Sindi-35

Package Leaflet: Information for the User

Syndi-35

2 mg + 0.035 mg, sugar-coated tablets

Cyproterone acetate + Ethinylestradiol

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this package 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Syndi-35 and what is it used for
• 2. Important information before taking Syndi-35
• 3. How to take Syndi-35
• 4. Possible side effects
• 5. How to store Syndi-35
• 6. Contents of the pack and other information

1. What is Syndi-35 and what is it used for

Syndi-35 is used to treat skin conditions such as acne, very oily skin, and excessive hair growth in women of childbearing age. Due to its contraceptive properties, this medicine should only be prescribed to a patient if the doctor considers that treatment with hormonal contraceptives is appropriate.
Patient should use Syndi-35 to treat acne only if there has been no improvement in the condition of the skin after using other anti-acne therapies, including local treatment and antibiotic treatment.

2. Important information before taking Syndi-35

General Notes

Before starting to take Syndi-35, the doctor will ask the patient a few questions about her health and the health of her close relatives. The doctor will also measure the patient's blood pressure and, if necessary, perform other diagnostic tests.
This package leaflet describes certain situations in which the patient should stop taking Syndi-35 or in which the effectiveness of Syndi-35 may be reduced. In such situations, the patient should not have sexual intercourse or use additional non-hormonal methods of contraception, such as a condom or other mechanical methods. The patient should not use the calendar method or the body temperature measurement method. These methods may be unreliable because Syndi-35 modifies the monthly changes in body temperature and cervical mucus.

Syndi-35 does not protect against HIV infection (AIDS) or other sexually transmitted diseases.

When not to take Syndi-35

The patient should inform the doctor if any of the following conditions are present before starting to take Syndi-35. The doctor may then recommend the use of another treatment:

• If the patient is taking another hormonal contraceptive.
• If the patient currently has (or has ever had) a blood clot in the leg (thrombophlebitis), a blood clot in the lungs (pulmonary embolism), or in any other part of the body.
• If the patient currently has (or has ever had) diseases that may be risk factors for a future heart attack (e.g., angina pectoris, which causes severe chest pain) or if the patient has had a "mini-stroke" (transient ischemic attack).
• If the patient has had a heart attack or stroke.
• If the patient has factors that may increase the risk of blood clots. These include:
• diabetes with vascular complications;
• very high blood pressure;
• very high levels of fat in the blood (cholesterol or triglycerides).
• If the patient has a blood clotting problem (e.g., protein C deficiency).
• If the patient currently has (or has ever had) migraine with visual disturbances.
• If the patient has had severe liver disease (which may cause yellowing of the skin or itching all over the body) and liver function tests are still abnormal.
• If the patient has had or currently has hormone-dependent malignant tumors (e.g., breast cancer or genital organ tumors).
• If the patient has had or currently has a malignant or benign liver tumor.
• If the patient has bleeding from the genital tract of unknown cause.
• If the patient is pregnant or thinks she may be pregnant.
• If the patient is breastfeeding.
• If the patient is allergic to cyproterone acetate, ethinylestradiol, or any of the other ingredients of this medicine (listed in section 6). This may cause itching, rash, or swelling.
• If the patient has hepatitis C and is taking antiviral medicines containing ombitasvir with paritaprevir and ritonavir, dasabuvir, glecaprevir with pibrentasvir, or sofosbuvir with velpatasvir and voxilaprevir (see section 2 "Syndi-35 and other medicines").
• If the patient has a meningioma or has been diagnosed with a meningioma (usually a benign tumor of the tissue layer between the brain and the skull).

If any of the above symptoms occur for the first time while taking Syndi-35, the patient should stop taking the medicine and consult a doctor. During this time, the patient should use non-hormonal methods of contraception (see the section "General Notes").
Syndi-35 should not be taken by men.

Special patient groups

Children and adolescents
Syndi-35 is not indicated for use in patients before their first menstrual period.
Elderly patients
Syndi-35 is not intended for use in women after menopause.
Patients with liver function disorders
Syndi-35 is contraindicated in women with severe liver function disorders until liver function tests return to normal. See the section "When not to take Syndi-35" and "Warnings and precautions".
Patients with kidney function disorders
The patient should consult a doctor. Available data do not indicate the need to change the way Syndi-35 is taken.

Warnings and precautions

When to consult a doctor

Stop taking the tablets and consult a doctor immediately if you notice symptoms that may indicate a blood clot, such as:

Before starting to take Syndi-35, discuss this with your doctor or pharmacist.

If you are taking Syndi-35, in any of the following situations, close medical supervision is necessary.
Therefore, before starting to take Syndi-35, inform your doctor if you:

• smoke (women over 35 years of age should stop smoking if they decide to use oral hormonal contraception),
• have diabetes,
• are obese (body mass index over 30 kg/m2),
• have high blood pressure,
• have heart valve problems or atrial fibrillation,
• have superficial vein inflammation,
• have varicose veins,
• have a history of blood clots, heart attack, or stroke in close relatives, currently or in the past,
• have had migraine (currently or in the past),
• have epilepsy,
• have high levels of cholesterol or triglycerides (fats) in the blood (also in the past or in close relatives),
• have a history of breast cancer in close relatives, currently or in the past,
• have liver or gallbladder disease,
• have Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease),
• have polycystic ovary syndrome,
• have systemic lupus erythematosus (SLE),
• have hemolytic uremic syndrome (a blood clotting disorder that causes kidney failure),
• have sickle cell anemia,
• have diseases that first occurred or worsened during pregnancy or previous use of steroid hormones [e.g., jaundice and (or) itching associated with bile stasis, gallstone formation, hearing loss associated with otosclerosis, a blood disease known as porphyria, a rash with blisters (pregnancy pemphigoid), a neurological disorder that causes abnormal movements of a body part (Sydenham's chorea)],
• have skin discoloration (pigmentation changes in the skin, especially on the face and neck, so-called chloasma) currently or in the past; in this case, you should avoid excessive sun exposure or ultraviolet radiation,
• if you experience symptoms of angioedema, such as: swelling of the face, tongue, and (or) throat, and (or) difficulty swallowing, or hives, potentially with breathing difficulties, you should contact your doctor immediately. Estrogen-containing products may cause or worsen symptoms of hereditary or acquired angioedema.

If any of the above symptoms occur for the first time, recur, or worsen while taking Syndi-35, you should consult your doctor.
If you have hirsutism, if the symptoms of the disease have occurred recently or worsened, you should immediately inform your doctor, who will make a proper diagnosis.
Syndi-35 also acts as an oral contraceptive. The patient and doctor should discuss all the usual rules for safe use of oral hormonal contraception.

Syndi-35 and blood clots

Blood clots (thrombosis)
Taking Syndi-35 may slightly increase the risk of blood clots in the patient (so-called thrombosis). The likelihood of blood clots in patients taking Syndi-35 is only slightly increased compared to women who do not take Syndi-35 or any other oral contraceptive. Not everyone recovers completely, 1-2% of cases can be fatal.
Blood clots in veins
A blood clot in a vein (known as "venous thrombosis") can block a vein. This can happen in the veins of the legs, lungs (pulmonary embolism), or in any other organ.
Taking a combined oral contraceptive increases the risk of such blood clots in women compared to women who do not take any combined oral contraceptives. The risk of developing a blood clot in the veins is highest during the first year of taking the oral contraceptive. The risk is not as high as the risk of blood clots during pregnancy.
The risk of blood clots in the veins increases additionally:

• with age;
• if the patient smokes. When taking a hormonal contraceptive like Syndi-35, it is strongly recommended to quit smoking, especially if the patient is over 35 years old;
• if the patient is overweight;
• if the patient has to undergo surgery, is immobilized for a longer period due to injury or illness, or has a leg in a cast.

If the above conditions apply to the patient, it is essential to inform the doctor about taking Syndi-35, as there may be a need to stop the treatment. The attending doctor may order the patient to stop taking Syndi-35 for a few weeks before surgery or when the patient's mobility is limited. The attending doctor will also inform the patient when they can start taking Syndi-35 again after returning to physical fitness.
Blood clots in arteries
Blood clots in arteries can cause severe disorders. For example, a blood clot in the artery in the heart can cause a heart attack, and in the brain, it can cause a stroke. This can be a serious threat to life or lead to death.
Taking combined oral contraceptives is associated with an increased risk of blood clots in arteries. This risk increases additionally:

• with age;
• if the patient smokes. When taking a hormonal contraceptive like Syndi-35, it is strongly recommended to quit smoking, especially if the patient is over 35 years old;
• if the patient is overweight;
• if the patient has high blood pressure;
• if a close relative of the patient had a heart attack or stroke at a young age;
• if the patient has a high level of fats in the blood (cholesterol or triglycerides);
• if the patient has migraines;
• if the patient has heart disease (valve damage, arrhythmia).

Symptoms caused by a blood clot

Stop taking the tablets and consult a doctor immediately if you notice symptoms that may indicate a blood clot, such as:

• unusual, sudden cough;
• severe chest pain, which may radiate to the left arm;
• shortness of breath;
• any unusual, severe, prolonged headache or worsening migraine;
• partial or complete loss of vision or double vision;
• slurred speech or loss of speech ability;
• sudden hearing, smell, or taste disorders;
• dizziness or fainting;
• weakness or numbness of any part of the body;
• severe abdominal pain;
• severe pain or swelling of any leg.

Not everyone recovers completely after a blood clot. Occasionally, thrombosis can cause permanent disability as well as death.
After childbirth, women are at increased risk of blood clots. The doctor should be consulted to determine how soon it is possible to start taking Syndi-35 after childbirth.
If the patient has any of the above risk factors for blood clots in veins or arteries, they should inform the doctor, as Syndi-35 may not be suitable for the patient. The more risk factors, the higher the risk of venous or arterial thrombosis. The risk also increases with the severity of each individual risk factor (see also "When not to take Syndi-35").

Syndi-35 and cancer

In women taking oral hormonal pills, breast cancer occurs slightly more often than in women of the same age who do not take them. It is not known whether this difference is caused solely by the treatment. The reason may also be that women taking hormonal contraception are examined more frequently and breast cancer is detected earlier. The described difference in the incidence of breast cancer decreases gradually and disappears within 10 years after stopping hormonal treatment.
Rarely, cases of benign or, even more rarely, malignant liver tumors have been reported in women taking combined oral contraceptives, which can cause life-threatening bleeding into the abdominal cavity. If severe abdominal pain occurs, the doctor should be informed immediately.
These tumors can be life-threatening or cause death.
There are reports of a more frequent occurrence of cervical cancer in women who have been taking hormonal contraceptives for a long time. However, this relationship may not be related to taking the pills but to sexual practices.
There have been reports of an increased risk of developing a benign brain tumor (meningioma) when taking high doses (25 mg or more) of cyproterone acetate. If a meningioma is detected in a patient, the doctor will stop treatment with products containing cyproterone, including Syndi-35, as a precautionary measure (see the section "When not to take Syndi-35").

Psychological disorders

Some women taking hormonal contraceptives, including Syndi-35, have reported depression or low mood. Depression can be severe and sometimes lead to suicidal thoughts. If mood changes and symptoms of depression occur, the doctor should be consulted immediately for further medical advice.

Syndi-35 and other medicines

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 make Syndi-35 less effective or cause unexpected bleeding. These include:

• medicines used to treat:
• epilepsy (e.g., primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, felbamate, topiramate),
• tuberculosis (e.g., rifampicin),
• other infections (e.g., antibiotics that induce enzymes, such as griseofulvin),
• products containing St. John's wort (Hypericum perforatum).

Other medicines may increase or decrease the level of Syndi-35 in the blood. These include:

• medicines used to treat HIV or hepatitis C virus (known as protease inhibitors or non-nucleoside reverse transcriptase inhibitors).

Do not take Syndi-35 if you have hepatitis C and are taking antiviral medicines containing ombitasvir with paritaprevir and ritonavir, dasabuvir, glecaprevir with pibrentasvir, or sofosbuvir with velpatasvir and voxilaprevir, as they may cause elevated liver function test results (increased ALT enzyme levels). The doctor will recommend an appropriate type of contraception before starting these medicines.
Syndi-35 can be resumed about 2 weeks after completing treatment with these medicines. See section 2 "When not to take Syndi-35".
Syndi-35 may also affect the action of other medicines, such as lamotrigine, cyclosporine.
Note: You should read the information about concomitant use of medicines to recognize possible interactions.

Pregnancy and breastfeeding

Pregnancy
Do not take Syndi-35 if you are pregnant or think you may be pregnant. If you suspect pregnancy, consult your doctor immediately.
Breastfeeding
Do not take Syndi-35 while breastfeeding. If you want to take contraceptive pills while breastfeeding, consult your doctor.

Driving and using machines

No effects of Syndi-35 on the ability to drive and use machines have been observed.

Regular check-ups

While taking Syndi-35, the doctor will inform you about the need for regular medical check-ups.

Syndi-35 contains lactose monohydrate and sucrose

If you have been diagnosed with intolerance to some sugars, you should consult your doctor before taking Syndi-35.

3. How to take Syndi-35

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

How to take Syndi-35

Regular intake of Syndi-35 ensures effective therapeutic action and prevents pregnancy. Irregular intake of Syndi-35 may lead to irregular bleeding and worsen the therapeutic and contraceptive properties of the medicine.

• When and how to take the tablets?The blister pack contains 21 tablets. On the packaging, each tablet is marked with the day of the week on which it should be taken. The tablets should be taken in the order indicated by the arrow on the packaging, every day, at about the same time, with a small amount of liquid if necessary. For 21 consecutive days, take 1 tablet per day, following the arrows on the blister. Each subsequent pack should be started after a 7-day break, during which no tablets are taken and when withdrawal bleeding usually occurs. This is called "withdrawal bleeding," which usually starts 2-3 days after taking the last tablet and may still occur after starting the next pack. This means that you should always start each subsequent pack on the same day of the week, and the bleeding will occur around the same days every month.
• Starting to take Syndi-35 for the first time
• If you have not taken oral contraceptives in the last month

Take the tablets on the first day of your natural menstrual cycle (i.e., on the first day of menstrual bleeding). You can also start taking the tablets between the 2nd and 5th day of your menstrual cycle; in this case, during the first cycle, it is recommended to use an additional mechanical method for the first 7 days of taking the tablets.

• If you have taken another combined oral contraceptive or used a vaginal ring or transdermal system

It is recommended to start taking Syndi-35 on the day after taking the last active tablet of the previous combined oral contraceptive, but no later than the day after the usual break in taking active tablets or placebo tablets of the previous combined oral contraceptive. When using a vaginal ring or transdermal system, you should start taking Syndi-35 on the day the ring or system is removed, but no later than the day the ring or system is scheduled to be reapplied.

• If you have taken a progestin-only pill (minipill)

You can stop taking the minipill at any time and start taking Syndi-35 at the same time. During the first 7 days, you should also use a mechanical method of contraception.

• If you have used injectable contraception, an implant, or an intrauterine system releasing progestogen

Start taking Syndi-35 on the day the next injection is scheduled or on the day the implant or intrauterine system is removed. If you have had sexual intercourse during the first 7 days of taking the tablets, use a mechanical method of contraception.

• After childbirth, miscarriage, or abortion
• After a miscarriage in the first trimester of pregnancy

You can start taking Syndi-35 immediately. In this case, there is no need to use additional methods of contraception.

• After childbirth or miscarriage in the second trimester of pregnancy

The doctor should inform you that you should start taking the tablets 21-28 days after childbirth or miscarriage in the second trimester of pregnancy. If you start taking the tablets later, the doctor should inform you about the need to use additional mechanical contraception for the first 7 days of taking the tablets. If you have had sexual intercourse before starting to take Syndi-35, make sure you are not pregnant or wait for your first menstrual period.
If you forget to take a tablet and do not experience the expected withdrawal bleeding during the first break in taking the tablets, it is possible that you are pregnant. Before starting the next pack of Syndi-35, consult your doctor.

What to do if you take more Syndi-35 than you should

Nausea, vomiting, or bleeding from the genital tract may occur (especially in young girls). There are no reports of serious side effects after taking multiple tablets of Syndi-35 at the same time.
If you have taken more Syndi-35 than you should or if a child has taken some, consult your doctor.

How long to take Syndi-35

Your doctor will tell you how long to take Syndi-35.

If you forget to take Syndi-35

If it has been less than 12 hourssince you forgot to take a tablet, the contraceptive effectiveness of Syndi-35 is not reduced. Take the tablet as soon as possible and take the next one at the usual time.
If it has been more than 12 hourssince you forgot to take a tablet, the effectiveness of Syndi-35 may be reduced. The more tablets you forget, the higher the risk of becoming pregnant. The risk of becoming pregnant is particularly high if you forget tablets at the beginning or end of the pack. In this case, follow the rules below (see also the scheme below).

• Forgot more than 1 tablet from the current packConsult your doctor.
• Forgot 1 tablet in the 1st week of taking the medicine from the current packTake the forgotten tablet as soon as possible (even if it means taking two tablets at the same time), and take the next tablets at the usual time. Use additional mechanical methods of contraception for the next 7 days.

If you had sexual intercourse during the week before forgetting the tablet, it is possible that you may become pregnant. Consult your doctor immediately.

• Forgot 1 tablet in the 2nd week of taking the medicine from the current packTake the forgotten tablet as soon as possible (even if it means taking two tablets at the same time), and take the next tablets at the usual time. The contraceptive effectiveness of Syndi-35 is maintained, and there is no need to use additional methods of contraception. However, if you made mistakes when taking the tablets earlier or forgot more than 1 tablet, you should use additional mechanical methods of contraception for 7 days.
• Forgot 1 tablet in the 3rd week of taking the medicine from the current packYou can choose one of the following options without the need to use additional methods of contraception, provided that you have taken the tablets correctly for the 7 days preceding the forgotten tablet. If not, you should use the first of the two options below and use additional mechanical methods of contraception for 7 days.
• 1. Take the forgotten tablet as soon as possible (even if it means taking two tablets at the same time), and take the next tablets at the usual time. Start taking the tablets from the next pack immediately after finishing the current one, without a 7-day break. Withdrawal bleeding will occur after finishing the second pack, but during the intake of tablets from this pack, spotting or bleeding may also occur.
• 2. You can also stop taking the remaining tablets from the current pack, take a break (not more than 7 days, counting from the day the tablet was forgotten), and then continue taking the tablets from the next pack.

If you forget to take a tablet and do not experience the expected withdrawal bleeding during the first break in taking the tablets, it is possible that you are pregnant. Before starting the next pack of Syndi-35, consult your doctor.

What to do in case of:

• gastrointestinal disorders (vomiting)

If vomiting occurs within 3-4 hours after taking a tablet, the active substances of Syndi-35 may not be fully absorbed. In this case, follow the same rules as for forgetting a tablet. If the patient does not want to change the schedule of taking the tablets, they should take an additional tablet from a new (additional) pack.
In case of severe gastrointestinal disorders, additional methods of contraception should be used.

• unexpected bleeding

In some women, during the use of Syndi-35, as well as during the use of other hormonal products, irregular bleeding from the genital tract may occur in the first few months. Despite this, the patient should continue taking the tablets. The problems usually disappear after 3 cycles of taking Syndi-35. If the bleeding persists, becomes heavy, or recurs, the patient should consult a doctor.

Stopping Syndi-35

If you have any further questions about taking this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Syndi-35 can cause side effects, although not everybody gets them.
Tell your doctor or pharmacist if you experience any side effects, especially if they are severe or persistent, as well as any changes in your health that seem to be the result of taking Syndi-35.

Severe side effects

Severe side effects related to taking Syndi-35 and the symptoms that accompany them are described in the following sections of the package leaflet: "Syndi-35 and blood clots/Syndi-35 and cancer".
Read these sections to get additional information and consult your doctor if necessary.
Consult your doctor immediately if you experience any of the following symptoms of angioedema: swelling of the face, tongue, and (or) throat, and (or) difficulty swallowing, or hives, potentially with breathing difficulties (see also the section "Warnings and precautions").

Other possible side effects

The following symptoms have been reported by patients taking Syndi-35, although they may not have been caused by the medicine.
These symptoms may occur in the first few months of taking Syndi-35 and usually disappear over time.
The following side effects may occur when taking Syndi-35:

Frequent(less than 1 in 10 people):

• nausea,
• abdominal pain,
• weight gain,
• headache,
• breast pain,

Infrequent(less than 1 in 100 people):

• vomiting, diarrhea,
• fluid retention,
• migraine,
• decreased libido,
• rash, hives,
• breast enlargement.

Rare(less than 1 in 1,000 people):

• intolerance to contact lenses,
• hypersensitivity,
• weight loss,
• increased libido,
• discharge, breast secretion,
• erythema nodosum, erythema multiforme,
• blood clot in a vein.

Frequency not known(cannot be estimated from the available data):
increased blood pressure.
In women with hereditary angioedema, exogenous estrogens may cause the occurrence or worsening of its symptoms (see the section "Warnings and precautions").
Some people may experience other side effects while taking Syndi-35.

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +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 Syndi-35

Keep this medicine out of the sight and reach of children.
Store in a temperature below 25°C.
Store in the original packaging. Do not use this medicine after the expiry date stated on the carton and blister after EXP. The expiry date refers to the last day of the month stated.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Syndi-35 contains

The active substances of Syndi-35 are cyproterone acetate 2 mg and ethinylestradiol 35 micrograms.
The other ingredients of the medicine are:
Core:
Lactose monohydrate
Cornstarch
Povidone K25
Talc
Magnesium stearate
Coating:
Sucrose
Calcium carbonate
Talc
Titanium dioxide (E 171)
Povidone K 90
Macrogol 6000
Glycerol 85%
Iron oxide yellow (E 172)
Montan glyceride wax

What Syndi-35 looks like and contents of the pack

Syndi-35 tablets are round, yellow, sugar-coated. One pack contains 1 blister pack of 21 tablets or 3 blister packs of 21 tablets each.

Marketing authorization holder and manufacturer

Marketing authorization holder

Symphar Sp. z o.o.
ul. Koszykowa 65
00-667 Warsaw

Manufacturer

Symphar Sp. z o.o.
ul. Chełmżyńska 249
04-458 Warsaw
Date of last revision of the package leaflet:October 2022