients, the medicine also contains:

Lactose monohydrate, maize starch, Lacquer pink or alternatively hypermellose 5cP,

titanium dioxide [E171], magnesium stearate, talc, ferric oxide [E172], cellulose

microcrystalline.

Each pink tablet contains: 48.180 mg lactose monohydrate.

Each white tablet contains: 23.205 mg lactose monohydrate.

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What the medicine looks like and the contents of the package

What the tablets look like?

The active tablets are pink, round and with a rounded surface; one side has “DS”

imprinted on it in a hexagon.

The inactive tablets are white, round, and with a rounded surface; one side has

“DP” imprinted on it in a hexagon.

Package contents:

Each

strip of Yaz contains 24 active, pink, film-coated tablets in the 1st, 2nd, 3rd and

4th rows, as well as 4 inactive, white, film-coated tablets in the 4th row.

tablets are provided in blister (tray) strips of 28 tablets. Each package

contains 1, 3 or 6 strips.

Not all package sizes may be marketed.

Registration holder and address: Bayer Israel Ltd., 36 Hacharash St., Hod Hasharon

45240.

Manufacturer name and address: Bayer Weimar GmbH und Co. KG, Weimar,

Germany.

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This leaflet was checked and approved by the Ministry of Health in December 2015

and updated according to the instructions of the Ministry of Health in September 2019.

Registration number of the medicine in the National Drug Registry of the

Ministry of Health: 141 04 32023 00

141 04 32023 01

DOR-YAZ-Tab-1219-06

1.

NAME OF THE MEDICINAL PRODUCT

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

24 light pink film-coated tablets:

Each film-coated tablet contains 0.020 mg ethinylestradiol (as betadex clathrate) and 3 mg

drospirenone.

Excipient with known effect: lactose monohydrate 48.18 mg

4 white placebo (inactive) film-coated tablets:

The tablet does not contain active substances.

Excipient with known effect: lactose monohydrate 23.205 mg

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Film-coated tablets

The active tablets are light pink, round with convex faces; one side embossed with the letters "DS"

in a regular hexagon.

The placebo tablets are white, round with convex faces, one side embossed with the letters "DP"

in a regular hexagon.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Oral contraception.

Treatment of moderate acne vulgaris in women who seek oral contraception.

Treatment of symptoms of premenstrual dysphoric disorder (PMDD) in women who have

chosen oral contraceptives as their method of birth control. The efficacy of YAZ for PMDD was

not assessed beyond 3 cycles. YAZ has not been evaluated for treatment of PMS

(premenstrual syndrome).

The decision to prescribe YAZ should take into consideration the individual woman’s current risk

factors, particularly those for venous thromboembolism (VTE), and how the risk of VTE with YAZ

compares with other Combined Hormonal Contraceptives (CHCs) (see sections 4.3 and 4.4).

4.2

Posology and method of administration

Method of administration: oral use

Posology

How to take YAZ

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

order shown on the blister pack. Tablet taking is continuous. One tablet is to be taken daily for 28

consecutive days. Each subsequent pack is started the day after the last tablet of the previous

pack. Withdrawal bleeding usually starts on day 2-3 after starting the placebo tablets (last row) and

may not have finished before the next pack is started.

How to start YAZ

No preceding hormonal contraceptive use (in the past month)

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

bleeding).

Changing from a combined hormonal contraceptive, (combined oral contraceptive (COC),

vaginal ring or transdermal patch)

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

containing the active substances) of her previous COC, but at the latest on the day following the

usual tablet-free or placebo tablet interval of her previous COC. In case a vaginal ring or

transdermal patch has been used the woman should start using YAZ preferably on the day of

removal, but at the latest when the next application would have been due.

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

progestogen-releasing intrauterine system (IUS)

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

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

these cases be advised to additionally use a barrier method for the first 7 days of tablet-taking.

Following first-trimester abortion

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

measures.

Following delivery or second-trimester abortion

Women should be advised to start at day 21 to 28 after delivery or second-trimester abortion.

When starting later, the woman should be advised to additionally use a barrier method for the first

7 days. However, if intercourse has already occurred, pregnancy should be excluded before the

actual start of COC use or the woman has to wait for her first menstrual period.

For breastfeeding women see section 4.6.

Management of missed tablets

Placebo tablets from the last (4

) row of the blister can be disregarded. However, they should be

discarded to avoid unintentionally prolonging the placebo tablet phase. The following advice only

refers to missed active tablets:

If the user is less than 24 hours late in taking any tablet, contraceptive protection is not reduced.

The woman should take the tablet as soon as she remembers and should take further tablets at

the usual time.

If she is more than 24 hours late in taking any tablet, contraceptive protection may be reduced.

