Diane-35 ED

New Zealand - English - Medsafe (Medicines Safety Authority)

Buy It Now

Active ingredient:
Cyproterone acetate 2 mg; Ethinylestradiol 0.035 mg
Available from:
Bayer New Zealand Limited
INN (International Name):
Cyproterone acetate 2 mg
Pharmaceutical form:
Film coated tablet
Composition:
Active: Cyproterone acetate 2 mg Ethinylestradiol 0.035 mg Excipient: Calcium carbonate Glycerol Glycol montanate Iron oxide yellow Lactose monohydrate Macrogol 6000 Magnesium stearate Maize starch Povidone   Purified talc   Sucrose Titanium dioxide Calcium carbonate Glycol montanate Lactose monohydrate Macrogol 6000 Magnesium stearate Maize starch Povidone   Purified talc   Sucrose
Units in package:
Blister pack, 1 x(21+7) sample pack, 28 tablets
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Bayer AG
Therapeutic indications:
· The treatment of signs of androgenisation in women, such as severe acne (involving inflammation or nodularity or risk of scarring) where prolonged oral antibiotics or local treatment alone has not been successful, or idiopathic hirsutism of mild to moderate degree.
Product summary:
Package - Contents - Shelf Life: Blister pack, 3 x (21+7) pack - 84 tablets - 60 months from date of manufacture stored at or below 25°C
Authorization number:
TT50-3101/1
Authorization date:
1992-03-31

1801 DIANE-35

ED CMI

Diane

®

-35 ED

(Di·ANNE Ee·Dee)

cyproterone acetate and ethinyloestradiol

Consumer Medicine Information

WHAT IS IN THIS

LEAFLET

This leaflet answers some common

questions about Diane-35 ED. It

does not contain all the available

information. It does not take the

place of talking to your doctor or

pharmacist.

All medicines have risks and

benefits. Your doctor

has weighed the risks of you taking

Diane-35 ED against the benefits

they expect it will have for you.

If you have any concerns, or are

unsure about taking this

medicine, ask your doctor or

pharmacist for more advice.

Keep this leaflet with the

medicine.

You may need to read it

again.

WHAT DIANE-35 ED IS

USED FOR

Diane-35 ED is used for the

treatment of signs of physical

male characteristics caused by the

male sex hormone, androgen,

produced by in women in small

amounts (androgenisation), such

severe acne where other

treatments have not been

successful

for excessive growth of facial

or body hair (known as

hirsutism) of a mild to

moderate degree, where no

underlying cause has been

found.

Diane-35 ED can also be used as a

contraceptive to prevent pregnancy

in women who are taking it for the

treatment of signs of physical

male characteristics as described

above. Diane-35 ED contains a

progestogen and an oestrogen

hormone, and therefore works

similarly to the combined oral

contraceptive birth control pill,

also known as ‘the Pill’. It should

not be used in combination with

another hormonal contraceptive.

While taking Diane-35 ED you

may also experience the

following benefits:

more regular and lighter

periods – potentially resulting

in a decreased risk in anaemia

(iron deficiency)

a decrease in period pain

reduction of greasiness in skin

and hair.

Some conditions such as pelvic

inflammatory disease, ovarian

cysts, ectopic pregnancy (where

the foetus is carried outside of

your womb), lumpy breasts and

cancer of the uterus (womb) and

ovaries may be less common in

women taking Diane-35 ED.

Ask your doctor if you have

any questions about why this

medicine has been prescribed

for you.

Your doctor may have prescribed

it for another reason.

BEFORE YOU TAKE

DIANE-35 ED

When you must not take

it

Do not take Diane-35 ED if you

have an allergy to:

cyproterone acetate and/or

ethinyloestradiol (the active

ingredients in Diane-35 ED)

any of the ingredients listed at

the end of this leaflet.

Some of the symptoms of an

allergic reaction may include:

shortness of breath

wheezing or difficulty in

breathing

swelling of the face, lips,

tongue or other parts of the

body

rash, itching or hives on the

skin.

Diane-35 ED is not for use in

men.

Do not take Diane-35 ED if you

are taking antiviral medicines

which contain ombitasvir,

paritaprevir, or dasabuvir, and

combinations of these.

These

antiviral medicines are used to

treat chronic (long-term) hepatitis

C (an infectious disease that

affects the liver, caused by the

hepatitis C virus).

Do not take Diane-35 ED if you

have, or have had, a blood clot

in:

the blood vessels of the legs

(deep vein thrombosis - DVT)

the lungs (pulmonary

embolism - PE)

the heart (heart attack)

the brain (stroke)

other parts of the body.

Do not take Diane-35 ED if you

are concerned about or have an

increased risk of blood clots.

Blood clots are rare. Very

occasionally blood clots may

cause serious permanent

disability and may even be fatal.

1801 DIANE-35

ED CMI

All combined oral contraceptive

pills, including Diane-35 ED,

increase the risk of having a blood

clot. However, the risk of having a

blood clot when taking Diane-35

ED is less than the risk of having a

blood clot during pregnancy.

Do not take Diane-35 ED if you

are concerned about an

increased risk of blood clots

because of age or smoking.

The risk of having a heart attack or

stroke increases as you get older. It

also increases if you smoke.

You should stop smoking when

taking Diane-35 ED, especially if

you are older than 35 years of age.

Do not take Diane-35 ED if you

have, or have had:

blood clots in your legs

any blood clotting disorders

such as Protein C deficiency,

Protein S deficiency, Leiden

Factor V mutation,

Antithrombin III deficiency

or other inherited blood

clotting conditions.

A confirmed blood test

showing:

increased levels of

homocysteine

antiphospholipid

antibodies (APLAs) e.g.

anticardiolipin-antibodies

and lupus anticoagulant

These may increase your

risk for blood clots or

pregnancy losses

(miscarriage).

major surgery after which you

have not been able to move

around for a period of time

angina (chest pain)

a mini-stroke (also known as

TIA or transient ischaemic

attack)

migraine, where you have also

had problems with seeing,

speaking or had weakness or

numbness in any part of your

body

high risk of blood clots due to

conditions such as diabetes

with blood vessel damage,

severe high blood pressure or

severe high or low level of fats

in your blood

pancreatitis (an inflammation

of the pancreas) associated

with high levels of fatty

substances in your blood

severe liver disease and your

liver function has not returned

to normal

cancer that may grow under the

influence of sex hormones (e.g.

of the breast or the genital

organs)

a benign or malignant liver

tumour

unexplained vaginal bleeding.

If any of these conditions

appear for the first time while

using Diane-35 ED, stop taking

it at once and tell your doctor.

In the meantime use non-

hormonal (barrier) methods of

contraception (such as

condoms or a diaphragm).

Do not take Diane-35 ED if you

are using another hormonal

contraceptive.

Do not take this medicine if you

are pregnant or think you

might be pregnant.

Do not breast-feed if you are

taking this medicine.

Do not give this medicine to a

child.

Do not take this medicine after

the expiry date printed on the

pack and blister.

The expiry

date is printed on the carton and

on each blister after “EXP” (e.g.

11 18 refers to November 2018).

The expiry date refers to the last

day of that month. If it has

expired return it to your

pharmacist for disposal.

Do not take this medicine if the

packaging is torn or shows

signs of tampering.

If the packaging is damaged,

return it to your pharmacist for

disposal.

If you are not sure whether you

should start taking this

medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have

allergies to any other

medicines, foods, preservatives

or dyes.

Tell your doctor if:

you smoke

you, or anyone in your

immediate family has had

blood clots in the legs (DVT),

or lungs (PE), a heart attack,

a stroke, breast cancer or high

cholesterol.

Tell your doctor if you have or

have had any of the following

medical conditions:

diabetes

high blood pressure

heart valve disorders or certain

heart rhythm disorders

migraine

cancer

polycystic ovary syndrome, a

hormonal condition which can

cause menstrual irregularity

and excess hair growth

hyperhomocysteinaemia, a

condition characterised by high

levels of the amino acid

homocysteine in the blood

severe high or low levels of

fats in the blood.

