KLIOFEM FILM-COATED TABLETS

Active substance: NORETHISTERONE ACETATE

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8-2850-01-001-2_v1-14:Layout 1

Regulatory Operations
Insert size: 800x100-004
Current: 5.0

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PACKAGE LEAFLET:
INFORMATION FOR THE USER

Improved DI28MKII

Kliofem® 2 mg/1 mg
film-coated tablets

Colour: PMS 280C

Estradiol/norethisterone acetate

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8
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Read this entire leaflet carefully
before you start taking this
medicine because it contains
important information for you.
• Keep this leaflet. You may need to
read it again.
• If you have further questions, ask
your doctor or pharmacist.
• This medicine has been prescribed
for you only. Do not pass it on to
others. It may harm them, even if
their signs of illness are the same
as yours.
• If you get any side effects, talk to
your doctor or pharmacist. This
includes any possible side effects
not listed in this leaflet. See section 4.
8-2850-01-001-2

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Code: 100% Direction
Length: Max. 29 mm (100%)

Page 1

What is in this leaflet:
1. What Kliofem® is and what it is
used for
2. What you need to know before
you take Kliofem®
3. How to take Kliofem®
4. Possible side effects
5. How to store Kliofem®
6. Contents of the pack and other
information
1. What Kliofem® is and what it is
used for
Kliofem® is a continuous combined
Hormone Replacement Therapy (HRT)
which is taken every day without
interruption. Kliofem® is used in postmenopausal women with at least
1 year since their last natural period.
The tablets contain 2 hormones:
estradiol 2 mg (an oestrogen identical
to the one made in the ovaries) and
norethisterone acetate 1 mg (a progestagen that acts in a similar way to
the body’s own hormone progesterone).
Kliofem® is used for:
Relief of symptoms occurring
after menopause
During the menopause, the amount
of the oestrogen produced by

a woman’s body drops. This can
cause symptoms such as hot face,
neck and chest (‘hot flushes’).
Kliofem® alleviates these symptoms
after menopause. You will only be
prescribed Kliofem® if your symptoms
seriously hinder your daily life.
Prevention of osteoporosis
After the menopause some women
may develop fragile bones (osteoporosis). You should discuss all
available options with your doctor.
If you are at an increased risk of
fractures due to osteoporosis and
other medicines are not suitable for
you, you can use Kliofem® to prevent
osteoporosis after menopause.
Kliofem® is prescribed for women
who have not had their womb
removed, and whose periods stopped
more than a year ago.
The experience of treating women
older than 65 years is limited.
2. What you need to know before
you take Kliofem®
Medical history and regular
check-ups
The use of HRT carries risks which
need to be considered when deciding

whether to start taking it, or whether
to carry on taking it.
The experience in treating women
with a premature menopause (due to
ovarian failure or surgery) is limited. If
you have a premature menopause the
risks of using HRT may be different.
Please talk to your doctor.
Before you start (or restart) HRT, your
doctor will ask about your own and
your family’s medical history. Your
doctor may decide to perform a physical examination. This may include an
examination of your breasts and/or an
internal examination, if necessary.
Once you have started on Kliofem®
you should see your doctor for regular check-ups (at least once a year).
At these check-ups, discuss with your
doctor the benefits and risks of
continuing with Kliofem®.
Go for regular breast screening, as
recommended by your doctor.
Do not take Kliofem®
If any of the following apply to you.
If you are not sure about any of the
points below, talk to your doctor
before taking Kliofem®.

Do not take Kliofem®:
• If you have, have had or suspect
having breast cancer.
• If you have, have had or suspect
having cancer of the womb
lining (endometrial cancer), or any
other oestrogen dependent cancer.
• If you have any abnormal vaginal
bleeding.
• If you have excessive thickening
of the womb lining (endometrial
hyperplasia) that is not being
treated.
• If you have or have ever had
a blood clot in a vein (venous
thromboembolism), such as in the
legs (deep venous thrombosis) or
the lungs (pulmonary embolism).
• If you have a blood clotting
disorder (such as protein C,
protein S, or antithrombin deficiency).
• If you have or previously have had
a disease caused by blood clots in
the arteries, such as a heart
attack, stroke or angina.
• If you have or have ever had a liver
disease and your liver function
tests have not returned to normal.

