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TRISEQUENS TABLETS

Active substance(s): ESTRADIOL / ESTRADIOL HEMIHYDRATE / NORETHISTERONE ACETATE

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PACKAGE LEAFLET: INFORMATION FOR THE USER

Trisequens® Tablets
(estradiol/norethisterone acetate)
This product is available using the above name but will be referred to as Trisequens
throughout the following leaflet:
Read this entire 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 or pharmacist.
 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 or pharmacist. This includes any possible
side effects not listed in this leaflet. See section 4.
What is in this leaflet:
1. What Trisequens is and what it is used for
2. What you need to know before you take Trisequens
3. How to take Trisequens
4. Possible side effects
5. How to store Trisequens
6. Contents of the pack and other information
1. What Trisequens is and what it is used for
Trisequens is a sequential combined Hormone Replacement Therapy (HRT) which is taken
every day without interruption. Trisequens is used in postmenopausal women with at least
6 months since their last natural period.
Trisequens contains 2 hormones, an oestrogen (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 oestrogen. Norethisterone acetate is
a synthetic progestagen, which acts in a similar manner as progesterone, another important
female sex hormone.
Trisequens is used for:
Relief of symptoms occurring after menopause
During the menopause, the amount of the oestrogen produced by a woman’s body drops.
This can cause symptoms such as hot face, neck and chest (‘hot flushes’). Trisequens
alleviates these symptoms after menopause. You will only be prescribed Trisequens if your
symptoms seriously hinder your daily life.
Prevention of osteoporosis
After the menopause some women may develop fragile bones (osteoporosis). You should
discuss all available 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 Trisequens
to prevent osteoporosis after menopause.
The experience of treating women older than 65 years is limited.
2. What you need to know before you take Trisequens
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 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.
Do not take Trisequens
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 Trisequens.
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 oestrogen 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 (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 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 liver function tests have not
returned to normal
 if you are allergic (hypersensitive) to estradiol, norethisterone acetate or any of the
other ingredients of Trisequens (listed in section 6 Contents of the pack and other
information)
 if you have a rare blood problem called ‘porphyria’ which is passed down in families
(inherited).
If any of the above conditions appear for the first time while taking Trisequens, stop taking it
at once and consult your doctor immediately.
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:
 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 Blood clots in a vein (venous
thromboembolism))
 increased risk of getting an oestrogen-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
If you notice any of the following when taking HRT:
 any of the conditions mentioned in the Do not take Trisequens 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 and dizziness)
migraine-like headaches which happen for the first time
if you become pregnant
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 oestrogen-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 protects you from 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 oestrogen-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.
Unexpected bleeding
You will have a bleed once a month (so-called withdrawal bleed) while taking Trisequens.
But if you have unexpected bleeding or drops of blood (spotting) besides your monthly
bleeding which:
 carries on for more than the first 6 months
 starts after you have been taking Trisequens more than 6 months
 carries on after you have stopped taking Trisequens
see your doctor as soon as possible.
Breast cancer
Evidence suggests that taking combined oestrogen-progestagen and possibly also
oestrogen-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.
Compare
Women aged 50 to 79 who are not taking HRT, on average, 9 to 17 in 1,000 will be
diagnosed with breast cancer over a 5-year period.
For women aged 50 to 79 who are taking oestrogen-progestagen HRT over 5 years, there
will be 13 to 23 cases in 1,000 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.
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. A slightly increased risk of ovarian cancer has been reported in
women taking HRT for at least 5 to 10 years. Women aged 50 to 69 who are not taking
HRT, on average, about 2 women in 1,000 will be diagnosed with ovarian cancer over a 5year period. For women who have been taking HRT for 5 years, there will be between 2
and 3 cases per 1,000 users (i.e. up to 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 nonusers, 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
section 3, If you need to have surgery).
 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.
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 oestrogen-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 oestrogen-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.
Using other medicines
Some medicines may interfere with the effect of Trisequens. This might lead to irregular
bleeding. This applies to the following medicines:
 Medicines for epilepsy (such as phenobarbital, phenytoin and carbamazepine)
 Medicines for tuberculosis (such as rifampicin and rifabutin)
 Medicines for HIV infection (such as nevirapine, efavirenz, ritonavir and nelfinavir)
 Medicines for hepatitis C infections (such as telaprevir)
 Herbal remedies containing St John’s Wort (Hypericum perforatum).
Other medicines may increase the effects of Trisequens:
 Medicines containing ketoconazole (a fungicide).
Trisequens may have an impact on a concomitant treatment with cyclosporine.
Please tell your doctor or pharmacist if you are taking or have recently taken any other
medicines including medicines obtained without a prescription, herbal medicines or other
natural products.

