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Package leaflet:
Information for the user
Trisequens®
Film-coated tablets
Estradiol/norethisterone acetate
Read this entire leaflet carefully before you start takingthis medicine because itcontains important informationfor you.
- Keep this leaflet. You may needto read it again.
- If you have any furtherquestions, ask your doctor orpharmacist.
- This medicine has beenprescribed for you only. Do notpass it on to others. It may harmthem, even if their signs of illnessare the same as yours.
8-2800-01-011-5
- If you get any side effects, talk to your doctor or pharmacist. Thisincludes any possible side effectsnot listed in this leaflet. Seesection 4.
What is in this leaflet
1. What Trisequens® is and what itis used for
2. What you need to know beforeyou take Trisequens®
3. How to take Trisequens®
4. Possible side effects
5. How to store Trisequens®
6. Contents of the pack and otherinformation
1. What Trisequens® is and whatit is used for
Trisequens® is a sequential combined Hormone Replacement Therapy(HRT) which is taken every daywithout interruption. Trisequens® isused in postmenopausal womenwith at least 6 months since theirlast natural period.
Trisequens® contains 2 hormones, an oestrogen (estradiol) and a progestagen (norethisterone acetate).The estradiol in Trisequens® is identical to the estradiol produced inthe ovaries of women, and is classified as a natural oestrogen.Norethisterone acetate is a synthetic progestagen, which acts ina similar manner as progesterone,another important female sexhormone.
Trisequens® is used for:
Relief of symptoms occurring after menopause
During the menopause, the amount of the oestrogen producedby a woman's body drops. This cancause symptoms such as hot face,neck and chest ('hot flushes').Trisequens® alleviates these symptoms after menopause. You willonly be prescribed Trisequens® ifyour symptoms seriously hinderyour daily life.
Prevention of osteoporosis
After the menopause some women may develop fragile bones (osteoporosis). You should discuss allavailable options with your doctor.
If you are at an increased risk of fractures due to osteoporosis andother medicines are not suitable foryou, you can use Trisequens® to prevent osteoporosis after menopause.The experience of treating womenolder than 65 years is limited.
2. What you need to knowbefore 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, orwhether to carry on taking it.
The experience in treating women with a premature menopause (due toovarian failure or surgery) is limited. Ifyou 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 yourown and your family's medical history. Your doctor may decide toperform a physical examination.This may include an examination ofyour breasts and/or an internalexamination, if necessary.
Once you have started on Trisequens®, you should see yourdoctor for regular check-ups (atleast once a year). At these checkups, discuss with your doctor thebenefits and risks of continuingwith 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 anyof the points below, talk to yourdoctor before taking Trisequens®.Do not take Trisequens®:
• if you have, have had or suspect having breast cancer
• if you have, have had or suspecthaving cancer of the womblining (endometrial cancer) orany other oestrogen dependentcancer
• if you have any unexplainedvaginal bleeding
• if you have excessivethickening of the womblining (endometrial hyperplasia)that is not being treated
• if you have or have ever had
a blood clot in a vein (venous thromboembolism), such as inthe legs (deep venousthrombosis) or the lungs(pulmonary embolism)
• if you have a blood clottingdisorder (such as protein C,protein S or antithrombindeficiency)
• if you have or previously havehad a disease caused by bloodclots in the arteries, such as
a heart attack, stroke or angina
• if you have or have ever hada liver disease and your liver
function tests have not returned to normal
• if you are allergic (hypersensitive)to estradiol, norethisteroneacetate or any of the otheringredients of Trisequens® (listedin section 6 Contents of the packand other information)
• if you have a rare bloodproblem 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 atonce and consult your doctorimmediately.
