Estradiol/Norethisterone acetate
Consumer Medicine Information
What is in this leaflet
This leaflet answers some common questions about Trisequens®. It does not contain all the available information. It does not take the place of
talking to your doctor or pharmacist.
All medicines have risks and benefits. Your doctor has weighed the risks of you using
Trisequens® against the benefits they expect it will have for you.
Ask your doctor or pharmacist if you have any concerns about using this medicine.
Keep this leaflet with the medicine.
You may need to read it again.
Trisequens® is available only by prescription at pharmacies.
When you must not use Trisequens®
Do not use Trisequens® or other estrogens, with or without a progestagen to prevent heart attacks, stroke
or dementia.
A study called the Women’s Health Initiative indicated increased risk of heart attack,
stroke, breast cancer, and blood clots in the legs or lungs in women receiving treatment
with a product containing conjugated estrogens 0.625 mg and the progestagen medroxyprogesterone
acetate (MPA). The researchers stopped the study after 5 years when it was determined
the risks were greater than the benefits in this group. The Women’s Health Initiative
Memory Study indicated increased risk of dementia in women aged 65-79 years taking
conjugated estrogens and MPA. There are no comparable data currently available for
other doses of conjugated estrogens and MPA or other combinations of estrogens and
progestagens. Therefore, you should assume the risks will be similar for other medicines
containing estrogen and progestagen combinations.
Talk regularly with your doctor about whether you still need treatment with Trisequens®.
Treatment with estrogens, with or without progestagens should be used at the lowest
effective dose and for the shortest period of time.
What Trisequens® is used for
Trisequens® is a type of hormone replacement therapy (HRT) that relieves the symptoms of estrogen
deficiency associated with the menopause. It is a short term symptomatic treatment,
also used where these symptoms arise from medical or surgical procedures affecting
the ovaries.
The menopause, a woman's last menstrual period, usually occurs between the ages of
45 and 55 years. During this natural life transition, a woman slowly stops producing
two female hormones called estrogen and progesterone. Menstrual periods become less
frequent until they finally stop.
The falling hormone levels may cause you to experience uncomfortable symptoms such
as hot flushes or night sweats.
Trisequens® contains two hormones, an estrogen (estradiol) and a progestagen (norethisterone
acetate). The estradiol in Trisequens® is identical to the estradiol produced in the ovaries of women, and is classified
as a natural estrogen. Norethisterone acetate is a synthetic progestagen which acts
in a similar manner as progesterone, another important female sex hormone.
The estrogen in Trisequens® relieves the symptoms caused by a lack of estrogen. The progestagen protects the
lining of your womb from overstimulation by estrogen.
Your doctor may have prescribed Trisequens® for another reason.
Ask your doctor if you have any questions about why Trisequens® has been prescribed for you.
Before you take Trisequens®
When you must not take it
Do not take Trisequens® if any of the following applies to you. Talk to your doctor before taking Trisequens® if you are not sure about any of the points below.
Do not take Trisequens®:
if you have, have had or suspect having breast cancer
if you have, have had or suspect having cancer of the womb lining (endometrial cancer),
or any other estrogen dependent cancer
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 or have ever had a blood clot in a vein (venous thromboembolism), such
as in the legs (e.g. deep vein 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 previously have had a disease caused by blood clots in the arteries,
such as a heart attack, stroke or angina
if you have or have ever had a liver disease and your blood test results have not
returned to normal
if you have a rare blood problem called 'porphyria' which is passed down in families
(inherited)
if you are allergic (hypersensitive) to estradiol, norethisterone acetate or any of
the other ingredients of Trisequens® (listed in the Ingredients section of this leaflet)
if you are pregnant or suspect you may be pregnant, or you are breast-feeding
it is after the expiry date ('Expiry') printed on the pack
the packaging is torn or shows signs of tampering.
Stop taking Trisequens® at once and consult your doctor immediately if any of the above conditions appear
for the first time while taking this medicine.
Before you start to take it
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.
Talk to your doctor if you have a premature menopause.
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.
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 Trisequens® 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 Trisequens®.
Go for regular breast screening as recommended by your doctor.
The experience of treating women older than 65 years’ is limited.
Warnings and precautions
Tell your doctor 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 Trisequens®.
If so, you should see your doctor more often for check-ups:
heart disease
fibroids inside your womb
growth of the 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 Blood clots in a vein (venous thromboembolism))
increased risk of getting an estrogen-sensitive cancer (such as having a mother, sister
or grandmother who has had breast cancer)
high blood pressure
a liver disorder, such as a benign liver tumour
diabetes
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)
a very high level of fat in your blood (triglycerides)
fluid retention due to cardiac or kidney problems
lactose intolerance.
