PREMARIN 0.625 MG COATED TABLETS - patient leaflet, side effects, dosage

The coating on the green tablets contains hypromellose, titanium dioxide (E171), quinoline yellow (E104), indigo carmine (E132), macrogol and polysorbate 80.

The coating on the maroon tablets contains hypromellose, titanium dioxide (E171), red aluminium lake (E129), indigo carmine (E132) and macrogol.

The coating on the yellow tablets contains hypromellose, titanium dioxide (E171), quinoline yellow (E104), sunset yellow (E110), macrogol and polysorbate 80.

These dyes are approved for use as food colourings.

What Premarin looks like and contents of the pack

Premarin contains either one blister of 21 tablets or three blisters of 28 tablets in a carton or 100 tablets in a securitainer of the same colour tablets.

Not all pack sizes may be marketed.

The marketing authorisation holder is Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ. United Kingdom.

The manufacturer is:

Pfizer Ireland Pharmaceuticals, Little Connell, Newbridge, County Kildare, Republic of Ireland.

Or

Pfizer Italia S.r.l., Localita Marino del Tronto, 63100 , Ascoli Piceno (AP), Italy

This leaflet applies to Premarin tablets only.

This leaflet was last revised in 09/2020.

Ref: PA 11_0

o painful swelling and redness of the legs

o sudden chest pain

o difficulty in breathing.

For more information, see section titled “Blood Clots in a vein (thrombosis)” be­low.

Premarin is not a contraceptive. If it is less than 12 months since your last menstrual period or you are under 50 years old, you may still need to use additional contraception to prevent pregnancy. Speak to your doctor for advice.

HRT and cancer

Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer)

Taking estrogen-only HRT will increase the risk of excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the womb lining (endometrial cancer).

Taking a progestogen in addition to the estrogen for at least 12 days of each 28 day cycle protects you from this extra risk. So your doctor will prescribe a progestogen separately if you still have your womb. If you have had your womb removed (a hysterectomy), discuss with your doctor whether you can safely take this product without a progestogen.

In women who still have a womb 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 aged 50 to 65 who still have a womb and who take estrogen-only HRT, between 10 and 60 women in 1000 will be diagnosed with endometrial cancer (i.e. between 5 and 55 extra cases), depending on the dose and for how long it is taken.

Premarin 0.625 mg and 1.25 mg tablets contain a higher dose of estrogens than other estrogen-only HRT products. The risk of endometrium cancer when using Premarin 0.625 mg and 1.25 mg tablets together with a progestogen is not known.

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. After stopping treatment risk may remain elevated for at least 10 years. In women with a uterus, use of estrogen-only HRT is not recommended because it increases the risk of endometrial cancer.

Irregular bleeding

If you get break-through bleeding or spotting, it’s usually nothing to worry about, especially during the first 3–6 months of taking HRT.

But if the bleeding or spotting:

§ carries on for more than the first 6 months

§ starts after you’ve been taking Premarin for more than 6 months

§ carries on even after you’ve stopped taking Premarin

0 Make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

Breast Cancer

Women who have breast cancer, or have had breast cancer in the past, should not take HRT.

Evidence shows that taking combined estrogen-progestogen or estrogen-only hormone replacement therapy (HRT) increases the risk of breast cancer. The extra risk depends on how long you use HRT. The additional risk becomes clear within 3 years of use. After stopping HRT the extra risk will decrease with time, but the risk may persist for 10 years or more if you have used HRT for more than 5 years.

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

Women aged 50 to 54 who are not taking HRT, on average, 13 to 17 in 1000 will be diagnosed with breast cancer over a 5-year period. For women aged 50 who start taking estrogen-only HRT for 5 years, there will be 16–17 cases in 1000 users (i.e. an extra 0 to 3 cases). For women aged 50 who are taking estrogen-progestogen HRT for 5 years, there will be 21 cases in 1000 users (i.e. an extra 4 to 8 cases).

Women aged 50 to 59 who are not taking HRT, on average, 27 in 1000 will be diagnosed with breast cancer over a 10-year period.

For women aged 50 who start taking estrogen-only HRT for 10 years, there will be 34 cases in 1000 users (i.e. an extra 7 cases).

For women aged 50 who start taking estrogen-progestogen HRT for 10 years, there will be 48 cases in 1000 users (i.e. an extra 21 cases).

Regularly check your breasts. See your doctor if you notice any changes such as:

§ dimpling of the skin

§ changes in the nipple

§ any lumps you can see or feel

Ovarian Cancer

Ovarian cancer is rare – much rarer than breast cancer , but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

The use of estrogen-only or combined estrogen-progestogen HRT has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50 to 54 who are not taking HRT, about 2 women in 2000 will be diagnosed with ovarian cancer over a 5-year period. For women who have been taking HRT for 5 years, there will be about 3 cases per 2000 users (i.e. about 1 extra case).