Ask your doctor to check if

you:

are overweight

have any hereditary or acquired

conditions that may make it

more likely for you to get

blood clots

1801 DIANE-35

ED CMI

have high cholesterol or

triglycerides

have liver disease

have jaundice (yellowing of the

skin) and/or pruritus (itching of

the skin) related to cholestasis

(condition in which the flow of

bile from the liver stops or

slows)

have gall bladder disease

have Crohn’s disease or

ulcerative colitis

(chronic inflammatory bowel

disease)

have systemic lupus

erythematosus (SLE – a disease

affecting the skin all over the

body)

have haemolytic uraemic

syndrome (HUS – a disorder of

blood coagulation causing failure

of the kidneys)

have sickle cell disease

have a condition that occurred

for the first time, or worsened

during pregnancy or previous

use of sex hormones (e.g.

hearing loss, a metabolic disease

called porphyria, a skin disease

called

herpes gestationis

neurological disease called

Sydenham’s chorea)

have chloasma (yellowish-brown

pigmentation patches on the

skin, particularly of the face) – if

so, avoid exposure to the sun or

ultraviolet radiation

have hereditary angio-oedema –

you should see your doctor

immediately if you experience

symptoms of angio-oedema,

such as swollen face, tongue

and/or pharynx and/or difficulty

swallowing, or hives together

with difficulty in breathing.

If any of the above conditions

appear for the first time, recur,

or worsen while taking Diane-35

ED, you should tell your doctor.

Diane-35 ED contains lactose.

If you have an intolerance to

some sugars, tell your doctor

before you start taking Diane-35

If you have not told your

doctor about any of the above,

tell him/her before you start

taking Diane-35 ED.

Taking other medicines

Tell your doctor or pharmacist

if you are taking any other

medicines, including any that

you get without a prescription

from your pharmacy,

supermarket or health food

shop.

Some medicines and Diane-35

ED may interfere with each

other. These include:

medicines used to treat

tuberculosis such as rifampicin,

rifabutin

medicines used to treat

epilepsy such as phenytoin,

primidone, barbiturates (e.g.

phenobarbitone),

carbamazepine, oxcarbazepine,

topiramate, felbamate,

lamotrigine

medicines used to treat HIV,

such as ritonavir or nevirapine

some medicines used to treat

Hepatitis C Virus (HCV) such

as boceprevir, telaprevir

macrolide antibiotics (e.g.

clarithromycin, erythromycin)

medicines used to treat fungal

infections, such

as ketoconazole and

griseofulvin

cyclosporin, an

immunosuppressant medicine

medicines used to treat high

blood pressure, chest pain

and/or irregular heartbeats such

as diltiazem, verapamil

etoricoxib, an anti-

inflammatory medicine used to

treat pain

tizanidine, melatonin or

midazolam which are

medicines used to relax the

body

theophylline, a medicine that

helps with breathing

herbal medicines containing St

John’s Wort

grapefruit juice.

These medicines may be affected

by Diane-35 ED, or may affect

how well it works. Your doctor

may need to alter the dose of

your medicine or prescribe a

different medicine.

Some medicines

can have an influence on the

blood levels of Diane-35 ED

can make it

less effective in

preventing pregnancy

can cause unexpected bleeding.

You may need to use additional

barrier methods of

contraception (such as

condoms or a diaphragm)

while you are taking any of

these medicines with Diane-35

ED and for some time after

stopping them.

Your doctor will be able to tell

you how long you will need to

use additional contraceptive

methods.

Your doctor and pharmacist have

more information on medicines

that you need to be careful with

or avoid while taking this

medicine.

HOW TO TAKE

DIANE-35 ED

Follow all directions given to

you by your doctor or

pharmacist carefully.

They may differ from the

information contained in this

leaflet.

1801 DIANE-35

ED CMI

If you do not understand the

instructions on the pack ask

your doctor or pharmacist for

help.

How to take it

Take one tablet daily at about the

same time every day. You must

take Diane-35 ED every day

regardless of how often you have

sex. This will also help you

remember when to take it.

Swallow the tablet whole with a

full glass of water.

It does not

matter if you take it before or after

food.

Each blister pack is marked with

the day of the week.

Take your first tablet from the

red area on the blister pack

corresponding to the day of the

week.

Follow the direction of the

arrows on the blister pack until

all the tablets have been taken.

A period should begin 2-3 days

after starting to take the white

inactive tablets (last row) and may

not have finished before the next

pack is started.

Always start a new blister pack

on the same day of the week as

your previous pack.

Taking Diane-35 ED for the

first time

If you are starting Diane-35 ED

after a natural cycle, and you have

not used a hormonal contraceptive

in the past month, start on the first

day of your period, i.e. on the first

day of your menstrual bleeding.

You must also use additional

barrier contraceptive

precautions (e.g. condoms or a

cap or diaphragm plus

spermicide) for the first 14 days

of tablet-taking when having

intercourse.

Your doctor will advise you

when to start if you:

are taking Diane-35 ED after

having a baby

have had a miscarriage or an

abortion.

Changing from another

contraceptive

Changing from a combined

oral contraceptive:

Start taking Diane-35 ED on the

day after taking the last active

tablet in your previous Pill pack.

Bleeding may not occur until the

end of the first pack of Diane-

35ED.

If you are not sure which were

the active/inactive tablets in

your previous Pill pack, ask

your doctor or pharmacist.

Your previous Pill pack may

have different colour tablets to

those of Diane-35 ED.

Changing from a vaginal ring:

Start taking Diane-35 ED on the

day of removal of the last vaginal

ring.

Changing from a progestogen-

only pill (‘minipill’):

Stop taking the minipill on any

day and start taking Diane-35 ED

at the same time the day after you

took your last minipill.

You must also use additional

barrier contraceptive

precautions (e.g. condoms or a

diaphragm) for the first 14

days of tablet-taking

when having intercourse.

Changing from a progestogen

only injection, implant or

intrauterine system (IUS):

Start taking Diane-35 ED when

your next injection is due, or on

the day that your implant or IUS

is removed.

You must also use additional

barrier contraceptive

precautions (e.g. condoms or a

diaphragm) for the first

14 days of tablet-taking

when having intercourse.

How long to take Diane-

35 ED

You may have to take Diane-35

ED for at least 6 months before

you see an improvement in your

condition. The length of

treatment depends on the severity

of the condition and how well it

responds to treatment.

You may be advised by your

doctor to stop Diane-35 ED 3 to

4 months after your symptoms

have completely resolved.

You should have regular check-

ups with your doctor to

determine how long to keep

taking Diane-35 ED.

Stopping Diane-35 ED

You can stop taking Diane-35

ED at any time.

It is possible that the original

condition may recur once Diane-

35 ED is stopped. Do not start

taking Diane-35 ED again

without seeing your doctor first.

If you do not wish to fall

pregnant, you should use

additional barrier contraceptive

precautions (e.g. condoms or a

diaphragm) when you stop taking

Diane-35 ED.

If you are considering becoming

pregnant, it is recommended that

you begin taking a vitamin

supplement containing folic acid.

It is best that you start taking

folic acid tablets before you stop

taking Diane-35 ED and not stop

1801 DIANE-35

ED CMI

until your doctor advises this. Ask

your doctor or pharmacist about

suitable supplements. It is both

safe and recommended that you

take folic acid during pregnancy.

If you forget to take Diane-

35 ED

If you miss a tablet and take the

missing tablet within 12 hours of

missing it, you should still be

protected against pregnancy.

If you are more than 12 hours late

follow these detailed instructions:

For Diane-35 ED to be most

effective, beige active tablets

need to be taken uninterrupted

for 7 days.

If you have been taking the beige

active tablets for 7 uninterrupted

days and miss a beige active

tablet, take the missed tablet as

soon as you remember, then go

back to taking your medicine as

you would normally, even if this

means taking two tablets in one

day at the same time.

You will

not need to use additional barrier

contraceptive precautions.

The chance of pregnancy after

missing a beige active tablet

depends on when you missed the

tablet.

There is a higher risk of

becoming pregnant if you miss a

beige tablet at the beginning or

end of a pack.

If after taking your missed tablet

you have less than 7 days of

beige active tablets left in a row,

you should finish the active

tablets in your pack but skip the

white inactive tablets and start a

new pack with the beige active

tablets corresponding to the

correct day of the week.

