Trisequens

Trisequens film-coated tablets

Estradiol hemihydrate and norethisterone acetate

Read all of this leaflet carefully before you start taking this medicine.

• Keep this leaflet. You may need to read it again


• If you have further questions, ask your doctor or pharmacist


• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours


• 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.

In this leaflet:

• 1. What Trisequens is and what it is used for


• 2. Before you take Trisequens


• 3. How to take Trisequens


• 4. Possible side effects


• 5. How to store Trisequens


• 6. Further information

What Trisequens Is And What It Is Used For

Trisequens belongs to a group of hormone replacement therapy (HRT) medicines, called sequential combined HRT, which are taken every day without interruptions. Trisequens contains the female sex hormone estradiol and norethisterone acetate. The estradiol in Trisequens is identical to the estradiol 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 the body’s own hormone progesterone, another important female sex hormone.

Trisequens is prescribed:

• To relieve unpleasant symptoms like hot flushes, night sweats and vaginal dryness, which occur when the oestrogen levels decline and the periods stop (menopause).


• For the prevention of osteoporosis (thinning of the bones) in postmenopausal women if they are at high risk of future fractures and if they are unable to take other medications for this purpose.

Trisequens is prescribed for women who have not had their womb removed. There is only limited experience of treating women older than 65 years with Trisequens.

Before You Take Trisequens

Medical check-ups

Before you start taking HRT, your doctor should ask about your own and your family’s medical history. Your doctor may decide to examine your breasts and/or your abdomen, and may do an internal examination - but only if these examinations are necessary for you, or if you have any special concerns. Once you’ve started on HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT.

For more information about the safety of HRT, see section 4 “Possible side effects”

Be sure to:

• 
  Go for regular breast screening and cervical smear tests
  


• 
  Regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel.

Do not take Trisequens

If any of the following applies to you, talk to your doctor. Do not start taking Trisequens:

• If you have or have had breast cancer, or if it is suspected


• If you have cancer of the womb lining (endometrium), or if such an oestrogen dependent cancer is suspected


• If you have any vaginal bleeding, which has not been diagnosed by your doctor


• If you have or have had endometrial hyperplasia (excessive growth of the womb lining) that is not being treated


• If you have or previously have had a blood clot in the blood vessels of the legs or the lungs (like deep vein thrombosis or lung embolism)


• If you have recently had a heart attack, stroke, or have angina


• If you have or have had a liver disorder and your liver tests have not returned to normal


• If you have porphyria (a liver enzyme disease)


• If you are allergic (hypersensitive) to estradiol, norethisterone acetate or any other ingredients in Trisequens (listed in section 6,“Further information”).

Take special care with Trisequens

If you have (or have had) any of the following conditions, tell your doctor.

Your doctor may then want to follow your treatment up more closely. Rarely, these conditions may come back or get worse during treatment with Trisequens:

• If you have any condition affecting the womb lining, such as fibroids, endometriosis (presence of womb lining tissue outside the womb) or have had endometrial hyperplasia (excessive growth of the womb lining)


• If you have a history of blood clots (thrombosis) or have risk factors for blood clots (these risk factors and symptoms for a blood clot are listed in section 4,“ Possible side effects”)


• If any of your immediate family has had breast cancer, or other cancers related to oestrogen (e.g. endometrial cancer)


• If you have high blood pressure


• If you have a liver disorder such as liver adenoma (a benign tumour)


• If you have a kidney or heart disorder


• If you have diabetes


• If you have gallstone disease


• If you have epilepsy


• If you have asthma


• If you get migraines or severe headaches


• If you have systemic lupus erythematosus (SLE)


• If you have high levels of fat in the blood (hypertriglyceridemia)


• If you have otosclerosis (hearing loss sometimes linked to pregnancy).

If you need a blood test, tell your doctor that you are taking Trisequens, since oestrogen can affect the results of certain laboratory tests.

If you are going to have surgery, talk to your doctor. You may need to stop taking these tablets 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start treatment again.

Stop taking Trisequens

If you experience any of the following conditions below, stop taking Trisequens, and contact your doctor immediately:

• If you get a migraine-type headache for the first time


• If you develop yellow skin or eyes (jaundice) or other liver problems


• If your blood pressure goes up while you’re taking Trisequens


• If you become pregnant


• If any of the conditions listed in Section 2“Before you take Trisequens”, occur.

Using other medicines

Some medicines may reduce the effects of Trisequens:

• Drugs used for epilepsy (such as phenobarbital, phenytoin and carbamazepine)


• Drugs used for tuberculosis (such as rifampicin, rifabutin)


• Drugs used for HIV infections (such as nevirapine, efavirenz, ritonavir and nelfinavir)


• Herbal products with St John’s Wort (Hypericum perforatum).

Other medicines may increase the effects of Trisequens:

• Drugs containing ketoconazole (a fungicide).

Taking Trisequens with food and drink

The tablets can be taken with or without food and drink,

Pregnancy and breast-feeding

Do not take Trisequens if you suspect being pregnant, are pregnant or breast-feeding.

Driving and using machines

Trisequens does not affect the use of any machines or the ability to drive safely.

Important information about some of the ingredients of Trisequens:

Trisequens contains lactose monohydrate. If you have an intolerance to some sugars, contact your doctor before taking Trisequens.

How To Use Trisequens

Always take Trisequens exactly as your doctor has told you. Check with your doctor or pharmacist if you are unsure.

Take one tablet once a day, at about the same time each day

Take the tablet with a glass of water.

Take a tablet every day without stopping. Begin by taking the blue tablets for 12 days followed by the white tablets for 10 days and finally the red tablets for 6 days.

After taking the last red tablet, treatment is continued with the first blue tablet of a new calendar pack on the next day without interruption.

See “USER INSTRUCTIONS” at the beginning of the package leaflet

You should start treatment with Trisequens on the fifth day of your bleed (whether it has stopped or not) if you are still having periods, or if you are switching from an HRT product where you have a monthly bleed. If you no longer have periods or they are infrequent, you can start treatment with Trisequens on any convenient day. This also applies if you are switching from an HRT product where you do not have a monthly bleed.

Your doctor should aim to prescribe the lowest dose for the shortest time that gives you relief from your symptoms. Talk to your doctor if your symptoms are not better after three months.

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, try and 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 want 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 product ask your doctor or pharmacist.

Trisequens Side Effects

Like all medicines, Trisequens can have side effects, although not everybody gets them.

Very common effects

May affect more than 1 in 10 women

• Breast pain or breast tenderness


• Irregular menstrual periods or excessive bleeding during your periods.

Common effects

May affect up to 1 in 10 women

• Fungal infection of the genitals or vaginal inflammation (thrush)


• Fluid retention


• Depression or worsening of existing depression


• Headache


• Migraine or existing migraine made worse


• Feeling sick (nausea)


• Pain, swelling or discomfort of the abdomen (stomach)


• Back pain


• Leg cramps


• Enlargement or swelling of the breasts (breast oedema)


• Uterine fibroids (benign tumour of the womb): aggravation or re-occurrence


• Swelling of arms or legs (Peripheral oedema)


• Weight increase.

Uncommon effects

May affect up to 1 in 100 women

• Allergic reaction (hypersensitivity)


• Nervousness


• Inflammation of a vein (superficial thrombophlebitiis)


• Flatulence (wind) or bloating


• Hair loss or increased facial or body hair or acne


• Itching


• Hives (urticaria)


• Painful periods


• Excessive growth of the lining of the womb (endometrial hyperplasia)


• No relief of symptoms (Drug ineffective)

Rare Effects

May affect up to 1 in 1,000 women

• Blood clots in the blood vessels of the legs or the lungs (deep vein thrombosis, lung embolism). See also section “Other side effects of HRT”


• Breast cancer. See also section “Other side effects of HRT”

Very Rare Effects

May affect up to 1 in 10,000 women

• Cancer of the lining of the womb (endometrial cancer). See also section “Other side effects of HRT”


• Insomnia


• Anxiety


• Changes in sexual desire


• Dizziness


• Visual disturbances


• Increase in blood pressure or worsening of high blood pressure


• Heart attack or stroke (see also section “Other side effects of HRT”)


• Heartburn or vomiting


• Gallbladder disease


• Gallstones, aggravation, occurrence or re-occurrence


• Greasy skin


• Rash


• Swelling of the skin or other tissues of sudden onset


• Vaginal and genital itching


• Weight decrease.

Effects on the skin

Brown patches in the face, skin rashes including red inflammation on the hands or the legs (erythema multiforme), formation of tender, red nodules on the front of the legs/knees (erythema nodosum) or a bruise-like rash.

Other side effects of HRT

As well as benefits, HRT has some risks which you need to consider when you’re deciding whether to take it, or whether to carry on taking it.

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 oestrogen-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 oestrogen plus progestogen HRT is higher than for oestrogen-only HRT (but oestrogen plus progestogen HRT is beneficial for the endometrium, see ‘Endometrial cancer’ below).

For all kinds of HRT, the extra risk of breast cancer goes up the longer you take it, but returns to normal within about 5 years after stopping HRT.

Your risk of breast cancer is also higher:

• If you have a close relative (mother, sister or grandmother) who has had breast cancer


• If you are seriously overweight.

Compare

Looking at women aged 50 who are not taking HRT - on average, 32 in 1000 will be diagnosed with breast cancer by the time they reach the age of 65.

For women who start taking oestrogen-only HRT at age 50 and take it for 5 years, the figure will be between 33 and 34 in 1000 (i.e. an extra 1-2 cases).

If they take oestrogen-only HRT for 10 years, the figure will be 37 in 1000 (ie an extra 5 cases).

For women who start taking oestrogen plus progestogen HRT at age 50 and take it for 5 years, the figure will be 38 in 1000 (i.e. an extra 6 cases).

If they take oestrogen plus progestogen HRT for 10 years, the figure will be 51 in 1000 (i.e. an extra 19 cases)

If you notice any changes in your breast, such as:

• Dimpling of the skin


• Changes in the nipple


• Any lumps you can see or feel.

Make an appointment to see your doctor as soon as possible.

Endometrial cancer

(cancer of the lining of the womb)

Taking oestrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking a progestogen as well as the oestrogen helps to lower the extra risk.

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

Your product, Trisequens, contains a progestogen.

Compare

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 oestrogen-only HRT, the number will be 2 to 12 times higher, depending on the dose and how long you take it.

The addition of a progestogen to oestrogen-only HRT substantially reduces the risk of endometrial cancer.

If you get breakthrough bleeding or spotting, it’s usually nothing to worry about, especially during the first few months of taking HRT.

But if the bleeding or spotting:

• Carries on for more than the first few months


• Starts after you’ve been on HRT for a while


• Carries on even after you’ve stopped taking HRT.

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

Ovarian cancer

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that taking HRT for more than 5 years may increase the risk of ovarian cancer.

Effects on your heart or circulation

Blood clots

HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year of taking it.

These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE.

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

You are more likely to get a blood clot:

• If you are seriously overweight


• If you have had a blood clot before


• If any of your close family have had blood clots


• If you have had one or more miscarriages


• If you have any blood clotting problem that needs treatment with a medicine such as warfarin


• If you’re off your feet for a long time because of major surgery, injury or illness


• If you have a rare condition called SLE.

If any of these things apply to you, 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, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot.

For women in their 60s who are taking HRT, the figure would be 17 in 1000.

If you get:

• Painful swelling in your leg


• Sudden chest pain


• Difficulty breathing.

See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These may be signs of a blood clot.

If you’re going to have surgery, make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

Heart disease

HRT is not recommended for women who have heart disease, or have had heart disease recently. If you have ever had heart disease, talk to your doctor to see if you should be taking HRT.

HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated oestrogen plus the progestogen MPA) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get:

• A pain in your chest that spreads to your arm or neck.

See a doctor as soon as possible and do not take any more HRT until your doctor says you can. This pain could be a sign of heart disease.

Stroke

Recent research suggests that HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:

• Getting older


• High blood pressure


• Smoking


• Drinking too much alcohol


• An irregular heartbeat

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT - on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 11 in 1000 would be expected to have a stroke.

For women in their 60s who are taking HRT, the figure would be 15 in 1000.

If you get:

• Unexplained migraine-type headaches, with or without disturbed vision.

See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

Dementia

There is no evidence that HRT improves processes of knowing, thinking, learning and judging (cognitive function). From a clinical study there is some evidence for an increased risk of dementia among women older than 65 years, who were using another oestrogen/progestogen combination than the one in Trisequens. It is not known whether this applies to younger women and to women taking other HRT preparations.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How To Store Your Trisequens

Keep out of the reach and sight of children.

Do not use Trisequens after the expiry date, which is stated on the label and outer carton after “Exp.”. The expiry date refers to the last day of that month.

Do not store above 25°C.

Do not refrigerate.

Keep the container in the outer carton in order to protect from light.

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

Further Information

What Trisequens contains

The active substances are estradiol and norethisterone acetate.

Each blue tablet contains estradiol 2mg (as estradiol hemihydrate)

Each white tablets contains estradiol 2mg (as estradiol hemihydrate) and norethisterone acetate 1 mg.

Each red tablet contains estradiol 1mg (as estradiol hemihydrate)

Other ingredients are: Lactose monohydrate, maize starch, gelatin and magnesium-stearate.

Film-coating (blue tablets): hypromellose, talc, indigo carmine (E132), titanium dioxide (E171) and macrogol 400

Film-coating (white tablets): hypromellose, triacetin and talc

Film-coating (red tablets): hypromellose, talc, iron oxide (E172), titanium dioxide (E171) and propylene glycol

What Trisequens looks like and contents of the pack

The film-coated tablets are round with a diameter of 6 mm. Each pack contains 12 blue tablets each engraved with NOVO 280, 10 white tablets each engraved with NOVO 281, and 6 red tablets each engraved with NOVO 282.

Pack sizes:

28 film-coated tablets

3 x 28 film-coated tablets

Not all pack sizes may be marketed.

Marketing authorisation holder

Novo Nordisk Limited

Broadfield Park

Brighton Road

Crawley

West Sussex

RH11 9RT

Manufacturer

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd

Denmark

This leaflet was last approved: July 2009

Trisequens is a trademark owned by

Novo Nordisk FemCare AG

Switzerland

© 1996/2008

Novo Nordisk A/S

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 (blue).

• 
  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.

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