MINESSE

PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE

PHARMACISTS

REGULATIONS (PREPARATIONS) - 1986

The preparation is dispensed with a doctor

s prescription only

MINESSE

®

Film-coated Tablets

Composition:

Active ingredients:

Each blister contains 28 tablets:

∙ 24 active pale yellow tablets; each tablet contains:

Ethinylestradiol 0.015 mg

Gestodene 0.060 mg

∙ 4 inactive white tablets

Inactive ingredients and allergens: See section 6 in the leaflet

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.

1. WHAT IS THE MEDICINE INTENDED FOR?

Minesse

is a preparation for birth control that belongs to a group of medicines called

oral contraceptive pills

Each of the pale yellow active tablets contains two female hormones: estrogen

(ethinylestradiol) and progestogen (gestodene).

The white tablets are inactive since

they do not contain any active ingredient.

Therapeutic group: Combined oral contraceptive pills, an estrogen-progestogen

combination.

A few things important to know about combination pills:

∙ When taken properly, combination pills are one of the most reliable reversible methods

of contraception.

∙ They may slightly increase the risk of thrombosis (blood clots) in the veins and arteries,

especially in the first year or following a break of 4 or more weeks.

∙ Be alert and refer to a doctor if you think you have symptoms of a blood clot (see

section 2,

Minesse

and thrombosis (blood clots)

2.

BEFORE USING THE MEDICINE

Before you start taking Minesse

, read the information about thrombosis (blood clots);

it is particularly important to read the part about thrombosis symptoms (see

section 2,

Minesse

and thrombosis (blood clots)

Do not take Minesse

if you have one of the conditions listed below; in such a case,

refer to the doctor.

The doctor will discuss with you about birth control methods that

are more appropriate for you.

Do not use the medicine:

if you have a known sensitivity (allergy) to any of the ingredients of the medicine; the

list of ingredients is provided in the

Further Information

section

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

legs (deep vein thrombosis), in the lungs (pulmonary embolism), or in other organs

if you are suffering/have suffered in the past from blood clotting problems or from a

disorder that affects your blood clotting, for example: impaired function of protein C,

protein S, antithrombin-III, from a hereditary disease called Factor V Leiden or from

antiphospholipid syndrome

if you are due to undergo surgery or are due to be inactive or immobile for a long

time (see

Minesse

and thrombosis (blood clots)

Do not use the medicine if you have suffered in the past from a heart attack or stroke

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

vessels of the heart (coronary arteries)

if you are suffering, or have suffered in the past, from angina pectoris (a condition

that causes severe chest pain and can be a first sign of a heart attack) or transient

ischemic attack (a temporary condition with stroke symptoms)

if you are suffering from one or more of the following conditions that may increase

the risk of developing a blood clot in the arteries: severe diabetes with blood vessel

damage, very high blood pressure, high levels of fats in the blood (cholesterol or

triglycerides), or from hyperhomocysteinemia

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

migraine with aura

if you are suffering, or have suffered in the past, from liver tumors (malignant or benign)

or recently suffered from a liver disease.

In such cases, the doctor will discontinue

the treatment with the medicine until your liver functions normally again

if you are suffering from unusual vaginal bleeding

if there is suspicion of, or you are suffering from, breast cancer, cancer of the uterus,

or from cancer sensitive to female hormones

if you are pregnant or suspect you are pregnant

if you are breastfeeding.

Special warnings regarding use of the medicine:

What you should know before taking Minesse

®

:

Before starting treatment with Minesse

, the doctor will examine you and ask you about

your medical status and the medical history of your relatives.

The doctor will measure

your blood pressure, and will perform a general examination and a comprehensive

gynecological examination (including breasts) and will confirm that you are not pregnant.

He may perform additional tests.

This leaflet contains information about different situations in which treatment with

Minesse

should not be continued or situations in which the activity of the pill

(contraception) may be reduced. In these situations, abstain from having sex or use

an additional non-hormonal contraceptive, e.g., a condom. Do not rely on methods

such as measuring body temperature or the

safe days method

to prevent pregnancy,

as Minesse

changes the monthly fluctuations in body temperature and cervical

discharge.

∙ If you have used other hormonal contraceptives or if you start taking the pills soon

after delivery or a termination of pregnancy, consult your doctor first.

∙ Unexpected bleeding can occur in the first few months of treatment with the medicine.

If this bleeding persists beyond a few months, or if it occurs after a few months of

use, consult the doctor.

If you are sensitive to any food or medicine, inform the doctor before taking the pills.

Minesse

®

, like all other oral contraceptive pills, does not prevent infection with

HIV infection (AIDS) or other sexually transmitted diseases!

Refer for medical care immediately:

∙ If you notice possible symptoms of a blood clot that may indicate that you are

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

in the lung (pulmonary embolism), heart attack or stroke (see

Minesse

®

and

thrombosis (blood clots)

).

For information about symptoms of these severe side effects, refer to the

How to

recognize symptoms of a blood clot?

Section.

If you are suffering from one or more of the following effects, consult the doctor before

starting treatment. Similarly, if one or more of the following effects develop or worsen

during the course of treatment with Minesse

®

, consult the doctor immediately:

∙ Blood tests that indicate high levels of sugar, cholesterol and fats or high levels of the

prolactin hormone

∙ Obesity

∙ A benign breast tumor or family history of breast cancer

∙ A disease of the uterus

∙ Epilepsy

∙ Migraine

∙ Hearing loss due to otosclerosis

∙ Asthma

∙ If you have Crohn

s disease or ulcerative colitis (a chronic bowel disease)

∙ Systemic lupus erythematosus (a disease that affects the immune system)

If you have hemolytic uremic syndrome (a blood clotting disorder causing kidney failure)

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

∙ If you have elevated levels of fats in the blood (hypertriglyceridemia) or if you have a

family history of this condition. Hypertriglyceridemia is associated with an increased

risk of developing pancreatitis

∙ If you are due to undergo surgery, or if you are due to be inactive or immobile for a

long time (see

Minesse

and thrombosis (blood clots)

∙ If you have just given birth, you are at an increased risk of developing blood clots. You

should ask the doctor when you will be able to resume using Minesse

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

∙ If you have varicose veins

∙ Blood clotting problems and a tendency to form blood clots or if there is a family history

of a tendency to form blood clots (e.g., blood clots in the legs, lungs or any other part

of the body, heart attack, stroke)

∙ If you suffered from skin disturbances that cause itching, red spots and blisters

(Pemphigoid (herpes) gestationis) during pregnancy or during the course of treatment

with another oral contraceptive pill

∙ Chloasma (spots on the face) during pregnancy or during the course of treatment with

another oral contraceptive pill.

In such a case, avoid direct exposure to the sun during

the course of treatment with Minesse

∙ Gallstones

∙ Heart, liver or kidney disease

∙ Depression

∙ Hypertension

∙ Chorea, characterized by sudden and involuntary movements

∙ If you are suffering from hereditary angioedema; preparations containing estrogen

may induce or worsen the symptoms of angioedema.