This is the best way to maintain

contraceptive protection. However,

you may not have a period until

the end of the beige active tablets

of the second pack. You may

have spotting or breakthrough

bleeding on tablet-taking days.

If you have been taking the

beige active tablets for less than

7 days and miss a beige active

tablet, take the missed tablet as

soon as you remember, then go

back to taking your medicine

as you would normally, even if

this means taking two tablets in

one day at the same time. In

addition, you must also use

additional barrier

contraceptive precautions (e.g.

condoms or a diaphragm) for

the next 7 days.

If you have had sexual

intercourse in the preceding 7

days, there is a possibility of

pregnancy and you may need

emergency contraception. You

should discuss this with your

doctor or pharmacist.

If you forget to take more than

one beige active tablet, seek

advice from your doctor or

pharmacist about what to do.

If you have had sexual

intercourse in the week before

missing your tablets, there is a

possibility of becoming pregnant.

You should discuss this with

your doctor or pharmacist.

If you miss a white inactive

tablet, you do not need to take

them later because they do not

contain any active ingredients.

However, it is important that you

discard the missed white tablet(s)

to make sure that the number of

days between taking active

tablets is not increased as this

would increase the risk of

pregnancy. Continue with the

next tablet at the usual time.

Please see the diagram at the

end of this leaflet entitled

“Summary of advice if you

missed an active tablet more

than 12 hours ago”.

Ask your doctor or pharmacist

to answer any questions you

may have.

If you take too much

(overdose)

Immediately telephone your

doctor or the Poisons

Information Centre (Australia:

13 11 26 or New Zealand: 0800

poison or 0800 764 766)

for advice, or go to the

Accident and Emergency

Department at your

nearest hospital, if you think

that you or anyone else may

have taken too much Diane-35

ED. Do this even if there are no

signs of discomfort or

poisoning.

You may need

medical attention.

If you take several beige active

tablets at once, you may feel sick

or vomit or may bleed from the

vagina. Even girls who have not

yet started to menstruate but have

accidentally taken this medicine

may experience such bleeding.

WHILE YOU ARE

TAKING DIANE-35 ED

Things you must do

Tell any other doctors, dentists,

and pharmacists who treat you

that you are taking this

medicine.

If you are about to have any

blood tests, tell your doctor

that you are taking this

medicine.

It may interfere with

the results of some tests.

Have regular check-ups with

your doctor.

When you are

taking Diane-35ED, your doctor

1801 DIANE-35

ED CMI

will tell you to return for regular

check-ups, including getting a

Cervical Screening Test. Your

doctor will advise how often you

need a Cervical Screening Test. A

Cervical Screening Test can detect

abnormal cells lining the cervix.

Sometimes abnormal cells can

progress to cancer.

If you are about to start on any

new medicine, remind your

doctor and pharmacist that you

are taking Diane-35 ED.

Stop taking Diane-35 ED and see

your doctor immediately or go to

the Emergency Department at

your nearest hospital if you

notice the following signs:

one-sided swelling of the leg

and/or foot or along a vein in the

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

sudden onset of unexplained

shortness of breath or rapid

breathing

sudden coughing or coughing up

of blood

sharp chest pain or sudden

severe pain in the chest which

may increase with deep

breathing

severe light headedness or

dizziness

rapid or irregular heartbeat

sudden pain, swelling and slight

blue discoloration of an

extremity

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, slurred speech

or aphasia; sudden partial or

complete loss of vision, double

vision, painless blurring of

vision which can progress to

loss of vision

sudden, severe or prolonged

headache with no known cause

loss of consciousness or

fainting with or without

seizure.

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

extreme weakness and anxiety

If you are going to have

surgery, tell the surgeon or

anaesthetist beforehand that

you are taking Diane-35 ED.

The risk of having blood clots is

temporarily increased as a result

of major surgery, any surgery to

the legs or pelvis, neurosurgery

or major trauma. In women who

take Diane-35 ED, the risk may

be higher.

In women at risk of prolonged

immobilisation (including major

surgery, any surgery to the legs

or pelvis, neurosurgery, or major

trauma), your doctor may tell you

to stop taking (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. Your doctor may

prescribe other treatment (e.g.

treatment for blood clots) if

Diane-35ED has not been

discontinued in advance.

Other risk factors for blood

clotting include temporary

immobilisation including air

travel of greater than 4 hours,

particularly in women with

other risk factors.

Consult your

doctor if you plan to air travel for

greater than 4 hours.

Consult your doctor if you

develop high blood pressure

while taking Diane-35 ED – you

may be told to stop taking it.

If you become pregnant while

taking this medicine, tell your

doctor immediately.

If you vomit within 3-4 hours

or have severe diarrhoea after

taking a beige active tablet, the

active ingredients may not have

been completely absorbed. This

is like missing a tablet. Follow

the advice for missed tablets.

If you have unexpected

bleeding and it continues,

becomes heavy, or occurs

again, tell your doctor.

When

taking these tablets for the first

few months, you can have

irregular vaginal bleeding

(spotting or breakthrough

bleeding) between your periods.

You may need to use sanitary

products, but continue to take

your tablets as normal. Irregular

vaginal bleeding usually stops

once your body has adjusted to

Diane-35 ED, usually after about

3 months.

If you have missed a period,

but you have taken all your

tablets, it is unlikely that

you are pregnant, as long as:

you have taken the beige active

tablets at the right time

you have not been taking

medicine(s) that may interfere

with Diane-35 ED.

you have not vomited or had

severe diarrhoea during this

cycle.

If this is so, continue to take

Diane-35 ED as usual. If you

1801 DIANE-35

ED CMI

have any concerns consult your

doctor or pharmacist.

If you miss your period twice in

a row, you may be pregnant even

if you have taken Diane-35 ED

correctly. Stop taking Diane-35

ED and seek advice from your

doctor. You must use a non-

hormonal method of

contraception, (such as condoms

or a diaphragm) until your

doctor rules out pregnancy.

Diane-35 ED will not protect you

from HIV-AIDS or any other

sexually transmitted infections

(STIs), such as chlamydia, genital

herpes, genital warts, gonorrhoea,

hepatitis B, human papilloma virus

and syphilis.

To protect yourself from STIs,

you will need to use additional

barrier contraceptives

(e.g. condoms).

Things you must not do

Do not take Diane-35 ED to treat

any other conditions, unless your

doctor tells you to.

Do not give your medicine to

anyone else.

Do not stop taking your

medicine or change the dosage

without checking with your

doctor.

You may become pregnant

if you are not using any other

contraceptive and you stop taking

Diane-35 ED, or do not take a

tablet every day.

SIDE EFFECTS

Tell your doctor or pharmacist

as soon as possible if you do not

feel well while you are taking

Diane-35 ED.

This medicine helps most women,

but it may have unwanted side

effects in some women.

All medicines can have side

effects. Sometimes they are

serious, most of the time they are

not. You may need medical

attention if you get some of the

side effects.

Do not be alarmed by the

following lists of side effects.

You may not experience any of

them.

Ask your doctor or pharmacist

to answer any questions you

may have.

The following list includes the

more common side effects of

Diane-35 ED. These are usually

mild and lessen with time.

If you notice any of the

following side effects and they

worry you, tell your doctor or

pharmacist:

nausea

stomach pain or discomfort

changes in weight

headache, including migraines

mood changes, including

depression

breast tenderness or pain.

The following list includes very

serious but rare side effects. You

may need urgent medical

attention or hospitalisation.

If you experience any of the

following, tell your doctor

immediately, or go to the

Emergency Department at

your nearest hospital:

pain in the chest, arm, or below

the breastbone

pain or discomfort that goes to

your back

breathlessness and/or difficulty

breathing

swelling, pain or tenderness of

one leg or along a vein in the

sudden weakness, numbness or

bad ‘pins and needles’ of the

face, arm or leg, especially on

one side of the body

sudden trouble walking,

dizziness, loss of balance or

coordination

severe, sudden stomach pains

a fainting attack or you

collapse

unusual headaches or

migraines that are worse than

usual

sudden problems with

speaking, seeing or

understanding what people are

saying to you.

The side effects listed above are

possible signs of a blood clot

(thrombosis).

jaundice (yellowing skin or

yellowing eyes)

you cough up blood

breast lumps

unexplained vaginal bleeding.