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

1. the recommended hormone-free tablet interval is 4 days

tablet-taking must never be

discontinued for longer than 7 days

2. 7 days of uninterrupted tablet-taking are required to attain adequate suppression of the

hypothalamic-pituitary-ovarian-axis.

Accordingly the following advice can be given in daily practice:

Day 1-7

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

two tablets at the same time. She then continues to take tablets at her usual time. In addition, a

barrier method such as a condom should be used for the next 7 days. If intercourse took place in

the preceding 7 days, the possibility of a pregnancy should be considered. The more tablets are

missed and the closer they are to the placebo tablet phase, the higher the risk of a pregnancy.

Day 8-14

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

two tablets at the same time. She then continues to take tablets at her usual time. Provided that

the woman has taken her tablets correctly in the 7 days preceding the first missed tablet, there is

no need to use extra contraceptive precautions. However, if she has missed more than 1 tablet,

the woman should be advised to use extra precautions for 7 days.

Day 15-24

The risk of reduced reliability is imminent because of the forthcoming placebo tablet phase.

However, by adjusting the tablet-intake schedule, reduced contraceptive protection can still be

prevented. By adhering to either of the following two options, there is therefore no need to use

extra contraceptive precautions, provided that in the 7 days preceding the first missed tablet the

woman has taken all tablets correctly. If this is not the case, she should follow the first of these two

options and use extra precautions for the next 7 days as well.

1. The user should take the last missed tablet as soon as she remembers, even if this means

taking two tablets at the same time. She then continues to take tablets at her usual time until

the active tablets are used up. The 4 placebo tablets from the last row must be discarded. The

next blister pack must be started right away. The user is unlikely to have a withdrawal bleed

until the end of the active tablets section of the second pack, but she may experience spotting

or breakthrough bleeding on tablet-taking days.

2. The woman may also be advised to discontinue active tablet-taking from the current blister

pack. She should then take placebo tablets from the last row for up to 4 days, including the

days she missed tablets, and subsequently continue with the next blister pack.

If the woman missed tablets and subsequently has no withdrawal bleed in the placebo tablet

phase, the possibility of a pregnancy should be considered.

Advice in case of gastro-intestinal disturbances

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

be complete and additional contraceptive measures should be taken. If vomiting occurs within 3-4

hours after active tablet-taking, a new (replacement) tablet should be taken as soon as possible.

The new tablet should be taken within 24 hours of the usual time of tablet-taking if possible. If

more than 24 hours elapse, the advice concerning missed tablets, as given in section 4.2

“Management of missed tablets”, is applicable. If the woman does not want to change her normal

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

How to postpone a withdrawal bleed

To delay a period the woman should continue with another blister pack of YAZ without taking the

placebo tablets from her current pack.The extension can be carried on for as long as wished until

the end of the active tablets in the second pack. During the extension the woman may experience

breakthrough-bleeding or spotting. Regular intake of YAZ is then resumed after the placebo tablet

phase.

To shift her periods to another day of the week than the woman is used to with her current

scheme, she can be advised to shorten her forthcoming placebo tablet phase by as many days as

she likes. The shorter the interval, the higher the risk that she does not have a withdrawal bleed

and will experience breakthrough-bleeding and spotting during the subsequent pack (just as when

delaying a period).

4.3

Contraindications

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

any of the conditions appear for the first time during CHC use, the product should be stopped

immediately.

Presence or risk of venous thromboembolism (VTE)

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

venous thrombosis [DVT] or pulmonary embolism [PE])

Known hereditary or acquired predisposition for venous thromboembolism, such as

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

deficiency, protein S deficiency

Major surgery with prolonged immobilisation (see section 4.4)

A high risk of venous thromboembolism due to the presence of multiple risk factors

(see section 4.4)

Presence or risk of arterial thromboembolism (ATE)

Arterial thromboembolism – current arterial thromboembolism, history of arterial

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

pectoris)

Cerebrovascular disease – current stroke, history of stroke or prodromal condition

(e.g. transient ischaemic attack, TIA)

Known hereditary or acquired predisposition for arterial thromboembolism, such as

hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies,

lupus anticoagulant)

History of migraine with focal neurological symptoms

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

to the presence of one serious risk factor such as:

diabetes mellitus with vascular symptoms

severe hypertension

severe dyslipoproteinaemia

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

returned to normal

Severe renal insufficiency or acute renal failure

Presence or history of liver tumours (benign or malignant)

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

breasts)

Undiagnosed vaginal bleeding

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

Yaz is contraindicated for concomitant use with the medicinal products containing

ombitasvir/paritaprevir/ritonavir and 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 YAZ 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 YAZ should be

discontinued.

