Cliane Consumer Medicine Information

Estradiol hemihydrate 2mg and norethisterone acetate 1mg tablets

What is in this leaflet

Please read this leaflet carefully before you start using CLIANE. This leaflet will provide information about the benefits and risks of using CLIANE. It will also advise you about how to take CLIANE properly and when to tell your doctor about health-related conditions. If you have any questions or need more advice, ask your doctor, professional health care provider or pharmacist. This product has been prescribed for you personally and you should not pass it on to others.

What is CLIANE used for and how does it work

CLIANE is intended for period-free hormone replacement therapy (HRT). Each blister pack of CLIANE contains 28 pink, film-coated tablets each containing 2.0mg estradiol (as hemihydrate) and 1.0mg norethisterone acetate as active substances.

How does CLIANE work?

CLIANE contains both types of hormone that are lost during the menopause ('the change of life'): estradiol and progestogen. Therefore it replaces the hormones that the body no longer makes. Although the change of life is natural, it often causes distressing symptoms, which are connected with the gradual loss of the hormones produced by the ovaries.

The estradiol prevents or relieves troublesome symptoms (menopausal complaints) such as hot flushes, sweats, sleep disturbances, nervousness, irritability, dizziness, headaches, as well as involuntary loss of urine, vaginal dryness and burning, and pain during sexual intercourse.

The use of estrogens alone over a prolonged period can lead to excessive development of the lining of the womb and, in this connection, can increase the incidence of cancer of the womb. The continuous addition of the progestogen (norethisterone acetate) prevents thickening of the lining of the womb and leads to a reduction and, in the majority of women, subsequent elimination of a menstruation-like bleeding.

In addition, the loss of the hormones produced by the ovaries leads to thinning of the bones. In some women this effect may be extensive (postmenopausal osteoporosis) resulting in fractures of the bones in later life.

From clinical studies with hormone replacement preparations it is known that long-term treatment reduces the risk of bone fractures.

What is CLIANE used for?

CLIANE provides hormone replacement therapy for the treatment of menopausal complaints in women who had their last menstrual bleed at least one year previously.

Some women are more likely than others to develop osteoporosis in later life depending on their medical history and lifestyle. If it is appropriate, you may be prescribed CLIANE to prevent osteoporosis. Your doctor will be able to advise you further.

Before you use CLIANE

A large clinical trial with a combination of hormones similar to CLIANE suggested that the risk of cardiovascular disease may be increased in women taking HRT. Although such data are not available for CLIANE, it should not be used to prevent heart disease or stroke.

Do not use CLIANE if you have or have had any of the conditions listed below. If any of these apply to you, tell your doctor before starting to use CLIANE.

You must not use CLIANE if:

  • you are pregnant or breast-feeding
  • you have vaginal bleeding
  • you have or there is a suspicion of cancer of the breast
  • you have or there is a suspicion of other cancers influenced by sex hormones
  • you have or have had a liver tumour (benign or malignant)
  • you have severe liver disease
  • you recently had a heart attack and/or stroke
  • you have or have had a thrombosis (the formation of a blood clot) in the blood vessels of the legs (deep venous thrombosis) or the lungs (pulmonary embolism) or thrombophlebitis (inflammation of a vein)
  • you have an inherited or acquired predisposition to venous thrombosis (formation of a blood clot in a vein) e.g. antithrombin III deficiency
  • you have severely elevated blood levels of triglycerides (special type of blood lipids)
  • you are allergic to any of the ingredients of CLIANE.

If any of these conditions appear for the first time while using CLIANE, stop taking it at once and consult your doctor.

Tell your doctor if:

If HRT is used in the presence of any of the conditions listed below or they appear for the first time, recur or worsen during treatment, you may need to be kept under close observation. Your doctor can explain this to you. Therefore, tell your doctor before starting to use CLIANE if:

  • you have an increased risk of thrombosis (blood clot formation) in your veins; the risk increases with age and may also be higher:
    • if anyone in your immediate family has ever had a thrombosis in the blood vessels of the legs or lungs
    • if you are overweight
    • if you have severe varicose veins
    If you are already using CLIANE, tell your doctor well in advance of any expected hospitalisation or surgery. This is because the risk of deep venous thrombosis is temporarily increased as a result of an operation or immobilisation (for example, when you have your leg or legs in plaster or splints) and may be further increased by the use of CLIANE. Your doctor may tell you to stop taking CLIANE several weeks before surgery or at the time of immobilisation. Your doctor will also tell you when you can start taking CLIANE again after you are back on your feet.

  • you have fibroids of the womb
  • you have or have had endometriosis (the presence of tissue of the lining of the womb in places in the body where it is not normally found)
  • you have liver or gall-bladder disease
  • you have had jaundice during pregnancy or previous use of sex steroids
  • you suffer from diabetes
  • you have elevated levels of triglycerides (a special type of blood lipids)
  • you have high blood levels of calcium (hypercalcaemia)
  • you have high blood pressure
  • you have or have had chloasma (yellow brown pigmentation patches on the skin, particularly of the face); if so, avoid too much exposure to the sun or ultraviolet radiation
  • you suffer from epilepsy
  • you have lumpy or painful breasts (benign breast disease)
  • you suffer from asthma
  • you suffer from migraine
  • you have the inherited disease called porphyria
  • you suffer from inherited deafness (otosclerosis)
  • you have systemic lupus erythematosus (SLE; a disease affecting the skin all over the body)
  • you suffer from chorea minor (Sydenham's chorea)

What else you should know

CLIANE cannot be used as a contraceptive.

The use of hormone replacement therapy (HRT) can increase the risk of a blood clot occurring in the deep veins of the legs. This is known as deep venous thrombosis. Blood clots occur rarely and can develop whether or not you are taking HRT. Very occasionally, such as when a blood clot breaks away from the veins and blocks the arteries of the lungs (pulmonary embolism), a blood clot may cause serious permanent disability or may even be fatal. The warning signs of a blood clot are listed under the section "When using CLIANE".

Oestrogens with or without progestogens should not be used for the long-term maintenance of general health, including the primary prevention of cardiovascular disease as the risks of long-term treatment with HRT in most circumstances, outweigh the benefits.

All prospective and current users of HRT should be advised of the risks and benefits of oestrogens and progestogens and the need for treatment with HRT should be reviewed on a yearly basis.

If there is a suspicion of an adenoma of the anterior lobe of the pituitary gland, this should be ruled out by your doctor before starting treatment.

Your doctor will carry out gynaecological, blood pressure and other examinations as appropriate. Your doctor will examine your breasts periodically during treatment, particularly if there is a history of breast cancer in your family.

If you are known to have any liver disease, your doctor will arrange for your liver function to be checked periodically.

HRT and cancer

The risk of cancer of the lining of the womb (endometrial cancer) increases when estrogens are used alone for prolonged periods. The progestogen in CLIANE opposes this risk.

In clinical studies breast cancer has been found slightly more often in women who have used HRT for several years compared to women of the same age who have never used HRT. The risk of having breast cancer diagnosed increases with length of treatment but this is comparable to the increased risk observed in women with a delayed menopause. If women stop taking HRT this increased risk decreases so that 5 years after stopping HRT, the risk of finding breast cancer is the same as for women who have never used HRT. Breast cancer seems less likely to have spread when found in women who have used HRT compared to women who have never used HRT. It is not known whether the difference is caused by HRT. It may be that women using HRT are examined more often, so that breast cancer is noticed earlier.

During or after the use of hormones such as those that are contained in CLIANE, benign liver tumors have rarely occurred, and malignant liver tumors even more rarely. In isolated cases, bleeding from such tumours into the abdominal cavity has endangered life. Although such events are extremely improbable, you should inform your doctor about any unusual feelings in your upper abdomen that do not disappear within a short time.

How to use CLIANE properly

  • Each pack covers 28 days of treatment. You have to take one tablet daily.
  • If you are using HRT for the first time, you may begin taking CLIANE at any time.
  • If you are changing from a sequential combined HRT treatment, you should start CLIANE tablets at the end of the scheduled bleed.

It does not matter at what time of the day you take your tablet, but once you have selected a particular time you should keep to it every day. The tablet should be swallowed whole with some liquid. When you have finished each pack start the next pack on the following day. Never leave a break between packs. Tablet taking should be continuous.

Please observe these instructions for use, otherwise you will not fully benefit from CLIANE.

What to do if you miss a dose

If you are less than 24 hours late, take it as soon as possible, and take the next one at your normal time. But if you are more than 24 hours late, leave the forgotten tablet in the blister pack. Continue to take the remaining tablets at the usual time.

If you discontinue tablet taking for several days, irregular bleeding may occur.

What to do when your bleeding pattern seems different

CLIANE has been made for women who are at least one year past their menopause, i.e. at least one year past their last natural bleeding. The treatment is designed to provide you with hormone replacement therapy without cyclical bleeding, but bleeding may occur in the first few cycles of use. The occurrence of the bleeding can be unpredictable but is unlikely to be excessive. Bleeding episodes should diminish significantly within the first 3 months of treatment and usually will cease.

If significant bleeding continues or if at any time bleeding or spotting becomes unacceptable for you, ask your doctor whether you should discontinue treatment or change to a sequential therapy.

