Active ingredients: Norelgestromin / Ethinylestradiol
EVRA transdermal patch 203 micrograms norelgestromin / 24 hours + 33.9 micrograms ethinylestradiol / 24 hours
Why is Evra used? What is it for?
EVRA contains two types of sex hormones, a progestin called norelgestromin and an estrogen called ethinyl estradiol.
Because it contains two hormones, EVRA is called a "combined hormonal contraceptive".
It is used to prevent pregnancy.
Contraindications When Evra should not be used
Before you start using EVRA 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").
Do not use EVRA:
Do not use EVRA 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 have to undergo an operation or if you will lie down for a long time;
- if you have ever had a heart attack or stroke;
- if you have (or have ever had) angina pectoris (a condition that causes severe chest pain and may be a first sign of a heart attack) or transient ischemic attack (TIA - temporary stroke symptoms);
- if you have any of the following diseases, which could increase the risk of blood 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 hyperhomocysteinemia
- if you have (or have ever had) a type of migraine called 'migraine with aura';
- if you are allergic to norelgestromin, ethinyl estradiol or any of the other ingredients of this medicine (listed in section 6)
- if you have been told that you may have cancer of the breast or uterus, cervix or vagina
- if you have ever had liver tumors or liver disease because your liver is not working properly
- if you have any unexplained vaginal bleeding. Do not use this medicine if you find yourself in any of the situations listed above. If you are not sure, ask your doctor, pharmacist or nurse before using this medicine.
When to take special care with EVRA
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 clot (thrombosis) ").
Precautions for use What you need to know before taking Evra
Before using this medicine you will need to go to your doctor for a consultation.
Tell your doctor if any of the following apply to you.
If this condition appears or worsens while you are using EVRA you should tell your doctor.
- if you have Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease); if you have systemic lupus erythematosus (SLE, a disease that affects 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) pancreatitis (inflammation of the pancreas);
- if you have to undergo an operation or if you will lie down for a long time;
- 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 [invented name];
- 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 EVRA 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 EVRA is low.
HOW TO RECOGNIZE A BLOOD CLOT
See a doctor immediately if you notice any of the following signs or symptoms.
- 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 pain in the stomach
- 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
- 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.
- swelling and pale blue discoloration of one extremity;
- severe stomach pain (acute abdomen)
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 EVRA 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 EVRA is low.
- Out of 10,000 women who are not using any combined hormonal contraceptive and 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 that contains etonorgestrel or norelgestromin, such as EVRA, about 6-12 will develop a blood clot in a year.
- The risk of a blood clot forming depends on your medical history
Risk of developing a blood clot in one year
Women who are not using a combined hormone pill / patch / ring 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 EVRA
About 6-12 out of 10,000 women
Factors that increase the risk of developing a blood clot in a vein
The risk of developing a blood clot with EVRA is low but some conditions cause it to increase. 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 EVRA a few weeks before surgery or during the period where you are less mobile. If you have to stop taking EVRA, 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 EVRA should be stopped.
Tell your doctor if any of the above conditions change while you are using EVRA, for example if a close relative has a thrombosis for no known reason or if you gain a lot of weight.
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 EVRA is very low but can increase:
- with increasing age (over 35 years);
- if you smoke. When using a combined hormonal contraceptive such as EVRA 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.
Tell your doctor if any of the above conditions change while you are using EVRA, 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.
In addition, talk to your doctor, pharmacist or nurse before using EVRA if you have any of the following conditions, or if these conditions develop or get worse: if you think you are pregnant
- if you have headaches that get worse or come more often
- if you weigh 90 kg or more
- if you have high blood pressure or blood pressure which tends to rise
- if you have gallbladder disease including gallstones or inflammation of the gallbladder
- if you have a blood disorder called "porphyria"
- if you have a nervous system disease that causes sudden body movements called "Sydenham's chorea"
- if you had a "blistered rash (called" gestational herpes ") during pregnancy
- if you have hearing loss
- if you have diabetes
- if you have depression
- if you have epilepsy or any other condition that can cause seizures
- if you have liver problems which include yellowing of the skin and whites of the eyes (jaundice)
- if you have or have had "pregnancy spots". These are yellow-brown spots, especially on the face (called "chloasma"). These spots may not go away completely after stopping EVRA. Protect your skin from sunlight or ultraviolet radiation. This can help prevent these spots from appearing or prevent them from getting worse
- if you have kidney problems.
If you are not sure if any of the above conditions apply to you, talk to your doctor or pharmacist before using EVRA.
Sexually transmitted diseases
This medicine will not protect you from HIV infection (AIDS) or any other sexually transmitted disease. These include chlamydia, genital herpes, warts acuminata, gonorrhea, hepatitis B, syphilis. Always use condoms to protect yourself from such diseases.
Clinical tests
If you need to have a blood or urine test, tell the doctor or the person collecting the biological sample that you are using EVRA, as hormonal contraceptives can affect some test results.
Children and adolescents
EVRA has not been studied in children and adolescents below 18 years of age. EVRA should not be used in children and adolescents who have not yet had their first menstrual period.
Interactions What drugs or foods can change the effect of Evra
Tell your doctor or pharmacist if you are taking, have recently taken or might use any other medicines.
Some medicines and herbal remedies can affect the effectiveness of EVRA. In this case you could become pregnant.
Tell your doctor if you are taking:
- some antiretroviral medicines used to treat HIV / AIDS (such as nelfinavir, ritonavir, nevirapine, efavirenz)
- medicines used to treat infections (such as rifampin, rifabutin and griseofulvin, penicillins and tetracyclines)
- medicines to treat seizures (some examples are topiramate, phenorbarbital, phenytoin, carbamazepine, primidone, oxycarbazepine, felbamate, eslicarbazepine acetate and rufinamide)
- fosaprepitant (a medicine to treat nausea)
- bosentan (a medicine to treat high blood pressure in the pulmonary arteries)
- St. John's wort (St. John's wort) (a herbal remedy used for depression). St. John's wort should not be taken when using EVRA.
If you take any of these medicines, you must also use an additional method of contraception (e.g. condom, diaphragm or spermicidal foam). The interfering effect of some of these medicines can last up to 28 days after you stop taking them. Ask your doctor or pharmacist about another method of contraception if you use EVRA concomitantly with any of the medicines listed above.
EVRA may decrease the effect of some medicines such as:
- medicines containing cyclosporine
- lamotrigine, a medicine used for epilepsy - this may increase the risk of fits (convulsions)
Your doctor may need to adjust the dose of other medicines. Ask your doctor or pharmacist for advice before taking any medicine.
Warnings It is important to know that:
Pregnancy and breastfeeding
- Do not use this medicine if you are pregnant or think you are pregnant
- Stop using this medicine right away if you are pregnant
- Do not use this medicine if you are breastfeeding or plan to breastfeed
If you are pregnant or planning to become pregnant, ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
You can drive and operate machinery while using this medicine.
Risks associated with the use of combined hormonal contraceptives
The following information is based on the information regarding combined contraceptive pills. Since the EVRA transdermal patch contains hormones similar to those used in combined contraceptive pills, it is likely to have the same risks as well. All combined contraceptive pills have risks that can cause disability or death.
A transdermal patch such as EVRA has not been proven to be safer than a combined hormonal contraceptive pill taken by mouth.
Combined hormonal contraceptives and cancer
Cancer of the cervix
Cervical cancer occurs more frequently in women taking combined hormonal contraceptives. However, this may be due to other causes, including sexually transmitted diseases.
Breast cancer
Women who use combined hormonal contraceptives have been observed to develop breast cancer more frequently than those who do not. However, it is possible that the combined hormonal contraceptive is not the cause of this. It may be that women taking combined hormonal contraceptives see their doctor more often. This could mean that there are more chances of diagnosing breast cancer. The increased risk of breast cancer gradually decreases once the use of combined hormonal contraceptives is stopped. After ten years, the chances of breast cancer are equal to those of women who have never used combined hormonal contraceptives.
Liver cancer
Rarely, non-cancerous cases and, even more rarely, cancerous cases of liver tumors have been reported in women using combined hormonal contraceptives. This type of tumor can cause internal bleeding, with severe abdominal pain. If this happens, contact your doctor immediately.
Dose, Method and Time of Administration How to use Evra: Posology
Always use this medicine exactly as your doctor or pharmacist has told you.
If she doesn't, she may be at a higher risk of becoming pregnant
If you are not sure, consult your doctor or pharmacist
Keep other non-hormonal contraceptives (such as condoms, foam or spermicidal sponges) as back-up methods in case you make mistakes while using the patch.
How many patches to use
Weeks 1, 2 and 3: Apply only one patch and keep it for exactly seven days
week 4: do not use the patch this week.
If you have not used a hormonal contraceptive during the previous cycle
You can start this medicine on the first day of your next cycle.
If one or more days have passed since the beginning of your period, talk to your doctor about temporarily using a non-hormonal contraceptive.
If you switch from the oral contraceptive pill to EVRA
If you are switching from an oral contraceptive pill to EVRA:
- wait for your period
- apply the first patch during the first 24 hours of your period.
If the patch is applied after Day 1 of your period:
You also use a non-hormonal contraceptive until Day 8, which is when you change your patch.If your period does not appear within 5 days of taking the last contraceptive pill, talk to your doctor before you start using this medicine.
If you switch from the progestogen-only pill, implant or injectable method to EVRA
- You can start this medicine any day after stopping the progestogen-only pill or the day the implant is removed or on the scheduled day for the next injection.
- Apply the patch on the first day after you stop using the progestogen-only pill, or after removing the implant or on the day of your next injection.
- Also use a non-hormonal contraceptive until Day 8, which is when you change your patch.
After a miscarriage or induced abortion before 20 weeks of pregnancy
- Talk to your doctor
- You can start this medicine right away
If one or more days have passed since the miscarriage or induced abortion when you start this medicine, talk to your doctor about the temporary use of a non-hormonal contraceptive.
After a miscarriage or induced abortion after 20 weeks of pregnancy
- Talk to your doctor
- You may decide to start this medicine on Day 21 after induced abortion or miscarriage, or on the first day of your period, whichever comes first.
After giving birth
- Talk to your doctor
- If you have had a baby and you are not breast-feeding, you should not use this medicine for four weeks after giving birth
- If it starts more than four weeks after giving birth, use another non-hormonal contraceptive in addition to this medicine for the first 7 days
- If you have had sex after having a baby, wait for your first period or consult your doctor to make sure you are not pregnant before starting this medicine
If you are breastfeeding
- Talk to your doctor
- Do not use this medicine if you are breastfeeding (see section 2 pregnancy and lactation).
Important information to consider when using the patch
- You change EVRA on the same day each week. The patch is formulated to work over 7 days
- Never let more than 7 consecutive days go by without using the patch
- Only use one patch at a time
- Do not cut or tamper with the patch in any way
- Avoid applying the patch to skin that is red, irritated or has cuts
- The patch must adhere completely to the skin for it to work properly
- Press the patch firmly until its edges adhere well
- Do not use creams, oils, lotions, talcum powder or makeup on the skin where you are applying the patch, or near the patch you have applied. This, in fact, could lead to the detachment of the patch
- Do not apply a new patch to the exact same area of skin as the patch you just took off. Otherwise, there will be a greater chance of irritation.
- Check each day to make sure the patch has not come off.
- Do not stop using the patches, even if you have sex only infrequently.
HOW TO USE THE PATCH
If you are using EVRA for the first time, wait until you have your period.
- Apply the first patch during the first 24 hours of your period
- If the patch is applied after Day 1 of your period, you will need to use a non-hormonal method of contraception until Day 8, when you change the patch.
- The day you apply your first patch will be Day 1. The "Patch Change Day" will then be this same day, every week.
Choose a place on your body to apply the patch to.
- Always apply the patch to clean, dry and hairless skin
- Apply the patch to your buttocks, abdomen, outer upper arm or upper back where it will not be rubbed by tight clothing.
- Never put the patch on your breasts.
Using your fingers, open the foil sachet.
- Open it by tearing it along the edge (do not use scissors)
- Now take one corner of the patch firmly and gently remove it from the patch sachet
- Sometimes the patches can stick to the inside of the sachet: be careful not to accidentally peel off the cling film while removing the patch
- Now, as shown in the figure, peel off half of the transparent protective film.
- Avoid touching the adhesive surface.
- Put the patch on the skin.
- Only then do you peel off the other half of the protective film
- Press hard on the patch with the palm of your hand for 10 seconds
- Make sure the edges fit snugly.
You wear the patch for 7 days (one week).
- On "Patch Change Day", which is Day 8, remove the used patch
- Apply a new patch immediately.
- On Day 15 (Week 3) remove the used patch
- Put on a new patch.
In all, there are three weeks in which the patches are worn.
To avoid irritation, do not apply the new patch to exactly the same place as the previous patch.
Do not use any patches on Week 4 (Day 22 to Day 28).
- You should have your period during this time
- During this week you will be protected from pregnancy, but only if you start using the next patch on time.
To start the next four-week cycle
- Put on a new patch on your normal "Patch Change Day", which is the day after Day 28
- It doesn't matter which day your period starts or ends.
If you want to change the "Patch Change Day" to another day of the week, please talk to your doctor.
You need to complete your current cycle and remove the third patch on the correct day. During Week 4 you can choose a new "Patch Change Day" and apply the first patch that day. You must not go more than 7 consecutive days without wearing the patch.
If you want to delay your period, also apply a patch at the beginning of Week 4 (Day 22). You may have spotting or intermenstrual bleeding. Do not wear more than 6 consecutive patches (so for no more than 6 weeks). If you have worn 6 consecutive patches (ie for 6 consecutive weeks), do not apply the Week 7 patch. After 7 days without the patch, apply a new patch and restart the cycle considering it as Day 1. Consult your doctor before deciding to delay your period.
Daily activities while using the patch
- Normal activities, such as bathing, showering, sauna or exercise, should not affect the patch's effectiveness.
- The patch is formulated to stay in place during these types of activities
- However, it is advisable to check that the patch has not come off after taking part in these activities
If you need to apply the patch in a new location on a day other than your "Patch Change Day"
If the patch you are using becomes uncomfortable or causes irritation:
- you can peel it off and replace it with a new patch applied in a different place, until the next "Patch Change Day"
- you only need to use one patch at a time.
If you find it difficult to remember to change your EVRA patch
Talk to your doctor, pharmacist or healthcare professional about how you can make it easier to change patches, or about using another method of contraception.
If the patch is peeling or has come off Less than a day (up to 24 hours):
try to reapply it immediately or apply a new patch immediately, no additional contraceptive method is required
- no longer adheres
- it has attached itself to itself or to another surface
- other materials adhered to it
- it is the second time it loosens or detaches.
For more than a day (24 hours or more) or if you are unsure for how long:
- start a new four-week cycle immediately by applying a new patch
- will now have a new Day 1 and a new "Patch Change Day"
- for the first week of your new cycle you will also need to use a non-hormonal method of contraception
You could get pregnant if you don't follow these instructions.
If you forget to replace the transdermal patch
At the start of any patch application cycle (Week 1 (Day 1)):
If you forget to apply the patch, you may be at a particularly high risk of becoming pregnant.
- You will therefore need to use a non-hormonal method of contraception for one week in addition
- Apply the first patch of the new cycle as soon as you remember
- You will now have a new "Patch Change Day" and a new Day 1.
In the middle of the patch application cycle (Week 2 or Week 3):
If you forget to replace the patch for one or two days (up to 48 hours):
- apply a new patch as soon as you remember
- apply the next patch on your regular "Patch Change Day". No additional contraception is needed.
For over two days (48 hours or more):
- if you forget to replace the patch for more than 2 days, you may become pregnant
- start a new four week cycle as soon as you remember, applying a new patch will now have a different "Patch Change Day" and a new Day 1
- you will also need to use an additional method of contraception for the first week of your new cycle.
At the end of the patch application cycle (Week 4):
If you forget to remove the patch:
- remove the patch as soon as you remember
- you start the next cycle on your normal "Patch Change Day", which is the day after Day 28.
No additional contraception is needed.
If you have no bleeding or irregular bleeding with EVRA
This medicine can cause unexpected vaginal bleeding or spotting during the weeks you are wearing the patch
- This usually ends after the first few cycles
- Mistakes in using the patches can cause spotting or light bleeding
- Continue to use this medicine and if the bleeding lasts longer than the first three cycles, talk to your doctor or pharmacist.
If your period does not appear during the week you are not wearing EVRA (Week 4), you should continue applying a new patch on your usual "Patch Change Day".
- If you are using this medicine correctly and you do not have a period, this does not necessarily mean that you are pregnant
- However, if your period does not occur for two consecutive cycles, talk to your doctor or pharmacist as you may be pregnant.
Overdose What to do if you have taken too much Evra
If you use more EVRA than you should (more than one EVRA patch at a time)
Remove the patches and contact your doctor immediately. Using too many patches could cause:
- malaise (nausea, vomiting)
- vaginal bleeding.
If you stop taking EVRA
You may have an irregular, light period, or none at all. This usually happens during the first 3 months, especially if your periods were not regular before you started using this medicine.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
Side Effects What are the side effects of Evra
Like all medicines, EVRA can cause side effects, although not everybody gets them. If you get any side effects, especially if they are severe or persistent, or if there is any change in your health that you think might be due to EVRA, 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 use EVRA ".
Very common side effects (affects more than 1 in 10 women):
- Headache
- Nausea
- Breast discomfort.
Common side effects (affects less than 1 in 10 women):
- Vaginal yeast infections, sometimes called candidiasis
- Mood disorders, such as depression, mood changes, mood swings, anxiety, crying
- Dizziness
- Migraine
- Stomach pain or stomach bloating
- Vomiting or diarrhea
- Acne, rash, itching or skin irritation
- Muscle spasms
- Breast problems such as breast pain, enlargement or lumps
- Changes in the characteristics of menstrual bleeding, uterine cramps, painful periods, vaginal discharge
- Application site reactions such as redness, irritation, itching or rash Tiredness or general malaise
- Weight gain.
Uncommon side effects (affects less than 1 in 100 women):
- Allergic reaction, urticaria
- Swelling due to water retention
- High levels of fat in the blood (such as cholesterol or triglycerides)
- Sleep disturbances (insomnia)
- Loss of libido
- Eczema, redness of the skin
- Abnormal production of breast milk
- Premenstrual syndrome
- Vaginal dryness
- Other reactions at the site of application of the patch
- Swelling
- High blood pressure or increased blood pressure
- Increased appetite
- Hair loss
- Sensitivity to sunlight.
Rare side effects (affects less than 1 in 1,000 women):
- harmful blood clots in a vein or artery, for example: in a leg or foot (DVT)
- in one lung (PE)
- heart attack
- stroke
- mini-stroke or temporary stroke-like symptoms, known as a transient ischemic attack (TIA)
- 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 condition that increases this risk
- Breast, cervical or liver cancer
- Problems caused by the patch coming into contact with the skin such as a rash with blisters or ulcers
- Non-cancerous (benign) breast or liver tumors
- Uterine fibroids (uterus)
- Anger or a feeling of frustration
- Increased libido
- Alteration of taste
- Problems wearing contact lenses
- Sudden sharp rise in blood pressure (hypertensive crisis)
- Inflammation of the gallbladder or colon
- Altered cells in the cervix
- Brownish spots or blotches on the face
- Gallstones or bile duct blockage
- Yellowing of the skin and whites of the eyes
- Abnormal blood sugar or insulin levels
- Swelling of the face, mouth, throat or tongue
- Rash with painful red nodules on the shins and legs
- Itching
- Scaly, flaky, itchy and red skin
- Breastfeeding suppressed
- Vaginal discharge
- Fluid retention in the legs
- Fluid retention
- Swelling of the arms, hands, legs or feet.
If you have stomach upset
- The amount of hormones released by EVRA should not be affected by vomiting or diarrhea
- You do not need to use additional contraception if you have stomach upset.
You may have spotting, light bleeding, breast discomfort or feel unwell during the first 3 cycles. The problem usually goes away but if it persists, check with your doctor or pharmacist.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the package after "EXP". The expiry date refers to the last day of that month.
Store in the original package to protect the patches from light and moisture.
Do not refrigerate or freeze.
Used patches still contain active hormones. To protect the environment, they must be disposed of carefully. To dispose of the used patch you should:
- lift the label to be used for disposal located on the outside of the sachet
- put the used patch inside the disposal label, open so that the sticky surface covers the shaded area
- close the label by sealing the used patch inside and dispose of it out of the reach of children.
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.
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.
01.0 NAME OF THE MEDICINAL PRODUCT
EVRA TRANSDERMAL PATCH 203 mcg / 24 HOURS + 33.9 mcg / 24 HOURS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 20 cm2 transdermal patch contains 6 mg of norelgestromin (NGMN) and 600 mcg of ethinylestradiol (EE).
Each transdermal patch releases an average of 203 mcg of NGMN and 33.9 mcg of EE in 24 hours. Drug exposure is more appropriately characterized by the pharmacokinetic profile (see section 5.2).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Transdermal patch.
Thin, matrix transdermal patch consisting of three layers.
The external part of the reinforcement layer is beige in color and has the wording "EVRA" thermo-printed.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Female contraception.
EVRA is intended for women of childbearing age. Its efficacy and safety have been established in women aged 18 to 45 years.
The decision to prescribe EVRA 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 EVRA and that associated with other CHCs (see sections 4.3 and 4.4).
04.2 Posology and method of administration
Dosage
To achieve maximum contraceptive efficacy, inform patients that they will need to use EVRA exactly as prescribed. For instructions on how to get started, see "Getting started with EVRA" below.
Only one transdermal patch should be worn at a time.
Each used transdermal patch should be removed and immediately replaced with a new one on the same day of the week (change day) on day 8 and day 15 of the cycle. You can replace the transdermal patch at any time of day on the change day. The fourth week, starting on day 22 of the cycle, the transdermal patch is not used.
A new contraceptive cycle begins the day after the week without a transdermal patch; the next EVRA transdermal patch should also be applied if there is no bleeding or if the bleeding has not yet stopped.
Never more than 7 days should pass without a transdermal patch between cycles. If more than 7 days elapse, the user may not be protected from pregnancy. In this case, a non-hormonal contraceptive must therefore be used concomitantly for 7 days. The risk of ovulation increases every day beyond the recommended contraceptive-free period. If intercourse occurs during such a prolonged interval without a transdermal patch, the possibility of pregnancy should be considered.
Special populations
Body weight equal to or greater than 90 kg
Contraceptive efficacy may be reduced in women weighing 90 kg or more.
Kidney failure
EVRA has not been studied in women with renal insufficiency. No dose adjustment is necessary, but as the medical literature suggests that the free fraction of ethinylestradiol is higher, EVRA should be administered to this carefully monitored population.
Hepatic insufficiency
EVRA has not been studied in women with hepatic insufficiency. EVRA is contraindicated in women with hepatic impairment (see section 4.3).
Postmenopausal women
EVRA is not indicated in postmenopausal women and should not be used as hormone replacement therapy.
Pediatric population
Safety and efficacy have not been established in adolescents under the age of 18. There is no relevant use of EVRA in pre-menarche children and adolescents.
Method of administration
EVRA should be applied to clean, dry, hairless, intact and healthy skin, on the buttock, abdomen, upper outer arm or upper torso, in a location where it will not be rubbed by tight clothing. EVRA it should not be applied to breasts or skin that is red, irritated or cut. Each consecutive EVRA transdermal patch should be applied to a different part of the skin to avoid irritation but may remain on the same anatomical area.
Press firmly on the transdermal patch until the edges adhere well.
To prevent interference with the adhesive properties of the transdermal patch, no makeup, cream, lotions, talc or other topical products should be applied to the area of skin where the transdermal patch is applied or where it is intended to be applied.
It is recommended that users visually inspect the transdermal patch every day to ensure proper adhesion.
EVRA transdermal patch must not be cut, damaged or altered in any way as it may compromise its contraceptive efficacy.
Used transdermal patches should be carefully discarded according to the instructions given in section 6.6.
How to start EVRA
If no hormonal contraceptive was used in the previous cycle
Contraception with EVRA begins on the first day of menstruation. A single transdermal patch is applied and worn for a full week (7 days). The day the first transdermal patch is applied (day 1 / start day) determines the next replacement days. The transdermal patch change day will be the same day each week (day 8, 15, 22 of the cycle and day 1 of the next cycle). The transdermal patch is not used for the fourth week, starting on day 22 of the cycle.
