Novadien - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Dienogest, Ethinylestradiol

NOVADIEN 2 mg / 0.03 mg film-coated tablets

Why is Novadien used? What is it for?

Novadien is a combination oral contraceptive belonging to a group of medicines often called the pill. It contains two types of hormones: an estrogen and a progestin.

Novadien is designed to prevent pregnancy.

The combination contraceptive pill protects you from pregnancy in three ways.

These hormones:

1. prevent the ovary from releasing an egg every month (ovulation)
2. they also make the fluid (in the neck of the uterus) denser, preventing the sperm from reaching the egg
3. they alter the lining of the uterus to reduce the chances of it accepting a fertilized egg.

Contraindications When Novadien should not be used

Before you start using Novadien you should read the information on blood clots in section 2. It is especially important that you read the symptoms of a blood clot (see section 2 "Blood clots").

In this leaflet, some cases are presented where you will need to stop taking Novadien or where the effectiveness of the pill may be reduced. In these cases you should not have sex or you should use extra non-hormonal contraceptive precautions (such as condoms or other barrier method) during intercourse to ensure effective contraception. Do not use the calendar method or the method of measuring body temperature upon waking as oral contraceptives can affect body temperature and the cyclical change in the composition of the cervical mucus.

Remember that combination oral contraceptive pills like Novadien do not protect you against sexually transmitted diseases (like AIDS). Only condoms can help you with that.

Do not use Novadien

Do not use Novadien if you have any of the conditions listed below. If you have any of the conditions listed below, please contact your doctor. Your doctor will discuss with you other birth control methods that may be more suitable for you.

• if you have (or have ever had) a blood clot in a blood vessel of the leg (deep vein thrombosis, DVT), lung (pulmonary embolism, PE) or other organs;
• if you know you have a disorder that affects blood clotting, such as protein C deficiency, protein S deficiency, antithrombin-III deficiency, factor V Leiden or antiphospholipid antibodies;
• if you are going to have an "operation or if you will be lying down for a long time (see section" Blood clots "); if you have ever had a heart attack or stroke; if you have (or have ever had) angina pectoris (a condition which causes severe chest pain and may be a first sign of a heart attack) or a transient ischemic attack (TIA - temporary stroke symptoms);
• if you have any of the following diseases, which could increase the risk of clots in the arteries: severe diabetes with damage to blood vessels, very high blood pressure, very high level of fat (cholesterol or triglycerides) in the blood, a disease known as hyperhomocysteinaemia
• if you have (or have ever had) a type of migraine called 'migraine with aura';
• if you are allergic to dienogest or ethinylestradiol or any of the other ingredients of this medicine (listed in section 6);
• if you smoke (see section "Warnings and precautions");
• if you have or have suffered in the past from severe liver disease and your liver function has not yet returned to normal; jaundice or itching all over the body may be signs of liver disease:
• if you have or have ever had liver cancer;
• if you have or have had or if there is a suspicion that you may have cancer of the breast or genital organs, such as ovarian cancer, cervical cancer or cancer of the uterus;
• if you experience unexplained vaginal bleeding;
• if you have (or have ever had) inflammation of the pancreas (pancreatitis).

If you get any of these conditions while taking Novadien, stop taking the pill and contact your doctor immediately. In the meantime, use another non-hormonal method of contraception.

Precautions for use What you need to know before you take Novadien

When should you see a doctor?

Contact a doctor urgently

• if you notice possible signs of a blood clot which may indicate that you are suffering from a blood clot in the leg (deep vein thrombosis), a blood clot in the lung (pulmonary embolism), a heart attack or a stroke (see section below " Blood clots ").

For a description of the symptoms of these serious side effects go to the section "How to recognize a blood clot".

Tell your doctor if any of the following apply to you.

If this condition appears or worsens while you are using Novadien you should tell your doctor.

• if a close relative has or has ever had breast cancer
• if you have liver or gallbladder disease
• if you have diabetes
• if you suffer from depression
• if you suffer from epilepsy (see "Other medicines and Novadien")
• if you have a disease that first appeared during pregnancy or previous use of sex hormones (for example, hearing loss, a blood disorder called porria, rash of the skin with blisters during pregnancy (herpes gravidicum), a nervous system disease that causes sudden body movements (Sydenham's chorea))
• if you have or have had in the past chloasma (a discoloration of the skin especially of the face or neck, also called "pregnancy patches"). If so, avoid direct exposure to sunlight or ultraviolet rays.
• if you have hereditary angioedema, products containing estrogen can induce or aggravate your symptoms. You should contact a doctor immediately if you experience symptoms of angioedema such as swelling of the face, tongue and / or pharynx and / or difficulty in swallowing or hives all together with difficulty in breathing.
• if you have Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease);
• if you have systemic lupus erythematosus (SLE, a disease that affects the natural defense system);
• if you have haemolytic uremic syndrome (HUS, a blood clotting disorder causing kidney failure);
• if you have sickle cell anemia (an inherited disease of the red blood cells);
• if you have high levels of fat in the blood (hypertriglyceridaemia) or a "positive family history of this condition." Hypertriglyceridaemia has been associated with an increased risk of developing pancreatitis (inflammation of the pancreas);
• if you are going to have an "operation or if you are going to lie down for a long time (see section 2" Blood clots ");
• if you have just given birth, your risk of developing blood clots is higher. Ask your doctor how long after having a baby you can start taking Novadien;
• if you have "inflammation of the veins under the skin (superficial thrombophlebitis);
• if you have varicose veins.

BLOOD CLOTS

Using a combined hormonal contraceptive such as Novadien increases your risk of developing a blood clot compared with not using one. In rare cases, a blood clot can block blood vessels and cause serious problems.

Blood clots can develop

• in veins (called "venous thrombosis", "venous thromboembolism" or VTE)
• in the arteries (referred to as 'arterial thrombosis', 'arterial thromboembolism' or ATE).

Recovery from blood clots is not always complete. Rarely, long-lasting severe effects can occur or, very rarely, they can be fatal.

It is important to remember that the overall risk of a harmful blood clot associated with Novadien is low.

HOW TO RECOGNIZE A BLOOD CLOT

See a doctor immediately if you notice any of the following signs or symptoms.

Do you have any of these signs? What are you probably suffering from?

• swelling of one leg or along a vein in the leg or foot, especially when accompanied by:
• pain or tenderness in the leg which may only be felt when standing or walking
• increased sensation of heat in the affected leg
• change in color of the skin on the leg, such as turning pale, red or blue

• sudden and unexplained shortness of breath or rapid breathing;
• sudden cough with no obvious cause, possibly causing blood to be emitted;
• sharp chest pain which may increase with deep breathing;
• severe light headedness or dizziness;
• rapid or irregular heartbeat;
• severe stomach pain If you are unsure, tell your doctor as some of these symptoms such as coughing or shortness of breath may be mistaken for a milder condition such as a "respiratory infection (eg a" common cold " ).

Pulmonary embolism Symptoms that occur most frequently in one eye:

• immediate loss of vision or
• painless blurring of vision which can progress to loss of vision

Retinal vein thrombosis (blood clot in the eye)

• chest pain, discomfort, feeling of pressure or heaviness
• sensation of squeezing or fullness in the chest, arm or below the breastbone;
• feeling of fullness, indigestion or choking;
• upper body discomfort radiating to the back, jaw, throat, arms and stomach;
• sweating, nausea, vomiting or dizziness;
• extreme weakness, anxiety, or shortness of breath;
• rapid or irregular heartbeats

Heart attack

• sudden numbness or weakness of the face, arm or leg, especially on one side of the body;
• sudden confusion, difficulty speaking or understanding;
• sudden difficulty seeing in one or both eyes;
• sudden difficulty walking, dizziness, loss of balance or coordination;
• sudden, severe or prolonged migraine with no known cause;
• loss of consciousness or fainting with or without seizures. Stroke symptoms can sometimes be brief, with almost immediate and complete recovery, but you still need to see a doctor urgently as you may be at risk for another stroke.