Warnings and precautions
Tell your doctor if you have ever had any of the following problems,before you start the treatment, asthese may return or become worseduring treatment with Trisequens®.If so, you should see your doctormore often for check-ups:
• fibroids inside your womb
• growth of womb lining outsideyour womb (endometriosis) ora history of excessive growth ofthe womb lining (endometrialhyperplasia)
• increased risk of developingblood clots (see Blood clots in
a vein (venous thromboembolism))
• increased risk of getting anoestrogen-sensitive cancer (suchas having a mother, sister orgrandmother who has hadbreast cancer)
• high blood pressure
• a liver disorder, such as a benignliver tumour
• diabetes
• gallstones
• migraine or severe headaches
• a disease of the immune systemthat affects many organs of thebody (systemic lupuserythematosus, SLE)
• epilepsy
• asthma
• a disease affecting the eardrumand hearing (otosclerosis)
• a very high level of fat in yourblood (triglycerides)
• fluid retention due to cardiac orkidney 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 mentionedin the Do not take Trisequens®section
• yellowing of your skin or thewhites of your eyes (jaundice).These may be signs of a liverdisease
• a large rise in your blood pressure(symptoms may be headache,tiredness and dizziness)
• migraine-like headaches whichhappen for the first time
• if you become pregnant
• if you notice signs of a blood clot, such as:
- painful swelling and redness ofthe legs
- sudden chest pain
- difficulty in breathing.
For more information, see Blood clots in a vein (venousthromboembolism).
Note: Trisequens® is not a contraceptive. If it is less than 12 months since your last menstrual period oryou are under 50 years old, youmay 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 (endometrialhyperplasia) and cancer of thelining of the womb (endometrialcancer)
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, onaverage, 5 in 1,000 will bediagnosed with endometrial cancerbetween the ages of 50 and 65.
For women aged 50 to 65 who still have a womb and who takeoestrogen-only HRT, between10 and 60 women in 1,000 will bediagnosed with endometrialcancer (i.e. between 5 and 55extra cases), depending on thedose 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 ofblood (spotting) besides yourmonthly bleeding which:
• carries on for more than the first6 months
• starts after you have beentaking Trisequens® more than6 months
• carries on after you have stoppedtaking Trisequens®
see your doctor as soon as possible. Breast cancer
Evidence suggests that taking combined oestrogen-progestagen and possibly also oestrogen-only HRTincreases the risk of breast cancer.The extra risk depends on howlong you take hRt. The additionalrisk becomes clear within a fewyears. However, it returns to normalwithin a few years (at most 5) afterstopping treatment.
Compare
Women aged 50 to 79 who are not taking HRT, on average, 9 to17 in 1,000 will be diagnosed withbreast cancer over a 5-year period.
For women aged 50 to 79 who are taking oestrogen-progestagenHRT over 5 years, there will be13 to 23 cases in 1,000 users(i.e. an extra 4 to 6 cases).
Regularly check your breasts. See your doctor if you noticeany changes such as:
• dimpling of the skin
• changes in the nipple
• any lumps you can see or feel.Additionally, you are advised to joinmammography screening programswhen offered to you. For mammogram screening, it is important thatyou inform the nurse/healthcareprofessional who is actually takingthe 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 thebreast is increased, mammographymay not detect all lumps.
Ovarian cancer
Ovarian cancer is rare - much rarer than breast cancer. The use ofoestrogen-only or combinedoestrogen-progestagen HRT hasbeen associated with a slightlyincreased risk of ovarian cancer.
The risk of ovarian cancer varies with age. For example, in womenaged 50 to 54 who are not takingHRT, about 2 women in 2,000 willbe diagnosed with ovarian cancerover a 5-year period. For womenwho have been taking HRT for5 years, there will be about3 cases per 2,000 users (i.e. about1 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 higherin HRT users than in non-users,especially during the first year oftaking it.
Blood clots can be serious, and if one travels to the lungs, it cancause chest pain, breathlessness,fainting or even death.
You are more likely to get a blood clot in your veins as you get olderand if any of the following appliesto you. Inform your doctor if any ofthese situations applies to you:
• you are unable to walk for a longtime because of major surgery,injury or illness (see section 3, Ifyou need to have surgery)
• you are seriously overweight(BMI > 30 kg/m2)
• you have any blood clottingproblem that needs long-term
treatment with a medicine used to prevent blood clots
• if any of your close relatives hasever had a blood clot in the leg,lung or another organ
• you have systemic lupuserythematosus (SLE)
• you have cancer.
For signs of a blood clot, see Stop taking Trisequens® and see a doctorimmediately.
Compare
Looking at women in their 50s who are not taking HRT, onaverage, over a 5-year period, 4 to7 in 1,000 would be expected toget a blood clot in a vein.
For women in their 50s who have been taking oestrogen-progestagenHRT for over 5 years, there will be9 to 12 cases in 1,000 users (i.e. anextra 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-progestagenHRT are slightly more likely todevelop heart disease than thosenot taking any HRT.
Stroke
The risk of getting stroke is about 1.5 times higher in HRT users thanin non-users. The number of extracases of stroke due to use of HRTwill increase with age.
Compare
Looking at women in their 50s who are not taking HRT, onaverage, 8 in 1,000 would beexpected to have a stroke overa 5-year period.
For women in their 50s who are taking HRT, there will be 11 casesin 1,000 users over 5 years (i.e. anextra 3 cases).
Other conditions
HRT will not prevent memory loss. There is some evidence of a higherrisk 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 mightlead to irregular bleeding. Thisapplies to the following medicines:
• Medicines for epilepsy (such asphenobarbital, phenytoin andcarbamazepine)
• Medicines for tuberculosis (suchas rifampicin and rifabutin)
• Medicines for HIV infection(such as nevirapine, efavirenz,ritonavir and nelfinavir)
• Medicines for hepatitis Cinfections (such as telaprevir)
• Herbal remedies containingSt John's Wort (Hypericumperforatum).
Other medicines may increase the effects of Trisequens®:
• Medicines containingketoconazole (a fungicide).
Trisequens® may have an impact on a concomitant treatment withcyclosporine.
Please tell your doctor or pharmacist if you are taking or haverecently taken any other medicinesincluding medicines obtained withouta prescription, herbal medicines orother natural products.
Laboratory tests
If you need a blood test, tell your doctor or the laboratory staff thatyou are taking Trisequens®,because this medicine can affectthe 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 usein postmenopausal women only. Ifyou become pregnant, stop takingTrisequens® and contact your doctor.
Breast-feeding: You should not take Trisequens® if you arebreast-feeding.
Driving and using machines
Trisequens® has no known effect on the ability to drive or usemachines.
Important information about some of the ingredients inTrisequens®
Trisequens® contains lactose monohydrate. If you have an intolerance to some sugars, contact your doctorbefore taking Trisequens®.
3. How to take Trisequens®
Always take this medicine exactly as your doctor has told you. Checkwith your doctor or pharmacist ifyou are unsure.
If you are not switching from another hormone replacementtherapy, you can start treatmentwith Trisequens® on any convenientday. If you are switching fromanother hormone replacement
RA Labelling & IT Insert size: 999x100-006Current: 2.0
Improved DI28MKII Colour: PMS 280C
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therapy, ask your doctor when you should start treatment withTrisequens®.
Take one tablet once a day, at about the same time eachday.
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 thetreatment 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 necessarySpeak to your doctor if you thinkthis dose is too strong or not strongenough.
Talk to your doctor if you do not experience symptom relief after3 months of treatment. You shouldonly continue treatment as long asthe 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 orpharmacist. An overdose ofTrisequens® could make you feelsick or vomit.
If you forget to take Trisequens®
If you forget to take your tablet at the usual time, take it within thenext 12 hours. If more than 12 hourshave gone by, start again as normal
the next day. Do not take a double dose to make up for a forgottentablet. Forgetting a dose mayincrease the likelihood of breakthrough bleeding and spotting.
If you stop taking Trisequens®
If you would like to stop taking Trisequens®, talk to your doctorfirst. Your doctor will explain theeffects of stopping treatment anddiscuss other possibilities with you.If you have any further questionson the use of this medicine, askyour doctor or pharmacist.
If you need to have surgery
If you are going to have surgery, tell the surgeon that you are takingTrisequens®. You may need to stoptaking Trisequens® about 4 to6 weeks before the operation toreduce the risk of a blood clot (seesection 2, Blood clots in a vein(venous thromboembolism)). Askyour doctor when you can starttaking Trisequens® again.
4. Possible side effects
Like all medicines, this medicine can have side effects, although noteverybody gets them.
The following diseases are reported more often in women using HRTcompared to women not usingHRT:
• breast cancer
• abnormal growth or cancer of thelining of the womb (endometrialhyperplasia or cancer)
• ovarian cancer
• blood clots in the veins of thelegs or lungs (venousthromboembolism)
• heart disease
• stroke
• probable memory loss if HRT isstarted over the age of 65.
For more information about these side effects, see section 2 Whatyou need to know before you takeTrisequens®.
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 mayinclude one or more of the following symptoms: hives, itching,swelling, difficulty in breathing, lowblood pressure (paleness and coldness of skin, rapid heartbeat), feeling dizzy, sweating, which could besigns of anaphylactic reaction/shock.If one of the mentioned symptomsappears, stop taking Trisequens®and seek immediate medicalhelp.
Very common side effects
• Breast pain or breast tenderness
• Irregular periods or excessivebleeding during your periods.
Common side effects
• Headache
• Weight gain caused by fluidretention
• Vaginal inflammation
• Vaginal infection with a fungus
• Migraine, new or worse thanbefore
• Depression, new or worse thanbefore
• Nausea
• Abdominal pain, swelling ordiscomfort
• Enlargement or swelling of thebreasts (breast oedema)
• Back pain
• Leg cramps
• Uterine fibroid (benign tumour),aggravation, occurrence orrecurrence
• Swelling of arms and legs(peripheral oedema)
• Weight increase.
Uncommon side effects
• Bloating or flatulence
• Acne
• Hair loss (alopecia)
• Abnormal (male pattern) hairgrowth
• Itching or hives (urticaria)
• Inflammation of a vein(superficial thrombophlebitis)
• Drug ineffective
• Allergic reaction
• Endometrial hyperplasia(excessive growth of the lining ofthe womb)
• Painful periods
• Nervousness.
Rare side effects
• Pulmonary embolism (blood clot)(see Blood clots in a vein insection 2 What you need toknow before you takeTrisequens®)
• Deep inflammation of a veinassociated with thrombosis(blood clot).
Very rare side effects
• Cancer of the lining of thewomb (endometrial cancer)
• Increase in blood pressure orworsening of high bloodpressure
• Gall bladder disease, gallstonesoccurrence/recurrence oraggravated
• Excessive secretion of sebum,skin eruption
• Acute or recurring attack ofoedema (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 usingthe 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 in10,000)
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-shapedreddening or sores (erythemamultiforme).
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. Thisincludes any possible side effectsnot listed in this leaflet. You canalso report side effects directly viaYellow Card Scheme Website:www.mhra.gov.uk/yellowcard. Byreporting side effects you can helpprovide more information on thesafety of this medicine.
5. How to store Trisequens®
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date, which is stated on thelabel and carton.
Do not refrigerate.
Keep the container in the outer carton in order to protect it fromlight.
Do not throw away any medicines via wastewater or householdwaste. Ask your pharmacist how tothrow away medicines you nolonger use. These measures willhelp protect the environment.
6. Contents of the pack andother information
What Trisequens® contains
- The active substances are estradiol and norethisteroneacetate.
The blue film-coated tablet contains: estradiol 2 mg(as estradiol hemihydrate).
The white film-coated tablet contains: estradiol 2 mg (asestradiol hemihydrate) andnorethisterone acetate 1 mg.
The red film-coated tablet contains: estradiol 1 mg (asestradiol hemihydrate).
- The other ingredients are: lactose monohydrate, maize starch,hydroxypropylcellulose, talc andmagnesium stearate.
Film-coating (blue tablets) contains: hypromellose, talc,titanium dioxide (E171), indigocarmine (E132) and macrogol 400.Film-coating (white tablets)contains: hypromellose, triacetinand talc.
Film-coating (red tablets) contains: hypromellose, talc,titanium dioxide (E171), red ironoxide (E172) and propylene glycol.
What Trisequens® looks like and contents of the pack
The film-coated tablets are round with a diameter of 6 mm. The blue
tablets are engraved with NOVO 280. The white tablets areengraved with NOVO 281. The redtablets are engraved withNOVO 282. Each pack of 28 tabletscontains 12 blue tablets, 10 whitetablets and 6 red tablets.
Pack sizes available:
• 1 x28 film-coated tablets
• 3x28 film-coated tablets
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Novo Nordisk Limited 3 City Place, Beehive Ring RoadGatwick, West Sussex, RH6 0PA
Manufacturer
Novo Nordisk A/S Novo Alle
DK-2880 Bagsrard, Denmark
This leaflet was last approved:
03/2016
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 plastictab.
3. Move the dial every day
On the next day, simply move the transparent dial clockwise 1 spaceas indicated by the arrow. Tip outthe next tablet. Remember to takeonly 1 tablet once a day.
You can only turn the transparent dial after the tabletin the opening has beenremoved.
Trisequens® is a trademark owned by Novo Nordisk Health Care AG,Switzerland
© 2016
Novo Nordisk A/S
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