For the first treatment cycle only, if cycle 1 therapy begins after the first day of menstruation, a non-hormonal contraceptive should be used simultaneously for the first 7 consecutive days.
If you change from a combined oral contraceptive
Treatment with EVRA should start on the first day of the withdrawal bleeding. If there is no withdrawal bleeding within 5 days of taking the last active tablet (containing hormones), the possibility of pregnancy should be ruled out before starting treatment. with EVRA If therapy is started after the first day of withdrawal bleeding, non-hormonal contraceptive means should be used concomitantly with EVRA for 7 days.
If more than 7 days have passed since taking the last active oral contraceptive pill, it is possible that the woman has ovulated. Therefore, inform you that you should consult your doctor before starting treatment with EVRA. If the woman has had sexual intercourse during such an extended pill-free interval, the possibility of pregnancy should be considered.
If you change from a progestogen-only method
The user can change from the progestogen-only pill on any day (from the day of removal in the case of an implant and from the day the injection was to be made in the case of an injectable contraceptive method), however in the first 7 days you will need to use an additional barrier method of contraception.
Following induced or spontaneous abortion
Following an induced or spontaneous abortion that occurred before 20 weeks of gestation, the user can start using EVRA immediately. If EVRA is started immediately, no additional contraceptive measures are required. Please note that ovulation may occur within 10 days of an induced or spontaneous abortion.
In the case of an induced or spontaneous abortion occurring at 20 weeks of gestation or later, EVRA can be started on day 21 after the abortion, or on the first day of the first spontaneous menstruation, whichever comes first. knows the incidence of ovulation on day 21 after abortion (at 20 weeks of gestation).
After giving birth
Users who choose not to breastfeed should start contraceptive therapy with EVRA no earlier than 4 weeks after delivery. With a later onset, inform the user of the need to use an additional barrier method for the first 7 days. However, if intercourse has already occurred, rule out the possibility of pregnancy before starting EVRA or wait for the first. period.
For breastfeeding women, see section 4.6.
What to do if the transdermal patch comes off partially or completely
If the EVRA transdermal patch partially or completely detaches and remains detached, the amount of medicinal product delivered will not be sufficient.
If EVRA remains even only partially detached:
• for less than one day (up to 24 hours): should be applied again in the same location or replaced immediately with a new EVRA transdermal patch. No other contraceptive measures are necessary. Apply the next EVRA transdermal patch on your usual "Change Day".
• for more than one day (24 hours or more) or if the user does not know when the transdermal patch has lifted or detached: the user may not be protected from pregnancy. The user must stop the contraceptive cycle and start a new one immediately, applying a new EVRA transdermal patch. There is now a new "day 1" and a new "change day". A non-hormonal method of contraception must also be used simultaneously, only for the first 7 days of the new cycle.
A transdermal patch should not be reapplied if it is no longer adhesive, replace it immediately with a new one. No other adhesives or bandages should be used to hold the EVRA transdermal patch in place.
In case of delays in the subsequent replacement days of EVRA transdermal patches
At the start of any cycle with the transdermal patch (first week / day 1):
The user may not be protected from pregnancy. She should apply the first transdermal patch of the new cycle as soon as she remembers. There is now a new "Change Day" and a new "Day 1". hormonal for the first 7 days of the new cycle In case of sexual intercourse during such an extended period without a transdermal patch, the possibility of pregnancy should be considered.
Mid-cycle (second week / day 8 or third week / day 15):
• for one to two days (up to 48 hours): The user should apply a new EVRA transdermal patch immediately. The next EVRA transdermal patch should be applied on the usual "change day". If during the 7 days preceding the first day if the transdermal patch is not applied, the user has worn the patch correctly, no further contraceptive measures are necessary.
• for more than two days (48 hours or more): The "user may not be protected from pregnancy. She should stop her current contraceptive cycle and immediately start a new four-week cycle by applying a new EVRA transdermal patch. You will now have a new one" day 1 "and a new" replacement day ". A non-hormonal contraceptive should be used concurrently for the first 7 consecutive days of the new cycle.
• at the end of the cycle (week 4 / day 22): If the user does not remove the EVRA transdermal patch at the beginning of week 4 (day 22), she must remove it as soon as possible. The next cycle should start with the normal "replacement day", which is the day after day 28. No additional contraceptive measures are necessary.
To change the replacement day
If the user wishes to postpone her period once, she should apply another transdermal patch at the beginning of week 4 (day 22), thus not observing the patch-free interval. You may have bleeding or spotting. after wearing the transdermal patch for 6 consecutive weeks, there should be a patch-free interval of 7 days, after which regular application of EVRA is resumed.
If the user wishes to move the change day, she must finish the current cycle by removing the third EVRA transdermal patch on the correct day. During the interval without a transdermal patch, she can choose a new change day by applying the first EVRA transdermal patch. of the next cycle as soon as the desired day arrives. Never more than 7 days should go without the transdermal patch. The shorter the patch-free interval, the higher the risk that the user will not have withdrawal bleeding and instead have metrorrhagia and spotting during the next treatment cycle.
In case of mild skin irritation
If using the transdermal patch causes a "nagging irritation, a new transdermal patch may be applied to another part" until the next replacement day is reached. Only one transdermal patch should be used at a time.
04.3 Contraindications
Combined hormonal contraceptives (combined hormonal contraceptives, COC) should not be used under the following conditions. If any of these symptoms occur while using EVRA, discontinue use immediately.
• 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)
• Arterial thromboembolism - current or previous 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
• Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
• Known or suspected breast cancer
• Endometrial cancer or other known or suspected estrogen-dependent neoplasms
• Altered liver function related to acute or chronic hepatocellular disease
• Liver adenomas or carcinomas
• Undiagnosed abnormal genital bleeding
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 EVRA 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 EVRA should be discontinued.
There is no clinical evidence to indicate that a transdermal patch is in any respect safer than COCs.
EVRA is not indicated in pregnancy (see section 4.6).
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. The risk associated with others. products such as EVRA can even be twofold. 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 EVRA. where your current risk factors influence 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 a COC is resumed after a break of 4 or more weeks.
About 2 out of 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).
It is estimated that out of 10,000 women who use a low-dose CHC containing levonorgestrel, about 6 [1] will develop a VTE in one year. Studies have suggested that the incidence of VTE in women who have used EVRA is up to two times higher than in users of COCs that contain levonorgestrel. These values are approximately 6-12 VTE per year for 10,000 women using EVRA. .
[1] Median value of the range 5-7 per 10,000 women / year, based on a relative risk of approximately 2.3-3.6 of levonorgestrel-containing COCs compared to non-use
In both cases, the number of VTEs per year is lower than the number expected in pregnant or postpartum women.
VTE can be fatal in 1-2% 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).
EVRA is contraindicated if a woman has multiple 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
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). EVRA 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
Symptoms of ATE
If symptoms of this type occur, women should 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 speaking 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 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.
Women using combined contraceptives should contact their doctor in the event of possible symptoms of thrombosis. If thrombosis is suspected or known, discontinue use of the hormonal contraceptive. Start adequate contraception due to the teratogenicity of anticoagulant therapy (coumarins).
Tumors
An increased risk of cervical cancer in long-term COC users has been reported in some epidemiological studies, but the degree to which this finding can be attributed to the confounding effect of sexual behavior and other factors such as human papillomavirus continues to be controversial ( HPV).
A meta-analysis of 54 epidemiological studies reported a slightly higher risk (RR = 1.24) of breast cancer diagnosis among women currently using COCs. The excess risk gradually disappears over the 10 years following discontinuation of COC use. Since breast cancer is rare in women under 40, the higher number of breast cancer diagnoses among current users and recent COCs is limited in relation to the overall risk of breast cancer. Breast cancer diagnosed in women who have used COC tends to be less clinically advanced than the cancers found in women who have never taken COC: The observed higher risk pattern may be due to an early diagnosis of breast cancer in COC users, the biological effects of COCs, or a combination of both.
In rare circumstances, benign liver tumors and, in even rarer circumstances, malignant liver tumors have been reported among COC users. In isolated cases, these tumors have led to life-threatening intra-abdominal haemorrhages. Therefore, consider the possibility of liver cancer in the differential diagnosis when an EVRA user has severe upper abdominal pain, liver enlargement or signs of intra-abdominal haemorrhage.
Other conditions
• Contraceptive efficacy may be reduced in women weighing 90 kg or more (see sections 4.2 and 5.1).
• Women with hypertriglyceridaemia, or a family history of it, may be at increased risk of pancreatitis while using combined hormonal contraceptives.
• Although small increases in blood pressure have been reported in many women taking hormonal contraceptives, clinically significant increases are rare. A definitive relationship between the use of hormonal contraceptives and clinical hypertension has not been established. If, during the use of a combined hormonal contraceptive in the presence of pre-existing hypertension, consistently high blood pressure or a significant increase in blood pressure does not respond adequately to antihypertensive treatment, discontinue the use of the combined hormonal contraceptive. This use may be resumed if it is possible to obtain normotensive values by means of anti-hypertensive therapy.
• The appearance, or deterioration, of the following conditions has been reported with both pregnancy and COC use. However, evidence of an association with COC use is not conclusive: jaundice and / o pruritus associated with cholestasis; gallbladder disease including cholecystitis and cholelithiasis; porphyria; systemic lupus erythematosus; haemolytic uremic syndrome; Sydenham's chorea; herpes gestationis; hearing loss associated with otosclerosis.
• Acute or chronic disturbances of liver function may necessitate the interruption of combined hormonal contraceptives until the markers of liver function return to normal values. require discontinuation of combined hormonal contraceptives.
• Although combined hormonal contraceptives may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence that the treatment regimen needs to be altered in diabetic patients while using combined hormonal contraception. However, diabetic women will need to be watched carefully, particularly in the early stages of using EVRA.
• Worsening of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis has been reported during COC use.
• Chloasma may occasionally arise with the use of hormonal contraception, especially in users with a history of chloasma gravidarum. Users with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while using EVRA. Chloasma is often not completely reversible.
Medical examinations / visits
Before initiating or resuming use of EVRA, a complete medical history (including family history) should be taken and pregnancy should be ruled out. Blood pressure should be measured and a clinical examination, guided by contraindications, should be performed (see section 4.3 ) and warnings (see section 4.4). It is important to draw a woman's attention to information relating to venous or arterial thrombosis, including the risk associated with EVRA compared to other CHCs, symptoms of VTE and ATE, known risk factors and what to do in case of suspected thrombosis.
The woman should also be advised of the need to read the package leaflet carefully and to follow its advice. The frequency and type of examinations should be based on established guidelines and should be adapted to the individual woman.
Women should be advised that oral contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases.
Irregular bleeding
As with all combined hormonal contraceptives, irregular blood loss (spotting or breakthrough bleeding) may occur, particularly in the first months of use. For this reason, a medical opinion about irregular blood loss will only be useful after an adjustment period of approximately three cycles. If bleeding persists, or occurs after previous regular cycles, when EVRA has been used on the recommended regimen. , a cause other than EVRA should be considered. Consider non-hormonal causes and, if necessary, take appropriate diagnostic measures to rule out the presence of organic disease or pregnancy. These measures may include curettage. In some women there may be no bleeding from suspension in the non-use interval of the transdermal patch. If EVRA has been taken according to the instructions in section 4.2, it is unlikely that the woman is pregnant. However, if EVRA has not been taken according to these instructions prior to the first skipped withdrawal bleed, or if the woman has missed two consecutive withdrawal bleeds, pregnancy must be ruled out before continuing to use EVRA.
Some users may have amenorrhea or oligomenorrhea after stopping hormonal contraception, particularly if these conditions were pre-existing.
04.5 Interactions with other medicinal products and other forms of interaction
Note: Consult the prescribing information for concomitant medications to identify possible interactions.
Influence of other medicinal products on EVRA
Interactions between oral contraceptives and other drugs can lead to blood loss and / or failure of contraceptive protection. The following interactions have been reported in the literature.
Hepatic metabolism
Interactions with hepatic enzyme-inducing medicinal products may be observed which may lead to increased clearance of sex hormones (e.g. phenobarbital, primidone, rifampicin, rifabutin, bosentan, (fos) aprepitant), some anti-epileptics (e.g. carbamazepine) , eslicarbazepine acetate, felbamate, oxycarbazepine, phenytoin, rufinamide, topiramate) and some medicines for the treatment of HIV (eg nelfinavir, ritonavir, nevirapine, efavirenz) and possibly also griseofulvin and products containing St John's wort (Hypericum perforatum). Maximal enzyme induction is generally observed in about 10 days but can be maintained for at least 4 weeks after discontinuation of therapy.
Do not use herbal preparations containing St. John's wort (Hypericum perforatum) while using EVRA.
Interference with the enterohepatic circle
Cases of contraceptive failure have also been reported with antibiotics such as penicillins and tetracyclines. The mechanism of this effect is not yet clear. In a pharmacokinetic interaction study, oral administration of tetracycline hydrochloride, 500 mg four times / day for 3 days prior to the application period of EVRA and for 7 days during that period, did not significantly affect the pharmacokinetics of norelgestromin or ethinyl estradiol. .
Management
Women on short-term treatment with any of the medicinal products belonging to one of the above classes or with active substances that induce liver enzymes (except rifampicin), should temporarily use a barrier method in addition to EVRA, i.e. during the period of concomitant use of these medicines and for 7 days after their discontinuation. For women being treated with rifampicin, a barrier method should be used in addition to EVRA in conjunction with the rifampicin period and for 28 days following its discontinuation.
For women on long-term therapy with any of the medicines belonging to one of the above classes, it is recommended to use another effective non-hormonal method of contraception.
Women on antibiotic treatment (except rifampicin, see above) will need to use the barrier method for up to 7 days after stopping the drug.
If concomitant medication continues beyond the end of the patch treatment week, the new patch should be applied immediately, starting a new course of treatment, without observing the usual patch-free interval.
Inhibition of the metabolism of ethinylestradiol
Etoricoxib has been shown to increase plasma levels of ethinylestradiol (50 to 60%) when taken concomitantly with a triphasic oral hormonal contraceptive. Etoricoxib is thought to increase ethinylestradiol levels by inhibiting sulfotransferase activity, thereby inhibiting the metabolism of ethinylestradiol.
Influence of EVRA on other medicinal products
Hormonal contraceptives can affect the metabolism of some active ingredients. Consequently, plasma and tissue concentrations may increase (e.g. cyclosporine). The dose of the concomitant medicine may need to be adjusted.
Lamotrigine: Combined hormonal contraceptives have shown a significant decrease in plasma concentrations of lamotrigine when co-administered possibly due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, lamotrigine dose adjustment may be necessary. .
Lab test
The use of steroid hormones with contraceptive action can influence the results of some laboratory tests including biochemical parameters relating to liver, thyroid, adrenal and renal function, plasma levels of proteins (carriers), such as, for example, blood-binding globulin corticosteroids and lipid / lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis Variations generally remain within normal laboratory limits.
04.6 Pregnancy and lactation
Pregnancy
EVRA is not indicated during pregnancy.
Epidemiological studies indicate a no greater risk of congenital defects in children born to women who used COCs prior to pregnancy. Furthermore, most recent studies have not indicated a teratogenic effect when COCs are inadvertently used during the early stages of pregnancy.
The limited data available on the outcomes of exposed pregnancies in women treated with EVRA do not allow conclusions regarding the safety of the transdermal patch during pregnancy.
Animal studies have shown undesirable effects during pregnancy and lactation (see section 5.3). Based on these animal data, undesirable effects due to the hormonal action of the active compounds cannot be excluded. However, general experience with COCs during pregnancy did not provide evidence of a real adverse effect in humans.
If you become pregnant while taking EVRA, stop using EVRA immediately.
The increased risk of VTE during the postpartum period should be considered when resuming EVRA (see sections 4.2 and 4.4).
Feeding time
Breastfeeding can be influenced by combined hormonal contraceptives, as they can reduce the volume and alter the composition of breast milk. Therefore, the use of EVRA is not recommended in mothers who breastfeed until the baby is completely weaned.
Fertility
In women, there may be a delay in conception after stopping EVRA.
04.7 Effects on ability to drive and use machines
EVRA has no or negligible influence on the ability to drive or use machines.
04.8 Undesirable effects
Summary of the safety profile
The most commonly reported adverse reactions in clinical trials were headache, nausea and breast discomfort, occurring in approximately 21.0%, 16.6% and 15.9% of women, respectively.
Adverse reactions that may occur at the start of treatment but which usually subside after the first three cycles include bleeding, breast discomfort and nausea.
Description of some adverse reactions
An increased risk of arterial and venous thrombotic and thromboembolic 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.
Table with list of adverse reactions
Safety was evaluated in 3,322 sexually active women who participated in three Phase III clinical trials designed to evaluate contraceptive efficacy. These patients received six or 13 cycles of contraception (EVRA or an oral contraceptive as a comparator). , took at least one dose of study medicinal product and provided safety data. Table 1 below reflects adverse reactions reported in clinical trials and post-marketing experience. MedDRA convention on frequency: very common (≥ 1/10); common (≥ 1/100 y
04.9 Overdose
No serious side effects have been reported following accidental ingestion of large quantities of oral contraceptives. Overdose can cause nausea and vomiting. Some women may experience vaginal bleeding. If overdose is suspected, eliminate all systems. of transdermal contraception and administering symptomatic treatment.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Sex hormones and modulators of the genital system, progestogens and estrogens, fixed association. ATC code: G03AA13.
Mechanism of action
EVRA acts through the gonadotropin suppression mechanism through the estrogenic and progestin action of ethinylestradiol and norelgestromin. The primary mechanism of action is the inhibition of ovulation, but also the alterations of the cervical mucus and of the endometrium can contribute to the efficacy of the product.
Clinical efficacy and safety
Pearl indices (see table):
*: DSG 150 mcg + 20 mcg EE
**: 50 mcg LNG +30 mcg EE for days 1-6, 75 mcg LNG + 40 mcg EE for days 7-11, 125 mcg LNG + 30 mcg EE for days 12-21
Exploratory analyzes were performed to determine whether in the phase III studies (n = 3319) population characteristics of age, race and weight could be associated with pregnancy. Analyzes did not indicate any association of age and race with pregnancy but, by weight, 5 of the 15 pregnancies reported with EVRA were in women with a body weight equal to or greater than 90 kg at baseline, which constituted
With the use of higher-dose COCs (50 mcg ethinylestradiol) the risk of endometrial and ovarian cancer is reduced. It remains to be confirmed whether this also applies to lower-dose combined hormonal contraceptives.
05.2 Pharmacokinetic properties
Absorption
After application of EVRA, serum norelgestromin and ethinyl estradiol levels reach a plateau within approximately 48 hours. steady state of norelgestromin and EE during one week of use of the transdermal patch are approximately 0.8 ng / mL and 50 pg / mL, respectively. In multiple-dose studies, serum concentrations and AUC for norelgestromin and EE increased. only slightly over time, when compared to week 1 of cycle 1.
The absorption of norelgestromin and ethinyl estradiol after application of EVRA was studied in the conditions found in the gym (sauna, Jacuzzi, treadmill and other aerobic exercises) and in a cold water bath. The results indicate that for norelgestromin there were no significant treatment effects for CSS or AUC compared to normal use. For EE, a slight increase from treadmill and other aerobic exercise was observed, but CSS values following these treatments remained within the reference range. There was no significant effect of cold water on these parameters.
The results of a study with EVRA on prolonged use of a single transdermal patch for 7 days and 10 days indicated that the target CSS for norelgestromin and ethinyl estradiol were maintained over a 3-day prolongation of use of EVRA. (10 days) These results suggest that clinical efficacy should be maintained even if the patch is forgotten for up to 2 full days.
Distribution
Norelgestromin and norgestrel (a serum metabolite of norelgestromin) are highly bound (> 97%) to serum proteins. Norelgestromin is linked to albumin and not to SHBG, while norgestrel is mainly linked to SHBG, which limits its biological activity. Ethinylestradiol is highly bound to serum albumin.
Biotransformation
Norelgestromin is metabolised by the liver and metabolites include norgestrel, which is extensively bound to SHGB, and various hydroxylated and conjugated metabolites. Ethinylestradiol is also metabolised to various hydroxylated products and their conjugates with glucuronides and sulphates.
Elimination
After removing the transdermal patch, the elimination half-lives of norelgestromin and ethinyl estradiol were approximately 28 hours and 17 hours, respectively. The metabolites of norelgestromin and ethinyl estradiol are eliminated via the kidney and faeces.
Transdermal contraceptives versus oral contraceptives
The pharmacokinetic profiles of combined transdermal and oral hormonal contraceptives are different and caution should be used when making a direct comparison between the pharmacokinetic parameters of these two formulations.
In a study comparing EVRA with an oral contraceptive containing norgestimate (precursor to norelgestromin) 250 mcg / ethinyl estradiol 35 mcg, Cmax values were 2-fold higher for norelgestromin and ethinyl estradiol in subjects administered the oral contraceptive compared to to EVRA, while the total exposure (AUC and Css) was comparable to that of the subjects treated with EVRA.
The inter-individual variability (% CV) in the pharmacokinetic parameters of EVRA was greater than that observed with oral contraceptives.
Effects of age, body weight and body surface area
The effects of age, body weight and body surface area on the pharmacokinetics of norelgestromin and ethinylestradiol were evaluated in 230 healthy women in nine pharmacokinetic studies with single applications of EVRA for 7 days. Increases in age, weight and body surface area were associated with slight decreases in Css and AUC values for both norelgestromin and EE. However, only a small percentage (10-20%) of the overall variability in the pharmacokinetics of norelgestromin and EE after application of EVRA may be associated with some or all of the above demographic parameters.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. Regarding reproductive toxicity, norelgestromin demonstrated fetal toxicity in rabbits, however the safety margin for this effect was sufficiently high. There are no data on the reproductive toxicity of the combination of norelgestromin with ethinyl estradiol. Data for the combination of norgestimate (the precursor of norelgestromin) with ethinyl estradiol indicate a reduction in fertility and efficacy in female animals. implantation (rats), an increase in fetal resorption (rats, rabbits) and, at high doses, a decrease in the viability and fertility of female births (rats). The relevance of these data to human exposure is unknown, as the effects were considered to be related to pharmacodynamic actions or specific actions for these animal species of an already known nature.
Studies conducted to examine the dermal effects of EVRA indicate that this system does not have the potential to produce sensitization and may only cause mild irritation when applied to rabbit skin.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Reinforcement layer
outer layer of low density pigmented polyethylene, inner layer of polyester.
Intermediate layer
polyisobutylene / adhesive polybutene, crospovidone, non-woven polyester fabric, lauryl lactate.
Third layer
polyethylene terephthalate (PET) film, polydimethylsiloxane coating.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years.
06.4 Special precautions for storage
Store in the original package in order to protect the patches from light and moisture.
Do not refrigerate or freeze.
06.5 Nature of the immediate packaging and contents of the package
Primary packaging material
Each sachet consists of four layers: a low density polyethylene film (the innermost layer), an aluminum foil, a low density polyethylene film and an outer layer of bleached paper.
Secondary packaging material
The sachets are packed in a cardboard box.
Each pack contains 3, 9 or 18 EVRA transdermal patches in individual strengthened sachets.
The sachets are wrapped, in groups of three, in a transparent perforated plastic film and packed in a cardboard box.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
The patch should be applied immediately after removing the protective sachet.
To prevent interference with the adhesive properties of EVRA, no creams, lotions or talc should be applied to the skin area where the EVRA transdermal patch is to be applied.
After use, the transdermal patch still contains a considerable amount of active ingredients. The residual hormonal active ingredients of the transdermal patch could have harmful effects if they reach the aquatic environment.Hence, the used transdermal patch should be carefully discarded. The label to use for deletion. placed on the outside of the sachet, it must be lifted. The used transdermal patch should be placed inside the open discard label so that the sticky surface covers the shaded area on the sachet. The label must then be closed by sealing the used transdermal patch inside. Unused medicines and waste derived from these medicines must be disposed of in accordance with local regulations. Used transdermal patches should not be disposed of in the toilet or in the elimination of waste by means of liquids.
07.0 MARKETING AUTHORIZATION HOLDER
JANSSEN-CILAG INTERNATIONAL N.V.
Turnhoutseweg, 30
B-2340 Beerse
Belgium
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/02/223/001
035684012
EU / 1/02/223/002
035684024
EU / 1/02/223/003
035684036
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 22 August 2002
Date of last renewal: 22 August 2012
10.0 DATE OF REVISION OF THE TEXT
01/2014