Stroke

• swelling and pale blue discoloration of one extremity;
• severe stomach pain (acute abdomen)

Blood clots that block 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 linked to an increased risk of blood clots forming in the veins (venous thrombosis). However, these side effects are rare. In most cases they occur in the first year of using a combined hormonal contraceptive.
• If a blood clot forms in a vein in the leg or foot, it can cause a deep vein thrombosis (DVT).
• If a blood clot travels from the leg and lodges in the lung, it can cause a "pulmonary embolism."
• Very rarely, a clot can form in another organ such as the eye (retinal vein thrombosis).

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

The risk of developing a blood clot in a vein is highest during the first year of taking a combined hormonal contraceptive for the first time. The risk may be even higher if you restart taking a combined hormonal contraceptive (the same drug or a different drug) after a break of 4 or more weeks.

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

When you stop taking Novadien 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 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 Novadien is low.

• Out of 10,000 women who are not using any combined hormonal contraceptive and who are not pregnant, about 2 will develop a blood clot in a year.
• Out of 10,000 women who are using a combined hormonal contraceptive that contains levonorgestrel, norethisterone or norgestimate, about 5-7 will develop a blood clot in a year.
• Out of 10,000 women who are using a combined hormonal contraceptive containing drospirenone, such as Novadien, about 9-12 will develop a blood clot in a year.
• The risk of a blood clot forming depends on your medical history (see under "Factors that increase the risk of a blood clot forming").

Risk of developing a blood clot in one year Women who are not using a combined hormone pill and who are not pregnant About 2 out of 10,000 women Women using a combined hormonal contraceptive pill containing levonorgestrel, norethisterone or norgestimate About 5-7 out of 10,000 women Women who use Novadien Not yet known

Factors that increase the risk of developing a blood clot in a vein

The risk of developing a blood clot with Novadien is low but some conditions will increase the risk. Its risk is greater:

• if you are severely overweight (body mass index or BMI above 30 kg / m2);
• if a member of your immediate family has had a blood clot in the leg, lung or other organ at a young age (less than about 50 years). In this case you could have an inherited blood clotting disorder;
• if you are going to have an operation or if you have to lie down for a long time because of an injury or illness or if you have a leg in a cast. You may need to stop taking Novadien a few weeks before the surgery or in the period in which you are less mobile. If you have to stop taking Novadien, ask your doctor when you can start taking it again;
• as you get older (especially over the age of 35);
• if you gave birth less than a few weeks ago.

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

Air travel (lasting> 4 hours) may temporarily increase the risk of a blood clot, especially if you have some of the other risk factors listed.

It is important that you tell your doctor if any of these apply to you, even if you are not sure. Your doctor may decide that Novadien needs to be stopped.

If any of the above conditions change while you are using Novadien, for example if a close relative has a thrombosis for no known reason or if you gain a lot of weight, contact your doctor.

BLOOD CLOTS IN AN ARTERY

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

Like blood clots in a vein, clots in an artery can cause serious problems, for example, they can cause a heart attack or stroke.

Factors that increase the risk of developing a blood clot in an artery

It is important to note that the risk of heart attack or stroke associated with the use of Novadien is very low but can increase:

• with increasing age (over 35 years);
• if you smoke. When using a combined hormonal contraceptive such as Novadien you are advised to stop smoking. If you are unable to stop smoking and are over the age of 35, your doctor may advise you to use a different type of contraceptive;
• if you are overweight;
• if you have high blood pressure;
• if a member of your immediate family has had a heart attack or stroke at a young age (less than about 50 years). In this case, you may also be at high risk of having a heart attack or stroke;
• if you or a close relative have a high level of fat in the blood (cholesterol or triglycerides);
• if you suffer from migraines, especially migraines with aura;
• if you have any heart problems (valve defect, a heart rhythm disorder called atrial fibrillation);
• if you have diabetes.

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

If any of the above conditions change while you are using Novadien, for example if you start smoking, if a close relative has a thrombosis for no known reason or if you gain a lot of weight, contact your doctor.

Novadien and tumors

Breast cancer has been detected slightly more frequently in women using combination pills, but it has not been established whether this is due to the treatment. For example, it may be that more cancers are diagnosed in women on combination pills as they undergo medical tests more frequently.

The incidence of breast cancer gradually decreases when the use of combination hormonal contraceptives is stopped. It is important that you regularly check your breasts and that you contact your doctor if you feel any lump.

Benign liver tumors and even more rarely malignant liver tumors have been reported rarely in women taking the Pill. Contact your doctor if you experience unusual severe abdominal pain.

An increased risk of cervical cancer has been reported in some epidemiological studies in women using the long-term combination pills, but controversy continues as to whether this finding relates to the confounding effects of sexual behavior and other factors, such as human papilloma virus.

Unexpected bleeding between menstrual periods

During the first few months of using Novadien, you may experience unexpected bleeding (bleeding that does not coincide with the interval period). If this bleeding occurs for more than a few months, or if it starts after a few months, your doctor should investigate the cause.

Regular checks

Once you have started taking the pill, your doctor will want to see you again for regular checkups. The frequency and nature of your visits will be determined by your doctor and will be tailored to your individual needs and health status.

Interactions Which drugs or foods may change the effect of Novadien

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Some medicines can prevent the pill from working properly, that is, they can reduce the effectiveness of birth control. The signs of reduced effectiveness can be bleeding from loss of control. These medicines are for example:

• medicines for the treatment of epilepsy such as phenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate, barbexaclone;
• rifampicin (for the treatment of tuberculosis);
• antibiotics to treat some infections (such as ampicillin, tetracycline, griseofulvin);
• ritonavir, rifabutin, nevirapine;
• modana l (agent used to treat narcolepsy, a nervous system disorder);
• the totherapy remedy commonly called St. John's wort (Hypericum perforatum).

Interactions of Novadien with other medicines may also cause increased or pronounced occurrence of side effects.

The following medicinal products may impair the tolerability of Novadien:

• paracetamol (for pain and fever)
• ascorbic acid (vitamin C)
• atorvastatin (to reduce blood fats)
• troleandomycin (an antibiotic)
• imidazole - antifungal drugs (against fungal infections) such as uconazole
• indinavir (for the treatment of HIV infection).

Novadien may affect the metabolism of other medicines

The efficacy or tolerability of the following medicinal products may be impaired by Novadien:

• ciclosporin (medicine for suppressing the immune system)
• theophylline (a medicine to treat "asthma)
• glucocorticoids (e.g. cortisone)
• some benzodiazepines (antidepressants) such as diazepam, lorazepam
• clofibrate (a medicine used to lower blood fats)
• acetaminophen (a pain and fever medicine)
• morphine (a very strong pain reliever)
• lamotrigine (a medicine to treat epilepsy).

Before prescribing any medicine, be sure to tell your doctor or dentist that you are taking Novadien. Your doctor or dentist can tell you if you need to use additional contraceptive precautions and for how long.

If you are taking any of these medicines in the short term, you will also need to use an additional method of contraception (eg condoms) while taking the other medicine and for 7 days after you stop taking it.

Women on rifampicin treatment should use a barrier method in addition to the combination oral contraceptive during the rifampicin administration period and for 28 days after its discontinuation. If concomitant drug administration goes beyond the end of the Novadien tablet blister pack, the next pack should be started without waiting for the tablet-free interval.

If you are taking so-called medicines with long-term liver enzyme inducing effects, talk to your doctor as Novadien may not be suitable for you. (Also read the package leaflets of these medicines). In some cases, you must choose a non-hormonal method of contraception.

Warnings It is important to know that:

Pregnancy and breastfeeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

If you are pregnant you should not take Novadien. If you become pregnant or if you think you may be pregnant stop taking Novadien immediately and contact your doctor.

If you are taking Novadien while breastfeeding, the tablet may reduce the amount and change the composition of the milk. Small amounts of contraceptive steroids and / or their metabolites may be excreted in the milk. These amounts may affect the baby. Therefore Novadien should not be taken during breastfeeding.

Driving and using machines

Novadien has no effect on the ability to drive and use machines.

Novadien contains lactose

If you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicinal product.

Dosage and method of use How to use Novadien: Dosage

Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.

Each Novadien blister pack contains 21 LM-coated tablets. The blister pack is designed to help you remember to take the pill.

