Meliane 0.075 mg/0.02 mg film-coated tablets

Patient Information Leaflet

Introduction

Patient Information Leaflet

Meliane 0.075 mg / 0.02 mg film-coated tablets

gestodene / ethinylestradiol

Read the entire leaflet carefully before starting to take this medicine, as it contains important information for you. Keep this leaflet, as you may need to read it again. If you have any questions, consult your doctor or pharmacist. This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, since it could harm them. If you experience any adverse effects, consult your doctor or pharmacist, even if these adverse effects are not listed in this leaflet. See section 4.

Important things you should 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 developing a blood clot in the veins and arteries, especially during the first year or when restarting a combined hormonal contraceptive after a break of 4 weeks or more.
• Be alert and consult your doctor if you think you may be experiencing symptoms of a blood clot (see section 2 “Blood clots”).

Package leaflet contents

1. What Meliane is and what it is used for
2. What you need to know before taking Meliane
3. How to take Meliane
4. Possible side effects
5. How to store Meliane
6. Contents of the pack and other 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 secretions (produced by the cervix). It is used to prevent pregnancy. It is also used in menstrual cycle disorders.

2. What you need to know before starting Meliane

General considerations

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

Do not use Meliane

Do 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 which 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 affecting blood clotting: for example, protein C deficiency, protein S deficiency, antithrombin III deficiency, factor V Leiden, or antiphospholipid antibodies.

• If you require surgery or if you will be immobile for a long time (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 causing severe chest pain and may be the first sign of a heart attack) or a transient ischaemic attack (TIA, temporary stroke-like symptoms).

• If you have any of the following conditions that may increase your risk of developing 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 valvular heart diseases (heart valve disorders that may lead to clots).

• If you have cardiac arrhythmias with a risk of clot formation (thrombogenic arrhythmias).

• If you have or have had severe liver disease, as long as liver function test results have not returned to normal.

• If you have or have had liver tumours (benign or malignant).

• If you have or are suspected of having malignant conditions of the genital organs or breasts.

• If you have vaginal bleeding of unknown cause.

• If you are pregnant or suspect you might be pregnant.

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

Warnings and precautions

When should you consult your doctor? Seek urgent medical attention If you notice possible signs of a blood clot, which may indicate that you are experiencing a blood clot in the leg (i.e., deep vein thrombosis), a blood clot in the lung (i.e., pulmonary embolism), a heart attack, or a stroke (see section “Blood clots” below). For a description of the symptoms of these serious adverse effects, see “How to recognize a blood clot”.

Consult your doctor or pharmacist before starting to take Meliane.

If any of the risk conditions listed below apply to you, your doctor should assess 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 have any of the following conditions.

If any of these conditions develop or worsen while you are taking 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 affecting your body's natural defense system).
• If you have hemolytic uremic syndrome (HUS, a blood clotting disorder causing kidney failure).
• If you have sickle cell anemia (a hereditary red blood cell disorder).
• 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 require surgery or will be immobile for a prolonged period (see section 2 “Blood clots”).
• If you have recently given birth, you are at higher risk of developing blood clots. Ask your doctor when you can start taking Meliane after childbirth.
• If you have inflammation of the veins beneath the skin (superficial thrombophlebitis).
• If you have varicose veins.
• If you have heart disease (particularly those causing certain types of heart rhythm disorders).
• If you have high blood pressure, especially if it worsens or does not improve while taking antihypertensive medications.
• If you have severe and recurrent migraines.
• If you have diabetes.
• If you have depression or a history of depression, as it may worsen or recur while using hormonal contraceptives.
• If you have certain types of jaundice (yellowing of mucous membranes, eyes, and/or skin) or liver function disorders.
• If you have itching, particularly if it occurred during a previous pregnancy.
• If you have permanent brown patches on the skin of your face, especially if you had them during a previous pregnancy. In such cases, avoid sunlight and ultraviolet radiation (e.g., sunbeds).
• If you experience symptoms of angioedema such as swelling of the face, tongue, and/or throat, and/or difficulty swallowing, or hives with possible breathing difficulties, contact a doctor immediately. Products containing estrogens may cause or worsen symptoms of hereditary or acquired angioedema.

Also contact your doctor if you think you might be pregnant.

BLOOD CLOTS

Using a combined hormonal contraceptive like Meliane increases your risk of developing a blood clot compared to not using one. Rarely, a blood clot can block blood vessels and cause serious health problems.

Blood clots can form:

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

Recovery from blood clots is not always complete. Rarely, there may be long-lasting serious effects, and 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.

Are you experiencing any of these signs?	What might you be suffering from?
Swelling in one leg or foot, or along a vein in the leg or foot, especially when accompanied by: Pain or tenderness in the leg, which may only be noticeable when standing or walking. Increased warmth in the affected leg. Change in skin color of the leg, e.g., turning pale, red, or blue.	Deep vein thrombosis
Sudden shortness of breath without known cause or rapid breathing. Sudden cough without clear cause, possibly bringing up blood. Sharp chest pain that may worsen when breathing deeply. Severe dizziness or lightheadedness. Rapid or irregular heartbeat. Severe stomach pain. If you are unsure, consult a doctor, as some of these symptoms such as cough or shortness of breath may be mistaken for a milder condition such as a respiratory infection (e.g., a "common cold").	Pulmonary embolism
Symptoms occurring more frequently in one eye: Sudden loss of vision. Or Painless blurred vision, which may progress to vision loss.	Retinal vein thrombosis (blood clot in the eye).
Pain, discomfort, pressure, or heaviness in the chest. Feeling of tightness or fullness in the chest, arm, or beneath the breastbone. Feeling of fullness, indigestion, or suffocation. Upper body discomfort spreading to the back, jaw, throat, arm, or stomach. Sweating, nausea, vomiting, or dizziness. Extreme weakness, anxiety, or shortness of breath. Rapid or irregular heartbeat.	Heart attack.
Sudden weakness or numbness of the face, arm, or leg, especially on one side of the body. Sudden confusion, difficulty speaking or understanding speech. Sudden vision problems in one or both eyes. Sudden difficulty walking, dizziness, loss of balance, or coordination. Sudden, severe, or prolonged headache without known cause. Loss of consciousness or fainting, with or without seizures. Sometimes stroke symptoms may be brief, with almost immediate and complete recovery, but you should still seek urgent medical attention as you may be at risk of another stroke.	Stroke
Swelling and slight bluish discoloration of a limb. Severe stomach pain (acute abdomen).	Blood clots blocking other blood vessels.

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 veins (venous thrombosis). However, these adverse effects are rare. They occur more frequently during the first year of using a combined hormonal contraceptive.
• If a blood clot forms in a vein of the leg or foot, it may cause deep vein thrombosis (DVT).
• If a blood clot travels from the leg and lodges in the lung, it may cause a pulmonary embolism.
• Very rarely, a clot may form in a vein of another organ such as the eye (retinal vein thrombosis).

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

The risk of developing 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 restart taking a combined hormonal contraceptive (the same or a different medicine) after a break of 4 weeks or more.

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

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

What is the risk of developing a blood clot?

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

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

• Among 10,000 women who do not use a combined hormonal contraceptive and who are not pregnant, about 2 will develop a blood clot within one year.

• Among 10,000 women who use a combined hormonal contraceptive containing levonorgestrel, norethisterone, or norgestimate, about 5 to 7 will develop a blood clot within one year.

• Among 10,000 women who use a combined hormonal contraceptive containing gestodene, such as Meliane, between 9 and 12 women will develop a blood clot within one year.

• Your risk of developing a blood clot will depend on your personal medical history (see “Factors that increase your risk of a blood clot” below).

	Risk of developing a blood clot in one year
Women who do not use a combined hormonal pill/patch/ring and who are not pregnant	About 2 out of 10,000 women
Women who use a combined oral contraceptive pill containing levonorgestrel, norethisterone, or norgestimate	About 5–7 out of 10,000 women
Women who use Meliane	About 9–12 out of 10,000 women

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

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

• If you are overweight (body mass index or BMI above 30 kg/m²).
• If any of your close relatives have had a blood clot in the leg, lung, or another organ at an early age (i.e., before approximately 50 years of age). In this case, you may have an inherited blood clotting disorder.
• If you require surgery or if you are immobile for long periods due to injury, illness, or having a leg in a cast. You may need to stop taking Meliane several weeks before surgery or while you are less mobile. If you need to stop taking Meliane, ask your doctor when you can start using it again.
• With increasing age (especially above about 35 years).
• If you have given birth within the last few weeks.

The risk of developing a blood clot increases the more of these conditions you have.

Air travel (more than 4 hours) may temporarily increase the risk of a blood clot, especially if you have any of the other risk factors listed above.

It is important to inform your doctor if you have any of the conditions listed above, even if you are uncertain. Your doctor may decide that you need to stop taking Meliane.

If any of the above conditions change while you are using Meliane—for example, a close relative experiences thrombosis without a known cause or you gain significant 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 clot in an artery can cause serious problems. For example, it may lead to a heart attack or stroke.

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

It is important to note that the risk of heart attack or stroke while using Meliane is very small, but it may increase:

• With age (especially 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 recommend using a different type of contraceptive.
• If you are overweight.
• If you have high blood pressure.
• If a close relative has had a heart attack or stroke at an early age (under about 50 years). In this case, you may also be at higher risk of heart attack or stroke.
• If you or a close relative have high levels of fat in the blood (cholesterol or triglycerides).
• If you suffer from migraines, especially migraines with aura.
• If you have a heart condition (valve disorders, heart rhythm disturbances such as atrial fibrillation).
• If you have diabetes.

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

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

• Tumors

A slightly increased frequency of breast tumors has been observed in women using oral contraceptives, but it is unknown whether this is due to the treatment. For example, more tumors may be detected in women using oral contraceptives because they visit their doctor more frequently. This increased frequency gradually decreases after stopping treatment. After ten years, the likelihood of developing breast tumors will be the same as in women who have never used oral contraceptives.

Some studies have reported an increased risk of cervical cancer in women who have used combined oral contraceptives (COCs) for long periods, but controversy remains regarding how much this finding may be attributed to other factors such as sexual behavior and sexually transmitted infections.

Benign liver tumors have been rarely reported, and malignant liver tumors even more rarely, in users of COCs. These may cause internal bleeding leading to severe abdominal pain. If this occurs, you should contact your doctor immediately.

A slight increase in relative risk of cervical cancer and cervical intraepithelial neoplasia (serious conditions of the cervix) has been observed. Given the biological influence of COCs on these lesions, it is recommended that cervical cytology (Pap smears) be performed periodically when prescribing a COC.

Malignant tumors can be life-threatening or fatal.

• Psychiatric disorders

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

If severe depression develops, treatment should be discontinued and an alternative contraceptive method used. Women with a history of depression should be closely monitored.

• Other conditions

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

Women previously treated for hyperlipidemia (elevated blood fats such as triglycerides and/or cholesterol) should be monitored if they decide to take oral contraceptives.

During COC use, many users may experience small increases in blood pressure, although clinically significant cases are rare. If sustained high blood pressure develops during COC use, consult your doctor.

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

The following conditions may appear or worsen during pregnancy and with COC use: jaundice (yellowing of mucous membranes, eyes, and/or skin) and/or pruritus (itching) related to cholestasis (reduced or stopped bile flow), gallstone formation, porphyria (a disorder of hemoglobin metabolism), systemic lupus erythematosus (inflammatory skin disease), hemolytic uremic syndrome (a blood disorder), Sydenham's chorea (involuntary movements), herpes gestationis (skin and mucous membrane lesions occurring during pregnancy), and hearing loss due to otosclerosis (a type of ear disorder).

Acute or chronic liver function disorders require discontinuation of COC use until liver function markers return to normal. Recurrence of cholestatic jaundice (yellowing of mucous membranes, eyes, and/or skin related to reduced or stopped bile flow), which first occurred during pregnancy or previous use of sex hormones, requires discontinuation of the COC.

COCs may alter peripheral insulin resistance and glucose tolerance. There is no evidence that the treatment regimen needs to be changed in diabetic women using low-dose COCs (with < 0.05 mg ethinylestradiol). Nevertheless, diabetic women should be carefully monitored while taking COCs.

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

Occasionally, chloasma (brown skin patches) may occur, especially in women with a history of chloasma gravidarum (occurring during pregnancy). If you are prone to chloasma, you should avoid exposure to sunlight or ultraviolet rays while taking COCs.

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

Medical examination and consultation

Before starting or restarting treatment with Meliane, your doctor must perform a complete medical history and physical examination to rule out contraindications and observe precautions. These should be repeated at least once a year during the use of combined oral contraceptives.

Reduced effectiveness

The effectiveness of COCs may decrease if you miss a tablet (see section “If you forgot to take Meliane”), if you experience gastrointestinal disorders such as vomiting or severe diarrhea (see section “Recommendations in case of gastrointestinal disorders”), or if you take other medications simultaneously (see section “Taking Meliane with other medicines”).

Irregularities in cycle control

During use of any COC, spotting or vaginal bleeding between periods may occur, especially during the first months of use. If these bleeding irregularities persist or occur after previously regular cycles, non-hormonal causes should be considered, and you should see your doctor for appropriate diagnostic measures to exclude malignancies, infections, or pregnancy.

In some women, withdrawal bleeding (period) may not occur during the rest week. If you have taken the COC according to the instructions in the section “How to take Meliane,” it is unlikely that you are pregnant. However, if you have not taken the COC as instructed before the first missed period, or if a second period is missed, pregnancy should be ruled out before continuing COC use.

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

Other medicines and Meliane

Inform your doctor or pharmacist if you are currently using, have recently used, or might need to use any other medicines.

Certain medicines may interact, and in such cases, it may be necessary to adjust the dose or discontinue treatment with one of the medicines. It is especially important that you inform your doctor if you are using any of the following medicines:

The following medicines may prevent combined hormonal contraceptives from working properly, and if this occurs, you could become pregnant:

• Treatment for hepatitis C virus 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).
• Some antiepileptic drugs (topiramate, barbiturates (phenobarbital), phenytoin, carbamazepine, primidone, oxcarbazepine, felbamate, ethosuximide).
• Antacids, including lansoprazole.
• Some mood-elevating substances (modafinil).
• Grapefruit juice.

You must not take herbal preparations containing St. John's wort (Hypericum perforatum) together with Meliane, as this may reduce its effectiveness, increasing the risk of unintended pregnancy and intermenstrual bleeding. The reduced contraceptive effect lasts up to two weeks after stopping St. John's wort.

It is advisable to use another reliable contraceptive method if you are taking any of the medicines listed above. The effect of some of these medicines may last up to 28 days after stopping treatment.

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

You should never take another medicine 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 medicines may cause increases in liver function test results (elevated liver enzyme ALT).

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

Meliane can be restarted approximately 2 weeks after completion of this treatment. See the section "Do not use Meliane."

You should consult the prescribing information of any medicines you are taking concurrently to identify possible interactions.

Laboratory tests

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

If you are scheduled for any laboratory test, inform your doctor that you are using oral contraceptives.

Pregnancy and breastfeeding

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

Meliane is not indicated during pregnancy. If you become pregnant, you must stop taking Meliane immediately and consult your doctor.

Small amounts of oral contraceptives may be excreted in breast milk during COC use, but there is no evidence that this adversely affects the child's health. Nevertheless, COCs are generally not recommended until breastfeeding has ended.

If you wish to use Meliane after childbirth or after a second-trimester abortion: see section “How to take Meliane.”

Driving and use of machines

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

Meliane contains lactose and sucrose

If your doctor has informed you that you have an intolerance to certain sugars, consult him before taking this medicine.

3. How to take Meliane

Follow exactly the instructions for use of this medicine given by your doctor. If in doubt, consult your doctor again.

Remember to take your medicine, as forgetting coated tablets may reduce the effectiveness of the preparation.

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

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

How to start taking Meliane

• If no hormonal contraceptive has been used previously (in the previous month)

Tablets should be started on day 1 of the woman's natural cycle (i.e., the first day of menstrual bleeding). Alternatively, they may be started on days 2 to 5 of the cycle; however, in this case, it is recommended to additionally use a barrier method, such as a condom, during the first 7 days of tablet intake.

• To replace a combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring, or transdermal patch)

You should preferably start taking Meliane the day after taking the last hormone-containing tablet of your previous COC, or at the latest, on the day after completing the usual tablet-free or placebo tablet interval of your previous COC. This means that treatment with Meliane should be started no later than the day a new pack (blister) of the previous COC would have been started. If using a vaginal ring or transdermal patch, you should preferably start taking Meliane on the day of removal of the last ring or patch of a cycle pack, or at the latest on the day the next application would have been due.

• To replace a progestogen-only method (progestogen-only pill, injection, implant), or a progestogen-releasing intrauterine system (IUS)

You may switch to Meliane from a progestogen-only pill on any day (if using an implant or IUS, on the same day of removal; if using an injectable, on the day the next injection would be due); however, in all cases, it is recommended to additionally use a barrier method, such as a condom, during the first 7 days of tablet intake.

• After a first-trimester abortion

You may start taking Meliane immediately. In this case, no additional contraceptive measures are necessary.

• After childbirth or a second-trimester abortion

It is recommended to start taking Meliane 21–28 days after childbirth or a second-trimester abortion. If you start later, you must use an additional barrier method during the first 7 days. However, if sexual intercourse has already occurred, pregnancy must be ruled out before starting the COC, or you must wait until your first menstrual period.

If you take more Meliane than you should

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

No serious adverse reactions due to overdose have been reported. Symptoms that may occur in such cases include: nausea, vomiting, or vaginal bleeding. This bleeding may even occur in girls who have not yet had their first menstrual period, if they have accidentally taken this medicine. There is no antidote, and treatment should be symptomatic.

If you forget to take Meliane

Contraceptive protection is not reduced if a tablet is taken less than 12 hours late. In this case, take the missed 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, no additional contraceptive measures are necessary.

If you are more than 12 hours late in taking a tablet, contraceptive protection may be reduced. The following two basic rules should be followed in case of a missed tablet:

1. You should never stop taking tablets 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.

Accordingly, and following the above guidelines, the following practical advice may be given:

• Week 1

Take the last missed tablet as soon as you remember, even if this means taking two tablets at the same time. Then continue taking the tablets at your usual time. Additionally, use a barrier method, such as a condom, for the next 7 days. If you have had sexual intercourse in the previous 7 days, consider the possibility of pregnancy. The more tablets you have missed and the closer you are to the rest week, the higher the risk of pregnancy.

• Week 2

Take the last missed tablet as soon as you remember, even if this means taking two tablets at the same time. Then continue taking the tablets at your usual time. If you have taken all tablets correctly in the 7 days before the missed tablet, you do not need to take additional contraceptive precautions. However, if you have missed more than one tablet, it is advisable to use additional precautions for 7 days.

• Week 3

The risk of reduced efficacy is imminent due to the proximity of the rest week. However, by adjusting the tablet-taking schedule, a decrease in contraceptive protection can still be prevented. Therefore, if you follow one of the two options below, you will not need additional contraceptive precautions, provided that you took all tablets correctly in the 7 days prior to the first missed tablet. If this is not the case, you must follow the first of the two options below and use additional contraceptive precautions for the next 7 days.

1. Take the last missed tablet as soon as you remember, even if this means taking two tablets at the same time. Then continue taking the tablets at your usual time. Start the next blister pack immediately after finishing the current one, without any break between packs. Withdrawal bleeding (menstruation) is unlikely to occur until after finishing the second pack, but you may experience spotting or breakthrough bleeding during tablet intake.
2. You may also stop taking tablets from the current blister pack. Then complete an interval of up to 7 days without tablets, including the days on which you missed tablets, and then restart with the next blister pack.

If, after missing tablets, you do not experience withdrawal bleeding (menstruation) during the first tablet-free interval, consider the possibility of pregnancy.

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

Recommendations in case of gastrointestinal disorders

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

If you vomit within 3–4 hours after taking a tablet, follow the advice for missed tablets as described in the section “If you forget to take Meliane”. If you do not wish to change your normal tablet-taking schedule, you should take the necessary extra tablet(s) from another pack.

How to delay withdrawal bleeding (menstruation)

To delay a period, continue with the next pack of Meliane without taking the usual 7-day break. You may continue this for as long as desired until the second pack is finished. During this time, you may experience bleeding or spotting. Then take the usual 7-day tablet-free interval and resume regular intake of Meliane.

To shift your period to a different day of the week than your current cycle, you may shorten the rest week by as many days as desired. The shorter the interval, the higher the risk of no withdrawal bleeding (menstruation) occurring and of experiencing intermenstrual bleeding or spotting during the next pack intake (as occurs when delaying a period).

Special populations

• Pediatric population

Meliane is only indicated after menarche (onset of first menstruation).

• Elderly population

Not applicable. Meliane is contraindicated after menopause.

• Patients with impaired hepatic function

Meliane is contraindicated in women with severe hepatic impairment.

• Patients with impaired renal function

Meliane has not been specifically studied in patients with impaired renal function. There are no available data suggesting a need to modify treatment in this patient population.

4. Possible adverse effects

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

All women who take combined hormonal contraceptives have an increased risk of developing blood clots in veins (venous thromboembolism (VTE)) or blood clots in arteries (arterial thromboembolism (ATE)). For more detailed information on the different risks associated with taking combined hormonal contraceptives, see section 2 “What you need to know before starting to take 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 hives with possible difficulty breathing (see also section “Warnings and precautions”).

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

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. Immune system disorders

Rare: allergic-type reactions such as urticaria (itching) and severe reactions accompanied by difficulty breathing, dizziness and even loss of consciousness.

Very rare: worsening of systemic lupus erythematosus (chronic inflammatory autoimmune disorder).

1. Metabolism and nutrition disorders

Uncommon: changes in appetite (increase or decrease).

Rare: glucose intolerance.

Very rare: worsening of porphyria (a disorder of haemoglobin 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, dizziness.

Very rare: worsening of chorea (a disease causing movement disorders).

1. Eye disorders

Rare: intolerance to contact lenses.

Very rare: optic neuritis, retinal vascular thrombosis (abnormalities in the eyes 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.
• Mini-stroke or temporary stroke-like symptoms, known as transient ischaemic attack (TIA).
• Blood clots in the liver, stomach/intestines, kidneys or eye.

The likelihood of developing 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: cramps, bloating.

Very rare: pancreatitis (inflammation of the pancreas), hepatic adenomas (common benign liver tumours), hepatocellular carcinoma (malignant liver tumour).

1. Hepatobiliary disorders

Rare: cholestatic jaundice (yellowish colouring of mucous membranes, eyes and/or skin related to interruption or reduction of bile flow).

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 pigmentation) which may persist, hirsutism (excessive hair growth), alopecia (hair loss).

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

Very rare: erythema multiforme (a type of skin inflammation).

1. Renal and urinary disorders

Very rare: haemolytic uraemic syndrome (a disease causing blood abnormalities).

1. Reproductive and breast disorders

Very common: bleeding, spotting.

Common: breast pain, breast tenderness, breast enlargement, breast discharge, dysmenorrhoea (painful menstruation), changes in menstrual flow, changes in vaginal discharge and cervical ectropion (alteration of the mucosa of the cervix), amenorrhoea (absence of menstruation).

1. General disorders and administration site conditions

Common: fluid retention, oedema (swelling), weight changes (gain or loss).

1. Investigations

Uncommon: changes in blood lipid levels (fats), including hypertriglyceridaemia.

Rare: decrease in blood folate levels (derivatives of folic acid).

Description of selected adverse reactions

Listed below are very uncommon adverse reactions or those with delayed onset of symptoms considered related to the group of combined oral contraceptives (see sections “Do not use Meliane” and “Warnings and precautions”).

Tumours

• The frequency of breast cancer diagnosis among users of COCs is very slightly increased. Since breast cancer is rare in women under 40 years of age, this increase is small in relation to the overall risk of breast cancer. Causality related to the use of COCs is unknown.
• Liver tumours (benign and malignant).

Other disorders

• Women with hypertriglyceridaemia (increased blood fats resulting in increased risk of pancreatitis when COCs are used).
• Hypertension.
• Onset or worsening of disorders whose association with COC use is not conclusive: jaundice and/or pruritus related to cholestasis (blocked bile flow); gallstone formation; a metabolic disorder called porphyria; systemic lupus erythematosus (a chronic autoimmune disease); haemolytic uraemic syndrome (a disease involving blood clots); a neurological disorder called Sydenham's chorea; herpes gestationis (a type of skin disorder occurring during pregnancy); hearing loss related to otosclerosis.
• Alterations in liver function.
• Changes in glucose tolerance or effect on peripheral insulin resistance.
• Crohn’s disease, ulcerative colitis.
• Chloasma (skin pigmentation).

Interactions

Interactions between oral contraceptives and other medicines (e.g. St. John’s wort, medications for epilepsy, tuberculosis, HIV and other infections) may lead to unexpected bleeding and/or contraceptive failure (see section “Taking Meliane with other medicines”).

Reporting of adverse effects

If you experience any kind of adverse effect, consult your doctor, pharmacist or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: http://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Meliane

Keep this medicine out of sight and reach of children.

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

Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of the month indicated.

Medicines must not be disposed of via wastewater drains or household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Meliane

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

Appearance of the product and contents of the pack

Meliane is available in a blister pack (the container holding the coated tablets) containing 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 most recent review of this leaflet: 10/2022

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