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 any 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. It may harm them, even if their symptoms are the same as yours.

In this leaflet:

• 1. What Indivina is and what it is used for.
• 2. Before you take Indivina.
• 3. How to take Indivina.
• 4. Possible side effects of Indivina.
• 5. Storing Indivina.

Marketing Authorisation Holder:

Manufacturer:

Marketing Authorisation Numbers

• UK: PL 27925/0011 - 13
• Ireland: PA 1327/5/1-3

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 have started on HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups, you 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.

Other medical conditions you may have

Do not start taking Indivina if you:

• Have or have had breast cancer
• Have or have had other estrogen dependent tumours such as endometrial cancer (cancer of the lining of the womb)
• Have recently had unusual vaginal bleeding (eg unexpected or unusually heavy periods) which has not been checked by a doctor
• Have endometrial hyperplasia (abnormal growth of the lining of the womb) which has not been treated
• Have had a recent or current blood clot of a vein in you leg or anywhere else (eg deep vein thrombosis or pulmonary embolism)
• Have had a recent or current blood clot of an artery (eg stroke or heart attack)
• Have or have had liver disease where you have been told the liver function is not yet normal
• Are allergic to any of the ingredients of Indivina (see the list of ingredients above)
• Have porphyria

Talk to you doctor if you have or have had any of the following conditions. Your doctor may need to see you more frequently for check-ups.

• If you feel you might be at risk of developing breast cancer or other estrogen-dependent tumours (see the section below on risks associated with developing cancer)
• Endometrial hyperplasia
• Uterine fibroids or endometriosis
• High blood pressure or other problems with your blood circulation
• Heart, kidney and liver disorders
• Diabetes mellitus
• Gallstones
• Migraine or severe headaches
• Systemic lupus erythematosus (SLE)
• Epilepsy
• Asthma
• Otosclerosis (loss of hearing because of bony growths in the ear)

Other Conditions

HRT may change the results of some laboratory tests (such as thyroid and liver function tests). If you are going to have any laboratory tests, tell you doctor/nurse that you are taking Indivina.

Tell your doctor if you have been told that you have high triglyceride levels. Very rarely, high triglyceride levels in women taking estrogen can cause pancreatitis (inflammation of the pancreas).

These tablets contain lactose. If you have been told that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

When should you stop taking Indivina

There are a number of situations in which you should stop HRT. Consult your doctor immediately about stopping Indivina treatment if you develop any of the following during treatment with Indivina.

• You develop any of the conditions under 'do not start taking Indivina'
• Signs of a blood clot in the veins (see the section below on blood clots)
• You have been told that your blood pressure has increased
• Yellowing of the skin or you have been told that you have a problem with your liver
• New onset of migraine-type headache
• If you think you are pregnant

You may need to stop taking Indivina before having surgery - please see the section on blood clots.

Important Information about the safety of HRT

As well as benefits, HRT has some risks that need to be considered when you are deciding whether to take HRT or whether you want to continuing taking HRT. These risks are:

• Effects on you heart or circulation - heart disease, stroke and blood clots
• Risks associated with developing cancers - breast cancer, ovarian cancer and endometrial cancer

Effects in 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 or see if you should be taking HRT.

HRT will not prevent heart disease

Studies with one type of HRT product (containing conjugated estrogen and 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 products, the risk is likely to be similar, although this is not yet certain.

If you get:

• A pain in your chest that spreads to you arm and neck

• See a doctor as soon as possible and do not take any more Indivina 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 Indivina.

Compare

Looking at women in their 50's 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 50's who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60's who are not taking HRT - an average, over a 5 year period, 11 in 1000 would be expected to have a stoke.

For women in their 60's 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 Indivina 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 (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 are off your feet for a long time as a result of major surgery, illness or injury
• 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 Indivina

Compare

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

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

For women in their 60's 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 your doctor as soon as possible and do not take any more Indivina until your doctor says you can. These may be signs of a blood clot.

If you are going to have surgery, make sure your doctor knows about it. You may need to stop taking Indivina 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 Indivina again.

Risks associate with 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 estrogen-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 estrogen plus progestogen HRT is higher than for estrogen-only HRT (but estrogen 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.

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 estrogen-only HRT at aged 50 and take it for 5 years, the figure will be between 33 and 34 in 1000 (ie an extra 1-2 cases).

If they take estrogen-only HRT for 10 years, the figure will be 37 in 1000 (ie an extra 5 cases)

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

If they take estrogen plus progestogen HRT for 10 years, the figure will be 51 in 1000 (ie 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 estrogen-only HRT products 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 estrogen helps to lower the extra risk.

If you still have a womb your doctor may prescribe a progestogen as well as estrogen. If so, these may be prescribed separately or as a combined HRT product like Indivina.

If you have had your womb removed (a hysterectomy) your doctor will discuss this with you whether you can safely take estrogen without progestogen. Indivina is not recommended for these women.

If you have 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 estrogen.

Your product, Indivina 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 years

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

The addition of progestogen to estrogen only HRT substantially reduces the risk of endometrial cancer

If you get breakthrough bleeding or spotting it is 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 have been on HRT for a while
• carries on even after you have stopped taking HRT

• Make an appointment to see your doctor. It could be a sign that you 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 no obvious signs of the disease.

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

Pregnancy and Breastfeeding

Indivina should not be taken if you are pregnant or breastfeeding. If you think that you might be pregnant, stop taking Indivina and contact your doctor.

Taking Indivina with other medicines

Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, even those not prescribed. Certain medicines, if taken together with Indivina, may decrease the effect of Indivina. These include:

• Antiepileptic medicines (e.g. Phenobarbital, phenytoin, carbamazepine)
• Anit-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz)
• HIV medicines (nelfinavir and ritonavir)
• Herbal medicines which contain St. Johns wort (Hypericum perforatum)

If you are in any doubt about taking other medicines with Indivina, talk to your doctor or your pharmacist.

If you take more Indivina than you should:

If you or somebody else has taken too many Indivina tablets, talk to your doctor or pharmacist. Estrogen overdose may cause nausea, headache and vaginal bleeding.

If you forget to take a tablet:

If you forget to take your tablet at the usual time, try to take it within the next 12 hours. Otherwise leave the forgotten tablet in the blister and take the next tablet at the usual time. Calendar days are printed on the blister sheet to help you follow your daily tablet intake.

Make sure you have an ample supply of your medicine for your holidays or travel.

If bleeding occurs:

When you first start taking Indivina you may get some irregular vaginal bleeding (Please also refer to the section above on Endometrial cancer). However, tell your doctor if this is still happening after a few months. Your doctor may also ask about any vaginal bleeding with Indivina at your regular check-ups. You may find it helpful to make a note of bleeding in your diary.

Your local representative:

UK:

Ireland: