Package Leaflet: Information for the User

Dretine 0.03 mg/3 mg Film-Coated Tablets

Ethinylestradiol/Drospirenone

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

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

Important things you should know about combined hormonal contraceptives (CHCs):

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

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

Each tablet contains a small amount of two different female hormones, known as drospirenona and ethinylestradiol.

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

When Not to Use Dretine

You should not use Dretine 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 leg vein (deep vein thrombosis, DVT), in the lungs (pulmonary embolism, PE), or in other organs
• If you know that 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 surgery or if you spend a lot of time without standing 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, symptoms of a stroke).
• If you have any of the following diseases that may increase your risk of forming a blood clot in the arteries:
• Severe diabetes with vascular 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 function well (renal insufficiency).
• If you have (or have ever had) a tumor in the liver.
• If you have (or have ever had), or if you suspect that you have breast cancer or cancer of the reproductive 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 medication (including in section 6). This may cause itching, rash, or inflammation.
• 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 “Taking Dretine with other medications”).

Additional Information on Special Populations

Children and Adolescents

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

Older Patients

Dretine is not indicated for use after menopause.

Women with Liver Insufficiency

Do not take Dretine if you have liver disease. See also the sections “Do not take Dretine” and “Warnings and Precautions”.

Women with Renal Insufficiency

Do not take Dretine if you have kidney dysfunction or acute renal insufficiency. See also the sections “When not to use Dretine” and “Warnings and Precautions”.

Warnings and Precautions

When to Have Special Care with Dretine

Consult your doctor or pharmacist before taking Dretine.

• If you notice possible signs of a blood clot that may mean you are suffering from a blood clot in the leg (deep vein thrombosis), a blood clot in the lungs (pulmonary embolism), a heart attack, or a stroke (see section “Blood Clots”).

For a description of the symptoms of these serious side effects, see “How to Recognize a Blood Clot”

In some situations, you should have special care while using Dretine or any other combined hormonal contraceptive, and you may need to have regular check-ups with your doctor.

Inform Your Doctor if You Suffer from Any of the Following Conditions

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

• If any of your close relatives have had breast cancer
• If you have any liver or gallbladder disease
• If you have diabetes
• If you have depression
• If you have inflammatory bowel disease (Crohn's disease or ulcerative colitis)
• If you have systemic lupus erythematosus (SLE, a disease that affects your natural defense system)
• If you have hemolytic uremic syndrome (HUS, a disorder of blood clotting that causes kidney failure)
• If you have sickle cell anemia (a hereditary disorder 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 surgery or spend a lot of time without standing up (see section 2 “Blood Clots”)
• If you recently gave birth, you are at higher risk of blood clots. Ask your doctor when you can start taking Dretine after delivery.
• If you have superficial thrombophlebitis (inflammation of the veins under the skin)
• If you have varicose veins
• If you have epilepsy (see “Dretine and use of other medications”)
• If you have any disease that first appeared during pregnancy or during early use of sex hormones (for example, hearing loss, a blood disorder called porphyria, skin rash with blisters during pregnancy (herpes gestationalis), a nervous disorder characterized by involuntary movements (Sydenham's chorea)
• If you have or have had melasma (a skin discoloration, especially on the face or neck, known as “pregnancy mask”). In this case, you should avoid direct exposure to the sun or ultraviolet light.
• If you have hereditary angioedema, estrogen-containing products may induce or worsen the symptoms of angioedema. You should seek medical attention immediately if you experience symptoms of angioedema such as swelling of the face, tongue, and/or throat, and/or difficulty swallowing or urticaria, along with difficulty breathing.

BLOOD CLOTS

The use of a combined hormonal contraceptive like Dretine increases your risk of suffering 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 veins (called “deep vein thrombosis”, “venous thromboembolism”, or VTE)
• In arteries (called “arterial thrombosis”, “arterial thromboembolism”, or ATE)

The recovery of blood clots is not always complete. In rare cases, there may be long-lasting or even fatal effects.

