MICROGYNON 30

Israel - English - Ministry of Health

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Active ingredient:
ETHINYLESTRADIOL; LEVONORGESTREL
Available from:
BAYER ISRAEL LTD
ATC code:
G03AA
Pharmaceutical form:
COATED TABLETS
Composition:
LEVONORGESTREL 150 MCG; ETHINYLESTRADIOL 30 MCG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
BAYER PHARMA AG, GERMANY
Therapeutic group:
PROGESTOGENS AND ESTROGENS, FIXED COMBINATIONS
Therapeutic indications:
Oral contraceptive.
Authorization number:
027 43 21707 00
Authorization date:
2012-07-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

24-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

13-09-2020

לע העדוה לע העדוה לע העדוה ( הרמחה ( הרמחה ( הרמחה

עדימ עדימ עדימ ל ןולעב )תוחיטב ל ןולעב )תוחיטב ל ןולעב )תוחיטב אפור אפור אפור

ןכדועמ( ןכדועמ( ןכדועמ(

.102.50

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__ םושירה רפסמו תילגנאב רישכת םש

00

-

21707

-

43

-

027

Microgynon 30

םושירה לעב םש

_

מ"עב לארשי רייאב

_

ה טורפל דעוימ הז ספוט דבלב תורמחה

תושקובמה תורמחהה

ןולעב קרפ

יחכונ טסקט

שדח טסקט

4.5

Interaction

with other medicinal

products and other

forms of interaction

Interactions

Hepatic enzyme inducers

Drugs which induce hepatic

enzymes (especially

cytochrome P450 3A4)

increase the

metabolism of contraceptive

steroids and hence may result

in breakthrough bleeding and

pregnancy. The following

have been shown to have

clinically important

interactions with

COCs:

Antiretroviral agents

ritonavir;

nelfinavir;

nevirapine.

Anticonvulsants

barbiturates (including

phenobarbitone);

primidone;

phenytoin;-

carbamazepine;

oxcarbazepine;

topiramate.

Antibiotics/antifungals

griseofulvin;

rifampacin.

Herbal remedies

St John’s wort

(Hypericum

perforatum)

Managing interactions with

hepatic enzyme inducers

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.

Women on short term

Interactions

Enzyme inducers

Interactions can occur with

drugs that induce microsomal

enzymes (especially

cytochrome P450 3A4) which

can result in increased

clearance of sex hormones and

which may lead to

breakthrough bleeding and/or

contraceptive failure.

treatment with any of these

drugs should temporarily use

a barrier method in addition

to the COC or choose another

method of contraception. The

barrier method should be

used during the time of

concomitant drug

administration and for 28

days after their

discontinuation. If the period

during which the barrier

method is used runs beyond

the end of a pack, the next

pack should be started

without a break. In this

situation, a withdrawal bleed

should not be expected until

the end of the second pack. If

the patient does not have a

withdrawal bleed during the

tablet-free interval following

the end of the second pack,

the possibility of pregnancy

must be ruled out before

resuming with the next pack.

For women receiving long-

term therapy with hepatic

enzyme inducers, another

method of

contraception should be used.

Substances increasing the

clearance of COCs (

diminished efficacy of COCs

by enzyme-induction), e.g.:

phenytoin, barbiturates,

primidone, carbamazepine,

rifampicin, and possibly also

oxcarbazepine, topiramate,

felbamate, griseofulvin and

products containing St.

John’s wort.

Substances

with

variable

effects

on

the

clearance

of

COCs, e.g.:

When co-administered with

COCs, many HIV/HCV

protease inhibitors and non-

nucleoside reverse

transcriptase inhibitors can

Women on short term

treatment with any of these

drugs should temporarily use a

barrier method in addition to

the COC or choose another

method of contraception. The

barrier method should be used

during the time of concomitant

drug administration and for 28

days after their discontinuation.

If the period during which the

barrier method is used runs

beyond the end of a pack, the

next pack should be started

without a break. In this

situation, a withdrawal bleed

should not be expected until

the end of the second pack. If

the patient does not have a

withdrawal bleed during the

tablet-free interval following

the end of the second pack, the

possibility of pregnancy must

be ruled out before resuming

with the next pack.

