Lesiplus

PACKAGE LEAFLET: INFORMATION FOR THE USER

Warning! Keep the leaflet. Information on the outer packaging 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
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 developing blood clots in veins and arteries, especially during the first year of use or after restarting following an interval of 4 weeks or more.
• Be vigilant and consult your doctor if you suspect symptoms of blood clot formation (see section 2 "Blood clots").

Please read the leaflet carefully 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 doubts, consult 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 you experience any adverse effects, including any not listed in this leaflet, inform 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" pills.

2. What you need to know before taking Lesiplus

General information
Before starting to take Lesiplus, 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").
Before you can start taking 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 several 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 monitoring. 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 take Lesiplus:
Do not take Lesiplus if you have any of the following conditions. If you have any of the following conditions, inform your doctor. Your doctor will discuss with you which alternative method of contraception may be more suitable.

• if you currently have (or have ever had) a blood clot in the veins of your legs (deep vein thrombosis), in the 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 previously had) 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 previously had) a type of migraine called "migraine with aura";
• if you currently have (or have previously had) liver disease and liver function remains abnormal;
• if you have kidney function disorders (kidney failure);
• if you currently have (or have previously had) liver tumour;
• if you currently have (or have previously 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 medicines containing ombitasvir/paritaprevir/ritonavir, dasabuvir or glecaprevir/pibrentasvir (see also section "Lesiplus with other medicines").

Additional information for special populations
Children and adolescents
Lesiplus is not intended for use in girls whose menstrual cycles have not yet started.
Elderly women
Lesiplus is not intended for use after menopause.
Women with impaired liver function
Do not take Lesiplus if you have liver disease. See also sections "When not to take Lesiplus" and "Warnings and precautions".
Women with impaired kidney function
Do not take Lesiplus if you have kidney failure or acute kidney failure. See also sections "When not to take 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 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 check-ups by your doctor may be necessary.
Inform 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 there is currently or has previously been 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 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 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 long time (see section 2 "Blood clots (thrombosis)");
• if you are immediately postpartum, as you are at increased risk of blood clots. Consult your doctor for advice on how soon you can start taking Lesiplus after childbirth;
• if you have superficial thrombophlebitis (inflammation of veins under the skin);
• if you have varicose veins;
• if you have epilepsy (see "Lesiplus with other medicines");
• if you have a condition that first appeared during pregnancy or previous use of sex hormones, for example, 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 previously had golden-brown skin discoloration (chloasma), also known as melasma, mainly on the face. If so, you should avoid direct exposure to sunlight or ultraviolet radiation;
• if you have hereditary angioedema, medicines containing estrogens may trigger or worsen symptoms. You should seek immediate medical advice if symptoms of angioedema occur, such as swelling of the face, tongue and (or) throat, and (or) difficulty swallowing or hives with breathing difficulties.

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 treatment.
In rare cases, a blood clot may 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 from 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 taking Lesiplus is low.

How to recognize 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 a vein?

• The use of combined hormonal contraceptives is associated with an increased risk of blood clots in veins (venous thromboembolism). 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 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 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 product) after a break of 4 weeks or more.
After the first year, the risk decreases, although it remains higher compared to not using combined hormonal contraceptives at all.
If a woman stops taking Lesiplus, the risk of blood clots returns to normal within a few weeks.

What factors influence the risk of blood clots in veins?
The risk depends on a woman’s natural risk of venous thromboembolic disease and the type of combined hormonal contraceptive used.
The overall risk of developing blood clots in the legs or lungs with the use of 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 blood clots in veins
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 needs to undergo 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 the use of Lesiplus for several weeks before surgery or immobilization. If the patient must stop taking 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 present.
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, e.g. 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?
Similar to 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 (over approximately 35 years);
• if the patient smokes. While 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 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 relative has had a heart attack or stroke at a young age (under
  50 years of age). 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 suffers from migraines, especially migraines with aura;
• if the patient has heart disease (valve disorder, 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 is
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, e.g. 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 hormonal contraceptives, breast cancer is observed slightly more frequently, but
it is not known whether this is caused by the medication. For example, it may be that more
tumors 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 breasts regularly and contact the doctor if the patient detects
any lump.
Benign liver tumors have been reported, rarely, in women using combined hormonal contraceptives, and malignant liver tumors have been reported even more rarely. 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 the expected bleeding does not occur twice in succession, this may indicate pregnancy. The patient should contact her doctor immediately. Do not start the next pack until
it is confirmed that the patient is not pregnant.
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, has recently taken, or 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 dosing of other medicines should be adjusted.
Do not administer Lesiplus to patients with hepatitis C virus infection who are taking medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir or
glecaprevir/pibrentasvir, as this may lead to increased liver 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 completing this treatment.
See section "When not to use Lesiplus".
Some medicines may affect the blood concentration of Lesiplus and may cause Lesiplus to be less effective in preventing pregnancy or may cause unexpected bleeding.
This applies to medicines used in the treatment of:
o epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine)
o tuberculosis (e.g. rifampicin)
o HIV and hepatitis C virus infection (protease inhibitors and
non-nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine,
efavirenz)
o fungal infections (griseofulvin, ketoconazole)
o arthritis, osteoarthritis (etoricoxib)
o pulmonary hypertension (bosentan)
o and herbal medicines containing St John's wort ( Hypericum perforatum )

• Lesiplus may affect the action of other medicines, for example:
  o medicines containing cyclosporine
  o antiepileptic medicines
  o theophylline (used for breathing problems)
  o tizanidine (used to treat muscle pain and/or muscle spasms)
  o medicines containing lamotrigine (may lead to increased frequency of epileptic seizures).

Consult a doctor or pharmacist before taking any medicine.
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 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 discontinue Lesiplus at any time (see also "Discontinuation of Lesiplus").
Before taking any medicine, consult your doctor or pharmacist.
Breast-feeding
Lesiplus is generally not recommended during breast-feeding. If the patient wishes to use a contraceptive during breast-feeding, she should contact her doctor.
Before taking any medicine, consult your doctor or pharmacist.
Driving and using machines
There is no information suggesting that Lesiplus affects the ability to drive or operate machinery.
Lesiplus contains monohydrate lactose
If the patient has been diagnosed with an intolerance to certain sugars, she should contact her doctor before taking this medicine.
Medicinal product Lesiplus contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, meaning the medicine is considered "sodium-free".

3. How to use Lesiplus

This medicine should always be taken as directed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
Each blister pack contains 24 pink tablets and 4 white placebo tablets.
The Lesiplus tablets in two different colours are arranged in a specific order within the blister.
One blister contains 28 tablets.
Take one Lesiplus tablet every day, with or without a small amount of water. 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
placebo tablets for the last 4 days. A new blister pack should be started immediately (24 pink
tablets followed by 4 white tablets). Therefore, there is no break between two blister packs.
Due to differences in tablet composition, treatment must begin with the first tablet in the top left
corner of the blister and continued daily in the correct order. To maintain the proper sequence,
follow the direction of the arrows printed on the blister.
Preparing the blister pack
To help remember how to take the contraceptive, each Lesiplus blister pack includes 7 self-adhesive
labels printed with the days of the week. Select the appropriate label according to the day of the week
on which tablet intake begins. For example, if the first day of treatment was Wednesday, select the label
starting with "Wed".
Attach the label along the top edge of the blister where it says "Plaats het etiket hier" (meaning
"Place the label here"), so that the first day of the week is positioned above the tablet marked "1".
This way, each tablet will have the corresponding day of the week above it, allowing you to verify
whether a tablet has been taken. The arrows indicate the order in which the tablets should be taken.
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 pack immediately, regardless of whether bleeding is still occurring. This means that each new
blister pack will begin on the same day of the week, and withdrawal bleeding will typically occur
around the same days each month.
If the patient takes Lesiplus exactly as described above, she is protected against pregnancy also
during the 4 days when taking the placebo tablets.
When to start the first blister pack

• 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 her period, she is immediately protected against pregnancy. Alternatively, treatment may begin on days 2 to 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 ring or transdermal patch Lesiplus may be started the day after taking the last active tablet (last tablet containing active ingredients) from 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 contraceptive vaginal ring or transdermal patch, follow your doctor's advice.

• Switching from a progestogen-only method (progestogen-only mini-pill, injection, implant, or intrauterine system releasing progestogen) Switching can occur on any day from progestogen-only mini-pills (on the day of removal for an implant or intrauterine system, or on the scheduled date of the next injection for injectable contraceptives), 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 giving birth, Lesiplus may be started between day 21 and 28 postpartum. If the patient starts taking the medicine later than day 28, a barrier method (e.g. condoms) must 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 occurs.

• If the patient is breastfeeding and wishes to (re)start taking Lesiplus after childbirth Please read section "Breastfeeding".

If the patient is unsure when to start taking the medicine, she should consult her doctor.
Taking more Lesiplus than recommended
There have been 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.
If too many Lesiplus tablets are taken or if a child swallows any tablets, 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 the patient misses one of these, the contraceptive efficacy of Lesiplus remains unchanged. The missed placebo tablet should be discarded.
If a pink active tablet (tablets 1–24 in 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 following 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 greater 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 pack. Therefore, follow the rules below (see also the chart below):
• Missing more than one tablet in a blister pack 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 remaining tablets at the usual time and use additional contraception (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 the same time. Continue taking the remaining 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 the same time. Continue taking the remaining tablets at the usual time. Instead of taking the white placebo tablets from this blister pack, discard them and immediately start taking tablets from the next blister pack (the starting day will be different).

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

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

yes
Did unprotected sexual intercourse occur in the week

1. – 7. preceding the missed tablet?

no

• Take the missed tablet as soon as possible
• Use a barrier method (condoms) for the next 7 days, and
• Continue taking tablets from the current blister pack
  Missed only one pink tablet (taken more than 24 hours late)
• Take the missed tablet
• Continue taking tablets from the blister pack
• Take the missed tablet and
• Finish taking the remaining pink tablets
• Discard the 4 white placebo tablets
• Start taking tablets from the next blister pack immediately
  Day 15. – 24. or
• Immediately stop taking the pink active tablets
• Proceed directly to the 4 white placebo tablets
• Start taking tablets from the next blister pack

What to do if vomiting or severe diarrhoea occurs
If vomiting occurs within 3 to 4 hours after taking the pink active tablet, or if severe diarrhoea occurs, there is a risk that the active substances have not been completely absorbed by the body. This situation is similar in effect to missing a tablet. After vomiting or diarrhoea, take another pink active tablet from a spare pack as soon as possible. If possible, take it within 24 hours of your usual tablet-taking time. If this is not possible or more than 24 hours have passed, follow the instructions under the section "Missed dose of Lesiplus".

Delayed withdrawal bleeding: what you should know
Although not generally recommended, it is possible to delay withdrawal bleeding by skipping the 4 white placebo tablets in the 4th row and moving directly to a new blister pack of Lesiplus, continuing until it is finished. Breakthrough bleeding or spotting may occur during the intake of tablets from the second blister pack. Finish the second blister pack by taking the 4 white placebo tablets from the 4th row. Then start taking tablets from the next blister pack.
You may 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 directed, bleeding will usually start during the week of placebo tablets. If you wish to change this day, you may do so by shortening the placebo tablet period (when taking the white placebo tablets), but never by extending it—by up to 4 days maximum. For example, if the placebo tablet period normally starts on Friday, and the patient wishes to change the bleeding day to Tuesday (3 days earlier), the new blister pack should be started 3 days earlier than usual.
Bleeding may not occur during these days. Breakthrough spotting or intermenstrual bleeding may occur as a result.
If the patient is unsure about what to do, she should consult her doctor.

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

If you have any further doubts regarding the use of this medicine, please 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, particularly severe and persistent ones, or any changes in health that the patient considers to be related to the use of Lesiplus, medical advice should be sought from a doctor.

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 the various risk factors associated with the use of combined hormonal contraceptives, please refer to section 2, "Important information before using Lesiplus".

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
  • 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, sensations of tingling and numbness
  • Migraine, varicose veins, high blood pressure
  • Abdominal pain, vomiting, dyspepsia, flatulence, gastritis, diarrhoea
  • Acne, itching, rash
  • Pain, for example back pain, limb pain, 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
  • Hormonal (endocrine) disorders
  • Increased appetite, loss of appetite, abnormally high blood potassium levels, abnormally low blood sodium levels
  • Inability to achieve orgasm, insomnia
  • Dizziness, tremor
  • Eye disorders, for example blepharitis, dry eye syndrome
  • Abnormally rapid heart rate
  • Phlebitis, nosebleeds, fainting
  • Abdominal distension, intestinal disease, feeling of fullness, abdominal hernia, oral candidiasis, constipation, dry mouth
  • Biliary tract or gallbladder pain, cholecystitis
  • Yellow-brown skin patches, eczema, abnormal hair growth (hirsutism), acneiform dermatitis, dry skin, nodular skin inflammation, excessive hair loss (alopecia), skin disorders, striae, dermatitis, photosensitivity, skin nodules
  • Dyspareunia (painful intercourse), vulvovaginitis (inflammation of the vulva and vagina), intermenstrual bleeding, withdrawal bleeding, breast cysts, increased number of breast cells (hyperplasia), malignant breast tumours, abnormal cervical mucosal growth, uterine mucosal spasm or thinning, 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 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 any adverse reactions not listed in this leaflet, inform a doctor or pharmacist. 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 the medicine Lesiplus

Keep this medicine out of the sight and reach of children.
Do not use Lesiplus after the expiry date stated on the outer carton and blister pack following the terms "Expiry date" or "EXP:". The expiry date refers to the last day of the stated month.
No special storage conditions are required.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures 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: monohydrate lactose, maize starch gelatinised, povidone K30, 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 K30, 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 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 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
Pharmachemie B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands
Teva Czech Industries s.r.o.
Ostravska 29, c.p. 305
74770 Opava-Komarov
Czech Republic
Teva Operations Poland Sp. z o.o
ul. Mogilska 80
31-546 Kraków
Poland
TEVA PHARMA S.L.U.
C/C, n. 4, Poligono Industrial
Malpica
50016 Zaragoza
Spain
Merckle GmbH
Ludwig-Merckle-Straße 3
89143 Blaubeuren
Germany
Teva Pharma B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands
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
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warszawa
Pharma Innovations Sp. z o.o.
ul. Jagiellońska 76
03-301 Warszawa
SHIRAZ PRODUCTIONS Sp. z o.o.
ul. Tymiankowa 24/28
95-054 Ksawerów
CANPOLAND SPÓŁKA AKCYJNA
ul. Beskidzka 190
91-610 Łódź
Dutch marketing authorisation number, country of export: RVG 109940
Parallel import authorisation number: 293/22