1mg / 0.5mg estradiol / norethisterone acetate tablets 

Read all of this leaflet carefully before you start taking this medicine. It contains information that is important to you.

  • Save this information, 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 give it to others. It can harm them, even if they show signs of illness similar to yours.
  • If you get any side effects, talk to your doctor or pharmacist. This also applies to any side effects not mentioned in this information. See section 4.

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

1. What Cliovelle is and what it is used for

Cliovelle is a preparation used for hormonal substitution therapy ( HormoneReplacement Therapy , HRT ). It contains two female sex hormones; estrogen and a progestogen.

Cliovelle is used for women whose menstruation has stopped ( menopause ), at least one year after their last natural menstruation.

Cliovelle is used to:

Relieve symptoms during and after menopause

When menstruation ceases ( menopause ), a woman’s estrogen drops. It can cause problems such as sweating and hot flashes. Cliovelle relieves these symptoms after menopause. Cliovelle should only be used if the problems cause problems in daily life.

Prevent osteoporosis

After menopause, some women suffer from osteoporosis. Discuss all possible options with your doctor.

If you have an increased risk of fractures (broken bones) and other medicines that are not suitable for you, you can use Cliovelle to prevent osteoporosis after menopause.

Estradiol and norethisterone acetate contained in Cliovelle may also be approved for the treatment of other conditions not mentioned in this product information. Ask your doctor, pharmacist, or other healthcare professional if you have any further questions and always follow their instructions.

2. What you need to know before you take Cliovelle

Do not use Cliovelle

Medical background and regular check-ups

The use of HRT involves risks that must be taken into account when deciding to start treatment or continue an ongoing treatment.

Experience is limited for the treatment of women whose menstruation has stopped prematurely (when the ovaries have stopped working or the uterus has been removed). If you belong to that group, the risks of HRT may be different. Talk to your doctor.

Before starting treatment (or resuming treatment), your doctor will ask about your own, and your family’s, medical background. Your doctor may do a general medical and gynecological examination, which also includes an examination of your breasts. Once you have started treatment, you should go for regular medical check-ups, at least once a year. During these check-ups, you should discuss with your doctor the benefits and risks of continued treatment.

Perform regular breast examinations according to your doctor’s recommendations.

Do not take Cliovelle:

if any of the following apply to you. If you are not sure, talk to your doctor before taking Cliovelle.

  • if you have or have had breast cancer or if there is a suspicion that you may have it.
  • if you have or have had estrogen-dependent cancer, such as cancer of the lining of the uterus (endometrium), or if there is a suspicion of such cancer.
  • if you have unexpected genital bleeding that has not been investigated by a doctor.
  • if you have endometrial hyperplasia (severe thickening of the uterine lining) and are not being treated for it.
  • if you have or have had a blood clot in a vein (venous thromboembolism ), in your legs (deep vein thrombosis ), or in your lungs ( pulmonary embolism ).
  • if you have a coagulation disorder, a condition with an increased risk of blood clots (lack of protein C, protein S, or antithrombin).
  • if you have or have had a disease caused by blood clots in the arteries are as heart attack, stroke (stroke), or angina.
  • if you have or have had any liver disease and still have abnormal liver values.
  • if you have porphyria, a rare inherited blood disorder.
  • if you are allergic to estradiol valerate, norethisterone acetate, or any of the other ingredients of this medicine (listed in section 6).

If any of the above affects you the first time you use Cliovelle, stop taking Cliovelle and contact your doctor immediately.

Warnings and cautions

Talk to your doctor if you have or have had any of the following problems before starting treatment. They may recur or worsen during treatment with Cliovelle. Should this occur, have more frequent check-ups with a doctor.

  • if you have any disease affecting the lining of the uterus, as well as muscle knots ( fibroids ), endometriosis, or have had endometrial hyperplasia (severe thickening of the uterine lining).
  • if you have an increased risk of getting a blood clot (see below “Blood clots in a vein ( thrombosis )”)
  • if a close relative has had breast cancer or other estrogen-dependent cancer.
  • high blood pressure
  • liver disease eg liver adenoma (benign tumor )
  • diabetes
  • gallstone disease
  • if you get a migraine or severe headache
  • if you have systemic lupus erythematosus ( SLE ) – an autoimmune disease that affects many organs in the body
  • epilepsy
  • asthma
  • otosclerosis (ossification of the middle ear leading to a hearing loss)
  • hypertriglyceridemia (elevated blood lipids)
  • fluid retention due to heart or kidney disease

You should contact a doctor immediately and discontinue treatment if any of the following occur:

  • any of the things mentioned in the section ‘Do not take Cliovelle’
  • if skin or whites of the eyes turn yellow (jaundice); it may be a symptom of liver disease
  • if your blood pressure rises sharply (symptoms may be headache, fatigue, or dizziness)
  • if you are experiencing migraine-like headaches for the first time
  • if you become pregnant
  • if you get symptoms of a blood clot, such as
    • painful swelling and redness of the legs
    • sudden chest pain
    • breathing difficulties

For further information, see below “Blood clots in a vein ( thrombosis )”

Note: Cliovelle is not a contraceptive. If it is less than 12 months since your last period, or if you are under 50, you may still need to use contraception to avoid pregnancy. Consult your doctor.

HRT and cancer

Severe thickening of the uterine lining ( endometrial hyperplasia ) and cancer of the uterine lining (endometrial cancer)

The use of HRT with estrogen alone increases the risk of severe thickening of the uterine lining and cancer of the uterine lining.

The progestogen in Cliovelle protects you against this extra risk.

Irregular bleeding

Irregular spotting or spotting may occur during the first 3 – 6 months of taking Cliovelle.

But about the bleeding

  • lasts longer than 6 months
  • begins after taking Cliovelle for 6 months
  • continues after you stop taking Cliovelle

you should see a doctor as soon as possible.

Breast cancer:

Data show that hormone replacement therapy ( HRT ) with a combination of estrogen-progestogen or with estrogen alone increases the risk of breast cancer. The increased risk depends on how long you use HRT. The increased risk is seen within 3 years. When treatment is stopped, the increased risk decreases over time, but it can persist for 10 years or more if you have used HRT for more than 5 years.

Comparison

Of 1,000 women aged 50-54 who do not take HRT, an average of 13-17 will be diagnosed with breast cancer over a 5-year period.

In women who are 50 years old and start taking HRT with estrogen alone for 5 years, 16-17 cases per 1,000 users (ie 0-3 extra cases) will occur.

In women who are 50 years old and start taking HRT with estrogen-progestogen for 5 years, there will be 21 cases per 1,000 users (ie 4-8 extra cases).

Among women aged 50–59 who do not use HRT, an average of 27 out of 1,000 will be diagnosed with breast cancer over a 10-year period.

In women who are 50 years old and start taking HRT with estrogen alone for 10 years, 34 cases per 1,000 users (ie 7 extra cases) will occur.

In women who are 50 years old and start taking HRT with estrogen-progestogen for 10 years, 48 ​​cases per 1,000 users (ie 21 extra cases) will occur.

Check your breasts regularly. Contact a doctor if you notice changes such as:

  • indentations or pits
  • changes of the nipple
  • nodules you can see or feel

In addition, it is recommended that you participate in a mammography examination when it is offered to you. At the mammogram, it is important that you tell the nurse/healthcare professional doing the examination that you are using HRT, as this medicine may increase the density of the breasts and it may affect the results of the mammogram. An increased density in the breasts can make it more difficult to detect lumps on the mammography images.

Ovarian cancer

Ovarian cancer is rare – much more rare than breast cancer. Use of HRT with estrogen alone or combined estrogen-progestogen has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. The diagnosis of ovarian cancer will, for example, be made on about 2 women out of 2,000 between the ages of 50 and 54 who do not take HRT for a 5-year period. For women who have taken HRT for 5 years, there will be about 3 cases per 2,000 users (ie about 1 extra case).

How HRT affects the heart and blood circulation

Blood clots in a vein ( thrombosis )

The risk of blood clots in the veins is 1.3–3 times higher for women who take HRT than for those who do not, especially during the first year of treatment.

Blood clots can be serious. If a blood clot ends up in the lungs, it can cause chest pain, shortness of breath, collapse or even lead to death.

You are more likely to get a blood clot in a vein if any of the following apply to you. Tell your doctor if any of the following apply to you:

  • you have not been able to walk or stand for a long time due to a major operation, injury or illness (see also section 3, “If you need surgery”)
  • you are severely overweight ( BMI over 30 kg / m 2 )
  • you have a coagulation disorder that requires long-term treatment with drugs that prevent blood clots
  • if a close relative has had a blood clot in the bone, lung, or another organ
  • you have SLE (systemic lupus erythematosus)
  • you have cancer

The symptoms of a blood clot are described in the section “You should contact a doctor immediately and stop the treatment”.

Comparison

For women in their 50s who do not take HRT, an average of 4 – 7 out of 1,000 people are expected to have a blood clot in a vein over a 5-year period.

For women in their 50s who have taken HRT with estrogen-progestogen for more than 5 years, 9 – 12 out of 1,000 users are expected to get a blood clot in a vein (ie 5 extra cases)

Heart disease (heart attack)

There is no evidence that HRT prevents heart attacks.

For women over the age of 60 who take HRT with estrogen-progestin, the risk of developing heart disease is slightly higher than those who do not take HRT.

Stroke (apoplexy)

The risk of stroke is about 1.5 times higher for those who take HRT compared to those who do not. The risk of stroke is age-dependent, therefore the number of cases of stroke increases due to the use of HRT with increasing age.

Comparison

For women in their 50s who do not take HRT, an average of 8 out of 1,000 people is expected to have a stroke over a 5-year period.

For women in their 50s who have taken HRT for more than 5 years, 11 out of 1,000 users are expected to have a stroke (ie 3 extra cases)

Other conditions

  • Using HRT does not prevent memory loss. The risk of memory loss may be slightly higher in women who start using HRT after the age of 65. Consult your doctor.
  • In women with hereditary angioedema, HRT may increase or worsen the symptoms.

Other medicines and Cliovelle

Some medicines may affect the way Cliovelle works, which may lead to irregular bleeding. The following applies:

  • Drugs for epilepsy (eg phenobarbital, phenytoin, and carbamazepine)
  • Medicines for tuberculosis (eg rifampicin, rifabutin)
  • Drugs for HIV – infection (for example, nevirapine, efavirenz, ritonavir, and nelfinavir telaprevir)
  • An herbal medicine containing St. John’s wort ( Hypericum perforatum )

Cliovelle may increase or decrease the effect of other medicines:

  • The effect of ciclosporin (used, for example, to prevent transplant rejection, treatment of rheumatoid arthritis, or psoriasis ) may increase.
  • The effect of lamotrigine (an epilepsy medicine) may be reduced and the dose of lamotrigine may need to be adjusted to control the risk of seizures.

Medicines containing ketoconazole ( antifungal ) can increase the effect of Cliovelle.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription and herbal remedies.

Results from blood test analyze

If you need to take a blood sample, tell your doctor, or the person taking the blood sample, that you are taking Cliovelle as it may affect the results of some tests.

Pregnancy and breastfeeding

Cliovelle is for women whose menstruation has stopped. If you become pregnant, stop taking Cliovelle and consult a doctor.

Driving and using machines

No effects on the ability to drive and use machines have been observed.

You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires sharpened attention. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects. Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.

Cliovelle contains lactose monohydrate:

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

How to take Cliovelle

Always take this medicine exactly as your doctor has told you. If you are not sure, talk to your doctor or pharmacist.

Take one tablet daily without pausing between tablets (blisters).

When you start taking Cliovelle, take the first tablet where the day of the week is indicated on the tablet map (eg “M” for Monday). Then follow the direction of the arrows from the first tablet and take one tablet every day, until the tablet map is finished. The next day you start with a new tablet map.

The tablets should be swallowed with a sufficient amount of water, preferably at the same time each day

Your doctor will strive to give you the lowest dose, which will give you symptom relief, and that you should use Cliovelle for the shortest possible time. Talk to your doctor if you do not get any relief from the symptoms, or feel that the dose is too high.

After an overdose, you may feel soreness in your breasts, feel sick or vomit, have irregular bleeding, feel down, feel tired, develop acne, or experience increased hair growth on your body or face.

If you accidentally take an extra dose, the usual dose should be taken the next day.

If you forget to take Cliovelle

If you forget to take a tablet, you can take it within 12 hours from the usual time, otherwise, discard the forgotten tablet and take the next tablet, as usual, the next day.

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

If you need surgery

If you are going to have surgery, tell your surgeon that you are taking Cliovelle. You may need to stop taking Cliovelle for 4 to 6 weeks before surgery to avoid the risk of blood clots (see section 2, “Blood clots in a vein ( thrombosis )”). Ask your doctor when it is appropriate to start taking Cliovelle again.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects are usually mild to moderate and do not usually mean that women need to stop taking their tablets.

The following diseases are more common in women who take HRT than those who do not:

  • breast cancer
  • severe thickening of the uterine lining ( endometrial hyperplasia ) or cancer of the uterine lining (endometrial cancer)
  • ovarian cancer ( ovarian cancer )
  • blood clots in veins in bones or lungs (venous thromboembolism )
  • heart disease
  • stroke (stroke)
  • probable memory loss, if treatment with HRT is started after the age of 65

See section 2 for more information on these side effects.

The following side effects may occur during treatment with Cliovelle:

Very common (affects more than 1 user in 10)

Vaginal bleeding. Pain or tenderness in the breasts.

Common (affects up to 1 in 10 people)

Fungal infection of the abdomen or inflammation of the vagina. Accumulation of fluid in the body. Depression or worsening of ongoing depression. Migraine or worsening of ongoing migraine, headache. Nausea. Back pain. Breast edema or breast enlargement. Uterine nodules ( fibroids ) or impaired or recurrent uterine nodules. Peripheral edema (swollen arms or legs). Weight gain.

Uncommon (affects up to 1 in 100 people)

Hypersensitivity ( allergic reaction ). Nervousness. Superficial venous inflammation associated with the blood clots. Pain, tension, or discomfort in the abdomen. Gases, bloating. Morbidly strong hair (increased hair growth on body and face), acne, hair loss. Itching . Hives. Leg cramps.

Rare (affects up to 1 in 1,000 people)

A blood clot in the lung (See also section 2 “What you need to know before taking Cliovelle”). Deep vein inflammation associated with blood clots.

Very rare (affects 1 in 10,000 people)

Anaphylactic reactions (sudden, severe, potentially life-threatening allergic reactions).

The following side effects have been reported with other HRTs:

  • The disease of the gallbladder
  • Various skin diseases:
    • dark skin spots, especially on the face and neck, so-called “pregnancy spots” (chloasma)
    • painful reddish-purple bumps on the skin (erythema nodosum)
    • annular redness or sore rash (erythema multiforme)
  • dry eyes
  • change in the composition of the tear fluid

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 to the Medical Products Agency, www.lakemedelsverket.se. By reporting side effects, you can help increase drug safety information. 

5. How to store Cliovelle

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister and carton after EXP. The expiration date is the last day of the specified month.

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

6. Contents of the packaging and other information

Content declaration

  • The active substances are estradiol 1 mg (as estradiol valerate) and norethisterone acetate 0.5 mg.
  • The other ingredients are crospovidone, lactose monohydrate , magnesium stearate, and corn starch.

What it looks like and the contents of the pack:

White, round, biconvex tablets, 6 mm in diameter.

Calendar blister packs of 28 and 84 tablets.

Blister packs of 30 and 90 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

DR. KADE Pharmazeutische Fabrik GmbH

Ringstrasse 2

D – 12277 Berlin

Germany

For further information about Cliovelle contact your local representative/agent:

CampusPharma AB

Karl Gustavsgatan 1A

SE – 411 25 Gothenburg

e-mail: info@campuspharma.se

Tel: +46 31 20 50 20

This medicinal product is authorized under the European Economic Area under the names:

Denmark: Cliovelle
Finland: Cliovelle 1 mg / 0.5 mg tablets
Norway: Cliovelle 1 mg / 0.5 mg tablets
Poland: Cliovelle 1 mg / 0.5 mg tablets
:
Germany: Cliovelle 1 mg / 0.5 mg tablets

Muhammad Nadeem

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