Effects of HRT on your heart or circulation

Blood Clots in a vein (thrombosis)

The risk of blood clots in the veins (also called deep vein thrombosis, or DVT), is about 1.3 to 3– times higher in HRT users than in non-users, especially during the first year of taking it.

Blood clots can be serious and 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 in your veins as you get older and if any of the following applies to you. Inform your doctor if any of these situations applies to you:

§ you are seriously overweight (BMI>30 kg/m2)

§ you have had a blood clot before

§ if any of your close family has ever had a blood clot in the leg, lung or another organ

§ you are pregnant or in your postpartum period

§ you have any blood clotting problem that needs treatment with a medicine used to prevent blood clots

§ you are unable to walk for a long time because of major surgery, injury or illness (see also “if you’re going to have surgery” below)

§ you have a rare condition called SLE (systemic lupus erythematosus)

§ you have cancer.

For signs of a blood clot, see section 2 Stop taking Premarin and see a doctor immediately.

Compare

Looking at women in their 50s who are not taking HRT, on average, over a 5-year period, 4 to 7 in 1000 would be expected to get a blood clot in a vein.

For women in their 50s who have had their womb removed and have been taking estrogen-only HRT for over 5 years, there will be 5 to 8 cases in 1000 users (i.e. 1 extra case).

If you’re going to have surgery, make sure your doctor knows about it or tell the surgeon that you are taking Premarin. You may need to stop taking Premarin 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 Premarin again.

Heart Disease (heart attack)

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.

There is no evidence that HRT will prevent a heart attack.

For women who have had their womb removed and are taking estrogen-only therapy there is no increased risk of developing a heart disease.

If you get:

§ a pain in your chest that spreads to your arm or neck

0 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

The risk of having a stroke is about 1.5 times higher in HRT users than in non-users. The number of extra cases of stroke due to use of HRT will increase with age. More recent analysis of risk in women aged 50 to 59 years suggests no increased risk for women taking 0.625 mg Premarin tablets.

Other things that can increase the risk of stroke include:

§ 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.

Compare

Looking at women in their 50s who are not taking HRT – on average, over a 5-year period, 8 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 11 in 1000 users, over a five year period (i.e. an extra 3 cases).

If you get:

§ unexplained migraine-type headaches, with or without disturbed vision

0 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.

Other conditions

HRT will not prevent memory loss. There is some evidence of a higher risk of memory loss in women who start using HRT after the age of 65. Speak to your doctor for advice.

Women with hypertriglyce­ridemia 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.

Other medicines and Premarin

Some medicines may interfere with the effect of Premarin. This might lead to irregular bleeding.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription, herbal remedies or other natural products.

In particular tell your doctor if you are taking:

• an anticonvulsant (used to treat epilepsy e.g. phenobarbital, phenytoin, carbamazepine)
• an anti-infective e.g. used to treat tuberculosis (rifampicin, rifabutin) or HIV (nevirapine, efavirenz, ritonavir and nelfinavir)
• other antibiotics or antifungal medicines (e.g. erythromycin, clarithromycin, ketoconazole, itraconazole)
• a herbal preparation such as St. John’s wort (Hypericum perforatum)
• metyrapone (most commonly used in the treatment of Cushing’s syndrome)
• cimetidine (used to treat stomach ulcers and reduce stomach acid)
• dexamethasone (a corticosteroid)

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

Premarin with food and drink

Drinking grapefruit juice may affect the way that your medicine works.

Laboratory tests

If you need a blood test, tell your doctor or the laboratory staff that you are taking Premarin, because this medicine can affect the results of some tests.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

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

Premarin contains Lactose monohydrate, Sucrose and the colouring agent Sunset Yellow

Lactose monohydrate and sucrose are sugars. 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 yellow tablets (1.25 mg), may cause allergic reactions.

3. How to take Premarin

Starting to take Premarin

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The usual dose is one tablet every day.

Your doctor will aim to give you the lowest dose for the shortest time to treat your symptoms for as short as necessary. Speak to your doctor if you think this dose is too strong or not strong enough.

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.

The recommended 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 0.3 mg 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 0.625 mg tablet every day but your doctor may advise you to use 1.25 mg 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.

Paediatric population

Safety and effectiveness in paediatric patients have not been established.

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 2 HRT and Cancer).

If you take more Premarin than you should

If you take too many tablets don’t worry. You may feel some nausea (sickness), breast tenderness, dizziness, abdominal pain and drowsiness/fatigue. 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.

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.

Do not take a double dose to make up for a forgotten tablet.

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 medicine, ask your doctor, pharmacist or nurse.