Indivina

Indivina 1 mg/2.5 mg tablets

Indivina 1 mg/5 mg tablets

Indivina 2 mg/5 mg tablets

estradiol /medroxyprogesterone

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, 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 gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

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. How to store Indivina

6. Further information

What Indivina Is And What It Is Used For

The name of your medicine is Indivina. It is a hormone replacement therapy (HRT) used to treat some of the symptoms which occur when the oestrogen levels decline and the periods stop (menopause) by replacing the oestrogen that your body is no longer producing. The tablets contain oestrogen and progestogen. Indivina is only recommended for women whose periods stopped more than three years ago and who still have their womb.

Indivina can also be used to help to prevent osteoporosis (thinning of the bones) if you are at an increased risk of fractures due to osteoporosis but are unable to take other treatments or if other therapies prove to be ineffective. Your doctor should discuss all the available options with you.

There is only limited experience of treating women older than 65 years with Indivina.

Before You Take Indivina

Medical check-ups

Before you start taking Indivina, your doctor will inform you about the risks and benefits of the treatment (see also section 4, “Other side effects of combined HRT”). Before you start treatment and regularly during treatment, your doctor will evaluate whether Indivina is the right treatment for you. Your doctor will tell you how often you should go for periodic check-ups, taking into account your general state of health. If you have any close relative (mother, sister, maternal or paternal grandmother), who has suffered from serious illness, e.g. blood clot or breast cancer, you might be at increased risk. You should therefore always tell your doctor about any close relative suffering from serious illness, and you should also tell your doctor about any changes, you might find in your breasts.

As well as regular check-ups with your doctor, be sure to:

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


• Go for regular breast screening (mammography) and cervical smear tests.
  
  
  • While you are receiving this medication, you should see your doctor regularly, at least every six to twelve months
  • If you have unusual symptoms such as unexplained pains in the chest, abdomen or legs you must consult your doctor immediately.
  • If you have a family history of breast cancer you should use this medication with great caution.

Do not take Indivina, if:

• you are allergic (hypersensitive) to estradiol valerate or medroxyprogesterone acetate or any of the other ingredients of Indivina (see section 6: Further information)


• you have or have had breast cancer in the past


• you have or have had an oestrogen-dependent tumour such as endometrial cancer (cancer of the lining of the womb)


• you have unusual vaginal bleeding that has not been checked by a doctor


• you have endometrial hyperplasia (abnormal growth of the lining of the womb) that is not being treated


• you have had a recent blood clot of an artery (leading to chest pain or heart attack)


• you have had liver disease and have been told by your doctor that your liver function has not yet returned to normal


• you have or have had a blood clot in a vein in your leg or anywhere else (a “deep vein thrombosis or pulmonary embolism”)


• you have porphyria (a genetic disorder).

Take special care with Indivina

As well as benefits, HRT has some risks which you need to consider when you are deciding whether to take it, or whether to carry on taking it. Tell your doctor if you have any of the following as you may need more frequent check ups’ if:

• you think you might be at risk of oestrogen dependent tumors such as breast cancer or endometrial cancer (see the section below on effects on your risk of developing cancer)


• you have had endometrial hyperplasia (thickening of the lining of the womb)


• you have uterine fibroids or endometriosis


• you feel you might be at risk of developing blood clots (see section below on blood clots)


• you have liver, kidney or heart problems


• you have gallstones


• you have asthma, epilepsy or diabetes


• you have high blood pressure


• you have otosclerosis (hearing problems due to bone overgrowth in the ear)


• you have been told that you have an intolerance to some sugars


• you have systemic lupus erythematosus (SLE)


• you have migraine or severe headaches


• you have been told you have high cholesterol or fat levels in your blood


• you are 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.

HRT may change the results of some laboratory tests. If you are going to have any laboratory tests, tell your doctor/nurse that you are taking Indivina.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

In particular tell your doctor if you are taking any of the following:

• antibiotics such as rifampicin, rifabutin


• anti-epileptic medicines such as phenytoin, phenobarbital and carbamazepine


• HIV medicines such as nelfinavir, ritonavir, nevirapine and efavirenz


• the herbal preparation St. Johns Wort.

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

Taking Indivina with food and drink

Indivina can be swallowed with a glass of water at the same time each day.