Refer to a doctor immediately if

you experience symptoms of angioedema such as swelling of the face, tongue and/or

pharynx and/or difficulty swallowing or rash (urticaria) accompanied with breathing

difficulty.

Minesse

®

and thrombosis (blood clots)

Use of a combination pill such as Minesse

, increases the risk of developing a blood

clot compared with the risk in women who do not take pills.

In rare cases, a blood clot

can block blood vessels and cause serious problems.

A blood clot can develop:

∙ in the veins (venous thrombosis)

∙ in the arteries (arterial thrombosis).

Recovery from a blood clot is not always complete. In rare cases, severe signs may

persist, or, in very rare cases, it can be fatal.

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

due to use of Minesse

®

, is small.

How to recognize symptoms of a blood clot?

Refer to a doctor urgently if you notice one or more of the following symptoms.

Are you experiencing one or more of the following 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 only manifest when

standing or walking

∙ warmth in the affected leg

∙ change in colour of the leg (pale red or blue).

Deep vein thrombosis

∙ sudden and unexplained breathing difficulty or rapid

breathing

∙ sudden cough without a cause, which may bring up blood

sharp chest pain which may increase with deep breathing

∙ light-headedness or dizziness

∙ rapid or irregular heartbeat

∙ severe stomach pain.

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

such as coughing or breathing difficulty, may be mistaken as

signs of a mild condition such as a respiratory tract infection

(e.g., the common cold).

Pulmonary embolism

Signs which most commonly occur in one eye:

∙ immediate loss of vision

∙ painless blurring of vision which can progress to loss of

vision.

Thrombosis in a blood

vessel in the eye

∙ chest pain, discomfort or heaviness, tightness

∙ sensation of pressure (squeezing) or fullness in the chest,

arm or below the breastbone

∙ feeling of fullness, indigestion or choking feeling

∙ upper body discomfort radiating to the back, jaw, throat,

arm and stomach

∙ sweating, nausea, vomiting or dizziness

∙ extreme weakness, anxiety, or shortness of breath

∙ rapid or irregular heartbeat.

Heart attack

∙ sudden weakness or numbness of the face, arm or leg,

especially on one side of the body

∙ sudden confusion, difficulty speaking or understanding

∙ sudden trouble seeing in one or both eyes

∙ sudden trouble walking, dizziness, loss of balance or

coordination

∙ sudden, severe or prolonged headache with no known

cause

∙ loss of consciousness or fainting, with or without seizure.

Sometimes the symptoms of stroke can be very brief with an

almost immediate and full recovery, but you should still seek

urgent medical attention, as you may be at risk of another

stroke.

Stroke

∙ swelling and slight blue discoloration of the

extremities

∙ severe stomach pain.

Blockage of a blood

vessel by a blood clot

Venous thrombosis

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

∙ The use of a combination pill is associated with an increase in the risk of development

of blood clots in the veins (venous thrombosis), however, this side effect is rare.

risk is higher in the first year of use of combination pills.

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

∙ If a blood clot travels from the leg to the lung it can cause a pulmonary embolism.

∙ In very rare cases, a blood clot may form in another organ, such as the eye (thrombosis

in a blood vessel of the eye).

When is the risk of developing a blood clot in a vein highest?

The highest risk of developing a blood clot in a vein is during the first year of taking

a combination pill for the first time. The risk may also be high if you resume taking

a combination pill (the same preparation you have taken in the past or a different

preparation) after a break of 4 weeks or more.

After the first year, the risk declines, but will always be slightly high in comparison to a

situation in which you had not taken a combination pill. When you stop taking Minesse

the risk of developing blood clots returns to normal within a few weeks.

What is the risk of developing a blood clot?

The risk depends on your natural tendency to develop venous thrombosis and on the

type of combination pill you are taking.

The overall risk of a blood clot in the leg or lungs (deep vein thrombosis or pulmonary

embolism) when using Minesse

is low.

∙ Out of every 10,000 women who are not using any combination pill and are not pregnant,

about two women will develop a blood clot in a year.

∙ Out of every 10,000 women who are using a combination pill that contains levonorgestrel,

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

∙ Out of every 10,000 women who are using a combination pill that contains gestodene,

such as Minesse

, about 9-12 will develop a blood clot in a year.

Your risk of developing a blood clot will vary according to your medical history (see

Conditions that may increase your risk of developing a blood clot

, below).

Risk of developing a blood clot

in a year

Women who are not using a combined hormonal

contraceptive (pill/patch/ring) and are not

pregnant

About 2 out of 10,000 women

Women using a combination pill containing

levonorgestrel, norethisterone or norgestimate.

About 5-7 out of 10,000 women

Women using Minesse

About 9-12 out of 10,000

women

The following conditions may increase the risk of developing a blood clot in the

veins:

The risk of developing a blood clot when taking Minesse

is low, but some conditions

may increase this risk

∙ With increasing age (especially over the age of 35)

∙ Obesity (BMI over 30)

∙ If one of your family members (first-degree) has suffered from a blood clot in the leg,

lung or other organ at a young age (below the age of 50). In such a case, you may

have a hereditary blood clotting problem

∙ If you are in a state of prolonged immobility due to surgery, illness or trauma, you may

need to stop taking Minesse

several weeks before the surgery or while you are less

mobile. If you need to stop taking Minesse

, ask your doctor when you can start taking

it again. Do not take Minesse

for two weeks after a surgery or bed rest, since the risk

of thrombosis increases after surgeries, inactivity or prolonged immobility, injuries and

fractures

∙ A few weeks after giving birth.

The risk of blood clot formation increases the more dangerous conditions you have.

Air travel (more than 4 hours) may temporarily increase the risk, particularly if you have

some of the other risk factors.

It is important to tell the doctor if any of the above mentioned conditions apply to you,

even if you are unsure. Your doctor may decide that you should stop taking Minesse

If one or more of the above conditions change, for example, if a family member (first-

degree) experiences a thrombosis for no known reason, or if you gain a lot of weight,

tell your doctor.

Arterial thrombosis

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, it can cause a heart attack or a stroke.

The following conditions may increase the risk of developing a blood clot in the

arteries:

It is important to note that the risk of a heart attack or stroke due to use of Minesse

very low but may increase:

∙ with increasing age (especially over the age of 35)

∙ if you smoke. When using a hormonal contraceptive like Minesse

, it is recommended

that you quit smoking. If you are unable to stop and are over the age of 35, your doctor

may advise you to use a different type of contraception

∙ if you suffer from obesity

∙ if a family member (first-degree relative) suffered from a heart attack or stroke at a

young age (below the age of 50). In this case, you could also be at high risk of having

a heart attack or stroke

∙ if you have hypertension

if you, or a first-degree relative, have high blood fat levels (cholesterol or triglycerides)

∙ if you suffer from migraine, especially migraines with aura

∙ if you have diabetes

∙ heart and/or blood system disturbances (e.g., heart valve problems, heart rhythm

disturbances).

