KLIOVANCE

Active substance: NORETHISTERONE ACETATE

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8-2901-01-053-6_v1-20:Layout 1

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
- 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. Do not pass it
on to others. It may harm them,
even if their symptoms are the
same as yours.

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RA Labelling & IT
Insert size: 999x100-006
Current: 2.0

2011-06-21

2:10 PM

Page 1

- If any of the side effects get
serious, or if you notice any side
effects not listed in this leaflet,
please tell your doctor or
pharmacist.
In this leaflet:
1. What Kliovance® is and what it is
used for
2 Before you take Kliovance®
3. How to use Kliovance®
4 Possible side effects
5. How to store Kliovance®
6. Further information
1. WHAT KLIOVANCE® IS AND
WHAT IT IS USED FOR
Kliovance® is a continuous
combined Hormone Replacement
Therapy (HRT). It contains the
hormones estradiol and
norethisterone acetate. Kliovance®
is suitable for postmenopausal
women with at least 1 year since
their last natural period.
The tablets contain 2 hormones:
estradiol 1 mg (an oestrogen
identical to the one made in the
ovaries) and norethisterone acetate
Improved DI28MKII
Colour: PMS 280C

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

0.5 mg (a progestagen that acts in
a similar way to the body’s own
hormone progesterone).
Kliovance® is indicated
• To relieve unpleasant symptoms
like hot flushes, night sweats and
vaginal dryness, which occur
when the oestrogen levels
decline and the periods stop
(menopause).
• For prevention of osteoporosis
(thinning of the bones) in
postmenopausal women if they
are at high risk of future
fractures and if they are unable
to take other medications for this
purpose.
Kliovance® 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. BEFORE YOU TAKE
KLIOVANCE®
Medical check-ups
Before you start taking Kliovance®,
your doctor will inform you about
the risks and benefits of the
treatment (see also section 4 Other
side effects of combined HRT).
Before you start treatment and
regularly during treatment, your
doctor will evaluate whether
Kliovance® is the right treatment
for you. Your doctor will perform a
physical examination. This includes
an examination of your breasts,
and may include an examination of
your abdomen or an internal
examination. Your doctor will tell
you how often you should go for
periodic check-ups, taking into
account your general state of
health. If you have any close
relatives (mother, sister, maternal or
paternal grandmother), who has
suffered from serious illness, e.g.
blood clot or breast cancer, you
might be at an increased risk of
developing the illness. You should

therefore always tell your doctor
about any close relatives suffering
from a serious illness, and you
should also tell your doctor about
any changes, you might find in
your breasts.
Once you have started on
Kliovance®, you should see your
doctor for regular check-ups (at
least once a year). At these checkups, your doctor may discuss the
benefits and risks of continuing
with Kliovance®.
As well as regular check-ups with
your doctor, be sure to:
• Regularly check your breasts
for any changes, such as
dimpling or sinking of the skin,
changes in the nipple, or any
lumps you can see or feel.
• Go for regular breast screening
(mammography) and cervical
smear tests.
Do not take Kliovance®
If any of the following applies to
you, talk to your doctor. Do not
start taking Kliovance®:

• If you have or have had breast
cancer, or if it is suspected.
• If you have or have had cancer
of the womb lining
(endometrium), or if an
oestrogen dependent cancer is
suspected.
• If you have abnormal vaginal
bleeding, which has not been
diagnosed by your doctor.
• If you have endometrial
hyperplasia (excessive
thickening of the womb lining)
that is not being treated.
• If you have or have had blood
clots in a vein (venous
thromboembolism), in the legs
(deep venous thrombosis) or the
lungs (pulmonary embolism).
• If you have a blood clotting
disorder (thrombophilic disorder,
such as protein C, protein S, or
antithrombin deficiency).
• If you have or have had a heart
attack, stroke, or have angina.
• If you have or have had liver
problems 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
other ingredients in Kliovance®
(listed in section 6 Further
information).
Take special care with Kliovance®
If you have (or have had) any of the
following conditions, tell your
doctor. He or she may want to see
you more often for check-ups.
These conditions may in rare cases
come back or get worse during
treatment with Kliovance®:
• If you have any condition
affecting the womb lining,
including fibroids, endometriosis
or have had endometrial
hyperplasia (excessive thickening
of the lining of the womb).
• If you have a history of blood











clots (thrombosis) or have risk
factors for developing blood
clots (see Blood clots in a vein)
(these risk factors and symptoms
for a blood clot are listed in
section 4 Other side effects of
combined HRT).
If any of your immediate
family has had breast cancer,
or other cancers related to
oestrogen (endometrial cancer).
If you have high blood pressure.
If you have a liver disorder such
as liver adenoma (a benign
tumour).
If you have cardiac or kidney
problems.
If you have diabetes or
gallstones.
If you have epilepsy or asthma.
If you get migraines or severe
headaches.
If you have systemic lupus
erythematosus (SLE) - an
autoimmune disease.

