DRETINE DIARIO 0.03 mg/3 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Dretine Daily 0.03 mg/3 mg Film-Coated Tablets EFG

Ethinylestradiol/Drospirenone

Important Things to Know About Combined Hormonal Contraceptives (CHCs):

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

Read the Entire Package Leaflet Carefully Before Starting to Take This Medication, as it Contains Important Information for You.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you only. Do not give it to others, as it may harm them.
• If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this package leaflet. See section 4.

Package Leaflet Contents:

1. What is Dretine Daily and What is it Used For
2. What You Need to Know Before You Start Taking Dretine Daily
3. How to Take Dretine Daily
4. Possible Side Effects
5. Storage of Dretine Daily
6. Pack Contents and Further Information

1. What is Dretine Daily and What is it Used For

Dretine Daily is a contraceptive pill and is used to prevent pregnancy.

Each of the 21 film-coated yellow tablets contains a small amount of two different female hormones, called drospirenone and ethinylestradiol.

The 7 film-coated white tablets do not contain active ingredients and are called placebo tablets.

Contraceptive pills that contain two hormones are known as "combined" pills.

2. What you need to know before starting to take Dretine daily

When you should not use Dretine daily

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

• if you have (or have ever had) a blood clot in a blood vessel of the legs (deep vein thrombosis, DVT), in the lungs (pulmonary embolism, PE) or in other organs
• if you know you have a disorder that affects blood clotting: for example, protein C deficiency, protein S deficiency, antithrombin III deficiency, factor V Leiden or antiphospholipid antibodies.
• if you need an operation or if you spend a lot of time without getting up (see section "blood clots").
• if you have ever had a heart attack or a stroke
• if you have (or have ever had) angina pectoris (a condition that causes severe chest pain and may be the first sign of a heart attack) or a transient ischemic attack (TIA, temporary symptoms of a stroke))
• if you have any of the following diseases that may increase your risk of forming a clot in the arteries:
• • Severe diabetes with blood vessel damage
  • Very high blood pressure
  • Very high levels of fat in the blood (cholesterol or triglycerides)
  • A condition called hyperhomocysteinemia
• if you have (or have ever had) a type of migraine called "migraine with aura"
• if you have (or have ever had) a liver disease and your liver function is not yet normal.
• if your kidneys do not work well (renal insufficiency).
• if you have hepatitis C and are taking medications that contain ombitasvir/paritaprevir/ritonavir, dasabuvir, glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir (see also the section "Other medicines and Dretine daily").
• if you have (or have ever had) a liver tumor.
• if you have (or have ever had), or if you suspect you have breast cancer or cancer of the sex organs.
• if you have vaginal bleeding, whose cause is unknown.
• if you are allergic to ethinylestradiol or drospirenone, or to any of the other components of this medicine (included in section 6). This may cause itching, rash or inflammation.
• if you have hepatitis C and are taking medications that contain ombitasvir / paritaprevir / ritonavir and dasabuvir (see also the section "Taking Dretine daily with other medicines")

Additional information on special populations

Children and adolescents

Dretine daily is not indicated for use in women whose periods have not yet started.

Elderly patients

Dretine daily is not indicated for use after menopause.

Women with liver insufficiency

Do not take Dretine daily if you have liver disease. See also the sections "Do not take Dretine daily" and "Warnings and precautions".

Women with renal insufficiency

Do not take Dretine daily if you have kidney dysfunction or acute renal failure. See also the sections "Do not take Dretine daily" and "Warnings and precautions".

Warnings and precautions

When you should be particularly careful with Dretine daily

Consult your doctor or pharmacist before taking Dretine daily

In some situations, you will need to be particularly careful while using Dretine daily or any other combined contraceptive, and it may be necessary for your doctor to examine you periodically.

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

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

• if a close relative has or has had breast cancer
• if you have any liver or gallbladder disease
• if you have diabetes
• if you have depression
• if you have Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease)
• if you have systemic lupus erythematosus (SLE, a disease that affects your natural defense system)
• if you have hemolytic uremic syndrome (HUS, a blood clotting disorder that causes kidney failure)
• if you have sickle cell anemia (a hereditary disease of red blood cells)
• if you have high levels of fat in the blood (hypertriglyceridemia) or a family history of this condition. Hypertriglyceridemia has been associated with an increased risk of pancreatitis (inflammation of the pancreas)
• if you need an operation or spend a lot of time without getting up (see section 2 "Blood clots")
• if you have just given birth, you are at a higher risk of blood clots. You should ask your doctor when you can start taking Dretine daily after childbirth.
• if you have inflammation of the veins that are under the skin (superficial thrombophlebitis).
• if you have varicose veins
• if you have epilepsy (see "Dretine daily and use of other medicines")
• if you have any disease that first appeared during pregnancy or during early use of sex hormones (e.g. hearing loss, a blood disease called porphyria, blistering skin rash during pregnancy (gestational herpes), a nervous disease in which involuntary movements appear (Sydenham's chorea))
• if you have or have ever had chloasma (a skin discoloration, especially on the face or neck, known as "pregnancy spots"). In this case, you should avoid direct exposure to the sun or ultraviolet light.
• If you experience symptoms of angioedema such as facial swelling, tongue and/or throat swelling, and/or difficulty swallowing or urticaria, with possible difficulty breathing, consult your doctor immediately. Medicines that contain estrogens may induce or worsen the symptoms of hereditary and acquired angioedema.

BLOOD CLOTS

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

Blood clots can form:

• in the veins (this is called "venous thrombosis", "venous thromboembolism" or VTE)
• in the arteries (this is called "arterial thrombosis", "arterial thromboembolism" or ATE)

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

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

HOW TO RECOGNIZE A BLOOD CLOT

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

BLOOD CLOTS IN A VEIN

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

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

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

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

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

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

What is the risk of a blood clot?

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

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

• Out of 10,000 women who do not use a combined hormonal contraceptive and are not pregnant, about 2 will have a blood clot in a year.
• Out of 10,000 women who use a combined hormonal contraceptive that contains levonorgestrel, norethisterone or norgestimate, about 5-7 will have a blood clot in a year.
• Out of 10,000 women who use a combined hormonal contraceptive that contains drospirenone, such as Dretine daily, between 9 and 12 women will have a blood clot in a year.
• The risk of a blood clot depends on your personal history (see "Factors that increase your risk of a blood clot" below)

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

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

• if you are overweight (body mass index or BMI over 30 kg/m2)
• if any of your close relatives have had a blood clot in the leg, lung or other organ at a young age (i.e. before the age of about 50). In this case, you may have a hereditary blood clotting disorder.
• if you need an operation or spend a lot of time without getting up due to an injury or illness or if you have a leg in a cast. You may need to stop using Dretine daily several weeks before the operation or while you have reduced mobility. If you need to stop using Dretine daily, ask your doctor when you can start using it again.
• as you get older (especially above about 35 years)
• if you have recently given birth

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

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

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

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

BLOOD CLOTS IN AN ARTERY

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

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

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

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

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

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

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

Dretine daily and cancer

There have been reports of a slightly higher incidence of breast cancer in women who use combined pills, but it is not known if this is due to the treatment. For example, it may be that more tumors are detected in women who take combined pills because they are examined by a doctor more frequently. The incidence of breast tumors decreases gradually after stopping combined hormonal contraceptives. It is important to have your breasts checked regularly and you should see your doctor if you notice any lump.

In rare cases, benign liver tumors, and even more rarely, malignant liver tumors, have been reported in users of combined pills. You should see your doctor if you experience severe unusual abdominal pain.

3. How to take Dretine daily

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

Each pack contains 21 active yellow pills and 7 white placebo pills.

The two different types of colored pills of Dretine daily are placed in order. A strip contains 28 pills.

Take one Dretine daily pill every day, with a small amount of water if necessary. You can take the pills with or without food, but all days approximately at the same time.

Do not get confused with the pill: take a yellow pill during the first 21 days, and then a white pill during the last 7 days. Then, you must start taking a new strip (21 yellow pills and 7 white pills). Therefore, there is no break between two strips.

Due to the different composition of the pills, it is necessary that you start with the first pill located in the upper left corner and then take one pill every day. For the correct order, follow the direction of the arrows on the strip.

Preparation of the strip

To help you remember the daily intake of the contraceptive, each strip (blister) of Dretine daily comes with seven adhesive stickers that have the days of the week printed on them. You must know the day of the week on which you will take the first pill.

According to the day of the week on which you will start taking the pills, you should choose the corresponding weekly adhesive sticker, for example, if you start on Wednesday, stick the one that says “WED” as the initial pill. Then, you must stick the corresponding sticker on the upper left part of the pack, in the “Start” position. This way, there is a day of the week indicated above each pill, and you can visually check if you have taken a certain pill. The arrows show the order in which you must take the pills.

During the 7 days in which you take the white placebo pills (the placebo days), bleeding usually begins (also called withdrawal bleeding). This usually starts on the second or third day after taking the last active yellow pill of Dretine daily. Once you have taken the last white pill, you must start with the next strip, whether the bleeding has stopped or not. This means that you should start all strips on the same day of the week, and menstruation should take place during the same days every month.

If you take Dretine daily in this way, you are also protected against pregnancy during the 7 days in which you are taking the placebo pills.

When can you start with the first strip

• If you have not used any hormonal contraceptive in the previous month.

Start taking Dretine daily on the first day of your cycle (i.e., the first day of your period). If you start Dretine daily on the first day of your period, you are immediately protected against pregnancy. You can also start on days 2-5 of your cycle, but then you must use additional contraceptive methods (e.g., a condom) during the first 7 days.

• Switching from a combined hormonal contraceptive, vaginal ring, or patch.

You can start taking Dretine daily preferably the day after the last active pill (the last pill containing the active ingredient) of your previous pill, but at the end of the next day after the usual pill-free interval of your previous pill (or after the last inactive pill of your previous pill). When switching from a combined vaginal ring or patch, follow your doctor's recommendations.

• Switching from a progestin-only method (progestin-only pill, injection, implant, or intrauterine system (IUS) of progestin)

You can switch from the progestin-only pill at any time (if it is an implant or IUS, on the day of its removal; if it is an injectable, when the next injection is due) but, in all cases, use additional contraceptive measures (e.g., a condom) during the first 7 days of pill taking.

• After an abortion.

Follow your doctor's recommendations.

• After having a child.

You can start taking Dretine daily between 21 and 28 days after having a child. If you start later, use a barrier method (e.g., a condom) during the first 7 days of taking Dretine daily.

If, after having a child, you have had sexual intercourse before starting to take Dretine daily again, you must be sure that you are not pregnant or wait for your next menstrual period.

• If you are breastfeeding and want to start taking Dretine daily again after having a child.

Read the section “Breastfeeding”.

Ask your doctor if you are not sure when to start.

If you take more Dretine daily than you should

No cases have been reported in which the ingestion of an overdose of ethinylestradiol/drospirenone has caused serious harm.

If you take many pills at the same time, you may have symptoms of nausea or vomiting or vaginal bleeding. Even girls who have not yet started menstruating but have accidentally taken this medication may experience this type of bleeding.

If you have taken too many Dretine daily pills, or discover that a child has taken them, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount taken. It is recommended to take the package and prospectus of the medication to the healthcare professional.

If you forget to take Dretine daily

The pills in the 4throw of the strip are the placebo pills. If you forget to take one of these pills, the effect of Dretine daily will not be affected. Discard the forgotten placebo pill.

If you forget to take an active yellow pill from rows 1, 2, or 3, you must follow these recommendations:

• If you are less than 12 hourslate in taking a pill, the protection against pregnancy will not decrease. Take the pill as soon as you remember and then take the following pills again at the usual time.
• If you are more than 12 hourslate in taking a pill, the protection against pregnancy may be reduced. The more pills you have forgotten, the higher the risk of becoming pregnant.

The risk of incomplete protection against pregnancy is maximum if you forget to take a yellow pill at the beginning or end of the strip. Therefore, you should take the following measures (see also the diagram below):

• More than one forgotten pill in a strip

Consult your doctor.

• One forgotten pill in week 1

Take the forgotten pill as soon as you remember, even if it means taking two pills at the same time. Continue taking the following pills at the usual time and use extra precautionsfor the next 7 days, for example, a condom. If you have had sexual intercourse in the week before forgetting the pill, you should know that there is a risk of pregnancy. In that case, consult your doctor.

• One forgotten pill in week 2

Take the forgotten pill as soon as you remember, even if it means taking two pills at the same time. Continue taking the following pills at the usual time. The protection against pregnancy will not decrease, and you do not need to take extra precautions.

• One forgotten pill in week 3

You can choose between two options:

1. Take the forgotten pill as soon as you remember, even if it means taking two pills at the same time. Continue taking the pills at the usual time. Instead of having a pill-free period, start taking the next strip.

You will probably have a period at the end of the second strip, but you may experience a small bleed or bleeding similar to menstruation during the second strip.

1. You can also stop taking the active yellow pills and go directly to a 7-day pill-free period (before taking the placebo pills, note the day you forgot to take your pill). If you want to start a new blister pack on your fixed start day, take the placebo pills for less than 7 days.

If you follow one of these two recommendations, you will remain protected against pregnancy.

• If you have forgotten to take any of the pills in the strip and do not have bleeding during the first pill-free period, you may be pregnant. See your doctor before continuing with the next strip.

What to do in case of vomiting or severe diarrhea

If you vomit within 3-4 hours after taking an active yellow pill or have severe diarrhea, there is a risk that the active ingredients of the pill will not be fully absorbed by your body. This is similar to what happens when you forget a pill. After vomiting or diarrhea, take another active yellow pill from a reserve strip as soon as possible. If possible, take it before 12 hourshave passed since the usual time you take your contraceptive. If it is not possible or more than 12 hours have passed, follow the advice given in “If you forget to take Dretine daily”.

Delayed menstrual period: what you should know

Although it is not recommended, it is possible to delay your menstrual period by not taking the white placebo pills from the 4th row and going directly to a new strip of Dretine daily and finishing it. You may experience small bleeds or bleeding similar to menstruation while using the next strip. Finish this second strip by taking the 7 white pills from the 4th row. Then, start your next strip.

You must consult your doctor before deciding to delay your menstrual period.

Changing the first day of your menstrual period: what you should know

If you take the pills according to the instructions, your menstrual period will begin during the placebo week. If you need to change this day, reduce the number of placebo days (but never increase them – 7 is the maximum!). For example, if you normally start taking the placebo pills on a Friday and want to change it to a Tuesday (3 days earlier), start a new strip 3 days earlier than usual. If you make the placebo period very short (e.g., 3 days or less), you may not have any bleeding during these days. Then, you may experience weak bleeding or bleeding similar to menstruation.

If you are not sure what to do, consult your doctor.

If you stop taking Dretine daily

You can stop taking Dretine daily whenever you want. If you do not want to become pregnant, consult your doctor about other effective methods of birth control. If you want to become pregnant, stop taking Dretine daily and wait until your period before trying to become pregnant. This way, you can more easily calculate the estimated date of delivery.

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

4. Possible Adverse Effects

Like all medicines, Dretine daily may produce adverse effects, although not all people suffer from them. If you suffer from any adverse effect, especially if it is severe and persistent, or have any change in health that you believe may be due to Dretine daily, consult your doctor.

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

Serious Adverse Effects

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

The following list of adverse effects has been related to the use of Drospirenone/Ethinylestradiol:

Frequent Adverse Effects (may affect up to 1 in 10 people):

• menstrual disorders, intermenstrual bleeding, breast pain, breast tenderness
• headache, depressive mood
• migraine
• nausea
• thick white vaginal discharge and vaginal fungal infection

Uncommon Adverse Effects (may affect up to 1 in 100 people):

• changes in sexual interest
• high blood pressure, low blood pressure
• vomiting, diarrhea
• acne, skin rash, intense itching, hair loss (alopecia)
• breast enlargement
• vaginal infection
• fluid retention and changes in body weight

Rare Adverse Effects (may affect up to 1 in 1,000 people):

• allergic reactions (hypersensitivity)
• asthma
• breast secretion
• hearing problems
• skin conditions such as erythema nodosum (characterized by painful nodules on the skin of a reddish color) or erythema multiforme (characterized by a skin rash with redness in the shape of a target or ulcers)
• harmful blood clots in a vein or artery, for example:
• • in a leg or foot (i.e., DVT)
  • in a lung (i.e., PE)
  • heart attack
  • stroke
  • mild stroke or temporary symptoms similar to those of a stroke, called a transient ischemic attack (TIA)
  • blood clots in the liver, stomach/intestine, kidneys, or eye

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

Reporting Adverse Effects

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

5. Storage of Dretine Daily

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

This medicine does not require special storage conditions.

Expiration Date

Do not take Dretine daily after the expiration date that appears on the blister pack and on the packaging after the phrase "Do not use after:" or "EXP:". The expiration date is the last day of the month indicated.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE collection point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Dretine Daily

A strip of Dretine daily contains 21 active yellow tablets in the 1st, 2nd, and 3rd rows of the strip and 7 white placebo tablets in the 4th row.

Active Tablets:

The active ingredients are ethinylestradiol and drospirenone.

Each tablet contains 0.03 mg of ethinylestradiol and 3 mg of drospirenone.

The other components are:

Tablet core: lactose monohydrate, cornstarch, pregelatinized cornstarch, crospovidone, povidone, polysorbate 80, magnesium stearate.

Coating: partially hydrolyzed polyvinyl alcohol, titanium dioxide (E-171), macrogol 3350, talc, and yellow iron oxide (E-172).

Placebo Tablets:

Tablet core: lactose, povidone, magnesium stearate.

Coating: partially hydrolyzed polyvinyl alcohol, titanium dioxide (E-171), macrogol 3350, talc.

Appearance of Dretine Daily and Package Contents

The active tablets are film-coated, round, and yellow in color.

The placebo tablets are film-coated, round, and white in color.

Dretine daily is available in boxes of 1, 2, 3, 6, and 13 blister packs, each with 28 tablets (21 active tablets and 7 placebo tablets).

Only some package sizes may be marketed.

Marketing Authorization Holder

Theramex Ireland Limited

3rd Floor, Kilmore House,

Park Lane, Spencer Dock,

Dublin 1

D01 YE64

Ireland

Manufacturer

Laboratorios León Farma, S.A.

C/ La Vallina, s/n, Polígono Industrial Navatejera.

Villaquilambre 24193 (León)

Spain

Local Representative

Theramex Healthcare Spain, S.L.

Calle Martínez Villergas 52, Edificio C, planta 2ª izquierda.

28027 Madrid (Spain)

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of the Last Revision of this Prospectus: September 2024

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