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

HOW TO RECOGNIZE A BLOOD CLOT

Seek Urgent Medical Assistanceif 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 veins (venous thrombosis). However, these adverse 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 may cause deep vein thrombosis (DVT)
• If a blood clot breaks loose from the leg and lodges in the lung, it may cause a pulmonary embolism
• In very rare cases, a blood clot can form in a vein in another organ, such as the eye (retinal vein thrombosis)

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

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

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

When you stop taking Dretine, your risk of a blood clot returns to normal in 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 is small.

• Of every 10,000 women who do not use a combined hormonal contraceptive and are not pregnant, 2 will develop a blood clot in a year.
• Of every 10,000 women who use a combined hormonal contraceptive containing levonorgestrel, noretisterone, or norgestimato, 5-7 will develop a blood clot in a year.
• Of every 10,000 women who use a combined hormonal contraceptive containing drospirenone like Dretine, 9-12 will develop a blood clot in a year.
• The risk of a blood clot will depend on your personal history (see “Factors that increase your risk of a blood clot” below)

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

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

• If you are overweight (body mass index (BMI) greater than 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 about 50 years). In this case, you may have an inherited disorder of blood clotting.
• If you need surgery or spend a lot of time without standing up due to an injury or disease or if you have a leg cast. You may need to interrupt the use of Dretine for several weeks before the surgical procedure or while you have reduced mobility. If you need to interrupt the use of Dretine, ask your doctor when you can start using it again.
• With increasing age (especially above about 35 years)
• If you have given birth recently

Your risk of a blood clot increases the more conditions you have.

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

It is essential to inform your doctor if you suffer from any of the conditions above, even if you are unsure. Your doctor may decide that you should interrupt the use of Dretine.

If any of the conditions above change while you are using Dretine, for example, a close relative experiences a blood clot without a 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 blood clot in an artery can cause serious problems. For example, it can cause a heart attack or a stroke.

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

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

• With age (above 35 years)
• If you smoke. When using a combined hormonal contraceptive like Dretine, you are advised to quit smoking. If you are unable to quit 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 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, arrhythmia called atrial fibrillation)
• If you have diabetes

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

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

Dretine and Cancer

Cancer of the breast has been observed slightly more frequently in women using combined hormonal contraceptives, but it is not known whether this is due to the treatment. For example, it may be that more tumors are detected in women taking combined hormonal contraceptives because they are examined by the doctor more frequently. The incidence of breast tumors decreases gradually after stopping combined hormonal contraceptives.

It is essential to have regular breast examinations and to consult your doctor if you notice any lump.

In rare cases, benign tumors in the liver and, even more rarely, malignant tumors have been reported in users of combined hormonal contraceptives. Consult your doctor if you experience severe abdominal pain.

Menstrual Bleeding

During the first few months of taking Dretine, you may experience unexpected bleeding (bleeding outside of the days of placebo pill use). If these bleeding episodes occur beyond a few months or start after a few months, your doctor should investigate what is wrong.

What to Do if You Do Not Have a Period During Placebo Days

If you have taken all the active pink pills correctly, have not had intense vomiting or diarrhea, and have not taken other medications, it is very unlikely that you are pregnant.

If your expected period does not come in two consecutive instances, you may be pregnant. Consult your doctor immediately. Do not start the next pack until you are sure you are not pregnant.

Mental Health Disorders

Some women who use hormonal contraceptives like Dretine have reported depression or a depressed mood. Depression can be severe and sometimes may induce suicidal thoughts. If you experience mood changes and depressive symptoms, consult your doctor for additional medical advice as soon as possible.

Taking Dretine with Other Medications

Some medications may affect the levels of Dretine in the blood and may make it less effective in preventing pregnancy or may cause unexpected bleeding. This may occur with:

• Medications used in the treatment of
• epilepsy (e.g., primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine)
• tuberculosis (e.g., rifampicin)
• infections with HIV and hepatitis C (the so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine, efavirenz)
• fungal infections (griseofulvin, ketoconazole)
• arthritis, osteoarthritis (etoricoxib)
• high blood pressure in the blood vessels of the lungs (bosentan)
• The medicinal herb St. John's Wort.

