Kliovance

Kliovance

Film-coated tablets

Estradiol hemihydrate and Norethisterone acetate

Read all of this leaflet carefully, before you start using this medicine.

• Keep this leaflet. You may need to read it again.


• If you have further questions, please ask your doctor or your pharmacist.


• This medicine has been prescribed for you personally and you should not pass it on to others.

In this leaflet:

• 1. What Kliovance is and what it is used for


• 2. Before you use Kliovance


• 3. How to use Kliovance


• 4. Possible side effects


• 5. Storing Kliovance

Kliovance film-coated tablets

The active substances are estradiol hemihydrate and norethisterone acetate.

One white tablet contains: Estradiol anhydrous 1 mg (as estradiol hemihydrate) and norethisterone acetate 0.5 mg.

Other ingredients

The tablet core contains: Lactose monohydrate, maize starch, copovidone, talc and magnesium stearate.

Film-coating:

Hypromellose, triacetin and talc.

Marketing authorisation holder

Novo Nordisk Limited

Broadfield Park

Brighton Road

Crawley

West Sussex

RH11 9RT

Manufacturer

Novo Nordisk A/S

Novo Nordisk Park

DK-2760 Maaloev

Denmark

What Kliovance Is And What It Is Used For

Kliovance contains the female sex hormones 17ß-estradiol and norethisterone acetate. The 17ß-estradiol is identical to the 17ß-estradiol produced in the ovaries of women, and is classified as a natural oestrogen. Norethisterone acetate is a synthetic progestogen, which acts in a similar manner as progesterone, another important female sex hormone.

Kliovance is a hormone replacement therapy (HRT) used to:

• Relieve or eliminate oestrogen deficiency symptoms (hot flushes, night sweats, vaginal dryness etc. due to lack of a female sex hormone produced by the ovaries) in women who still have their womb and are more than one year after their menopause.

Women lose a certain amount of their bone mass during the years after the menopause, which in some women can lead to fracture in later life. This loss of bone mass is called osteoporosis. If you are at increased risk of fractures due to osteoporosis (thinning of the bones) but are unable to take other treatments or if other therapies prove to be ineffective, Kliovance may also be used for this purpose. Your doctor should discuss all the available options with you.

The experience of treating women older than 65 years is limited.

Kliovance comes in 1 or 3 calendar dial packs each containing 28 film-coated tablets. Kliovance film-coated tablets are engraved with NOVO 288 on one side and the APIS bull on the other.

Before You Use Kliovance

You should not take Kliovance if you:

• Have or suspect you have, or have had breast cancer


• Have or suspect you have a hormone dependent tumour (e.g. cancer of the lining of the womb)


• Have recently had any vaginal bleeding, other than a normal period


• Have a condition called endometrial hyperplasia (excessive growth of the lining of the womb) and are not being treated for this


• Have or have had deep vein thrombosis or pulmonary embolism (formation of a blood clot in the blood vessels in the legs or the lungs)


• Have or have recently had thromboembolic events in your arteries (e.g. angina or heart attack)


• Have or have had liver problems where your liver tests have not returned to normal


• Are allergic to estradiol or norethisterone acetate or any of the other ingredients in Kliovance


• Have porphyria (a metabolic disease with disturbed production of blood pigment).

Safety of HRT

As well as benefits, HRT has some risks which you need to consider when you’re deciding whether to take it, or whether to carry on taking it.

Medical check-ups

Before you start taking HRT, your doctor should ask about your own and your family’s medical history. Your doctor may decide to examine your breasts and/or your abdomen, and may do an internal examination - but only if these examinations are necessary for you, or if you have any special concerns. Once you’ve started on HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT.

Be sure to:

• 
  go for regular breast screening and cervical smear tests


• 
  regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel.

Conditions which need supervision

Inform your doctor if you have or have had the following conditions as your doctor may want to follow you more closely. These conditions may, in rare cases, recur or be made worse during treatment with Kliovance.

• Conditions affecting the lining of the womb such as fibroids, endometriosis (where the cells from the lining of the womb move to places outside the womb causing excessive period pain or discomfort) and endometrial hyperplasia (excessive growth of the lining of the womb)


• History of blood clots or risk factors for blood clots (see below)


• Risk factors for oestrogen dependent tumours, e.g. family history for breast cancer (see below)


• High blood pressure


• Liver disorders such as liver adenoma (a benign tumour)


• Diabetes mellitus


• Gallstones


• Migraine or severe headache


• Systemic lupus erythematosus (autoimmune disease)


• Epilepsy


• Asthma


• Otosclerosis (Progressing hearing loss due to a chronic disease of the inner ear).

Reasons for stopping treatment immediately

You should stop treatment immediately if you develop

• Any of the conditions mentioned in the section; “You should not take Kliovance if you:”


• Jaundice (yellow colouring of the skin and eyes) or other liver problems


• If your blood pressure goes up whilst taking Kliovance your doctor may tell you to stop taking it


• New onset of migraine-type headache


• Pregnancy.

Effects on your risk of developing cancer

Breast cancer

Women who have breast cancer, or have had breast cancer in the past, should not take HRT.

Taking HRT slightly increases the risk of breast cancer; so does having a later menopause. The risk for a post-menopausal woman taking oestrogen-only HRT for 5 years is about the same as for a woman of the same age who’s still having periods over that time and not taking HRT. The risk for a woman who is taking oestrogen plus progestogen HRT is higher than for oestrogen-only HRT (but oestrogen plus progestogen HRT is beneficial for the endometrium, see ‘Endometrial cancer’ below).

For all kinds of HRT, the extra risk of breast cancer goes up the longer you take HRT, but returns to normal within about 5 years after stopping HRT.

Your risk of breast cancer is also higher:

• if you have a close relative (mother, sister or grandmother) who has had breast cancer


• if you are seriously overweight.

Compare

Looking at women aged 50 who are not taking HRT, on average, 32 in 1000 will be diagnosed with breast cancer by the time they reach the age of 65.

For women who start taking oestrogen-only HRT at age 50 and take it for 5 years, the figure will be between 33 and 34 in 1000 (i.e. an extra 1-2 cases). If they take oestrogen-only HRT for 10 years, the figure will be 37 in 1000 (i.e. an extra 5 cases).

For women who start taking oestrogen plus progestogen HRT at age 50 and take it for 5 years, the figure will be 38 in 1000 (i.e. an extra 6 cases).

If they take oestrogen plus progestogen HRT for 10 years, the figure will be 51 in 1000 (i.e. an extra 19 cases).

If you notice

any changes in your breast, such as:

• dimpling of the skin


• changes in the nipple


• any lumps you can see or feel

• 
  Make an appointment to see your doctor as soon as possible.

Endometrial cancer (cancer of the lining of the womb)

Taking oestrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking a progestogen as well as the oestrogen helps to lower the extra risk.

If you still have your womb, your doctor will usually prescribe a progestogen as well as oestrogen. These may be prescribed separately, or as a combined HRT product.

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take oestrogen without a progestogen.

If you’ve had your womb removed because of endometriosis, any endometrium left in your body may be at risk. So your doctor may prescribe HRT that includes a progestogen as well as an oestrogen. Your product, Kliovance, contains a progestogen.

Compare

Looking at women who still have a uterus and who are not taking HRT - on average 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50 and 65.

For women who take oestrogen-only HRT, the number will be 2 to 12 times higher, depending on the dose and how long you take it.

The addition of a progestogen to oestrogen-only HRT substantially reduces the risk of endometrial cancer.

If you get

breakthrough bleeding or spotting, it’s usually nothing to worry about, especially during the first few months of taking HRT.

But if the bleeding or spotting:

• carries on for more than the first few months


• starts after you’ve been on HRT for a while


• carries on even after you’ve stopped HRT

• 
  Make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

Ovarian cancer

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that taking oestrogen-only HRT for more than 5 years may increase the risk of ovarian cancer. It is not yet known whether other kinds of HRT increase the risk in the same way.

Effects on your heart or circulation

Heart disease

HRT is not recommended for women who have heart disease, or have had heart disease recently. If you have ever had heart disease, talk to your doctor to see if you should be taking HRT.

HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated oestrogen plus the progestogen MPA) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get:

• a pain in your chest that spreads to your arm or neck

• 
  See a doctor as soon as possible and do not take any more HRT until your doctor says you can. This pain could be sign of heart disease.

Stroke

Recent research suggests that HRT slightly increases the risk of having a stroke. Other things that increase the risk of stroke include:

• getting older


• high blood pressure


• smoking


• drinking too much alcohol


• an irregular heartbeat.

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT - on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000. Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 11 in 1000 would be expected to have a stroke.

For women in their 60s who are taking HRT, the figure would be 15 in 1000.

If you get:

• unexplained migraine-type headaches, with or without disturbed vision

• 
  See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

Blood clots

HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year of taking it.

These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE.

DVT and PE are examples of a condition called venous thromboembolism, or VTE. You are more likely to get a blood clot:

• if you are seriously overweight


• if you have had a blood clot before


• if any of your close family have had blood clots


• if you have had one or more miscarriages


• if you have had any blood clotting problem that needs treatment with a medicine such as warfarin


• if you’re off your feet for a long time because of major surgery, injury or illness


• if you have a rare condition called SLE.

If any of these things apply to you, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT - on average, over a 5-year period, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot. For women in their 60s who are taking HRT, the figure would be 17 in 1000.

If you get:

• painful swelling in your leg


• sudden chest pain


• difficulty breathing

• 
  See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These may be signs of a blood clot.

If you’re going to have surgery, make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

Other conditions

Your doctor may want to follow you more closely:

• If you have kidney or heart disease


• If you have hypertriglyceridemia (high levels of fat in the blood).

If you need a blood test, tell your doctor that you are taking Kliovance since oestrogen can affect the results of certain tests. There is no evidence that HRT will prevent memory loss. In one study of women who started using one type of HRT (containing conjugated oestrogen plus the progestogen MPA) after the age of 65, a small increase in the risk of dementia was observed. It is not known whether this applies to younger post-menopausal women or other HRT products.

