Orlifique

Package leaflet: Information for the patient

Orlifique, 0.10 mg + 0.02 mg, coated tablets
Levonorgestrel + Ethinylestradiol
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

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 use following a break of 4 weeks or more.
• Be vigilant and consult your doctor if you suspect symptoms of blood clot formation (see section 2. "Blood clots").

Leaflet contents

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

1. What Orlifique is and what it is used for

Orlifique is a contraceptive tablet used to prevent pregnancy.
Each pink tablet contains a small amount of two different female hormones:
levonorgestrel (a progestogen) and ethinylestradiol (an oestrogen).
The white tablets do not contain active substances and are called placebo tablets.
Contraceptive tablets containing two hormones are called "combined" pills.
Orlifique is referred to as a low-dose contraceptive pill because it contains only a small amount of hormones.

2. Important information before using Orlifique

General notes
Before starting treatment with Orlifique, you should read the information about blood clots in section 2. It is particularly important to become familiar with the symptoms of blood clots – see section 2. "Blood clots".
Before you can start using Orlifique, 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, in individual cases, may carry out additional examinations.
This patient leaflet describes several situations in which you should stop taking Orlifique or in which the effectiveness of Orlifique may be reduced.
In such situations, you should avoid sexual intercourse or use additional non-hormonal contraceptive methods, such as condoms or other mechanical methods.
During this time, you should not use the calendar method or temperature-based methods. These methods may be ineffective because Orlifique affects monthly changes in body temperature and cervical mucus.
When used correctly, the failure rate of combined oral contraceptives is approximately 1% per year.
The failure rate may increase if tablets are missed or taken incorrectly, in case of gastrointestinal disorders, or when taking other medications or herbal products.
Orlifique, like other hormonal contraceptives, does not protect against HIV infection (AIDS) or other sexually transmitted diseases.

When not to take Orlifique:
Do not take Orlifique if you have any of the conditions listed below. If any of the following conditions apply to you, inform your doctor. Your doctor will discuss with you which alternative method of contraception may be more suitable.

• if you have (or have ever had) a blood clot in the leg veins (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 require surgery or will be immobile for a prolonged period (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 (or have ever had) any of the following diseases that may increase the risk of arterial thrombosis:
  • severe diabetes with blood vessel damage;
  • very high blood pressure;
  • very high levels of fats in the blood (cholesterol or triglycerides);
  • a condition called hyperhomocysteinemia;
• if you have (or have ever had) a certain type of migraine (so-called migraine with aura);
• if you have (or have ever had) severe liver disease and liver function has not returned to normal;
• if you have (or have ever had) liver tumour;
• if you currently have (or have ever had) diagnosed or suspected breast cancer or cancer of the genital organs;
• if you have any unexplained vaginal bleeding;
• if you are pregnant or suspect you might be pregnant;
• if you are allergic to levonorgestrel or ethinylestradiol, soy, peanuts, azo dyes, or any of the other ingredients of this medicine (listed in section 6). This may cause itching, rash, or swelling.
• Do not take Orlifique if you have hepatitis C and are taking medicines containing ombitasvir/paritaprevir/ritonavir, dasabuvir, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir (see also section "Orlifique with other medicines"). If any of these conditions occur during treatment with Orlifique, stop taking the tablets immediately and consult your doctor.

Warnings and precautions
When should you contact your doctor?
Seek immediate medical advice if:

• you notice possible symptoms of blood clots, which may indicate a blood clot in the leg (deep vein thrombosis), in the lungs (pulmonary embolism), heart attack, or stroke (see section below "Blood clots"). For a description of symptoms of these serious adverse effects, see subsection "How to recognize blood clots".

Inform your doctor if any of the following conditions apply to you.
Special caution may be needed when using Orlifique or any other combined hormonal contraceptive, and regular medical check-ups may be necessary. If any of the following conditions occur or worsen during treatment with Orlifique, you should also consult your doctor:

• 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 damage);
• if you have sickle cell anaemia (an inherited disorder of red blood cells);
• if you have high blood fat levels (hypertriglyceridaemia) or a family history of this condition. Hypertriglyceridaemia is associated with an increased risk of pancreatitis;
• if you require surgery or will be immobile for a prolonged period (see section 2. "Blood clots");
• if you have recently given birth, as you are then at increased risk of blood clots. Consult your doctor for advice on how soon after delivery you can start taking Orlifique;
• if you have phlebitis (inflammation of superficial veins);
• if you have varicose veins;
• if a close relative has or has ever had breast cancer;
• if you have liver or gallbladder disease;
• if you have diabetes;
• if you have depression;
• if you have epilepsy (see "Orlifique 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 nervous system disorder causing uncontrolled body movements (Sydenham's chorea));
• if you have or have ever had chloasma (skin pigmentation, especially on the face and neck, also known as "melasma"). In such cases, avoid direct exposure to sunlight and 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, seek immediate medical attention. Medicines containing estrogens may cause or worsen symptoms of both hereditary and acquired angioedema.

BLOOD CLOTS
Using combined hormonal contraceptives such as Orlifique is associated with an increased risk of blood clots compared to not using such therapy.
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 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 caused by using Orlifique 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 veins?

• The use of combined hormonal contraceptives is associated with an increased risk of developing blood clots in veins (venous thrombosis), although these adverse effects 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 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 than when not using combined hormonal contraceptives.
If a woman stops taking Orlifique, the risk of developing blood clots returns to normal within a few weeks.

What factors influence the risk of developing blood clots in veins?
The risk depends on the individual's natural risk of venous thromboembolic disease and the type of combined hormonal contraceptive used.
The overall risk of developing blood clots in the leg or lungs with the use of Orlifique 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.
• The risk of developing blood clots depends on the individual's medical history (see "Factors increasing the risk of venous blood clots" below).

Factors increasing the risk of blood clots in veins
The risk of blood clots associated with the use of Orlifique is small, but certain factors may increase this risk. The risk is higher:

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

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

• if the patient needs to undergo surgery or will be immobilised for a prolonged period due to injury, illness or has a leg in plaster. It may be necessary to stop taking Orlifique several weeks before surgery or immobilisation. If the patient needs to stop taking Orlifique, ask the doctor when it is safe to restart the medication.

• with increasing age (especially over 35 years);

• if the patient has recently 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, especially if the patient has other risk factors 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 Orlifique.
Inform the doctor if any of the above conditions change during treatment with Orlifique, for example, if a close relative is diagnosed with unexplained thrombosis or if the patient gains significant weight.

BLOOD CLOTS IN ARTERIES
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 blood clots in arteries
It is important to note that the risk of heart attack or stroke associated with the use of Orlifique is very small, but may increase:

• with age (over approximately 35 years);
• if the patient smokes. While using a hormonal contraceptive such as Orlifique, 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 suffers from migraines, particularly migraines with aura;
• if the patient has heart disease (valve damage, 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 Orlifique, for example, if the patient starts smoking, a close relative is diagnosed with unexplained thrombosis, or if the patient gains significant weight.

Orlifique and cancer
Breast cancer has been observed slightly more frequently in women using combined hormonal contraceptives, but it is not known whether this is caused by the use of these drugs. It is possible, for example, that more tumours are detected in women using contraceptives because they visit the doctor more frequently for check-ups. The incidence of breast cancer gradually decreases after stopping combined hormonal contraceptives.
It is important that the patient regularly examines her breasts and contacts the doctor if any lumps are detected.
Benign liver tumours (non-cancerous) have rarely been observed in women using combined hormonal contraceptives, and malignant liver tumours (cancer) have been observed even more rarely. Contact the doctor immediately if the patient experiences severe abdominal pain.

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

Breakthrough bleeding
During the first few months of taking Orlifique, unexpected bleeding (outside the placebo tablet week) may occur. If bleeding persists for more than a few months or occurs after several months of regular use, the patient should consult the doctor to determine the cause.

What to do if bleeding does not occur during the placebo tablet period
If the patient has taken all the active pink tablets correctly, has not vomited or had severe diarrhoea, and has not taken any other medications, it is unlikely that she is pregnant.
If this is not the case, or if two consecutive bleedings do not occur, the patient may be pregnant. In this case, contact the doctor immediately, as pregnancy must be ruled out before continuing treatment. Before starting the next pack, ensure that the patient is not pregnant.

Orlifique and other medicines
Inform the doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines she plans to take, including herbal products available without a prescription. The patient should also inform any other doctor, including a dentist prescribing another medicine, and the pharmacist dispensing a medicine, that she is taking Orlifique. They may advise whether additional contraceptive methods (e.g. condoms) should be used, and if so, for how long.
Some medicines may affect the blood levels of Orlifique and reduce its effectiveness in preventing pregnancy, or may cause unexpected bleeding. These include:

• medicines used to treat:
  • epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate or felbamate);
  • tuberculosis (e.g. rifampicin);
  • HIV and hepatitis C virus infections (protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine, efavirenz);
  • fungal infections (e.g. griseofulvin, azole antifungals such as itraconazole, voriconazole, fluconazole);
  • bacterial infections (macrolide antibiotics, e.g. clarithromycin, erythromycin);
  • certain heart conditions, high blood pressure (calcium channel blockers, e.g. verapamil, diltiazem);
  • arthritis, osteoarthritis (etoricoxib);
  • high blood pressure in the pulmonary blood vessels (bosentan);
• herbal medicines containing St John's wort (Hypericum perforatum);
• grapefruit juice.

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

• medicines containing cyclosporine (a medicine that reduces the body's immune response);
• the antiepileptic medicine lamotrigine (this may lead to increased frequency of seizures);
• melatonin (a medicine for insomnia);
• theophylline (a medicine used to treat breathing problems);
• midazolam (a sedative, also used in epilepsy treatment);
• tizanidine (a muscle relaxant).

Orlifique must not be used in patients with hepatitis C who are taking medicines containing ombitasvir/paritaprevir/ritonavir, dasabuvir, glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir, as these medicines may cause abnormal liver function test results in the blood (increased liver enzyme ALT activity). Before starting these medicines, the doctor will prescribe another type of contraception.
Orlifique may be restarted approximately 2 weeks after completing the above-mentioned treatment. See section "When not to take Orlifique".

Inform the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines she plans to take.

Laboratory tests
If a blood test is required, inform the doctor or laboratory staff that the patient is taking a contraceptive, as hormonal contraceptives may affect the results of certain tests.

Pregnancy, breastfeeding and fertility
Pregnancy
Orlifique must not be taken if the patient is pregnant. If the patient becomes pregnant while taking Orlifique, she should stop taking the medicine immediately and contact her doctor. If the patient plans to become pregnant, she may stop taking Orlifique at any time (see also "Stopping Orlifique").

Before taking any medicine, consult a doctor or pharmacist.

Breastfeeding
Orlifique is not recommended during breastfeeding unless advised by a doctor. If the patient wishes to use a contraceptive during breastfeeding, she should consult her doctor.

Driving and using machines
There is no information indicating that Orlifique affects the ability to drive or operate machinery.

Orlifique contains lactose, soya, Allura red AC (E129) and indigo carmine lake (E132)
Orlifique contains lactose. If the patient has previously been diagnosed with intolerance to certain sugars, she should consult her doctor before taking this medicine.
Orlifique contains azo dyes – Allura red AC (E129) and indigo carmine lake (E132). The medicine may cause allergic reactions.
Orlifique contains soya oil. Do not use if hypersensitivity to peanuts or soya has been diagnosed.

3. How to take Orlifique

This medicine should always be taken exactly as described in this patient leaflet or as directed by your doctor. If in doubt, consult your doctor or pharmacist.

If you have previously used another contraceptive medicine before starting Orlifique (28-tablet pack), remember that most contraceptive pills contain 21 tablets. With these types of pills, tablets are taken for 21 days, followed by a 7-day break.

The regimen for Orlifique, a 28-tablet pack, is different. After taking the 21 pink tablets, you must continue treatment by taking 7 placebo tablets. Therefore, there is no break between packs, but rather a "placebo week" (during which you take the 7 placebo tablets from the 4th row).

Taking a tablet every day without interruption between blister packs becomes a routine and thus reduces the risk of forgetting a dose.

Orlifique tablets of two different colours are arranged in a specific order within the blister pack. Each blister contains 28 tablets.

Take one Orlifique tablet daily, with water if necessary. Tablets should be taken at the same time each day.

Do not confuse the tablets: Take the pink tablets for the first 21 days, followed by the white tablets for the next 7 days. Start a new blister pack immediately (21 pink tablets followed by 7 white tablets). Do not interrupt tablet intake between blister packs.

Each blister pack contains 28 tablets. It is important to take the medicine every day for 28 consecutive days to maintain contraceptive effectiveness.

Each blister pack comes with adhesive labels showing the days of the week. Choose the label starting with the day of the week on which you begin taking the medicine. Apply the label to the top of the blister pack in the area marked with an arrow indicating “Apply label here”. Each row of tablets will then correspond to a day of the week. It is important to take the tablets daily. Begin by taking the first tablet in the first row indicated by the word “START”.

Take the tablets in the order indicated by the arrows on the blister pack. First take the pink tablets for 21 days, then the white tablets for 7 days, until all 28 tablets are taken. Then start the next pack immediately. Do not interrupt tablet intake between packs.

During the 7 days when the white placebo tablets are taken, withdrawal bleeding (so-called “withdrawal bleed”) should occur. This bleeding usually begins on the 2nd or 3rd day after taking the last active pink tablet of Orlifique.

After taking the last white tablet, start the next blister pack immediately, regardless of whether bleeding is still ongoing. This means each new pack will begin on the same day of the week, and bleeding should occur on the same days each month.

When taken according to these instructions, Orlifique provides protection against pregnancy even during the 7 days of taking placebo tablets.

When to start the first blister pack

• If you have not used any hormonal contraceptive in the previous month: Start taking Orlifique on the first day of your cycle (i.e. the first day of menstrual bleeding). If you start Orlifique on the first day of your period, you are protected against pregnancy immediately. You may also start between days 2 and 5 of your cycle, but in this case, you must use additional contraceptive methods (e.g. condoms) for the first 7 days.

• Switching from another combined hormonal contraceptive pill, combined contraceptive vaginal ring, or transdermal contraceptive patch: Start Orlifique the day after taking the last active tablet (last tablet containing active ingredients) of your previous pack, but no later than the day after the tablet-free interval of your previous hormonal contraceptive ends (or after the last inactive tablet of your previous contraceptive). If switching from a combined contraceptive vaginal ring or transdermal patch, start Orlifique on the day of removal of the last device, or no later than the day the next device would have been applied.

• Switching from a progestogen-only method (mini-pill, injection, implant, or intrauterine system): You may switch at any time from progestogen-only tablets (from an implant or intrauterine system on the day of removal, from an injection on the day the next injection would have been due), but in all cases, you must use additional contraceptive methods (e.g. condoms) for the first 7 days of taking Orlifique tablets.

• After miscarriage or termination of pregnancy in the first trimester: Follow your doctor’s advice.

• After childbirth or miscarriage or termination of pregnancy in the second trimester: Orlifique may be started between day 21 and day 28 after childbirth, miscarriage, or termination in the second trimester. If you start later than day 28, use an additional mechanical contraceptive method (e.g. condoms) for the first 7 days of taking Orlifique. If you have had sexual intercourse after childbirth before (re)starting Orlifique, you must first ensure you are not pregnant or wait until your next menstrual bleed.

• If you are breastfeeding and wish to (re)start taking Orlifique after childbirth: Please read section “Breast-feeding”.

If you are unsure when to start taking the medicine, consult your doctor.

Children and adolescents
Orlifique should not be used in girls before the onset of menstruation.

Elderly patients
Orlifique should not be used after menopause.

Patients with hepatic impairment
Orlifique should not be used in women with severe liver disease.

Patients with renal impairment
Consult your doctor before using Orlifique if you have impaired kidney function.

Taking more Orlifique than you should

There are no reports that taking too many Orlifique tablets causes serious harmful effects. If several tablets are taken at once, nausea and vomiting may occur. Vaginal bleeding may occur in young girls. Such bleeding may even occur in girls who have not yet started menstruating but have accidentally taken the medicine.

If you take more Orlifique tablets than recommended or if a child swallows any tablets, consult your doctor or pharmacist.

If you forget to take Orlifique

The tablets in the 4th row of the blister are placebo tablets. If you miss one of these, the contraceptive effectiveness of Orlifique remains unchanged. Discard the missed placebo tablet.

If you miss a pink tablet containing active ingredients (tablets from rows 1, 2, and 3), follow the instructions below:

• If less than 12 hours have passed since you missed the tablet, protection against pregnancy is not reduced. Take the missed tablet as soon as you remember, even if this means taking two tablets at the same time, and continue taking the following tablets at your usual time.

• If more than 12 hours have passed since you missed the tablet, protection against pregnancy may be reduced. The more tablets you miss, the higher the risk of pregnancy. The risk of incomplete protection is greatest if you forget a pink tablet at the beginning or end of the pack (from row 1 or 3). Therefore, follow the rules below (see also the chart below):

  • Never interrupt tablet intake for more than 7 days.
  • The effectiveness of Orlifique depends on uninterrupted intake for 7 consecutive days.

• If more than 12 hours have passed since you missed a tablet in Week 1 (first row) (see also chart): Take the missed tablet as soon as you remember, even if this means taking two tablets at the same time. Continue taking the following tablets at your usual time. In addition, use mechanical contraceptive methods such as condoms for the next 7 days. If you had sexual intercourse within the 7 days before missing the tablet, consider the possibility of pregnancy. The more tablets missed and the fewer days remaining until the placebo tablet period, the higher the risk of pregnancy. Contact your doctor.

• If more than 12 hours have passed since you missed a tablet in Week 2 (second row) (see also chart): Take the missed tablet as soon as you remember, even if this means taking two tablets at the same time. Continue taking the following tablets at your usual time. Additional contraceptive methods are not necessary, provided you have taken your tablets correctly during the 7 days before missing the first tablet. If you have not taken tablets correctly or have missed more than one tablet, use additional contraceptive methods for the next 7 days.

• If more than 12 hours have passed since you missed a tablet in Week 3 (third row) (see also chart): The risk of reduced contraceptive effectiveness is unavoidable due to the approaching placebo tablet period. However, reduced contraceptive protection can be prevented by adjusting the dosing schedule. If you follow the recommendations below, additional contraceptive methods are not required, provided all tablets were taken correctly during the 7 days before missing the first tablet. If this is not the case, follow the first of the two options below and also use additional contraceptive methods for the next 7 days.

1. Take the missed tablet as soon as you remember, even if this means taking two tablets at the same time. Continue taking the following tablets at your usual time. Instead of taking the white placebo tablets from this pack, discard them and immediately start taking tablets from the next blister pack (the starting day of the new pack will differ). Bleeding will most likely occur at the end of the second pack, during the placebo tablet period, but spotting or bleeding may also occur during active tablet intake in the second pack.

2. Alternatively, stop taking the active pink tablets and proceed directly to the 7 white placebo tablets (note the day on which you forgot to take the tablet before starting the placebo tablets). Then start the next blister pack. If you wish to start the new pack on the day you usually start, you may shorten the placebo tablet period to fewer than 7 days.

If you forget to take any tablet from the pack and do not experience bleeding during the placebo tablet period, this may indicate that you are pregnant.

What to do if vomiting or severe diarrhoea occurs
Vomiting or diarrhoea may reduce the effectiveness of Orlifique in preventing pregnancy.
If vomiting or severe diarrhoea occurs within 3-4 hours after taking the pink active tablet,
there is a risk that the active substances in the tablet have not been completely
absorbed by the body. This situation is almost equivalent to missing a tablet. After
vomiting or diarrhoea, take another pink active tablet from a spare blister pack as soon as possible.
If possible, take the tablet within 12 hours of your usual tablet-taking time. If this is not possible or if more than 12 hours have passed, follow the instructions described
in the section "Missed dose of Orlifique".
If the patient does not wish to change her regular tablet-taking schedule, she may take an additional
tablet from another pack.
If vomiting or diarrhoea persists, consult a doctor. Additional contraceptive methods will be necessary.

Delayed menstruation: what you should know
Although not recommended, it is possible to delay menstruation by skipping the white placebo tablets and immediately starting tablets from a new Orlifique blister pack until the pack is finished.
During the intake of tablets from the second blister pack, breakthrough bleeding or spotting may occur.
Finish the second blister pack by taking the 7 white placebo tablets from row 4. Then start taking tablets from the next blister pack.
Before deciding to delay menstruation, the patient should consult her doctor.

Changing the first day of menstruation: what you should know
If the patient takes the tablets as directed, withdrawal bleeding will occur during the week of placebo tablets. If it is necessary to change this day, it can be done by shortening (but never extending—maximum 7 days!) the placebo tablet period—when the white placebo tablets are taken.
For example, if the placebo tablet period starts on Friday, and the patient wishes to change it to Tuesday (3 days earlier), she should start the new blister pack 3 days earlier than usual. It may happen that withdrawal bleeding does not occur at that time. Instead, light bleeding or spotting may occur.
If the patient is unsure how to proceed, she should consult her doctor.

Discontinuation of Orlifique
The patient may discontinue Orlifique at any time. If she does not wish to become pregnant, she should consult her doctor regarding other effective contraceptive methods. If the patient plans to become pregnant, she should stop taking the tablets and wait until after the next menstrual period before trying to conceive. This allows for easier calculation of the expected delivery date.
If there are any further doubts regarding the use of this medicine, consult a doctor or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone will experience them. If any adverse effects occur, especially severe and persistent ones, or changes in health which the patient considers to be related to the use of Orlifique, the patient should consult her doctor.

Serious adverse effects

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 urticaria, which may cause breathing difficulties (see also section "Warnings and precautions").

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, refer to section 2, "Important information before taking Orlifique".

The following is a list of adverse effects associated with the use of Orlifique:

Common (may occur in less than 1 in 10 women):

• mood swings; depression;
• headache;
• nausea, abdominal pain;
• breast pain or tenderness;
• weight gain.

Uncommon (may occur in less than 1 in 100 women):

• decreased libido;
• rash;
• migraine;
• vomiting, diarrhoea;
• itching or raised lumps on the skin;
• breast swelling;
• fluid retention.

Rare (may occur in less than 1 in 1,000 women):

• intolerance to contact lenses;
• allergic reactions;
• increased libido;
• breast discharge or vaginal discharge;
• red skin lesions or nodules;
• skin redness or skin spots;
• weight loss;
• harmful blood clots in a vein or artery, for example:
  • in the leg or foot (deep vein thrombosis),
  • in the lungs (pulmonary embolism),
  • heart attack,
  • stroke,
  • mini-stroke or transient ischaemic attack (TIA), or blood clots in the liver, stomach and/or intestines, 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 risk factors for blood clots and symptoms of blood clots).

Description of selected adverse effects

Below are very rare adverse effects or those with delayed onset, considered to be associated with the use of combined oral contraceptives (see also sections "When not to take Orlifique" and "Warnings and precautions").

Neoplasms

• A slightly increased incidence of breast cancer has been observed in women using combined hormonal contraceptives, although it is not known whether this is caused by the use of these medicines. It is possible, for example, that more tumours are detected in women using combined hormonal contraceptives because they visit their doctor more frequently for check-ups. Since breast cancer is rare in women under 40 years of age, the number of diagnoses is small in relation to the overall risk of breast cancer.
• liver tumours (benign and malignant).

Other conditions

• women with elevated levels of blood lipids (hypertriglyceridaemia), leading to an increased risk of pancreatitis during use of combined oral contraceptives;
• high blood pressure;
• occurrence or worsening of conditions for which a link to combined oral contraceptives has not been established: jaundice and/or itching associated with cholestasis (blocked bile flow); gallstone formation; a blood disorder called porphyria; systemic lupus erythematosus (a disease affecting the body's immune system); haemolytic uraemic syndrome (a blood clotting disorder); a nerve disorder called Sydenham's chorea; a type of skin condition occurring during pregnancy (pregnancy pemphigoid); hearing loss (associated with otosclerosis);
• in women with hereditary angioedema (symptoms include sudden swelling, e.g. of eyes, lips, throat, etc.), oestrogen-containing medicines may trigger or worsen angioedema symptoms;
• liver function disorders;
• in women with diabetes, use of the medicine may affect blood glucose control. Generally, no change in diabetes treatment is required during use of Orlifique;
• Crohn's disease or ulcerative colitis (chronic inflammatory bowel diseases);
• chloasma (skin pigmentation, especially on the face and/or neck, known as "melasma").

Interactions

Unexpected bleeding and/or contraceptive failure may result from interactions between other medicines and oral contraceptives (e.g. St. John's wort, or medicines for epilepsy, tuberculosis, HIV infection and other infections). See section "Orlifique with other medicines".

The following conditions may occur or worsen during use of oral contraceptives: Crohn's disease, ulcerative colitis, migraine, cervical cancer, porphyria (metabolic disorders causing abdominal pain and psychiatric disturbances), systemic lupus erythematosus (a disease in which the body attacks and damages its own organs and tissues), pemphigoid gestationis, Sydenham's chorea (rapid involuntary movements or spasms), haemolytic uraemic syndrome (a condition following diarrhoea caused by E. coli), liver diseases manifesting as jaundice, gallbladder disorders or gallstone formation, hearing loss.

Reporting of adverse effects

If any adverse effects occur, including any not listed in this leaflet, inform a doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring 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
Adverse effects can also be reported to the responsible entity.

Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Orlifique

Keep this medicine out of sight and reach of children.
There are no special storage instructions for this medicine.
Expiry date
Do not use this medicine after the expiry date stated on the carton and blister after: EXP. The expiry date refers to the last day of the stated month.
The marking on the packaging after the abbreviation EXP indicates the expiry date, and after the abbreviation Lot/LOT indicates the batch number.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Orlifique contains
Coated tablets containing active substances (pink):

• The active substances in this medicinal product are levonorgestrel and ethinylestradiol. Each pink coated tablet contains 0.10 mg levonorgestrel and 0.02 mg ethinylestradiol.
• Other ingredients are: Core: lactose, povidone K-30, magnesium stearate; Coating: polyvinyl alcohol, talc, titanium dioxide (E171), macrogol 3350, Allura red AC (E129) lake, soya lecithin, iron oxide red (E172), indigo carmine (E132) lake.

Placebo coated tablets (white):
Each white coated tablet contains only excipients (no active substances).
Core: lactose, povidone K-30, magnesium stearate;
Coating: polyvinyl alcohol, talc, titanium dioxide (E171), macrogol 3350.

What Orlifique looks like and contents of the pack
The tablets containing active substances are pink, round, coated tablets.
The placebo tablets are white, round, coated tablets.
Orlifique is available in blisters of 28 tablets:
21 pink tablets containing active substances and 7 white placebo tablets.
Orlifique is available in packs containing 1, 3 or 6 blisters, each with 28 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19
83-200 Starogard Gdański
tel. + 48 22 364 61 01

Manufacturer
Laboratorios León Farma, S.A.
C/La Vallina s/n, Pol. Ind. Navatejera,
24193 Villaquilambre - Leon
Spain