Tell your doctor or pharmacist

if you notice anything that is

making you feel unwell.

Other side effects not listed

above may also occur in some

people.

Blood clots and Diane-35

ED

Blood clots may block blood

vessels in your body. This type of

blood clot is also called

thrombosis.

Blood clots sometimes occur in

the deep veins of the legs. If a

blood clot breaks away from the

veins where it has formed, it may

reach and block the blood vessels

of the lungs, causing pulmonary

embolism.

Blood clots can also occur in the

blood vessels of the heart

(causing a heart attack) or the

brain (causing a stroke).

Blood clots are a rare occurrence

and can develop whether or not

you are taking Diane-35 ED.

1801 DIANE-35

ED CMI

They can also happen during

pregnancy. The risk of having

blood clots is higher in Diane-35

ED users than in non users, but not

as high as during pregnancy.

The risk of a blood clot is highest

during the first year of taking

Diane-35 ED for the first time, or

after having a break from Diane-35

ED for 4 weeks or more.

If you notice possible signs of a

blood clots, stop taking Diane-35

ED and consult your doctor

immediately.

To prevent

pregnancy, you must also use

additional barrier contraceptive

precautions (e.g. condoms or a

diaphragm).

If you are concerned about an

increased risk of blood clots

while on Diane-35 ED, speak to

your doctor.

Cancer and Diane-35 ED

Diane-35 ED contains a

progestogen and an oestrogen

hormone, and therefore works

similarly to the combined oral

contraceptive birth control pill, the

Pill.

Breast cancer has been diagnosed

slightly more often in women who

take the Pill than in women of the

same age who do not take the Pill.

This slight increase in the numbers

of breast cancer diagnoses

gradually disappears during the

course of the 10 years after women

stop taking the Pill.

It is not known whether the

difference is caused by the Pill. It

may be that these women were

examined more often, so that the

breast cancer was noticed earlier.

It is important that you check

your breasts regularly and

contact your doctor if you feel

any lumps.

In rare cases benign liver

tumours and, even more rarely,

malignant liver tumours have

been reported in users of the Pill.

These tumours may lead to

internal bleeding.

Contact your doctor

immediately if you have severe

pain in your abdomen.

Cervical cancer has been

reported to occur more often in

women who have been taking the

Pill for a long time. This finding

may not be caused by the Pill,

but may be related to sexual

behaviour and other factors.

AFTER TAKING

DIANE-35 ED

Storage

Keep your tablets in the blister

pack until it is time to take

them.

If you take the tablets out

of the pack they may not keep

well.

Keep your tablets in a cool dry

place where the temperature

stays below 25°C.

Do not store your tablets or

any other medicine in the

bathroom, near a sink, or on a

window-sill. Do not leave

medication in the car.

Heat and damp can destroy some

medicines.

Keep Diane-35 ED where

children cannot reach it.

A locked cupboard at least one-

and-a-half metres above the

ground is a good place to store

medicines.

Disposal

If your doctor tells you to stop

taking this medicine or the expiry

date has passed, ask your

pharmacist what to do with any

medicine that is left over.

Return any unused medicine to

your pharmacist.

PRODUCT

DESCRIPTION

What it looks like

Diane-35 ED active tablets are

beige and round.

Diane-35 ED inactive tablets are

white and round.

Diane-35 ED comes in a box

containing either 1 or 3 blister

packs. Each blister pack contains

21 beige active tablets and 7

white inactive tablets.

Ingredients

Each beige active tablet

contains:

Active ingredients:

2 mg of cyproterone acetate

35 micrograms of

ethinyloestradiol

Inactive ingredients:

lactose

maize starch

povidone

magnesium stearate

sucrose

macrogol 6000

calcium carbonate

purified talc

glycerol

titanium dioxide

iron oxide yellow

glycol montanate

purified water

Each white inactive tablet

contains:

lactose

maize starch

povidone

magnesium stearate

1801 DIANE-35

ED CMI

sucrose

macrogol 6000

calcium carbonate

glycol montanate

titanium dioxide

Tablets do not contain gluten.

Tablets also do not contain

tartrazine or any other azo dyes.

Supplier

Made in Germany for:

Bayer Australia Ltd.

ABN 22 000 138 714

875 Pacific Highway

Pymble NSW 2073

Bayer New Zealand Limited

3 Argus Place, Hillcrest,

North Shore

Auckland 0627

Australian Registration

Number

Diane-35 ED - AUST R 33647

Date of Preparation

JAN 2018

See TGA website

(www.ebs.tga.gov.au) for latest

Australian Consumer Medicine

Information.

See MEDSAFE website

(www.medsafe.govt.nz) for latest

New Zealand Consumer Medicine

Information.

® Registered Trademark of the

Bayer group, Germany

©Bayer Australia Ltd

All rights reserved.

Missed taking Diane-35

ED?

See the end of this leaflet

1801 DIANE-35

ED CMI

Summary of advice if you missed an active tablet more than 12 hours

ago.

Before missing

your tablet, did

you take beige

active tablets

for the previous

7 days?

No

Did you

have sex in

the 7 days

before

missing the

tablet?

No

Take the tablet missed AND use extra

barrier precaution for 7 days. If there are

fewer than 7 beige active tablets left in

the pack, finish the beige active tablets

and go straight to the beige active tablets

of the next pack. This means you skip the

white inactive tablets.

Yes

See your Doctor or Pharmacist for advice.

Yes

Does your

pack still

have 7

active

beige

tablets in a

row to

follow?

No

Take the tablet you missed AND complete

taking the beige active tablets. Skip

the white inactive tablets. Start your next

pack with beige active tablets.

Yes

Take the tablet you missed AND

complete the pack as normal.

180413 Diane-35 ED DS

NEW ZEALAND DATA SHEET

1.

PRODUCT NAME

DIANE

35 ED cyproterone acetate 2 mg, ethinylestradiol 35 micrograms, film coated

tablet

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each active beige tablet contains:

Cyproterone acetate

2 mg

Ethinylestradiol

35 micrograms

For full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

21 beige, round active tablets.

7 white, round placebo tablets.

All tablets have a lustrous sugar coating. Tablets cannot be halved.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

The treatment of signs of androgenisation in women, such as severe acne (involving

inflammation or nodularity or risk of scarring) where prolonged oral antibiotics or local

treatment alone has not been successful, or idiopathic hirsutism of mild to moderate

degree.

DIANE-35 ED will also provide effective oral contraception in this patient group. It

should

used

combination

with

other

hormonal

contraceptives

(see

CONTRAINDICATIONS).

If the hirsutism has only recently appeared or has lately intensified to a considerable

extent the cause (androgen-producing tumour or an adrenal-enzyme defect) must be

clarified by differential diagnosis.

180413 Diane-35 ED DS

4.2

Dose and method of administration

DIANE-35 ED is to be taken regularly in order to achieve the therapeutic efficacy and

the required contraceptive protection. Previously used hormonal contraception should

be discontinued. The dose regimen of DIANE-35 ED is similar to the usual regimen of

most combined oral contraceptives. Thus, the same administration rules must be

considered. Combined oral contraceptives, when taken correctly, have a failure rate of

approximately 1 % per year.

The irregular intake of DIANE-35 ED can lead to intermenstrual bleeding and could

deteriorate the therapeutic and contraceptive reliability.

Length of Use

Treatment will probably need to be continued for about 6 months and probably much

longer to gain an acceptable therapeutic effect, especially if Diane-35 ED is being used

for the treatment of excessive hair. The length of use depends on the severity of the

symptoms of androgenisation and their response to treatment. Acne and seborrhoea

usually respond sooner than hirsutism. The need to continue treatment should be

evaluated periodically by the treating doctor. It is possible that the original condition will

recur once treatment with Diane-35 ED is stopped.

Diane-35 ED should be withdrawn 3 to 4 cycles after the treated condition has

completely resolved. Repeat course of Diane-35 ED may be given if the androgen-

dependent condition(s) recur. In case of a restart of DIANE-35 ED (following a 4 week

or greater pill free interval), the increased risk of VTE should be considered (see

Warnings and Precautions).

