Skip to Content

PREMARIN 0.3MG COATED TABLETS

Active substance(s): CONJUGATED ESTROGENS / CONJUGATED ESTROGENS / CONJUGATED ESTROGENS

View full screen / Print PDF » Download PDF ⇩

PDF Transcript

Package leaflet: Information for the user

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
because it contains important
information for you.
- Keep this leaflet. You may need to read it
again.
- If you have any further questions, ask
your doctor, pharmacist or nurse.
- This medicine has been prescribed for
you only. Do not pass it on to others. It
may harm them, even if their signs of
illness are the same as yours.
- If you get any side effects, talk to your
doctor, pharmacist or nurse. This includes
any possible side effects not listed in this
leaflet. See section 4.
What is in this leaflet
1. What Premarin is and what it is used for

3. How to take Premarin
4. Possible side effects
5. How to store Premarin
6. Contents

of the pack and other
information

1. What

Premarin is and what it is
used for
Premarin is a Hormone Replacement Therapy
(HRT). It contains the female hormone estrogen.
Premarin is used to treat some of the symptoms
and conditions associated with the menopause.
Premarin is used for:
Relief of symptoms occurring after
menopause
During the menopause, the amount of the
estrogen produced by a woman’s body
drops. This can cause symptoms such as hot
face, neck and chest (“hot flushes”). Premarin
alleviates these symptoms after menopause.
You will only be prescribed Premarin if your
symptoms seriously hinder your daily life.

After the menopause some women may be at
risk of developing fragile bones (osteoporosis).
You should discuss all available treatment
options with your doctor.
If you are at an increased risk of fractures due to
osteoporosis and other medicines are not
suitable for you, you can use Premarin 0.625 mg
or 1.25 mg Coated Tablets to prevent
osteoporosis after menopause.
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.

2. What

you need to know before
you take Premarin
Medical history and regular check-ups
The use of HRT carries risks which need to be
considered when deciding whether to start
taking it, or whether to carry on taking it.
The experience in treating women with a
premature menopause (due to ovarian failure
or surgery) is limited. If you have a premature
menopause the risks of using HRT may be
different. Please talk to your doctor.
Before you start (or restart) HRT, your doctor
will ask about your own and your family’s
medical history. Your doctor may decide to
perform a physical examination. This may
include an examination of your breasts and/or
an internal examination, if necessary.
Once you have started on Premarin you should
see your doctor for regular check-ups (at least
once a year). At these check-ups, discuss with
your doctor the benefits and risks of continuing
with Premarin.
Go for regular breast screening, as
recommended by your doctor.
2.1

Do not take Premarin

If any of the following applies to you. If you
are not sure about any of the points below,
talk to your doctor before taking Premarin.
Do not take Premarin:
§

I
f you are allergic (hypersensitive) to
conjugated estrogens or any of the other
ingredients of this medicine (listed in
section 6).

§
§

§
§
§

§
§
§
§
§

I
f you have or have ever had breast cancer,
or if you are suspected of having it.
If you have cancer which is sensitive to

estrogens such as cancer of the lining of
the womb (endometrium) or if you are
suspected of having it.
If you have any unexplained vaginal

bleeding.
If you have excessive thickening of the

womb lining (endometrial hyperplasia) that
is not being treated.
If you have ever had a blood clot in a

vein (thrombosis), such as in the legs
(deep venous thrombosis) or the lungs
(pulmonary embolism).
If you have a blood clotting disorder (such

as protein C, protein S, or antithrombin
deficiency).
If you have or recently have had a disease

caused by blood clots in the arteries, such
as a heart attack, stroke or angina.
If you have or have previously had liver

disease.
If you have a rare blood problem called

“porphyria” which is passed down in
families (inherited).
If you are pregnant, or you are breast
feeding.

