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PACKAGE LEAFLET: INFORMATION FOR THE USER
Cliovelle 1 mg/0.5 mg tablets
Estradiol/Norethisterone Acetate
Read all 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 to others. It could harm them,
even their symptoms are the same as yours.
 If any of this side effects get serious or if you notice any side effects not listed in this
leaflet, please tell your doctor or pharmacist.
This package leaflet contains information about:
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What Cliovelle is and what it is used for
Before you take Cliovelle
How to take Cliovelle
Possible side effects
How to store Cliovelle
Further information
WHAT CLIOVELLE IS AND WHAT IT IS USED FOR
Cliovelle is a hormone preparation for continuously supplying estrogens in combination with
progestogens.
Cliovelle is used by women more than one year after menopause with an intact uterus in order to
treat symptoms of estrogen deficiency. The treatment is sometimes called HRT which comes
from the English term: Hormone Replacement Therapy.
The main symptoms of estrogen deficiency are hot flushes, night sweats and vaginal dryness. The
estrogen treatment of typical symptoms is fully effective within a few weeks of treatment.
Cliovelle is sometimes also used to prevent bone loss (osteoporosis) in women, who after the
menopause are at increased risk of fractures (broken bones) and cannot take other medicinal
products for this purpose.
When estrogen is used alone the risk of uterine cancer is increased. The addition of a progestogen
prevents this risk.
The experience of treating women older than 65 years is limited.
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BEFORE YOU TAKE CLIOVELLE
Before starting treatment with Cliovelle you will be informed by your doctor about the benefits
and risks of the treatment. Before the start of treatment and at regular intervals during the
treatment your doctor will assess whether Cliovelle is a suitable treatment for you. Your doctor
will decide how often regular examination should be carried out, taking into account your general
state of health. If you have a close relative (mother, sister, maternal or paternal grandmother) who
has had a serious medical condition, for example a blood clot or breast cancer, the risk to you can
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also be increased. You must therefore always inform your doctor if you have close relatives with
serious illnesses and also inform the doctor if you notice changes in your breasts.
Do not take Cliovelle:
You must not take Cliovelle if you:
 have or have had breast cancer or you are suspected of having breast cancer.
 have an estrogen-related tumour, e.g. cancer of the uterus or you are suspected of having such
a tumour.
 have abnormal uterine bleeding that has not been investigated by a doctor or have untreated
abnormal growth of the mucous membrane of the uterus (endometrial hyperplasia).
 have blood clots (known as deep vein thrombosis) or have previously had blood clots.
 suffer from disorders which are associated with an increased tendency for formation of blood
clots (e.g. deficiency of protein C, protein S or antithrombin),
 have or have recently had symptoms of vascular spasms or heart attack.
 have an acute liver disease or have previously had a liver disease and still have abnormal liver
function values.
 have the metabolic disease porphyria.
 if you are allergic (hypersensitive) to estradiol valerate, norethisterone acetate or any of the
other ingredients of Cliovelle.
Take special care with Cliovelle:
Also talk to your doctor if you have or have had any medical problems and particularly if you
have or have had any of the following diseases/conditions, which in rare cases can recur or
worsen during treatment with Cliovelle:
 if you have had an abrasion or a similar procedure due to abnormal growths in the mucous
membrane of the uterus (endometrial hyperplasia)
 endometriosis (endometrial mucous membrane outside the uterus)
 benign tissue tumours in the uterus (myoma)
 risk factors for estrogen dependent tumours; e. g. breast cancer in first-degree relatives (e. g.
mother or sister)
 gallstone disease
 diabetes
 liver disease or liver tumour (e.g. adenoma)
 asthma
 epilepsy
 migraine or severe headache
 high blood pressure
 if you are at a higher risk of developing blood clots (see below)
 otosclerosis (ossification of the middle ear leading to sudden loss of hearing)
 systemic lupus erythematosus (SLE)
You must contact your doctor immediately and discontinue the treatment if any of the
following occur:
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jaundice or worsening of the liver function
marked increase in blood pressure
suddenly occurring migraine or severe headache
pregnancy
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 if something occurs that is set out under the heading ”Do not take Cliovelle”.
Treatment with HRT has been shown to increase the risk of the following conditions:
Abnormal growth of the mucous membrane of the uterus and cancer:
If estrogen is administered alone for a long time there is a risk of over-stimulation of the mucous
membrane of the uterus, which can lead to endometrial cancer. The reported increase in
endometrial cancer risk among estrogen-only users varies from 2- to 12-fold greater compared
with non-users, depending on the duration of treatment and estrogen dose. After stopping
treatment risk may remain elevated for at least 10 years. The addition of progestogen (corpus
luteum hormone) for at least 12 days each month prevents this risk. Progestogen (corpus luteum
hormone) is therefore contained in each tablet.