• If you have a rare blood problem
called ‘porphyria’ which is passed
down in families (inherited).
• If you are allergic (hypersensitive) to
estradiol, norethisterone acetate
or any of the other ingredients of
Kliofem® (listed in section 6 Contents
of the pack and other information).
Warnings and precautions
Tell your doctor if you have ever had
any of the following problems, before
you start the treatment, as these may
return or become worse during treatment with Kliofem®. If so, you should
see your doctor more often for
check-ups:
• fibroids inside your womb.
• growth of the womb lining outside
your womb (endometriosis) or a
history of excessive growth of the
womb lining (endometrial
hyperplasia).
• increased risk of developing blood
clots (see Blood clots in a vein
(venous thromboembolism)).
• increased risk of getting
a oestrogen-sensitive cancer

(such as having a mother, sister or
grandmother who has had breast
cancer).
• high blood pressure.
• a liver disorder, such as a benign
liver tumour.
• diabetes.
• gallstones.
• migraine or severe headaches.
• a disease of the immune system
that affects many organs of the
body (systemic lupus
erythematosus, SLE).
• epilepsy.
• asthma.
• a disease affecting the eardrum
and hearing (otosclerosis).
• a very high level of fat in your
blood (triglycerides).
• fluid retention due to cardiac or
kidney problems.
• lactose intolerance.
Stop taking Kliofem® and see
a doctor immediately
If you notice any of the following
when taking HRT:

• any of the conditions mentioned in
the Do not take Kliofem® section.
• yellowing of your skin or the
whites of your eyes (jaundice).
These may be signs of a liver disease.
• a large rise in your blood pressure
(symptoms may be headache,
tiredness, dizziness).
• migraine-like headaches which
happen for the first time.
• if you become pregnant.
• if you notice signs of a blood clot,
such as:
painful swelling and
redness of the legs.
sudden chest pain.
difficulty in breathing.
For more information, see Blood clots
in a vein (venous thromboembolism)
Note: Kliofem® is not a contraceptive.
If it is less than 12 months since your
last menstrual period or you are
under 50 years old, you may still need
to use additional contraception to
prevent pregnancy. Speak to your
doctor for advice.

HRT and cancer
Excessive thickening of the lining
of the womb (endometrial
hyperplasia) and cancer of the
lining of the womb (endometrial
cancer)
Taking oestrogen-only HRT will increase
the risk of excessive thickening of the
lining of the womb (endometrial
hyperplasia) and cancer of the womb
lining (endometrial cancer).
The progestogen in Kliofem® protects
you from this extra risk.
Compare
In women who still have a womb
and who are not taking HRT, on
average, 5 in 1,000 will be
diagnosed with endometrial cancer
between the ages of 50 and 65.
For women aged 50 to 65 who still
have a womb and who take
oestrogen-only HRT, between
10 and 60 women in 1,000 will be
diagnosed with endometrial cancer
(i.e. between 5 and 55 extra cases),
depending on the dose and for how
long it is taken.

Irregular bleeding
You may have irregular bleeding or
drops of blood (spotting) during
the first 3-6 months of taking
Kliofem®. However, if the irregular
bleeding:
• carries on for more than the first
6 months
• starts after you have been taking
Kliofem® for more than 6 months
• carries on after you have stopped
taking Kliofem®
see your doctor as soon as
possible.
Breast cancer
Evidence suggests that taking
combined oestrogen-progestogen
and possibly also oestrogen-only
HRT increases the risk of breast
cancer. The extra risk depends on
how long you take HRT. The additional
risk becomes clear within a few years.
However, it returns to normal within
a few years (at most 5) after stopping
treatment.

Code start
Code: 100% Direction
Length: Max. 29 mm (100%)

Compare
Women aged 50 to 79 who are not
taking HRT, on average, 9 to 17 in
1,000 will be diagnosed with breast
cancer over a 5-year period. For
women aged 50 to 79 who are
taking oestrogen-progestogen HRT
over 5 years, there will be 13 to
23 cases in 1,000 users (i.e. an
extra 4 to 6 cases).
• Regularly check your breasts.
See your doctor if you notice
any changes such as:

dimpling of the skin

changes in the nipple

any lumps you can see or
feel
Ovarian cancer
Ovarian cancer is rare. A slightly
increased risk of ovarian cancer has
been reported in women taking
HRT for at least 5 to 10 years.