In case of suspected or confirmed VTE or ATE, CHC use should be discontinued. In case

anticoagulant therapy is started, adequate alternative contraception should be initiated because of

the teratogenicity of anticoagulant therapy (coumarins).

Circulatory Disorders

Risk of venous thromboembolism (VTE)

The use of any combined hormonal contraceptive (CHC) increases the risk of venous

thromboembolism (VTE) compared with no use. Products that contain levonorgestrel,

norgestimate or norethisterone are associated with the lowest risk of VTE. Other products

such as YAZ 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 YAZ, 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 drospirenone between 9 and

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

in women who use a

levonorgestrel-containing CHC.

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

or in the postpartum period.

VTE may be fatal in 1-2% of the cases.

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

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

hepatic, mesenteric, renal or retinal veins and arteries.

Risk factors for VTE

The risk for venous thromboembolic complications in CHC users may increase substantially in a

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

YAZ 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).

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

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 YAZ has not been discontinued in advance.

Positive family history (venous

thromboembolism ever in a sibling or parent

especially at a relatively early age e.g. before

50).

If a hereditary predisposition is suspected, the

woman should be referred to a specialist for

advice before deciding about any CHC use

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 discolouration

of an extremity.

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

progress to loss of vision. Sometimes loss of vision can occur almost immediately.

Risk of arterial thromboembolism (ATE)

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

thromboembolism (myocardial infarction) 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). YAZ 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

Risk factor

Comment

Obesity (body mass index over 30 kg/m

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;

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.

Tumours

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

some epidemiological studies, but there continues to be controversy about the extent to which this

finding is attributable to the confounding effects of sexual behaviour and other factors such as

human papilloma virus (HPV).

A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative

risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using COCs. The

excess risk gradually disappears during the course of the 10 years after cessation of COC use.

Because breast cancer is rare in women under 40 years of age, the excess number of breast

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

cancer. These studies do not provide evidence for causation. The observed pattern of increased

risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of

COCs or a combination of both. The breast cancers diagnosed in ever-users tend to be less

advanced clinically than the cancers diagnosed in never-users.

In rare cases, benign liver tumours, and even more rarely, malignant liver tumours have been

reported in users of COCs. In isolated cases, these tumours have led to life-threatening intra-

abdominal haemorrhages. A hepatic tumour should be considered in the differential diagnosis

when severe upper abdominal pain, liver enlargement or signs of intra-abdominal haemorrhage

occur in women taking COCs.

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

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

Other conditions

The progestin component in YAZ is an aldosterone antagonist with potassium sparing properties.

In most cases, no increase of potassium levels is to be expected. In a clinical study, however in

some patients with mild or moderate renal impairment and concomitant use of potassium-sparing

medicinal products serum potassium levels slightly, but not significantly, increased during

drospirenone intake. Therefore, it is recommended to check serum potassium during the first

treatment cycle in patients presenting with renal insufficiency and a pretreatment serum potassium

in the upper reference range, and particularly during concomitant use of potassium sparing

medicinal products. See also section 4.5.

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

pancreatitis when using COCs.

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

clinically relevant increases are rare. Only in these rare cases an immediate discontinuation of

COC use is justified. If, during the use of a COC in pre-existing hypertension, constantly elevated

blood pressure values or a significant increase in blood pressure do not respond adequately to

antihypertensive treatment, the COC must be withdrawn. Where considered appropriate, COC use

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

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

use, but the evidence of an association with COC use is inconclusive: jaundice and/or pruritus

related to cholestasis; gallstones; porphyria; systemic lupus erythematosus; haemolytic uremic

syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss.

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

of angioedema.

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

until markers of liver function return to normal. Recurrence of cholestatic jaundice and/or

cholestasis-related pruritus which previously occurred during pregnancy or during previous use of

sex steroids necessitates the discontinuation of COCs.

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

no evidence for a need to alter the therapeutic regimen in diabetics using low-dose COCs

(containing < 0.05 mg ethinylestradiol). However, diabetic women should be carefully observed,

particularly in the early stage of COC use.

Worsening of endogenous depression, of epilepsy, of Crohn’s disease and of ulcerative colitis has

been reported during COC use.

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 treatment.

Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum.

Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation

whilst taking COCs.

Each light pink tablet of this medicinal product contains 48.180 mg lactose monohydrate per tablet,

each white tablet contains 23.205 mg lactose monohydrate. Patients with rare hereditary problems

of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption who are

on a lactose-free diet should take this amount into consideration.

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 frequent in women using ethinylestradiol-containing medications such as

combined hormonal contraceptives (CHCs) (see sections 4.3 and 4.5).