For women receiving long-

term therapy with hepatic

enzyme inducers, another

method of

contraception should be used.

The following have been

shown to have clinically

important interactions with

COCs:

Anticonvulsants:

barbiturates (including

phenobarbitone), primidone,

phenytoin, carbamazepine,

oxcarbazepine, topiramate

Antibiotics/antifungals:

griseofulvin , rifampicin.

Herbal remadies: St. John’s

wort (Hypericum perforatum)

Antiretroviral agents: ritonavir,

nelfinavir, nevirapine.

Note: There are other

antiretroviral agents that may

increase plasma concentration

increase or decrease plasma

concentrations of estrogen or

progestin. These changes may

be clinically relevant in some

cases.

Effects on other drugs

Oral contraceptives may

affect the metabolism of

certain other drugs.

Accordingly, plasma and

tissue concentrations may

either increase (e.g.

cyclosporin) or decrease (e.g.

lamotrigine).

Note: The prescribing

information of concomitant

medications should be

consulted to

identify potential interactions.

of sex

hormones.

Substances decreasing the

clearance of COCs (enzyme

inhibitors )

Strong and moderate CYP3A4

inhibitors such as azole

antifungals (e.g. itraconazole,

voriconazole, fluconazole) and

macrolides (e.g. erythromycin)

can increase plasma

concentrations of oestrogen or

the progestin or both.

Etoricoxib doses of 60 to 120

mg/day have been shown to

increase plasma concentrations

of ethinylestradiol 1.4 to 1.6-

fold, respectively when taken

concomitantly with a combined

hormonal contraceptive

containing 0.035 mg

ethinylestradiol.

Effects on other drugs

Oral contraceptives may affect

the metabolism of certain other

drugs. Accordingly, plasma

and tissue concentrations may

either increase (e.g.

cyclosporine, tizanidine,

theophylline) or decrease (e.g.

lamotrigine).

1.

NAME OF THE MEDICINAL PRODUCT

Microgynon 30

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains:

Actives:

Levonorgestrel

150 mcg

Ethinylestradiol

30 mcg

Excipients:

Lactose monohydrate

32.970 mg

Sucrose

19.371 mg

For a full list of excipients, see section 6.1

3.

PHARMACEUTICAL FORM

Sugar-coated tablets

Each tablet is beige

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Oral contraception.

The decision to prescribe Microgynon 30 should take into consideration the individual

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

how the risk of VTE with Microgynon 30 compares with other combined hormonal

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

4.2

Posology and method of administration

Tablets must be taken orally in the order directed on the blister package at about the same time

every day, with some liquid if necessary.

First treatment cycle:

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

Contraceptive protection begins immediately.

Subsequent cycles:

Tablet-taking from the next pack of Microgynon 30 is continued after a 7-day

tablet-free interval, beginning on the same day of the week as the first pack. A

withdrawal bleed usually occurs during the tablet-free interval.

Changing from 21-day combined oral contraceptives:

The first tablet of Microgynon 30

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

course. Additional contraceptive precautions are not required.

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

Microgynon 30 should be started after taking the last active tablet from the Every Day Pill

pack. The first Microgynon 30 tablet is taken the next day. Additional contraceptive

precautions are not then required.

Changing from a progestogen-only pill (POP):

The first tablet of Microgynon 30 should be taken on the first day of bleeding, even if a POP has

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

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

Post-partum and post-abortum use:

After pregnancy, oral contraception can be started 21

days after a vaginal delivery, provided that the patient is fully ambulant and there are no

puerperal complications. Additional contraceptive precautions will be required for the first 7 days

of tablet taking. Since the first post-partum ovulation may precede the first bleeding, another

method of contraception should be used in the interval between childbirth and the first course of

tablets. After a first-trimester abortion, oral contraception may be started immediately in which

case no additional contraceptive precautions are required.

