KLIOVANCE

Active substance: NORETHISTERONE ACETATE

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includes any possible side effects
not listed in this leaflet. See
section 4.
Package leaflet:
Information for the user

Kliovance®
1 mg/0.5 mg film-coated tablets
Estradiol/norethisterone acetate
Read all of this 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 any 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

What is in this leaflet
1. What Kliovance® is and what it is
used for
2. What you need to know before
you take Kliovance®
3. How to take Kliovance®
4. Possible side effects
5. How to store Kliovance®
6. Contents of the pack and other
information
1. What Kliovance® is and what
it is used for
Kliovance® is a continuous
combined Hormone Replacement
Therapy (HRT). It contains two
types of female hormones, an
oestrogen and a progestagen.
Kliovance® is used in
postmenopausal women with at
least 1 year since their last natural
period.

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Insert size: 999x100-006
Current: 2.0

Improved DI28MKII
Colour: PMS 280C

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Kliovance® is used for:
Relief of symptoms occurring
after menopause
During the menopause, the
amount of oestrogen produced by
a woman’s body drops. This can
cause symptoms such as hot face,
neck and chest (‘hot flushes’).
Kliovance® alleviates these
symptoms after menopause. You
will only be prescribed Kliovance® 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 Kliovance® to
prevent osteoporosis after
menopause.

Kliovance® is prescribed for women
who have not had their womb
removed, and whose periods
stopped more than a year ago.
There is only limited experience of
treating women older than
65 years with Kliovance®.
2. What you need to know
before you take Kliovance®
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 Kliovance®
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 Kliovance®.
Go for regular breast screening, as
recommended by your doctor.
Do not take Kliovance®
If any of the following applies to
you. If you are not sure about any
of the points below, talk to your
doctor before taking Kliovance®.
Do not take Kliovance®:
• If you have, have had or suspect
having breast cancer.
• If you have, or have had cancer
which is sensitive to
oestrogens, such as cancer of
the womb lining (endometrium),
or if you are suspected of
having it.

• If you have any unexplained
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
(thrombosis), 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 Kliovance® (listed
in section 6 ‘Contents of the
pack and other information’).
If any of the above conditions appear
for the first time while taking
Kliovance®, stop taking it at once
and consult your doctor immediately.
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 Kliovance®.
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 (thrombosis)’)

• 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 Kliovance® 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 Kliovance®’
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 (thrombosis)’.

Note: Kliovance® 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 progestagen in Kliovance®
protects you from this extra risk.

Irregular bleeding
You may have irregular bleeding or
drops of blood (spotting) during the
first 3-6 months of taking Kliovance®.
However, if the irregular bleeding:
• carries on for more than the first
6 months
• starts after you have been taking
Kliovance® for more than
6 months
• carries on after you have stopped
taking Kliovance®
see your doctor as soon as possible.
Breast cancer
Evidence suggests that taking
combined oestrogen-progestagen
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.

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-progestagen
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.
Women aged 50 to 69 who are not
taking HRT, on average, about
2 women in 1,000 will be diagnosed

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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
(thrombosis)
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 applies
to you. Inform your doctor if any of
these situations applies 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 Kliovance® 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-progestagen
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-progestagen 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 Kliovance®. 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 infections
(such as nevirapine, efavirenz,
ritonavir and nelfinavir)
• Herbal remedies containing
St John’s Wort (Hypericum
perforatum)

• Medicines for hepatitis C
infections (such as telaprevir).
Other medicines may increase the
effects of Kliovance®:
• Medicines containing
ketoconazole (a fungicide).
Kliovance® 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.
Laboratory tests
If you need a blood test, tell your
doctor or the laboratory staff that
you are taking Kliovance®, because
this medicine can affect the results
of some tests.
Taking Kliovance® with food
and drink
The tablets can be taken with or
without food and drink.

Pregnancy and breast-feeding
Pregnancy: Kliovance® is for use in
postmenopausal women only. If
you become pregnant, stop taking
Kliovance® and contact your doctor.
Breast-feeding: You should
not take Kliovance® if you are
breast-feeding.
Driving and using machines
Kliovance® has no known effect on
the ability to drive or use machines.
Important information about
some of the ingredients in
Kliovance®:
Kliovance® contains lactose
monohydrate. If you have an
intolerance to some sugars, contact
your doctor before taking
Kliovance®.
3. How to take Kliovance®
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.
Once you have finished all the
28 tablets in the pack, start a new
pack continuing the treatment
without interruption.
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
Kliovance® 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 symptom for as short as necessary. Speak
to your doctor if you think this dose
is too strong or not strong enough.
If you take more Kliovance®
than you should
If you have taken more Kliovance®
than you should, talk to a doctor or

pharmacist. An overdose of
Kliovance® could make you feel
sick or vomit.
If you forget to take Kliovance®
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, skip the
missed dose and 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 Kliovance®
If you would like to stop taking
Kliovance®, talk to your doctor first.
Your doctor will explain the effects
of stopping treatment and discuss
other possibilities with you.
If you have any further questions
on the use of this medicine, ask
your doctor or pharmacist.

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If you need to have surgery
If you are going to have surgery,
tell the surgeon that you are taking
Kliovance®. You may need to stop
taking Kliovance® about 4 to 6 weeks
before the operation to reduce the
risk of a blood clot (see section 2,
‘Blood clots in a vein (thrombosis)’).
Ask your doctor when you can start
taking Kliovance® again.
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)

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• 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
Kliovance®’.
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 heart beat),
feeling dizzy, sweating, which
could be signs of anaphylactic
reaction/shock. If one of the
mentioned symptoms appears,
stop taking Kliovance® and seek
immediate medical help.

Very common side effects
(affects more than 1 user in 10)
• Breast pain or breast tenderness
• Vaginal bleeding.
Common side effects (affects 1 to
10 users in 100)
• 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
• Enlargement or swelling of the
breasts (breast oedema)
• Back pain
• Uterine fibroid (benign tumour),
aggravation, occurrence or
reoccurrence
• Swelling of arms and legs
(peripheral oedema)
• Weight increase.

Uncommon side effects (affects
1 to 10 users in 1,000)
• Bloating, abdominal pain,
swelling, discomfort or flatulence
• Acne
• Hair loss (alopecia)
• Abnormal (male pattern) hair
growth
• Itching or hives (urticaria)
• Inflammation of a vein
(superficial thrombophlebitis)
• Leg cramps
• Drug ineffective
• Allergic reaction
• Nervousness.
Rare side effects (affects 1 to
10 users in 10,000)
• Blood clots in the blood vessels
of the legs or the lungs (deep
vein thrombosis, lung embolism).
Very rare side effects (affects less
than 1 user in 10,000)
• Cancer of the lining of the
womb (endometrial cancer)
• Excessive thickening of the lining
of the womb (endometrial
hyperplasia)

• Increase in blood pressure or
worsening of high blood
pressure
• Gall bladder disease, gall stones
occurrence/reoccurrence 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.
Other side effects of combined
HRT
• gall bladder disease
• 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)
– red or purple discolorations of
the skin and/or mucous
membranes (vascular purpura)
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 Kliovance®
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 outer carton after ‘EXP’.

The expiry date refers to the last
day of that month.
Do not store above 25°C
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 Kliovance® contains
– The active substances are
estradiol 1 mg (as estradiol
hemihydrate) and norethisterone
acetate 0.5 mg.
– The other ingredients are: lactose
monohydrate, maize starch,
copovidone, talc and magnesium
stearate.
– The film-coating contains:
hypromellose, triacetin and talc.

What Kliovance® 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 288 on one side and the
Novo Nordisk logo (an Apis bull) on
the other side.
Pack sizes:
• 1×28 film-coated tablets in
a calendar pack
• 3×28 film-coated tablets in
calendar packs
Not all pack sizes may be
marketed.
Marketing Authorisation Holder
and Manufacturer
Marketing Authorisation Holder:
Novo Nordisk Limited
3 City Place
Beehive Ring Road
Gatwick
West Sussex
RH6 0PA

Manufacturer:
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd
Denmark
This medicinal product is
authorised in the Member
States of the EEA under the
following names:
Member States of the EEA:
Activelle® – except for United
Kingdom: Kliovance®.
This leaflet was last revised in:
MM/YYYY

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. How to 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.

Kliovance® is a trademark owned
by Novo Nordisk FemCare AG,
Switzerland
© 2014
Novo Nordisk A/S

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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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