Kliofem

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 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
• 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 Kliofem® is and what it is used for
2. Before you take Kliofem®
3. How to use Kliofem®
4. Possible side effects
5. How to store Kliofem®
6. Further information

Kliofem® is prescribed:

• 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 the 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.

Kliofem® 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 Kliofem®.

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.

For more information about the safety of HRT, see section 4 “Possible side effects”

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.

Do not take Kliofem®

If any of the following apply to you, talk to your doctor. Do not start taking Kliofem®:

• If you have or have had breast cancer, or if it is suspected
• If you have cancer of the womb lining (endometrium), or if such an oestrogen dependent cancer is suspected
• If you have any vaginal bleeding, which has not been diagnosed by your doctor
• If you have or have had endometrial hyperplasia (excessive growth of the womb lining) that is not being treated
• If you have or previously have had a blood clot in the blood vessels of the legs or the lungs (like deep vein thrombosis or lung embolism)
• If you have recently had a heart attack, stroke, or have angina
• If you have or have had a liver disorder and your liver tests have not returned to normal
• If you have porphyria (a liver enzyme disease)
• If you are allergic (hypersensitive) to estradiol, norethisterone acetate or any other ingredients in Kliofem® (listed in section 6, “Further information”).

Take special care with Kliofem®

If you have (or have had) any of the following conditions, tell your doctor. Your doctor may then want to follow your treatment up more closely. Rarely, these conditions may come back or get worse during treatment with Kliofem®:

• If you have any condition affecting the womb lining, such as fibroids, endometriosis (presence of womb lining tissue outside the
• If any of the conditions listed in Section 2 “Before you take Kliofem®”, occur.

Using other medicines

Some medicines may reduce the effects of Kliofem®:

• 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 Kliofem®:

• Drugs containing ketoconazole (a fungicide).

Taking Kliofem® with food and drink

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

Pregnancy and breast-feeding

Do not take Kliofem® if you suspect being pregnant, are pregnant or breast-feeding.

Driving and using machines

Kliofem® does not affect the use of any machines or the ability to drive safely.

Important information about some of the ingredients of Kliofem®:

Kliofem® contains lactose monohydrate. If you have an intolerance to some sugars, contact your doctor before taking Kliofem®.

If you take more Kliofem® than you should

If you have taken more Kliofem® than you should, talk to your doctor or pharmacist. An overdose of Kliofem® could make you feel sick or vomit.

If you forget to take Kliofem®

If you forget to take your tablet at the usual time, try and 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 stop taking Kliofem®

If you want to stop taking Kliofem®, talk to your doctor first. Your doctor will explain the effects of stopping treatment and discuss other possibilities with you.

Bleeding with Kliofem®

Kliofem® will not cause regular monthly bleeding, but 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.

But contact your doctor as soon as possible:

• If bleeding carries on for more than the first few months
• If bleeding starts after taking HRT for a while
• If bleeding continues after stopping HRT.

Your doctor may ask you about any vaginal bleeding with Kliofem® at your regular check-ups. You may find it helpful to make a note of any bleedings in a diary.

Very common effects

May affect more than 1 in 10 women

• Breast pain or breast tenderness
• Irregular menstrual periods or excessive bleeding during your periods.

Common effects

May affect up to 1 in 10 women

• Fungal infection of the genitals or vaginal inflammation (thrush)
• Fluid retention
• Depression or worsening of existing depression
• Headache
• Migraine or existing migraine made worse
• Feeling sick (nausea)
• Pain, swelling or discomfort of the abdomen (stomach)
• Back pain
• Leg cramps
• Enlargement or swelling of the breasts (breast oedema)
• Uterine fibroids (benign tumour of the womb): aggravation or re-occurrence
• Swelling of arms or legs (Peripheral oedema)
• Weight increase.

Uncommon effects

May affect up to 1 in 100 women

• Allergic reaction (hypersensitivity)
• Nervousness
• Inflammation of a vein (superficial thrombophlebitis)
• Flatulence (wind) or bloating
• Hair loss or increased facial or body hair or acne
• Itching
• Hives (urticaria)
• Painful periods
• Excessive growth of the lining of the womb (endometrial hyperplasia)
• No relief of symptoms (Drug ineffective)

Rare Effects

May affect up to 1 in 1,000 women

• Blood clots in the blood vessels of the legs or the lungs (deep vein thrombosis, lung embolism). See also section “Other side effects of HRT”
• Breast cancer. See also section “Other side effects of HRT”

Very Rare Effects

May affect up to 1 in 10,000 women

• Cancer of the lining of the womb (endometrial cancer). See also section “Other side effects of HRT”
• Insomnia
• Anxiety
• Changes in sexual desire
• Dizziness
• Visual disturbances
• Increase in blood pressure or worsening of high blood pressure
• Heart attack or stroke (see also section “Other side effects of HRT”)
• Heartburn or vomiting
• Gallbladder disease
• Gallstones, aggravation, occurrence or re-occurrence
• Greasy skin
• Rash
• Swelling of the skin or other tissues of sudden onset
• Vaginal and genital itching
• Weight decrease.

Effects on the skin

Brown patches on the face, skin rashes including red inflammation on the hands or the legs (erythema multiforme), formation of tender, red nodules on the front of the legs/- knees (erythema nodosum) or a bruise-like rash.

Other side effects of combined 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.

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 postmenopausal 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 it, 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 may prescribe a progestogen as well as oestrogen. If so, 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, Kliofem®, 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 taking 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 HRT for more than 5 years may increase the risk of ovarian cancer.

Effects on your heart or circulation

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 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.

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 a sign of heart disease.

Stroke

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

Dementia

There is no evidence that HRT improves processes of knowing, thinking, learning and judging (cognitive function). From a clinical study there is some evidence for an increased risk of dementia among women older than 65 years, who were using another oestrogen/progestogen combination than the one in Kliofem®. It is not known whether this applies to younger women and to women taking other HRT preparations.

What Kliofem® contains

The active substances are estradiol and norethisterone acetate. Each tablet contains estradiol 2 mg and norethisterone acetate 1 mg.

Other ingredients are: Lactose monohydrate, maize starch, hydroxypropylcellulose and magnesium stearate.

The film-coating contains:

Hypromellose, triacetin and talc.

What Kliofem® looks like and contents of the pack

The film-coated tablets are white, round with a diameter of 6 mm. The tablets are engraved with NOVO 281.

Pack sizes:

28 film-coated tablets

3 × 28 film-coated tablets

Not all pack sizes may be marketed.

Marketing authorisation holder

Manufacturer

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 one space as indicated by the arrow. Tip out the next tablet. Remember to take only one tablet once a day.
You can only turn the transparent dial after the tablet in the opening has been removed.