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 even higher.

If one or more of these conditions change while you are using Minesse

, for example,

if you start smoking, if a family member (first-degree) experiences a thrombosis for no

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

Oral contraceptive pills and cancer

Breast cancer is slightly more common among women who take oral contraceptive

pills versus women who do not take pills. It is unclear if the pill causes breast cancer.

Women taking pills may be examined more frequently, and the disease is therefore

detected earlier.

There are studies that indicate increased risk of cervical cancer in women taking pills for

a long time, but it is unclear whether the increased risk depends on the pill or is related

to sexual behavior (e.g., multiple partners) and other factors.

Reports of benign or malignant liver tumors in women taking pills are rare.

Refer to a

doctor if you experience sudden, severe abdominal pain.

Bleeding between periods

During the first few months of treatment with Minesse

, unexpected bleeding, such as

blood stains or intermenstrual bleeding (namely, bleeding that occurs outside of the

period when the white inactive tablets are taken).

If this irregular bleeding lasts longer

than a few months, or if it begins after a few months of treatment with Minesse

, refer

to the doctor to investigate the cause.

If menstrual bleeding does not occur when taking the inactive tablets:

If you have taken all the tablets as instructed and have not had vomiting or severe diarrhea

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

If menstrual bleeding does not occur twice in succession, you may be pregnant. Refer to

the doctor immediately.

In any case, you must confirm that you are not pregnant before

starting the next

blister.

If bleeding does not occur after you stop taking the pills:

When you stop taking the pills, it may take time for your periods to return. If you do not

get your period for a long time, please refer to a doctor.

If you are taking, or have recently taken, other medicines, including non-prescription

medicines and nutritional supplements, tell the doctor or pharmacist.

In some

cases, the doctor or pharmacist will advise you to use an additional contraceptive (e.g.,

a condom) for a certain period of time.

Certain medicines may affect the levels of the medicine in the blood, reduce the

contraceptive efficacy of the pill or cause unusual bleeding and irregular periods; inform

the doctor or pharmacist, especially if you are taking:

∙ medicines to treat HIV and Hepatitis C viral infections (called protease (enzyme)

inhibitors and reverse transcriptase inhibitors)

∙ a medicine to treat epilepsy (phenobarbital, phenytoin, primidone, oxcarbazepine,

carbamazepine or topiramate)

∙ medicines to treat tuberculosis (e.g., rifabutin, rifampicin)

∙ medicines to treat fungal infections (griseofulvin, antifungals from the azole family, e.g.,

itraconazole, voriconazole, fluconazole)

∙ medicines to treat bacterial infections (macrolide antibiotics, e.g., clarithromycin,

erythromycin)

∙ medicines to treat heart disease or high blood pressure (calcium channel blockers,

e.g., verapamil, diltiazem)

∙ medicines to treat arthritis (etoricoxib)

∙ a medicine to treat sleep disorders (modafinil)

∙ a preparation that contains the Hypericum plant (St. John

s Wort) to treat depression

∙ grapefruit juice

∙ troleandomycin (a macrolide antibiotic) may increase the risk for intrahepatic

cholestasis.

Similarly, the pill may also affect the activity of other medicines that break down in the

liver, and increase the risk of inefficacy and side effects, for example:

∙ lamotrigine (to treat epilepsy)

∙ ciclosporin (to suppress the immune system)

∙ theophylline (to treat asthma)

∙ tizanidine

To prevent risks or inefficacy arising from drug interactions when using Minesse

®

,

consult the doctor or pharmacist before taking any other medicine.

Pregnancy

Do not use this medicine if you are pregnant or suspect that you are pregnant.

If you discover that you are pregnant during the course of treatment with Minesse

, stop

the treatment and refer to the doctor.

Use a non-hormonal contraceptive e.g., a condom, until the pregnancy is confirmed.

If you plan to become pregnant, consult the doctor.

Breastfeeding

If you are breastfeeding, use of Minesse

is not recommended.

If you would like to breastfeed and take an oral contraceptive pill, the doctor will

recommend taking a different type of pill that is appropriate for you.

Driving and use of machines

The effect of the preparation on the ability to drive and use machines has not been studied.

The preparation is not expected to affect the ability to drive or use machines. Dizziness

has been reported as a side effect of use of this preparation. If you experience dizziness,

do not drive and do not operate machines until this effect passes.

Smoking

It is recommended that you quit smoking during the period of treatment with oral

contraceptive pills, especially if you are over the age of 35; See section 2

Minesse

and thrombosis (blood clots)

If you smoke – inform the doctor before starting treatment with the pill.

Important information regarding some of the ingredients of the medicine

The medicine contains lactose. If you suffer from an intolerance to certain sugars, consult

the doctor before you start using Minesse

Each tablet contains approximately 40 mg lactose.

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 about the instructions for use.

About the pack

The pack was designed to help you take the pill on time.

Each blister contains 28 tablets: 24 pale yellow active tablets and 4 white inactive

tablets. The two types of tablets are arranged in order in the blister. A number is labeled

above each tablet.

START/הלחתה

is indicated above the first tablet. The empty cells

in the center of the blister indicate the days of the week. A day of the week is indicated

above each cell.

Dosage and method of administration:

Always

according

doctor

instructions.

Check

with

the doctor or pharmacist

if you are uncertain.

The recommended dosage unless otherwise instructed by the doctor is: One tablet

at the same time every day, for 28 consecutive days (take a pale yellow tablet for the

first 24 days and a white tablet for the last 4 days).

Swallow the tablet with a large glass of water.

There is no information regarding crushing, halving or chewing the tablet.

∙ Begin by taking tablet number 1 (located near the words

START/הלחתה

); make sure

to take the tablets in order; the arrows indicate the direction of progression.

∙ Perforate the aluminum foil of the empty cell (in the center of the blister) on the day

of the week on which you take the first tablet. This is the day on which you should

also start the next blisters. This is also the day of the week on which you will take pill

number 8, 15 and 22 (the location of these pills is marked by a yellow circle). This sign

will help you confirm that you took all the tablets correctly.

∙ Continue taking the tablets in the direction of the arrows until you finish all of the

tablets.

∙ Bleeding usually begins on the second-third day after taking the last active pill and

does not stop before starting the next blister.

∙ The tablet can be taken at any time, but swallow the tablet at the same time each day; it

is usually convenient to take the tablet either at bedtime or first thing in the morning.

∙ Start using the next blister immediately after the last day of the previous blister.

Namely,

there is no break between the end of one blister and the beginning of a new blister.

Each blister will be started on the same day of the week.

When can you start using the first pack?

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

On the first day of menstrual bleeding - take tablet number 1 located near the word

START

If you are switching from another combination pill (that contains two hormones)

to Minesse

®

:

Finish the current blister of the other pill and

start taking Minesse

®

the next day (if the

blister of the other pills also contains inactive pills, do not take them); namely,

there is

no pill-free break.