You should try to take the pill at about the same time every day; if necessary with some liquid, in the order shown on the blister pack.

You must take one tablet a day until you have finished all 21 pills in the pack. Then he will have 7 days in which he does not have to take any pills.

During the 7 pill-free days, on the second or third day, you will have a menstrual-like withdrawal bleeding, which is your monthly cycle.

Start the next pack on the eighth day (after the seventh day of the week gap), even if the bleeding has not yet stopped. As long as you continue to take Novadien correctly, you will always start each new pack on the same day of the week and have your period. monthly, always on the same day of the month.

If you use Novadien in this way, you will be protected from pregnancy even during the 7 days you are not taking the tablet.

When to start the first pack

If you have not used any oral contraception during the previous cycle

Take the first pill on the first day of your period, which is the first day of your period, the day you start bleeding. Take a pill marked with that day of the week.

If you start using Novadien on the first day of your period you are immediately protected from pregnancy. It can also start on days 2 to 5 of your period, but in this case you must use additional protective methods (for example, a condom) for the first 7 days.

Changing from a combination hormonal contraceptive (combination oral contraceptive, vaginal ring, transdermal patch)

Start taking Novadien preferably the day after taking the last active tablet (the last tablet containing the active ingredients) of your previous pill, but at the latest on the day after the tablet-free days of your previous pill have finished (or after the last inactive tablet of your previous pill). If you change from a vaginal ring or patch, follow your doctor's advice.

Switching from progesterone-only method (progesterone-only pill, injection, implant, progesterone-releasing intrauterine device (IUS))

Switching from the progesterone-only pill can occur on any day (from an implant or IUS on the day of removal, from an injectable contraceptive on the day the next injection would be given) but in all these cases you will need to take additional protective measures (for example, a condom) for the first 7 days of taking the tablets.

If you have any concerns or other questions, ask your doctor or pharmacist.

After giving birth

If you have just given birth, you can start taking Novadien between 21 and 28 days after the event. If you start after 28 days, you must use an additional barrier method (for example, a condom) during the first 7 days. of using Novadien If, after having a baby, you have had sexual intercourse before starting Novadien (or restarting), you must first make sure that you are not pregnant or wait for your next period.

If you are breast-feeding, please read the section "Pregnancy and breast-feeding".

After a miscarriage or an abortion

After a miscarriage or abortion, your doctor should advise you on taking the pill.

Overdose What to do if you have taken too much Novadien

If you take more Novadien than you should

There are no data on overdose of Novadien. Acute oral toxicity due to overdose with other oral contraceptives in adults and children is slow. Symptoms that can possibly occur in these cases are: nausea, vomiting and slight vaginal bleeding in young girls. In general, no special treatment is necessary; if necessary, treatment should be symptomatic.

If you notice that a child has taken more than one tablet, contact a doctor.

If you forget to take Novadien

If the delay is less than 12 hours

If you take the pill as soon as you remember, you are still protected against pregnancy. Continue taking the next pills at the usual time. This can mean taking two pills on the same day.

If the delay is more than 12 hours

If you are more than 12 hours late in taking the pill, the protection against pregnancy may be reduced. The risk of becoming pregnant is higher if you forget to take the pill at the start of a pack or before the end of a pack . In this case he must follow the following rules:

If you have forgotten to take more than one pill

If you have forgotten more than one pill, ask your doctor for advice. Remember that your contraceptive protection is not effective.

What to do if you forget to take the pill at 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. Then she should continue taking the tablets at the usual time. He must also use a barrier method, eg. the condom, for the next 7 days. If you have had sexual intercourse during the previous 7 days, you should consider the possibility of pregnancy. In this case, ask your doctor for advice as soon as possible.

What to do if you forget to take the pill at 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. Then she should continue taking the tablets at the usual time. You do not need to take additional contraceptive measures as long as you have taken your tablets correctly in the 7 days preceding the forgotten tablet.

What to do if you forget to take the pill at week 3

It is not necessary to take additional contraceptive measures, provided that you have taken your tablets correctly in the 7 days preceding the first missed tablet and that you follow one of the following two options:

1. You should take the last forgotten tablet as soon as you remember, even if this means taking two tablets at the same time. Then she should continue taking the tablets at the usual time. You must then start the next pack immediately after taking the last tablet in the pack, ie skipping the tablet-free interval between the two packs. Withdrawal bleeding is unlikely after the second pack is finished, but there may be 'spotting' or loss of control bleeding on the days you take the tablets.
2. You can also stop taking the tablets from the current pack. In this case, you must go straight to the tablet-free period of up to 7 days including those when you have forgotten your tablets, and then continue with the next pack. If you want to start a new pack on the usual day of the week, you can choose a tablet-free period of less than 7 days.

If you have forgotten to take your tablets, and do not have withdrawal bleeding during the normal tablet-free interval, the possibility of pregnancy should be considered. In this case, you should speak to your doctor before starting the next pack.

What to do if you have stomach problems

If you have vomited or had diarrhea within 3-4 hours of taking the pill, the active substances in the pill may not be fully absorbed by your body. In this case, the advice on forgotten pills described above should be followed. another pill as soon as possible, no later than 12 hours. If it has been more than 12 hours, please follow the instructions under "If you forget to take Novadien".

What to do if you want to delay your period

If you want to delay your period, you must continue with the next pack of Novadien, after taking the last tablet of the current pack, skipping the pill-free period. From this second pack you can take as many pills as you like, up to the end of the second pack. blister. While using the second pack, you may experience withdrawal bleeding or blood spots (spotting). Regular intake of Novadien is resumed after the usual 7-day tablet-free interval.

What to do if you want to move the cycle

If you take Novadien correctly, you will always have your monthly cycle every 4 weeks on the same day of the week. If you want to shift your period to another day of the week instead of what you are used to with your current pill, you can shorten (but not lengthen) your next pill-free interval by as many days as you like. For example, if your monthly cycle usually starts on a Friday, and you want it to start on a Tuesday (ie three days earlier), you must start the next pack of Novadien three days earlier. The shorter the pill-free interval, the greater the chance that you will not have withdrawal bleeding and may have loss of control bleeding or blood stains during the second pack.

If you miss a cycle

If you have taken all the pills correctly, and have not had stomach problems, or have not used any other medicines, then it is unlikely that you are pregnant. Continue to take Novadien as usual.

If you have missed two consecutive cycles then you may be pregnant and you should see your doctor immediately. You are only allowed to continue taking the pill after taking the pregnancy test and on the advice of your doctor.

If you want to stop taking Novadien

You can stop taking Novadien at any time. If you do not want to get pregnant, ask your doctor to recommend other reliable methods of contraception.

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

Side Effects What are the side effects of Novadien

Like all medicines, Novadien can cause side effects, although not everybody gets them.

If you have any unwanted effects, especially if they are severe or persistent, or if there is any change in your health that you think may be due to Novadien, please tell your doctor.

An increased risk of developing blood clots in the veins (venous thromboembolism (VTE)) or blood clots in the arteries (arterial thromboembolism (ATE)) is present in all women taking combined hormonal contraceptives. For more detailed information on the different risks from "taking combined hormonal contraceptives, see section 2" What you need to know before you take Novadien ".

The following undesirable effects were observed in clinical trials with medicinal products containing 2 mg dienogest and 0.03 mg ethinylestradiol.

Common side effects (may affect up to 1 in 10 people):

• headache
• chest pain including breast discomfort and tenderness

Uncommon side effects (may affect up to 1 in 100 people):

• inflammation of the genitals (vaginitis / vulvovaginitis), fungal infections of the vagina (candidiasis, vulvovaginal infections)
• increased appetite
• depressed mood
• dizziness
• migraine
• low or high blood pressure
• abdominal pain (including pain in the upper and lower quadrant of the abdomen, discomfort / gon hours)
• nausea, vomiting or diarrhea
• acne
• hair loss (alopecia)
• skin rash (including spotted skin rash)
• itching (in some cases all over the body)
• irregular withdrawal bleeds including heavy bleeding (menorrhagia), weak bleeding (hypomenorrhea), rare bleeding (oligomenorrhea) and no withdrawal bleeding (amenorrhea)
• bleeding between periods (vaginal bleeding and metrorrhagia)
• menstrual pain (dysmenorrhea), pelvic pain
• breast enlargement including breast swelling, breast edema
• vaginal discharge
• ovarian cysts
• extreme exhaustion including weakness, fatigue and general indisposition
• weight changes (increase, decrease or use)

Rare side effects (may affect up to 1 in 1000 people):

• inflammation of the tube of the uterus or ovary
• inflammation of the cervix (cervicitis)
• inflammation of the urinary tract, in ammation of the bladder (cystitis)
• breast inflammation (mastitis)
• fungal infections (e.g. candida), viral infections, cold sores
• fever (flu), bronchitis, upper respiratory tract infections, paranasal infection (sinusitis)
• asthma
• increased breathing rate (hyperventilation)
• benign proliferation in the uterus (myoma)
• benign proliferation in fatty breast tissue (breast lipoma)
• anemia
• allergic reactions (hypersensitivity)
• masculinization (virilism)
• loss of appetite (anorexia)
• depression, mood swings, irritability, aggression
• drowsiness, sleep disturbances
• circulatory disorders of the brain or heart, stroke
• dystonia (muscle disorder causing e.g. abnormal posture)
• dry or sore eyes
• visual disturbances
• sudden deafness (hearing loss), impaired sense of hearing
• tinnitus
• vestibular disorders
• accelerated heart rate
• thrombosis, pulmonary embolism
• inflammation of the veins (thrombus and bitis)
• varicose veins (varicosis), discomfort or pain in the veins
• increased diastolic blood pressure (lower blood pressure value)
• dizziness or fainting when rising from a sitting or lying position (orthostatic dysregulation)
• hot flashes
• inflammation of the gastric mucosa (gastritis), in intestinal inflammation (enteritis)
• stomach upset (dyspepsia)
• skin reactions / disorders, including allergic reactions, neurodermatitis / atopic dermatitis, eczema, psoriasis
• strong perspiration
• brown and gold pigment spots (called pregnancy spots), particularly on the face (chloasma), pigmentation disorders / increased pigmentation
• oily skin (seborrhea)
• dandruff
• excess body hair (hirsutism)
• orange peel skin (cellulite)
• star nevus (a central red spot and reddish extensions that radiate outward like a spider's web)
• back pain, chest pain
• discomfort in the bones and muscles, muscle pain (myalgia), pain in the arms and legs
• cervical dysplasia (abnormal growth of cells on the surface of the uterine cervix)
• pain or cyst in the uterus tube and ovaries
• cysts in the breasts, benign growths in the breasts (brocystic mastopathy), congenital additional mammary gland swelling outside the breast (accessory breast)
• pain during intercourse
• secretion from the mammary glands, mammary secretion
• menstrual disturbances
• peripheral edema (accumulation of fluid in the body)
• flu-like illness, in admissions, pyrexia (fever)
• increased levels of triglycerides or cholesterol in the blood (hypertriglyceridaemia, hypercholesterolemia)
• Harmful blood clots in a vein or artery, for example: o in a leg or foot (DVT) or lung (PE), or heart attack, or stroke, or mini-stroke or temporary symptoms similar to those of stroke, known as transient ischemic attack (TIA) or blood clots in the liver, stomach / intestines, kidneys or eye.

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

Other side effects observed in pill users but whose exact frequency is unknown: increased or decreased sexual desire (libido), contact lens incompatibility, hives, erythema nodosum or multiforme.

If you suffer from hereditary angioedema, estrogen-containing medicines can induce or exacerbate angioedema disorders (see section 2 "Warnings and precautions").

The following side effects have been reported in women using combination oral contraceptives and are discussed under "Warnings and precautions":

• blood clots
• high blood pressure
• liver tumors
• brown spots on the face and body (chloasma).

The frequency of breast cancer diagnoses is very slightly increased among oral contraceptive users. Since breast cancer is rare in women under 40, the excess number is small in relation to the overall risk of breast cancer.

For more information, see the sections "Do not take Novadien" and "Warnings and precautions".

Reporting of side effects

If you get any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. Undesirable effects can also be reported directly via the national reporting system at "www.agenziafarmaco.gov.it/it/responsabili". By reporting side effects you can help provide more information on the safety of this medicine. .

Expiry and Retention

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date. The expiry date refers to the last day of that month.

Store in the original package to protect the medicine from light. Store below 30 ° C.

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Composition and pharmaceutical form

What Novadien contains

• The active ingredients are dienogest and ethinyl estradiol.

Each tablet contains: 2 mg of dienogest and 0.03 mg of ethinylestradiol.

• The other ingredients are:

Tablet core:

Lactose monohydrate Maize starch

Povidone 30 K

Sodium starch glycolate

Magnesium stearate

Purified water

Coating:

Hypromellose

Hydroxypropylcellulose

Talc

Hydrogenated cottonseed oil

Titanium dioxide (E171)

What Novadien looks like and contents of the pack

White, round, biconvex, film-coated tablets.

Novadien 2 mg / 0.03 mg film-coated tablets are packed in PVC / PVDC / Aluminum blisters of 21 tablets.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Novadien can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction 04.6 Pregnancy and lactation 04.7 Effects on ability to drive and use machines 04.8 Undesirable effects 04.9 Overdose 05.0 PHARMACOLOGICAL PROPERTIES 05.1 Pharmacodynamic properties 05.2 Pharmacokinetic properties 05.3 Preclinical safety data 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the primary packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER CIO 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

NOVADIEN 2 MG / 0.03 MG TABLETS COATED WITH FILM

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

One film-coated tablet contains 2 mg of dienogest and 0.03 mg of ethinylestradiol.

Excipient:

Each film-coated tablet contains 57.17 mg of lactose monohydrate.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Film-coated tablet.

Appearance: White, rounded, biconvex coated tablet.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Oral contraception.

The decision to prescribe Novadien should take into account the individual woman's current risk factors, particularly those related to venous thromboembolism (VTE) and the comparison between the risk of VTE associated with Novadien and that associated with other Combined Hormonal Contraceptives (COCs). (see sections 4.3 and 4.4).

04.2 Posology and method of administration

Dosage

How to take Novadien

The tablets should be taken every day at about the same time, if necessary with a little liquid, according to the order indicated on the blister pack. Each tablet should be taken daily for 21 consecutive days. Each subsequent pack will be started after an interval 7 tablet-free days, during which withdrawal bleeding usually occurs. This usually starts on the second or third day after the last tablet and may not have stopped before the next pack is started.

How to start taking Novadien

In case of no previous use of a hormonal contraceptive (during the last month)

The use of Novadien should start on the first day of the woman's natural cycle (ie the first day of her menstruation). If taken correctly, contraceptive protection is achieved from the first day of taking the tablet. If taking the tablet is started between the second and fifth day, an additional non-hormonal method of contraception (barrier method) should be used during the first seven days of tablet-taking.

When changing from another combination hormonal contraceptive method (combination oral contraceptive, vaginal ring, transdermal patch)

The woman should start taking Novadien preferably the day after taking the last active tablet (the last tablet containing the active substances) of her previous combination oral contraceptive, but at the latest the following day at the usual tablet-free free interval. or with placebo from your previous combination oral contraceptive.

In case of use of a vaginal ring or transdermal patch, the woman should start using Novadien preferably on the day of removal, but at the latest when the next application should have taken place.

If you change from a progesterone-only method of contraception (progesterone-only pill, injection, implant, or progesterone-releasing intrauterine device (IUS))

If you have previously taken the mini-pill, the change can be made on any day of the week; the transition from an implant or an IUS must be done on the day of removal; switching from an injectable contraceptive must be done on the day the next injection would be given. In all these cases, the additional use of a non-hormonal method of contraception (barrier method) is required for the first 7 days of taking Novadien.

After a first trimester abortion

The woman can start therapy immediately; in doing so, you do not need to take additional contraceptive measures.