If any of the above conditions
appear for the first time while taking
Premarin, stop taking it at once and
consult your doctor immediately.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before
taking Premarin if you have ever had any of
the following problems, before you start the
treatment, as these may return or become worse
during treatment with Premarin. If so, you should
see your doctor more often for check-ups:
• fibroids inside your womb
• growth of womb lining outside your womb
(endometriosis) or a history of excessive
growth of the womb lining (endometrial
hyperplasia)
• increased risk of developing blood clots
(see section 2.3 “Blood Clots in a vein
(thrombosis)” for more detail)
• increased risk of getting estrogen-sensitive
cancer (such as having a mother, sister or
grandmother who has had breast cancer)
(see section 2.2 “HRT and cancer”)
• high blood pressure
• heart disease
• a liver disorder (e.g. a benign liver tumour)
• kidney disease
• fluid retention due to cardiac or kidney
problems
• diabetes
• gallbladder disease or gallstones









migraine or severe headaches
a disease of the immune system that affects
many organs of the body (systemic lupus
erythematosus, SLE)
epilepsy
asthma
a disease affecting the eardrum and
hearing (otosclerosis)
low blood calcium levels (hypocalcaemia)
a very high level of fat in your blood
(triglycerides).

Stop taking Premarin and see a doctor
immediately
If you notice any of the following when taking HRT:

any
of the conditions mentioned in the “Do
not take Premarin” section
• yellowing of the skin or the whites of your
eyes (jaundice). These may be signs of a liver
disease
• a large rise in your blood pressure (symptoms
may be headache, tiredness, dizziness)
• migraine-like headaches which happen for
the first time
• if you become pregnant
• have an allergic reaction, signs of which
include a rash, itching, shortness of breath,
difficulty in breathing and a swollen face
• if you notice signs of a blood clot, such as:
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.
2.2

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.

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

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.

Evidence suggests that taking combined estrogenprogestogen and possibly also estrogen-only
HRT increases the risk of breast cancer. The extra
risk depends on how long you take HRT. The
additional risk becomes clear within a few years.
However, it returns to normal within a few years
(at most 5) after stopping treatment.

Premarin 0.625 mg and 1.25 mg tablets contain
a higher dose of estrogens than other estrogenonly 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
Ø 
Make an appointment to see your
doctor. It could be a sign that your
endometrium has become thicker.

For women who have had their womb removed
and who are using estrogen-only HRT for 5 years,
little or no increase in breast cancer risk is shown.
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 79 who are not taking
HRT, on average, 9 to 17 in 1000 will be
diagnosed with breast cancer over a 5-year
period. For women aged 50 to 79 who are
taking estrogen-progestogen HRT over 5 years,
there will be 13 to 23 cases in 1000 users
(i.e. an extra 4 to 6 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.

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.
PAA079231

2. What

you need to know before you take
Premarin

Prevention of osteoporosis

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

0.3 mg, 0.625 mg & 1.25 mg Coated Tablets
conjugated estrogens

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 to 1 extra case).

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

2.3

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.

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.

Ø

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.

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.

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
Ø 
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

2.4

ee a doctor as soon as possible
S
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

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.
2.5

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)

2.6

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.
2.7

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.
2.8

Driving and using machines

There is no evidence to suggest that taking
Premarin will affect your ability to drive or to
operate machinery.
2.9

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
3.1

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.

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

Premarin with food and drink
Drinking grapefruit juice may affect the way
that your medicine works.

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.

3.2

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.
3.3

While you are taking Premarin

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.

4. Possible side effects
Like all medicines, this medicine can cause side
effects, although not everybody gets them.
The following diseases are reported more often
in women using HRT compared to women not
using HRT:
• breast cancer
• abnormal growth or cancer of the lining of the
womb (endometrial hyperplasia or cancer)
• ovarian cancer
• blood clots in the veins of the legs or lungs
(venous thromboembolism)
• heart disease
• stroke
• probable memory loss if HRT is started over
the age of 65

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

For more information about these side effects, see
section 2.

