Premarin Tablets

PREMARIN 0.3 mg, 0.625 mg & 1.25 mg Coated Tablets (Conjugated Estrogens)

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 further questions, please 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.

In this leaflet:

1. What Premarin is and what it is used for

2. Before you take Premarin

3. How to take Premarin

4. Possible side effects

5. How to store Premarin

6. Further information

What Premarin Is And What It Is Used For?

Premarin is one of a group of medicines called Hormone Replacement Therapy (HRT). It is used to treat some of the symptoms and conditions associated with the menopause. Premarin is an estrogen-only HRT.

The menopause is due to lowered levels of the hormones estrogen and progesterone. You may experience a number of unpleasant symptoms, including hot flushes, night sweats and vaginal dryness, around the time of menopause. Premarin can relieve some of these symptoms by replacing some of the lost estrogen.

After the menopause some women may develop bone thinning (osteoporosis). 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, Premarin 0.625mg or 1.25mg Coated Tablets 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 for 12-14 days per month as well as the Premarin tablets.

Before You Take Premarin

1 Do not take Premarin if:

• you are allergic (hypersensitive) to conjugated estrogens or any of the ingredients of Premarin; the ingredients are listed in Section 6 of this leaflet


• you have or have had breast cancer


• you have endometrial cancer (cancer of the lining of the womb) or have been told you have another type of estrogen dependent cancer


• you have been told you have a blood circulation disorder or have had a blood clot


• you have a heart condition such as angina or have had a heart attack


• you have porphyria (a rare inherited metabolic disorder).

If any of the following applies to you discuss this with your doctor before taking Premarin, as it may not be suitable for you:

• you have recently had unexpected or very heavy vaginal bleeding


• you have been told that you have endometrial hyperplasia (abnormal growth of the lining of the womb)


• you have or have previously had liver disease


• you are pregnant, or you are breast-feeding.

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.

Some diseases may be made worse by HRT. Therefore, if you have or have ever had any of the following conditions inform your doctor as he or she may want to monitor you more closely:

• uterine fibroids or endometriosis


• risk factors for blood clots (see section titled ‘Blood Clots’ below)


• a close relative who has had breast cancer or an estrogen dependent cancer, such as cancer of the womb or ovaries


• high blood pressure


• heart disease


• kidney disease


• diabetes


• gallbladder disease or gallstones


• migraine


• systemic lupus erythematosus (SLE - a rare chronic inflammatory disease)


• epilepsy


• asthma


• otosclerosis (hearing loss due to a problem with the bones in your ear)


• low blood calcium levels (hypocalcaemia)


• high levels of fatty substances in the blood (hypertriglyceridaemia).

If there is a change in any of the above conditions whilst taking Premarin tell your doctor.

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.

2 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 estrogens 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, 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 (systemic lupus erythematosus).

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.

3 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 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 it, but returns to normal within about 5 years after stopping HRT.

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 estrogen-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 estrogen-only HRT for 10 years, the figure will be 37 in 1000 (i.e. 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 (i.e. an extra 6 cases).

If they take estrogen 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 estrogen-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 estrogen helps to lower the extra risk.

If you still have your womb, your doctor may prescribe a progestogen as well as estrogen. 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 estrogen 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 estrogen.

Your product, Premarin, is an estrogen-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 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 a progestogen to estrogen-only HRT substantially reduces the risk of endometrial cancer.

If you get break-through 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 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 increase the risk in the same way.

4 Other conditions

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.

Women with hypertriglyceridaemia may experience large increases of their plasma triglycerides, which can lead to inflammation of the pancreas (pancreatitis). Symptoms of pancreatitis may include abdominal pain, abdominal swelling, fever and feeling or being sick.

If you are taking thyroid hormone replacement therapy (e.g. thyroxine), your doctor may monitor your thyroid function more often when you start treatment.

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.