Use an additional non-hormonal contraceptive (e.g., a condom) during the first

7 days of use of Minesse

®

.

If you are switching from a progestogen-only contraceptive (pill, injection, implant)

to Minesse

®

:

You can switch to Minesse

®

- on the day after discontinuing use of the other pill at

the same time, on the day the implant is removed or on the day the next injection is

supposed to be administered.

Use an additional non-hormonal contraceptive (e.g., a condom) during the first

7 days of use of Minesse

®

.

Starting Minesse

®

after a termination of pregnancy that occurred during the first

trimester:

You can start taking Minesse

®

immediately, but first consult with the doctor.

Starting Minesse

®

after childbirth or after a termination of pregnancy that occurred

during the second trimester:

The doctor will advise you regarding use of the pills.

Since the period immediately after

childbirth or a termination of pregnancy is associated with a higher risk of formation of

blood clots, do not start taking Minesse

®

before 28 days have passed from the delivery

or second-trimester termination of pregnancy, and on condition that the childbirth took

place without complications, you are not breastfeeding and you are fully mobile.

an additional non-hormonal contraceptive (e.g., a condom), as a backup, for the first

7 days of use of the pill.

If you have had sex after childbirth/second-trimester termination of pregnancy, confirm that

you are not pregnant or wait until your next period before starting use of Minesse

If you forget to take Minesse

®

:

If you have forgotten to take a pill, there is a risk that you will become pregnant.

If less than 12 hours have passed since the time at which you were due to take a

pale yellow tablet,

take one as soon as you remember, and continue to take the next

tablets as usual.

If more than 12 hours have passed since the time at which you were due to take a

pale yellow tablet,

there is a risk of you becoming pregnant, therefore:

∙ Take the last pale yellow tablet that you forgot, as soon as you remember and continue

to take the rest of the tablets as usual, even if it means taking 2 tablets on the same

day.

∙ Continue taking Minesse

until you finish the blister.

∙ In addition, use another contraceptive (e.g., a condom, spermicide, etc.) for the next

7 days.

∙ If the 7 days on which use of extra contraception is necessary, run beyond the day

on which you take the last pale yellow tablet in the current blister, throw away all the

white tablets that remain in the current blister and start the next blister the day after

taking the last pale yellow tablet of the current blister.

If you forget to take a pale yellow tablet and you do not have the expected menstrual

bleeding, which starts when taking the white tablets, you may be pregnant; refer to the

doctor immediately.

If you forget to take one or more white tablets, you are still protected from becoming

pregnant, on the condition that the interval between taking the last pale yellow tablet in

the current blister and taking the first pale yellow tablet in the new blister does not exceed

4 days.

Consult the doctor.

If you suffer from diarrhea or vomiting:

The pill may not work. If the diarrhea or vomiting occurs within 4 hours of taking the

tablet,

this

situation

similar

forgetting

take

tablet.

Therefore,

after

vomiting or

diarrhea, take an additional tablet from a spare blister as soon as possible.

If possible,

take the tablet within 12 hours of the time you usually take it.

If you cannot, or if more

than 12 hours from the usual time have elapsed, follow the instructions in the

If you

forget to take Minesse

…. if more than 12 hours have passed

section.

If the vomiting or diarrhea persist for a few days, use an additional contraception method

(e.g., a condom) during this period, until you start using a new blister.

Consult the doctor.

Examinations, follow-up and laboratory tests:

∙ During use of the medicine, you must undergo medical tests: liver function tests,

and as standard for prolonged use of hormonal preparations – if you are taking

the preparation for a long period, visit your doctor every six months for a routine

gynecological examination.

∙ Before undergoing blood tests, inform the doctor that you are taking an oral contraceptive

pill because this preparation may affect the test results.

If you are visiting a doctor or clinic for any reason, tell them that you are taking oral

contraceptive pills.

If you accidentally take a higher dosage:

Overdose may cause digestive system effects (e.g., nausea, vomiting, abdominal pain),

breast tenderness, dizziness, sleepiness, fatigue, vaginal bleeding.

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

proceed to a hospital emergency room and bring the package of the medicine with you.

If you want to stop taking the medicine:

You can stop taking Minesse

at any time.

If you are not interested in becoming pregnant,

consult the doctor regarding other effective contraceptives.

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 Minesse

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 are suffering from a side effect, especially if it is severe or prolonged, or if you

experience any change in your health that you are worried may have resulted from the

use of Minesse

, refer to the doctor.

An increased risk of formation of blood clots in the veins (venous thrombosis) or in the

arteries (arterial thrombosis) exists in all women using combined hormonal contraceptives.

For more detailed information, see section 2

Before using the medicine

Stop

treatment

and

refer to a doctor

immediately

if

you

experience

any of the

following side effects:

∙ A severe allergy to the medicine (unknown frequency): Symptoms include sudden

wheezing, difficulty in breathing or dizziness, swelling of the eyelids, face, lips or throat,

skin rash, hives.

∙ Retinal vein thrombosis (unknown frequency): Symptoms most commonly occur in one

eye, painless blurring of vision which can progress to loss of vision, immediate loss of

vision.

∙ Hemolytic uremic syndrome (a condition which affects the blood vessels and kidneys) -

(unknown frequency): Symptoms include vomiting, diarrhea (which may be bloody),

fever, weakness, reduced urine volume.

∙ Pancreatitis - (rare frequency, between 1 and 10 users in 10,000): Symptoms include

upper abdominal pain which may radiate to the back.

∙ Erythema multiforme - (unknown frequency): Symptoms include skin rash with pink-red

blotches especially on the palms of hands or soles of feet which may blister. You may

also have ulcers in the mouth, eyes or genitals and fever.

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

∙ headache, including migraine

∙ abdominal pain

∙ breast pain

∙ breast tenderness

∙ very light or no periods

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

∙ a vaginal infection, including vaginal fungal infection

∙ bleeding between periods

∙ mood changes (e.g., depression) or change in libido

∙ nervousness or dizziness

∙ nausea, vomiting

∙ feeling bloated

∙ acne

∙ painful menstrual bleeding

∙ changes in blood flow during your period

∙ changes in vaginal discharge or changes to the cervix (ectropion)

∙ fluid retention or edema

∙ weight loss or gain

∙ rash

∙ hair loss

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

∙ increased appetite

∙ decreased appetite

∙ excessive hairiness

∙ appearance of pigmented patches on the face (chloasma)

∙ changes in laboratory test results, such as increase in cholesterol, triglycerides and

blood pressure

∙ discharge from the nipple

∙ increased breast size

∙ worsening of varicose veins

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

∙ formation of thrombosis in a vein or artery for example:

∙ a blood clot in the legs (deep vein thrombosis)

∙ a blood clot in the lungs (pulmonary embolism)

∙ heart attack

∙ stroke

∙ mini-stroke or temporary condition in which you have stroke-like symptoms (transient

ischemic attack)

∙ blood clot in the liver, stomach/intestine, kidneys or eye.

The chance of having a blood clot is higher if you have any other condition that increases

this risk (please see section 2 for more information on the conditions that increase risk

for blood clots and the symptoms of a blood clot).

∙ liver or biliary disease (such as hepatitis or abnormal function of the liver)

∙ gallbladder disease including gallstones or worsening of this condition

Side effects occurring at an unknown frequency:

∙ benign liver tumor (called focal nodular hyperplasia or hepatic adenoma) or malignant

liver tumor

worsening of an immune system disease (lupus), of a liver disease (porphyria) or of a

disease known as chorea characterized by irregular, sudden, involuntary movements

∙ obstruction of the bile flow in the liver or worsening of this condition

∙ ischemic bowel disease, possible aggravation of inflammatory bowel disease -

symptoms include abdominal cramps and pain, diarrhea (which may be bloody),

weight loss.

∙ intolerance to a sugar called glucose

∙ contact lens intolerance

∙ abdominal cramps

∙ jaundice (yellowing of the skin or eyes)

∙ skin reaction called erythema nodosum

∙ inflammation of the optic nerve which can lead to partial or total loss of vision

If one of the side effects worsens, or if you suffer from a side effect not mentioned in

the leaflet, consult the doctor.

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

Effects of Drug Treatment” found on the Ministry of Health homepage (www.health.gov.il)

that directs you to the online form for reporting side effects, or by entering the link:

https://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffe

ctMedic@moh.gov.il

5.

HOW SHOULD THE MEDICINE BE STORED?

∙ Avoid poisoning! This medicine and any other medicine must be kept in a safe place

out of the reach 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.

∙ Store below 25°C.

6.

FURTHER INFORMATION

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

Lactose Monohydrate, Magnesium Stearate, Microcrystalline Cellulose, Montanglycol

Wax (Wax E Pharma), Opadry White (white tablet), Opadry Yellow (pale yellow tablet),

Polacrilin Potassium, Polyethylene Glycol 1450.

What the medicine looks like and the contents of the package:

∙ A carton package that contains one blister

∙ A carton package that contains 3 blisters

Each blister contains 28 film-coated tablets: 24 pale yellow tablets and 4 white tablets.

The carton package contains a carry case intended to protect the blister you are using.

License holder: Pfizer PFE Pharmaceuticals Israel Ltd., 9 Shenkar St., Herzliya Pituach

46725

Manufacturer name: Pfizer Ireland Pharmaceuticals, Newbridge, Ireland

This leaflet was checked and approved by the Ministry of Health in September 2016

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

Health:

122-57-30271

Minesse LPD 18 Sep 2016

רשואו קדבנ ונכותו תואירבה דרשמ י"ע עבקנ הז ןולע טמרופ

SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

MINESSE

60 micrograms / 15 micrograms

film-coated tablets

2.

QUANTITATIVE AND QUALITATIVE COMPOSITION

Gestodene : ..... ............ ………60 micrograms

Ethinylestradiol: ........... ………15 micrograms

For one pale-yellow, film-coated tablet (active tablet)

Excipient with known effect: lactose

The white, film-coated tablets do not contain any active ingredients (placebo).

Excipient with known effect: lactose

For the full list of excipients, see section 6.1

3.

PHARMACEUTICAL FORM

Film-coated tablet.

The active tablet is a pale-yellow round tablet with convex faces embossed with “60”on one

side and “15”on the other.

The placebo tablet is a white round tablet with convex faces.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Oral hormonal contraception.

The decision to prescribe Minesse should take into consideration the individual woman’s

current risk factors, particularly those for venous thromboembolism (VTE), and how the risk

of VTE with Minesse compares with other combined hormonal contraceptives (CHCs) (see

sections 4.3 and 4.4).

4.2

Posology and method of administration

Posology

Take regularly and without omission, one tablet daily at the same time of the day, for 28

consecutive days (one pale-yellow, active tablet during the first 24 days, one white, inactive

tablet during the 4 following days) with no free interval between each blister pack. A

withdrawal bleed usually starts on day 2-3 after the last active tablet and may not have

finished before the next pack is started.

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Minesse LPD 18 Sep 2016

How to start Minesse

No preceding hormonal contraceptive use in the past month:

Take the first tablet on the first day of menstrual bleeding.

Changing from another combined oral contraceptive (COC):

The woman should start Minesse

on the day after the last active tablet of her previous COC.

-

Changing from a progestin-only method (minipill, injection, implant):

The woman may switch any day from the minipill and should begin Minesse the next day. She

should start Minesse on the day of an implant removal or, if using an injection, the day the next

injection would be due. In all of these situations, the woman should be advised to additionally

use a non-hormonal back-up method for the first 7 days of tablet-taking.

-

Following first-trimester abortion:

The woman may start Minesse immediately. Additional contraceptive measures are not

needed.

-

Following delivery or second-trimester abortion:

Since the immediate post-partum period is associated with an increased risk of

thromboembolism, COCs should be started no earlier than days 21 to 28 after delivery or

second-trimester abortion. The woman should be advised to additionally use a non-hormonal

back-up method for the first 7 days of tablet-taking. 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.

Omission of one or more

tablets

Contraceptive reliability may be reduced if pale-yellow tablets are missed, and

particularly if tablets are missed during the first days of the pack.

If the woman becomes aware of the omission of a pale-yellow tablet

within 12

hours

of the normal time of intake, the tablet should be taken immediately and

treatment pursued normally, the next tablet being taken at the usual time.

If the woman becomes aware of the omission of a pale-yellow tablet

more than 12

hours after the normal time of intake

contraception is no longer assured. The last

forgotten tablet should be taken immediately, even if this means taking two tablets in

one day, and oral contraceptive treatment pursued to the end of the blister pack, together

with a non-hormonal back-up method of contraception (condoms, spermicides, etc.)

which should be used for the next seven days. If the seven days where a back-up method

is required run beyond the last active tablet in the current pack, the next pack must be

started on the day following the intake of the last active tablet in the current pack and

inactive tablets should be discarded. The user is unlikely to have a withdrawal bleed

until the inactive-tablet interval of the second pack, but she may experience spotting or

breakthrough bleeding. If the user does not have a withdrawal bleed at the end of the

second pack, the possibility of pregnancy must be excluded before resuming tablet-

taking.

Errors in taking one or more white tablets have no consequence, provided the interval

between the last pale-yellow tablet of the current pack and the first pale-yellow tablet of the

following pack does not exceed four days.

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Minesse LPD 18 Sep 2016

In case of gastrointestinal upset:

The onset of intercurrent digestive disorders within four hours after taking the tablet, such as

vomiting or severe diarrhoea, may cause transient inefficacy of the method by reducing COC

hormone absorption and such events should be dealt with in the same way as the case where

a tablet has been forgotten for less than 12 hours. The extra tablet should be taken from a

back-up pack. If these episodes recur over several days, a non-hormonal back-up

contraceptive method should then be used, (condom, spermicide, etc.) until the beginning of

the next blister pack.

Paediatric population

Safety and efficacy was evaluated in subjects aged 18 years and above.

Limited data available for use in adolescents below 18 years.

Elderly patients

Minesse is not indicated after menopause.

Patients with hepatic impairment

Minesse is contraindicated in women with severe hepatic diseases. See also section

‘Contraindications’.

Patients with renal impairment

Minesse has not been specifically studied in renally impaired patients.

Method of administration

Oral use.

4.3

Contraindications

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

If one of these disorders occurs during the use of MINESSE, MINESSE must be

discontinued immediately.

-

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

-

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)

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Minesse LPD 18 Sep 2016

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

-

Known or suspected carcinoma of the breast

-

Carcinoma of the endometrium or other known or suspected estrogen-dependent

neoplasia

-

Hepatic adenomas or carcinoma, or active liver disease, as long as liver function tests

have not returned to normal

Undiagnosed genital bleeding

4.4

Special warnings and precautions for use

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

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 Minesse

should be discontinued.

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 Minesse 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 Minesse,

how her current risk factors influence this risk, and that her VTE risk is highest in the

first ever year of use. There is also some evidence that the risk is increased when a

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

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

VTE over the period of one year. However, in any individual woman the risk may be far

higher, depending on her underlying risk factors (see below).

It is estimated

that out of 10,000 women who use a CHC containing gestodene between 9

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

in women who

use a levonorgestrel-containing CHC.

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

pregnancy or in the postpartum period.

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

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Minesse LPD 18 Sep 2016

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

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

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Extremely rarely, thrombosis has been reported to occur in CHC users in other blood

vessels, e.g. hepatic, mesenteric, renal or retinal veins and arteries.

Risk factors for VTE

The risk for venous thromboembolic complications in CHC users may increase

substantially in a woman with additional risk factors, particularly if there are multiple risk

factors (see table).

Minesse is contraindicated if a woman has multiple risk factors that put her at high risk of

venous thrombosis (see section 4.3). If a woman has more than one risk factor, it is

possible that the increase in risk is greater than the sum of the individual factors – in this

case her total risk of VTE should be considered. If the balance of benefits and risks is

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

Table: Risk factors for VTE

Risk factor

Comment

Obesity (body mass index over 30

kg/m²)

Risk increases substantially as BMI rises.

Particularly important to consider if other risk factors

also present.

Prolonged immobilisation, major

surgery, any surgery to the legs or

pelvis, neurosurgery, or major trauma

Note: temporary immobilisation

including air travel >4 hours can also

be a risk factor for VTE, particularly in

women with other risk factors

In these situations it is advisable to discontinue use of

the pill (in the case of elective surgery at least four

weeks in advance) and not resume until two weeks after

complete remobilisation. Another method of

contraception should be used to avoid unintentional

pregnancy.

Antithrombotic treatment should be considered if

Minesse 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

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Minesse LPD 18 Sep 2016

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

thrombophlebitis in the onset or progression of venous thrombosis.

The increased risk of thromboembolism in pregnancy, and particularly the 6 week period of

the puerperium, must be considered (for information on “Pregnancy and lactation” see

section 4.6).

Symptoms of VTE (deep vein thrombosis and pulmonary embolism)

In the event of symptoms women should be advised to seek urgent medical attention and to

inform the healthcare professional that she is taking a CHC.

Symptoms of deep vein thrombosis (DVT) can include:

- unilateral swelling of the leg and/or foot or along a vein in the leg;

- pain or tenderness in the leg which may be felt only when standing or walking,

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

Symptoms of pulmonary embolism (PE) can include:

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

- sudden coughing which may be associated with haemoptysis;

- sharp chest pain;

- severe light headedness or dizziness;

- rapid or irregular heartbeat.

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

might be misinterpreted as more common or less severe events (e.g. respiratory tract

infections).

Other signs of vascular occlusion can include: sudden pain, swelling and slight blue

discoloration of an extremity.

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

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

immediately.

Risk of arterial thromboembolism (ATE)

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). Minesse is contraindicated if a woman

has one serious or multiple risk factors for ATE that puts her at high risk of arterial

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Minesse LPD 18 Sep 2016

thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the

increase in risk is greater than the sum of the individual factors - in this case her total risk

should be considered. If the balance of benefits and risks is considered to be negative a CHC

should not be prescribed (see section 4.3).

Table: Risk factors for ATE

Risk factor

Comment

Increasing age

Particularly above 35 years

Smoking

Women should be advised not to smoke if they wish to

use a CHC. Women over 35 who continue to smoke

should be strongly advised to use a different method of

contraception.

Hypertension

Obesity (body mass index over 30

kg/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:

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Minesse LPD 18 Sep 2016

- 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.

GYNAECOLOGICAL CANCERS

A meta-analysis of data from 54 international studies demonstrated a slightly higher risk of

breast cancer diagnosis among users of oral contraceptives. This increased risk does not

appear to be dependent upon the duration of use. The influence of risk factors such as

nulliparity or a family history of breast cancer is not established.

This increased risk is transient and disappears 10 years after the oral contraceptive is

discontinued.

It is possible that the more regular clinical monitoring of women taking oral contraceptives,

with increased likelihood of earlier diagnosis, may play an important role in the higher

number of breast cancers diagnosed.

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 lifetime risk of

breast cancer. Breast cancers diagnosed in ever-users tend to be less advanced clinically than

the cancers diagnosed in never-users.

An increased risk of cervical cancer in long-term users of COCs has been reported in some

epidemiological studies. However, there continues to be controversy about the extent to

which these findings may be due to the confounding effects of sexual behaviour and other

factors such as human papilloma virus (HPV).

The published data do not compromise the use of oral contraceptives, as the potential risks

appear to be outweighed by the benefits.

In addition, oral contraception decreases the risk of ovarian and endometrial cancers.

HEPATIC NEOPLASIA /LIVER DISEASE

In rare cases benign liver tumours (e.g. focal nodular hyperplasia, hepatic adenomas) 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 haemorrhage.

Cholestasis has been reported to occur or deteriorate with both pregnancy and COC use, but

the evidence of an association with COC use is inconclusive.

Hepatic and hepatobiliary disorders have been reported with COC use. Acute or chronic

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

of liver function return to normal.

HEADACHE

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The onset or exacerbation of migraine or development of headache with a new pattern that is

recurrent, persistent, or severe requires discontinuation of COCs and evaluation of the cause.

HYPERTENSION

Although uncommon, increases in blood pressure have been reported in women taking

COCs.

In women with hypertension, a history of hypertension or hypertension related diseases

(including certain renal diseases), another method of contraception may be preferable. If

COCs are used in such cases, close monitoring is recommended and, if a significant increase

in blood pressure occurs, COCs should be discontinued.

OTHER

Medical examination/consultation

Prior to the initiation or reinstitution of Minesse 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 Minesse

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.

Caution should be exercised in women with:

-

Metabolic disorders such as uncomplicated diabetes.

-

Hyperlipidemia (hypertriglyceridemia, hypercholesterolemia). Women who are

being treated for hyperlipidemias should be followed closely if they elect to use COCs.

Persistent hypertriglyceridemia may occur in a small proportion of COC users.

In patients with elevated triglycerides, estrogen-containing preparations may be associated

with rare but large elevations of plasma triglycerides that may lead to pancreatitis.

Obesity (body mass index=Weight/Height2

Benign tumours of the breast and uterine dystrophy (hyperplasia, fibroma)

Hyperprolactinemia with or without galactorrhea.

Close surveillance should also be ensured in the presence of conditions, which have been

reported to occur or deteriorate with pregnancy or COC use, respectively in patients

presenting or with a history of: epilepsy, migraine, otosclerosis, asthma, family history of

vascular disease, varicose veins, herpes gestationis, gallstones, systemic lupus

erythematosus, cardiac, renal or hepatic dysfunction, depression, hypertension, chorea,

haemolytic uremic syndrome.

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Exogenous estrogens may induce or exacerbate symptoms of angioedema, particularly in

women with hereditary angioedema.

In clinical trials, amenorrhea, not linked to pregnancy, was observed in 7% of cycles

(occurring in 24% of women over the total duration of the clinical trials) and 3.6% of women

experienced consecutive amenorrheic cycles. In the clinical trials, only and 1% of women

discontinued because of amenorrhea.

When Minesse is taken according to directions, in the occurrence of one amenorrheic cycle,

there is no reason for discontinuation and performance of a pregnancy test. If Minesse is not

taken according to directions or if amenorrhea occurs after a long period of regular menstrual

bleeding, pregnancy should be ruled out.

Some women may encounter post-therapeutic amenorrhea (possibly with anovulation) or

oligomenorrhea, especially when such a condition was pre-existing. It usually resolves

spontaneously. If prolonged, investigations should be carried out into the possibility of

pituitary disorders before any further prescription.

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. Further diagnostic measures may include curettage.

Cases of depression have been reported during COC use. Women with a history of

depression who use COCs should be carefully observed.

If melasma/chloasma has appeared during pregnancy or with previous COC use, exposure to

sunlight should be avoided to minimize exacerbation of this condition.

Diarrhea and/or vomiting may reduce COC hormone absorption (see Section 4.2).

Women should be advised that hormonal contraceptives do not protect against HIV infection

(AIDS) or other sexually transmitted diseases.

Due to the presence of lactose, this medicinal product is not recommended for use in women

with lactose intolerance.

4.5

Interaction with other medicinal products and other forms of interaction

Interactions between ethinylestradiol or gestodene and other substances may lead to decreased

or increased plasma and tissue concentrations of ethinylestradiol or gestodene.

Decreased ethinylestradiol serum concentrations may cause an increased incidence of

breakthrough bleeding and menstrual irregularities and may possibly reduce efficacy of the

COC.

Concomitant use not recommended:

*Enzyme inducing agents such as: anticonvulsants (phenobarbital, phenytoin, primidone,

carbamazepine, topiramate); rifabutin; rifampicine; griseofulvine, and possibly St. John’s

Wort. Reduction in the efficacy of contraception through increased hepatic metabolism

during treatment and for one cycle following treatment discontinuation. Preference should be

given to a nonhormonal contraceptive method.

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When co-administered with COCs many HIV/HCV protease inhibitors and non-nucleoside

reverse transcriptase inhibitors can increase or decrease plasma concentrations of estrogen or

progestin. These changes may be clinically relevant in some cases. Please see the

corresponding SmPC of each HIV or HCV protease inhibitors and nonnucleoside reverse

transcriptase inhibitors for specific recommendation.

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

voriconazole, fluconazole), macrolides (e.g. clarithromycin, erythromycin), verapamil,

diltiazem and grapefruit juice can increase plasma concentrations of the estrogen or the

progestin or both.

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

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

hormonal contraceptive containing 0.035 mg ethinylestradiol.

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

Modafinil: risk of a decreased contraceptive efficacy during treatment and for one cycle

following treatment discontinuation.

*Flunarizine: risk of galactorrhea due to increased sensitivity of mammary tissue to prolactin

through the action of flunarizine.

Troleandomycin may increase the risk for intrahepatic cholestasis during co-administration

with COCs.

Effects of COCs on other medicinal products:

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

tissue

concentrations

either

increase

(e.g.

cyclosporin)

decrease

(e.g.

lamotrigine).

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

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

plasma concentration.

The labelling of concomitant medications should be consulted to identify potential

interactions.

4.6

Fertility,pregnancy and lactation

Fertility

Minesse is indicated for the prevention of pregnancy.

Women may experience post treatment amenorrhoea following discontinuation of treatment

(see section 4.4).

Pregnancy

This medicine is not indicated during pregnancy.

In clinical use to date, and in contrast with diethylstilbestrol, the results of numerous

epidemiological studies have made it possible to discount the risk of malformation with

estrogen administered alone or in combination during early pregnancy.

In addition, the risks concerning foetal sex differentiation (particularly female) which were

described with early, highly androgenomimetic progestogens cannot be extrapolated to more

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recent progestogens (such as that employed in this proprietary medicinal product) which are

markedly less androgenomimetic, if at all.

Consequently, the discovery of pregnancy in a woman receiving an estrogen-progestogen

combination does not justify an abortion.

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

starting Minesse (see section 4.2 and 4.4).

Breast-feeding

The use of this medicine in breast-feeding mothers is not advisable since estrogen-

progestogens can be found in breast milk.

During lactation a different method of contraception should be proposed.

4.7

Effects on ability to drive and use machines

The impact of Minesse on the ability to drive and use machines has not been systematically

evaluated. Minesse is not expected to influence the ability to drive or use machines. Cases of

dizziness have been reported. Patients should exercise caution until they know that Minesse

does not affect these abilities.

4.8

Undesirable effects

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 undesirable effects have been reported in users of COCs:

For serious adverse effects in COC users see

section 4.4

.

The occurrence of amenorrhea was reported in 15% of women during clinical trial, see

section 4.4. Some most frequently (greater than 10 %) reported adverse events during phase

III studies and postmaketing surveillances in women using Minesse are headache, including

migraines, abdominal pain, breast pain, breast tenderness.

Other adverse events have been reported in women taking COC:

System Organ

Class

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

Vaginitis,

including

candidiasis

Neoplasms

benign,

malignant and

unspecified

(including cysts

and polyps)

Hepatocellular

carcinoma and

benign hepatic

tumours (e.g. focal

nodular

hyperplasia, hepatic

adenoma)

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Immune system

disorders

Anaphylactic/anaph

ylactoid reaction,

including very rare

cases of

angioedema, severe

reactions with

respiratory and

circulatory

symptoms and

urticaria.