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 2.2 HRT and Cancer).

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

3.4

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.
3.5

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

§

§
§
§
§
§
§
§
§
§
§
§
§
§
§
§
§
§
§

bdominal uterine bleeding such as
a
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 (dementia)
a worsening of chorea (an existing

neurological disorder characterised by
involuntary spasmodic movements of the body)
a worsening of asthma

worsening of hypocalcaemia (low blood
a
levels of calcium)
gallbladder disease or jaundice (e.g.

gallstones or yellowing of the skin)
growth of benign meningioma (a tumour of the

membranes around the brain or spinal cord)
inflammation of the colon (part of the intestine)

which may present as lower left sided
abdominal pain and/or bloody diarrhoea
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.
Reporting of side effects
If you get any side effects, talk to your doctor,
pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. You can also
report side effects directly (see details below). By
reporting side effects you can help provide more
information on the safety of this medicine.
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
Malta
ADR Reporting
Website: www.medicinesauthority.gov.mt/
adrportal

5. How to store Premarin
Keep this medicine out of the sight and reach
of children.
Do not use this medicine after the expiry date
which is stated on the carton and blister after
EXP. The expiry date refers to the last day of
that month.
Do not store above 25oC.
Do not throw away any medicines via
wastewater or household waste. Ask your
pharmacist how to throw away any medicines
you no longer use. These measures will help
protect the environment.

6. Contents

of the pack and other
information
6.1

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 0.3 mg conjugated
estrogens, the maroon tablets marked with
‘0.625’ contain 0.625 mg conjugated
estrogens and the yellow tablets marked with
‘1.25’ contain 1.25 mg conjugated estrogens.
The other ingredients are lactose
monohydrate, microcrystalline cellulose,
magnesium stearate, hypromellose, sucrose,
hydroxypropyl cellulose, macrogol, carnauba
wax, edible ink and coating.
The edible ink on the green and maroon
tablets contains hypromellose, titanium
dioxide (E171) and propylene glycol
(E1520). The edible ink on the yellow tablets
contains hypromellose, iron oxide black
(E172) and propylene glycol (E1520).
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.
6.2

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.
This leaflet applies to Premarin tablets only.
This leaflet was last revised in O5/2016.
Ref: PA 9_1

PAA079231

Package leaflet: Information for the user

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 because it contains important information for you.

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).

3.5 If you forget to take Premarin

Other things that can increase the risk of stroke include:
• high blood pressure
• smoking
• drinking too much alcohol
• an irregular heartbeat.

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

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.

What is in this leaflet
1. What Premarin is and what it is used for
2. What you need to know before you take Premarin
3. How to take Premarin
4. Possible side effects
5. How to store Premarin
6. Contents of the pack and other information

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.

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.

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.

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 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.

1. What Premarin is and what it is used for

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 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.

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.

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.

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.

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.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following diseases are reported more often in women using HRT compared to women not using HRT:
• breast cancer
• abnormal growth or cancer of the lining of the womb (endometrial hyperplasia or cancer)
• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• heart disease
• stroke
• probable memory loss if HRT is started over the age of 65
For more information about these side effects, see section 2.

2.4 Other conditions

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

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.

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.

Relief of symptoms occurring after menopause

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

During the menopause, the amount of the estrogen produced by a woman’s body drops. This can cause symptoms such as hot
face, neck and chest ("hot flushes"). Premarin alleviates these symptoms after menopause. You will only be prescribed Premarin
if your symptoms seriously hinder your daily life.

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.

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.

Prevention of osteoporosis

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.

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)

• abdominal uterine bleeding such as 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 (dementia)
• a worsening of chorea (an existing neurological disorder characterised by involuntary spasmodic movements of the body)
• a worsening of asthma
• a worsening of hypocalcaemia (low blood levels of calcium)
• gallbladder disease or jaundice (e.g. gallstones or yellowing of the skin)
• growth of benign meningioma (a tumour of the membranes around the brain or spinal cord)
• inflammation of the colon (part of the intestine) which may present as lower left sided abdominal pain and/or bloody diarrhoea
• 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.