How to take DIANE-35 ED

Tablets must be taken in the order directed on the package every day at about the

same time with some liquid as needed. One tablet is to be taken daily. Do not halve the

tablet. Each subsequent pack is started immediately following the previous pack.

Withdrawal bleeding should usually occur on day 2 to 3 after the last beige active tablet

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

How to start DIANE-35 ED

No preceding hormonal contraceptive use (in the past month)

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

menstrual bleeding). The first tablet should be selected from the red starting section of

the pack.

Additional non-hormonal contraceptive methods must be used for the first 14 days of

tablet-taking.

Changing from another Combined Oral Contraceptive (COC), vaginal ring,

or transdermal patch

The woman should start DIANE-35 ED in the red section on the day after the last active

tablet of her previous COC.

In case a vaginal ring or transdermal patch has been used, the woman should start

taking DIANE-35 ED preferably on the day of removal.

180413 Diane-35 ED DS

Changing from a Progestogen-only-method (Minipill, Injection, Implant) or

from a progestogen-releasing intrauterine system (IUS)

The woman may switch from the minipill on any day, from an implant or the IUS on the

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

of these cases she should be advised to additionally use a non-hormonal method of

contraception for the first 14 days of tablet-taking.

Following First-Trimester Abortion

The woman may start immediately. Additional non-hormonal contraceptive methods

are necessary for the first 14 days of tablet-taking.

Following Delivery or Second-Trimester Abortion

For breast-feeding woman, see PRECAUTIONS.

Women should be advised to start 21 to 28 days after delivery or second-trimester

abortion.

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

for the first 14 days of tablet taking. However, if intercourse has already occurred,

pregnancy should be excluded before the actual start of DIANE-35 ED use or the

woman has to wait for her first menstrual period.

Management of Missed Tablets

Errors in taking the white placebo tablets contained in DIANE-35 ED can be ignored.

However they should be discarded to avoid unintentionally prolonging the placebo

tablet phase. The following advice only refers to missed beige active tablets (rows 1 -3

of the blister):

If the woman is less than 12 hours late in taking any beige active tablet, contraceptive

protection

reduced.

woman

should

take

tablet

soon

remembers and should take further tablets at the usual time.

woman

more

than

12

hours

late

taking

beige

active

tablet,

contraceptive protection may be reduced.

There is a particularly high risk of pregnancy if tablets are missed at the beginning or

end of the week of the white placebo tablets. If tablets are missed in the first week of

taking active tablets and intercourse took place in the preceding 7 days the possibility

of pregnancy should be considered.

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

rules:

Tablet taking must never be discontinued for longer than 7 days

Seven days of uninterrupted tablet taking are required to attain adequate

suppression of the hypothalamic-pituitary-ovarian axis.

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

normal placebo-taking interval, the possibility of a pregnancy should be considered.

180413 Diane-35 ED DS

These rules form the basis of the instructions to patients provided in the package

insert.

Extra Contraceptive Precautions

When you need extra contraceptive precautions, either:

don’t have sex; or

use a cap plus spermicide; or

use a condom

Do not use the rhythm or temperature methods as extra contraceptive precautions.

This is because oral contraceptives alter the usual menstrual cycle changes such as

changes in temperature and cervical mucus.

The 7 Day Rule

Continue taking your pills.

You will not be protected from pregnancy until you have taken your daily

small beige active pill for the next 7 days in a row.

Use another method of contraception (extra contraceptive precautions) such

as condoms or do not have sexual intercourse for the next 7 days while

taking the next 7 small beige active pills.

If there are fewer than 7 small beige active pills left in the pack, finish the

small active pills and go straight on to the small beige active pills of the next

pack. This means that you miss out the large white placebo pills in the 28-

day pack. You may not have a period until the end of the next pack. This is

not harmful.

Advice in Case of Gastrointestinal Disturbances

In case of severe gastrointestinal disturbances, absorption may not be complete and

additional contraceptive measures should be taken. The advice concerning missed

tablets should be followed.

If vomiting occurs within 3-4 hours after tablet taking, absorption may not be complete.

If the woman does not want to change her normal tablet-taking schedule, she has to

take the extra active tablet(s) needed from another pack.

How to Shift Periods or How to Delay a Period

To delay a period the woman should continue with active tablets from another pack of

DIANE-35 ED without taking the white placebo tablets. The extension can be carried

on for as long as desired until the end of the second pack. During the extension the

woman may experience breakthrough bleeding or spotting.

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

current scheme, she can be advised to shorten her forthcoming tablet-free interval or

omit the white placebo tablets in DIANE-35 ED by as many days as she likes. The

shorter the interval, the higher the risk that she does not have a withdrawal bleed and

180413 Diane-35 ED DS

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

when delaying a period).

4.3

Contraindications

Preparations containing oestrogen/progestogen combinations should not be used in

the presence of any of the conditions listed below. Should any of the conditions appear

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

Presence or risk of venous thromboembolism (VTE) (see 4.4 Special warnings

and precautions for use)

Current VTE (on anticoagulants) or history of deep venous thrombosis

[DVT] or pulmonary embolism [PE]

Known hereditary or acquired predisposition for VTE, such as

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

protein C deficiency, protein S deficiency

Major surgery with prolonged immobilisation

A high risk of VTE due to the presence of multiple risk factors

Presence or risk of arterial thromboembolism (ATE) (see 4.4 Special warnings

and precautions for use)

Current ATE or history of ATE (e.g. myocardial infarction [MI] or stroke)

or prodromal condition (e.g. angina pectoris or transient ischaemic

attack [TIA])

Known hereditary or acquired predisposition for ATE, such as

hyperhomocysteinaemia and antiphospholipid-antibodies (e.g.

anticardiolipin-antibodies and lupus anticoagulant)

History of migraine with focal neurological symptoms

A high risk of ATE due to multiple risk factors or to the presence of one

serious risk factor such as:

diabetes mellitus with vascular symptoms

severe hypertension

severe dyslipoproteinaemia

Severe hepatic disease as long as liver function values have not returned to

normal

Use of direct-acting antiviral (DAA) medicinal products containing ombitasvir,

paritaprevir, or dasabuvir, and combinations of these (see INTERACTIONS)

Presence or history of liver tumours (benign or malignant)

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

organs or the breasts

Undiagnosed vaginal bleeding

Concomitant use with another hormonal contraceptive

Known or suspected pregnancy

Lactation

Hypersensitivity to any of the ingredients in DIANE-35 ED.

DIANE-35 ED is not for use in men.

180413 Diane-35 ED DS

4.4

Special warnings and precautions for use

Diane-35 ED is composed of the progestogen cyproterone acetate and the oestrogen

ethinylestradiol and is administered for 21 days of a monthly cycle. It has a similar

composition to that of a COC. The clinical

and epidemiological experience with

oestrogen/progestogen combinations like DIANE-35 ED is predominantly based on

COC. Therefore, the following warnings related to the use of COC apply also for

DIANE-35 ED.

If any of the conditions/risk factors mentioned below are present, the benefits of

DIANE-35 ED should be weighed against the possible risks for each individual woman

and discussed with the woman before she decides to start taking it. In the event of

aggravation, exacerbation or first appearance of any of these conditions or risk factors,

the woman should contact her doctor. The doctor should then decide whether DIANE-

35 ED should be discontinued.

Circulatory Disorders

Epidemiological studies have suggested an association between the use of COCs

containing ethinylestradiol and an increased risk of arterial and venous thrombotic and

thromboembolic diseases such as MI, stroke, DVT and PE. These events occur rarely

in average-risk women.

Risk of venous thromboembolism (VTE)

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

compared with no use. The woman should be advised that her VTE risk is highest in

the first ever year of use and that there is some evidence that the risk is increased

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

Data from a large, prospective 3-armed cohort study suggest that this increased risk is

mainly present during the first 3 months.

This study has shown that the frequency of VTE diagnosis range from 8 to 10 per

10,000 woman years in low oestrogen dose (< 50 µg ethinylestradiol) COC users. The

most recent data suggest that the frequency of VTE diagnosis is approximately 4.4 per

10,000 woman years in non-pregnant non-COC users, and range from 20 to 30 per

10,000 in pregnancy or the post-partum period.

