1. What Kliofem® is and what it is used for
Kliofem® is a continuous combined Hormone Replacement Therapy (HRT) which is taken every day without interruption. Kliofem® is used in postmenopausal women with at least 1 year since their last natural period.
The tablets contain 2 hormones: estradiol 2 mg (an oestrogen identical to the one made in the ovaries) and norethisterone acetate 1 mg (a progestagen that acts in a similar way to the body’s own hormone progesterone).
Kliofem® is used for:
Relief of symptoms occurring after menopause
During the menopause, the amount of the oestrogen produced by a woman’s body drops. This can cause symptoms such as hot face, neck and chest (‘hot flushes’). Kliofem® alleviates these symptoms after menopause. You will only be prescribed Kliofem® 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 Kliofem® to prevent osteoporosis after menopause.
Kliofem® 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. What you need to know before you take Kliofem®
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 Kliofem® 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 Kliofem®.
Go for regular breast screening, as recommended by your doctor.
Do not take Kliofem®
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 Kliofem®.
Do not take Kliofem®:
- if you have, have had or suspect having breast cancer
- if you have, have had or suspect having cancer of the womb lining (endometrial cancer), or any other oestrogen dependent cancer
- 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 (venous thromboembolism), 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 Kliofem® (listed in section 6 Contents of the pack and other information).
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 Kliofem®. 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 (venous thromboembolism))
- increased risk of getting an 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
- migraine or severe headaches
- a disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE)
- 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
- if you are taking medicine for an underactive thyroid gland your doctor will perform tests while you are taking HRT to ensure that your thyroid hormone level remains acceptable
- a hereditary condition causing recurrent episodes of severe swelling (hereditary angioedema) or if you have had episodes of rapid swelling of the hands, face, feet, lips, eyes, tongue, throat (airway blockage) or digestive tract
- lactose intolerance.
Stop taking Kliofem® 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 Kliofem® 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:
For more information, see Blood clots in a vein (venous thromboembolism)
- painful swelling and redness of the legs
- sudden chest pain
- difficulty in breathing.
Note: Kliofem® 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 Kliofem® protects you from this extra risk.
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 between the ages of 50 and 65.
For women aged 50 to 65 who still have a womb and who take oestrogen-only HRT, between 10 and 60 women in 1,000 will be diagnosed with endometrial cancer (i.e. between 5 and 55 extra cases), depending on the dose and for how long it is taken.
You may have irregular bleeding or drops of blood (spotting) during the first 3-6 months of taking Kliofem®. However, if the irregular bleeding:
- carries on for more than the first 6 months
- starts after you have been taking Kliofem® for more than 6 months
- carries on after you have stopped taking Kliofem®
see your doctor as soon as possible.
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 becomes clear within a few years. However, it returns to normal within a few years (at most 5) after stopping treatment.
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.
Additionally, you are advised to join mammography screening programs when offered to you. For mammogram screening, it is important that you inform the nurse/healthcare professional who is actually taking the x-ray that you use HRT, as this medication may increase the density of your breasts which may affect the outcome of the mammogram. Where the density of the breast is increased, mammography may not detect all lumps.
Ovarian cancer is rare - much rarer than breast cancer. The use of oestrogen-only or combined oestrogen-progestagen HRT has been associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer varies with age. For example, in women aged 50 to 54 who are not taking HRT, about 2 women in 2,000 will be diagnosed with ovarian cancer over a 5-year period. For women who have been taking HRT for 5 years, there will be about 3 cases per 2,000 users (i.e. about 1 extra case).
Effect of HRT 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 non-users, 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 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 Kliofem® and see a doctor immediately.
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.
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.
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).
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 Kliofem®. 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 infection (such as nevirapine, efavirenz, ritonavir and nelfinavir)
- Medicines for hepatitis C infections (such as telaprevir)
- Herbal remedies containing St John’s Wort (Hypericum perforatum).
Other medicines may increase the effects of Kliofem®:
- Medicines containing ketoconazole (a fungicide).
Kliofem® 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.
Taking Kliofem® with food and drink
The tablets can be taken with or without food and drink.
If you need a blood test, tell your doctor or the laboratory staff that you are taking Kliofem®, because this medicine can affect the results of some tests.
Pregnancy and breast-feeding
Pregnancy: Kliofem® is for use in postmenopausal women only. If you become pregnant, stop taking Kliofem® and contact your doctor.
Breast-feeding: You should not take Kliofem® if you are breast-feeding.
Driving and using machines
Kliofem® has no known effect on the ability to drive or use machines.
Important information about some of the ingredients in Kliofem®
Kliofem® contains lactose monohydrate. If you have an intolerance to some sugars, contact your doctor before taking Kliofem®.
3. How to take Kliofem®
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. 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.
For further information on the use of the calendar pack, see USER INSTRUCTIONS at the end of the package leaflet.
You may start treatment with Kliofem® 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 Kliofem® than you should
If you have taken more Kliofem® than you should, talk to a doctor or pharmacist as soon as possible. Taking more oestrogens than prescribed by your doctor may cause breast tenderness, nausea, vomiting and/or irregular vaginal bleeding (metrorrhagia). Taking more progestagens than prescribed by your doctor may lead to depressive mood, fatigue, acne and growth of body or facial hair (hirsutism).
If you forget to take Kliofem®
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 Kliofem®
If you would like to stop taking Kliofem®, 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 Kliofem®. You may need to stop taking Kliofem® about 4 to 6 weeks before the operation to reduce the risk of a blood clot (see section 2, Blood clots in a vein (venous thromboembolism)). Ask your doctor when you can start taking Kliofem® 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
- probable memory loss if HRT is started over the age of 65.
For more information about these side effects, see section 2 What you need to know before you take Kliofem®.
Hypersensitivity/allergy (uncommon side effect – may affect up to 1 in 100 people)
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 heartbeat), feeling dizzy, sweating, which could be signs of anaphylactic reaction/shock. If one of the mentioned symptoms appears, stop taking Kliofem® and seek immediate medical help.
Very common side effects (may affect more than 1 in 10 people)
- Breast pain or breast tenderness
- Vaginal bleeding.
Common side effects (may affect up to 1 in 10 people)
- 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
- Abdominal pain, swelling or discomfort
- Enlargement or swelling of the breasts (breast oedema)
- Back pain
- Leg cramps
- Uterine fibroid (benign tumour), aggravation, occurrence or recurrence
- Swelling of arms and legs (peripheral oedema)
- Weight increase.
Uncommon side effects (may affect up to 1 in 100 people)
- Bloating or flatulence
- Hair loss (alopecia)
- Abnormal (male pattern) hair growth
- Itching or hives (urticaria)
- Inflammation of a vein (superficial thrombophlebitis)
- Drug ineffective
- Allergic reaction
Rare side effects (may affect up to 1 in 1,000 people)
- Blood clots in the blood vessels of the legs or the lungs (deep vein thrombosis, lung embolism).
Very rare side effects (may affect up to 1 in 10,000 people)
- Cancer of the lining of the womb (endometrial cancer)
- Excessive growth of the lining of the womb (endometrial hyperplasia)
- Increase in blood pressure or worsening of high blood pressure
- Gall bladder disease, gallstones occurrence/recurrence 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
- Vaginal and genital itching
- Heart attack and stroke.
Other side effects of combined HRT
The following side effects have been reported with other HRTs:
- Various skin disorders:
- discolouration 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 discolourations of the skin and/or mucous membranes (vascular purpura)
- Dry eyes
- Tear film composition changes.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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.