Special circumstances requiring additional contraception

Incorrect administration:

A single delayed tablet should be taken as soon as possible, and if this

can be done within 12 hours of the correct time, contraceptive protection is maintained. With

longer delays, additional contraception is needed. Only the most recently delayed tablet should be

taken, earlier missed tablets being omitted, and additional non-hormonal methods of contraception

(except the rhythm or temperature methods) should be used for the next 7 days, while the next 7

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

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

bleed should not be expected until the end of the second pack. Some breakthrough bleeding may

occur on tablet taking days but this is not clinically significant. If the patient does not have a

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

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

Gastro-intestinal upset

: Vomiting or diarrhoea may reduce the efficacy of oral

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

taking Microgynon tablet-taking from the current pack should be continued. Additional non-

hormonal methods of contraception (except the rhythm or temperature methods) should be used

during the gastro-intestinal upset and for 7 days following the upset. If these 7 days overrun the

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

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

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

pregnancy must be ruled out before starting the next pack. Other methods of contraception should

be considered if the gastro-intestinal disorder is likely to be prolonged.

Children: Not applicable.

Elderly: Not applicable.

4.3

Contraindications

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

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

stopped immediately.

Presence or risk of venous thromboembolism (VTE)

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

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

Known hereditary or acquired predisposition for venous thromboembolism, such as

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

C deficiency, protein S deficiency

Major surgery with prolonged immobilisation (see section 4.4)

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

(see section 4.4)

Presence or risk of arterial thromboembolism (ATE)

Arterial thromboembolism – current arterial thromboembolism, history of arterial

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

pectoris)

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

(e.g. transient ischaemic attack, TIA)

Known hereditary or acquired predisposition for arterial thromboembolism, such as

hyperhomocysteinaemia and anti-phospholipid antibodies (anticardiolipin-

antibodies, lupus anticoagulant)

History of migraine with focal neurological symptoms

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

4.4) or to the presence of one serious risk factor such as:

diabetes mellitus with vascular symptoms

severe hypertension

severe dyslipoproteinaemia

Presence or history of severe hepatic disease, e.g. active viral hepatitis and

severe

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

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

Current or history of breast cancer.

Hypersensitivity to the active substance(s) or to any of the excipients listed in section

6.1.

Microgynon 30 is contraindicated for concomitant use with medicinal products containing

ombitasvir/paritaprevir/ritonavir, dasabuvir,

glecaprevir/pibrentasvir and

ofosbuvir/velpatasvir/voxilaprevir

(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

Microgynon 30 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 Microgynon 30 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,

such as Microgynon 30, norgestimate or norethisterone are associated with the lowest risk of

VTE. The decision to use Microgynon 30 should be taken after a discussion with the woman

to ensure she understands the risk of VTE with Microgynon 30, 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 that contains levonorgestrel, about 6

will develop a VTE in a year.

This number of VTEs per year is fewer than the number expected in women during

pregnancy or in the postpartum period.

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

________

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

of approximately 2.3 to 3.6.

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

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

hepatic, mesenteric, renal, cerebral or retinal veins and arteries.

Risk factors for VTE

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

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

Microgynon 30 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

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.

VTE, particularly in women with other risk

factors.

Antithrombotic treatment should be considered

if Microgynon 30 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

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). Microgynon 30 is contraindicated if a woman has

one serious or multiple risk factors for ATE that puts her at high risk of arterial thrombosis (see

section 4.3). If a woman has more than one risk factor, it is possible that the increase in risk is

greater than the sum of the individual factors - in this case her total risk should be considered. If

the balance of benefits and risks is considered to be negative a CHC should not be prescribed (see

section 4.3).

Table: Risk factors for ATE

Risk factor

Comment

Increasing age

Particularly above 35 years

Smoking

Women should be advised not to smoke if they

wish to use a CHC. Women over 35 who

continue to smoke should be strongly advised to

use a different method of contraception.

Hypertension

Obesity (body mass index over 30 kg/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.

Medical Examination/Consultation

Prior to the initiation or reinstitution of Microgynon 30 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 Microgynon 30 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.

Undiagnosed vaginal bleeding that is suspicious for underlying conditions should be

investigated.

Conditions which require strict medical supervision

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

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

factors may indicate that use of the oral contraceptive should be discontinued. The

woman should contact her physician, who should then decide on whether COC use should be

discontinued:

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

neuropathy

Hypertension that is adequately controlled, i.e. systolic >140 to159 mm Hg or diastolic > 90

to 94 mm Hg (see also Section 4.4 ‘Reasons for stopping oral contraception immediately’)

porphyria

obesity

migraine

cardiovascular diseases

Reasons for stopping oral contraception immediately:

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

contraceptive protection is maintained.