Breast cancer:
Results from studies suggest an increased risk of breast cancer in women being treated with
estrogens in combination with progestogens. The increased risk becomes apparent after about
3 years. Also when estrogen is used alone the risk may possibly be increased, but study results
indicate a substantially lower risk than found in users of a combined HRT. The risk of breast
cancer in women using a HRT increases with the duration of treatment, but decreases after the end
of treatment so that within a few years (at most five years) it has returned to the same level as in
non-users.
In order to be able to detect a breast tumour early it is recommended that women pay attention to
any changes in the breasts and report them to their doctor. It is also important to take part in
screening examinations with mammography.
Blood clots
If a blood clot is suspected, e.g. in the event of sudden swelling, redness and pain in one leg,
sudden breathlessness or sudden cough without an obvious cause, a doctor must be consulted
immediately and the treatment stopped.
The risk of being affected by blood clots (deep vein thrombosis, pulmonary embolism) is about
1.3-3 times greater in women using HRT. Blood clots occur more often during the first year of
treatment than later. If you are affected by a blood clot, there is a risk of the clot detaching from
the blood vessel where it has formed and being conveyed to the lungs where it can become stuck
in the small blood vessels (pulmonary embolism). In rare cases a blood clot can result in
permanent damage.
The risk of blood clots is increased if you have had blood clots before or if they occur in your
closest relatives, if you have had repeated miscarriages or if you are very overweight (BMI>30)
or if you have SLE (serious connective tissue disease). You should talk to your doctor about these
conditions. It is not known if varicose veins can increase the risk of blood clots.
If you suffer from any disorder associated with an increased disposition to thrombosis (e.g.
a deficiency of the natural clotting inhibitors protein C, protein S or antithrombin) you must not
take Cliovelle (see section “Do not take Cliovelle”).
The risk of blood clots can also be increased as a result of accidents, operations or anything else
that involves you being confined to bed. In such situations the treating doctor must be informed
that you are taking Cliovelle as you may need to interrupt the hormone treatment. In the case of
planned operations where it is known that the risk of blood clots is increased, it is recommended
to interrupt treatment with Cliovelle 4 - 6 weeks before the operation. Your doctor will tell you
when you can start taking Cliovelle again (usually 2 weeks after you are back on your feet again
at te earliest).
If you are taking medication to prevent blood clots you must only take Cliovelle if your doctor
considers that the benefits of the treatment clearly outweigh the increased risk of blood clots.
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Stroke:
HRT slightly increases the risk of having a stroke. The overall risk of stroke in women who use a
HRT will increase with age. If you have previously had a stroke you must discuss with your
doctor whether the benefits of treatment outweigh a possible increased risk.
Heart disease:
It has not been possible to demonstrate that HRT will protect from heart attacks. The risk of
developing cardiovascular disease is slightly increased during a combined estrogen-progestogen
HRT. No increased risk was found in women using estrogen-only therapy.
If you have had vascular spasms or a heart attack you must discuss with your doctor whether the
benefits outweigh the risks of treatment.
Ovarian cancer:
Ovarian cancer is much rarer than breast cancer. Women using estrogens alone for at least
5 - 10 years may be at a slightly increased risk of developing ovarian cancer compared with
women who have never been treated with HRT. Some studies suggest that the long-term use of a
combined treatment with estrogen/progestogen may be associated with a similar or slightly
smaller risk.
Other conditions:
HRT can cause fluid to accumulate in the body (edema), particularly in women suffering from
impaired heart or kidney function.
HRT can bring about an increase in blood fat values (triglycerides), which in women with
increased levels of blood fats can involve a risk of inflammation of the pancreas (pancreatitis).
HRT can affect the results of certain laboratory tests (e.g. thyroid gland and liver function tests).
Women who require thyroid hormone replacement therapy should have their thyroid function
monitored regularly while on HRT to ensure that thyroid hormone levels remain in an acceptable
range.
In women with hereditary angioedema HRT may increase or exacerbate the symptoms.
HRT use does not improve intellectual capacity (cognitive function). There is some evidence of
an increased risk of probable dementia in women who started to use a HRT after the age of 65.
Evidence regarding the risks which may be associated with HRT in the treatment of an early onset
of menopause is limited. The risks of HRT may possibly be lower in these patients due to the
generally lower risk level in younger women.
Taking other medicines:
Talk to your doctor or pharmacist if you are taking or have recently taken any other medicinal
product, including medicines obtained without prescription.
Certain medicinal products can reduce the effect of Cliovelle. Examples of these are:
 drugs for epilepsy (which contain, e.g. phenobarbital, phenytoin, carbamazepine)
 drugs for tuberculosis (which contain rifampicin, rifabutine)
 certain drugs for treating HIV infections (which contain, e.g. nevirapine, efavirenz, ritonavir,
nelfinavir)
Natural medicinal products containing St John’s Worth can also reduce the effect of Cliovelle.
Cliovelle can increase or decrease the effect of other medicinal products:
 The effect of cyclosporine (e. g. used for prevention of transplant rejection, treatment of
symptoms of rheumatoid arthritis or psoriasis) may be increased.