After childbirth or after an abortion in the second trimester

Women should be advised to start using Novadien between 21 and 28 days after delivery or second trimester abortion. If starting later, the woman should be advised to use an additional barrier method for the first few. However, if she has already had sexual intercourse, pregnancy must be ruled out before the actual start of use of the combination oral contraceptive or the patient must wait for her first menstrual period.

Use of Novadien in women who are breastfeeding

For lactation see section 4.6.

Management of forgotten tablets

If she is less than 12 hours late in taking any tablet, contraceptive protection is not reduced. The patient should take the tablet as soon as she remembers and should take the following tablets at the usual time.

If you are more than 12 hours late in taking any tablet, contraceptive protection may be reduced. The management of missed tablets can follow the following two basic rules:

• tablet-taking must never be interrupted for more than 7 days;

• 7 days of uninterrupted tablet-taking is required to achieve adequate suppression of the hypothalamic-pituitary-ovarian axis.

Consequently, the following can be recommended in daily practice:

Week 1

The patient should take the last missed tablet as soon as she remembers, even if this will involve taking two tablets at the same time. She will then continue to take the tablets at the usual time. In addition, you must use a barrier method such as a condom for the following 7 days. If there has been intercourse within the previous 7 days, the possibility of pregnancy should be considered. The more tablets are forgotten and the closer they are to the tablet-free interval, the greater the risk of pregnancy.

Week 2

The patient should take the last missed tablet as soon as she remembers, even if this will involve taking two tablets at the same time. She will then continue to take the tablets at the usual time. Provided the patient has taken her tablets correctly in the 7 days preceding the first missed tablet, there is no need to use additional birth control precautions. However, if more than one tablet has been forgotten, additional precautions will need to be taken for 7 days.

Week 3

The risk of decreased reliability is considerable due to the upcoming 7-day tablet-free interval. However, by changing the tablet-taking schedule, the reduction in contraceptive protection can still be prevented.

By adhering to one of the following two options, therefore, there is no need to resort to additional contraceptive precautions, provided that in the 7 days preceding the first forgetfulness the patient has taken all the tablets correctly. If not, you should follow the first of these two options and take additional precautions for the next 7 days as well.

The patient should take the last missed tablet as soon as she remembers, even if this will involve taking two tablets at the same time. She will then continue to take the tablets at the usual time. The next blister pack should be started as soon as the one in use ends, i.e. with no gap between the two packs. The patient is unlikely to have a withdrawal period before completion of the second pack, however she may experience some spotting or breakthrough bleeding on tablet-taking days.

The patient can also stop taking the tablets from the current blister pack. She should then have a tablet-free interval of up to 7 days, including the days when she forgot tablets, and then continue with the next blister pack.

If the patient forgets the tablets and subsequently does not experience withdrawal bleeding during the first tablet-free interval, the possibility of pregnancy should be considered.

Warnings in case of gastro-intestinal disorders

If vomiting or severe diarrhea occurs within 3-4 hours after taking the film-coated tablet, absorption may not be complete and additional contraceptive measures should be taken.

In these cases, a new (replacement) tablet should be taken as soon as possible. If possible, the new tablet should be taken within 12 hours of the usual time of tablet taking. If more than 12 hours have passed, the warning regarding missed tablets as described in section 4.2 "Handling of missed tablets" applies. . If the woman does not wish to change her normal tablet-taking schedule, she must take the extra tablet (s) from another blister pack.

How to postpone a withdrawal bleed

To delay a period the woman should continue with another blister pack of Novadien avoiding the tablet-free interval. The duration of the delay can be extended as desired until the tablets from the second pack are completely used. During the duration of the delay the woman may experience breakthrough bleeding or the appearance of spotting. The regular intake of Novadien will then be resumed after the usual 7-day tablet-free interval.

To shift her period to a different day of the week than the woman is used to according to her current schedule, she may be advised to shorten the tablet-free interval by as many days as she wishes. The shorter the interval, the higher is the likelihood that you will not have a withdrawal bleed but instead experience breakthrough bleeding and spotting during the next pack (just like when you delay a period).

04.3 Contraindications

Combined hormonal contraceptives (COCs) should not be used in the following conditions. If any of these conditions occurs for the first time while using the combination oral contraceptive, the product should be discontinued immediately.

Novadien should not be used in any of the following cases:

• Presence or risk of venous thromboembolism (VTE)

• Venous thromboembolism - current (with anticoagulant intake) or previous VTE (eg deep vein thrombosis [DVT] or pulmonary embolism [PE])

• Known hereditary or acquired predisposition to venous thromboembolism, such as resistance to activated protein C (including Factor V Leiden), antithrombin III deficiency, protein C deficiency, protein S deficiency

• Major surgery with prolonged immobilization (see section 4.4)

• High risk of venous thromboembolism due to the presence of multiple risk factors (see section 4.4)

• Presence or risk of arterial thromboembolism (ATE)

• Current or previous arterial thromboembolism-arterial thromboembolism (eg myocardial infarction) or prodromal conditions (eg angina pectoris)

• Cerebrovascular disease-current or previous stroke or prodromal conditions (eg transient ischemic attack (transient ischaemic attack, TIA))

• Known hereditary or acquired predisposition to arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant)

• History of migraine with focal neurological symptoms

• A high risk of arterial thromboembolism due to the presence of multiple risk factors (see section 4.4) or the presence of a serious risk factor such as:

- diabetes mellitus with vascular symptoms

- severe hypertension

- severe dyslipoproteinemia

• Smoking (see section 4.4);

• Severe liver disease present or in history until the values ​​of liver function tests have returned to normal;

• Liver tumors (benign or malignant) present or in history;

• Known or suspected sex steroid-related cancers (eg of the genital organs or breasts);

• Undiagnosed vaginal bleeding;

• current or previous ancreatitis if associated with severe hypertriglyceridaemia;

• Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

[1] Median value of the range 5-7 per 10,000 women-years, based on a relative risk of approximately 2.3-3.6 of levonorgestrel-containing COCs compared with non-use.

04.4 Special warnings and appropriate precautions for use

Warnings

If any of the conditions or risk factors mentioned below are present, the suitability of Novadien should be discussed with the woman.

In the event of worsening or first appearance of any of these risk factors or conditions, the woman should contact her physician to determine whether the use of Novadien should be discontinued.

Circulation disturbances

Risk of venous thromboembolism (VTE)

The use of any combined hormonal contraceptive (COC) results in an increased risk of venous thromboembolism (VTE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with a lower risk of VTE. It is not yet known in how the risk associated with Novadien compares with these lower risk products. The decision to use a product other than those associated with a lower risk of VTE should only be made after discussions with the woman to ensure that she understands the risk of VTE associated with CHCs, how its current risk factors affect that risk, and the fact that the risk of developing a VTE is highest in the first year of use. There is also some evidence that the risk increases when taking of a COC is resumed after a break of 4 or more weeks.

About 2 in 10,000 women who do not use a CHC and who are not pregnant will develop a VTE over a period of one year. In a single woman, however, the risk can be much higher, depending on her underlying risk factors (see below).

Epidemiological studies in women using low-dose COCs (1 will develop a VTE in one year. Limited epidemiological data suggest that the risk of VTE associated with dienogest-containing CHCs may be similar to the risk associated with levonorgestrel-containing CHCs.

The number of VTEs per year is less than the number expected in pregnancy or in the postpartum period. VTE can be fatal in 1 to 2% of cases.

Very rarely, thrombosis has been reported in CHC users in other blood vessels, e.g. hepatic, mesenteric, renal or retinal veins and arteries.

Risk factors for VTE

The risk of venous thromboembolic complications in CHC users may increase substantially if additional risk factors are present, especially if there are more than one risk factors (see table).

Novadien is contraindicated if a woman has several risk factors that increase her risk of venous thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the increased risk is greater than the sum of the individual factors; in this case her total risk of VTE should be considered. If the benefit-risk ratio is considered to be negative, a COC should not be prescribed (see section 4.3).