Laboratory tests
If you need a blood test, tell your doctor or the laboratory staff that you are taking
Trisequens, because this medicine can affect the results of some tests.
Taking Trisequens with food and drink
The tablets can be taken with or without food and drink.
Pregnancy and breast-feeding
Pregnancy: Trisequens is for use in postmenopausal women only. If you become
pregnant, stop taking Trisequens and contact your doctor.
Breast-feeding: You should not take Trisequens if you are breast-feeding.
Driving and using machines
Trisequens has no known effect on the ability to drive or use machines.
Important information about some of the ingredients in Trisequens
Trisequens contains lactose monohydrate. If you have an intolerance to some sugars,
contact your doctor before taking Trisequens.
3. How to take Trisequens
Always take this medicine exactly as your doctor has told you. Check with your doctor or
pharmacist if you are unsure.
If you are not switching from another hormone replacement therapy, you can start
treatment with Trisequens on any convenient day. If you are switching from another
hormone replacement therapy, ask your doctor when you should start treatment with
Trisequens.
Take one tablet once a day, at about the same time each day.
Each pack contains 28 tablets
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.
Take the tablets with a glass of water.
Once you have finished the pack, start a new pack continuing the treatment without
interruption. A menstruation-like bleeding (period) usually occurs at the beginning of a new
pack.
For further information on the use of the calendar pack, see USER INSTRUCTIONS at the
end of the package leaflet.
Your doctor will aim to prescribe the lowest dose to treat your symptom for as short as
necessary. Speak to your doctor if you think this dose is too strong or not strong enough.
Talk to your doctor if you do not experience symptom relief after 3 months of treatment.
You should only continue treatment as long as the benefit outweighs the risk.
If you take more Trisequens than you should
If you have taken more Trisequens than you should, talk to a doctor or pharmacist. An
overdose of Trisequens could make you feel sick or vomit.
If you forget to take Trisequens
If you forget to take your tablet at the usual time, take it within the next 12 hours. If more
than 12 hours have gone by, start again as normal the next day. Do not take a double dose
to make up for a forgotten tablet. Forgetting a dose may increase the likelihood of
breakthrough bleeding and spotting.
If you stop taking Trisequens
If you would like to stop taking Trisequens, talk to your doctor first. Your doctor will explain
the effects of stopping treatment and discuss other possibilities with you.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
If you need to have surgery
If you are going to have surgery, tell the surgeon that you are taking Trisequens. You may
need to stop taking Trisequens about 4 to 6 weeks before the operation to reduce the risk
of a blood clot (see section 2, Blood clots in a vein (venous thromboembolism)). Ask your
doctor when you can start taking Trisequens again.
4. Possible side effects
Like all medicines, this medicine can have 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, What you need to know
before you take Trisequens.
Hypersensitivity/allergy
(uncommon side effect - affects 1 to 10 users in 1,000)
Though it is an uncommon event, hypersensitivity/allergy may occur. Signs of
hypersensitivity/allergy may include one or more of the following symptoms: hives, itching,
swelling, difficulty in breathing, low blood pressure (paleness and coldness of skin, rapid
heartbeat), feeling dizzy, sweating, which could be signs of anaphylactic reaction/shock. If
one of the mentioned symptoms appears, stop taking Trisequens and seek immediate
medical help.
Very common side effects
 Breast pain or breast tenderness
 Irregular periods or excessive bleeding during your periods.
Common side effects
 Headache
 Weight gain caused by fluid retention
 Vaginal inflammation
 Vaginal infection with a fungus
 Migraine, new or worse than before
 Depression, new or worse than before
 Nausea
 Abdominal pain, swelling or discomfort
 Enlargement or swelling of the breasts (breast oedema)
 Back pain
 Leg cramps
 Uterine fibroid (benign tumour), aggravation, occurrence or recurrence
 Swelling of arms and legs (peripheral oedema)
 Weight increase.
Uncommon side effects
 Bloating or flatulence
 Acne
 Hair loss (alopecia)
 Abnormal (male pattern) hair growth
 Itching or hives (urticaria)
 Inflammation of a vein (superficial thrombophlebitis)
 Drug ineffective
 Allergic reaction
 Endometrial hyperplasia (excessive growth of the lining of the womb)
 Painful periods
 Nervousness.
Rare side effects
 Pulmonary embolism (blood clot) (see Blood clots in a vein in section 2 What you need
to know before you take Trisequens)
 Deep inflammation of a vein associated with thrombosis (blood clot).