This medicine contains lactose; if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking it.

Pregnancy and breast-feeding

Do not take Kliovance if you are pregnant or breast-feeding.

Using other medicines

Please inform your doctor or pharmacist if you are taking or have recently taken any other medicine, even those not prescribed. The following drugs may reduce the effect of Kliovance:

Anti-convulsants (e.g. phenobarbital, phenytoin and carbamazepin) and antiinfectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz, ritonavir and nelfinavir). Herbal preparations containing St John’s Wort (Hypericum perforatum).

Drugs containing ketoconazole (a fungicide) may increase the effect of Kliovance.

How To Use Kliovance

Always take Kliovance exactly as your doctor has instructed you to. You should check with your doctor or pharmacist if you are unsure. You may start treatment with Kliovance on any convenient day. However, if you are switching from a sequential hormone replacement therapy product, treatment should start right after your withdrawal bleeding has ended.

Take one tablet with a sufficient quantity of liquid (e.g. a glass of water) once a day, at about the same time each day. Take the tablet every day without interruptions.

After all 28 tablets of a calendar pack have been used treatment is continued with the next calendar pack.

Your doctor will aim to prescribe the lowest effective dose for the shortest duration that gives you symptom relief. Talk to your doctor if you do not experience symptom relief after 3 months of treatment.

If you would like to stop your treatment with Kliovance, for any reason, please discuss your decision with your doctor. He/she will explain the effects of stopping treatment and discuss other possibilities of treatment with you.

If you use more Kliovance than you should:

If you have taken more Kliovance tablets than you should, talk to a doctor. An overdose of Kliovance could make you feel sick or vomit.

If you forget to take Kliovance:

Do not take a double dose to make up for forgotten individual doses. If you forget to take a tablet one day, discard the tablet and continue treatment as usual. Forgetting a dose may increase the likelihood of breakthrough bleeding and spotting.

Kliovance Side Effects

Like all medicines, Kliovance can have side effects.

The following side effects may occur during your Kliovance treatment:

Very common (> 10% - more than 1 per 10)

• Breast pain or breast tenderness


• Vaginal bleeding.

Common (≥ 1% and < 10% - less than 1 per 10 but more than 1 per 100)

• Vaginal thrush or vaginal inflammation


• Fluid retention


• Depression or aggravation of present depression


• Headache, migraine or aggravation of present migraine


• Nausea (feeling sick)


• Back pain


• Swollen breasts


• Uterine fibroids or aggravation or re-occurrence of uterine fibroids


• Swelling of arms or legs (Peripheral oedema)


• Weight increase.

Uncommon (≥ 0.1% and < 1% - less than 1 per 100 but more than 1 per 1000)

• Allergic reaction to one or more of the tablet ingredients, most often seen as a skin rash appearing soon after taking a tablet


• Nervousness


• Thrombophlebitis (Painful swelling of a visible vein, most often on the leg, associated with a blood clot)


• Abdominal pain (stomach), distension or discomfort


• Flatulence or bloating


• Hair loss or increased facial or body hair or acne


• Itching


• Hives


• Leg cramps


• Drug ineffective (no relief of symptoms).

Rare (≥ 0.01% and < 0.1% - less than 1 per 1,000 but more than 1 per 10,000)

• Pulmonary embolism (blood clot) (see also section 2. ‘Before you use Kliovance’)


• Deep vein thrombosis (see also section 2. ‘Before you use Kliovance’).

Very rare (up to 0.01% - less than 1 per 10,000)

• Endometrial cancer (cancer of the lining of the womb) (see also section ‘Endometrial cancer’ above)


• Insomnia


• Anxiety


• Changes in sexual desire


• Dizziness


• Visual disturbances


• Increase in blood pressure or worsening of high blood pressure in women already treated for this


• Indigestion


• Vomiting


• Gallbladder disease, gallstones, aggravation or re-occurrence of gallstones


• Greasy skin


• Rash


• Severe allergic reaction with skin rash and swelling


• Endometrial hyperplasia (excessive growth of the lining of the womb)


• Vaginal and genital itching


• Weight decrease.

The following side effects have been reported to be associated with oestrogen/progestogen treatment:

• Brown patches on the skin, skin rashes including red inflammation of the skin or bruise like rash


• Heart attack and stroke (see also section 2. ‘Before you use Kliovance’)


• Breast cancer (see under ‘Breast cancer’ above)


• Dementia (see under ‘Other conditions‘ above).

If you notice any side effects, including those not mentioned in this leaflet, please inform your doctor or pharmacist.

Storing Kliovance

Keep out of the reach and sight of children. Do not store above 25°C. Do not refrigerate. Keep the container in the outer carton in order to protect from light.

Do not use Kliovance after the expiry date stated on the label and carton.

This leaflet was issued: August 2005

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

© 1999/2006

Novo Nordisk A/S

Instructions for the use of 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 tablet
  

Break the plastic tab and tip out the first tablet.

• 
  3. Every day
  

Simply move the transparent dial clockwise one space as indicated by the arrow. Tip out the next tablet.

The transparent dial can only be turned after the tablet in the opening has been removed.

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