• If you have high levels of fat in
the blood (hypertriglyceridaemia).
• If you have otosclerosis
(hearing loss).
• If you have lactose intolerance.
If you need a blood test, tell your
doctor that you are taking
Kliovance® since oestrogen can
affect the results of certain
laboratory tests.
If you are going to have
surgery, talk to your doctor. You
may need to stop taking these
tablets 4 to 6 weeks before the
operation to reduce the risk of a
blood clot. Your doctor will tell you
when you can start again.
Stop taking Kliovance®
If you are experiencing any of the
following conditions below, stop
taking Kliovance® and contact your
doctor immediately:
• If you get a migraine-type
headache for the first time.
• If you develop yellow skin or

eyes (jaundice) or other liver
problems.
• If your blood pressure goes up
significantly while you are taking
Kliovance® (symptoms of high
blood pressure e.g. headache,
tiredness and dizziness).
• If you get signs of a blood clot
(painful swelling and redness of
the legs, sudden chest pain,
difficulty in breathing).
• If you become pregnant.
• If any of the conditions listed
in section 2 Do not take
Kliovance® occur.
Kliovance® and cancer
Excessive thickening of the
lining of the womb
(endometrial hyperplasia) and
cancer of the womb lining
(endometrial cancer)
In women with an intact womb
taking oestrogen-only HRT over a
long period of time, the risk of
excessive thickening of the lining of

the womb (endometrial hyperplasia)
and cancer of the womb lining
(endometrial cancer) is increased.
Taking a progestagen in addition to
the oestrogen, such as Kliovance®,
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.
For women who still have a
womb and take oestrogen-only
HRT, the number of extra cases
could vary between 5 and 55 in
1,000 users between the ages of
50 and 65 depending on the
dose and for how long it is taken.
The addition of a progestagen to
oestrogen-only HRT substantially
reduces the risk of endometrial
cancer.

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 is visible after about
3 years. However, it returns to
normal within a few years (at most
5) after stopping treatment.
Compare
Women aged 50 to 65 who are
not taking HRT, on average 9 to
12 in 1,000 will be diagnosed
with breast cancer over a 5-year
period.
For women aged 50 to 65 who
are taking oestrogen-progestagen
HRT over 5 years, the number of
extra cases will be 6 in 1,000
users. Looking at women aged 50
to 79 who are not taking HRT, on
average 14 in 1,000 will be

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diagnosed with breast cancer
over a 5-year period.
For women aged 50 to 79 who
are taking oestrogen-progestagen
HRT over 5 years, the number of
extra cases will be 4 in 1,000
users.
Ovarian cancer
Ovarian cancer is much rarer than
breast cancer. A slightly increased
risk of ovarian cancer has been
reported in women taking HRT for
a least 5 to 10 years. Some studies
suggest that the long-term use of
combined HRT may carry a similar
or slightly smaller risk.
For women who have been taking
HRT for over 5 years, there will be
1 extra case per 2,500 users.

Effect of Kliovance® 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 nonusers, especially during the first
year of taking it.
Blood clots are not always serious,
but if one travels to the lungs, it
can cause chest pain,
breathlessness, collapse or even
death.
You are generally more likely to get
a blood clot in your veins if one or
more of the following applies to
you. Inform your doctor if any of
these situations apply to you:
• You are older
• You are pregnant or have
recently had a baby
• You use oestrogens containing
preparations
• You or any of your close relatives
have ever had a blood clot in the
leg, lung or another organ

• You are seriously overweight
• You have systemic lupus
erythematosus (SLE)
• You have a blood clotting problem
that needs long-term treatment
with a medicine used to prevent
blood clots (anticoagulant)
• You are unable to walk or stand
for a long time because of major
surgery, injury or illness
(prolonged immobilisation)
• You have cancer
Compare
Women in their 50s who are not
taking HRT, on average over a
5-year period, 4 in 1,000 would
be expected to get a blood clot in
a vein.
For women in their 50s who have
been taking oestrogenprogestagen HRT for over 5 years,
the number of extra cases will be
5 in 1,000 users.