Very rare side effects
Cancer of the lining of the womb (endometrial cancer)
Increase in blood pressure or worsening of high blood pressure
Gall bladder disease, gallstones occurrence/recurrence or aggravated
Excessive secretion of sebum, skin eruption
Acute or recurring attack of oedema (angioneurotic oedema)
Insomnia, dizziness, anxiety
Change in sexual desire
Visual disturbances
Weight decreased
Vomiting
Heartburn
Vaginal and genital itching
Heart attack and stroke.
The frequency of possible side effects listed above is defined using the following
convention:
Very common (affects more than 1 user in 10)
Common (affects 1 to 10 users in 100)
Uncommon (affects 1 to 10 users in 1,000)
Rare (affects 1 to 10 users in 10,000)
Very rare (affects less than 1 user in 10,000)
Not known (frequency cannot be estimated from the available data).
Other side effects of combined HRT
The following side effects have been reported with other HRTs:
 various skin disorders:
– discolouration of the skin especially of the face or neck known as ‘pregnancy
patches’ (chloasma)
– painful reddish skin nodules (erythema nodosum)
– rash with target-shaped reddening or sores (erythema multiforme).
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 via the
Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects, you can
help provide more information on the safety of this medicine.















5. How to store Trisequens
 Trisequens Tablets should be stored in the original packaging. Do not store above
25°C. Protect from light. Do not refrigerate. Do not remove the tablets from the calendar
dial pack except when taking them.
 Keep out of the sight and reach of children.
 Do not use this medicine after the expiry date, which is stated on the label or carton.
The expiry date refers to the last day of that month.
 Do not throw away any medicines via wastewater or household waste. Ask your
pharmacist how to throw away medicines you no longer use. These measures will help
protect the environment.
 If the tablets become discoloured or show signs of any deterioration, you should seek
the advice of your pharmacist.
6. Contents of the pack and other information
What Trisequens contains
Your medicine is called Trisequens. The calendar dial-pack consists of:
12 blue biconvex tablets coded NOVO 280 on one side and blank on the other, each
containing 2mg estradiol (as hemihydrate), which is an oestrogen.
10 white biconvex tablets coded NOVO 281 on one side and blank on the other, each
containing 2mg estradiol (as hemihydrate) and 1mg norethisterone acetate, which is a
progesterone.
6 red biconvex tablets coded NOVO 282 on one side and blank on the other, each
containing 1mg estradiol (as hemihydrate).
The other ingredients are: lactose monohydrate, maize starch, hyroxypropylcellulose, talc
and magnesium stearate.
Film-coating (blue tablets) contains: hypromellose, talc, titanium dioxide (E171), indigo
carmine (E132) and macrogol 400.
Film-coating (white tablets) contains: hypromellose, triacetin and talc.
Film-coating (red tablets) contains: hypromellose, talc, titanium dioxide (E171), red iron
oxide (E172) and propylene glycol.
Trisequens are available as a carton containing 3 calendar dial-packs, each of 28
sequential tablets.
POM
PL No: 15814/0158
This product is manufactured by Novo Nordisk A/S, 2880 Bagsvaerd, Denmark and is
procured from within the EU and repackaged by the Product Licence holder: O.P.D.
Laboratories Ltd., Unit 6 Colonial Way, Watford, Herts WD24 4PR.
Leaflet revision and issue date (Ref.) 20.01.2016
Trisequens is a trade mark of Novo Nordisk FemCare AG.
USER INSTRUCTIONS
How to use the calendar pack:
1. Set the day reminder
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 1 space as
indicated by the arrow. Tip out the next
tablet. Remember to take only 1 tablet
once a day.
You can only turn the transparent dial
after the tablet in the opening has
been removed.

To request a copy of this leaflet in Braille, large print or audio please call 01923 332 796.

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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.

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