Stop taking Trisequens® and see a doctor immediately
Stop taking Trisequens® and see a doctor immediately if you notice any of the following when taking HRT:
any of the conditions mentioned in the ‘When you must not take it’ section
yellowing of your 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
sudden development of visual problems
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 Blood clots in a vein (venous thromboembolism).
Note: Trisequens® 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).
The progestagen in Trisequens® reduces this extra risk.
Compare
In women who still have a womb and who are not taking HRT, on average, 5 in 1,000
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 1,000 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.
Irregular bleeding
You may have irregular bleeding or drops of blood (spotting) during the first 3-6
months of taking Trisequens®. However, see your doctor as soon as possible if the irregular bleeding:
carries on for more than the first 6 months
starts after you have been taking Trisequens® for more than 6 months
carries on after you have stopped taking Trisequens®.
Breast cancer
Evidence shows that taking combined estrogen-progestagen 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.
Compare
Women aged 50 to 54 who are not taking HRT, on average, 13 to 17 in 1,000 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 1,000 users (i.e. an extra 0 to 3 cases).
For women aged 50 who start taking estrogen-progestagen HRT for 5 years, there will
be 21 cases in 1,000 users (i.e. an extra 4 to 8 cases).
Women aged 50 to 59 who are not taking HRT, on average, 27 in 1,000 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 1,000 users (i.e. an extra 7 cases).
For women aged 50 who start taking estrogen-progestagen HRT for 10 years, there will
be 48 cases in 1,000 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.
Additionally, you are advised to join mammography screening programs when offered
to you. For mammogram screening, it is important that you inform the nurse/healthcare
professional who is actually taking the x-ray that you use HRT, as this medication
may increase the density of your breasts which may affect the outcome of the mammogram.
Where the density of the breast is increased, mammography may not detect all lumps.
Ovarian cancer
Ovarian cancer is rare - much rarer than breast cancer. The use of estrogen-only or
combined estrogen-progestagen 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 2,000 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 2,000 users (i.e. about 1 extra case).
Effect of HRT on heart and circulation
Blood clots in a vein (venous thromboembolism)
The risk of blood clots in the veins 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, fainting or even death.
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 unable to walk for a long time because of major surgery, injury or illness
(see also If you need to have surgery, below)
you are seriously overweight (BMI >30 kg/m²)
you have any blood clotting problem that needs long-term treatment with a medicine
used to prevent blood clots
if any of your close relatives has ever had a blood clot in the leg, lung or another
organ
you have systemic lupus erythematosus (SLE)
you have cancer.
For signs of a blood clot, see Stop taking Trisequens® and see a doctor immediately, above.
Compare
Looking at women in their 50s who are not taking HRT, on average, over a 5-year period,
4 to 7 in 1,000 would be expected to get a blood clot in a vein.
For women in their 50s who have been taking estrogen-progestagen HRT for over 5 years,
there will be 9 to 12 cases in 1,000 users (i.e. an extra 5 cases).
Heart disease (heart attack)
There is no evidence that HRT will prevent a heart attack. Women over the age of 60
years who use estrogen-progestagen HRT are slightly more likely to develop heart disease
than those not taking any HRT.
Stroke
The risk of getting 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.
Compare
Looking at women in their 50s who are not taking HRT, on average, 8 in 1,000 would
be expected to have a stroke over a 5-year period.
For women in their 50s who are taking HRT, there will be 11 cases in 1,000 users over
5 years (i.e. an extra 3 cases).
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.
Tell your doctor or the laboratory staff that you are taking Trisequens® if you need a blood test.
This is because this medicine can affect the results of some tests.
Taking other medicines
Tell your doctor if you are taking or plan to take other medicines, including:
other estrogen medicines
medicines to help you sleep, including barbiturates
medicines for epilepsy e.g. phenytoin, carbamazepine, lamotrigine
some antibiotics and other anti-infective medicines e.g. rifampicin, penicillin, cyclosporin,
rifabutin, nevirapine, efavirenz, ritonavir, nelfinavir, ketoconazole
medicines for hepatitis C infections (such as telaprevir)
St. John’s Wort – used to treat depression
antihistamines – used to treat allergies
anticoagulants and antifibrinolytics – used to manage blood clotting processes
antidiabetic drugs – used to treat diabetes
medicines which decrease serum folate
thyroid hormones – used to treat malfunction of the thyroid gland
corticosteroids – used to treat inflammatory conditions.
Or other specific medicines including:
imipramine
pethidine.
Tell your doctor or pharmacist if you are taking any other medicines, including any
that you buy without a prescription from your pharmacy, supermarket or health food
shop.
The effect of Trisequens® can be reduced by other medicines, and may affect your vaginal bleeding pattern.
How to take Trisequens®
How to take it
Read carefully the instructions included in this leaflet, in order to correctly use
the calendar pack.