5 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:

• an anticonvulsant (used in the treatment of epilepsy e.g. phenobarbital, phenytoin, carbamazepine)


• an anti-infective (e.g. rifampicin, rifabutin, nevirapine, efavirenz, erythromycin, ketoconazole, ritonavir, nelfinavir)


• a herbal preparation such as St. John’s wort (Hypericum perforatum)


• metyrapone (most commonly used in the treatment of Cushing’s syndrome).

The way that Premarin works may be altered if other medicines are used at the same time.

6 Pregnancy and breast-feeding

You should stop taking Premarin and tell your doctor immediately if you know or suspect you are pregnant, or if you are breast-feeding.

Premarin is not a contraceptive. It is important that you use a reliable form of non-hormonal contraception (e.g. condom or diaphragm) if there is any possibility that you may still become pregnant. You should discuss this with your doctor.

7 Driving and using machinery

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

8 Important information about some of the ingredients in Premarin

Premarin contains lactose and sucrose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

The colouring agent E110 (sunset yellow), that is used in the maroon and yellow tablets, may cause allergic reactions.

The green tablets contain methyl p-hydroxybenzoate and propyl p-hydroxybenzoate. These ingredients may cause allergic reactions (possibly delayed).

How To Take Premarin

1 Starting to take Premarin

Always take Premarin exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure. The usual dose is one tablet every day.

Take your tablet at the same time each day as this will help to remind you to take your medicine.

If you are not already taking an HRT product or if you are taking an HRT product that does not give you a monthly bleed you may start your first pack of Premarin at any convenient time.

If you are changing from an HRT product that gives you a monthly bleed, start Premarin the day after you finish the course of the previous product, unless instructed otherwise by your doctor.

While you are taking Premarin you will have no tablet-free days. You should start your next pack the day after you finish the previous one.

2 The usual dose

For menopausal symptoms the usual dose is one tablet every day. Your doctor will prescribe the lowest dose that will control your symptoms. Premarin 0.3mg is the lowest starting dose. If your symptoms are not adequately controlled higher doses of Premarin can be used.

For the treatment of osteoporosis the usual dose is one 0.625mg tablet every day but your doctor may advise you to use 1.25mg each day. You and your doctor should review the need for treatment regularly.

Do not try to take off the coating, divide or crush the tablets as this could affect the way Premarin works.

3 While you are taking Premarin

If you have had a hysterectomy you are not expected to have a period.

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" (estrogen plus the additional progestogen) may experience a gradual reduction in withdrawal bleeding and it may eventually stop; this is quite normal. If you experience troublesome bleeding or it continues beyond the first 3 months of treatment discuss this with your doctor (see section titled Endometrial Cancer above).

4 If you take more Premarin than you should

If you take too many tablets don’t worry. You may feel some nausea (sickness) and if you have not had a hysterectomy you may experience a short period of vaginal bleeding, but it is unlikely that serious problems will occur. If you are concerned, talk to your doctor or pharmacist.

5 If you forget to take Premarin

If you forget to take a tablet don’t worry. Take it as soon as you remember and then carry on taking the remaining tablets at the usual time.

If more than one tablet has been forgotten, do not take extra to try to make up for the missed tablets.

Missed tablets may cause a short period of light bleeding in women who have not had a hysterectomy.

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

Premarin Tablets Side Effects

Like all medicines, Premarin can cause side effects, although not everybody gets them.

Stop Taking Premarin and tell your doctor immediately if you:

• have an allergic reaction, signs of which include rash, itching, shortness of breath, difficulty breathing and a swollen face


• experience a migraine type headache (typically a throbbing headache and nausea preceded by visual disturbances) for the first time


• develop signs of jaundice (yellowing of the skin or the whites of the eyes)


• become pregnant


• experience a significant increase in your blood pressure


• develop a contraindication (see section titled Before you take Premarin)

Do not take any more tablets until your doctor says you can.

HRT can increase the risk of heart disease, stroke, blood clots, breast cancer, endometrial cancer and ovarian cancer. Please see Section 2 (Before you take Premarin).

In addition to those discussed in section 2, the following side effects have been reported in women taking HRT:

• breakthrough bleeding or spotting, changes in menstrual flow, pelvic pain, vaginal inflammation and vaginal discharge


• a tendency to get thrush


• breast pain, breast tenderness, swollen breasts, discharge from the nipples and changes in breast tissue


• feeling or being sick, a feeling of being bloated, abdominal pain


• headache or migraine


• dizziness


• changes in mood including anxiety, depression and irritability


• joint pain, leg cramps


• changes in your interest in sex (increased or decreased libido)


• visible swelling of the face or ankles


• rash, itchiness, acne and dark or red patches on the skin


• changes in hair growth (loss or increase)


• minor changes to the eye, difficulty wearing contact lenses


• changes in weight (increase or decrease)


• changes in your triglyceride levels (fatty substances in the blood)


• an intolerance to glucose


• memory loss


• a worsening of chorea (an existing neurological disorder characterised by involuntary spasmodic movements of the body).


• induce or exacerbate symptoms of angioedema, which consists of generalized swelling of parts of the body, most frequently around the face, mouth, tongue and neck areas, particularly in women with hereditary angioedema.

These side effects are usually temporary and should get better over time.

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.

How To Store Premarin

Keep out of the reach and sight of children.

Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of that month.

Do not store above 25°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help the environment.

Further Information

1 What Premarin contains

The active substance is a mixture of hormones called conjugated estrogens.

Premarin is available in three different strengths; the green tablets marked with ‘0.3’ in white ink contain 0.3mg conjugated estrogens, the maroon tablets marked with ‘0.625’ contain 0.625mg conjugated estrogens and the yellow tablets marked with ‘1.25’ contain 1.25mg conjugated estrogens.

The other ingredients in your tablets are lactose, methylcellulose, magnesium stearate, sucrose, glyceryl monooleates, macrogol, carnauba wax, calcium sulphate anhydrous, microcrystalline cellulose, pharmaceutical glaze (shellac), titanium dioxide (E171), stearic acid, edible ink and coating.

The edible ink on the green and maroon tablets contains titanium dioxide (E171), purified water, shellac (E904), ethanol, n-butyl alcohol, propylene glycol (E1520), ammonia solution and ethyl acetate. The edible ink on the yellow tablets contains iron oxide black (E172), purified water, shellac (E904), ethanol, n-butyl alcohol, propylene glycol (E1520), ammonia solution and ethyl acetate.

The coating on the green tablets contains sucrose, yellow iron oxide (E172), indigo carmine (E132), titanium dioxide (E171), polyvinyl pyrrolidone, sodium benzoate, methyl p-hydroxybenzoate (E218), propyl p-hydroxybenzoate (E216), and purified water.

The coating on the maroon tablets contains sucrose, purified water, erythrosine (E127), titanium dioxide (E171), sunset yellow (E110), indigo carmine (E132), polyvinylpyrrolidone and sodium benzoate.

The coating on the yellow tablets contains quinoline yellow (E104) and sunset yellow (E110).

These dyes are approved for use as food colourings.

2 What Premarin looks like and contents of the pack

Your Premarin carton contains three calendar blister packs, each containing 28 tablets of the same colour. Not all pack sizes may be marketed.

The marketing authorisation holder is

John Wyeth & Brother Ltd

trading as Wyeth Pharmaceuticals

Huntercombe Lane South

Taplow

Maidenhead

Berkshire

SL6 0PH

The manufacturer is

Wyeth Medica Ireland

Little Connell

Newbridge

County Kildare

Republic of Ireland

This leaflet applies to Premarin tablets only.

This leaflet was last approved in 07/2010.

* Trademark

Doc ID 58114 (clean version of doc 58113)