Medical examination/consultation

Prior to the initiation or reinstitution of YAZ 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 YAZ 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 be advised that hormonal contraceptives do not protect against HIV infections

(AIDS) and other sexually transmitted diseases.

Reduced efficacy

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

gastro-intestinal disturbances during active tablet taking (see section 4.2) or concomitant

medication (see section 4.5).

Reduced cycle control

With all COCs, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during

the first months of use. Therefore, the evaluation of any irregular bleeding is only meaningful after

an adaptation interval of about three cycles.

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. These may include curettage.

In some women withdrawal bleeding may not occur during the placebo tablet phase. If the COC

has been taken according to the directions described in section 4.2, it is unlikely that the woman is

pregnant. However, if the COC has not been taken according to these directions prior to the first

missed withdrawal bleed or if two withdrawal bleeds are missed, pregnancy must be ruled out

before COC use is continued.

4.5

Interaction with other medicinal products and other forms of interaction

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

potential interactions.

Effects of other medicinal products on YAZ

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

clearance of sex hormones and which

may lead to breakthrough bleeding and/or contraceptive

failure.

Management

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

induction is generally seen within a few weeks. After the cessation of drug therapy enzyme

induction may be sustained for about 4 weeks.

Short-term treatment

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

another method of contraception in addition to the COC. The barrier method must be used during

the whole time of the concomitant drug therapy and for 28 days after its discontinuation. If the drug

therapy runs beyond the end of the active tablets in the COC pack, the placebo tablets must be

discarded and the next COC pack should be started right away.

Long-term treatment

In women on long-term treatment with hepatic enzyme-inducing active substances, another

reliable, non-hormonal, method of contraception is recommended.

The following interactions have been reported in the literature.

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

induction), e.g.:

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

ritonavir, nevirapine and efavirenz and possibly also felbamate, griseofulvin, oxcarbazepine,

topiramate and products containing the herbal remedy St. John's Wort (hypericum perforatum).

Substances with variable effects on the clearance of COCs:

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

nucleoside reverse transcriptase inhibitors, including combinations with HCV inhibitors can

increase or decrease plasma concentrations of estrogen or progestins. The net effect of these

changes may be clinically relevant in some cases.

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

to identify potential interactions and any related recommendations. In case of any doubt, an

additional barrier contraceptive method should be used by women on protease inhibitor or non-

nucleoside reverse transcriptase inhibitor therapy.

Substances decreasing the clearance of COCs (enzyme inhibitors)

The clinical relevance of potential interactions with enzyme inhibitors remains unknown.

Concomitant administration of strong CYP3A4 inhibitors can increase plasma concentrations of

the estrogen or the progestin or both.

In a multiple dose study with a drospirenone (3 mg/day) / ethinylestradiol (0.02 mg/day)

combination, co-administration of the strong CYP3A4 inhibitor ketoconazole for 10 days increased

the AUC(0-24h) of drospirenone and ethinylestradiol 2.7-fold and 1.4-fold respectively.

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 of YAZ on other medicinal products

COCs may affect the metabolism of certain other active substances. Accordingly, plasma and

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

Based on in vivo interaction studies in female volunteers using omeprazole, simvastatin or

midazolam as marker substrate, a interaction of drospirenone at doses of 3 mg with the

cytochrome P450 mediated metabolism of other active substances is unlikely.

Clinical data suggests that ethinylestradiol is inhibiting the clearance of CYP1A2 substrates

leading to a weak (e.g. theophylline) or moderate (e.g. tizanidine) increase in their plasma

concentration.

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, Yaz-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. Yaz can be restarted 2 weeks following completion of treatment with this combination

drug regimen.

In patients without renal insufficiency, the concomitant use of drospirenone and ACE-inhibitors or

NSAIDs did not show a significant effect on serum potassium. Nevertheless, concomitant use of

YAZ with aldosterone antagonists or potassium-sparing diuretics has not been studied. In this

case, serum potassium should be tested during the first treatment cycle. See also section 4.4.

Other forms of interactions

Laboratory tests

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

biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of (carrier)

proteins, e.g. corticosteroid-binding globulin and lipid/lipoprotein fractions, parameters of

carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally

remain within the normal laboratory range.

Drospirenone causes an increase in plasma renin activity and plasma aldosterone induced by its

mild antimineralocorticoid activity.

4.6

Fertility, pregnancy and lactation

Pregnancy

YAZ is not indicated during pregnancy.

If pregnancy occurs during use of with YAZ, the preparation should be withdrawn immediately.

Extensive epidemiological studies have revealed neither an increased risk of birth defects in

children born to women who used COCs prior to pregnancy, nor a teratogenic effect when COCs

were taken inadvertently during pregnancy.

