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ACTIVELLE

Active substance(s): ESTRADIOL HEMIHYDRATE / NORETHISTERONE ACETATE

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Kliovance® / Activelle®
(estradiol hemihydrate & norethisterone acetate)
This medicine is known by any of the above names but will be referred to as Kliovance
throughout this leaflet.
Package leaflet: Information for the user
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 includes any
possible side effects not listed in this leaflet. See section 4.
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.
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 oestrogenonly 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 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 nonusers, 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.

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).

Taking Kliovance with food and drink
The tablets can be taken with or without food and drink.

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.

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.
The days of the week are printed on the dial in Greek and the following is a translation:ΔE
Mon

TP
Tue

TE
Wed

ΠE
Thu

ΠA
Fri

ΣA
Sat

KY
Sun

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.
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)
• heart disease
• stroke
• probable memory loss if HRT is started over the age of 65.

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, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. You can also report side effects directly on 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 out of the sight and reach of children.
Do not store above 25°C. Store in a dry place protected from light.
Do not refrigerate.
Do not use Kliovance after the expiry date stated on the label and carton. The expiry date
refers to the last day of that month.
If you notice that your medicine is discoloured or shows any other signs of deterioration,
consult your doctor or pharmacist who will tell you what to do.
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. CONTENTS OF THE PACK AND OTHER INFORMATION
What Kliovance contains
Each tablet contains 1mg estradiol (as hemihydrate) and 0.5mg norethisterone acetate. The
tablets are white, round, film-coated tablets with “Novo” and “288” on one side and a logo on
the other side. The tablets are supplied in a calendar dial pack of 28 or 3x28 film coated
tablets. The tablets also contain lactose monohydrate, maize starch, crospovidone, talc,
magnesium stearate, hypromellose and glycerol triacetate (triacetin).
Kliovance is manufactured by Novo Nordisk A/S, Novo Alle, DK-2880 Bagsvaerd, Denmark.
Procured from within the EU by the product licence holder: Caseview (PL) Limited, 20 Alliance
Court, Alliance Road, London W3 0RB.
Repackaged by OPD Laboratories Limited, Unit 6 Colonial Way, Watford, Herts WD24 4PR.
PL 13826/1141

POM
Kliovance® / Activelle®
Leaflet revision date (ref): 06/05/2015

Kliovance and Activelle are registered trademarks of Novo Nordisk FemCare AG.
To request a copy of this leaflet in Braille, large print or audio please call 01923 332 796.
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.

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.

2. How to take the first day’s tablet
Break the plastic tab and tip out the first tablet.

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.

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.

Expand view ⇕

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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