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

frequent or unusually severe headaches

Sudden disturbances of vision, of hearing or other perceptual disorders

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

stabbing pains on breathing or coughing for no apparent reason). Feeling of pain and

tightness in the chest

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

surgery to the legs, medical treatment for varicose veins or prolonged immobilisation, e.g.

after accidents or surgery. Do not restart until 2 weeks after full ambulation. In case of

emergency surgery, thrombotic prophylaxis is usually indicated e.g. subcutaneous heparin

Onset of jaundice, hepatitis, itching of the whole body

Significant rise in blood pressure

Severe upper abdominal pain or liver enlargement

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

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

during previous COC use’ under 'Other conditions')

Tumours

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

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

that high dose combined oral contraceptives offer substantial protection against both ovarian and

endometrial cancer. However, it is not clear whether low dose COCs confer protective effects to

the same level.

Breast cancer

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

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

oral contraceptives (COCs). The observed pattern of increased risk may be due to an earlier

diagnosis of breast cancer in COC users, the biological effects of COCs or a combination of both.

The additional breast cancers diagnosed in current users of COCs or in women who have used

COCs in the last ten years are more likely to be localised to the breast than those in women who

never used COCs.

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

Whilst this background risk increases with age, the excess number of breast cancer diagnoses in

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

chart).

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

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

important and the excess risk gradually disappears during the course of the 10 years after stopping

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

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

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

against the risk of developing certain other cancers (e.g. ovarian and endometrial cancer).

Cervical Cancer

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

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

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

attributable to confounding effects, e.g., cervical screening and sexual behaviour including use of

barrier contraceptives.

Liver Cancer

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

life-threatening intra-abdominal haemorrhage have been observed after the use of hormonal

substances such as those contained in Microgynon 30. If severe upper abdominal complaints,

liver enlargement or signs of intra-abdominal haemorrhage occur, the possibility of a liver tumour

should be included in the differential diagnosis.

Other conditions

The possibility cannot be ruled out that certain chronic diseases may occasionally deteriorate

during the use of combined oral contraceptives.

Known hyperlipidaemias

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

pancreatitis when using COCs.

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

‘Risk of arterial thromboembolism (ATE)’). However routine screening of women on COCs is not

appropriate.

Blood pressure

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

arterial thromboembolism (ATE)’).Although small increases in blood pressure have been reported

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

hypertension develops during the use of a COC, antihypertensive treatment should normally be

instigated at a level of 160/100 mm Hg in uncomplicated patients or at 140/90 mm Hg in those

with target organ damage, established cardiovascular disease, diabetes or with increased

cardiovascular risk factors. Decisions about the continued use of the COC should be made at

lower BP levels, and alternative contraception may be advised.

Conditions which deteriorate in pregnancy or during previous COC use

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

COC use. Consideration should be given to stopping Microgynon 30 if any of the following occur

during use:

jaundice and/or pruritus related to cholestasis

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

systemic lupus erythematosus

herpes gestationis

otosclerosis-related hearing loss

sickle cell anaemia

renal dysfunction

hereditary angioedema

any other condition an individual woman has experienced worsening of during

pregnancy or previous use of COCs.

Angioedema

Exogenous oestrogens may induce or exacerbate symptoms of hereditary and acquired

angioedema.

Disturbances of liver function

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

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

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

necessitates the discontinuation of COCs.

Diabetes (without vascular involvement)

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

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

considered when prescribing COCs. Diabetics with existing vascular disease are

contraindicated from using COCs (see section 4.3 Contraindications).

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

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

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

while taking COCs.

Psychiatric disorders

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

(see section 4.8). Depression can be serious and is a well-known risk factor for suicidal behaviour

and suicide. Women should be advised to contact their physician in case of mood changes and

depressive symptoms, including shortly after initiating the treatment.

Chloasma

Chloasma 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.

Menstrual Changes

Reduction of menstrual flow:

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

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

Missed menstruation:

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

been taken correctly, pregnancy is very unlikely. If withdrawal bleeding fails to occur at the end

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

pack.

Intermenstrual bleeding

: Irregular bleeding (spotting or breakthrough bleeding) may occur

especially during the first months of use. Therefore, the evaluation of any irregular bleeding is

only meaningful after an adaptation interval of about three cycles. If bleeding irregularities persist

or occur after previously regular cycles, then non-hormonal causes should be considered and

adequate diagnostic measures are indicated to exclude malignancy or pregnancy. This may include

curettage.

Some women may experience amenorrhoea or oligomenorrhoea after discontinuation of oral

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

of this possibility.

Lactose and Sucrose Intolerance

Each tablet of this medicinal product contains 32.97 mg lactose and 19.371 mg sucrose per

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

fructose intolerance or glucose-galactose malabsorption or sucrase-isomaltase should not take this

medicine.

Reduced efficacy

The efficacy of COCs may be reduced, in the event of missed tablets , vomiting or diarhhoea, or

concomitant medication.

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).

ALT elevations have also been observed

with HCV anti-viral medicinal products containing glecaprevir/pibrentasvir and

sofosbuvir/velpatasvir/voxilaprevir

(see sections 4.3 and 4.5).

4.5

Interaction with other medicinal products and other forms of interaction

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

potential interactions.

Interactions

Enzyme inducers

Interactions can occur with drugs that induce microsomal enzymes (especially cytochrome P450

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

breakthrough bleeding and/or contraceptive failure.

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

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

induction may be sustained for about 4 weeks.

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

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

used during the time of concomitant drug administration and for 28 days after their

discontinuation. If the period during which the barrier method is used runs beyond the end of a

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

withdrawal bleed should

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

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

must be ruled out before resuming with the next pack.

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

contraception should be used.

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

Anticonvulsants

: barbiturates (including phenobarbitone), primidone, phenytoin, carbamazepine,

oxcarbazepine, topiramate.

Antibiotics/antifungals:

griseofulvin , rifampicin.

Herbal remedies:

St. John’s wort

(Hypericum perforatum)

Antiretroviral agents

: ritonavir, nelfinavir, nevirapine.

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

hormones.

Substances decreasing the clearance of COCs

(enzyme inhibitors)

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

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

of the oestrogen or the progestin or both.

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

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

contraceptive containing 0.035 mg ethinylestradiol.

Effects on other drugs

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

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

(e.g. lamotrigine).

Pharmacodynamic interactions

Concomitant use with medicinal products containing ombitasvir/paritaprevir/ritonavir dasabuvir,

with or without ribavirin,

glecaprevir/pibrentasvir and

sofosbuvir/velpatasvir/voxilaprevir,

may increase the risk of ALT elevations (see sections 4.3 and

4.4).

Therefore, Microgynon 30-users must switch to an alternative method of contraception (e.g.,

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

these

drug

regimens. Microgynon 30 can be restarted 2 weeks following completion of treatment with these

drug regimens.

Laboratory tests

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

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

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

carbohydrate metabolism and parameters of coagulation and fibrinolysis. Laboratory staff should

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

4.6

Pregnancy and lactation

Microgynon 30 is not indicated during pregnancy. If pregnancy occurs during treatment with

Microgynon 30, further intake must be stopped. However, extensive epidemiological studies have

revealed neither an increased risk of birth defects in children born to women who used COCs prior

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

pregnancy.

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

Microgynon 30 (see section 4.2 and 4.4).

The use of Microgynon 30 during lactation may lead to a reduction in the volume of milk

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

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

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

contraception.

4.7

Effects on ability to drive and to use machines

Ethinylestradiol / levonorgestrel has no effects or negligible influence on the ability to drive and

use machines.

4.8

Undesirable Effects

Summary of the safety profile

The most commonly reported adverse reactions with Microgynon 30 are nausea, abdominal pain,

increased weight, headache, depressed mood, altered mood, breast pain, breast tenderness. They

occur in ≥1% of users.

Serious adverse reactions are arterial and venous thromboembolism.

The following adverse events have been reported during use of ethinylestradiol /

levonorgestrel:

System Organ

Class

Adverse events reported in clinical trials

Adverse events

reported post

marketing

Common

(≥ 1/100)

Uncommon

(≥ 1/1000,

< 1/100)

Rare

(<1/1000)

Eye disorders

contact lens

intolerance

Gastrointestinal

disorders

nausea,

abdominal

pain

vomiting,

diarrhea

Crohn’s disease,

ulcerative colitis

Immune system

disorders

hypersensitivity

exacerbation of

hereditary

angioedema

Investigations

weight

increased

weight decreased

Metabolism and

fluid retention

Hypertriglycerid

nutrition disorders

emia

Nervous system

disorders

headache

migraine

exacerbation of

chorea

Vascular system

disorders

Venous

thromboembolis

m (VTE),

Arterial

thromboembolis

m (ATE)

Hepatobiliary

disorders

liver function

disturbances

Psychiatric

disorders

depressed

mood, mood

altered

libido decreased

libido increased

Reproductive

system and breast

disorders

breast pain,

breast

tenderness

breast

hypertrophy

vaginal

discharge

breast

discharge

reduced

menstrual flow,

spotting,

breakthrough

bleeding and

missed

withdrawal

bleeding, post

pill amenorrhoea

Skin and

subcutaneous

tissue disorders

rash, urticaria

erythema

nodosum,

erythema

multiforme

chloasma

Description of selected adverse reactions

An increased risk of arterial and venous thrombotic and thrombo-embolic events, including

myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary

embolism has been observed in women using CHCs, which are discussed in more detail in section

4.4.

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

discussed in section 4.4 ‘Special warnings and precautions for use’:

Venous thromboembolic disorders

Arterial thromboembolic disorders

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

Hypertension

Liver tumours (benign and malignant)

Exogenous oestrogens may induce or exacerbate symptoms of hereditary and acquired

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 ‘Contraindications’ and 4.4 ‘Special warnings and precautions for

use’.

Conditions reported to deteriorate with pregnancy or previous COC use

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

erythematosus; herpes gestationis; otosclerosis-related hearing loss; sickle cell anaemia; renal

dysfunction; hereditary angioedema; porphyria; cervical cancer.

Changes in glucose tolerance or effect on peripheral insulin resistance have been reported in

women using COCs (see section 4.4).

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 have been no reports of serious effects from overdose. Overdosage may cause nausea,

vomiting and, in females, withdrawal bleeding. Withdrawal bleeding may even occur in girls

before their menarche, if they accidentally take the medicinal product.

There are no specific antidotes and treatment should be symptomatic.

5.

PHARMACOLOGICAL PARTICULARS

5.1

Pharmacodynamic properties

Microgynon 30 is an oestrogen-progestogen combination which acts by inhibiting ovulation by

suppression of the mid-cycle surge of luteinising hormone, the inspissation of cervical mucus

producing a barrier to sperm, and the rendering of the endometrium unreceptive to implantation.

5.2

Pharmacokinetic properties

Levonorgestrel

Levonorgestrel is absorbed quickly and completely. Maximum active substance levels of

approx 3 ng/ml were reached in serum just one hour after ingestion of Microgynon 30. The serum

concentrations subsequently fell in 2 phases with half-lives of around 0.5 hours and 20 hours. The

metabolic clearance rate from plasma is approx. 1.5 ml/min/kg.

Levonorgestrel is eliminated not in unchanged form, but in the form of metabolites with a

half-life of around one day and in almost equal proportions via the kidney and bile.

Levonorgestrel is extensively metabolised. The major metabolites in plasma are the unconjugated

and conjugated forms of 3α, 5β-tetrahydrolevonorgestrel. Based on

in vitro

in vivo

studies,

CYP3A4 is the main enzyme involved in the metabolism of levonorgestrel.

Levonorgestrel is bound to serum albumin and SHBG. Only around 1.5% of the respective

total concentration is present in unbound form, while approx. 65% is bound to SHBG. The

relative proportions (free, albumin-bound, SHBG-bound) depend on the concentration of

SHBG. After induction of the binding protein, the portion bound to SHBG increases, while the

free portion and that bound to albumin decreases.

After daily repeated ingestion, levonorgestrel accumulates by about the factor 2. A steady

state is reached during the second half of the treatment cycle. The pharmacokinetics of

levonorgestrel are dependent on the concentration of SHBG in plasma. Under treatment

with Microgynon, an increase in the levels of SHBG effect a concomitant increase in the

specific binding capacity and therefore also an increase in levonorgestrel serum levels.

The levonorgestrel serum levels do not change any further after 1 - 3 cycles of use owing to the

fact that SHBG induction is concluded. Compared to a single administration, 3 - 4 fold higher

levonorgestrel serum levels are reached in the steady state.

The absolute bioavailability of levonorgestrel amounts to almost 100%.

Approx. 0.1% of the maternal dose can be passed on to a baby with the breast milk.

Ethinylestradiol

Orally administered ethinylestradiol is absorbed quickly and completely. Ingestion of

Microgynon 30 leads to maximum plasma levels of approx. 100 pg/ml after 1 - 2 hours. The

substance concentration then falls in 2 phases for which half-lives of around 1 - 2 hours and about

20 hours have been determined. For technical reasons, these data can only be calculated at higher

dosages.

An imaginary distribution volume of around 5 l/kg and a metabolic clearance rate from

plasma of approx. 5 ml/min/kg have been determined for ethinylestradiol. Ethinylestradiol is

bound non-specifically to serum albumin to the extent of 98%.

Ethinylestradiol is metabolised even during its absorption phase and during its first liver

transit, leading to reduced and individually varying oral bioavailability. Ethinylestradiol is

eliminated not in unchanged form, but in the form of metabolites with a half-life of around

one day. The excretion ratio is 40 (urine) : 60 (bile).

Because of the half-life of the terminal elimination phase from plasma, a steady state

characterised by a 30 - 40% higher plasma substance level becomes established after approx. 5 - 6

daily administrations.

The absolute bioavailability of ethinylestradiol is subject to considerable interindividual

variations. After oral ingestion, it amounts to around 40 - 60% of the dose.

In women with fully established lactation, around 0.02% of the maternal dose can be passed on to

the baby with the breast milk.

Other drugs can have a negative or positive effect on the systemic availability of

ethinylestradiol. No interaction with vitamin C takes place. On continuous use,

ethinylestradiol induces the hepatic synthesis of CBG and SHBG, the extent of SHBG

induction being dependent on the type and dose of the simultaneously administered progestogen.

5.3

Preclinical safety data

None stated

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Each tablet contains:

Lactose monohydrate

Sucrose

maize starch

Calcium carbonate

Talc

Macrogol 6000

Povidone 25000

Titanium dioxide (E171)

Povidone 700000

Glycerol 85%

Magnesium stearate

Montanglycol wax

Ferric oxide pigment, yellow (E172)

6.2

Incompatibilities

None known.

6.3

Shelf life

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

6.4

Special precautions for storage.

Do not store above 25

6.5

Nature and contents of container.

Deep drawn strips made of polyvinyl chloride film with counter-sealing foil made of

aluminium with heat sealable coating.

Presentation:

Each carton contains either 1 or 3 blister calendar packs. Each blister calendar pack contains 21

tablets.

6.6

Special precautions for disposal

No special requirements.

MANUFACTURER

Bayer pharma AG, Berlin, Germany

REGISTRATION HOLDER

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

4527702

Revised in September 2020.

דומע

ךותמ

רבמבונ

2019

,ה/דבכנ ה/אפור

,ה/דבכנ ת/חקור

:ןודנה

Microgynon 30

ןוניגורקימ

30

Coated Tablets

150 mcg

Levonorgestrel

30 mcg

Ethinylestradiol

יכ עידוהל תדבכתמ רייאב תרבח תינכרצלו אפורל םינולעה

רישכתה לש .ונכדוע

תויוותה

תורשואמ

Oral contraception.

וז העדו לכ לו םי

םינוכדיע

דבלב םייתוהמה

עיפומ ןלהלש טוריפב

הנושש קרפ לכ ךותמ ,םינולעב

.ןכדעתהש עדימה קר תפסות טסקט

תנמוסמ ןותחת וקב

תנמוסמ טסקט תקיחמ .הצוח וקב

לעב םינוכדעה אפורל ןו

:

4.3

Contraindications

Microgynon 30 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

Psychiatric disorders

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

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

risk factor for suicidal behaviour and suicide. Women should be advised to contact

their physician in case of mood changes and depressive symptoms, including shortly

after initiating the treatment.

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)

דומע

ךותמ

4.5

Interaction with other medicinal products and other forms of interaction

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.

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, Microgynon 30-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. Microgynon 30 can be

restarted 2 weeks following completion of treatment with this combination drug

regimen.

4.9

Overdose

There have been no reports of serious effects from overdose. Overdosage may

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

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

product.

תינכרצל ןולעב םינוכדעה

:

2

(

הפורתב שומישה ינפל

:םא הפורתב שמתשהל ןיא

מ תלבוס ךנה דבכ תקלד

גוסמ

יטפה) סיט

ו ( תא פר םירישכת תלטונ מה םייאו םיליכ /ריבסאטיבמוא ריבאנוטיר /ריברפאטיראפ

ריבובאסאד יאר)

םג

" ףיעסב קול תא םא

,הנורחאל תחקל םא וא

תופורת תורחא

("

תורהזא

הפורתב שומישל תועגונה תודחוימ

וירטאיכיספ תוערפה

ת

דומע

ךותמ

מל םיילנומרוה םיעצמאב תושמתשמה תומייוסמ םישנ ןוירה תעינ ללוכ ורקימ ןוניג

בצמ וא ןואכיד לע וחוויד םייוניש הווח ךנה םא .תוינדבוא תובשחמל ליבוהל םיתעלו יניצר תויהל לולע ןואכיד .ינואכיד חור ה בצמב

חו מיסו

םימוט

םדקהב ףסונ יאופר ץועייל ךלש אפורה םע רשק ירצ ןואכיד לש

.ירשפאה

לא תשת ב ישמ ןוניגורקימ

ה םא בוס ךנ מ תל דבכ תקלד

גוסמ

סיטיטפה)

םירישכת תלטונ תאו ( םייאופר ראפ /ריבסאטיבמוא םיליכמה רפאטי ריבאנוטיר /ריב

ו רחאמ ריבובאסאד םורגל לולע שומישה

הילע דבכה ידוקפת לש םד תוקידב תואצותב זנאב הילע) םי

גוסמ דבכ

ךלש אפורה שרי

לש רחא ג נמ יעצמא

הע

ינפל

תליחת

לופיט

ה תא שדחל ןתינ .הלאה םייאופרה םירישכת שומיש

ןוניגורקימב

ס רחאל םייעובשכ לופיטה םוי

."םא הפורתב שמתשהל ןיא" ףיעס יאר

ןוירה

,

הקנה

וירופו

ת

יגורקימ לוטיל ןונ

רהב ךנה .ןוי

ספת םרטב ןוירה תקידב יעצב ,ןוירהב ךנהו ןכתייש תבשוח תא םא א לוטיל יקי .הפורתה ת

שומישה ןוניגורקימב

תויומכ .ובכרה תא תונשלו רצוימה בלחה חפנב התחפהל ליבוהל לולע הקנה ןמזב םאה בלחב תושרפומ םיליעפה םירמוחה לש תוריעז

ומכ

לא תו ע עיפשהל תולולע ה

דחוימב ,קוניתה ךלהמב

ובשה הדילה רחאל םינושארה תוע

3

(

שמתשת דציכ

י

ורתב ?הפ

םא

רתוי הובג ןונימ תועטב תלטנ

יפויו ןכתיי ךא ,קזנ םורגת תחא הילבטמ רתוי לש הליטנש ריבס אל ניגו םומיד וא תואקה ,תוליחב וע

.יל םומיד עיפוהל לולע הזכ

ב םג תודלי

עיפוה םרט

לצא

תסוו

.הפורתה תא תועטב ולטנ

יצעוויה

םא אפורב תא הווח

סתהמ דחא ימ .וללה םינ

טנ םא רתי תנמ תל

בהו םילוח תיב לש ןוימ רדחל וא אפורל דימ ינפ ,הפורתה ןמ דלי עלב תועטב םא וא

יא .ךתיא הפורתה תזירא

אפורל ןולעה

כרצל ןולעה תינ

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

שרחה

דוה

ןורשה :ןופלט ,

7626700

,הכרבב

לארשי רייאב

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