Your doctor will tell you when to start taking the tablets. If you are still having
periods, you would usually take the first tablet on the fifth day after the start
of your period. If your periods have stopped or have become infrequent, the first
tablet can be taken as soon as you get the product.
Take one tablet a day, preferably at the same time each day, until all 28 tablets
have been taken.
Days 1–12:
Take one blue tablet every day for 12 days.
Days 13–22:
Take one white tablet every day for 10 days.
Days 23–28:
Take one red tablet every day for 6 days.
Swallow each tablet with a glass of water. When you have finished each pack, start
the next pack immediately.
How long to take it
HRT should be prescribed at the lowest effective dose and for the shortest duration
necessary (see Before you start to take it). The continuation of the treatment should
be re-evaluated annually. Women who have undergone a premature menopause (e.g. hysterectomy)
may require longer term treatment.
If you forget to take it
You can always see if you have taken your tablet by looking at the day on the calendar
pack.
If you forget to take a tablet at the usual time, throw away the tablet you missed
and take your next dose when you are meant to.
You may have vaginal bleeding or spotting if you forget to take more than 1 tablet.
Ask your doctor for advice.
Do not take a double dose to make up for a forgotten tablet.
If you take too much (overdose)
If you take more tablets than you have been prescribed, contact your doctor for advice.
Overdose may cause nausea and vomiting, headache, dizziness, swelling due to fluid
retention (oedema), breast enlargement and build up of the lining of the womb.
If you need to have surgery
Tell the surgeon that you are taking Trisequens® if you are going to have surgery.
You may need to stop taking Trisequens® about 4 to 6 weeks before the operation to reduce the risk of a blood clot (see Blood
clots in a vein (venous thromboembolism)).
Ask your doctor when you can start taking Trisequens® again.
While you are taking Trisequens®
You can expect your symptoms to improve within a few months of starting Trisequens®. You will normally have a period while taking the red tablets or the last few white
tablets. This is because Trisequens® mimics the natural menstrual cycle.
Trisequens® can be stopped at any time. You should discuss this with your doctor.
At your routine check-up, your doctor may reassess your continued need for Trisequens®.
Stop taking Trisequens® and contact your doctor if you become pregnant.
Do not take Trisequens® if you are breast-feeding.
If you have any concerns about taking Trisequens®, ask your doctor or pharmacist.
If your doctor tells you to stop taking Trisequens®, return any unused medicine to your pharmacist.
Things you must not do
This medicine is for you only. Do not give it to someone else even if they seem to
have the same symptoms as you.
Do not take Trisequens® to treat any other complaints unless your doctor tells you to.
Do not change the way you take Trisequens® or lower the dosage, without checking with your doctor.
Side effects
All medicines can have side effects. Sometimes they are serious, most of the time
they are not.
Tell your doctor or pharmacist if you experience any side effects while you are taking
Trisequens® (whether or not they are mentioned below).
You may need medical treatment if you experience some of the side effects.
When you start taking Trisequens® your body has to adjust to new hormone levels. You may experience the following side
effects:
breast tenderness, pain or enlargement
irregular periods or excessive bleeding during your periods
period pain
abdominal (stomach) pain, indigestion, feeling sick (nausea), vomiting, diarrhoea,
bloating, flatulence
skin rash or itching, skin reactions, acne, changes in hair growth, hair loss
inflammation of a vein
headache, migraine, dizziness
changes in sexual appetite, problems getting to sleep, nervousness
gall bladder problems, gallstones
leg cramps
back pain
weight change
swelling due to fluid retention (oedema)
visual disturbances
aggravation, occurrence or recurrence of uterine fibroids (benign tumours)
fungal infection of the vagina (thrush), vaginal inflammation or itching
Trisequens® does not treat your symptoms effectively.
These side effects are usually temporary and disappear.
Tell your doctor if:
you think you may be suffering from depression
you are not feeling well or find any side effect too uncomfortable or unacceptable
any side effect becomes worse
vaginal bleeding or spotting suddenly becomes heavier.
Tell your doctor immediately if any of the following conditions occur (because you
may be told to stop taking Trisequens®):
severe pain or swelling in your legs
any type of blood clots
yellow colouring of the skin and eyes (jaundice)
migraine or sudden severe headache, and you have not previously had migraines
problems with your eyesight which develop suddenly
marked rise in blood pressure
you can see or feel a lump in your breast, or you notice dimpling of the skin or changes
in the nipple
you know or suspect you are pregnant.
Tell your doctor immediately or go to Accident and Emergency at your nearest hospital
if you notice any of the following:
skin rashes over a large part of the body
shortness of breath, wheezing
swelling of the face, lips or tongue
fast pulse
sweating.
This list includes very serious side effects. You may need urgent medical attention
or hospitalisation. These side effects are very rare.