Pregnancy and breast-feeding

• Pregnancy – Do not take Indivina if you are pregnant, think you are pregnant or planning to become pregnant


• Breast feeding – Do not take Indivina if you are breast feeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Indivina should not affect your ability to drive or operate machinery.

Important information about some ingredients of Indivina

This medicine contains lactose. If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicinal product.

How To Take Indivina

Always take Indivina as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Take one Indivina tablet every day, preferably at about the same time each day. Calendar days are printed on the blister sheet to help you follow your daily tablet intake. Swallow the tablet whole with a drink if necessary. You will normally start on the lowest dose of Indivina and this will be increased, if necessary. Your doctor should aim to prescribe the lowest dose for the shortest time that gives you relief from your symptoms. Talk to your doctor if your symptoms are not better after three months. If you feel that the effect of Indivina is too strong or too weak, do not change the dose or stop taking the tablets yourself, but ask your doctor for advice.

If you are not having periods and you have not previously taken HRT or you are changing from another continuous combined HRT product, treatment with Indivina may be started on any day.

If you switch from a cyclic HRT regimen, start Indivina treatment one week after taking the last tablet of the cyclic HRT. Talk to your doctor or pharmacist if you are unsure.

Whilst taking this medicine

When you first start taking Indivina you may get some bleeding at odd times for a few months (Please also refer to the section above on Endometrial cancer). However, if this is still happening after a few months or if you experience heavy bleeding tell your doctor.

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. An overdose of Indivina could make you feel sick or make you get a headache or uterine bleeding.

If you forget to take Indivina:

It is best to take the tablet at the same time each day. If you forget to take a tablet leave the forgotten tablet. You should then continue by taking the next tablet at your usual time. Missing a tablet or irregular use of Indivina tablets may cause breakthrough bleeding or spotting.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

If you stop taking Indivina

If you want to stop taking Indivina, talk to your doctor first. He/she will explain the effects of stopping treatment and discuss other possibilities with you.

Indivina Side Effects

Like all medicines, Indivina may cause side effects although not everybody gets them, particularly early on (in the first few months of treatment), for example irregular bleeding may occur. These often disappear with continued treatment.

There are a number of situations in which you may have to stop taking Indivina. Tell your doctor immediately if you develop any of the following conditions:

Common (affecting more than 1 person in 100):

• feeling sick, stomach pain


• headache


• breast tenderness, breast enlargement, breakthrough bleeding


• weight increase or decrease


• changes in mood including anxiety and depressive mood, changes in libido


• increase in size of uterine muscle lumps (fibroids)


• swelling caused by fluid retention

Uncommon (affecting more than 1 in 1,000 but less than 1 in 100)

• dizziness, migraine


• leg cramps


• increased blood pressure


• vaginal thrush (candidiasis)


• indigestion/heartburn


• wind, vomiting


• gall bladder disease and/or gallstones

Rare (affecting more than 1 in 10,000 but less than 1 in 1,000)

• skin rash, itching


• blood clots


• hair loss, excessive hair growth (hirsutism)

Other side effects of combined HRT

The following side effects have been reported after taking other oestrogen/progestagen products:

Oestrogen dependent tumours, heart attack, stroke, disorders of skin and underlying tissues.

Endometrial hyperplasia and endometrial cancer

In women with an intact uterus, the risk of excessive growth of the womb lining (endometrial hyperplasia) is increased. Treatment with unopposed oestrogens for long periods of time increases the risk of cancer of the lining of the womb (endometrial cancer). Adding a progestagen, which Indivina contains, greatly reduces this increased risk.

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

Breast cancer

Every woman is at risk of getting breast cancer whether or not she takes HRT. There is a small increase in this risk for women who have been using HRT compared with women of the same age who have never used HRT. This risk increases with the duration of intake of HRT, but returns to normal within a few (at most five) years of having stopped HRT. The risk seems to be higher for women who use oestrogen in combination with progestagen as compared to oestrogen alone.

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).

To be able to detect a breast tumour as early as possible, it’s important to regularly check your breasts for any changes and to discuss any changes with your doctor. Also go for regular health check, including mammography. If you are anxious about the risk of developing breast cancer, you should talk to your doctor about the risks and benefits of hormone replacement therapy.

Blood clots in the deep veins

Every woman is at risk of getting a blood clot whether or not she takes HRT.

HRT may increase the risk of blood clots in the veins up to3 times, especially in the first year of taking it.

If you suspect you are suffering from a blood clot, seek immediate medical attention.

You are also more likely to get a blood clot:

• If you are very overweight


• If you have had a blood clot before, or have had any blood clotting problem that needs treatment with a medicine such as Warfarin


• If any of your close family has had blood clots


• If you have had a miscarriage


• If you are off your feet for a long time through surgery, injury or illness


• If you have Systemic Lupus Erythematosus ((SLE) – an autoimmune disease)

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 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 60’s who are taking HRT, the figure would be 17 in 1000.

Symptoms that may be indicative of blood clots:

• Pain and swelling in your leg


• Sudden chest pain


• Difficulty breathing.

Seek immediate medical help. Stop taking HRT until your doctor says you can.

Heart disease

If you ever have had angina or heart attack, you should talk to your doctor about the risks and benefits of hormone replacement therapy.

There is no evidence from clinical trials of beneficial effects on the risks of cardiovascular disease with hormone replacement therapy in the menopause. Results from two large clinical studies showed that women, who used another type of oestrogen/progestagen combination, had a slightly increased risk of heart disease in the first year of use.

For other HRT products there are only very limited data from trials examining the effects on the risk of cardiovascular disease.

Stroke

There may be a slightly higher chance of having a stroke if you are taking HRT.

Other things that also increase the risk of stroke are:

• Getting older


• High blood pressure


• Smoking


• Drinking too much alcohol


• An irregular heartbeat.

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 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 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. Stop taking HRT until your doctor says you can.

Ovarian cancer

Long-term (at least 5 or 10 years) use of oestrogen-only HRTs and oestrogen plus progestogen HRTs has been associated with an increased risk of ovarian cancer in some epidemiological studies.

Dementia

HRT will not prevent memory loss. In one study of women who started using combined HRT after the age of 65, a small increase in the risk of dementia was observed.

Effects on the skin

Brown patches in the face (chloasma), 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 (vascular purpura).

If you notice any side effects not listed in this leaflet or if any of the side effects mentioned gets serious please tell your doctor or pharmacist.

How To Store Indivina

Keep out of the reach and sight of children. Do not use Indivina after the expiry date which is stated on the pack. Do not store above 30 ºC. Store in the original package in order to protect from moisture. Medicines should not be disposed via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information

What Indivina contains:

The active ingredients of Indivina tablets are estradiol valerate and medroxyprogesterone acetate. Three different strengths of tablets are available.

Indivina 1 mg/2.5 mg tablets contain 1 mg of estradiol valerate and 2.5 mg medroxyprogesterone acetate.

Indivina 1 mg/5 mg tablets contain 1 mg of estradiol valerate and 5 mg medroxyprogesterone acetate.

Indivina 2 mg/5 mg tablets contain 2 mg of estradiol valerate and 5 mg medroxyprogesterone acetate.

The other ingredients of all Indivina tablets are lactose monohydrate, maize starch, gelatin, and magnesium stearate

What Indivina looks like and contents of the pack:

Indivina 1 mg/2.5 mg tablets are white, round, bevelled-edge, diameter 7 mm, flat tablets with a code ‘1 + 2.5’on one side.

Indivina 1 mg/5 mg tablets are white, round, bevelled-edge, diameter 7 mm, flat tablets with a code ‘1 + 5’on one side.

Indivina 2 mg/5 mg tablets are white, round, bevelled-edge, diameter 7 mm, flat tablets with a code ‘2 + 5’on one side.

The tablets are packed in a PVC/PVDC-aluminium blister of 28 tablets. The pack sizes available are 1 x 28 tablets and 3 x 28 tablets for all three strengths. All pack sizes may not be available in your country.

Marketing Authorisation Holder:

Orion Corporation

Orionintie 1

FIN-02200 Espoo

FINLAND

Manufactured by:

Orion Corporation

Tengströminkatu 8

FIN-20360 Turku

FINLAND

This medicinal product is authorised in the Member States of the EEA under the following names:

Indivina, Duova

This leaflet was last revised: June 2010