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

Based on these animal data, undesirable effects due to hormonal action of the active compounds

cannot be excluded. However, general experience with COCs during pregnancy did not provide

evidence for an actual adverse effect in humans.

The available data regarding the use of YAZ during pregnancy are too limited to permit

conclusions concerning negative effects of YAZ on pregnancy, health of the foetus or neonate. To

date, no relevant epidemiological data are available.

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

YAZ (see section 4.2 and 4.4).

Breastfeeding

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

composition of breast milk. Therefore, the use of COCs should generally not be recommended

until the breast-feeding mother has completely weaned her child. Small amounts of the

contraceptive steroids and/or their metabolites may be excreted with the milk during COC use.

These amounts may affect the child.

Fertility

Yaz is indicated for the prevention of pregnancy. For information on return to fertility, see section

5.1.

4.7

Effects on ability to drive and use machines

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

effects on ability to drive and use machines have been observed in users of COCs.

4.8

Undesirable effects

For serious undesirable effects in COC users see also section 4.4.

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

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

The frequencies are based on clinical trial data. The most appropriate MedDRA term is used to

describe a certain reaction and its synonyms and related conditions.

Adverse drug reactions which have been associated with the use of YAZ as oral

contraceptive or in the treatment of moderate acne vulgaris according to the MedDRA

system organ classes and MedDRA terms

System Organ Class

(MedDRA version

9.1)

common

(≥1/100 to <1/10)

uncommon

(≥1/1,000 to <1/100)

rare

(≥1/10,000 to

<1/1,000)

not known

(cannot be

estimated from

the available

data)

Infections and

infestations

Candidiasis

Blood and lymphatic

system disorders

Anemia

Thrombocythemia

Immune system

disorders

Allergic reaction

Hypersensitivity

Endocrine disorders

Endocrine disorder

Metabolism and

nutrition disorders

Increased appetite

Anorexia

Hyperkalemia

Hyponatremia

Psychiatric disorders

Emotional lability

Depression

Nervousness

Somnolence

Anorgasmia

Insomnia

Nervous system

disorders

Headache

Dizziness

Paresthesia

Vertigo

Tremor

Eye disorders

Conjunctivitis

Dry eye

Eye disorder

Cardiac disorders

Tachycardia

Vascular disorders

Migraine

Varicose vein

Hypertension

Phlebitis

Vascular disorder

Epistaxis

Syncope

Venous thrombo-

embolism (VTE)

Arterial thrombo-

embolism (ATE)

System Organ Class

(MedDRA version

9.1)

common

(≥1/100 to <1/10)

uncommon

(≥1/1,000 to <1/100)

rare

(≥1/10,000 to

<1/1,000)

not known

(cannot be

estimated from

the available

data)

Gastrointestinal

disorders

Nausea

Abdominal pain

Vomiting

Dyspepsia

Flatulence

Gastritis

Diarrhea

Abdomen enlarged

Gastrointestinal

disorder

Gastrointestinal

fullness

Hiatus hernia

Oral candidiasis

Constipation

Dry mouth

Hepatobiliary

disorders

Biliary pain

Cholecystitis

Skin and

subcutaneous tissue

disorders

Acne

Pruritus

Rash

Chloasma

Eczema

Alopecia

Dermatitis acneiform

Dry skin

Erythema nodosum

Hypertrichosis

Skin disorder

Skin striae

Contact dermatitis

Photosensitive

dermatitis

Skin nodule

Erythema

multiforme

Musculoskeletal and

connective tissue

disorders

Back pain

Pain in extremity

Muscle cramps

Reproductive system

and breast disorders

Breast pain

Metrorrhagia*

Amenorrhea

Vaginal candidiasis

Pelvic pain

Breast enlargement

Fibrocystic breast

Uterine / Vaginal

bleeding*

Genital discharge

Hot flushes

Vaginitis

Menstrual disorder

Dysmenorrhea

Hypomenorrhea

Menorrhagia

Vaginal dryness

Papanicolaou smear

suspicious

Libido decreased

Dyspareunia

Vulvovaginitis

Postcoital bleeding

Withdrawal bleeding

Breast cyst

Breast hyperplasia

Breast neoplasm

Cervical polyp

Endometrial atrophy

Ovarian cyst

Uterine enlargement

System Organ Class

(MedDRA version

9.1)

common

(≥1/100 to <1/10)

uncommon

(≥1/1,000 to <1/100)

rare

(≥1/10,000 to

<1/1,000)

not known

(cannot be

estimated from

the available

data)

General disorders

and administration

site conditions

Asthenia

Sweating increased

Oedema

(Generalized

oedema,

Peripheral oedema,

Face oedema)

Malaise

Investigations

Weight increase

Weight decrease

* bleeding irregularities usually subside during continued treatment

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;

Arterial thromboembolic disorders;

Hypertension;

Liver tumours;

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

conclusive: Crohn’s disease, ulcerative colitis, epilepsy, uterine myoma, porphyria, systemic

lupus erythematosus, herpes gestationis, Sydenham's chorea, haemolytic uremic syndrome,

cholestatic jaundice;

Chloasma;

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

until markers of liver function return to normal.