Effects on your heart or circulation
Heart disease
Talk to your doctor to see if you should be taking HRT if you have ever had 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,
HRT will not help to prevent heart disease.
Studies with one type of HRT (containing conjugated estrogen plus the progestagen
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.
See a doctor as soon as possible and do not take any more HRT until your doctor says
you can if you get:
a pain in your chest that spreads to your arm or neck.
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.
Talk to your doctor to see if you should take HRT if you are worried about any of
these things, or if you have had a stroke in the past.
See a doctor as soon as possible and do not take any more HRT until your doctor says
you can if you get:
unexplained migraine-type headaches, with or without disturbed vision. 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
you have had a blood clot before
any of your close family have had blood clots
you have had one or more miscarriages
you have any blood clotting problem that needs treatment with a medicine such as warfarin
you’re off your feet for a long time because of major surgery, injury or illness
you have a rare condition called systemic lupus erythematosus (SLE – an autoimmune
disease).
If any of these things apply to you, talk to your doctor to see if you should take
HRT.
See a doctor as soon as possible and do not take any more HRT until your doctor says
you can if you get:
painful swelling in your leg
sudden chest pain
difficulty breathing.
These may be signs of a blood clot.
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 progestagen HRT
is higher than for estrogen-only HRT (but estrogen plus progestagen 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 seems to return to normal 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
you are seriously overweight.
Make an appointment to see your doctor as soon as possible 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.
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 progestagen as well as the estrogen helps
to lower the extra risk.
If you still have your womb, your doctor may prescribe a progestagen 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 progestagen.
If you have 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 progestagen
as well as an estrogen.
Your product, Trisequens®, contains a progestagen.
If you get breakthrough bleeding or spotting, it’s usually nothing to worry about,
especially during the first few months of taking HRT.
Make an appointment to see your doctor 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.
It could be a sign that your endometrium has become thicker.
Ovarian cancer
Long-term (at least 5 - 10 years’) use of estrogen-only HRTs and estrogen plus progestagen
HRTs has been associated with an increased risk of ovarian cancer in some epidemiological
studies.
In addition to the possible side effects listed above, dementia has been reported
with HRT.
Do not be alarmed by these lists of possible side effects.
You may not experience any of them.
Storage
Keep all medicines out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and label.
The expiry date refers to the last day of that month.
Keep Trisequens® in a cool dry place where the temperature stays below 25°C. Do not put Trisequens® in the refrigerator.
Keep the calendar pack in the outer carton in order to protect from light.
Do not throw away any medicines down the sink or in your household rubbish. Ask your
pharmacist how to throw away medicines you no longer use.
These measures will help to preserve the environment.
Product Description
What Trisequens® looks like
Trisequens® comes in a calendar dial pack. Each pack holds 28 round tablets.
Trisequens® contains:
12 blue tablets marked 'NOVO 280' on one side.
10 white tablets marked 'NOVO 281' on one side
6 red tablets marked 'NOVO 282' on one side
Ingredients
Each blue tablet contains 2 mg estradiol (as hemihydrate) as the active ingredient
and indigo carmine CI73015 (E132) as a colouring agent.
Each white tablet contains 2 mg estradiol (as hemihydrate) and 1mg norethisterone
acetate as the active ingredients.
Each red tablet contains 1 mg estradiol (as hemihydrate) as the active ingredient
and iron oxide red CI77491 (E172) as a colouring agent.
The tablets also contain lactose, maize starch, purified talc, magnesium stearate,
hyprolose, hypromellose, titanium dioxide (E171) (red and blue tablets only), triacetin
(white tablets only), macrogol 400 (blue tablets only) and propylene glycol (red tablets
only).
Trisequens® is gluten-free.
Manufacturer
Trisequens® is made in Denmark and supplied in Australia by:
Novo Nordisk Pharmaceuticals Pty Ltd
Level 10
118 Mount Street
North Sydney NSW 2060
This leaflet was prepared on 25 October 2021.
Australian Registration Number:
AUST R 192476
Trisequens® is a trademark owned by Novo Nordisk Health Care AG, Switzerland.
NovoCare® is a trademark owned by Novo Nordisk A/S.
© 2021
Novo Nordisk A/S
Further information
For further information call the NovoCare® Customer Care Centre on 1800 668 626.
Always check the following websites to ensure you are reading the most recent version
of the Trisequens® consumer medicine information:
www.novonordisk.com.au
https://www.ebs.tga.gov.au/
User instructions
How to use the calendar dial pack
Turn the inner disc to set the day of the week opposite the little plastic tab.
2. Take the first day’s tablet
Break the plastic tab and tip out the first tablet.
3. Move the dial every day
On the next day simply move the transparent dial clockwise one space as indicated
by the arrow. Tip out the next tablet. Remember to take only one tablet once a day.
You can only turn the transparent dial after the tablet in the opening has been removed.