Lesiplus

PACKAGE LEAFLET: INFORMATION FOR THE USER

Warning! Keep the leaflet; the information on the immediate packaging is in a foreign language!
Lesiplus (Drospirenone/Ethinylestradiol 3/0.02 mg 24+4 Theramex)
3 mg + 0.02 mg, coated tablets
Drospirenonum + Ethinylestradiolum
Lesiplus and Drospirenone/Ethinylestradiol 3/0.02 mg 24+4 Theramex are different trade names for 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 use following a break of 4 weeks or more
• Be vigilant and consult a doctor if a woman suspects symptoms of blood clot formation (see section 2 "Blood clots")

Please read this leaflet carefully before taking the medicine, as it contains important information for the patient

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. The medicine may harm someone else.
• If any side effects occur in the patient, including any side effects not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents
1. What Lesiplus is and what it is used for
2. What you need to know 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 tablets contains a small amount of two different female hormones, namely drospirenone and ethinylestradiol.
• The 4 white tablets, which do not contain active substances, are also known as placebo tablets.
• Contraceptive tablets containing two hormones are called "combined" tablets.

2. What you need to know before taking Lesiplus

General considerations
Before starting Lesiplus, you should read the information about blood clots (thrombosis) in section 2. It is especially important to be aware of the symptoms of blood clots (see section 2 "Blood clots").
Before starting Lesiplus, your doctor will ask several questions about your health and that of your close relatives. Your doctor will also measure your blood pressure and, depending on your individual case, may perform other tests.
This leaflet describes situations in which you should stop taking Lesiplus or in which the effectiveness of Lesiplus may be reduced. In such cases, 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 methods. These methods may be unreliable because Lesiplus alters the monthly changes in body temperature and cervical mucus.
Lesiplus, like other hormonal contraceptives, does not protect against HIV (AIDS) infection or other sexually transmitted diseases.

When not to use Lesiplus:
Do not take Lesiplus if any of the following apply to you. If any of the following conditions apply to you, inform your doctor. Your doctor will discuss with you which alternative contraceptive method would be more suitable.

• if you currently have (or have ever had) a blood clot in the veins of your legs (deep vein thrombosis), in your lungs (pulmonary embolism), or in other organs;
• if you know you have blood clotting disorders — for example, protein C deficiency, protein S deficiency, antithrombin III deficiency, factor V Leiden mutation, or antiphospholipid antibodies;
• if you are undergoing surgery or will be immobile for a long time (see section "Blood clots");
• 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:
  o severe diabetes with blood vessel damage;
  o very high blood pressure;
  o very high levels of fats in the blood (cholesterol or triglycerides);
  o 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 dysfunction (kidney failure);
• if you currently have (or have ever had) a 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 virus and are taking medicines containing ombitasvir/paritaprevir/ritonavir, dasabuvir, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir (see also section "Lesiplus and other medicines").

Additional information for special populations

Children and adolescents
Lesiplus is not intended for use in girls who have not yet started menstruating.
Older women
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?
Seek immediate medical advice if:

• you notice possible symptoms of blood clots, which may indicate 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 side 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.
Tell your doctor if you have any of the following conditions.
If any of these conditions develop or worsen during treatment with Lesiplus, inform your doctor.

• if breast cancer is currently present or has occurred in the past 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 body's natural defence system);
• if you have haemolytic uraemic syndrome (a blood clotting disorder causing kidney failure);
• if you have sickle cell anaemia (an inherited disorder of red blood cells);
• if you have been diagnosed with high levels of fats in the blood (hypertriglyceridaemia) or have a positive family history of this condition. Hypertriglyceridaemia is associated with an increased risk of developing pancreatitis;
• if you are undergoing surgery or will be immobile for a long time (see section 2 "Blood clots (thrombosis)");
• if you have recently given birth, as you are at increased risk of blood clots. Consult your doctor for advice on how soon after delivery you can start taking Lesiplus;
• if you have inflammation of the veins under the skin (superficial thrombophlebitis);
• if you have varicose veins;
• if you have epilepsy (see "Lesiplus and 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 nervous system disorder with involuntary body movements (Sydenham's chorea));
• if you currently have or have ever had in the past brownish skin discoloration (chloasma), commonly 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, which may cause breathing difficulties, seek immediate medical attention. Medicines containing estrogens may cause or worsen symptoms of both hereditary and acquired angioedema.

Discuss this with your doctor or pharmacist before starting Lesiplus.

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 disorders");
• in arteries (referred to as "arterial thrombosis" or "arterial thromboembolic disorders").

Full recovery after a blood clot is not always possible. 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 caused by taking Lesiplus is small.
How to recognize the occurrence of blood clots
Seek immediate medical advice if you notice any of the following symptoms.

Blood clots in veins
What can happen if blood clots form in veins?

• 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 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 first-time use of combined hormonal contraceptives. 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 being 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 depends on the individual medical history of the woman (see "Factors that increase the risk of 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 family member 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 such a 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 a cast. It may be necessary to discontinue Lesiplus several weeks before surgery or reduced mobility. If the patient needs to stop taking Lesiplus, she should consult her doctor about when she can resume taking the medicine;
• with increasing age (particularly over 35 years);
• if the patient has recently given birth (within the past few weeks)

The risk of venous 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,
especially if the patient has another risk factor listed above.
It is important to inform the doctor if any of these risk factors apply to the patient,
even if uncertain. The doctor may decide to discontinue the use of Lesiplus.
The patient should inform her doctor if any of the above conditions change during treatment with Lesiplus, for example, if a close family member 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 lead to 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 (above approximately 35 years);
• if the patient smokes. When using a hormonal contraceptive such as Lesiplus, smoking should be discontinued. If the patient is unable to stop smoking and is over 35 years of age, the doctor may recommend using another type of contraception;
• if the patient is overweight;
• if the patient has high blood pressure;
• if a close family member 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 family member has high levels of fats in the blood (cholesterol or triglycerides);
• if the patient suffers from migraines, particularly migraines with aura;
• if the patient has heart disease (valve damage, heart rhythm disorder known as 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.
The patient should inform her doctor if any of the above conditions change during treatment with Lesiplus, for example, if she starts smoking, a close family member is diagnosed with unexplained thrombosis, or if she gains significant weight.

Lesiplus and cancer
In women using combined hormonal contraceptives, breast cancer is observed slightly more frequently, but it is not known whether this is caused by the use of the medicine. For example, it may be that more tumours are 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 the breasts regularly and to contact the doctor if any lump is detected.
In rare cases, benign liver tumours and, even more rarely, malignant liver tumours have been reported in women using combined hormonal contraceptives. If the patient experiences unusual, severe abdominal pain, she should contact her doctor.

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

What to do if no bleeding occurs during the placebo tablet period
If all the pink active tablets have been taken correctly, without vomiting, severe diarrhoea, or concomitant use of other medicines, it is very unlikely that the patient is pregnant.
If the expected withdrawal bleeding does not occur twice in succession, this may indicate pregnancy. The patient should contact her doctor immediately. She should 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, in some cases, may lead to suicidal thoughts.
If mood changes or symptoms of depression occur, the patient should contact her 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 she plans to take. The patient should also inform any other doctor or dentist prescribing another medicine (or a pharmacist) that she is using Lesiplus. They may advise whether additional contraceptive methods (e.g. condoms) are needed, for how long, or whether other medicines need to be adjusted.
Lesiplus must not be given 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 lead to increased liver function test results (increased blood liver enzyme AlAT activity).
The doctor will prescribe another type of contraception before starting treatment with these medicines.
Lesiplus may be restarted approximately 2 weeks after completing this treatment. See section "When not to use Lesiplus".
Some medicines may affect the blood levels of Lesiplus and may make Lesiplus less effective in preventing pregnancy or may cause unexpected bleeding. These include medicines used to treat:
• epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine)
• tuberculosis (e.g. rifampicin)
• HIV and hepatitis C virus infection (protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine, efavirenz)
• fungal infections (griseofulvin, ketoconazole)
• arthritis, osteoarthritis (etoricoxib)
• pulmonary hypertension (bosentan)
• and herbal products containing St John's wort (Hypericum perforatum)

• Lesiplus may affect the action of other medicines, for example:
  • cyclosporine-containing medicines
  • antiepileptic medicines
  • theophylline (used for breathing problems)
  • tizanidine (used to treat muscle pain and/or muscle spasms)
  • lamotrigine-containing medicines (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 blood tests are required, inform the doctor or laboratory staff that the patient is using hormonal contraceptives, as the hormones may affect the results of certain tests.

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 to become pregnant, 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 consult 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 an intolerance to certain sugars, she should consult her doctor before taking this medicine.

Lesiplus medicinal product 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 taken exactly as directed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
Each blister contains 24 pink coated tablets and 4 white placebo tablets.
Lesiplus tablets in two different colours are arranged in a specific order within the blister.
One blister contains 28 tablets.
Take one Lesiplus tablet daily, with or without water.
You may take the tablets 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 placebo tablets
for the last 4 days. Start a new blister immediately (24 pink, 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 top left corner of the
blister and continue taking tablets each day. To maintain the correct order, move in the direction of the arrows
on the blister.

Preparing the blister
To help remember how to take the contraceptive, each Lesiplus blister includes 7 self-adhesive strips printed
with the days of the week. Choose the appropriate strip according to the day of the week on which tablet
intake began.
For example, if the first day of intake was Wednesday, select the strip where the first day is marked “Wed”.
Apply the label along the top edge of the blister where it says "Place strip here", so that the first day is above
the tablet marked "1". This way, each tablet will have the corresponding day of the week above it, helping
you check whether a tablet has been taken. Arrows indicate the order of tablet intake.

During the 4 days when white placebo tablets are taken (placebo days), withdrawal bleeding (so-called
"withdrawal bleeding") should occur. This bleeding usually starts on the 2nd or 3rd day after taking the last
active pink tablet of Lesiplus. After taking the last white tablet, start the next blister immediately, regardless
of whether bleeding continues. 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 takes Lesiplus as described above, protection against pregnancy is maintained even during
the 4 days when placebo tablets are taken.

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 cycle (i.e. the first day of menstruation). If the patient starts taking Lesiplus on the first day of her period, immediate protection against pregnancy is provided. Alternatively, treatment may be started between days 2–5 of the cycle, but in this case, additional contraceptive methods (e.g. condoms) must be used for the first 7 days.
• Switching from a combined hormonal contraceptive or a combined contraceptive vaginal system or transdermal system Lesiplus may be started the day after taking the last active tablet (the last tablet containing active substances) from the previous pack, but no later than the day after completing the tablet-free interval of the previous contraceptive (or after the last inactive tablet of the previous contraceptive). When switching from a combined contraceptive vaginal system or transdermal system, follow your doctor’s advice.
• Switching from a progestogen-only method (progestogen-only mini-pill, injection, implant, or intrauterine system releasing progestogen) You may switch on any day from progestogen-only mini-pills (from an implant or intrauterine system on the day of removal, or from injections on the day of the next scheduled injection), but in all these cases, additional contraceptive methods (e.g. condoms) must be used

for the first 7 days of tablet intake.

• After miscarriage Follow your doctor’s advice.
• After childbirth After delivery, you may start taking Lesiplus between day 21 and 28 postpartum. If the patient starts taking the medicine later than on day 28, a barrier method (e.g. condoms) should be used for the first seven 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.
• If the patient is breastfeeding and wishes to (re)start taking Lesiplus after childbirth Read section “Breast-feeding”.

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

Taking more than the recommended dose of Lesiplus
There are no reports of serious harmful effects from taking too many Lesiplus tablets.
If several tablets are taken at once, nausea and vomiting or vaginal bleeding may occur.
Such bleeding may even occur in girls who have not yet started menstruating but have accidentally taken the medicine.
If too many Lesiplus tablets are taken or if a child swallows them, consult a doctor or pharmacist.

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

If a pink tablet containing active substances (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 more tablets missed, the higher the risk of pregnancy. The risk of incomplete 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 once. Continue taking the remaining tablets at the usual time and use additional protection (e.g. condoms) 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)

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. Protection against pregnancy is not reduced and additional protection is not required.

• Missing one tablet between days 15–24 (third and fourth rows)

There are two options:

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 start taking tablets from the next blister (the starting day will be different).

Bleeding will most likely occur at the end of taking tablets from the second blister, during the placebo tablets, but breakthrough bleeding or spotting may also occur during the intake of the second blister.

2. Alternatively, stop taking the active pink tablets and go 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 the patient missed any tablet from the blister and no bleeding occurred during the placebo tablet period, this may indicate that the patient is pregnant. In this case, contact your doctor before starting the next blister.

Missed more than 1
active pink tablet from 1 blister
yes

Day
Did sexual intercourse occur in the week
1–7
preceding the missed tablet?

no

• Take the missed tablet
• Use barrier method (condoms) for the next 7 days
• Finish taking tablets from the blister
  Only 1 pink tablet missed
  Day
• Take the missed tablet
  (tablet taken more than 24 hours late)
  8–14
• Finish taking tablets from the blister
• Take the missed tablet and
• Finish taking the pink tablets
• Discard the 4 white placebo tablets
• Start taking tablets from the next blister

Day
or

15–24

• Immediately stop taking the pink tablets
• Go directly to the 4 white placebo tablets
• Start taking tablets from the next blister

What to do if vomiting or severe diarrhoea occurs
If vomiting occurs within 3 to 4 hours after taking a pink tablet containing active substances, or if severe diarrhoea occurs, there is a risk that the active substances have not been completely 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 under “Missed dose of Lesiplus”.

Delaying withdrawal bleeding: what you should know
Although not routinely recommended, withdrawal bleeding can be delayed by skipping the white placebo tablets in the fourth row and immediately starting a new Lesiplus blister until it is finished. Breakthrough bleeding or spotting may occur during intake of the second blister. Complete the second blister by taking the 4 white placebo tablets from the fourth row. Then start the next blister.
Consult your doctor for advice before deciding to delay withdrawal 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 it is necessary to change this day, it can be done by shortening the placebo tablet period (when white placebo tablets are taken)—but never by extending it—by up to 4 days maximum.
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
You may stop taking Lesiplus 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 the next menstrual period before trying to conceive. This makes it easier to calculate the expected delivery date.
If you have any further doubts about using 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 disease) or blood clots in the arteries (arterial thromboembolic disorders). For detailed information on various risk factors associated with the use of combined hormonal contraceptives, see section 2, "Important information before taking Lesiplus".

Serious adverse reactions
Seek immediate medical advice if the patient experiences any of the following symptoms of angioedema: swelling of the face, tongue and/or throat and/or difficulty swallowing, or urticaria, which may lead to breathing difficulties (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 swings
  • headache
  • nausea
  • breast pain, 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, "pins and needles" sensation, numbness
  • migraine, varicose veins, high blood pressure
  • abdominal pain, vomiting, indigestion, flatulence, gastritis, diarrhoea
  • acne, itching, rash
  • pain, for example back pain, limb pain, painful muscle cramps
  • vaginal fungal infection, 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 (Papanicolaou classification), decreased libido
  • lack of energy, increased sweating, fluid retention
  • weight gain

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

  • candidiasis (fungal infection)
  • anaemia, increased platelet count
  • allergic reactions
  • endocrine disorders (hormonal imbalances)
  • 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 fast heart rate
  • phlebitis, nosebleeds, fainting
  • abdominal distension, bowel disease, feeling of fullness, hernia, oral fungal infection, constipation, dry mouth
  • pain in the biliary tract or gallbladder, cholecystitis
  • yellow-brown skin patches, eczema, abnormal hair growth (hirsutism), acneiform dermatitis, dry skin, nodular dermatitis, excessive hair loss (alopecia), skin disorders, stretch marks, dermatitis, photosensitive dermatitis, skin nodules
  • painful and difficult sexual intercourse, vulvovaginitis (inflammation of vulva and vagina), intermenstrual bleeding, withdrawal bleeding, breast cysts, increased number of nipple cells (hyperplasia), malignant breast tumours, abnormal growth of cervical mucosa, uterine mucosa contraction or thinning, ovarian cysts, uterine enlargement
  • general malaise
  • weight loss
  • harmful blood clots in a vein or artery, 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 stroke-like symptoms, known as transient ischaemic attack
    • 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 (see section 2 for further information on factors increasing the risk of blood clots and symptoms of blood clot formation).

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 those not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, 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 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 outer carton and blister after "Expiry date" or "EXP:". The expiry date refers to the last day of the stated month.
No special storage conditions apply.
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 Lesiplus contains

• The active substances in this medicine are ethinylestradiol and drospirenone.
• Each pink coated tablet contains the 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:
• Tablet core: lactose monohydrate, pregelatinized corn starch, povidone K 30, sodium croscarmellose, polysorbate 80, magnesium stearate.
• Tablet 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:
• Tablet core: lactose, povidone K 30, magnesium stearate.
• Tablet 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 containing active substances in rows 1, 2, 3 and 4 of the blister, and 4 white placebo coated tablets in row 4.
• Lesiplus tablets, both pink and white, are coated tablets; the tablet core is coated.
• Lesiplus is available in cartons containing 1 blister with 28 tablets (24 + 4).

For more detailed 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:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Repackaged in:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Marketing Authorisation Number in the Netherlands, country of export: RVG 109940
Parallel Import Licence Number: 150/20