In women with hereditary angioedema exogenous estrogens may induce or exacerbate

symptoms of angioedema

The frequency of diagnosis of breast cancer is very slightly increased among 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 and 4.4.

Interactions

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

(enzyme inducers) with oral contraceptives (see section 4.5).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. 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

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

with combined oral contraceptives, symptoms that may possibly occur in case of taking an

overdose of active tablets are nausea, vomiting and withdrawal bleeding. Withdrawal bleeding may

even occur in girls before their menarche, if they accidentally take the medicinal product.

There

are no antidotes and further treatment should be symptomatic.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

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

ATC Code: G03AA12

Pearl Index for method failure: 0.41 (upper two-sided 95 % confidence limit: 0.85)

Overall Pearl Index (method failure + patient failure): 0.80 (upper two-sided 95% confidence limit:

1.30)

The contraceptive effect of YAZ is based on the interaction of various factors, the most important

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

In a 3-cycle ovulation inhibition study comparing drospirenone 3 mg / ethinylestradiol 0.020 mg in

a 24-day-regimen and a 21-day-regimen, the 24-day-regimen was associated with greater

suppression of follicular development. After intentionally introduced dosing errors during the third

cycle of treatment, a greater proportion of women in the 21-day-regimen showed ovarian activity

including escape ovulations compared to the women taking the 24-day-regimen. Ovarian activity

returned to pre-treatment levels during the post-treatment cycle in 91.8% of the women who took

the 24-day regimen.

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

therapeutic dosage, drospirenone also possesses antiandrogenic and mild antimineralocorticoid

properties. It has no estrogenic, glucocorticoid and antiglucocorticoid activity. This gives

drospirenone a pharmacological profile closely resembling the natural hormone progesterone.

There are indications from clinical studies that the mild antimineralocorticoid properties of YAZ

result in a mild antimineralocorticoid effect.

Two multicenter, double blind, randomized, placebo controlled studies were performed to evaluate

the efficacy and safety of YAZ in women with moderate acne vulgaris.

After six months of treatment, in comparison with placebo, YAZ showed a statistically significantly

greater reduction of 15.6% (49.3% versus 33.7%) in inflammatory lesions, 18.5% (40.6% versus

22.1%) in non-inflammatory lesions, and 16.5% (44.6% versus 28.1%) in total lesion counts. In

addition, a higher percentage of subjects, 11.8% (18.6% versus 6.8%), showed a ‘clear’ or ‘almost

clear’ rating on the Investigator’s Static Global Assessment (ISGA) scale.

5.2

Pharmacokinetic properties

Drospirenone

Absorption

Orally administered drospirenone is rapidly and almost completely absorbed. Maximum

concentrations of the active substance in serum of about 38 ng/ml are reached at about 1-2 h after

single ingestion. Bioavailability is between 76 and 85 %. Concomitant ingestion of food has no

influence on the bioavailability of drospirenone.

Distribution

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

Drospirenone is bound to serum albumin and does not bind to sex hormone binding globulin

(SHBG) or corticoid binding globulin (CBG). Only 3 - 5 % of the total serum concentrations of the

active substance are present as free steroid. The ethinylestradiol-induced increase in SHBG does

not influence the serum protein binding of drospirenone. The mean apparent volume of distribution

of drospirenone is 3.7 ± 1.2 l/kg.

Biotransformation

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

are the acid form of drospirenone, generated by opening of the lactone ring, and the 4,5-dihydro-

drospirenone-3-sulfate, formed by reduction and subsequent sulfatation. Drospirenone is also

subject to oxidative metabolism catalyzed by CYP3A4.

Elimination

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

excreted only in trace amounts in unchanged form. The metabolites of drospirenone are excreted

with the faeces and urine at an excretion ratio of about 1.2 to 1.4. The half-life of metabolite

excretion with the urine and faeces is about 40h.

Steady-State Conditions

During a treatment cycle, maximum steady-state concentrations of drospirenone in serum of about

70 ng/ml are reached after about 8 days of treatment. Serum drospirenone levels accumulated by

a factor of about 3 as a consequence of the ratio of terminal half-life and dosing interval.