Overdosage

Overdosage may cause nausea, vomiting and irregular bleeding. No specific treatment is necessary but you should consult your doctor if you are concerned.

When using CLIANE

Tell your doctor immediately if:

You should stop treatment and see your doctor immediately if you get a blood clot while you are taking CLIANE. Warning signs to look for are:

  • an unusual cough or coughing blood
  • unusual pains or swelling of your arm or leg
  • severe pain in the chest which may reach the left arm
  • breathlessness
  • your very first attack of migraine (typically a throbbing headache and nausea preceded by visual disturbances)
  • worsening of pre-existing migraine; any unusually frequent or severe headaches
  • partial or complete loss of vision, or double vision
  • slurring or speech disability
  • sudden changes to your hearing, sense of smell, or taste
  • dizziness or fainting
  • weakness or numbness in any part of your body
  • severe pain in your abdomen
  • inflamed veins (phlebitis)

CLIANE must also be stopped at once if you become pregnant or if you develop jaundice.

If bleeding occurs after a prolonged interval of amenorrhoea, talk to your doctor as this may need to be investigated.

Tell your doctor if:

Contact your doctor as soon as possible if:

  • you notice any changes in your own health, especially involving any of the items mentioned in this leaflet; do not forget about the items related to your immediate family
  • you feel a lump in your breast
  • you are to be immobilised or are to have surgery (consult your doctor at least four weeks in advance; see information on deep venous thrombosis in the "Before you use CLIANE" section).

Tell your doctor if you are taking any other medications

Oral contraceptives should not be used while taking CLIANE, but should not be required in any case, as you should be at least one year past your menopause.

Some medicinal products may prevent HRT from working properly. These include medicinal products used for the treatment of epilepsy (e.g. hydantoins, barbiturates, primidone, carbamazepine) and tuberculosis (e.g. rifampicin); and antibiotics (e.g. penicillins and tetracyclines) for some other infectious diseases. Always tell the doctor who prescribes HRT which medicinal products you are already using. Also tell any other doctor or dentist who prescribes another medicinal product (or the dispensing pharmacist) that you use CLIANE.

If you are diabetic your doctor may alter the dose of the diabetes medication.

If you are in doubt about any medicinal products you are taking, ask your doctor.

Excess intake of alcohol during use of HRT may lead to increased blood levels of estradiol.

The use of HRT may affect the results of certain laboratory tests. Always tell your doctor or the laboratory staff that you are using hormone replacement therapy.

Side effects

Serious side effects

Serious reactions associated with the use of HRT preparations such as CLIANE, as well as the related symptoms, are described in the sections "Before you use CLIANE" and "When using CLIANE". Please read these sections carefully and consult your doctor where appropriate.

Other possible side effects

During the first few months of treatment you may experience some vaginal bleeding at unexpected times (breakthrough bleeding and spotting) and some breast tenderness or enlargement. These are usually temporary and normally disappear with continued treatment. If they do not, contact your doctor.

The following symptoms, which may or may not have been caused by HRT, and which in some cases were probably symptoms of the menopause, have been reported in users of various oral HRT preparations:

  • Reproductive system and breast disorders: changes in vaginal bleeding pattern and abnormal bleeding or flow, breakthrough bleeding, spotting (bleeding irregularities usually subside during continued treatment); dysmenorrhoea (painful menstruation), changes of vaginal secretion, premenstrual-like syndrome, breast pain, tenderness or enlargement
  • Gastrointestinal disorders: dyspepsia (indigestion), bloating, nausea, vomiting, abdominal pain
  • Skin and subcutaneous tissue disorders: rashes, various skin disorders (including pruritus, eczema, urticaria, acne, hirsutism, hair loss, erythema nodosum)
  • Nervous system disorders: headache, migraine, dizziness, anxiety/depressive symptoms, fatigue
  • Miscellaneous: palpitations, oedema, muscle cramps, changes in body weight, increased appetite, changes in libido (sexual drive), visual disturbances, intolerance to contact lenses, hypersensitivity reaction.

If you notice any unwanted effects not mentioned in this leaflet, or if you are unsure about the effect of this product, please inform your doctor or pharmacist.

Storage

Do not use after the expiry date stated on the package.

Store all drugs properly and keep them out of reach of children.

Further information

CLIANE tablets contain:

active substances (per tablet)

estradiol (2.0mg, as hemihydrate) and norethisterone acetate (1.0mg)

other substances

lactose monohydrate, maize starch, pre-gelatinised maize starch, povidone 25 000, talc, magnesium stearate, hydroxypropylmethylcellulose, macrogol 6000, titanium dioxide, ferric oxide pigment (red)

If you have any further questions, please consult your doctor or pharmacist.

This leaflet was last revised on 10 August 2003.