 The effect of lamotrigine (an antiepileptic drug) may be decreased, and dosage adjustment of
lamotrigine may be necessary for seizure control.
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 The results from some laboratory tests may be influenced, such as tests for glucose tolerance or
thyroid function.
Medicinal products which contain ketoconazole (an antifungal) can increase the effect of
Cliovelle.
Pregnancy and breast-feeding:
Do not use Cliovelle if you are pregnant or are planning to become pregnant. If you become
pregnant during Cliovelle therapy, you should stop taking Cliovelle immediately.
Do not use Cliovelle while you are breastfeeding.
Driving and using machines:
No effects on the ability to drive vehicles and use machines have been observed.
Important information about some of the ingredients of Cliovelle:
Cliovelle tablets contain lactose monohydrate. Patients with any of the following rare hereditary
conditions should not use this medicinal product: galactose intolerance, total lactase deficiency or
glucose-galactose malabsorption.
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HOW TO TAKE CLIOVELLE
Always take Cliovelle as your doctor has told you. You should check with your doctor or
pharmacist if you are not sure.
The lowest effective dose that alleviates your symptoms should be used for the shortest possible
period when treating postmenopausal symptoms.
Take one tablet a day without a break between tablet cards (blister packs). The tablets must be
swallowed with an adequate quantity of water, preferably at the same time each day.
If you feel that the effect of Cliovelle is too strong or too weak consult your doctor or pharmacist.
If you take more Cliovelle than you should:
If you have taken too much of the medicinal product, contact your doctor or hospital to assess the
risk and for advice.
If you have taken an extra dose by mistake, the usual dose should nevertheless be taken on the
next day.
Symptoms of overdose can be nausea and vomiting.
If you forgot to take Cliovelle:
If you forgot to take a tablet you can take it within 12 hours of the usual time, otherwise you must
discard the forgotten tablet and take the next tablet as usual on the next day.
Do not take a double dose to make up for a forgotten tablet.
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POSSIBLE SIDE EFFECTS
Like all medicines, Cliovelle can cause side effects, although not everybody gets them. Most of
the side effects are mild to moderate and do not mean that women have to stop taking their tablets.
Abnormal bleeding (breakthrough bleeding/spotting) can occur during the first months of
treatment. You must contact your doctor if the irregular bleeding continues for longer than a few
months or occurs after you have been on the treatment for some time or continues after you have
stopped treatment as the cause may need to be investigated further.
The following side effects can occur during treatment with Cliovelle:
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Very common (more than 1 in 10)
Pain or tenderness in the breasts. Vaginal bleeding.
Common (fewer than 1 in 10 but more than 1 in 100)
Fungal infections in the genital area or vaginal inflammation. Accumulation of fluid in the body.
Depression or worsening of existing depression. Headache, migraine or worsening of existing
migraine. Nausea. Back pain. Breast edema or breast enlargement. Uterine tumours (myoma) or
aggravated or recurrent uterine tumours. Peripheral edema (swollen arms and legs). Weight gain.
Uncommon (fewer than 1 in 100 but more than 1 in 1000)
Hypersensitivity (allergic reaction). Nervousness. Superficial vein inflammation combined with
blood clots. Pains, feelings of tightness or discomfort in the abdomen. Gases, bloating. Hair loss,
morbidly increased hirsutism (increased hair growth on the body and face), acne. Itching. Nettle
rash. Cramps in the legs.
Rare (fewer than 1 in 1000 but more than 1 in 10.000)
Blood clots in the lungs (see also section 2 “Before you take Cliovelle”). Deep vein inflammation
combined with blood clots.
Very rare (fewer than 1 in 10.000)
Anaphylactic reactions (sudden, severe, potentially life-threatening allergic reactions).
For information about breast cancer and endometrial cancer, see section 2 “Before you take
Cliovelle”.
Other side effects that can occur in connection with hormone treatment with estrogens/
progestogens are: tumours, blood clots, heart attack, stroke, gallbladder disease, pigment changes
in the skin (chloasma) and other skin diseases (erythema nodosum, erythema multiforme, vascular
purpura), dementia over the age of 65. See also section 2 “Before you take Cliovelle”.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
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HOW TO STORE CLIOVELLE
Keep out of the sight and reach of children.
Do not use Cliovelle after the expiry date which is stated on blister and on the carton. The expiry
date refers to the last day of that month.
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.
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FURTHER INFORMATION
What Cliovelle contains
 The active substances are estradiol 1 mg (as estradiol valerate) and norethisterone acetate
0.5 mg.
 The other ingredients are copovidone, lactose monohydrate, magnesium stearate and maize
starch.
What Cliovelle looks like and contents of the pack:
White, round, flat tablets 6 mm in diameter.
Blister packs (calendar packs) with 28, 30, 84 and 90 tablets.
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Not all pack sizes may be marketed.
Marketing authorisation holder:
To be completed nationally.
This package leaflet was last approved on
16 March 2011