Metabolism and

nutrition

disorders

Increased

appetite,

decreased

appetite

Glucose tolerance

impaired

Psychiatric

disorders

Mood altered,

including

depression,

nervousness,

change in libido

Nervous system

disorders

Headache

(including

migraines)

Dizziness

Optic neuritis,

chorea aggravated

Eye disorders

Contact lens

intolerance

Vascular

disorders

Aggravation of

varicose veins

Venous

thromboembolis

m and arterial

thromboembolis

Gastrointestinal

disorders

Abdominal pain,

Vomitting,

nausea, bloating

Pancreatitis

Colitis ischaemic,

possible

aggravation of

inflammatory

bowel disease,

abdominal cramps

Hepato-biliary

disorder

Hepatic and

hepatobiliary

disorders (e.g.

hepatitis, hepatic

function

abnormal),

biliary lithiasis

gallbladder

disease

Jaundice

cholestatic,

cholestasis

Skin and

subcutaneous

tissue disorders

Acne, rash,

alopecia

Chloasma

which may

persist,

hirsutism

Erythema

multiforme,

erythema nodosum

Musculoskeletal

and connective

tissue disorders

Exacerbation of

systemic lupus

erythematosus

Renal and urinary

disorders

Haemolytic

uraemic syndrome

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Reproductive

system and breast

disorders

Breast pain,

Breast

tenderness,

Breakthrough

bleeding,

spotting,,

dysmenorrhoea,

change in

menstrual flow,

change in

cervical

ectroption and

secretion.

Breast secretion,

breast

enlargement

Congenital,

familial and

genetic disorders

Exacerbation of

porphyria

General disorders

administration

Fluid

retention/oedema

Investigations

Weight

increased, weight

decreased

Blood pressure

increased, lipids

increased

COCs may worsen existing biliary lithiasis and cholestasis

COCs may worsen existing gallbladder disease and may accelerate the development of this disease in

previously asymptomatic women.

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

(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedi

c@moh.health.gov.il ) or by email (adr@MOH.HEALTH.GOV.IL ).

4.9

Overdose

Symptoms of oral contraceptive overdose in adults and children may include nausea,

vomiting, breast tenderness, dizziness, abdominal pain, drowsiness / fatigue; withdrawal

bleeding may occur in females. There are no antidotes and further treatment should be

symptomatic.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

PROGESTOGENS AND ESTROGENS IN FIXED COMBINATION

ATC Code: G03AA10 (genitourinary system and sex hormones).

Single-phase estrogen-progestogen combination. Non-corrected Pearl index: 0.24 (21,521

cycles).

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The contraceptive efficacy of Minesse arises from three complementary mechanisms of

action:

Ovulation is inhibited at the level of the hypothalamo-hypophysial axis,

Cervical secretions become impermeable to the migration of spermatozoids,

The endometrium becomes unsuitable to nidation.

5.2

Pharmacokinetic properties

Ethinylestradiol:

Absorption

Ethinylestradiol is rapidly and completely absorbed after oral ingestion. After administration

of 15 µg, peak plasma concentrations of 30 pg/mL are reached after 1- 1.5 hours.

Ethinylestradiol undergoes an extensive first pass effect, which displays great interindividual

variation. The absolute bioavailability is approximately 45%.

Distribution

Ethinylestradiol has an apparent volume of distribution of 15 L/kg and binding to plasma

proteins is approximately 98%. Ethinylestradiol induces the hepatic synthesis of sex-

hormone binding globulins (SHBG) and corticoid-binding globulins (CBG). During

treatment with 15 µg ethinylestradiol the plasma concentration of SHBG increases from 86 to

about 200 nmol/L.

Biotransformation

Ethinylestradiol is metabolised completely (metabolic plasma clearance approximately 10

mL/min/kg). The metabolites formed are excreted in the urine (40%) and feces (60%).

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

The elimination half-life of ethinylestradiol is approximately 15 hours. 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.

Steady state conditions

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

levels of ethinylestradiol accumulate by a factor of about 1.4 to 2.1.

Gestodene

Absorption

After oral administration gestodene is rapidly and completely absorbed. The absolute

bioavailability is about 100%. After oral intake of a single 60 µg gestodene dose, peak

plasma concentrations of 2 ng/mL are reached in about 60 minutes. The plasma

concentrations are strongly dependent on the SHBG concentrations.

Distribution

Gestodene has an apparent volume of distribution of 1.4 L/kg following a single 60

g dose.

It is 30% bound to plasma albumin and 50 – 70% bound to SHBG.

Biotransformation

Gestodene is extensively metabolised by the steroid metabolic pathway. The metabolic

clearance is about 0.8 mL/min/kg following a single 60

g dose. The non-active metabolites

formed are excreted in urine (60%) and faeces (40%).

Elimination

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Minesse LPD 18 Sep 2016

The apparent elimination half-life of gestodene is about 13 hours. The half-life is prolonged

to 20 hours after concomitant administration with ethinylestradiol.

Steady state conditions

After multiple dosing concomitantly with ethinylestradiol the plasma concentration increases

approximately by a factor of 2-4.

5.3

Preclinical safety data

Toxicological studies have been performed on all components individually and on their

combination.

Acute toxicity studies in animals showed no evidence of a risk of acute symptoms arising

after accidental overdosage.

General safety studies with repeated administration have shown no evidence of any effects

suggesting any unexpected risks in man.

Long term and repeated dose carcinogenicity studies have not demonstrated any carcinogenic

potential; however, it is important to remember that sex steroids are capable of promoting the

development of certain tissues into hormone-dependent tumours.

Teratogenicity studies have not indicated any particular risk when estrogen-progestogen

combinations are used correctly; it is however essential to discontinue treatment immediately

if taken in error at the beginning of pregnancy.

Mutagenicity studies have not revealed any mutagenic potential for ethinylestradiol or

gestodene.

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of excipients

Pale-yellow tablet (active): lactose monohydrate, microcrystalline cellulose, magnesium

stearate, polacrilin potassium, OPADRY yellow YS-1-6386-G [hypromellose, titanium

dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172)], macrogol 1450, wax E

(montanglycol wax).

White tablet (placebo): lactose monohydrate, microcrystalline cellulose, magnesium stearate,

polacrilin potassium, OPADRY white Y-5-18024-A [hypromellose, hydroxypropylcellulose,

titanium dioxide (E 171), macrogol 400], polyethylene glycol 1450, wax E (montanglycol

wax).

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

34 months

6.4

Special precautions for storage

Store below 25°C.

6.5

Nature and contents of the container

24 pale-yellow tablets and 4 white tablets in blister pack (PVC/Aluminium).

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Minesse LPD 18 Sep 2016

The pack sizes are 1 x 28, 3 x 28 and 6 x 28. Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling

No special requirements.

License Holder

Pfizer PFE Pharmaceuticals Israel Ltd.

9 Shenkar St.

Hertzliya Pituach 46725

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

checked and approved in Sep 2016

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