Heart disease (heart attack)
There is no evidence that HRT will
help to 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 risk of stroke
strongly depends on age. Therefore,
the number of extra cases of stroke
due to use of HRT will rise with
more advanced age.
Compare
For women in their 50s who are
taking HRT, the number of extra
cases will be 3 in 1,000 users over
5 years.

Other conditions
HRT will not prevent memory loss.
The risk of probable memory loss
may be somewhat higher in
women who start using any kind of
HRT after the age of 65.
Using other medicines
Some medicines may reduce the
effects of Kliovance®:
• Drugs used for epilepsy (such as
phenobarbital, phenytoin and
carbamazepine)
• Drugs used for tuberculosis
(such as rifampicin, rifabutin)
• Drugs used for HIV infections
(such as nevirapine, efavirenz,
ritonavir and nelfinavir)
• Herbal products with St John’s
Wort (Hypericum perforatum)
Other medicines may increase the
effects of Kliovance®:
• Drugs containing ketoconazole
(a fungicide)
Concomitant administration of
cyclosporine may cause increased
blood levels of 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 Kliovance® with food
and drink
The tablets can be taken with or
without food and drink.
Pregnancy and breast-feeding
Pregnancy: You should not take
Kliovance® if you are pregnant.
If you become pregnant stop
taking Kliovance® immediately and
contact your doctor.
Breast-feeding: You should not
use 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 USE KLIOVANCE®
Always take Kliovance® 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.
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 for the shortest
time that gives you relief from your
symptoms. Talk to your doctor if
your symptoms are not better after
3 months.
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, 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.

8-2901-01-053-6_v1-20:Layout 1

He/she will explain the effects of
stopping treatment and discuss
other possibilities with you.
If you have any further questions
on the use of this product, ask your
doctor or pharmacist.
4. POSSIBLE SIDE EFFECTS
Like all medicines, Kliovance® can
have side effects, although not
everybody gets them.
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.

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Page 2

Bleeding with Kliovance®
Kliovance® will not cause regular
monthly bleeding. When first
starting the tablets, some women
experience slight vaginal bleeding
or spotting.
If you get breakthrough bleeding or
spotting, it is usually nothing to
worry about, especially during the
first few months of taking HRT.
However, contact your doctor as
soon as possible:
• If bleeding carries on for more
than the first 3 months.
• If bleeding only starts after
taking HRT for a while.
• If bleeding continues after
stopping HRT.
Your doctor may ask you about any
vaginal bleeding with Kliovance® at
your regular check-ups. You may
find it helpful to make a note of
any bleeding in your diary.
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)
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

• 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
• 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
• 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 thickening of the lining
of the womb (endometrial
hyperplasia)
• Increase in blood pressure or
worsening of high blood pressure
• Gallbladder disease, gallstones
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
Women using HRT have a slightly
increased risk of developing the
following diseases:

• Breast cancer
• Excessive thickening 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
• Skin and subcutaneous disorders:
- Darkening of the skin
(chloasma)
- Severe condition of the skin
that may affect the mouth
and other parts of the body
(erythema multiforme)
- Red-purple swellings on the
shins, thighs and, less
commonly, the arms. Joint
and muscle pains and fever
may also occur (erythema
nodosum)
- Purple or red-brown spots
visible through the skin
(vascular purpura)

• Probable memory loss if HRT is
started over the age of 65.
For more information about these
side effects, see section 2.
If any of the side effects get
serious, or if you notice any side
effects not listed in this leaflet,
please tell your doctor or
pharmacist.
5. HOW TO STORE KLIOVANCE®
Keep out of the reach and sight of
children.
Do not use Kliovance® 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 from light.
Medicines should not be disposed
of via wastewater or household
waste. Ask your pharmacist how to
dispose of medicines no longer
required. These measures will help
to protect the environment.

6. FURTHER INFORMATION
What Kliovance® contains
The active substances are estradiol
1 mg (as estradiol hemihydrate)
and norethisterone acetate 0.5 mg.
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 imprinted
NOVO 288 on one side and the
Novo Nordisk logo (an APIS bull) on
the other side.
Pack sizes available:
• 28 film-coated tablets
• 3×28 film-coated tablets
Not all pack sizes may be marketed

Marketing Authorisation Holder
and Manufacturer
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 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 approved
in: June 2011

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.

Kliovance® is a trademark owned by
Novo Nordisk FemCare AG,
Switzerland
© 2010
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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