Sisten Conti

Leaflet accompanying the packaging: information for the user

SYSTEN CONTI

3.2 mg + 11.2 mg, transdermal system, patch
Estradiol + Norethisterone acetate

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

1 .What Systen Conti is and what it is used for.

• 2. Important information before using Systen Conti.
• 3. How to use Systen Conti.
• 4. Possible side effects.
• 5. How to store Systen Conti.
• 6. Contents of the packaging and other information.

1. What Systen Conti is and what it is used for

Systen Conti is a medicine used in hormone replacement therapy (HRT). It is a transdermal system in the form of a patch, for application to the skin. It contains estradiol, a female hormone belonging to estrogens, and norethisterone acetate, which is a progestogen. The estradiol contained in the medicine is identical to the hormone naturally produced by the ovaries in women before menopause.
Systen Conti is used to:
relieve symptoms associated with menopause
During menopause, the amount of estrogen produced in a woman's body decreases, which can cause symptoms such as a feeling of heat on the face, neck, and chest ("hot flashes"), sleep problems, irritability, and depression. Systen Conti alleviates these symptoms associated with menopause. Systen Conti may be prescribed to a patient only if the symptoms significantly interfere with her daily life.
Experience in treating women over 65 years of age is limited.

2. Important information before using Systen Conti

Medical history and regular medical examinations

The use of HRT involves risks that should be considered when the patient decides whether to use hormone replacement therapy or continue its use.
Experience in treating women in premature menopause (due to ovarian failure or surgical procedure) is limited. If the patient is experiencing premature menopause, the risk associated with HRT may differ. You should talk to your doctor.
Before starting (or resuming) HRT, the doctor should take a medical history, including a family history. The doctor may decide to perform tests, including a breast examination and/or gynecological examination, if necessary.
If the patient starts using Systen Conti, she should regularly undergo medical examinations (at least once a year). During these examinations, she should discuss with her doctor the benefits and risks of continuing to use Systen Conti.
The patient should regularly undergo breast examinations, in accordance with the doctor's recommendations.

When not to use Systen Conti

In the event of any of the following conditions or in case of doubt, you should tell your doctorbefore using Systen Conti.
Do not start using Systen Conti:

• if the patient is allergicto estradiol, norethisterone acetateor any of the other ingredients of this medicine (listed in section 6);
• if the patient has or has had breast canceror is suspected of having it;
• if the patient has or is suspected of having an estrogen-dependent tumor(e.g. endometrial cancer);
• if the patient has untreated endometrial hyperplasia- endometrial hyperplasia;
• if the patient has bleeding from the genital tract of unknown origin;
• if the patient is pregnant or breastfeeding;
• if the patient has or has had liver disease, and liver function test results have not returned to normal;
• if the patient has or has had blood clots in the veins(venous thromboembolic disease) e.g. in the veins of the lower limbs (deep vein thrombosis), in the lungs (pulmonary embolism);
• if the patient has blood coagulation disorders(deficiency of protein C, protein S or antithrombin);
• if the patient has or has had thromboembolic arterial disorders(e.g. stroke, angina pectoris, myocardial infarction);
• if the patient has a rare, inherited blood disease - porphyria.

If any of the above conditions occur for the first time during the use of Systen Conti, its use should be discontinued and a doctor consulted.

Warnings and precautions

Before starting treatment, you should inform your doctor about any of the following conditions that you have had in the past, as they may recur or worsen during the use of Systen Conti.
In such a case, the doctor may decide that the patient requires more frequent monitoring:

• uterine fibroids;
• endometriosis (presence of fragments of endometrial tissue in atypical locations for this tissue) or endometrial hyperplasia (excessive growth of endometrial tissue) in the past;
• increased risk of blood clots (see below "Blood clots in the veins (venous thromboembolic disease)";
• increased risk of estrogen-dependent tumors, e.g. breast cancer in the mother, sister, or grandmother;
• hypertension;
• liver disease (e.g. liver tumor);
• diabetes;
• gallstones;
• migraine or (severe) headaches;
• immune system disease affecting many organs (systemic lupus erythematosus);
• epilepsy;
• asthma;
• otosclerosis (ear disease leading to gradual hearing loss);
• mastopathy;
• high triglyceride levels in the blood;
• fluid retention due to impaired heart or kidney function;
• a condition in which the thyroid gland does not produce enough thyroid hormones (hypothyroidism) and the patient is undergoing thyroid hormone replacement therapy;
• a hereditary and acquired condition that causes recurring episodes of edema (hereditary and acquired angioedema) or a history of sudden swelling of the hands, face, feet, lips, eyes, tongue, throat (respiratory tract obstruction) or gastrointestinal tract.

In the event of the following conditions occurring during HRT, Systen Conti should be discontinued and a doctor consulted immediately:

• if any of the conditions listed in the "When not to use Systen Conti" section occur;
• if the skin or whites of the eyes turn yellow (jaundice), which may be a sign of liver function disorders;
• significant increase in blood pressure (symptoms may include: headache, fatigue, and dizziness);
• if a migraine-type headache occurs for the first time;
• if pregnancy is detected;
• if facial, tongue, and/or throat swelling and/or difficulty swallowing or hives occur, in combination with difficulty breathing, suggesting angioedema;
• if symptoms of a blood clot occur, such as:
• painful swelling and redness of the lower limbs,
• sudden chest pain,
• breathing difficulties. For more information, see the section Blood clots in the veins (venous thromboembolic disease). Note:Systen Conti is not a contraceptive. If it has been less than 12 months since the last menstrual period or the patient is under 50 years of age, it may be necessary to use an additional method of contraception. You should talk to your doctor.

Hormone replacement therapy and cancer

Endometrial hyperplasia (endometrial hyperplasia) and endometrial cancer (endometrial cancer)

The use of estrogen-only HRT increases the risk of endometrial hyperplasia and endometrial cancer.
The progestogen in Systen Conti helps to reduce this additional risk.
Comparison
In women aged 50-65 with an intact uterus and not using HRT, endometrial cancer is diagnosed in an average of 5 out of 1000 women.
In women aged 50-65 with an intact uterus and using estrogen-only HRT, the number of cases of endometrial cancer ranges from 10 to 60 per 1000 women (i.e. 5-55 additional cases), depending on the duration of treatment and the dose of estrogen used.

Irregular bleeding

During the first 3 to 6 months of using Systen Conti, irregular bleeding or spotting may occur. However, if irregular bleeding:

• persists for longer than the first 6 months;
• occurs after using Systen Conti for more than 6 months;
• persists after discontinuing Systen Conti; you should consult a doctor as soon as possible.

Breast cancer
Data confirm that taking hormone replacement therapy (HRT) in the form of combined estrogen and progestogen or estrogen alone increases the risk of breast cancer. The additional risk depends on how long the patient uses HRT. This additional risk becomes apparent after 3 years of using HRT. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or longer if HRT lasted more than 5 years.
Comparison
In the case of women aged 50-54 who do not use HRT, breast cancer is diagnosed in an average of 13 to 17 out of 1000 women over a period of 5 years.
In the case of women aged 50 who start 5-year estrogen-only HRT, the number of cases will be 16-17 per 1000 patients (i.e. 0-3 additional cases).
In the case of women aged 50 who start 5-year combined estrogen-progestogen HRT, the number of cases will be 21 per 1000 patients (i.e. 4-8 additional cases).
In the case of women aged 50-59 who do not use HRT, breast cancer is diagnosed in an average of 27 out of 1000 women over a period of 10 years.
In the case of women aged 50 who start 10-year estrogen-only HRT, the number of cases will be 34 per 1000 patients (i.e. 7 additional cases).
In the case of women aged 50 who start 10-year combined estrogen-progestogen HRT, the number of cases will be 48 per 1000 patients (i.e. 21 additional cases).

You should regularly examine your breasts. You should consult a doctor if you notice any of the following changes:

• wrinkling of the skin;
• changes in the nipple;
• any noticeable or palpable lumps.

In addition, it is recommended to participate in offered breast cancer screening programs.
It is important to inform the nurse or medical staff performing the X-ray examination about the use of hormone replacement therapy, as this medicine may increase breast density, which can affect the result of the mammogram. Not all tumors can be detected during a mammogram in areas of increased breast density.
Ovarian cancer
Ovarian cancer occurs less frequently than breast cancer. In some epidemiological studies, during long-term (at least 5 to 10 years) use of hormone replacement therapy, including only estrogens, an increased risk of ovarian cancer was found in women who had undergone a hysterectomy. Some studies, including the WHI study, suggest that long-term use of combined HRT may cause similar or slightly lower risk.

Hormone replacement therapy and its effect on the heart and circulation

Blood clots in the veins (venous thromboembolic disease)

The use of HRT is associated with an increased risk of developing venous thromboembolic disease, i.e. deep vein thrombosis or pulmonary embolism.
Studies have shown a 2-3-fold increase in the risk of venous thromboembolic disease in women taking hormone replacement therapy compared to women not taking it.
The occurrence of this complication is more likely in the first year of using HRT than later.
Blood clots can be life-threatening and if they move to the lungs, they can cause chest pain, shortness of breath, loss of consciousness, and even death.
The risk of blood clots in the veins is higher if the patient is older and if the following factors occur. You should inform your doctor if:

• the patient is unable to walk for a long time due to severe injuries or surgical procedures (see section 3. If surgery is planned);
• obesity is present (body mass index - BMI >30 kg/m );
• thromboembolic disorders occur that require long-term use of anticoagulant medications;
• any close relative has had blood clots in the past in the lower limbs, lungs, or other organs;
• systemic lupus erythematosus occurs.

If symptoms of a blood clot occur, see In the event of the following conditions occurring during HRT, Systen Conti should be discontinued and a doctor consulted immediately.
There is no consensus on the potential role of varicose veins in venous thromboembolic disease.
Women already undergoing anticoagulant therapy should discuss the balance of benefits and risks of using HRT with their doctor.

Hormone replacement therapy and coronary heart disease

There is no evidence that HRT prevents myocardial infarction.
In women over 60 years of age who use combined estrogen-progestogen HRT, the risk of coronary heart disease is slightly higher than in women not using HRT.

Hormone replacement therapy and stroke

The risk of stroke is approximately 1.5 times higher in women using HRT than in women not using it. The number of additional cases of stroke caused by HRT will increase with age.
Comparison
In women aged 50-59 who do not use HRT, the average number of stroke cases over 5 years is estimated to be 8 per 1000 women. In women aged 50-59 who use HRT, the number of cases over 5 years will be 11 per 1000 women (i.e. 3 additional cases).

Conditions requiring observation during estrogen therapy:

• liver disorders or mild liver failure;
• jaundice with bile stasis in the history;
• HRT does not improve cognitive function. There is evidence of an increased risk of probable dementia in women starting continuous, combined, or estrogen-only therapy at an age over 65.

In women with an intact uterus using unopposed estrogen therapy, an increased risk of hyperplasia and endometrial cancer has been found. Therefore, to reduce the risk of hyperplasia and endometrial cancer in women with an intact uterus, it is recommended to administer estrogen in combination with a progestogen, as during the use of Systen Conti.
Systen Conti should be stored in a place inaccessible to children and pets.

Children and adolescents

Systen Conti should not be used in children.

Systen Conti and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Some medicines may affect the effectiveness of Systen Conti, which can lead to irregular bleeding. These include:

• antiepileptic drugs (such as phenobarbital, phenytoin, and carbamazepine),
• antituberculosis drugs (such as rifampicin, rifabutin),
• medicines used to treat HIV infection (such as nevirapine, efavirenz, ritonavir, and nelfinavir),
• medicines used to treat hepatitis C virus (HCV) infection (such as telaprevir)
• herbal products containing St. John's wort (Hypericum perforatum).

Hormone replacement therapy may affect the action of other medicines:

• antiepileptic drugs (lamotrigine), as it may increase the frequency of seizures.
• medicines used to treat hepatitis C virus (HCV) infection, such as treatment regimens using ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin or without ribavirin, using glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir, may cause increased liver function test results in the blood (increased ALT enzyme activity) in women using combined hormonal contraceptives containing ethinyl estradiol. Systen Conti contains estradiol instead of ethinyl estradiol. It is not known whether increased ALT enzyme activity may occur when using Systen Conti with such a treatment regimen.

You should tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including over-the-counter medicines, herbal medicines, and natural products. Your doctor will provide you with appropriate instructions.

Lab tests

If a blood test is necessary, you should inform your doctor or laboratory staff about the use of Systen Conti, as it may affect the results of some tests, such as a glucose tolerance test or thyroid function tests.

Pregnancy and breastfeeding

Systen Conti is contraindicated in pregnancy. If pregnancy is detected during the use of Systen Conti, the product should be discontinued immediately.
The use of Systen Conti is contraindicated during breastfeeding.

Driving and using machines

No studies have been conducted on the effect of Systen Conti on the ability to drive and use machines.

3. How to use Systen Conti

This medicine should always be used as directed by your doctor. If you are unsure, you should consult your doctor.
HRT should only be continued for as long as the benefits of alleviating severe symptoms outweigh the risks of using HRT.
Your doctor should prescribe the lowest effective dose for the shortest possible time that will provide symptom relief. If you think the dose of the medicine is too high or too low, you should consult your doctor.

Dosage

Your doctor will adjust the dose of the medicine according to its effectiveness in a given woman.
Systen Conti should be used continuously (without interruption), applying patches to the skin of the torso below the waistline twice a week. Patches should be changed every 3 or 4 days. For example, if the application of the first patch occurs on Monday, it should be replaced on Thursday, and then on the following Monday. When determining these days, you can use the following table based on the first day of patch application:
To make it easier to remember the days of patch replacement, you should mark their configuration in the designated place on the packaging:

In the treatment of menopausal symptoms, the doctor will recommend the lowest effective dose.
If the patch is partially or completely detached before the planned replacement, a new patch should be applied immediately. However, the same day of patch replacement should be maintained.
Wearing a patch for a period longer than 4 days or being without a patch for any period (missing a dose) increases the likelihood of irregular bleeding, intermenstrual bleeding, or spotting.

Using Systen Conti in patients with renal and/or hepatic impairment

There is insufficient data on dosing in patients with severe hepatic or renal impairment.
Estrogens may cause fluid retention in the body, so patients with heart or kidney failure should be closely monitored during the use of Systen Conti.

Using Systen Conti in elderly women

There is insufficient data to support the use of Systen Conti in women over 65 years of age.

Method of administration

The patch should be applied to clean, dry, healthy, and intact skin on the torso below the waistline. Cream, body lotion, or powder may interact with the adhesive layer of the patch and should not be used at the site of application. Systen Conti should not be applied to the skin of the breast or its surroundings. The site where the patch is applied should be changed. To apply a patch to the same site, a minimum of one week should be allowed to pass
Systen Conti should be used immediately after opening the sachet.
After opening the sachet containing the patch, one part of the protective foil should be removed.
Then, without bending, the exposed part of the patch should be applied to the site where it is to be attached, from its edge to the center.

The patient should remove the second part of the protective foil and press the patch onto the skin with their hand, again without bending it, and press the patch onto the skin with their hand for at least 10 seconds, warming it with their hand to body temperature, which is crucial for achieving the best patch adhesion. During the application of the patch, the patient should not directly touch the adhesive layer with their fingers.

It is not necessary to remove the patch during bathing or showering. However, it is recommended to remove the patch before using a sauna, and after the sauna, a new patch should be applied immediately. To remove the patch, you should grasp its edge and gently peel it off the skin. After use, the patch should be folded in half and thrown away in the trash (do not flush down the toilet). Any remaining adhesive on the skin after removing the patch can be removed with soap and water or rubbed off with your fingers.

Using more than the recommended dose of Systen Conti

In the event of using a higher dose than recommended, you should immediately consult a doctor or pharmacist.
Symptoms of overdose of combined estrogen and progestogen therapy may include: nausea, intermenstrual bleeding, breast pain and tenderness, cramps, and abdominal bloating. The mentioned symptoms are temporary and disappear without specific treatment after removal of the transdermal system.

Missing a dose of Systen Conti

If the patient forgets to replace a patch, the missed patch should be applied as soon as possible.
However, the previously scheduled patch replacement day should be maintained. Forgetting to use the medicine may increase the likelihood of bleeding and intermenstrual spotting.

If surgery is planned

If surgery is planned for the patient, she should inform the surgeon that she is taking Systen Conti. It may be necessary to discontinue the use of Systen Conti 4 to 6 weeks before surgery to minimize the risk of blood clots (see section 2. Blood clots in the veins (venous thromboembolic disease)). Before resuming the use of Systen Conti, you should consult your doctor.

4. Possible side effects

Like all medicines, Systen Conti can cause side effects, although not everybody gets them.
Women using HRT are at increased risk of developing the following diseases compared to women not using HRT:

• breast cancer;
• endometrial hyperplasia or cancer (endometrial hyperplasia or cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolic disease);
• coronary heart disease;
• stroke;
• possibly dementia if HRT is started at an age over 65.

For more information, see section 2 "Important information before using Systen Conti".
The following side effects have been observed in clinical trials and reported after the marketing of Systen Conti.
Very common(may affect more than 1 in 10 people):

• redness at the application site, itching at the application site, rash at the application site, reaction at the application site.

Common(may affect up to 1 in 10 people):

• hypersensitivity;
• depression, insomnia, anxiety nervousness;
• disorders of sensation - paresthesia, headache;
• palpitations;
• hypertension, varicose veins, vasodilation;
• abdominal pain, diarrhea*, nausea;
• flushing;
• joint pain, back pain;
• breast pain, cervical polyp, endometrial hyperplasia (hyperplasia of the endometrium), discharge, painful menstruation, heavy menstrual bleeding, menstrual disorders, uterine bleeding;
• pain, swelling, edema at the application site*, fatigue;
• weight gain.

Uncommon(may affect up to 1 in 100 people):

• candidiasis;
• decreased libido;
• migraine;
• bloating*;
• pruritus, rash*;
• muscle pain*;
• generalized edema, peripheral edema*.

Rare(may affect up to 1 in 1000 people):

• epilepsy*;
• thrombophlebitis*.

Frequency not known(frequency cannot be estimated from the available data)

• breast cancer, endometrial cancer (endometrial cancer);
• mood swings;
• cerebrovascular incident, dizziness;
• deep vein thrombosis;
• pulmonary embolism;
• abdominal distension;
• gallstones;
• Stevens-Johnson syndrome;
• breast enlargement.

* Additional side effects reported in clinical trials of Systen 50 (containing only estradiol).
Other side effects associated with oral estrogen-progestogen replacement therapy:

• dizziness;
• nausea, vomiting;
• limb pain, myasthenia;
• breast tenderness, uterine cramps, vaginal infection;
• uterine fibroids, ovarian cyst;
• increased liver enzyme activity - aminotransferases - in laboratory tests
• gallbladder disease, jaundice;
• skin and subcutaneous tissue disorders: lupus erythematosus, erythema multiforme, erythema nodosum, purpura, acne, dry skin, alopecia;
• probable dementia in women over 65 years of age;
• dry eye syndrome;
• change in tear composition.

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the
Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Jerozolimskie Avenue 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Systen Conti

Store at a temperature not exceeding 25°C.
The medicine should be stored in a place out of sight and reach of children.
This recommendation also applies to used patches.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date (EXP) refers to the last day of the month stated.
Medicines should not be disposed of via wastewater. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Systen Conti contains

The Systen Conti transdermal system, patch contains as active substances:

• 3.2 mg of estradiol (Estradiolum), in the form of estradiol hemihydrate;
• 11.2 mg of norethisterone acetate (Norethisteroni acetas). The other ingredients of the medicine are:
• Adhesive layer: acrylic copolymer, guar gum.
• Protective layer (outer protective layer): polyester.
• Protective layer (to be removed): polyethylene terephthalate.

What Systen Conti looks like and contents of the pack

8 transdermal systems, patches in sachets, placed in a cardboard box.
The Systen Conti transdermal system, patch has a surface area of 16 cm and contains 3.2 mg of estradiol, which corresponds to a nominal release of 50 μg of estradiol over 24 hours, and 11.2 mg of norethisterone acetate, which is released in a nominal amount of 170 μg over 24 hours.

Marketing authorization holder:

Theramex Ireland Limited
3rd Floor, Kilmore House,
Park Lane, Spencer Dock,
Dublin 1
D01 YE64
Ireland

Manufacturer:

Aesica Pharmaceuticals GmbH
Alfred-Nobel-Str. 10
40789 Monheim am Rhein
Germany
To obtain more detailed information, you should contact the local representative of the marketing authorization holder at phone number: 22 307 71 66.
Date of last revision of the leaflet:July 2025