Table: Risk factors for VTE

Risk factor Comment Obesity (body mass index (BMI) above 30 kg / m2) The risk increases considerably as the BMI increases. Especially important to consider if other risk factors are also present. Prolonged immobilization, major surgery, any type of leg and pelvis surgery, neurosurgery, or major trauma In these situations it is advisable to stop using the patch / pill / ring (in case of elective surgery at least four weeks earlier) and not restart it until two weeks after complete resumption of mobility. To avoid unwanted pregnancy, another method of contraception must be used. Note: Temporary restraint, including air travel lasting> 4 hours, can also be a risk factor for VTE, especially in women with other risk factors If Novadien has not been discontinued earlier, antithrombotic treatment should be considered. Positive family history (venous thromboembolism in a sibling or parent, especially at a relatively young age, i.e. before age 50) If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding to take any COCs. Other medical conditions associated with VTE Cancer, systemic lupus erythematosus, haemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia. Old age Particularly above the age of 35

There is no agreement on the possible role of varicose veins and superficial thrombophlebitis in the onset and progression of venous thrombosis.

The increased risk of thromboembolism in pregnancy, particularly the 6-week period of the puerperium, must be considered (for information on "Pregnancy and lactation" see section 4.6).

Symptoms of VTE (deep vein thrombosis and pulmonary embolism)

If symptoms of this type occur, women should seek immediate medical attention and inform them that they are taking a CHC.

Symptoms of deep vein thrombosis (DVT) can include:

- unilateral swelling of the leg and / or foot or along a vein in the leg;

- pain or tenderness in the leg which may only be felt when standing or walking;

- increased sensation of heat in the affected leg; skin on the leg that is red or discolored.

Symptoms of pulmonary embolism (PE) can include:

- sudden and unexplained onset of shortness of breath and rapid breathing;

- sudden cough which may be associated with hemoptysis;

- sharp pain in the chest;

- severe light headedness or dizziness;

- rapid or irregular heartbeat.

Some of these symptoms (such as "shortness of breath" and "cough") are non-specific and may be misinterpreted as more common or less serious events (eg respiratory tract infections).

Other signs of vascular occlusion may include: sudden pain, swelling or a pale blue discoloration of one "extremity.

If the occlusion takes place in the eye, symptoms can range from painless blurring of vision to loss of vision. Sometimes vision loss occurs almost immediately.

Risk of arterial thromboembolism (ATE)

Epidemiological studies have associated the use of CHCs with an increased risk of arterial thromboembolism (myocardial infarction) or of cerebrovascular accidents (eg transient ischemic attack, stroke). Arterial thromboembolic events can be fatal.

Risk factors of ATE

The risk of arterial thromboembolic complications or a cerebrovascular accident in CHC users increases in the presence of risk factors (see table). Novadien is contraindicated if a woman has one serious risk factor or multiple risk factors for ATE that increase her risk of arterial thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors; in this case her total risk should be considered. If the benefit-risk balance is believed to be negative, a CHC should not be prescribed (see section 4.3).

Table: Risk factors of ATE

Risk factor Comment Old age Particularly above the age of 35. Smoke Women should be advised not to smoke if they wish to use a CHC. Women over the age of 35 who continue to smoke should be strongly advised to use a different method of contraception. Hypertension Obesity (body mass index (BMI) above 30 kg / m2) The risk increases considerably as the BMI increases. Especially important in women with other risk factors. Positive family history (arterial thromboembolism in a sibling or parent, especially at a relatively young age, i.e. before age 50) If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding to take any COCs. Migraine An increase in migraine frequency or severity during CHC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation. Other medical conditions associated with adverse vascular events Diabetes mellitus, hyperhomocysteinemia, atrial valvulopathy and fibrillation, dyslipoproteinemia and systemic lupus erythematosus.

Symptoms of ATE

If symptoms of this type occur, women must contact a healthcare professional immediately and inform them that they are taking a CHC.

Symptoms of cerebrovascular accident can include:

- sudden numbness or weakness of the face, arm or leg, especially on one side of the body;

- sudden difficulty walking, dizziness, loss of balance or coordination;

- sudden confusion, difficulty in elocution or understanding;

- sudden difficulty seeing in one or both eyes;

- sudden, severe or prolonged migraine with no known cause;

- loss of consciousness or fainting with or without convulsions.

Temporary symptoms suggest it is a transient ischemic attack (TIA)

Symptoms of myocardial infarction (MI) can include:

- pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm or below the breastbone;

- discomfort radiating to the back, jaw, throat, arms, stomach;

- feeling of fullness, indigestion or choking;

- sweating, nausea, vomiting or dizziness;

- extreme weakness, anxiety or shortness of breath;

- rapid or irregular heartbeats.

The presence of a single serious risk factor or multiple risk factors for venous or arterial disease, respectively, is a contraindication. The possibility of implementing anticoagulant therapy should also be considered. Users of COCs should be specifically advised to contact their doctor in case of possible symptoms of thrombosis. In the event of a suspected or confirmed thrombosis, use of the oral contraceptive should be discontinued. An adequate contraceptive alternative should be initiated given the teratogenicity of anticoagulant therapy (coumarins).

Tumors

An increased risk of developing cervical cancer has been reported in some epidemiological studies in long-term use of combination oral contraceptives (> 5 years), but controversy continues as to how far this may be. related to the confounding effects of sexual behavior and other factors, such as human papilloma virus (HPV).

A meta-analysis from 54 epidemiological studies reported that there is a slight increased relative risk (RR = 1.24) of being diagnosed with breast cancer in women who normally use COCs. The increased risk gradually disappears over the course of 10 years after oral contraceptive use is discontinued. Since breast cancer is a rare event in women under 40 years of age, the over-number of breast cancer diagnosis in current and recent oral contraceptive users is small in relation to the overall risk of developing breast cancer.

In rare cases, benign liver tumors, and even more rarely, malignant liver tumors have been observed in women using COCs. In isolated cases, these tumors have produced life-threatening intra-abdominal haemorrhages. The presence of liver cancer should be considered as part of a differential diagnosis when severe pain in the upper abdominal quadrants, enlarged liver or signs of intra-abdominal haemorrhage occur in women taking an oral contraceptive.

Other pathologies

Women with hypertriglyceridaemia or for whom this is in a family history may be at increased risk of pancreatitis when using combination oral contraceptives.

Although modest increases in blood pressure have been reported in many women taking COCs, clinically significant increases are rare. An "immediate discontinuation" of the use of the oral contraceptive is justified only in these rare cases. If, during the use of an oral contraceptive in a previously hypertensive woman, constant high blood pressure values ​​or a significant increase in blood pressure do not respond adequately to antihypertensive treatment, the oral contraceptive should be discontinued. correct behavior, oral contraceptive use can be resumed if normal blood pressure values ​​can be achieved with antihypertensive therapy.

It has been noted that the following conditions may occur or worsen with both pregnancy and oral contraceptive use, but evidence of an association with oral contraceptive use is inconclusive: jaundice and / or itching due to cholestasis; gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea; herpes gravidarum; hearing loss related to otosclerosis. In women with hereditary angioedema, exogenous estrogens can induce or aggravate symptoms of angioedema.

Acute or chronic disturbances of liver function may require discontinuation of combination oral contraceptive use until liver function indices return to normal. A relapse of cholestatic jaundice and / or cholestasis-related pruritus that occurred in earlier in the course of a pregnancy or during previous use of sex steroids requires discontinuation of the combination oral contraceptive.

Although combination oral contraceptives may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for the need to change the treatment regimen in diabetics using combination oral contraceptives. However, diabetic women should be retained. under careful observation, particularly in the early stages of use of a combination oral contraceptive.

Worsening of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis has been reported during use of combination oral contraceptives.

Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet rays while using combined oral contraceptives.

Medical examination / visit

Before initiating or resuming use of Novadien, a complete medical history (including family history) must be taken and pregnancy must be ruled out. Blood pressure should be measured and clinical examination, guided by contraindications (see section 4.3) and warnings (see section 4.4) performed. It is important to draw a woman's attention to information relating to venous or arterial thrombosis, including the risk associated with Novadien compared to other CHCs, symptoms of VTE and ATE, known risk factors and what to do in the event of a suspected thrombosis. woman should also be advised of the need to read the package leaflet carefully and follow its advice Frequency and type of examinations should be based on established guidelines and should be adapted to the individual woman.

Women should be advised that hormonal contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases.

Reduction of effectiveness

The efficacy of contraceptives may be reduced if, for example, tablets are forgotten (see section 4.2), if gastrointestinal disturbances occur (see section 4.2) or during concomitant therapy (see section 4.5).

Reduction of cycle control

With all combination oral contraceptives, irregular bleeding (appearance of blood spots or breakthrough bleeding) may occur, especially during the first months of use. Therefore, the evaluation of irregular bleeding only makes sense after a period of adaptation. about three cycles.

If irregular bleeding persists or occurs after regular previous cycles, then non-hormonal causes must be considered and adequate diagnostic investigations are indicated to rule out malignancy or pregnancy. Among them there may also be scraping.

In some women, withdrawal bleeding may not occur during the tablet-free interval. If the oral contraceptive has been taken according to the directions described in section 4.2, it is unlikely that the woman is pregnant. However, if the contraceptive was not taken according to these directions before the first missed withdrawal bleed or if the latter did not occur twice in a row, pregnancy must be ruled out before continuing use of the combination oral contraceptive.

Interactions with other medicinal products that increase the clearance of sex steroids may cause breakthrough bleeding and reduced contraceptive efficacy (see section 4.5).

Herbal medicinal specialties containing St. John's wort ( Hypericum perforatum) should not be taken concomitantly with Novadien due to the plasma-lowering effect and clinical efficacy of the enogest-ethinylestradiol combination (see section 4.5).

This medicinal product contains 57.17 mg of lactose monohydrate per tablet.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

04.5 Interactions with other medicinal products and other forms of interaction

Interactions with other medicines

Interactions between oral contraceptives and other medicinal products can lead to breakthrough bleeding and / or contraceptive failure. The following interactions have been reported in the literature.

The following active ingredients can reduce the serum concentration of the sex steroids contained in Novadien:

- all medicinal products that increase gastrointestinal motility, eg. metaclopramide;

- active ingredients that induce microsomal enzymes in the liver, eg. rifampicin, rifabutin, barbiturates, antiepileptic medicines (such as barbexaclone, carbamazepine, oxcarbazepine, phenytoin, primidone, topiramate and felbamate), griseofulvin, modafinil, St. John's wort (Hypericum perforatum); both HIV protease inhibitors (eg ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg nevirapine) have been reported to affect hepatic metabolism;

- some antibiotics (e.g. ampicillin, tetracycline) in some women, possibly due to reduced enterohepatic circulation of estrogens.

Women on short-term treatment (up to 1 week) with any of the drug classes listed above or with the individual active substances must temporarily use a barrier method in addition to the combination oral contraceptive or during administration of the concomitant drug and for 7 days. after its suspension.

For women being treated with rifampicin, a barrier method in addition to the combination oral contraceptive should be used for the duration of rifampicin administration and for 28 days after its discontinuation. If concomitant drug administration proceeds beyond the end of the tablets in the combination oral contraceptive blister pack, the next oral contraceptive pack should be started without the usual tablet-free interval.

In women on long-term treatment with active substances that induce liver enzymes, another reliable non-hormonal method of contraception is recommended.

The following active ingredients can increase the serum concentration of the sex steroids contained in Novadien:

- active substances which inhibit the sulfation of ethinylestradiol in the gastrointestinal wall, eg ascorbic acid or paracetamol;

- atorvastatin (AUC of ethinylestradiol increased by 20%);

- active substances that inhibit microsomal enzymes in the liver, such as antifungal imidazoles (e.g. fluconazole), indinavir and troleandomycin.

Based on inhibition studies in vitro, dienogest does not inhibit the cytochrome P450 enzyme within the applied concentration, therefore no interactions with this medicinal product are expected.

Oral contraceptives can affect the metabolism of other active ingredients. Therefore, plasma and tissue concentrations may increase (e.g. cyclosporine, diazepam and some other benzodiazepines, theophylline, glucocorticoids) or decrease (e.g. lamotrigine, chlorofibrate, paracetamol, morphine, lorazepam and other benzodiazepines).

Laboratory tests

The use of contraceptive steroids can affect the results of some laboratory tests, including biochemical parameters of the liver, thyroid and renal and adrenal function, plasma levels of proteins (with transport functions), such as globulin at which corticosteroids and lipid / lipoprotein fractions, the parameters of carbohydrate metabolism and the parameters of coagulation and fibrinolysis are bound.The variations generally remain within the normal reference values.

04.6 Pregnancy and lactation

Pregnancy

Novadien is not indicated during pregnancy.

If pregnancy occurs during use of Novadien, the preparation should be discontinued immediately. Extensive epidemiological studies have shown no increased risk of birth defects in children born to women who used a combination oral contraceptive before pregnancy. nor a teratogenic effect when the oral contraceptive was taken inadvertently during pregnancy These studies did not include Novadien.

The available data on the use of Novadien during pregnancy are too limited to allow any conclusion on the adverse effects of Novadien on pregnancy and the health of the fetus or newborn. To date, no relevant epidemiological data are available.

Studies in animals have shown undesirable effects during pregnancy and lactation (see section 5.3). Effects in humans are not known; however, general experience with COCs during pregnancy does not document that such side effects actually occur in humans.

The increased risk of thromboembolism in the postpartum period should be taken into account when Novadien is restarted (see sections 4.2 and 4.4).

Feeding time

Breastfeeding can be influenced by combination oral contraceptives, as they can reduce the amount of breast milk and alter its composition. Small amounts of contraceptive steroids and / or their metabolites may be excreted with milk during use of oral contraceptives. Association. These quantities can have an effect on the baby. Therefore, Novadien should not be used during breastfeeding.

04.7 Effects on ability to drive and use machines

Novadien does not affect the ability to drive or use machines.

04.8 Undesirable effects

For serious undesirable effects in users of COCs, see section 4.4.

The frequencies of undesirable effects during the use of 2 mg dienogest and 0.03 mg ethinyl estradiol for oral contraception and for the treatment of moderately severe acne in clinical trials (N = 4,942) are summarized in the following table.

The frequency rates of undesirable effects are based on the following categories:

• Very common (≥1 / 10)

• Common (≥1 / 100,

• Uncommon (≥1 / 1000,

• Rare (≥1 / 10,000,

• Very rare (

• Not known (frequency cannot be estimated from the available data)

Within each frequency group, undesirable effects are presented in descending order of severity.

System and organ classification common Uncommon Rare Not known Infections and infestations Vaginitis / vulvovaginitis Vaginal candidiasis or vulvovaginal fungal infections Salpingo-oophoritis, urinary tract infection, cystitis, mastitis, cervicitis, fungal infections, candidiasis, oral herpes, influenza, bronchitis, sinusitis, upper respiratory tract infections, viral infections Neoplasms benign, malignant and unspecified (including cysts and polyps) Uterine leiomyoma, breast lipoma Disorders of the blood and lymphatic system Anemia Disorders of the immune system Hypersensitivity Endocrine pathologies Virilism Metabolism and nutrition disorders Increased appetite Anorexia Psychiatric disorders Depressed mood Depression, mental disorders, insomnia, sleep disturbances, aggression Changes in mood, increased or decreased libido Nervous system disorders Headache Dizziness, migraine Ischemic stroke, cerebrovascular disorders, dystonia Eye disorders Dry eyes, sore eyes, oscillopsia, deterioration of vision Contact lens intolerance Ear and labyrinth disorders Loss of hearing, tinnitus, dizziness, deterioration of the ability to hear Cardiac pathologies Cardiovascular disorders, tachycardia 1 Vascular pathologies Hypertension, hypotension Venous thromboembolism, arterial thromboembolism, thrombophlebitis, pulmonary embolism diastolic hypertension, orthostatic dysregulation, hot flashes, varicose veins, vein discomfort, vein pain Respiratory, thoracic and mediastinal disorders Asthma, hyperventilation Gastrointestinal disorders Abdominal pain2, nausea, vomiting, diarrhea Gastritis, enteritis, dyspepsia Skin and subcutaneous tissue disorders Acne, alopecia, skin rash3, pruritus4 Allergic dermatitis, atopic dermatitis / neurodermatitis, eczema, psoriasis, hyperhidrosis, chloasma, pigment changes / hyper-pigmentation, seborrhea, dandruff, hirsutism, skin changes, skin reactions, orange peel skin, star nevus Urticaria, erythema nodosum, erythema multiforme Musculoskeletal and connective tissue disorders Back pain, musculoskeletal disorders, myalgia, pain in extremities Diseases of the reproductive system and breast Breast pain 5 Irregular withdrawal bleeding6, breakthrough bleeding7, breast enlargement8, breast edema, dysmenorrhea, vaginal discharge, ovarian cyst, pelvic pain Cervical dysplasia, adnexal cyst, uterine adnexal pain, breast cyst, fibrocystic mastopathy, dyspareunia, galactorrhea, menstrual disorders Breast discharge Congenital, familial and genetic disorders Accessory breast General disorders and administration site conditions Fatigue 9 Chest pain, peripheral edema, flu-like illness, inflammation, pyrexia, irritability Fluid retention Diagnostic tests Weight changes 10 Increase in blood triglyceride levels, hypercholesterolemia

1 including accelerated heart rate

2 including upper and lower abdominal quadrant pain, abdominal discomfort / swelling

3 including macular rash

4 including generalized itching

5 including breast discomfort and breast tenderness

6 including menorrhagia, hypomenorrhea, oligomenorrhea and amenorrhea

7 consisting of vaginal bleeding and metrorrhagia

8 including breast swelling / swelling

9 including asthenia and general indisposition

10 including weight gain, weight reduction and fluctuation

Description of some adverse reactions

An increased risk of arterial and venous thrombotic and thrombotic events, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism has been observed in CHC users and this risk is discussed in more detail in section 4.4.

The following side effects have been reported in women using COCs, which are also discussed in section 4.4:

• hypertension;

• liver tumors;

• appearance or worsening of conditions for which the association with COCs has not been conclusive: Crohn's disease, ulcerative colitis, porphyria, systemic lupus erythematosus, gestational herpes, Sydenham's chorea, hemolytic uremic syndrome, cholestatic jaundice;

• chloasma.

The frequency of breast cancer diagnosis is slightly increased among women using oral contraceptives. Since breast cancer is rare under the age of 40, the excess number is small compared to the overall risk of breast cancer.

For further information, see sections 4.3 and 4.4.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national pharmacovigilance system to "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

04.9 Overdose

The acute oral toxicity of overdose with ethinylestradiol and dienogest is low. With multiple intakes of Novadien the likelihood of toxic symptoms is low even in children.

Symptoms that are likely to occur in these cases are: nausea, vomiting and, in young girls, mild vaginal bleeding. In general, no specific treatment is necessary; if necessary, treatment should be symptomatic.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: progestogens and estrogens, fixed combinations

ATC code: G03AA16

Novadien is a combination oral contraceptive with antiandrogenic effect containing ethinyl estradiol as estrogen and dienogest as progestin.

Mechanism of action

The contraceptive effect of Novadien is based on the interaction of various factors; the most important of which are considered the inhibition of ovulation and the alteration of the endometrium.

Dienogest is a derivative of norethisterone, with a 10-30 times lower affinity for the progestin receptor in vitro compared to other synthetic progestogens. In vivo dienogest has no significant androgenic, mineralocorticoid or glucocorticoid effects.

On its own, dienogest inhibits ovulation at a dose of 1 mg / day.

05.2 Pharmacokinetic properties

Ethinylestradiol (0.03 mg)

Absorption

Ethinylestradiol is rapidly and completely absorbed after ingestion. After ingestion of the product, peak plasma concentrations of 67 pg / ml are reached within 1.5 - 4 hours after ingestion. Ethinylestradiol undergoes extensive first pass metabolism and is extensively metabolised. Absolute bioavailability is approximately 44%.

Distribution

Ethinylestradiol is highly, but not specifically bound to serum albumin (approximately 98%). Ethinylestradiol induces an increase in serum concentrations of sex hormone binding globulin (SHBG). The apparent volume of distribution of ethinylestradiol is 2.8-8.6 l / kg.

Biotransformation

Ethinylestradiol is subject to conjugation in the enteric mucosa and liver. The main metabolic pathway is represented by aromatic hydroxylation, but its metabolism also produces a broad spectrum of hydroxylated and methylated metabolites, which are found in free and conjugated form with glucuronides and sulphates. Clearance is approximately 2.3-7ml / min / kg.

Elimination

Plasma levels of ethinylestradiol decrease in 2 phases, with half-lives of 1 and 10-20 hours. Ethinylestradiol is not excreted unchanged in significant amounts. Ethinylestradiol metabolites are excreted with a urine / bile ratio of 4: 6. The half-life of metabolite excretion is approximately one day.

Steady state conditions

Steady state conditions are reached during the second half of the therapeutic cycle and serum levels of ethinylestradiol accumulate by a factor of approximately 2.

Dienogest

Absorption

Dienogest is rapidly and completely absorbed after oral administration. Peak plasma concentrations of 51 ng / mL are achieved within 2.5 hours. When administered with ethinylestradiol, the absolute bioavailability is 96%.

Distribution

Dienogest binds to serum albumin and does not bind to SHBG or corticosteroid-binding globulin (CBG). The fraction of free dienogest in plasma is 10%, while 90% does not bind specifically to albumin. Dienogest has an apparent volume of distribution of 37-45 l / kg.

Biotransformation

Dienogest is metabolised mainly via hydroxylation and alternatively via glucuronidation. Its metabolites are inactive and are rapidly eliminated from the plasma; therefore the metabolites cannot be detected in significant amounts in plasma except for unchanged dienogest. Total clearance after single dose administration (Cl / F) is 3.6 L / h.

Elimination

The half-life of dienogest is approximately 9 hours. The fraction of unchanged dienogest eliminated via the kidney is not significant. of about 3.2. After oral administration approximately 86% is eliminated within 6 days, 42% of which is eliminated within 24 hours, mainly in the urine.

Steady state conditions

The pharmacokinetics of dienogest are not affected by plasma SHBG levels. Serum levels of dienogest are accumulated by a factor of approximately 1.5 and steady state is reached within 4 days.

05.3 Preclinical safety data

In laboratory animals, the effects of dienogest and ethinylestradiol were limited to those associated with the recognized pharmacological action.

Reproductive toxicity studies have shown typical effects of progestogens, such as increased pre- and post-implantation abnormalities, prolongation of the gestational period, increased perinatal mortality in puppies. The fertility of the offspring was impaired after administration of high doses of dienogest during the last stage of pregnancy or breastfeeding.

Ethinylestradiol is the estrogenic component of most combination oral contraceptives. At high doses it has embryotoxic effects and has a negative influence on the development of the urogenital organs.

In addition to the above-mentioned factors, specific for the use of combination oral contraceptives in general, the results of conventional toxicity studies do not indicate particular risks of genotoxicity and carcinogenic potential in humans.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Core of the tablet:

Lactose monohydrate

Cornstarch

Povidone

Sodium starch glycolate

Magnesium stearate

Purified water

Coating:

Hypromellose

Hydroxypropylcellulose

Talc

Hydrogenated cottonseed oil

Titanium dioxide (E171)

06.2 Incompatibility

Not relevant.

06.3 Period of validity

3 years

06.4 Special precautions for storage

Store in the original package to protect the medicine from light. Store below 30 ° C.

06.5 Nature of the immediate packaging and contents of the package

PVC / PVDC / Aluminum blisters

Packs of 21 and 63 tablets.

06.6 Instructions for use and handling

No special instructions.

Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.

07.0 MARKETING AUTHORIZATION HOLDER

FARMITALIA s.r.l.

Viale Alcide de Gasperi 165 / B

95127 Catania (Italy)

08.0 MARKETING AUTHORIZATION NUMBER

1 blister of 21 tablets: AIC n. 041390016

3 blisters of 21 tablets: AIC n. 041390028

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

April 2013

10.0 DATE OF REVISION OF THE TEXT

April 2014

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL