Premarin

PREMARIN®

UK PATIENT INFORMATION LEAFLET
(Marketed)

PREMARIN* TABLETS (Conjugated Oestrogens)

Please read this leaflet carefully before you start taking your tablets. It contains important information about Premarin tablets which have been prescribed for you by your doctor. If you have any questions or are not sure about anything, ask your doctor or pharmacist (chemist).

WHAT IS IN MY TABLETS?

The name of your medicine is Premarin. It contains a mixture of natural hormones called conjugated oestrogens. Premarin is available in two different strengths: the maroon tablets contain 0.625mg conjugated oestrogens and the yellow tablets contain 1.25mg conjugated oestrogens

Premarin tablets also contain lactose, methylcellulose, magnesium stearate, sucrose, glyceryl mono-oleate, polyethylene glycol, carnauba wax, calcium sulphate anhydrous, microcrystalline cellulose, pharmaceutical glaze (shellac) and titanium dioxide (E171).

Dyes are used to colour the tablets:

Maroon tablets:

E110, sunset yellow
E132, indigo carmine
E127, erythrosine BS
Yellow tablets:

E104, quinoline yellow
E110, sunset yellow
Your tablets are supplied in calendar blister packs, each pack containing three strips of 28 tablets of the same colour.

Premarin is one of a group of medicines called Hormone Replacement Therapy (HRT), and is used to treat some of the symptoms of the menopause or "change of life".

Product Licence Holder

John Wyeth and Brother Limited
Trading as Wyeth Laboratories
Huntercombe Lane South
Taplow
Maidenhead, Berks, SL6 0PH.

Manufacturer

Wyeth Medica Ireland
Little Connell
Newbridge
Co. Kildare

Republic of Ireland

WHAT ARE MY TABLETS USED FOR?

During the menopause, the level of the oestrogen in your body will decrease. Oestrogen is one of the main hormones responsible for maintaining your normal menstrual cycle. As the amount of oestrogen produced by your body decreases, the menstrual cycle may become irregular and a period may only occur once every few months. Eventually your periods will stop altogether.

The lack of oestrogen which causes the menopause is also responsible for many of the unpleasant symptoms you have at this time. By replacing the oestrogen that your body no longer produces, Premarin can relieve some of these symptoms.

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

Premarin is usually prescribed for women who have had their womb removed (hysterectomy). However, women who have not had this operation can still take Premarin and their doctor may prescribe a second type of tablet containing another hormone called a progestogen to be taken 12-14 days per month as well as the Premarin tablets.

ARE THERE REASONS FOR NOT TAKING HRT?

You should not take Premarin if:

You know or suspect you are pregnant or you are breast-feeding
You have or have had breast cancer[*]You have oestrogen-dependent tumours such as cancer of the lining of the womb
You have any abnormal vaginal bleeding which has not been evaluated by your doctor
You have any abnormal growth of the lining of the womb (endometrial hyperplasia). Symptoms of endometrial hyperplasia include abnormal irregular vaginal
bleeding and the recurrence of bleeding in women whose periods have stopped.
You have a blood clot in a vein in your leg or anywhere else (a "deep vein thrombosis"), a blood clot that has travelled to your lung or another part of the body (an "embolus"), or you have had one of these in the past
You are suffering from a disorder which causes clotting in the blood vessels and you do not take a medication for prevention of blood clots
You have serious liver disease
You have serious heart disease
You are allergic to any of the ingredients of Premarin tablets (listed above)
You have porphyria (a metabolic disorder)

WHAT SHOULD I KNOW BEFORE TAKING MY TABLETS?

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

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've started on HRT, 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 HRT.

You are advised 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

Certain diseases may be made worse by HRT. If you have or have had any of the following conditions inform your doctor who will monitor you closely: uterine fibroids, endometriosis, a family history of clots in the blood vessels, if there is anyone in your family who has ever had an oestrogen-dependent cancer, such as cancer of the reproductive organs (womb, ovary) or breast cancer, high blood pressure, liver disorders, diabetes, gallstones, migraine, systemic lupus erythematosus, endometrial cancer, epilepsy, asthma, otosclerosis, thyroid deficiency. Tell your doctor if you notice any change in your condition whilst taking Premarin.

Oestrogens may cause fluid retention.

Also inform your doctor if you have or have had any heart or kidney disease, as the doctor may want to follow you more closely.

Effects on 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 to see if you should be taking HRT.

HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated oestrogen plus 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, the risk is likely to be similar, although this is not yet certain.
If you get:

a pain in your chest that spreads to your arm or neck
see a doctor as soon as possible and do not take any more HRT 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 HRT.

Looking at women in their 50s 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, /b>]11 in 1000 would be expected to have a stroke.

For women in their 60s 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 HRT 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 (also 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're off your feet for a long time because of major surgery, injury or illness[*]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 HRT.

Looking at women in their 50s 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 60s 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 a doctor as soon as possible and do not take any more HRT until your doctor says you can. These may be signs of a blood clot.

If you're 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.

Effects on your risk of 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 oestrogen-only HRT for 5 years is about the same as for a woman the same age who's still having periods over that time and not taking HRT. The risk for a woman who is taking oestrogen plus progestogen HRT is higher than for oestrogen-only HRT (but oestrogen 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 it, 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

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).
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 oestrogen-only HRT 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 oestrogen helps to lower the extra risk.

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

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take oestrogen without a progestogen.

If you've 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 oestrogen.

Your product, Premarin, is an oestrogen-only product.

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 for 5 years, the figure will be 9 in 1000 (i.e. an extra 4 cases).

If they take oestrogen-only HRT for 10 years, the figure will be 15 in 1000 (i.e. an extra 10 cases).

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

If you get breakthrough bleeding or spotting, it's 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've been on HRT for a while
carries on even after you've stopped taking HRT
- Make an appointment to see your doctor. It could be a sign that your 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 often no obvious signs of the disease.

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

Other Conditions

HRT may affect some medical tests. If you visit a hospital or clinic for any medical tests, you should tell the doctor concerned that you are taking HRT.
Women with pre-existing hypertriglyceridaemia (a disease resulting in an increase in triglycerides; fatty substances in the blood) may experience large increases of their plasma triglycerides, which can lead to inflammation of the pancreas (pancreatitis). If you have this condition your doctor will monitor you closely.
The colouring agent E110, which is present in the maroon and yellow tablets, can cause allergic-type reactions, including asthma, in some people. Such reactions are most common in people who are also allergic to aspirin.
If you have hypocalcaemia tell your doctor as HRT should be used with caution. Symptoms of hypocalcaemia (low calcium levels in your blood) include muscle cramps, abdominal cramps and spasms.
If you are taking thyroid hormone replacement therapy (e.g. thyroxine), your doctor may monitor your thyroid function more often when you start treatment.

What medicines should I avoid when using Premarin?

The effect of Premarin may be affected if other medicines are used at the same time. Therefore, always tell your doctor if you are taking other drugs, even those that do not require a prescription, especially herbal preparations and in particular those containing St. John's wort.

Medicines that may affect Premarin include anticonvulsants (e.g. phenobarbital, phenytoin, carbamazepine), anti-infectives (e.g. rifampicin rifabutin, nevirapine, efavirenz), ritonavir, nelfinavir and metyrapone.

Will Premarin affect my driving?

There is no evidence to suggest that taking Premarin will affect your ability to drive or to operate machinery.

HOW DO I TAKE MY TABLETS?

You may start your first pack at any convenient time.

For women with a uterus if you are transferring from a sequential HRT product (an HRT product that gives you a monthly bleed), treatment should begin the day following completion of the prior product unless instructed otherwise by your doctor.

The usual dose is one tablet per day, to be swallowed with a drink of water.

Do not leave a break between packs unless your doctor tells you to. Do not stop taking Premarin without first discussing it with your doctor.

How long do I need to take Premarin for?