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

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

Premarin with food and drink
Drinking grapefruit juice may affect the way that your medicine works.

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.

After the menopause some women may be at risk of developing fragile bones (osteoporosis). You should discuss all available
treatment options with your doctor.

420935200

conjugated estrogens

PREMARIN®

If you are at an increased risk of fractures due to osteoporosis and other medicines are not suitable for you, you can use Premarin
0.625 mg or 1.25 mg Coated Tablets to prevent osteoporosis after menopause.

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.

2. What you need to know before you take Premarin

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

Medical history and regular check-ups
The use of HRT carries risks which need to be considered when deciding whether to start taking it, or whether to carry on taking it.

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

The experience in treating women with a premature menopause (due to ovarian failure or surgery) is limited. If you have a premature
menopause the risks of using HRT may be different. Please talk to your doctor.

Evidence suggests that taking combined estrogen-progestogen and possibly also estrogen-only HRT increases the risk of breast
cancer. The extra risk depends on how long you take HRT. The additional risk becomes clear within a few years. However, it
returns to normal within a few years (at most 5) after stopping treatment.

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 start (or restart) HRT, your doctor will ask about your own and your family’s medical history. Your doctor may decide
to perform a physical examination. This may include an examination of your breasts and/or an internal examination, if necessary.
Once you have started on Premarin you should see your doctor for regular check-ups (at least once a year). At these check-ups,
discuss with your doctor the benefits and risks of continuing with Premarin.
Go for regular breast screening, as recommended by your doctor.
2.1 Do not take Premarin

conjugated estrogens

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

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.

- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are
the same as yours.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this
leaflet. See section 4.

Premarin is a Hormone Replacement Therapy (HRT). It contains the female hormone estrogen. Premarin is used to treat some
of the symptoms and conditions associated with the menopause.
Premarin is used for:

PREMARIN®

2.2 HRT and cancer

If any of the following applies to you. If you are not sure about any of the points below, talk to your doctor before taking Premarin.

For women who have had their womb removed and who are using estrogen-only HRT for 5 years, little or no increase in breast
cancer risk is shown.
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 79 who are not taking HRT, on average, 9 to 17 in 1000 will be diagnosed with breast cancer over a 5-year
period. For women aged 50 to 79 who are taking estrogen-progestogen HRT over 5 years, there will be 13 to 23 cases in 1000
users (i.e. an extra 4 to 6 cases).

Do not take Premarin:

420935200

• If you are allergic (hypersensitive) to conjugated estrogens or any of the other ingredients of this medicine (listed in section 6).
• If you have or have ever had breast cancer, or if you are suspected of having it.
• If you have cancer which is sensitive to estrogens such as cancer of the lining of the womb (endometrium) or if you are suspected
of having it.
• If you have any unexplained vaginal bleeding.
• If you have excessive thickening of the womb lining (endometrial hyperplasia) that is not being treated.
• If you have ever had a blood clot in a vein (thrombosis), such as in the legs (deep venous thrombosis) or the lungs (pulmonary
embolism).
• If you have a blood clotting disorder (such as protein C, protein S, or antithrombin deficiency).
• If you have or recently have had a disease caused by blood clots in the arteries, such as a heart attack, stroke or angina.
• If you have or have previously had liver disease.
• If you have a rare blood problem called “porphyria” which is passed down in families (inherited).
• If you are pregnant, or you are breast-feeding.
If any of the above conditions appear for the first time while taking Premarin, stop taking it at once and consult your
doctor immediately.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Premarin if you have ever had any of the following problems, before you
start the treatment, as these may return or become worse during treatment with Premarin. If so, you should see your doctor
more often for check-ups:
• fibroids inside your womb
• growth of womb lining outside your womb (endometriosis) or a history of excessive growth of the womb lining (endometrial
hyperplasia)
• increased risk of developing blood clots (see section 2.3 “Blood Clots in a vein (thrombosis)” for more detail)
• increased risk of getting estrogen-sensitive cancer (such as having a mother, sister or grandmother who has had breast cancer)
(see section 2.2 “HRT and cancer”)
• high blood pressure
• heart disease
• a liver disorder (e.g. a benign liver tumour)
• kidney disease
• fluid retention due to cardiac or kidney problems
• diabetes
• gallbladder disease or gallstones
• migraine or severe headaches
• a disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE)
• epilepsy
• asthma
• a disease affecting the eardrum and hearing (otosclerosis)
• low blood calcium levels (hypocalcaemia)
• a very high level of fat in your blood (triglycerides).
Stop taking Premarin and see a doctor immediately
If you notice any of the following when taking HRT:








any of the conditions mentioned in the “Do not take Premarin” section
yellowing of the skin or the whites of your eyes (jaundice). These may be signs of a liver disease
a large rise in your blood pressure (symptoms may be headache, tiredness, dizziness)
migraine-like headaches which happen for the first time
if you become pregnant
have an allergic reaction, signs of which include a rash, itching, shortness of breath, difficulty in breathing and a swollen face
if you notice signs of a blood clot, such as:
• painful swelling and redness of the legs
• sudden chest pain
• 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.

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).
2.3 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.

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.
2.5 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.

2.6 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.
2.7 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.
2.8 Driving and using machines
There is no evidence to suggest that taking Premarin will affect your ability to drive or to operate machinery.
2.9 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
3.1 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.

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.

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

DVT and PE are examples of a condition called venous thromboembolism, or VTE.

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.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.
You can also report side effects directly (see details below). By reporting side effects you can help provide more information on
the safety of this medicine.
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
Malta
ADR Reporting
Website: www.medicinesauthority.gov.mt/adrportal
5. How to store Premarin
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date refers to the
last day of that month.
Do not store above 25oC.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away any medicines
you no longer use. These measures will help protect the environment.
6. Contents of the pack and other information
6.1 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 0.3 mg conjugated
estrogens, the maroon tablets marked with ‘0.625’ contain 0.625 mg conjugated estrogens and the yellow tablets marked with
‘1.25’ contain 1.25 mg conjugated estrogens.
The other ingredients are lactose monohydrate, microcrystalline cellulose, magnesium stearate, hypromellose, sucrose, hydroxypropyl
cellulose, macrogol, carnauba wax, edible ink and coating.

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.

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.

For signs of a blood clot, see section 2.1 Stop taking Premarin and see a doctor immediately.

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.

These dyes are approved for use as food colourings.

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.

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

6.2 What Premarin looks like and contents of the pack

Paediatric population
Safety and effectiveness in paediatric patients have not been established.

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.

3.3 While you are taking Premarin

Not all pack sizes may be marketed.

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

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

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 2.2 HRT and Cancer).

The manufacturer is:
Pfizer Ireland Pharmaceuticals, Little Connell, Newbridge, County Kildare, Republic of Ireland.
Or
Pfizer Italia S.r.l., Località Marino del Tronto, 63100 , Ascoli Piceno (AP), Italy

3.4 If you take more Premarin than you should

This leaflet was last revised in 09/2016.

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.

Ref: PA 10_0

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
• 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.

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 edible ink on the green and maroon tablets contains hypromellose, titanium dioxide (E171) and propylene glycol (E1520).
The edible ink on the yellow tablets contains hypromellose, iron oxide black (E172) and propylene glycol (E1520).
The coating on the green tablets contains hypromellose, titanium dioxide (E171), quinoline yellow (E104), indigo carmine (E132),
macrogol and polysorbate 80.

3.2 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.

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.

This leaflet applies to Premarin tablets only.

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide