MELIANE 0.075 mg / 0.02 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Meliane 0.075 mg / 0.02 mg coated tablets

gestodene / ethinylestradiol

Important things to know about combined hormonal contraceptives (CHCs):

• They are one of the most reliable reversible contraceptive methods if used correctly.
• They slightly increase the risk of having a blood clot in the veins and arteries, especially in the first year or when restarting a combined hormonal contraceptive after a break of 4 weeks or more.
• Be alert and see your doctor if you think you might have symptoms of a blood clot (see section 2 “Blood clots”).

Contents of the package leaflet

1. What Meliane is and what it is used for
2. What you need to know before you start taking Meliane
3. How to take Meliane
4. Possible side effects
5. Storing Meliane
6. Package contents and further information

1. What Meliane is and what it is used for

Meliane is a combined oral hormonal contraceptive. It inhibits ovulation and produces changes in cervical secretion (produced by the neck of the uterus). It is used to prevent pregnancy. It is also used for menstrual cycle disorders.

2. What you need to know before taking Meliane

General considerations

Before starting to use Meliane, you should read the information about blood clots in section 2. It is particularly important that you read the symptoms of a blood clot (see section 2 "Blood clots").

Do not use Meliane

You should not use Meliane if you have any of the conditions listed below. Inform your doctor if you have any of the conditions listed below. Your doctor will discuss with you what other form of contraception would be more suitable.

• If you are allergic to the active substances or to any of the other components of this medicine (listed in section 6).
• If you have (or have ever had) a blood clot in a blood vessel in your legs (deep vein thrombosis, DVT), in your lungs (pulmonary embolism, PE) or in other organs.
• If you know you have a disorder that affects blood clotting: for example, protein C deficiency, protein S deficiency, antithrombin III deficiency, factor V Leiden or antiphospholipid antibodies.
• If you need an operation or if you spend a long time sitting or lying down (see section "Blood clots").
• If you have ever had a heart attack or a stroke.
• If you have (or have ever had) angina pectoris (a condition that causes severe chest pain and may be the first sign of a heart attack) or a transient ischemic attack (TIA, temporary stroke symptoms).

• If you have any of the following diseases that may increase your risk of forming a blood clot in the arteries:

• Severe diabetes with blood vessel damage.
• Very high blood pressure.
• Very high levels of fat in the blood (cholesterol or triglycerides).
• A condition called hyperhomocysteinemia.

• If you have (or have ever had) a type of migraine called "migraine with aura".
• If you have thrombogenic valvulopathies (heart valve diseases that can cause blood clots).

• If you have heart rhythm disorders that can cause blood clots (thrombogenic arrhythmias).

• If you have or have had a severe liver disease, unless the liver function test values have returned to normal.
• If you have or have had liver tumors (benign or malignant).
• If you have or suspect you have malignant diseases of the genital organs or breasts.
• If you have vaginal bleeding of unknown cause.
• If you are pregnant or think you may be pregnant.

Do not use Meliane if you have hepatitis C and are taking medicines that contain ombitasvir/paritaprevir/ritonavir, dasabuvir, glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir (see also section "Other medicines and Meliane").

Warnings and precautions

Consult your doctor or pharmacist before starting to take Meliane.

If some of the risk situations mentioned below are present, your doctor should weigh the benefits of using Meliane against the possible risks and discuss them with you before you decide to start using it.

Tell your doctor if you suffer from any of the following conditions.

If the condition develops or worsens while you are using Meliane, you should also inform your doctor.

• If you have Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease).
• If you have systemic lupus erythematosus (SLE, a disease that affects your natural defense system).
• If you have hemolytic uremic syndrome (HUS, a blood clotting disorder that causes kidney failure).
• If you have sickle cell anemia (an inherited disease of red blood cells).
• If you have high levels of fat in the blood (hypertriglyceridemia) or a known family history of this condition. Hypertriglyceridemia has been associated with an increased risk of pancreatitis (inflammation of the pancreas).
• If you need an operation or spend a long time sitting or lying down (see section 2 "Blood clots").
• If you have just given birth, you are at a higher risk of blood clots. You should ask your doctor when you can start taking Meliane after childbirth.
• If you have inflammation of the veins just under the skin (superficial thrombophlebitis).
• If you have varicose veins.
• If you have heart disease (those that cause certain types of heart rhythm disorders).
• If you have high blood pressure, especially if it worsens or does not improve with anti-hypertensive medications.
• If you have severe and recurrent headaches (migraines).
• If you have diabetes.
• If you have depression or a history of depression, as it may worsen or recur when using hormonal contraceptives.
• If you have certain types of jaundice (yellowing of the skin, eyes, and/or mucous membranes) or liver function disorders.
• If you have itching, especially if it occurred during a previous pregnancy.
• If you have brown patches on the skin of your face, especially if you had them during a previous pregnancy. If so, avoid sunlight and ultraviolet radiation (e.g., sunlamp).
• If you experience symptoms of angioedema such as swelling of the face, tongue, and/or throat, and/or difficulty swallowing or urticaria with possible difficulty breathing, contact a doctor immediately. Products containing estrogens may cause or worsen the symptoms of hereditary and acquired angioedema.

Also, contact your doctor if you think you may be pregnant.

BLOOD CLOTS

The use of a combined hormonal contraceptive like Meliane increases your risk of blood clots compared to not using it. In rare cases, a blood clot can block blood vessels and cause serious problems.

Blood clots can form:

• In the veins (called "venous thrombosis", "venous thromboembolism" or VTE).
• In the arteries (called "arterial thrombosis", "arterial thromboembolism" or ATE).

Recovery from blood clots is not always complete. In rare cases, there can be serious long-term effects or, very rarely, they can be fatal.

It is important to remember that the overall risk of a harmful blood clot due to Meliane is small.

HOW TO RECOGNIZE A BLOOD CLOT

Seek urgent medical attention if you notice any of the following signs or symptoms.

BLOOD CLOTS IN A VEIN

What can happen if a blood clot forms in a vein?

• The use of combined hormonal contraceptives has been associated with an increased risk of blood clots in the veins (venous thrombosis). However, these side effects are rare. They occur more frequently in the first year of use of a combined hormonal contraceptive.
• If a blood clot forms in a vein in your leg or foot, it can cause deep vein thrombosis (DVT).
• If a blood clot moves from your leg and lodges in your lung, it can cause a pulmonary embolism.
• In very rare cases, a blood clot can form in a vein in another organ such as the eye (retinal vein thrombosis).

When is the risk of a blood clot in a vein higher?

The risk of a blood clot in a vein is higher during the first year you take a combined hormonal contraceptive for the first time. The risk may also be higher if you start taking a combined hormonal contraceptive (the same medicine or a different one) after a break of 4 weeks or more.

After the first year, the risk decreases, but it is always slightly higher than if you were not taking a combined hormonal contraceptive.

When you stop taking Meliane, your risk of a blood clot returns to normal within a few weeks.

What is the risk of a blood clot?

The risk depends on your natural risk of VTE and the type of combined hormonal contraceptive you are taking.

The overall risk of a blood clot in the leg or lung (DVT or PE) with Meliane is small.

• Out of 10,000 women who do not use a combined hormonal contraceptive and are not pregnant, about 2 will have a blood clot in a year.
• Out of 10,000 women who use a combined hormonal contraceptive that contains levonorgestrel, norethisterone or norgestimate, about 5-7 will have a blood clot in a year.
• Out of 10,000 women who use a combined hormonal contraceptive that contains gestodene like Meliane, about 9-12 will have a blood clot in a year.

• The risk of a blood clot will depend on your personal history (see "Factors that increase your risk of a blood clot" below).

Factors that increase your risk of a blood clot in a vein

The risk of a blood clot with Meliane is small, but some conditions increase the risk. Your risk is higher:

• If you are overweight (body mass index or BMI over 30 kg/m2).
• If any of your close relatives have had a blood clot in the leg, lung or other organ at a young age (i.e., before the age of about 50).
• If you need an operation or spend a long time sitting or lying down due to an injury or illness or if you have your leg in a cast. You may need to stop using Meliane several weeks before surgery or while you have reduced mobility. If you need to stop using Meliane, ask your doctor when you can start using it again.
• As you get older (especially above about 35 years).
• If you have recently given birth.

The risk of a blood clot increases with the number of risk factors you have.

Long-haul flights (more than 4 hours) may temporarily increase the risk of a blood clot, especially if you have any of the other risk factors listed.

It is important to inform your doctor if you suffer from any of the above conditions, even if you are not sure. Your doctor may decide that you should stop using Meliane.

If any of the above conditions change while you are using Meliane, for example, a close relative experiences a thrombosis without known cause or you gain much weight, inform your doctor.

BLOOD CLOTS IN AN ARTERY

What can happen if a blood clot forms in an artery?

Like a blood clot in a vein, a blood clot in an artery can cause serious problems. For example, it can cause a heart attack or a stroke.

Factors that increase your risk of a blood clot in an artery

It is important to note that the risk of a heart attack or stroke due to Meliane is very small, but it can increase:

• With age (above about 35 years).
• If you smoke.When using a combined hormonal contraceptive like Meliane, you are advised to stop smoking. If you are unable to stop smoking and are over 35 years old, your doctor may advise you to use a different type of contraceptive.
• If you are overweight.
• If you have high blood pressure.
• If any of your close relatives have had a heart attack or stroke at a young age (less than about 50 years). In this case, you may also be at higher risk of having a heart attack or stroke.
• If you or any of your close relatives have high levels of fat in the blood (cholesterol or triglycerides).
• If you have migraines, especially migraines with aura.
• If you have a heart problem (those that cause certain types of heart rhythm disorders).
• If you have diabetes.

If you have one or more of these conditions or if any of them are particularly severe, the risk of a blood clot may be increased further.

If any of the above conditions change while you are using Meliane, for example, you start smoking, a close relative experiences a thrombosis without known cause or you gain much weight, inform your doctor.

• Tumors

There have been reports of breast cancer with a slightly higher frequency in women using oral contraceptives, but it is not known if this is due to the treatment. For example, it could be that more tumors are detected in women using oral contraceptives because they visit their doctor more frequently. This increased frequency decreases gradually after stopping treatment. After ten years, the likelihood of having breast cancer will be the same as for women who have never used oral contraceptives.

In some studies, an increased risk of cervical cancer has been reported in users who have been taking combined oral contraceptives for long periods of time, but there is still controversy about the extent to which this finding can be attributed to the effect of other factors, such as sexual behavior and sexually transmitted diseases.

Rarely, benign and, even more rarely, malignant liver tumors have been reported in users of combined oral contraceptives. This can cause internal bleeding that leads to severe abdominal pain. If this happens, you should contact your doctor immediately.

A slight increase in the relative risk of cervical cancer and cervical intraepithelial neoplasia (severe diseases of the cervix) has been observed. Given the biological influence of combined oral contraceptives on these lesions, it is recommended that, when prescribing a combined oral contraceptive, regular cervical smears should be performed.

Malignant tumors can be life-threatening or have a fatal outcome.

• Psychiatric disorders

Some women using hormonal contraceptives like Meliane have reported depression or a depressed mood. Depression can be severe and sometimes can induce suicidal thoughts. If you experience mood changes and depressive symptoms, contact your doctor for further medical advice as soon as possible.

If a severe depression occurs, the medication should be stopped and an alternative contraceptive method should be used. Women with a history of depression should be monitored.

• Other conditions

In women with hypertriglyceridemia (elevated triglycerides in the blood) or a family history of this condition, there may be an increased risk of pancreatitis (inflammation of the pancreas) during the use of combined oral contraceptives.

Women who have been treated for hyperlipidemias (elevated blood fats) should be monitored closely. Women with hypertriglyceridemia or a family history of this condition should be monitored closely.

Women with hypertriglyceridemia (elevated levels of triglycerides) and/or hypercholesterolemia (elevated levels of cholesterol) should be monitored if they decide to take oral contraceptives.

During the use of Combined Oral Contraceptives (COCs), it has been observed that many users present small increases in blood pressure, although cases with clinical relevance are rare. If sustained arterial hypertension appears during the use of COCs, you should consult your doctor.

In women with endometrial hyperplasia (thickening of the inner lining of the uterus), the doctor should carefully assess the risk-benefit ratio before prescribing COCs and closely monitor the patient during the treatment period, performing periodic cervical cytologies.

The following conditions may appear or worsen with pregnancy and the use of COCs: jaundice (yellowish color in mucous membranes, eyes, and/or skin) and/or pruritus (itching) related to cholestasis (stop or decrease in bile flow), formation of bile stones, porphyria (disease of hemoglobin metabolism), systemic lupus erythematosus (inflammatory dermatitis), hemolytic uremic syndrome (disease that produces alterations in the blood), Sydenham's chorea (involuntary movements), herpes gestationis (skin and mucous membrane lesions that appear during pregnancy), and hearing loss due to otosclerosis (a type of ear condition).

Acute or chronic liver function disorders require the suspension of COC use until liver function markers return to normal values. The reappearance of cholestatic jaundice (yellowish color in mucous membranes, eyes, and/or skin related to the stop or decrease in bile flow), which first appeared during pregnancy or during previous use of sex hormones, requires the suspension of COCs.

COCs can alter peripheral insulin resistance and glucose tolerance. There is no evidence that it is necessary to alter the therapeutic regimen in diabetic women using low-dose COCs (with <0.05 mg of ethinylestradiol). However, diabetic women should be closely monitored while taking COCs.

The use of COCs has been associated with Crohn's disease and ulcerative colitis (inflammatory bowel diseases).

Occasionally, chloasma (brown spots on the skin) may occur, especially in women with a history of chloasma gravidarum (occurring during pregnancy). If you have a tendency to chloasma, you should avoid sun exposure or ultraviolet rays while taking COCs.

Women should be warned that oral contraceptives do not protect against HIV (AIDS) infection or other sexually transmitted diseases.

Medical examination and consultation

Before starting or resuming treatment with Meliane, it is necessary for your doctor to perform a complete medical history and physical examination, aimed at ruling out contraindications and observing precautions, and these should be repeated at least once a year during the use of combined oral contraceptives.

Reduced efficacy

The efficacy of COCs may decrease if you forget to take a pill (see section "If you forgot to take Meliane"), if you have gastrointestinal disorders such as vomiting or intense diarrhea (see section "Recommendations in case of gastrointestinal disorders"), or if you take other medications simultaneously (see section "Taking Meliane with other medications").

Irregularities in cycle control

During the use of any COC, spotting or vaginal bleeding between two periods may appear, especially during the first months of use. If these bleeding irregularities persist or occur after previously regular cycles, possible non-hormonal causes should be considered, and therefore, you should consult your doctor so that he or she can take appropriate diagnostic measures to rule out malignant processes, infections, or pregnancy.

In some women, withdrawal bleeding (menstruation) may not occur during the week of rest. If you have taken the COC following the instructions described in the section "How to take Meliane", it is unlikely that you are pregnant. However, if you have not taken the COC following these instructions before the first missed period, or if a second missed period occurs, pregnancy should be ruled out before continuing to take the COC.

If you have any doubts about the above points, consult your doctor before taking Meliane.

Other medications and Meliane

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medication.

Certain medications may interact, and in these cases, it may be necessary to change the dose or interrupt treatment with one of the medications. It is especially important that you inform your doctor if you use any of the following medications:

The medications listed below may prevent combined hormonal contraceptives from working properly, and if this happens, you may become pregnant:

• Treatment for hepatitis C and HIV (protease inhibitors, e.g., ritonavir and nelfinavir, and non-nucleoside reverse transcriptase inhibitors, e.g., nevirapine) and other infections (griseofulvin).
• Treatment for tuberculosis (rifampicin, rifabutin).
• Treatment for fungal infections (griseofulvin, azole antifungals, e.g., itraconazole, voriconazole, fluconazole).
• Treatment for bacterial infections (macrolide antibiotics, e.g., clarithromycin, erythromycin).
• Treatment for certain heart conditions and high blood pressure (calcium channel blockers, e.g., verapamil, diltiazem).
• Treatment for arthritis and osteoarthritis (etoricoxib).
• Certain antiepileptics (topiramate, barbiturates (phenobarbital), phenytoin, carbamazepine, primidone, oxcarbazepine, felbamate, ethosuximide).
• Antacids, including lansoprazole.
• Certain substances for mood elevation (modafinil).
• Grapefruit juice.

You should not take herbal preparations containing St. John's Wort (Hypericum perforatum) simultaneously with Meliane, as its efficacy may be reduced, with a risk of unexpected pregnancy and intermenstrual bleeding. The decrease in the contraceptive effect lasts up to two weeks after stopping the St. John's Wort preparation.

It is advisable to use another reliable contraceptive method if you take any of the above-mentioned medications. The effect of some of these medications can last up to 28 days after treatment has been suspended.

Meliane may decrease the effect of oral anticoagulants, analgesics (such as paracetamol and salicylates), fibrates (medications to reduce triglyceride and/or cholesterol levels), lamotrigine (anticonvulsant), oral antidiabetics, and insulin, and increase the effect of other medications such as beta-blockers (metoprolol), theophylline (for asthma treatment), corticosteroids (such as prednisolone), cyclosporine (increasing the risk of liver toxicity), flunarizine (increasing the risk of milk secretion), midazolam, melatonin, and tizanidine.

You should never take another medication on your own initiative without your doctor's recommendation, as some combinations should be avoided.

Do not take Meliane if you have hepatitis C and are taking medications containing ombitasvir/paritaprevir/ritonavir, dasabuvir, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir, as these medications can produce increases in liver test results (elevation of liver enzyme ALT).

Your doctor will prescribe another type of contraceptive before starting treatment with these medications.

Meliane can be taken again approximately 2 weeks after the end of this treatment. Consult the section "Do not use Meliane".

You should consult the prescribing information for the medications you are taking concurrently to identify potential interactions.

Laboratory tests

The use of oral contraceptives can affect the results of certain laboratory tests.

If you are indicated to undergo any laboratory test, inform your doctor that you are using oral contraceptives.

Pregnancy and lactation

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Meliane is not indicated during pregnancy. In case of pregnancy, you should immediately stop taking Meliane and consult your doctor.

During the use of COCs, small amounts of oral contraceptives may be eliminated in breast milk, but there is no evidence that this adversely affects the health of the child. However, COCs should not be used until the end of the lactation period.

If you want to use Meliane after childbirth or abortion in the 2nd trimester: see section "How to take Meliane".

Driving and using machines

No effects on the ability to drive or use machinery have been observed.

Meliane contains lactose and sucrose

If your doctor has told you that you have an intolerance to certain sugars, consult with him or her before taking this medication.

3. How to Take Meliane

Follow the administration instructions for this medication exactly as indicated by your doctor. In case of doubt, consult your doctor again.

Remember to take your medication, as forgetting coated tablets can reduce the effectiveness of the preparation.

Combined oral contraceptives, when taken correctly, have an error rate of approximately 1% per year. The error rate may increase if tablets are forgotten or taken incorrectly.

The first tablet is extracted from one of the boxes marked with the corresponding day of the week (e.g., "MON" for Monday). The tablets should be taken every day at approximately the same time, with a little liquid if necessary, and in the order indicated on the blister pack. A daily tablet will be taken for 21 consecutive days. A new pack will be started after a 7-day interval without taking tablets, during which a withdrawal bleed (period) usually occurs. The withdrawal bleed, similar to a period, will appear two or three days after taking the last tablet, and it is possible that it may not have finished before starting the next pack.

How to Start Taking Meliane

• If you have not taken any hormonal contraceptive previously (in the previous month)

The tablets will be started on the 1st day of the woman's natural cycle (i.e., the first day of menstrual bleeding). It can also be started on days 2 to 5 of the cycle, but in that case, it is recommended to use an additional barrier method, such as a condom, during the first 7 days of tablet taking.

• To Replace a Combined Hormonal Contraceptive (Combined Oral Contraceptive (COC), Vaginal Ring, or Transdermal Patch)

You should start taking Meliane preferably the day after taking the last hormone-containing tablet of the previous COC, or at the latest, the day after the usual tablet-free interval or hormone-free tablet interval of your previous COC. This means that, at the latest, you should start treatment with Meliane on the same day you would start a new pack (blister) of your previous COC. In the case of using a vaginal ring or transdermal patch, you should start taking Meliane preferably on the day of removal of the last ring or patch from a pack for a cycle, or at the latest when the next application would have been due.

• To Replace a Progestogen-Only Method (Progestogen-Only Pill, Injection, Implant), or an Intrauterine System (IUS)

You can replace the progestogen-only pill with Meliane on any day (if it's an implant or an IUS, on the same day of its removal; if it's an injectable, on the day the next injection is due), but in all cases, it is recommended to use an additional barrier method, such as a condom, during the first 7 days of tablet taking.

• After a First-Trimester Abortion

You can start taking Meliane immediately. When you do so, you do not need to take additional contraceptive measures.

• After Childbirth or a Second-Trimester Abortion

It is recommended that you start taking Meliane 21-28 days after childbirth or a second-trimester abortion. If you do so later, you should use an additional barrier method during the first 7 days. However, if you have already had sexual intercourse, you should rule out the possibility of pregnancy before starting to take the COC, or you should wait until you have your first menstrual period.

If You Take More Meliane Than You Should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service (Tel: 91 562 04 20), indicating the medication and the amount ingested. It is recommended to bring the package and prospectus to the healthcare professional.

No serious adverse reactions have been reported due to overdose. The symptoms that may appear in this case are: nausea, vomiting, or vaginal bleeding. This bleeding can appear even in girls who have not yet had their first period, if they have accidentally taken this medication. There is no antidote, and treatment should be symptomatic.

If You Forget to Take Meliane

Contraceptive protection is not reduced if the taking of a tablet is delayed by less than 12 hours. In such a case, you should take the tablet as soon as you remember and continue taking the following tablets at the usual time (even if this means taking two tablets on the same day). In this case, you do not need to take any additional contraceptive measures.

If you delay taking more than 12 hours, contraceptive protection may be reduced. The guidelines to follow in case of forgetfulness are governed by two basic rules:

1. Tablet taking should never be suspended for more than 7 days.
2. It is necessary to take tablets continuously for 7 days to achieve adequate suppression of the hypothalamic-pituitary-ovarian axis.

Consequently, and following the above indications, in daily practice, the following can be advised:

• Week 1

You should take the last forgotten tablet as soon as you remember, even if this means taking two tablets at the same time. From then on, you will continue taking the tablets at your usual time. Additionally, during the following 7 days, you should use a barrier method, such as a condom. If you have had sexual intercourse in the 7 days prior to the forgotten tablet, you should consider the possibility of becoming pregnant. The more tablets you have forgotten and the closer you are to the week of rest, the higher the risk of pregnancy.

• Week 2

You should take the last forgotten tablet as soon as you remember, even if this means taking two tablets at the same time. From then on, you will continue taking the tablets at your usual time. If in the 7 days prior to the forgotten tablet you have taken the tablets correctly, you will not need to take additional contraceptive precautions. However, if you have forgotten to take more than 1 tablet, it is advisable to take additional precautions for 7 days.

• Week 3

The risk of reduced efficacy is imminent due to the proximity of the rest week. Nevertheless, by adjusting the tablet-taking schedule, it is still possible to prevent the reduction of contraceptive protection. Therefore, if you follow one of the two options below, you will not need to take additional contraceptive precautions, provided that in the 7 days prior to the first forgetfulness you have taken all the tablets correctly. If this is not the case, you should follow the first of the two options indicated below and take additional contraceptive precautions in the following 7 days.

1. You should take the last forgotten tablet as soon as you remember, even if this means taking two tablets at the same time. From then on, you will continue taking the tablets at your usual time. You should start the next blister pack as soon as the current one is finished, without leaving a separation between them. It is unlikely that you will have a withdrawal bleed (period) until you finish the second pack, but you may experience spotting or breakthrough bleeding during tablet taking.
2. You can also stop taking the tablets from the current blister pack. Then, you should complete an interval of up to 7 days without taking tablets, including the days you forgot to take the tablets, and then start again with the next blister pack.

If, in case of forgetting to take tablets, you do not experience a withdrawal bleed (period) in the first tablet-free interval, you should consider the possibility of becoming pregnant.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Recommendations in Case of Gastrointestinal Disorders

In case of severe gastrointestinal disorders, absorption may not be complete, and you should take additional contraceptive measures.

If you suffer from vomiting within 3-4 hours after taking the tablet, you should follow the advice regarding forgetting to take the tablet, as explained in the section "If You Forget to Take Meliane". If you do not want to change your normal tablet-taking schedule, you should take the extra tablet(s) needed from another pack.

How to Delay a Withdrawal Bleed (Period)

To delay a period, you should continue with the next pack of Meliane without leaving the usual week of rest. You can maintain this duration for as long as you want until you finish the second pack. During this time, you may experience bleeding or spotting. Then, you should leave the usual 7-day tablet-free interval and resume regular Meliane taking.

To change your period to another day of the week that you are used to according to your current cycle, you can advise that you shorten the week of rest by as many days as you want. The shorter the interval, the higher the risk that a withdrawal bleed (period) will not appear and that you will experience intermenstrual bleeding or spotting during the taking of the next pack (as occurs when delaying a period).

Special Populations

Pediatric Population

Meliane is only indicated after menarche (first period).

Geriatric Population

Not applicable. Meliane is contraindicated after menopause.

Patients with Hepatic Impairment

Meliane is contraindicated in women with severe hepatic impairments.

Patients with Renal Impairment

Meliane has not been specifically studied in patients with renal impairment. There are no available data suggesting a change in treatment in this patient population.

4. Possible Adverse Effects

Like all medications, this medication can cause adverse effects, although not all people experience them. If you experience any adverse effect, especially if it is severe and persistent, or if you have any change in health that you think may be due to Meliane, consult your doctor.

All women who take combined hormonal contraceptives are at a higher risk of developing blood clots in the veins (venous thromboembolism (VTE)) or blood clots in the arteries (arterial thromboembolism (ATE)). For more detailed information on the different risks of taking combined hormonal contraceptives, see section 2 "What you need to know before taking Meliane".

Serious Adverse Effects

Contact a doctor immediately if you experience any of the following symptoms of angioedema: swelling of the face, tongue, and/or throat, and/or difficulty swallowing or urticaria with possible difficulty breathing (see also section "Warnings and Precautions").

Adverse effects are listed in decreasing order of severity within each frequency interval.

Very Common: May affect more than 1 in 10 people

Common: May affect up to 1 in 10 people

Uncommon: May affect up to 1 in 100 people

Rare: May affect up to 1 in 1,000 people

Very Rare: May affect up to 1 in 10,000 people

1. Infections and Infestations

Common: Vaginitis (inflammation of the vagina), including candidiasis (fungal infection in the vagina).

1. Disorders of the Immune System

Rare: Allergic reactions such as urticaria (hives) and severe reactions accompanied by difficulty breathing, dizziness, and even loss of consciousness.

Very Rare: Worsening of systemic lupus erythematosus (a chronic autoimmune inflammatory disorder).

1. Metabolic and Nutrition Disorders

Uncommon: Changes in appetite (increased or decreased).

Rare: Glucose intolerance.

Very Rare: Worsening of porphyria (a disorder of hemoglobin metabolism).

1. Psychiatric Disorders

Common: Mood changes, including depression; changes in libido (sexual desire).

1. Nervous System Disorders

Very Common: Headaches, including migraines.

Common: Nervousness, vertigo.

Very Rare: Worsening of chorea (a disorder that causes movement disturbances).

1. Eye Disorders

Rare: Intolerance to contact lenses.

Very Rare: Optic neuritis, retinal vascular thrombosis (eye abnormalities and visual disturbances).

1. Vascular Disorders

Uncommon: Increased blood pressure.

Rare: Harmful blood clots in a vein or artery, for example:

• In a leg or foot (i.e., DVT).
• In a lung (i.e., PE).
• Heart attack.
• Stroke.
• Transient ischemic attack (TIA) or similar temporary symptoms.
• Blood clots in the liver, stomach/intestine, kidneys, or eye.

The risk of having a blood clot may be higher if you have any other condition that increases this risk (see section 2 for more information on conditions that increase the risk of blood clots and symptoms of a blood clot).

Very Rare: Worsening of varicose veins.

1. Gastrointestinal Disorders

Common: Nausea, vomiting, abdominal pain.

Uncommon: Colic, bloating.

Very Rare: Pancreatitis (inflammation of the pancreas), hepatic adenomas (non-cancerous liver tumors), hepatocellular carcinoma (malignant liver tumor).

1. Hepatobiliary Disorders

Rare: Cholestatic jaundice (yellowing of the skin, eyes, and/or mucous membranes related to bile flow obstruction).

Very Rare: Cholecystopathy (gallbladder disorders), including gallstones.

1. Skin and Subcutaneous Tissue Disorders

Common: Acne.

Uncommon: Skin rash, hypersensitivity reactions (abnormal increase in skin sensitivity), chloasma (skin patches) that may persist, hirsutism (excessive hair growth), alopecia (hair loss).

Rare: Erythema nodosum (a type of skin inflammation with the appearance of nodules on the legs).

Very Rare: Erythema multiforme (a type of skin inflammation).

1. Renal and Urinary Disorders

Very Rare: Hemolytic uremic syndrome (a disorder that causes blood abnormalities).

1. Reproductive System and Breast Disorders

Very Common: Bleeding, spotting.

Common: Breast pain, breast tension, breast enlargement, breast secretion, dysmenorrhea (painful menstruation), changes in menstrual flow, changes in vaginal secretion, and cervical ectropion (alteration of the cervical mucosa), amenorrhea (absence of menstruation).

1. General Disorders and Administration Site Conditions

Common: Fluid retention, edema (swelling), weight changes (gain or loss).

1. Investigations

Uncommon: Changes in blood lipid levels, including hypertriglyceridemia.

Rare: Decreased blood folate levels.

Description of Selected Adverse Reactions

The following are very rare or delayed adverse reactions that are considered related to the group of combined oral contraceptives (see sections "Do not use Meliane" and "Warnings and Precautions").

Tumors

• The frequency of breast cancer diagnosis among COC users is slightly increased. Since breast cancer is rare in women under 40 years old, this increase is low in relation to the overall risk of breast cancer. The causality related to COC use is unknown.
• Hepatic tumors (benign and malignant).

Other Alterations

• Women with hypertriglyceridemia (increased blood fats resulting in an increased risk of pancreatitis when using COCs).
• Hypertension.
• Appearance or worsening of alterations whose association with COC use is not conclusive: jaundice and/or pruritus related to cholestasis (bile flow obstruction); formation of gallstones; a metabolic disorder called porphyria; systemic lupus erythematosus (a chronic autoimmune disease); hemolytic uremic syndrome (a disorder that causes blood clots); a neurological disorder called Sydenham's chorea; gestational herpes (a type of skin disorder that occurs during pregnancy); hearing loss related to otosclerosis.
• Liver function alterations.
• Changes in glucose tolerance or effect on peripheral insulin resistance.
• Crohn's disease, ulcerative colitis.
• Chloasma (skin patches).

Interactions

Interactions between oral contraceptives and other medications (e.g., St. John's Wort, medications for epilepsy, tuberculosis, HIV, and other infections) can lead to unexpected bleeding and/or contraceptive failure (see section "Taking Meliane with other medications").

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medications: http://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Meliane

Keep this medication out of sight and reach of children.

Do not store above 25°C. Keep in the original packaging to protect from light.

Do not use this medication after the expiration date shown on the box after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and medications you no longer need at the SIGRE collection point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Packaging Content and Additional Information

Meliane Composition

• The active ingredients are: gestodene and ethinylestradiol. Each Meliane coated tablet contains 0.075 mg of gestodene and 0.02 mg of ethinylestradiol.
• The other components are: lactose monohydrate, corn starch, povidone K 25, magnesium stearate (E470b), sucrose, povidone K 90, macrogol 6000, calcium carbonate (E170), talc (E553b), and montan glycol wax.

Product Appearance and Packaging Content

Meliane is presented in a blister pack (the packaging where the coated tablets are found) of 21 round white coated tablets.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Bayer Hispania, S.L.

Av. Baix Llobregat, 3 - 5

08970 Sant Joan Despí (Barcelona)

Spain

Manufacturer

Bayer AG

Müllerstrasse 178

13353 Berlin

Germany

Date of the Last Revision of this Leaflet:10/2022

Detailed information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.