Overall the risk of VTE in users of low oestrogen dose (< 50 µg ethinylestradiol) COCs

is two to threefold higher than for non-users of COCs who are not pregnant and

remains lower than the risk associated with pregnancy and delivery.

Epidemiological studies have shown that the incidence of VTE is 1.5 to 2 times higher

in users of DIANE-35 than in users of levonorgestrel-containing COCs.

The user group of DIANE-35 is likely to include patients that may have an inherently

increased

cardiovascular

risk

such

that

associated

with

polycystic

ovarian

syndrome.

An additional increase in VTE risk for CHCs containing ≥ 50 μg ethinylestradiol cannot

be excluded.

180413 Diane-35 ED DS

The increased risk of VTE during the postpartum period must be considered (see 4.2

Dose and method of administration, 4.6 Fertility, pregnancy and lactation).

VTE may be life threatening or may have a fatal outcome (in 1-2% of the cases).

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

venous

thromboembolic

complications

users

increase

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

factors (see list below).

DIANE-35 ED is contraindicated if a woman has multiple risk factors that put her at

high risk of venous thrombosis. 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.

When considering risk/benefit, the doctor should take into account that the adequate

treatment of a condition may reduce the associated risk of thrombosis.

Risk factors for VTE

Obesity (body mass index over 30 kg/m²). Risk increases substantially as BMI rises

Prolonged immobilisation, major surgery, any surgery to the legs or pelvis,

neurosurgery, or major trauma

Temporary immobilisation including air travel >4 hours can also be a risk factor for

VTE, particularly in women with other risk factors

Positive family history (VTE ever in a sibling or parent especially at a relatively

early age e.g. before 50)

Biochemical factors that may be indicative of hereditary or acquired predisposition

for VTE include Activated Protein C (APC) resistance (including Factor V Leiden),

antithrombin-III deficiency, protein C deficiency, protein S deficiency

Other medical conditions associated with VTE include:

Cancer

Systemic lupus erythematosus

Haemolytic uraemic syndrome

Chronic inflammatory bowel disease (e.g. Crohn’s disease or ulcerative colitis)

Sickle cell disease

Increasing age, particularly above 35 years

Smoking

In women at risk of prolonged immobilisation (including major surgery, any surgery to

the legs or pelvis, neurosurgery, or major trauma), it is advisable to discontinue use of

DIANE-35 ED (in the case of elective surgery at least four weeks in advance) and not

resume

until

weeks

after

complete

remobilisation.

Another

method

contraception

should

used

avoid

unintentional

pregnancy.

Antithrombotic

treatment should be considered if DIANE-35 ED has not been discontinued in

advance.

180413 Diane-35 ED DS

If a hereditary predisposition to VTE is suspected, the woman should be referred to a

specialist for advice before deciding about any CHC use.

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

thrombophlebitis in VTE.

Symptoms of VTE (DVT and PE)

Women should be informed of the symptoms of VTE and be advised to seek

urgent medical attention if VTE symptoms develop and to inform the healthcare

professional that she is taking a CHC.

Symptoms of 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 PE can include:

sudden onset of unexplained shortness of breath or rapid breathing

sudden coughing which may be associated with haemoptysis

sharp chest pain or sudden severe pain in the chest which may increase with

deep breathing

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

ATE (e.g. MI, angina pectoris, stroke or TIA). Arterial thromboembolic events may be

fatal.

The risk of arterial thromboembolic complications in CHC users increases in women

with risk factors. DIANE-35 is contraindicated if a woman has one serious or multiple

risk factors for ATE that puts her at high risk of arterial thrombosis. 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.

180413 Diane-35 ED DS

Risk factors for ATE

Increasing age, particularly above 35 years

Smoking

Hypertension

Obesity

Positive family history (ATE ever in a sibling or parent especially at relatively early

age e.g. below 50)

Biochemical factors that may be indicative of hereditary or acquired predisposition

for ATE include: hyperhomocysteinaemia and antiphospholipid antibodies (e.g.

anticardiolipin antibodies, and lupus anticoagulant)

Migraine

Other medical conditions associated with adverse vascular events:

Diabetes mellitus

Polycystic ovary syndrome

Hyperhomocysteinaemia

Valvular heart disease

Atrial fibrillation

Dyslipoproteinaemia

Systemic lupus erythematosus

Women should be advised not to smoke if they wish to use a CHC. Women over 35

years who continue to smoke should be strongly advised to use a different method of

contraception.

If a hereditary predisposition is suspected, the woman should be referred to a

specialist for advice before deciding about any CHC use.

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.

The user group of Diane-35 ED is likely to include patients that may

have an

inherently increased cardiovascular risk.

Symptoms of ATE

Women should be informed of the symptoms of ATE and be advised to seek

urgent medical attention if ATE symptoms develop and to inform the healthcare

professional that she is taking a CHC.

Symptoms of stroke 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, slurred speech or aphasia; sudden partial or complete loss of

vision; diplopia

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).

180413 Diane-35 ED DS

Symptoms of MI can include:

pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the

chest arm, or below the breastbone

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

feeling of being full, having indigestion or choking

sweating, nausea, vomiting or dizziness

extreme weakness, anxiety, or shortness of breath

rapid or irregular heartbeats

Tumours

The most important risk factor for cervical cancer is persistent human papillomavirus

(HPV) infection. Some epidemiological studies have indicated that long-term use of

COCs

further

contribute

this

increased

risk

there

continues

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.

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 taking COCs. The excess risk gradually disappears during the course of

the 10 years after cessation of COC use. Because breast cancer is rare in women

under 40 years of age, the excess number of breast cancer diagnoses in current and

recent COC users is small in relation to the overall risk of breast cancer. These studies

do not provide evidence for causation. The observed pattern of increased risk may be

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

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

less advanced clinically than the cancers diagnosed in never-users.

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

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

threatening intra-abdominal haemorrhages. A liver tumour should be considered in the

differential diagnosis when severe upper abdominal pain, liver enlargement or signs of

intra-abdominal haemorrhage, occur in women taking COCs.

Malignancies may be life threatening or have a fatal outcome.

Other Conditions

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

risk of pancreatitis when using COCs.

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

COCs,

clinically

relevant

increases

rare.

However,

sustained

clinically

significant hypertension develops during the use of a COC then it is prudent for the

doctor to withdraw the COC and treat the hypertension. Where considered appropriate,

resumed

normotensive

values

achieved

with

antihypertensive therapy.

following

conditions

have

been

reported

occur

deteriorate

with

both

pregnancy and COC use, but the evidence of an association with COC use is

inconclusive:

jaundice

and/or

pruritus

related

cholestasis;

gallstone

formation;

porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenham’s

chorea; herpes gestationis; otosclerosis-related hearing loss.

180413 Diane-35 ED DS

women

with

hereditary

angioedema

exogenous

oestrogens

induce

exacerbate symptoms of angioedema.

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

COC use until markers of liver function return to normal. Recurrence of cholestatic

jaundice

which

occurred

first

during

pregnancy

previous

steroids

necessitates the discontinuation of COCs.

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

tolerance, there is no evidence for a need to alter the therapeutic regimen in women

with

diabetes

taking

COCs.

However,

women

with

diabetes

should

carefully

observed while taking COCs.

Crohn’s disease and ulcerative colitis have been associated with COC use.

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

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

ultraviolet radiation whilst taking COCs.

Each beige active tablet contains 31.12 mg of lactose and each white placebo tablet

contains 48.25 mg of lactose. Patients with rare hereditary problems of galactose

intolerance, Lapp lactase deficiency or glucose-galactose malabsorption who are on a

lactose free diet should take this amount into consideration.

Medical Examination/Consultation

A complete medical history and physical examination should be taken prior to the

initiation or reinstitution DIANE-35 ED, guided by the contraindications and warnings.

This should be repeated periodically during the use of DIANE-35 ED. Periodic medical

assessment is also of importance because contraindications (e.g. a transient ischaemic

attack, etc.) or risk factors (e.g. a family history of venous or arterial thrombosis) may

appear for the first time during the use of DIANE-35 ED. The frequency and nature of

these assessments should be adapted to the individual woman but should generally

include special reference to blood pressure, breasts, abdomen and pelvic organs,

including cervical cytology, and relevant laboratory tests.