Compare
Women aged 50 to 69 who are not
taking HRT, on average about
2 women in 1,000 will be diagnosed
with ovarian cancer over a 5-year
period. For women who have been
taking HRT for 5 years, there will be
between 2 and 3 cases per
1,000 users (i.e. up to 1 extra case).
Effect of HRT on heart and
circulation
Blood clots in a vein (venous
thromboembolism)
The risk of blood clots in the veins
is about 1.3 to 3 times higher in HRT
users than in non-users, especially
during the first year of taking it.
Blood clots can be serious, and if one
travels to the lungs, it can cause chest
pain, breathlessness, fainting or even
death.
You are more likely to get a blood
clot in your veins as you get older and
if any of the following apply to you.
Inform your doctor if any of these
situations apply to you:

• you are unable to walk for a long
time because of major surgery,
injury or illness (see also section 3,
If you need to have surgery)
• you are seriously overweight
(BMI >30 kg/m2)
• you have any blood clotting
problem that needs long-term
treatment with a medicine used to
prevent blood clots
• if any of your close relatives has
ever had a blood clot in the leg,
lung or another organ
• you have systemic lupus
erythematosus (SLE)
• you have cancer.
For signs of a blood clot, see Stop
taking Kliofem® and see a doctor
immediately.
Compare
Looking at women in their 50s who
are not taking HRT, on average, over
a 5-year period, 4 to 7 in 1,000 would
be expected to get a blood clot in
a vein.
For women in their 50s who have
been taking oestrogen-progestogen
HRT for over 5 years, there will be
9 to 12 cases in 1,000 users
(i.e. an extra 5 cases).

Heart disease (heart attack)
There is no evidence that HRT will
prevent a heart attack. Women over
the age of 60 years who use oestrogen-progestogen HRT are slightly
more likely to develop heart disease
than those not taking any HRT.
Stroke
The risk of getting stroke is about
1.5 times higher in HRT users than in
non-users. The number of extra cases
of stroke due to use of HRT will
increase with age.
Compare
Looking at women in their 50s who
are not taking HRT, on average, 8 in
1,000 would be expected to have
a stroke over a 5-year period. For
women in their 50s who are taking
HRT, there will be 11 cases in
1,000 users, over 5 years
(i.e. an extra 3 cases).
Other conditions
HRT will not prevent memory loss.
There is some evidence of a higher
risk of memory loss in women who
start using HRT after the age of 65.
Speak to your doctor for advice.

Using other medicines
Some medicines may interfere with
the effect of Kliofem®. This might
lead to irregular bleeding. This applies
to the following medicines:
• Medicines for epilepsy (such as
phenobarbital, phenytoin and
carbamazepine)
• Medicines for tuberculosis (such
as rifampicin and rifabutin)
• Medicines for HIV infection
(such as nevirapine, efavirenz,
ritonavir and nelfinavir)
• Herbal remedies containing
St John’s Wort (Hypericum
perforatum).
Other medicines may increase the
effects of Kliofem®:
• Medicines containing
ketoconazole (a fungicide).
Kliofem® may have an impact on
a concomitant treatment with
cyclosporine.
Please tell your doctor or
pharmacist, if you are taking or have
recently taken any other medicines
including medicines obtained without
a prescription, herbal medicines or
other natural products.

Taking Kliofem® with food and
drink
The tablets can be taken with or
without food and drink.
Laboratory tests
If you need a blood test, tell your
doctor or the laboratory staff that you
are taking Kliofem®, because this
medicine can affect the results of
some tests.
Pregnancy and breast-feeding
Pregnancy: Kliofem® is for use in
postmenopausal women only. If you
become pregnant, stop taking
Kliofem® and contact your doctor.
Breast-feeding: You should not take
Kliofem® if you are breast-feeding.
Driving and using machines
Kliofem® has no known effect on the
ability to drive or use machines.
Important information about
some of the ingredients in
Kliofem®
Kliofem® contains lactose
monohydrate. If you have an intolerance to some sugars, contact your
doctor before taking Kliofem®.

8-2850-01-001-2_v1-14:Layout 1

3. How to take Kliofem®
Always take this medicine exactly as
your doctor has told you. Check with
your doctor or pharmacist if you are
unsure.
Take one tablet once a day, at
about the same time each day.
Take the tablet with a glass of water.
Take a tablet every day without
stopping. After you have used all
28 tablets in a calendar pack, go
straight to using the next pack.
For further information on the use of
the calendar pack, see USER
INSTRUCTIONS at the end of the
package leaflet.
You may start treatment with
Kliofem® on any convenient day.
However, if you are switching from
an HRT product when you have
monthly bleeding, start your treatment straight after the bleeding has
ended.
Your doctor should aim to prescribe
the lowest dose to treat your symptoms for as short as necessary. Speak
to your doctor if you think this dose is
too strong or not strong enough.