• Dretine may affect the effect of other medications, for example:
• medications containing ciclosporin
• the antiepileptic lamotrigine (may lead to an increase in seizure frequency)
• theophylline (used to treat respiratory problems)
• tiagabine (used to treat muscle pain or cramps).

Do not use Dretine if you have hepatitis C and are taking medications that contain ombitasvir/paritaprevir/ritonavir, dasabuvir, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir, as these medications may cause increases in liver function parameters in the blood (elevated liver enzyme ALT).

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

Dretine can be restarted approximately 2 weeks after completing this treatment. See section “When not to use Dretine”.

Consult your doctor or pharmacist before using any medication.

Taking Dretine with Food and Drinks

Dretine can be taken with or without food, and with a little water if necessary.

Laboratory Tests

If you need a blood test, inform your doctor or the laboratory staff that you are taking the pill, as hormonal contraceptives may affect the results of some tests.

Pregnancy and Lactation

Pregnancy

If you are pregnant, do not take Dretine. If you become pregnant during treatment with Dretine, stop the treatment immediately and consult your doctor.If you want to become pregnant, you can stop taking Dretine at any time (see “If you want to stop taking Dretine”)

Consult your doctor or pharmacist before taking any medication.

Lactation

Generally, it is not recommended to take Dretine during lactation. If you want to take the contraceptive while breastfeeding, consult your doctor.

Consult your doctor or pharmacist before taking any medication.

Driving and Operating Machinery

There is no information to suggest that the use of Dretine has any effect on your ability to drive or operate machinery.

Dretine Contains Lactose

If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking the medication.

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

Take one Dretine tablet every day with a glass of water if necessary. You can take the tablets with or without food, but approximately at the same time every day.

The strip contains 21 tablets. The day of the week when you should take the tablet is printed next to each tablet. For example, if you start on a Wednesday, you should take a tablet with "WED" next to it. Follow the direction of the arrow on the packaging until you have taken all 21 tablets.

Do not take any tablets for 7 days after that. During those 7 days without tablets (also called a break or rest week), menstruation should occur. Usually, menstruation, also known as withdrawal bleeding, begins on the second or third day of the rest week.

On the 8th day after taking the last Dretine tablet (i.e., after the 7-day rest week), you should start with the next strip, even if menstruation has not ended. This means that you should start all strips on the same day of the week and that menstruation should occur on the same days every month.

If you use Dretine in this way, you will also be protected against pregnancy during the 7 days when you are not taking any tablets.

When to start with the first strip

• If you have not used any hormone-containing contraceptives in the past month.

Start taking Dretine on the first day of your cycle (i.e., the first day of your period). If you start Dretine 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 should use additional contraceptive methods (e.g., a condom) for the first 7 days.

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

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

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

You can switch from the pill only with progestin on any day (if it's an implant or IUS, on the day of its removal; if it's an injection, on the day of the next injection) but, in all cases, use additional contraceptive methods (e.g., a condom) for the first 7 days of tablet-taking.

• After an abortion.

Follow your doctor's recommendations.

• After giving birth.

You can start taking Dretine between 21 and 28 days after giving birth. If you start later, use one of the barrier methods (e.g., a condom) for the first 7 days of Dretine use.

If, after giving birth, you have already had sex before starting Dretine (again), you should be sure you are not pregnant or wait for your next menstrual period.

• If you are breastfeeding and want to start taking Dretine (again) after giving birth.

Read the section "Breastfeeding".

Ask your doctor if you are unsure when to start.

If you take more Dretine than you should

No serious cases of overdose of etinilestradiol/drospirenona have been reported.

If you take many tablets at once, you may experience 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 tablets, or if 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 bring the packaging and the medication leaflet to the healthcare professional.

If you forget to take Dretine

• If you are lateless than 12 hoursin taking a tablet, the protection against pregnancy does not decrease. Take the tablet as soon as you remember and then take the next tablets again at the usual time.
• If you are latemore than 12 hoursin taking a tablet, the protection against pregnancy may decrease. The more tablets you have forgotten, the higher the risk of pregnancy.

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

• More than one tablet forgotten in a strip

Consult your doctor.

• One tablet forgotten in week 1

Take the forgotten tablet as soon as you remember, even if this means taking two tablets at once. Continue taking the next tablets at the usual time and useextra precautions, for the next 7 days, for example, a condom. If you have had sex in the week before forgetting the tablet, you should know that there is a risk of pregnancy. In that case, consult your doctor.

• One tablet forgotten in week 2

Take the forgotten tablet as soon as you remember, even if this means taking two tablets at once. Continue taking the next tablets at the usual time. The protection against pregnancy does not decrease and you do not need to take extra precautions.

• One tablet forgotten in week 3

You can choose between two options:

You may experience small bleeding or bleeding similar to menstruation while using the next strip. After the usual 7-day break without tablets, continue with the next strip.

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

• If you have forgotten to take one of the tablets in the strip and do not have bleeding during the first break without tablets, you may be pregnant. Consult your doctor before continuing with the next strip.

What to do in case of vomiting or intense diarrhea

If you have vomiting in the 3-4 hours after taking a tablet or have intense 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 tablet. After the vomiting or diarrhea, take another tablet from a reserve strip as soon as possible. If possible, take itbefore 12 hourshave passed since your usual time for taking the contraceptive. If this is not possible or more than 12 hours have passed, you should follow the advice given in "If you forget to take Dretine".

Delayed menstrual period: what you should know

Although not recommended, it is possible to delay your menstrual period by going directly to a new Dretine strip instead of starting the break without tablets and finishing it. You may experience small bleeding or bleeding similar to menstruation while using the next strip. After the usual 7-day break without tablets, continue with the next strip.

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

Change in the first day of menstrual period: what you should know

If you take the tablets according to the instructions, your menstrual period will start during the break without tablets. If you need to change this day, reduce the number of days without tablets (but never increase it – 7 is the maximum!). For example, if your break without tablets starts on a Friday and you want to change it to a Tuesday (3 days earlier), start a new strip 3 days earlier than usual. If you make the break without tablets 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.

Ask your doctor if you are unsure what to do.

If you want to stop taking Dretine

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

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

Like all medications, Dretine may cause side effects, although not everyone will experience them. If you experience any side effect, especially if it is severe and persistent, or if you have any health changes that you think may be related to Dretine, consult your doctor.

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

The following list of side effects has been associated with the use of Drospirenona/Ethinylestradiol:

Frequent side effects(may affect up to 1in 10 women):

• menstrual disorders, intermenstrual bleeding, breast pain, breast tenderness.
• headaches, depressive mood
• migraines
• nausea
• thick, white vaginal discharge and vaginal yeast infection

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

• changes in sex drive
• 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 side effects(may affect up to 1in 1,000 people):

• allergic reactions (hypersensitivity), asthma
• breast secretion
• hearing problems
• skin conditions such as erythema nodosum (characterized by painful red nodules on the skin) or erythema multiforme (characterized by skin rash with red rings 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 or temporary stroke-like symptoms, known as 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 of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Vigilance of Medicinal Products for Human Use Website: www.notificaRAM.es

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

This medication does not require special storage conditions.

Do not take this medication after the expiration date that appears on the blister and packaging after the phrase “Do not use after:” or “EXP:”. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Dretine

The active principles are etinilestradiol and drospirenona.

Each tablet contains 0.03 mg of etinilestradiol and 3 mg of drospirenona.

The other components are:

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

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

Appearance of Dretine and packaging contents

Coated tablets, round, yellow in color.

Dretine is available in boxes of 1, 2, 3, 6, and 13 blisters, each containing 21 tablets

Only some packaging sizes may be marketed.

Marketing authorization holder and manufacturer

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.

Navatejera Industrial Estate;

La Vallina s/n;

24008-Villaquilambre, León

Spain

Or

Merckle GmbH

Ludwig-Merckle-Street, 3

Blaubeuren

Germany

Local Representative

Theramex Healthcare Spain, S.L.

Calle Martínez Villergas 52, Edificio C, 2nd floor left.

28027 Madrid

Spain

This medicine is authorized in the member states of the European Economic Area with the following names:

Last review date of this leaflet: October 2022

For detailed and updated information on this medicine, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/