Sexually Transmitted Infections including HIV infections and AIDS

Women should be advised that preparations like DIANE-35 ED do not protect against

HIV infections (AIDS) and other sexually transmissible infections (STIs). The woman

should be advised that additional barrier contraceptive measures are needed to

prevent transmission of STIs.

Reduced Efficacy

The efficacy of DIANE-35 ED may be reduced in the event of missed beige active

tablets (see 4.2 Dose and method of administration – Management of Missed Tablets),

vomiting or diarrhoea during active tablet-taking (see 4.2

Dose

method

administration – Advice in Case of Gastrointestinal Disturbances) or concomitant

medication (see 4.5 Interaction with other medicines and other forms of interaction).

Reduced Cycle Control

With oestrogen/progestogen combinations, irregular bleeding (spotting or breakthrough

bleeding)

occur,

especially

during

first

months

use.

Therefore,

180413 Diane-35 ED DS

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

considered

adequate

diagnostic

measures

indicated to exclude malignancy or pregnancy. These may include curettage.

In some women withdrawal bleeding may not occur during the tablet-free interval. If the

COC has been taken according to the directions (see 4.2

Dose

method

administration), it is unlikely that the woman is pregnant. However, if the COC has not

been taken according to these directions prior to the first missed withdrawal bleed or if

two withdrawal bleeds are missed, pregnancy must be ruled out before COC use is

continued.

Children and Adolescents

Diane-35 ED is only indicated after menarche.

Use in the Elderly

Diane-35 ED is not indicated after menopause.

Patients with Hepatic Impairment

Diane-35 ED is contraindicated in women with severe hepatic diseases as long as liver

function values have not returned to normal (see CONTRAINDICATIONS).

Patients with Renal Impairment

Diane-35 ED has not been specifically studied in renally impaired patients.

4.5

Interaction with other medicines and other forms of interaction

Effects of other medicines on Diane-35 ED

Interactions can occur with medicines that induce microsomal enzymes 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 prescribed any of these medicines should temporarily use a barrier method in

addition to DIANE-35 ED 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 the hormone-containing beige coated tablets in the Diane-35

ED pack, the hormone-free white coated tablets should be omitted and the next pack

be started.

180413 Diane-35 ED DS

Substances increasing the clearance of Diane-35 ED (diminished efficacy

of Diane-35 ED by enzyme-induction) e.g.:

Phenytoin, barbiturates, primidone, carbamazepine, rifabutin, rifampicin and possibly

also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing St

John’s Wort (Hypericum perforatum).

Substances with variable effects on the clearance of Diane-35 ED, e.g.:

When

co-administered

with

COCs,

many

human

immunodeficiency

virus

(HIV)/

hepatitis C Virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase

inhibitors can increase or decrease plasma concentration of oestrogen or progestogen.

These changes may be clinically relevant in some cases.

Substances decreasing the clearance of COCs (enzyme inhibitors)

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

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

erythromycin), diltiazem and grapefruit juice can increase plasma concentrations of the

oestrogen or the progestogen 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 35 μg ethinylestradiol.

Influence of DIANE-35 ED on other Medication

Oestrogen/progestogen

combinations

like

DIANE-35

interfere

with

metabolism of other medicines. Accordingly, plasma and tissue concentrations may be

either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine).

clinical

studies,

administration

hormonal

contraceptive

containing

ethinylestradiol did not lead to any

increase or only to a weak increase in plasma

concentrations of CYP3A4 substrates (e.g. midazolam) while plasma concentrations of

CYP1A2

substrates

increase

weakly

(e.g.

theophylline)

moderately

(e.g.

melatonin and tizanidine).

Pharmacodynamic interactions

Co-administration of ethinylestradiol-containing medicinal products with direct-acting

antiviral (DAA) medicinal products containing ombitasvir, paritaprevir, or dasabuvir, and

combinations of these has been shown to be associated with increases in alanine

aminotransferase (ALT) levels to greater than 20 times the upper limit of normal in

healthy female subjects and HCV infected women (see CONTRAINDICATIONS).

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

identify potential interactions.

4.6

Fertility, pregnancy and lactation

Pregnancy

The administration of DIANE-35 ED is contraindicated during pregnancy.

If pregnancy occurs during treatment with DIANE-35 ED, further intake must be

stopped.

180413 Diane-35 ED DS

Breast-feeding

administration

DIANE-35

also

contraindicated

during

lactation.

Cyproterone acetate is transferred into the milk of lactating women. About 0.2% of the

maternal dose will reach the newborn via milk corresponding to a dose of about 1

mcg/kg.

During

established

lactation

0.02

daily

maternal

dose

ethinylestradiol could be transferred to the newborn via milk.

4.7

Effects on ability to drive and use machines

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

performed. No effects on ability to drive and use machines have been observed in

users of COCs.

4.8

Undesirable effects

The most serious undesirable effects associated with the use of COCs such as DIANE-

35 ED have been referred to in the Warnings and Precautions section. These include

venous and arterial thromboembolic disorders.

most

commonly

reported

adverse

reactions

with

Diane-35

nausea,

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

pain, breast tenderness. They occur in ≥ 1 % of users.

Other side effects that have been reported in users of DIANE-35 ED but for which the

association has been neither confirmed nor refuted are:

System Organ

Class

Common

(≥ 1/100 to <1/10)

Uncommon

(1/1,000 to

< 1/100)

Rare

(≥ 1/10,000 to

<1/1,000)

Eye disorders

Contact lens

intolerance

Gastrointestinal

disorders

Nausea,

Abdominal pain

Vomiting,

Diarrhoea

Immune system

disorders

Hypersensitivity

Investigations

Increased weight

Decreased weight

Metabolism and

nutrition disorders

Fluid retention

Nervous system

disorders

Headache

Migraine

Psychiatric

disorders

Depressed mood,

Altered mood

Decreased libido

Increased libido

Reproductive

Breast pain,

Breast

Vaginal

180413 Diane-35 ED DS

System Organ

Class

Common

(≥ 1/100 to <1/10)

Uncommon

(1/1,000 to

< 1/100)

Rare

(≥ 1/10,000 to

<1/1,000)

system and breast

disorders

Breast

tenderness

hypertrophy

discharge,

Breast discharge

Skin and

subcutaneous

tissue disorders

Rash, Urticaria

Erythema

nodosum,

Erythema

multiforme

Vascular Disorders

Thromboembolism

Laboratory Tests

The use of preparations like DIANE-35 ED may influence the results of certain

laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal

function,

plasma

levels

proteins,

e.g.

corticosteroid

binding

globulin

lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of

coagulation and fibrinolysis. Changes generally remain within the normal laboratory

range.

4.9

Overdose

There have been no reports of serious deleterious effects from overdose.

Symptoms that may occur in case of taking an overdose of beige active tablets are:

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

before their menarche, if they have accidentally taken Diane-35 ED.

There are no antidotes and further treatment should be symptomatic.

For advice on the management of overdose please contact the National Poisons

Centre on 0800 POISON (0800 764766).

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

The pilosebaceous unit comprises the sebaceous gland and the hair follicle and is an

androgen-sensitive skin component. Acne, seborrhoea, hirsutism and androgenic

alopecia are clinical conditions which result from aberrations of this target organ. The

clinical conditions may be caused by either an increased sensitivity to or by higher

plasma

levels

androgen.

Both

substances

contained

DIANE-35

beneficially influence the hyperandrogenic state. Cyproterone acetate is a competitive

antagonist on the androgen receptor, has inhibitory effects on the androgen-synthesis

in target cells and produces a decrease on the androgen blood concentration through

anti-gonadotropic

effect.

This

anti-gonadotropic

effect

amplified

ethinylestradiol

which

also

up-regulates

synthesis

Sex-Hormone-Binding-

180413 Diane-35 ED DS

Globulin (SHBG) in plasma. By this mechanism, it reduces free, biologically available

androgen in the circulation.

Post Authorisation Safety Studies (PASS) have shown that the frequency of VTE

diagnosis ranges from 7-10 per 10,000 woman-years in low-oestrogen-dose (< 50 μg

ethinylestradiol) COC users. The most recent data suggest that the frequency of VTE

diagnosis is approximately 4 per 10,000 woman-years in non-pregnant non-COC users

and ranges from 20 to 30 per 10,000 pregnant women or post-partum.Treatment with

DIANE-35 ED leads – usually after 3 to 4 months of therapy – to the healing of existing

acne

efflorescences.

excessive

greasiness

hair

skin

generally

disappears earlier. The loss of hair which frequently accompanies seborrhoea likewise

diminishes. In women experiencing mild forms of hirsutism and in particular, slightly

increased facial hair, results do not, however become apparent until after several

months of use.

The contraceptive effect of DIANE-35 ED is based on the interaction of various factors,

the most important of which are seen as the inhibition of ovulation and the changes in

the cervical secretion. As well as protection against pregnancy, oestrogen/progestogen

combinations have several positive properties which, next to the negative properties,

can be useful in deciding on the method of birth control. The cycle is more regular and

the menstruation is often less painful and bleeding is lighter. The latter may result in a

decrease in the occurrence of iron deficiency.

Apart from this, with the higher-dosed COCs containing 50 mcg ethinylestradiol, there

is evidence of a reduced risk of fibrocystic tumours of the breasts, ovarian cysts, pelvic

inflammatory disease, ectopic pregnancy and endometrial and ovarian cancer. This

may also apply to lower-dosed COCs.

5.2

Pharmacokinetic properties

Cyproterone acetate

Absorption

Orally administered cyproterone acetate is rapidly and completely absorbed. Peak

serum concentrations of 15 ng/mL are reached at about 1.6 hours after ingestion of a

single tablet. Bioavailability is approximately 88 %.

Distribution

Cyproterone acetate is almost exclusively bound to serum albumin. Only 3.5 – 4.0 %

of the total serum drug concentrations are present as free steroid. The ethinylestradiol-

induced increase in sex hormone binding globulin (SHBG) does not influence the

serum protein binding of cyproterone acetate. The apparent volume of distribution of

cyproterone acetate is approximately 986 ± 437 L.

Biotransformation

Cyproterone acetate is almost completely metabolised. The main metabolite in plasma

was identified as 15beta-OH-CPA which is formed via the cytochrome P450 enzyme

CYP3A4. The clearance rate from serum is about 3.6 mL/min/kg.

180413 Diane-35 ED DS

Elimination

Cyproterone acetate serum levels decrease in two phases which are characterised by

half-lives of about 0.8 h and about 2.3 – 3.3 days. Cyproterone acetate is partly

excreted in unchanged form. Its metabolites are excreted at a urinary to biliary ratio of

about 1:2. The half-life of metabolite excretion is approximately 1.8 days.

Steady-state conditions

Cyproterone acetate pharmacokinetics are not influenced by SHBG levels. Following

daily ingestion drug serum levels increase about 2.5-fold reaching steady-state

conditions during the second half of a treatment cycle.

Ethinylestradiol

Absorption

Orally administered ethinylestradiol is rapidly and completely absorbed. Peak serum

concentrations of approximately 71 pg/mL are reached at 1.6 hours. During absorption

and first-liver passage, ethinylestradiol is metabolised extensively, resulting in a mean

oral bioavailability of approximately 45 % with a large interindividual variation of

approximately 20-65 %.

Distribution

Ethinylestradiol is highly but non-specifically bound to serum albumin (approximately

98%) and induces an increase in the serum concentrations of SHBG. An apparent

volume of distribution of about 2.8 – 8.6 L/kg was determined.

Biotransformation

Ethinylestradiol is subject to pre-systemic conjugation in both small bowel mucosa and

the liver. Ethinylestradiol is primarily metabolised by aromatic hydroxylation but a wide

variety of hydroxylated and methylated metabolites are formed, and these are present

as free metabolites and as conjugates with glucuronides and sulphate. The clearance

rate was reported to be approximately 2.3-7 mL/min/kg.

Elimination

Ethinylestradiol serum levels decrease in two disposition phases characterised by half-

lives of about 1 h and 10-20 h, respectively. Unchanged drug is not excreted.

Ethinylestradiol metabolites are excreted at a urinary to biliary ratio of 4:6. The half-life

of metabolite excretion is approximately 1 day.

Steady-state conditions

Steady-state conditions are reached during the second half of a treatment cycle when

serum drug levels are higher by 60 % as compared to single dose.

5.3

Preclinical Safety Data

Ethinylestradiol

The toxicity profile of ethinylestradiol is well known. There are no preclinical data of

relevance to the prescriber that provide additional safety information to those already

included in other sections of the product information.

180413 Diane-35 ED DS

Cyproterone acetate

Preclinical data reveal no specific risk for humans based on conventional studies of

repeated dose toxicity.

No animal-experimental studies into a possible sensitising effect of ethinylestradiol and

cyproterone acetate have been carried out.

Embryotoxicity/Teratogenicity

Investigations into embryotoxic or teratogenic effects, using the combination of the two

active ingredients, showed no effects indicative of a general teratogenic effect following

treatment during organogenesis before development of the external genital organs.

Administration

cyproterone

acetate

during

hormone-sensitive

differentiation

phase of the genital organs (after approx. day 45 of pregnancy) could lead to signs of

feminisation in male foetuses following higher doses. Observation of male newborn

children who had been exposed in utero to cyproterone acetate did not show any signs

of feminisation. However, pregnancy is a contraindication for the use of DIANE-35 ED.

Genotoxicity and Carcinogenicity

Recognised first-line tests of genotoxicity gave negative results when conducted with

cyproterone acetate. However, further tests showed that cyproterone acetate was

capable of producing adducts with DNA (and an increase in DNA repair activity) in liver

cells from rats and monkeys and also in freshly isolated human hepatocytes, whereas

the DNA-adduct level in dog liver cells was extremely low.

This DNA-adduct formation occurred at exposures that might be expected to occur in

the recommended dose regimens for cyproterone acetate. In vivo consequences of

cyproterone acetate treatment were the increased incidence of focal, possibly pre-

neoplastic, liver lesions in which cellular enzymes were altered in female rats and an

increase of mutation frequency in transgenic rats carrying a bacterial gene as target for

mutations.

Clinical experience and well conducted epidemiological trials to-date would not support

an increased incidence of hepatic tumours in man. Nor did investigations into the

tumourigenicity of cyproterone acetate in rodents reveal any indication of a specific

tumourigenic potential. However, it must be borne in mind that sex steroids can

promote the growth of certain hormone-dependent tissues and tumours.

On the whole, the available findings do not raise any objection to the use of DIANE-35

ED in humans if used in accordance with the directions for the given indication and at

the recommended dose.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Lactose monohydrate

Maize starch

Povidone

Magnesium stearate

180413 Diane-35 ED DS

Sucrose

Macrogol 6000

Calcium carbonate

Purified talc

Glycerol

Titanium dioxide

Iron oxide yellow

Glycol montanate.

6.2

Incompatibilities

In the absence of compatibility studies, this medicine must not be mixed with other

medicines.

6.3

Shelf life

5 years

6.4

Special precautions for storage

Store below 25°C

6.5

Nature and contents of container

3 calendar-packs containing 28 tablets.

DIANE-35 ED tablets are contained in blister packs consisting of deep-drawn strips

made of polyvinyl chloride film with counter sealing foil made of aluminum with heat

sealable coating.

6.6

Special precautions for disposal

No special requirements.

Any unused medicine or waste material should be disposed of in accordance with local

requirements.

7.

MEDICINE SCHEDULE

Prescription Medicine

8.

SPONSOR

Bayer New Zealand Limited

3 Argus Place

Hillcrest

North Shore

Auckland 0627

180413 Diane-35 ED DS

Free Phone 0800 233 988

9.

DATE OF FIRST APPROVAL

31 March 1992

10.

DATE OF REVISION OF THE TEXT

13 April 2018

Summary table of changes

Section changed

Summary of new information

4.3 Contraindications

Updates regarding VTE and ATE

4.4 Special warnings and

precautions for use

Updates regarding the risk of VTE and ATE, including

explanation about the risk factors and symptoms of VTE

and ATE.

All sections

Minor editorial changes for consistency and update

cross-referencing within document.

Similar products

Search alerts related to this product

Share this information