That really depends on why you and your doctor have decided on a course of treatment. If you are taking HRT to relieve your immediate menopausal symptoms, you may be prescribed HRT for a relatively short period of time.

If, however, you or your doctor are worried about osteoporosis, you may be prescribed HRT for longer.

What if I miss a tablet or tablets?

If you forget to take a dose, take it as soon as you remember, then go on as before. If more than one tablet has been missed take the tablet for the day that you remember and continue as normal. Do not take double your dose to make up for your missed tablet.

Missed pills may cause breakthrough bleeding in women with a uterus.

Is Premarin like the Contraceptive Pill?

No. The contraceptive Pill uses higher doses of synthetic hormones to prevent ovulation and fertilisation of eggs. Premarin is NOT a contraceptive. For women with a uterus it is important that you use a reliable form of non-hormonal contraception if there is any possibility that you may still become pregnant. You should discuss this with your doctor.

My periods have stopped. Will they start again whilst taking Premarin?

If you have had a hysterectomy you are not expected to have a period. However, if you have not had a hysterectomy, you may be taking an additional progestogen tablet for 12-14 days each month, and you will probably have a "period", or withdrawal bleed each month at about the time you finish the additional progestogen tablets. This is caused by the hormones in the HRT and is perfectly natural. Some women taking "combined HRT" (oestrogen plus the additional progestogen) may experience a gradual reduction in withdrawal bleeding and it may eventually stop; this is quite normal. If you have any heavy or irregular bleeding you should tell your doctor.

What if I take too many tablets?

Do not worry. Premarin contains natural hormones and it is unlikely that serious problems will occur. If in any doubt consult your doctor or pharmacist.

You may feel some nausea (sickness), or experience a short period of vaginal bleeding (unless you have had a hysterectomy) if you take too many tablets.

Can I wash off the coating or crush the tablets?

It is best not to try to take off the coating or crush the tablets, as this could affect the way Premarin works. The dyes used are approved for use as food colourings. They are needed so that Premarin can be identified from other tablets, and so that the different strengths of Premarin can be easily recognised.

ARE THERE ANY SIDE EFFECTS?

Report these or any other unusual side effects to your doctor immediately. Do not take any more tablets unless your doctor tells you to.

a first migraine attack
a sudden loss or change in vision
shortness of breath
sharp pains in the chest
yellowing of the skin or whites of the eyes
painful swelling of a leg

See also "What should I know before taking my tablets; Breast Cancer, Endometrial Hyperplasia, Venous Thrombosis, Coronary Artery Disease, Stroke, Ovarian Cancer and Other Conditions"

Premarin may cause some unwanted effects, most of which are not serious and you need only tell your doctor if you are troubled by any of the following symptoms:

Breast pain, enlargement, tender breasts, discharge and changes in breast tissue
A tendency to thrush, vaginal discharge, inflammation of the vagina, breakthrough bleeding/spotting, change in menstrual flow, dysmenorrhoea (lower back & abdominal pain)
Feeling or being sick, a feeling of being bloated, abdominal pain
Skin rashes or discolouration, swellings or red patches on the skin, itching loss of or increases in hair
Minor eye changes which may cause difficulties if you wear contact lenses
Headaches, migraine, dizziness, and mood changes including: depression, nervousness and irritability
Weight changes (increase or decrease)
Changes in sex drive (libido)
Joint pain, leg cramps
A worsening of asthma, epilepsy and otosclerosis (inherited deafness)
A worsening of glucose tolerance

You should also tell your doctor or pharmacist if you notice any other unwanted effects whilst you are taking Premarin.

HOW DO I STORE MY TABLETS?

Keep out of the sight and reach of children.
Do not use this medicine after the date stated on the packaging.
If the pack has been opened or damaged return it to your pharmacist.
Do not let anyone else take your Premarin tablets even if they seem to have the same problem as you - it may harm them.
Return any unused medicine to your pharmacist. Only keep it if your doctor tells you to.

Leaflet approved: 10th February 2004.

* Trade mark