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Page 2

If you take more Kliofem® than
you should
If you have taken more Kliofem® than
you should, talk to your doctor or
pharmacist. An overdose of Kliofem®
could make you feel sick or vomit.
If you forget to take Kliofem®
If you forget to take your tablet at
the usual time, take it within the next
12 hours. If more than 12 hours have
gone by, start again as normal the
next day. Do not take a double dose
to make up for a forgotten tablet.
Forgetting a dose may increase the
likelihood of breakthrough bleeding
and spotting if you still have your
womb.
If you stop taking Kliofem®
If you would like to stop taking
Kliofem®, talk to your doctor first.
Your doctor will explain the effects of
stopping treatment and discuss other
possibilities with you.
If you need to have surgery
If you are going to have surgery, tell
the surgeon that you are taking
Kliofem®. You may need to stop
taking Kliofem® about 4 to 6 weeks

before the operation to reduce the
risk of a blood clot (see section 2,
Blood clots in a vein (venous thromboembolism)). Ask your doctor when
you can start taking Kliofem® again.
If you have any further questions on
the use of this medicine, ask your
doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can
have side effects, although not
everybody gets them.
The following diseases are reported
more often in women using HRT
compared to women not using HRT:
• breast cancer
• abnormal growth or cancer of the
lining of the womb (endometrial
hyperplasia or cancer)
• ovarian cancer
• blood clots in the veins of the legs
or lungs (venous thromboembolism)
• heart disease
• stroke
• probable memory loss if HRT is
started over the age of 65
For more information about these side
effects, see Section 2, What you need
to know before you take Kliofem®.

Hypersensitivity/allergy
(uncommon side effect – affects
1 to 10 users in 1,000)
Though it is an uncommon event,
hypersensitivity/allergy may occur.
Signs of hypersensitivity/allergy may
include one or more of the following
symptoms: hives, itching, swelling,
difficulty in breathing, low blood
pressure (paleness and coldness of
skin, rapid heartbeat), feeling dizzy,
sweating, which could be signs of
anaphylactic reaction/shock. If one of
the mentioned symptoms appears,
stop taking Kliofem® and seek
immediate medical help.
Very common side effects
• Breast pain or breast tenderness
• Vaginal bleeding.
Common side effects
• Headache
• Weight gain caused by fluid
retention
• Vaginal inflammation
• Migraine, new or worse than
before
• Vaginal infection with a fungus
• Depression, new or worse than
before

• Nausea
• Abdominal pain, swelling or
discomfort
• Enlargement or swelling of the
breasts (breast oedema)
• Back pain
• Leg cramps
• Uterine fibroid (benign tumour),
aggravation, occurrence or
recurrence
• Swelling of arms and legs
(peripheral oedema)
• Weight increase.
Uncommon side effects
• Bloating or flatulence
• Acne
• Hair loss (alopecia)
• Abnormal (male pattern) hair
growth
• Itching or hives (urticaria)
• Inflammation of a vein (superficial
thrombophlebitis)
• Drug ineffective
• Allergic reaction
• Nervousness.
Rare side effects
• Blood clots in the blood vessels of
the legs or the lungs (deep vein
thrombosis, lung embolism).

Very rare side effects
• Cancer of the lining of the womb
(endometrial cancer)
• Excessive growth of the lining of
the womb (endometrial
hyperplasia)
• Increase in blood pressure or
worsening of high blood pressure
• Gallbladder disease, gallstones
occurrence/recurrence or
aggravated
• Excessive secretion of sebum, skin
eruption
• Acute or recurring attack of
oedema (angioneurotic oedema)
• Insomnia, dizziness, anxiety
• Change in sexual desire
• Visual disturbances
• Weight decreased
• Vomiting
• Heartburn
• Vaginal and genital itching
• Heart attack and stroke.
The frequency of possible side effects
listed below is defined using the
following convention:
Very common (affects more
than 1 user in 10)
Common (affects 1 to 10 users
in 100)

Uncommon (affects 1 to 10 users in
1,000)
Rare (affects 1 to 10 users in 10,000)
Very rare (affects less than 1 user in
10,000)
Not known (frequency cannot be
estimated from the available data).
Other side effects of combined HRT
The following side effects have been
reported with other HRTs:
• various skin disorders:
discoloration of the skin
especially of the face or
neck known as ‘pregnancy
patches’ (chloasma)
painful reddish skin
nodules (erythema
nodosum)
rash with target-shaped
reddening or sores
(erythema multiforme)
Reporting of side effects
If you get any side effects, talk to
your doctor or pharmacist. This
includes any possible side effects not
listed in this leaflet. You can also
report side effects directly via the
Yellow Card Scheme Website:
www.mhra.gov.uk/yellowcard .

By reporting side effects you can help
provide more information on the
safety of this medicine.
5. How to store Kliofem®
Keep this medicine out of the sight
and reach of children.
Do not use this medicine after the
expiry date, which is stated on the
label and carton.
Do not refrigerate.
Keep the container in the outer
carton in order to protect it from light.
Do not throw away any medicines via
wastewater or household waste. Ask
your pharmacist how to throw away
medicines you no longer use. These
measures will help protect the
environment.
6. Contents of the pack and other
information
What Kliofem® contains
The active substances are estradiol
2 mg (as estradiol hemihydrate) and
norethisterone acetate 1 mg.
The other ingredients are: lactose
monohydrate, maize starch, hydroxypropylcellulose, talc and magnesium
stearate.

The film-coating contains:
hypromellose, triacetin and talc.
What Kliofem® looks like and
contents of the pack
The film-coated tablets are white,
round with a diameter of 6 mm.
The tablets are engraved NOVO 281.
Pack sizes available:
• 1×28 film-coated tablets
• 3×28 film-coated tablets
Not all pack sizes may be marketed.
Marketing authorisation holder
Novo Nordisk Limited
Broadfield Park, Brighton Road,
Crawley, West Sussex RH11 9RT
Manufacturer
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd, Denmark
This leaflet was last approved:
12/2013

USER INSTRUCTIONS
How to use the calendar pack
1. Set the day reminder
Turn the inner disc to set the day
of the week opposite the little
plastic tab.

2. Take the first day’s tablet
Break the plastic tab and tip out the
first tablet.

3. Move the dial every day
On the next day, simply move the
transparent dial clockwise 1 space as
indicated by the arrow. Tip out the
next tablet. Remember to take only
1 tablet once a day.
You can only turn the transparent
dial after the tablet in the
opening has been removed.
Kliofem®is a trademark owned by
Novo Nordisk FemCare AG,
Switzerland
© 2013
Novo Nordisk A/S

8-2850-01-201-2_v1-3:Layout 1

RA Labelling & IT
8-2850-01-201-2

Label Ø: 44-201
Current: 4.0
Improved Di28MkII
Colour:
PMS 280C + PMS 494C

EXP:
Batch:

Kliofem® 2 mg/1 mg
film-coated tablets
Estradiol/norethisterone acetate
28 film-coated tablets
Excipients include lactose monohydrate.
See leaflet for further information
Oral use
Product Licence Holder:

Novo Nordisk Limited
Broadfield Park
Brighton Road, Crawley
West Sussex RH11 9RT
Manufacturer:

Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark

2013-11-26

9:48 AM

Page 1

8-2850-01-301-3_v1-6:Layout 1

2013-11-27

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Page 1

RA Labelling & IT
Carton: 22-241-19-306
Current: 5.0

Lacquerform: 30023-1
Lacquer free area:

Estradiol/norethisterone acetate
3×28 film-coated tablets

Braille No.: 2851-01-1
Placement: Panel 1
(Front)

22-241-19

film-coated tablets

Kliofem® 2 mg/1 mg

Colour:
PMS 280C + PMS 494C

Estradiol/
norethisterone acetate
3×28 film-coated tablets

PL 03132/0080

Product licence holder:

Novo Nordisk Limited
Broadfield Park
Brighton Road
Crawley
West Sussex RH11 9RT
Manufactured by:

Kliofem® 2 mg/1 mg

film-coated tablets

film-coated tablets

POM

Kliofem® 2 mg/1 mg
Estradiol/norethisterone acetate
3×28 film-coated tablets

Code end
Code: 200% Direction
Length: Max. 23 mm (100%)

Oral use. Do not refrigerate
Keep the container in the outer carton in
order to protect it from light
Keep out of the sight and reach of
children
Read the package leaflet before use
Return unused product to the pharmacy
Each film-coated tablet contains:
Estradiol 2 mg (as estradiol hemihydrate),
norethisterone acetate 1 mg.
Excipients include lactose monohydrate.
See leaflet for further information

Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark

8-2850-01-301-3
EXP/
Batch:

8
1
2 7

Code centre line
Code: 100% Direction

8-2850-01-301-3_v1-6:Layout 1

2013-11-27

1:05 PM

Page 2

RA Labelling & IT
Carton: 22-241-19-306
Current: 5.0

Braille No.: 2851-01-1
Placement: Panel 1
(Front)

kliofem

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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