Lesiplus

Package leaflet: Information for the user

Warning! Keep this leaflet. Information on the immediate packaging in a foreign language.
Lesiplus (Drospirenone/Ethinylestradiol 3/0.02 mg 24+4 Theramex)
3 mg + 0.02 mg, film-coated tablets
Drospirenonum + Ethinylestradiolum
Lesiplus and Drospirenone/Ethinylestradiol 3/0.02 mg 24+4 Theramex are different brand names
of the same medicine.
Important information about combined hormonal contraceptives

• When used correctly, they are one of the most reliable, reversible methods of contraception.
• They slightly increase the risk of blood clots in veins and arteries, especially during the first year of use or after restarting following a break of 4 weeks or more.
• Be vigilant and consult a doctor if the patient suspects symptoms of blood clots (see section 2 "Blood clots (thrombosis)").

Read the entire leaflet before taking this medicine, as it contains important information for the patient

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm others.
• If the patient experiences any adverse effects, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

1. What Lesiplus is and what it is used for

• Lesiplus is a contraceptive medicine used to prevent pregnancy.
• Each of the 24 pink film-coated tablets contains a small amount of two different female hormones, namely drospirenone and ethinylestradiol.
• The 4 white film-coated tablets are inactive (placebo tablets).
• Contraceptive tablets containing two hormones are known as "combined" pills.

2. Important information before using Lesiplus

General notes
Before starting treatment with Lesiplus, you should read the information about
blood clots (thrombosis) in section 2. It is particularly important to be aware of the symptoms
of blood clots (see section 2 "Blood clots (thrombosis)").
Page 1 of 17
Before you can start taking Lesiplus, your doctor will ask you several questions about your
health and that of your close relatives. Your doctor will also measure your blood pressure and,
depending on your individual situation, may carry out additional tests.
This leaflet describes several situations in which you should stop taking Lesiplus or in
which the effectiveness of Lesiplus may be reduced. In such situations, you should either avoid sexual intercourse or use additional non-hormonal contraceptive methods,
such as condoms or other mechanical methods. Do not use calendar-based methods or temperature measurement. These methods may be unreliable because Lesiplus alters
monthly changes in body temperature and cervical mucus.
Lesiplus, like other hormonal contraceptives, does not protect against HIV infection (AIDS)
or other sexually transmitted diseases.
When not to use Lesiplus:
Do not take Lesiplus if you have any of the conditions listed below.
If you have any of the conditions listed below, inform your doctor. Your doctor will discuss with you which alternative method of contraception would be more suitable.

• if you currently have (or have ever had) a blood clot in the deep leg veins (deep vein thrombosis), in the lungs (pulmonary embolism), or in other organs;
• if you know you have blood clotting disorders—such as protein C deficiency, protein S deficiency, antithrombin III deficiency, factor V Leiden mutation, or antiphospholipid antibodies;
• if you require surgery or will be immobile for a prolonged period (see section "Blood clots (thrombosis)");
• if you have had a heart attack or stroke;
• if you have (or have had in the past) angina pectoris (a condition causing severe chest pain and may be the first sign of a heart attack) or transient ischaemic attack (temporary stroke-like symptoms);
• if you have any of the following conditions that may increase the risk of arterial blood clots:
  • severe diabetes with blood vessel damage;
  • very high blood pressure;
  • very high levels of blood fats (cholesterol or triglycerides);
  • a condition called hyperhomocysteinemia;
• if you currently have (or have had in the past) a type of migraine called "migraine with aura";
• if you currently have (or have ever had) liver disease and liver function remains abnormal;
• if you have kidney function disorders (kidney failure);
• if you currently have (or have ever had) liver tumour;
• if you currently have (or have ever had) or are suspected of having breast cancer or genital organ cancer;
• if you have any unexplained vaginal bleeding;
• if you are allergic to ethinylestradiol or drospirenone or any of the other ingredients of Lesiplus (listed in section 6). This allergy may cause itching, rash, or swelling;
• if you have hepatitis C and are taking medications containing ombitasvir/paritaprevir/ritonavir, dasabuvir, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir (see also section "Lesiplus with other medicines").

Additional information for special populations
Children and adolescents
Page 2 of 17
Lesiplus is not intended for use in girls whose menstrual cycles have not yet started.
Women of advanced age
Lesiplus is not intended for use after menopause.
Women with liver function disorders
Do not take Lesiplus if you have liver disease. See also sections "When not to use Lesiplus" and "Warnings and precautions".
Women with kidney function disorders
Do not take Lesiplus if you have kidney failure or acute kidney failure. See also sections "When not to use Lesiplus" and "Warnings and precautions".
Warnings and precautions
When should you contact your doctor?
You should contact your doctor immediately:

• if you notice possible symptoms of blood clots, which may indicate that you have a blood clot in your leg (deep vein thrombosis), in your lungs (pulmonary embolism), a heart attack, or a stroke (see section below "Blood clots (thrombosis)").

For a description of symptoms of these serious adverse effects, see "How to recognize blood clots".
In certain situations, special caution is required when using Lesiplus or any other combined hormonal contraceptive, and regular medical check-ups may be necessary.
You should inform your doctor if you have any of the following conditions.
If any of these conditions develop or worsen during treatment with Lesiplus, you should also inform your doctor.

• if there is a current or past history of breast cancer in your close family;
• if you have liver or gallbladder disease;
• if you have diabetes;
• if you have depression;
• if you have Crohn's disease or ulcerative colitis (chronic inflammatory bowel diseases);
• if you have systemic lupus erythematosus (a disease affecting the natural immune system);
• if you have haemolytic uraemic syndrome (a blood clotting disorder leading to kidney failure);
• if you have sickle cell anaemia (an inherited disorder of red blood cells);
• if you have hypertriglyceridaemia (elevated blood fat levels) or a family history of this condition. Hypertriglyceridaemia is associated with an increased risk of developing pancreatitis;
• if you require surgery or will be immobile for a prolonged period (see section 2 "Blood clots (thrombosis)");
• if you have recently given birth, as you are then at increased risk of blood clots. Consult your doctor to determine how soon after delivery you can start taking Lesiplus;
• if you have superficial thrombophlebitis (inflammation of veins under the skin);
• if you have varicose veins;

Page 3 of 17

• if you have epilepsy (see "Lesiplus with other medicines");
• if you have a condition that first occurred during pregnancy or previous use of sex hormones (e.g., hearing loss, a blood disorder called porphyria, blistering skin rash during pregnancy (pemphigoid gestationis), a neurological disorder with involuntary body movements (Sydenham's chorea));
• if you currently have or have ever had chloasma (yellow-brown skin discoloration), also known as "pregnancy mask," mainly on the face. If so, you should avoid direct exposure to sunlight 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 that may cause breathing difficulties, contact your doctor immediately. Medicines containing estrogens may cause or worsen symptoms of both hereditary and acquired angioedema.

Before starting Lesiplus, discuss this with your doctor or pharmacist.
Blood clots (thrombosis)
Using combined hormonal contraceptives such as Lesiplus is associated with an increased risk of
blood clots compared to not using such therapy.
In rare cases, a blood clot can block a blood vessel and cause serious complications.
Blood clots may occur

• in veins (referred to as "venous thrombosis" or "venous thromboembolic disease")
• in arteries (referred to as "arterial thrombosis" or "arterial thromboembolic events").

Recovery after a blood clot is not always complete. In rare cases, the consequences of a blood clot may be permanent or, very rarely, fatal.
Remember that the overall risk of harmful blood clots associated with the use of Lesiplus is low.
How to recognize blood clots
Seek immediate medical attention if you experience any of the following symptoms.
Do you experience any of these symptoms? What might be the likely cause?

• swelling of the leg or swelling along a vein in the leg Deep vein thrombosis or in the foot, especially if accompanied by:
  • pain or tenderness in the leg, which may occur only when standing or walking;
  • increased warmth in the affected leg;
  • change in skin colour of the leg, such as pallor, redness, or cyanosis.
• sudden unexplained shortness of breath or Pulmonary embolism rapid breathing;
• sudden coughing without an obvious cause, which may be associated with coughing up blood;

Page 4 of 17

Blood clots in veins
What can happen if blood clots form in veins?
Page 5 of 17

• The use of combined hormonal contraceptives is associated with an increased risk of developing blood clots in veins (venous thrombosis). Although these adverse events are rare, they most commonly occur during the first year of using combined hormonal contraceptives.
• If blood clots form in the veins of the leg or foot, this may lead to the development of deep vein thrombosis.
• If a blood clot travels from the leg and lodges in the lungs, it may cause pulmonary embolism.
• In very rare cases, a blood clot may form in another organ, such as the eye (retinal vein thrombosis).

When is the risk of developing blood clots in veins the highest?
The risk of developing blood clots in veins is greatest during the first year of using combined hormonal contraceptives for the first time. The risk may also be higher when restarting combined hormonal contraceptives (the same or a different medicine) after a break of 4 weeks or more.
After the first year, the risk decreases, although it remains higher than in women who do not use combined hormonal contraceptives.
If a woman stops taking Lesiplus, the risk of blood clots returns to normal within a few weeks.

What factors influence the risk of developing blood clots in veins?
The risk depends on a woman’s natural risk of developing venous thromboembolic disease and the type of combined hormonal contraceptive used.
The overall risk of developing blood clots in the legs or lungs associated with using Lesiplus is low.

• In the course of one year, about 2 out of 10,000 women who do not use combined hormonal contraceptives and are not pregnant will develop blood clots.
• In the course of one year, about 5–7 out of 10,000 women who use combined hormonal contraceptives containing levonorgestrel, norethisterone, or norgestimate will develop blood clots.
• In the course of one year, about 9 to 12 out of 10,000 women who use combined hormonal contraceptives containing drospirenone, such as Lesiplus, will develop blood clots.
• The risk of developing blood clots in veins depends on the individual’s medical history (see “Factors increasing the risk of developing venous blood clots” below).

Factors increasing the risk of venous blood clots
The risk of blood clots associated with the use of Lesiplus is small, however,
some factors may increase this risk. The risk is higher:

• if the patient is significantly overweight (body mass index (BMI) above 30 kg/m²);

• if a close relative of the patient has had blood clots in the legs, lungs or other organs at a young age (e.g. under 50 years of age). In this case, the patient may have an inherited clotting disorder;

• if the patient requires surgery, is immobilized for a prolonged period due to injury or illness, or has a leg in plaster. It may be necessary to discontinue the use of Lesiplus
  Page 6 of 17
  Lesiplus several weeks before surgery or reduced mobility. If the patient needs
  to discontinue Lesiplus, ask the doctor when it is safe to restart the medication;

• with increasing age (especially over 35 years);

• if the patient has given birth within the last few weeks.

The risk of developing blood clots increases with the number of risk factors present in the patient.
Air travel (>4 hours) may temporarily increase the risk of blood clots,
particularly if the patient has another risk factor listed above.
It is important to inform the doctor if any of the listed factors apply to the patient,
even if uncertain. The doctor may decide to discontinue the use of Lesiplus.
Inform the doctor if any of the above conditions change during treatment with Lesiplus, for example, if a close relative is diagnosed with unexplained thrombosis or if the patient gains significant weight.

Arterial blood clots
What can happen if blood clots form in arteries?
As with venous blood clots, arterial clots can cause serious consequences, such as heart attack or stroke.

Factors increasing the risk of arterial blood clots
It is important to emphasize that the risk of heart attack or stroke associated with the use of Lesiplus is very small, but may increase:

• with age (over approximately 35 years);
• if the patient smokes. When using a hormonal contraceptive such as Lesiplus, it is recommended to stop smoking. If the patient is unable to stop smoking and is over 35 years old, the doctor may recommend using a different type of contraception;
• if the patient is overweight;
• if the patient has high blood pressure;
• if a close relative has had a heart attack or stroke at a young age (under 50 years). In this case, the patient may also be at increased risk of heart attack or stroke;
• if the patient or a close relative has high levels of fats in the blood (cholesterol or triglycerides);
• if the patient has migraines, especially migraines with aura;
• if the patient has heart disease (valve disorder, heart rhythm disorder called atrial fibrillation);
• if the patient has diabetes.

If the patient has more than one of the above conditions, or if any of them are particularly severe, the risk of blood clots may be further increased.
Inform the doctor if any of the above conditions change during treatment with Lesiplus, for example, if the patient starts smoking, a close relative is diagnosed with unexplained thrombosis, or if the patient gains significant weight.

Lesiplus and cancer
In women using combined oral contraceptives, breast cancer is observed slightly more frequently, but it is not known whether this is caused by the medication. For example, more tumours may be detected in women using combined hormonal contraceptives because these women are examined more frequently by doctors. The incidence of breast cancer gradually decreases after stopping combined hormonal contraceptives.
It is important to examine breasts regularly and contact the doctor if any lump is detected.
Page 7 of 17
In rare cases, benign liver tumours have been reported in women using combined oral contraceptives, and even more rarely, malignant liver tumours. If the patient experiences unusual, severe abdominal pain, she should contact the doctor.

Breakthrough bleeding
During the first few months of taking Lesiplus, unexpected bleeding (bleeding outside the placebo tablet period) may occur. If such bleeding lasts longer than a few months, or if it starts after several months, the doctor should investigate the cause.

What to do if withdrawal bleeding does not occur during the placebo tablet period
If all pink active tablets have been taken correctly, without vomiting or severe diarrhoea, and no other medications have been taken, it is very unlikely that the patient is pregnant.
If withdrawal bleeding does not occur in two consecutive cycles, this may indicate pregnancy. The patient should contact her doctor immediately. Do not start the next blister pack until pregnancy has been ruled out.

Psychiatric disorders
Some women using hormonal contraceptives, including Lesiplus, have reported depression or low mood. Depression can be severe and sometimes lead to suicidal thoughts. If mood changes or symptoms of depression occur, contact the doctor as soon as possible for further medical advice.

Lesiplus and other medicines
Always inform the doctor or pharmacist about all medicines or herbal products the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. Also inform any other doctor or dentist prescribing another medicine (or pharmacist) that the patient is using Lesiplus. They may advise whether additional contraceptive methods (e.g. condoms) are needed, for how long, or whether the use of other medicines needs to be adjusted.
Do not administer Lesiplus to patients with hepatitis C virus infection who are taking medicinal products containing ombitasvir/paritaprevir/ritonavir, dasabuvir,
glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir, as this may cause increased liver function test results (increased activity of the liver enzyme AlAT).
The doctor will prescribe another type of contraception before starting treatment with these medicines.
Lesiplus may be restarted approximately 2 weeks after completion of this treatment.
See section “When not to use Lesiplus”.
Some medicines may affect the blood levels of Lesiplus and may cause Lesiplus to be less effective in preventing pregnancy or may cause unexpected bleeding.
This includes medicines used to treat:

• epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine)
• tuberculosis (e.g. rifampicin)
• HIV and hepatitis C virus infection (so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine, efavirenz)
• fungal infections (griseofulvin, ketoconazole)
• arthritis, degenerative joint disease (etoricoxib)
• pulmonary hypertension (bosentan)
• and herbal remedies containing St John's wort ( Hypericum perforatum ).

Lesiplus may affect the action of other medicines, for example:

• medicines containing cyclosporine

Page 8 of 17

• antiepileptic drugs
• theophylline (used for breathing problems)
• tizanidine (used to treat muscle pain and/or muscle spasms)
• medicines containing lamotrigine (may lead to increased frequency of epileptic seizures).

Before taking any medicine, consult a doctor or pharmacist.

Lesiplus with food and drinks
Lesiplus may be taken with or without food, and if needed, with a small amount of water.

Laboratory tests
If a blood test is required, inform the doctor or laboratory staff about the use of hormonal contraceptives, as the hormones used in contraception may affect the results of certain tests.

Pregnancy and breastfeeding
Pregnancy
Lesiplus must not be used during pregnancy. If the patient becomes pregnant while taking Lesiplus, she must stop taking it immediately and contact her doctor.
If the patient plans a pregnancy, she may stop taking Lesiplus at any time (see also “Discontinuing Lesiplus”).
Before taking any medicine, consult your doctor or pharmacist.

Breastfeeding
Lesiplus is generally not recommended while breastfeeding. If the patient wishes to use a contraceptive during breastfeeding, she should contact her doctor.
Before taking any medicine, consult your doctor or pharmacist.

Driving and operating machinery
There is no information suggesting that Lesiplus affects the ability to drive or operate machinery.

Lesiplus contains lactose
If the patient has been diagnosed with intolerance to certain sugars, she should consult her doctor before taking this medicine.

Lesiplus contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. the medicine is considered "sodium-free".

3. How to use Lesiplus

This medicine should always be used according to the instructions given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
Each blister contains 24 pink coated tablets and 4 white coated tablets – placebo.
Lesiplus tablets in two different colours are arranged in a specific order within the blister.
One blister contains 28 coated tablets.
Take one Lesiplus tablet every day, with or without a small amount of water.
Page 9 of 17
The tablets may be taken with or without food, but they should be taken daily at approximately the same time.
Do not confuse the tablets: take the pink tablets for the first 24 days, followed by the white tablets for the last 4 days. A new blister should be started immediately (24 pink tablets, then 4 white tablets). Therefore, there is no break between two blisters.
Due to differences in tablet composition, it is essential to start from the first tablet in the upper left corner of the blister and continue taking one tablet each day. To maintain the correct order, proceed in the direction of the arrows printed on the blister.

Preparing the blister
To help remember how to take the contraceptive, each Lesiplus blister is supplied with 7 self-adhesive labels printed with the days of the week. Select the appropriate label corresponding to the day of the week on which you started taking the tablets. For example, if the first day of treatment was Wednesday, choose the label where the first day of the week is “Wed”.
Apply the label along the top edge of the blister where it says “start Plaats het etiket hier”.
This way, each tablet will be marked with the corresponding day of the week, allowing you to check whether a tablet has been taken. The arrows indicate the order of tablet intake.

During the 4 days when the white placebo tablets are taken (placebo days), withdrawal bleeding should occur (so-called withdrawal bleed). This bleeding usually starts on the 2nd or 3rd day after taking the last active pink tablet of Lesiplus. After taking the last white placebo tablet, start the next blister immediately, regardless of whether bleeding is still ongoing. This means that each new blister will begin on the same day of the week, and bleeding should occur approximately on the same days each month.
If the patient uses Lesiplus as directed, protection against pregnancy is maintained even during the 4 days when taking placebo tablets.

When to start the first blister

• If no hormonal contraceptive has been used in the previous month
  Start taking Lesiplus on the first day of the menstrual cycle (i.e. the first day of menstruation). If the patient starts taking Lesiplus on the first day of menstruation, immediate protection against pregnancy is provided. Alternatively, treatment may be started between days 2 and 5 of the cycle, but in this case, an additional contraceptive method (e.g. a condom) must be used for the first 7 days.

• Switching from a combined hormonal contraceptive or a combined vaginal contraceptive system or a transdermal contraceptive system
  Start taking Lesiplus the day after taking the last active tablet (last tablet containing active ingredients) of the previous pack, but no later than the day after the tablet-free interval of the previous contraceptive ends (or after the last inactive tablet of the previous contraceptive). When switching from a combined vaginal contraceptive system or a transdermal contraceptive system, follow your doctor’s advice.

• Switching from a progestogen-only method (progestogen-only mini-pill, injection, implant, or intrauterine system releasing progestogen)
  Switch can occur on any day from the progestogen-only pill (on the day of removal for an implant or intrauterine system, or on the scheduled date of the next injection for injectable forms), but in all these cases, an additional contraceptive method (e.g. a condom) must be used for the first 7 days of tablet intake.

• After miscarriage
  Follow your doctor’s instructions.

• After childbirth
  Lesiplus may be started between day 21 and day 28 after delivery. If treatment is started later than day 28, a barrier method (e.g. a condom) must be used for the first 7 days of taking Lesiplus. If sexual intercourse has occurred after childbirth, before (re)starting Lesiplus, the patient should first confirm she is not pregnant or wait until the next menstrual bleeding occurs.

• If the patient is breastfeeding and wishes to (re)start taking Lesiplus after childbirth
  Refer to the section “Breastfeeding”.

If the patient is unsure when to start taking the medicine, she should consult her doctor.

Taking more Lesiplus than recommended
There are no reports of serious harmful effects from taking too many Lesiplus tablets.
If several tablets are taken at once, nausea, vomiting, or vaginal bleeding may occur. Such bleeding may even occur in girls who have not yet started menstruating but have accidentally taken this medicine.
In case of overdose or accidental ingestion by a child, consult a doctor or pharmacist immediately.

Missed dose of Lesiplus
The last four tablets in the fourth row of the blister are placebo tablets. If a patient misses one of these, contraceptive efficacy of Lesiplus is maintained. Discard the missed placebo tablet.

If a pink active tablet (tablets 1–24 of the blister) is missed, follow the instructions below:

• If less than 24 hours have passed since the missed tablet, protection against pregnancy is not reduced. Take the missed tablet as soon as possible, then continue taking the next tablets at the usual time.
• If more than 24 hours have passed since the missed tablet, protection against pregnancy may be reduced. The greater the number of missed tablets, the higher the risk of pregnancy.

The risk of inadequate protection is greatest if a pink tablet is missed at the beginning or end of the blister. Therefore, follow the rules below (see also the chart below):

• Missing more than one tablet in a blister
  Contact your doctor.

• Missing one tablet between days 1–7 (first row)
  Take the missed tablet as soon as possible, even if this means taking two tablets at the same time. Continue taking the following tablets at the usual time and use additional contraception (e.g. a condom) for the next 7 days. If sexual intercourse occurred in the week before the missed tablet, there is a risk of pregnancy. In this case, contact your doctor.

• Missing one tablet between days 8–14 (second row)
  Page 11 of 17
  Take the missed tablet as soon as possible, even if this means taking two tablets at once. Continue taking the following tablets at the usual time.
  Protection against pregnancy is not reduced and no additional contraception is needed.

• Missing one tablet between days 15–24 (third and fourth rows)
  Two options are available:

1. Take the missed tablet as soon as possible, even if this means taking two tablets at once. Continue taking the remaining tablets at the usual time. Instead of taking the white placebo tablets from this blister, discard them and immediately start taking tablets from the next blister (the starting day will be different).
   Bleeding will most likely occur at the end of the second blister, during the placebo tablet days, but spotting or breakthrough bleeding may also occur during the second blister.

2. Alternatively, stop taking the active pink tablets and proceed directly to the 4 white placebo tablets ( before starting the placebo tablets, note the day on which the tablet was missed ). If the patient wishes to start the new blister on her usual starting day, take the placebo tablets for a period shorter than 4 days.

If either of these two options is followed, protection against pregnancy will be maintained.

• If a patient has missed any tablet from the blister and no bleeding occurs during the placebo tablet period, this may indicate that the patient is pregnant. In this case, contact a doctor before starting the next blister.

Page 12 of 17
What to do if vomiting or severe diarrhoea occurs
If vomiting occurs within 3 to 4 hours after taking a pink active tablet or if severe diarrhoea occurs, there is a risk that the active ingredients have not been fully absorbed. This situation has similar consequences to missing a tablet. After vomiting or diarrhoea, take another pink tablet from a spare pack as soon as possible. If possible, take it within 24 hours of the usual tablet-taking time. If this is not possible or more than 24 hours have passed, follow the advice given in the section “Missed dose of Lesiplus”.

Page 13 of 17
Delaying the onset of bleeding: what you should know
Although not routinely recommended, it is possible to delay the onset of bleeding by skipping the white placebo tablets in the 4th row and immediately starting a new Lesiplus blister until it is finished. Spotting or breakthrough bleeding may occur during the second blister. Complete the second blister by taking the 4 white placebo tablets from the 4th row. Then start the next blister.
You may wish to consult your doctor for advice before deciding to delay bleeding.

Changing the first day of bleeding: what you should know
If the patient takes the tablets as instructed, bleeding will start during the placebo tablet week. If a change in this day is desired, it can be achieved by shortening the placebo tablet period (when the white placebo tablets are taken) – but never by extending it – by up to 4 days.
For example, if the placebo tablet period starts on Friday and the patient wishes to change it to Tuesday (3 days earlier), start the new blister 3 days earlier than usual. Bleeding may not occur during these days. As a result, spotting or breakthrough bleeding may occur.
If the patient is unsure how to proceed, she should contact her doctor.

Stopping use of Lesiplus
Lesiplus may be discontinued at any time. If the patient does not wish to become pregnant, she should consult her doctor about other effective methods of birth control. If the patient wishes to become pregnant, stop taking Lesiplus and wait for a menstrual period before trying to conceive. This makes it easier to calculate the expected date of delivery.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any adverse reactions occur, especially severe and persistent ones, or changes in health status that the patient considers related to the use of Lesiplus, medical advice should be sought.
All women using combined hormonal contraceptives have an increased risk of developing blood clots in the veins (venous thromboembolic disorders) or blood clots in the arteries (arterial thromboembolic disorders). For detailed information on various risk factors associated with the use of combined hormonal contraceptives, refer to section 2, "Important information before using Lesiplus".

Serious adverse reactions
Seek immediate medical attention if the patient experiences any of the following symptoms of angioedema: swelling of the face, tongue and/or throat and/or difficulty swallowing, or hives, which may cause difficulty breathing (see also section "Warnings and precautions").

The following adverse reactions have been associated with the use of Lesiplus.

• Common adverse reactions (may occur in up to 1 in 10 people):

  • Mood changes;
  • Headaches;
  • Nausea;
  • Breast tenderness, menstrual disorders such as irregular menstruation, absence of menstruation.

• Uncommon adverse reactions (may occur in up to 1 in 100 people):

  • Depression, nervousness, drowsiness;
  • Dizziness, "tingling and numbness" sensations;
  • Migraine, varicose veins, high blood pressure;
  • Abdominal pain, vomiting, indigestion, intestinal gas, gastritis, diarrhoea;
  • Acne, itching, rash;
  • Pain, for example back pain, limb pain, painful muscle cramps;
  • Vaginal candidiasis, pelvic pain, breast enlargement, benign breast lumps, uterine and/or vaginal bleeding (which usually resolves during treatment), vaginal discharge, hot flushes, vaginal inflammation (vaginitis), menstrual disorders, painful menstruation, scanty menstruation, very heavy menstruation, vaginal dryness, abnormal Pap smear results according to Papanicolaou classification, decreased libido.

• Rare adverse reactions (may occur in up to 1 in 1000 people):

  • Candidiasis (fungal infection);
  • Anaemia, increased platelet count;
  • Allergic reactions;
  • Endocrine disorders (hormonal disorders);
  • Increased appetite, loss of appetite, abnormally high potassium levels in blood, abnormally low sodium levels in blood;
  • Inability to achieve orgasm, insomnia;
  • Dizziness, tremor;
  • Eye disorders, for example blepharitis, dry eye syndrome;
  • Abnormally rapid heart rhythm;
  • Phlebitis, nosebleeds, fainting;
  • Abdominal distension, intestinal disease, feeling of fullness, abdominal hernia, oral candidiasis, constipation, dry mouth;
  • Biliary or gallbladder pain, cholecystitis;
  • Yellowish-brown skin patches, eczema, abnormal hair growth (hirsutism), acneiform dermatitis, dry skin, nodular skin inflammation, excessive hair loss (alopecia), skin disorders, striae, dermatitis, photosensitive dermatitis, skin nodules;
  • Painful and difficult sexual intercourse, vulvovaginitis (inflammation of the vulva and vagina), intermenstrual bleeding, withdrawal bleeding, breast cysts, increased number of nipple cells (hyperplasia), malignant breast tumours, abnormal growth of the cervical mucosa, constriction or thinning of the endometrium, ovarian cysts, uterine enlargement;
  • General malaise;
  • Weight loss;
  • Harmful blood clots in veins or arteries, for example:
    • In the leg or foot (e.g. deep vein thrombosis);
    • In the lungs (e.g. pulmonary embolism);
    • Heart attack;
    • Stroke;
    • Mini-stroke or transient ischaemic attack (TIA);
    • Blood clots in the liver, stomach and intestine, kidneys or eye.

The likelihood of developing blood clots may be higher if the patient has any other risk factors that increase this risk (see section 2 for further information on risk factors and symptoms associated with blood clots).

The following adverse reactions have been reported, but their frequency cannot be estimated from the available data: hypersensitivity, erythema multiforme (a rash with red, painful rings).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Lesiplus

Keep this medicine out of sight and reach of children.
Do not use Lesiplus after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
No special storage instructions apply.
Medicines must 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 Lesiplus contains

• The active substances in this medicine are ethinylestradiol and drospirenone.
• Each pink coated tablet contains the following active substances: 0.02 milligrams of ethinylestradiol and 3 milligrams of drospirenone.
• The white coated tablets do not contain any active substances.
• Other ingredients are:
  Pink coated tablets containing active substances: lactose monohydrate, pregelatinized corn starch, povidone K 30, sodium croscarmellose, polysorbate 80, magnesium stearate.
  Coating: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172).
  White coated placebo tablets: lactose, povidone K 30, magnesium stearate.
  Coating: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc.

What Lesiplus looks like and contents of the pack

• Each Lesiplus blister pack contains 24 pink coated tablets with active substances in rows 1, 2, 3 and 4, and 4 white coated placebo tablets in row 4.
• Lesiplus tablets, both pink and white, are film-coated tablets; the tablet core is coated.
• Lesiplus is available in cardboard boxes containing one blister with 28 coated tablets (24 + 4).

Page 16 of 17
For further information, please contact the marketing authorisation holder or the parallel importer.
Marketing Authorisation Holder in the Netherlands, country of export:
Theramex Ireland Limited
3rd Floor, Kilmore House, Park Lane, Spencer Dock
Dublin 1, D01 YE64, Ireland
Manufacturer:
Laboratorios León Farma, S.A.
C/ La Vallina s/n, Pol Ind
Navatejera 24008-León
Spain
Parallel Importer:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Marketing Authorisation Number in the Netherlands, country of export: RVG 109940
Parallel Import Licence Number: 37/21
Page 17 of 17