Special Populations

Effect of renal impairment

Steady-state serum drospirenone levels in women with mild renal impairment (creatinine clearance

CLcr, 50-80 mL/min) were comparable to those of women with normal renal function. The serum

drospirenone levels were on average 37 % higher in women with moderate renal impairment

(CLcr, 30 - 50 mL/min) compared to those in women with normal renal function. Drospirenone

treatment was also well tolerated by women with mild and moderate renal impairment.

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

concentration.

Effect of hepatic impairment

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

with moderate hepatic impairment as compared to those with normal liver function. The observed

decline in drospirenone clearance in volunteers with moderate hepatic impairment did not translate

into any apparent difference in terms of serum potassium concentrations. Even in the presence of

diabetes and concomitant treatment with spironolactone (two factors that can predispose a patient

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

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

with mild or moderate hepatic impairment (Child-Pugh B).

Ethnic groups

No clinically relevant differences in the pharmacokinetics of drospirenone or ethinylestradiol

between Japanese and Caucasian women have been observed.

Ethinylestradiol

Absorption

Orally administered ethinylestradiol is absorbed rapidly and completely. Peak serum

concentrations of about 33 pg/ml are reached within 1 - 2 hours after single oral administration.

Absolute bioavailability as a result of presystemic conjugation and first-pass metabolism is

approximately 60 %. Concomitant intake of food reduced the bioavailability of ethinylestradiol in

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

Distribution

Serum ethinylestradiol levels decrease in two phases, the terminal disposition phase is

characterized by a half-life of approximately 24 hours. Ethinylestradiol is highly but non-specifically

bound to serum albumin (approximately 98.5 %), and induces an increase in the serum

concentrations of SHBG and corticoid binding globulin (CBG). An apparent volume of distribution

of about 5 l/kg was determined.

Biotransformation

Ethinylestradiol is subject to

significant gut and hepatic first-pass metabolism. Ethinylestradiol is

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

metabolites are formed, and these are present as free metabolites and as conjugates with

glucuronides and sulfate. The metabolic clearance rate of ethinylestradiol is about 5 ml/min/kg.

In vitro ethinylestradiol is a reversible inhibitor of CYP2C19, CYP1A1 and CYP1A2 as well as a

mechanism based inhibitor of CYP3A4/5, CYP2C8 and CYP2J2.

Elimination

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

ethinylestradiol are excreted at a urinary to biliary ratio of 4:6. The half-life of metabolite excretion

is about 1 day.

Steady-state conditions

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

of ethinylestradiol accumulate by a factor of about 2.0 to 2.3.

5.3

Preclinical safety data

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

associated with the recognised pharmacological action. In particular, reproduction toxicity studies

revealed embryotoxic and fetotoxic effects in animals which are considered as species specific. At

exposures exceeding those in users of YAZ, effects on sexual differentiation were observed in rat

foetuses but not in monkeys. Environmental risk assessment studies have shown that

ethinylestradiol and drospirenone have the potential of posing a risk to the aquatic environment

(see section 6.6).

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Active film-coated tablets (light pink):

Placebo film-coated tablets (white)

Tablet core:

Lactose monohydrate

Maize starch

Magnesium stearate

Cellulose microcrystalline

Lactose monohydrate

Magnesium stearate

Tablet film-coating:

Lacquer pink

or alternatively

Hypromellose 5cP

Talc

Titanium dioxide (E171)

Iron oxide red (E172)

Hypromellose 5cP

Talc

Titanium dioxide (E171)

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

The expiry ate of the product is indicated on the packaging materials.

6.4

Special precautions for storage

This medical product does not require any special storage conditions.

It is recommended to store at room temperature.

6.5

Nature and contents of container

Transparent PVC/Aluminium blister in a cardboard wallet.

Pack sizes:

1x28 tablets

3x28 tablets

6x28 tablets

Each blister contains 24 light pink active film-coated tablets and 4 white placebo film-coated

tablets.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal

This medicinal product may pose a risk to the environment (see section 5.3). Any unused

medicinal product or waste material should be disposed of in accordance with local requirements.

Registration Number:

141 04 32023 00/01

Manufacturer:

Bayer Weimar GmbH und Co. KG, Weimar, Germany.

Registration Holder:

Bayer Israel Ltd., 36 Hacharash St., Hod Hasharon 45240.

The content of this leaflet was approved by the Ministry of Health in December 2015 and updated

according to the guidelines of the Ministry of Health in September 2019.

דומע

ךותמ

רבמבונ

ה/אפור

,ה/דבכנ

,ה/דבכנ ת/חקור

:ןודנה

z

Ya

זאי

ral tablets

ethinylestradiol

3 mg

drospirenone

ונא

םישקבמ םכעידוהל

ןולעהש

ל ןולעהו אפור תינכרצ

רישכתה לש כדעתה ונ

תויוותה

תורשואמ

- Oral contraception.

