Estrofem ® 1 mg/2 mg Film-Coated Tablets

Estrofem ® is a hormone replacement therapy (HRT) that is used:

• To relieve unpleasant symptoms like hot flushes, night sweats, vaginal dryness which occur when the estrogen levels decline and the periods stop (menopause).
• For the prevention of osteoporosis (thinning of the bones), if you are at high risk of future fracture and if you are unable to take other medicines for this purpose.

Estrofem ® is prescribed for women who have had their womb removed (have had a hysterectomy). There is only limited experience of treating women older than 65 years with Estrofem ®.

Do not take Estrofem ®:

If any of the following applies to you, do not take Estrofem ®:

• If you are allergic (hypersensitive) to estradiol or any other ingredients in Estrofem ® (see section 6).
• If you have, have had or suspect you have breast cancer.
• If you have a family history of breast cancer.
• If you have or suspect you have or have had a hormone dependent tumour (e.g. cancer of the lining of the womb).
• If you have any vaginal bleeding, which has not been diagnosed by your doctor.
• If you have endometrial hyperplasia (excessive growth of the womb lining) that is not being treated.
• If you have a blood clot (like deep vein thrombosis (DVT) or lung embolism) or previously have had a blood clot without obvious cause e.g. in connection with surgery or pregnancy (see section “Blood clots”).
• Have a blood clotting disorder (such as protein C, protein S or antithrombin deficiency).
• Have or previously have had a disease caused by blood clots in the arteries, such as a heart attack or angina.
• If you have high blood pressure.
• 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 pregnant.
• If you are known to have inherited genetic changes called BRCA1 and/or BRCA2 genes.
• If you started your menstrual periods early (before the age of 12 years).
• If you have a history of non-cancerous breast diseases such as atypical hyperplasia or lobular carcinoma in situ.
• If you had any previous treatment using radiation therapy to the chest or breast.
• If you have been treated or exposed while in your mother's womb to a medicine called diethylstilbestrol (DES).

Warnings and precautions

Take special care with Estrofem ®:

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 Estrofem ®:

• If you have any condition affecting the womb lining, such as a leiomyoma (benign tissue tumour), endometriosis (presence of womb lining tissue outside the womb) or have had endometrial hyperplasia (excessive growth of the womb lining).
• If you have a history of blood clots (thrombosis) or have risk factors for blood clots (these risk factors and symptoms for a blood clot are listed in section “Blood clots”).
• If any of your immediate family has had cancers related to estrogen (endometrial cancer).
• If you have a liver disorder such as liver adenoma (a benign tumour).
• If you have a kidney or heart disorder.
• If you have diabetes or gallstones.
• If you have epilepsy (fits) or asthma.
• If you have migraine or severe headache.
• If you have systemic lupus erythematosus (SLE, autoimmune collagen disease, which may affect many organ systems).
• If you have high levels of fat in your blood (hypertriglyceridemia).
• If you have otosclerosis (hearing loss sometimes linked to pregnancy).
• You are on treatment for depression.
• You have had depression with previous use of estrogen and/or progesterone/progestogen-containing medicines.
• You have a substance abuse problem.
• You have an underlying psychiatric disorder such as post-traumatic stress disorder or bipolar disorder.
• You have a family history of mental disorders.
• You have a history of physical or sexual abuse.

Estrogen containing medicines, including Estrofem ®, may cause mood changes and depression, which may be severe. Severe depression is associated with a higher risk of suicidal thoughts/behaviour (e.g. talking about suicide, withdrawing from social contact, having mood swings, being preoccupied with death or violence, feeling hopeless about a situation, increasing use of alcohol/drugs, doing self-destructive things, personality changes) and suicide. Contact your doctor in case of mood changes and depressive symptoms, including shortly after beginning treatment of Estrofem ®.

If you need a blood test, tell your doctor that you are taking Estrofem ®, since estrogen can affect the results of certain laboratory tests. If you are going to have surgery, talk to your doctor. You may need to stop taking these tablets 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start treatment again.

Stop taking Estrofem ® If you are experiencing any of the following conditions below, stop taking Estrofem ®, and contact your doctor immediately:

• If you get a migraine-type headache for the first time.
• If you develop yellow skin or eyes (jaundice) or other liver problems.
• If you have symptoms of significant increase in blood pressure (e.g. headache).
• If you become pregnant.
• If any of the conditions listed contraindications “Do not take Estrofem ®” occur.

Medical check-ups

Before you start taking Estrofem ®, 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 Estrofem ®, 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 Estrofem ®.

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. Additionally, you are advised to join mammography screening programs when offered to you. For mammogram screening, it is important that you inform the nurse/health care provider who is actually taking the x-ray that you use Estrofem ®, as this medicine 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.

Safety of HRT

As well as benefits, Estrofem ® has some risks which you need to consider when you’re deciding whether to take it or whether to carry on taking it.

Do not share medicines prescribed for you with any other person. Always take Estrofem ® exactly as your doctor has told you. You should check with your doctor or pharmacist if you are unsure.

If your womb has been removed or if you have no vaginal bleeding and you are not taking other hormone therapy products, you can start treatment on any convenient day.

• 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.
• Tablets can be taken with or without food and drink.

For instructions on the use of the calendar pack, see “How to use the calendar dial pack