- Treatment of moderate acne vulgaris in women who seek oral contraception.

- Treatment of symptoms of premenstrual dysphoric disorder (PMDD) in women who have

chosen oral contraceptives as their method of birth control. The efficacy of Yaz for PMDD was not assessed

beyond 3 cycles. Yaz has not been evaluated for treatment of PMS (premenstrual syndrome).

וז העדוהב םילולכ

כדיע םינו

דבלב םייתוהמה

עיפומ ןלהלש טוריפב

הנושש קרפ לכ ךותמ ,םינולעב

.ןכדעתהש עדימה קר תפסות טסקט

תנמוסמ ןותחת וקב

תנמוסמ טסקט תקיחמ .הצוח וקב

אפורל ןולעב םינוכדיעה

4.3 Contraindications

Yaz is contraindicated for concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir

and dasabuvir, (see sections 4.4 and 4.5).

4.4 Special warnings and precautions for use

Other conditions

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 treatment.…

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 frequent in women using

ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs) (see sections 4.3 and

4.5).

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, Yaz-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. Yaz can be restarted 2

weeks following completion of treatment with this combination drug regimen.

דומע

ךותמ

4.9 Overdose

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

oral contraceptives, symptoms that may possibly occur in case of taking an overdose of active tablets are: nausea

vomiting and in young girls, slight vaginal withdrawal bleeding. Withdrawal bleeding may even occur in girls before

their menarche, if they accidentally take the medicinal product. There are no antidotes and further treatment should

be symptomatic.

ה

תינכרצל ןולעב םינוכדע

:

2

)

הפורתב שומיש ינפל

ב שמתשהל ןיא רישכת

:םא

גוסמ דבכ תקלדמ תלבוס ך

סיטיטפה(

אטיבמוא םיליכמה םייאופר םירישכת תלטונ תאו )

/ריברפאטיראפ/ריב ריבובאסאדו ריבאנוטיר

ףיעסב םג יאר(

"

תובוגת ת ןיב תויתפור

.)"

תורהזא

תועגונה תודחוימ

ל

הפורתב שומיש

תוירטאיכיספ תוערפה

רפסמ

ינמ יעצמאב ושמתשהש םיש םיילנומרוה הע כ , ללו

זא ויד , וחו

וא ןואכיד לע לע

בצמ

אכודמ חור ןואכיד . לוכי

תויהל לו יניצר םיתיע

ולע

בוה .תוינדבוא תובשחמל לי

םא תא וח יש הו

בצמב םי

חורה

,םיינואכד םינימסתו ל ינפ ךלש אפור תלבקל ץועיי

יאופר

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ןיב תובוגת

ת

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תוית

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יב זא דבכ תקלדמ תלבוס ךנה םא

גוסמ

טפה סיטי

םייאופר םירישכת תלטונ תאו ) םיליכמה רפאטיראפ /ריבסאטיבמוא ריבאנוטיר /ריב רחאמ ריבובאסאדו

ל םורגל לולע שומישה לש םד תוקידב תואצותב הילע זנאב הילע( דבכה ידוקפת

גוסמ דבכ

ש אפורה .) שרי ךל ךל םו לש רחא גוס עצמא ינפל העינמ י

תליח

לופיטה

רה םירישכת לאה םייאופ תינ .ה ה תא שדחל ן שומיש

זאי

לופיטה םויס רחאל םייעובשכ

תב הלא םירישכ

יאר

ףיעס

ןיא" ."םא הפורתב שמתשהל

3

)

?הפורתב ישמתשת דציכ

א

רתוי הובג ןונימ תועטב תלטנ ם

רומח תוקיזמ תואצות לע םיחוויד םימייק אל .זאי תוילבט ידימ רתוי תליטנ רחאל תו

תואקה תוליחבמ ילבסתו ןכתיי וידחי זאי תוילבט רפסמ תועטב תלטנ םא וא רנ םומידמ יקית

םג עיפוהל לולע הזכ םומיד הפורתה תא תועטב ולטנו תסווה ןלצא העיפוה םרטש תודליב

צ תורענ יע תור תולולע

לובסל

םומידמ .יקיתרנ

אפורל ןולעה

כרצל ןולעה

חלשנ

םוסרפל

רגאמב

תופורתה

רתאבש

דרשמ

תואירבה

https://www.old.health.gov.il/units/pharmacy/trufot/index.asp

ןתינ

לבקל

ספדומ םי

"

הינפ

תרבחל

רייאב

לארשי

חר

רחה

דוה

ןורשה :ןופלט ,

09-7626700

,הכרבב

סנוי הלאה

הנוממ תחקור

ייאב לארשי ר

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