DULOXETINE COMBIX 60 mg GASTRO-RESISTANT HARD CAPSULES

Introduction

Package Leaflet: Information for the User

Duloxetine Combix 60 mg Hard Gastro-Resistant Capsules EFG

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information:

1. What is Duloxetine Combix and what it is used for
2. What you need to know before you take Duloxetine Combix
3. How to take Duloxetine Combix
4. Possible side effects
5. Storing Duloxetine Combix
6. Contents of the pack and other information

1. What is Duloxetine Combix and what it is used for

Duloxetine Combix contains the active substance duloxetine. Duloxetine Combix increases the levels of serotonin and noradrenaline in the nervous system.

Duloxetine Combix is used in adults to treat:

• depression

• generalized anxiety disorder (a persistent feeling of anxiety or nervousness)

• diabetic neuropathic pain (often described as burning, shooting, stabbing, stinging, or like an electric shock. There may be loss of sensation in the affected area, or it may occur that when the area is touched or comes into contact with heat, cold, or pressure, pain is produced).

Duloxetine Combix starts to work in most people with depression or anxiety within 2 weeks of starting treatment, but it may take between 2 and 4 weeks before you start to feel better. Inform your doctor if you do not notice an improvement after this time. Your doctor may continue to give you Duloxetine Combix when you are feeling better to prevent your depression or anxiety from returning.

In people with diabetic neuropathic pain, it may take a few weeks before you start to feel better. You should consult a doctor if it gets worse or if it does not improve after 2 months.

2. What you need to know before you take Duloxetine Combix

Do not takeDuloxetineif:

• you are allergic to duloxetine or any of the other ingredients of this medicine (listed in section 6)
• you have liver failure
• you have severe kidney disease
• you are taking or have taken within the last 14 days another medicinal product called a monoamine oxidase inhibitor (MAOI) (see "Using Duloxetine with other medicines")
• you are taking fluvoxamine, which is usually used to treat depression, ciprofloxacin, or enoxacin, which are used to treat some infections
• you are taking other medicines that contain duloxetine (see "Using Duloxetine with other medicines")

Consult your doctor if you have high blood pressure or heart disease. Your doctor will tell you if you should take Duloxetine.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Duloxetine. Duloxetine may not be suitable for you due to the following reasons:

• you are using other medicines to treat depression (see "Using Duloxetine with other medicines")
• you are taking St. John's Wort, a herbal remedy (Hypericum perforatum)
• you have any kidney disease
• you have had seizures (epileptic fits)
• you have had mania
• you suffer from bipolar disorder
• you have eye problems, such as some types of glaucoma (increased eye pressure)
• you have had bleeding problems (tendency to develop bruises)
• you are at risk of having low sodium levels (for example, if you are taking diuretics, especially if you are an elderly person).
• you are being treated with other medicines that may cause liver damage
• you are taking other medicines that contain duloxetine (see "Using Duloxetine with other medicines")

Duloxetine may cause a feeling of restlessness or inability to sit or stand still. If this happens, you should tell your doctor.

Some medicines in the same class as Duloxetine Combix (called SSRIs/SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms persist after stopping treatment.

Suicidal thoughts and worsening of your depression or anxiety

If you are depressed and/or suffer from anxiety disorders, you may sometimes have thoughts of self-harm or suicide. These thoughts may increase at the start of treatment with antidepressants, as all these medicines take time to work, usually about two weeks but sometimes longer.

You are more likely to have these thoughts if:

• you have previously had thoughts of self-harm or suicide
• you are a young adult. There is information from clinical trials that has shown an increased risk of suicidal behavior in adults under 25 years who are being treated for a psychiatric disorder with antidepressants.

Contact your doctor or go directly to the hospital at the moment you have any thoughts of self-harm or suicide.

It may be useful for you to tell a relative or close friend that you are depressed or suffer from an anxiety disorder and ask them to read this leaflet. You can ask them to tell you if they notice that your depression or anxiety is getting worse, or if they are worried about changes in your behavior.

You should also contact your doctor:

If you experience signs and symptoms of agitation, hallucinations, loss of coordination, rapid heartbeat, increased body temperature, rapid changes in blood pressure, overactive reflexes, diarrhea, coma, nausea, vomiting, as you may be suffering from serotonin syndrome.

In its most severe form, serotonin syndrome can resemble Neuroleptic Malignant Syndrome (NMS). The signs and symptoms of NMS can include a combination of fever, rapid heartbeat, sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test).

Children and adolescents

Duloxetine should not normally be used in children and adolescents under 18 years. Also, you should know that patients under 18 years when taking this class of medicines have an increased risk of side effects such as suicidal attempts, suicidal thoughts, and hostility (mainly aggression, oppositional behavior, and anger). Despite this, your doctor may prescribe Duloxetine to patients under 18 years because they decide it may be beneficial for the patient. If your doctor has prescribed Duloxetine to a patient under 18 years and you want to discuss it, please go back to your doctor. You must inform your doctor if any of the above symptoms appear or worsen in patients under 18 years who are taking Duloxetine. Also, in this age group, the long-term safety effects of Duloxetine related to growth, maturation, and cognitive and behavioral development have not yet been demonstrated.

UsingDuloxetinewith other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

The main component of Duloxetine Combix, duloxetine, is used in other medicines for other treatments: diabetic neuropathic pain, depression, anxiety, and urinary incontinence.

It should be avoided to use more than one of these medicines at the same time. Check with your doctor if you are already using other medicines that contain duloxetine.

Your doctor will decide if you can take Duloxetine with other medicines. Do not start or stop taking any medicine, including those bought without a prescription and herbal remedies, without first talking to your doctor.

You should also tell your doctor if you are taking any of the following medicines:

Monoamine oxidase inhibitors (MAOIs):you should not take Duloxetine if you are taking, or have taken in the last 14 days, another antidepressant medicine called a monoamine oxidase inhibitor (MAOI). Examples of MAOIs include moclobemide (an antidepressant) and linezolid (an antibiotic). Taking an MAOI with many prescription medicines, including Duloxetine, can cause serious side effects, even life-threatening. You should wait at least 14 days after stopping an MAOI before taking Duloxetine. Similarly, you should wait at least 5 days after stopping Duloxetine before starting an MAOI.

Medicines that cause drowsiness:These include medicines prescribed by your doctor such as benzodiazepines, strong painkillers, antipsychotics, phenobarbital, and antihistamines.

Medicines that increase serotonin levels: Triptans, tramadol, tryptophan, selective serotonin reuptake inhibitors (SSRIs, such as paroxetine and fluoxetine), serotonin-norepinephrine reuptake inhibitors (SNRIs, such as venlafaxine), tricyclic antidepressants (such as clomipramine, amitriptyline), pethidine, St. John's Wort, and MAOIs (such as moclobemide and linezolid). These medicines increase the risk of side effects; if you notice any unusual symptoms when using any of these medicines with Duloxetine, you should tell your doctor.

Oral anticoagulants or antiplatelet agents:Medicines that thin the blood or prevent blood clots. These medicines may increase the risk of bleeding.

TakingDuloxetinewith food, drinks, and alcohol

Duloxetine can be taken with or without food. You should be careful if you drink alcohol while being treated with Duloxetine.

Pregnancy and breastfeeding

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

Pregnancy

Tell your doctor if you become pregnant or are trying to become pregnant while being treated with Duloxetine. You should only use Duloxetine after discussing the potential benefits and risks with your doctor.

Make sure your midwife and/or doctor know you are taking Duloxetine. Other similar medicines (SSRIs), taken during pregnancy, may increase the risk of a serious condition in babies called persistent pulmonary hypertension of the newborn (PPHN), which makes the baby breathe faster and turn blue. These symptoms usually start during the first 24 hours after birth. If this happens to your baby, you should contact your midwife and/or doctor immediately.

If you take Duloxetine near the end of your pregnancy, your baby may have some symptoms when it is born. These usually start at birth or in the first few days after birth. These symptoms include weak muscles, trembling, restlessness, difficulty feeding, breathing problems, and seizures. If your baby has any of these symptoms when it is born, or if you are worried about your baby's health, contact your doctor or midwife, who will be able to advise you.

Breastfeeding

Tell your doctor if you are breastfeeding. Duloxetine is not recommended during breastfeeding.

Driving and using machines

During treatment with Duloxetine, you may feel drowsy or dizzy. Do not drive or operate tools or machines until you know how the treatment with Duloxetine affects you.

Duloxetinecontains sucrose

This medicine contains sucrose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Duloxetine Combix

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

Duloxetine Combix should be taken by mouth. You should swallow the capsule whole with water.

For depression and diabetic neuropathic pain:

The recommended dose of Duloxetine Combix is 60 mg once a day, but your doctor will prescribe the dose that is best for you.

For generalized anxiety disorder:

The usual starting dose of Duloxetine Combix is 30 mg once a day, after which most patients will receive 60 mg once a day, but your doctor will prescribe the dose that is best for you. The dose may be adjusted up to 120 mg a day depending on your response to Duloxetine Combix.

To help you remember to take Duloxetine Combix, you can take it at the same time every day.

Discuss with your doctor how long you should take Duloxetine Combix. Do not stop taking Duloxetine Combix, or change your dose, without talking to your doctor. It is important to treat your condition properly to help you improve. If you do not treat it, your condition may not disappear and may become more severe and more difficult to treat.

If you take moreDuloxetine Combixthan you should

Call your doctor or pharmacist immediately if you take more Duloxetine Combix than prescribed by your doctor. Symptoms produced by an overdose include drowsiness, coma, serotonin syndrome (a rare reaction that can cause a feeling of intense happiness, drowsiness, clumsiness, restlessness, feeling drunk, fever, sweating, or muscle stiffness), seizures, vomiting, and rapid heartbeat.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to takeDuloxetine Combix

If you forget to take a dose, take it as soon as you remember. However, if it is time for your next dose, skip the missed dose and take a single dose as you normally would. Do not take a double dose to make up for missed doses. Do not take more Duloxetine Combix than prescribed for you in one day.

If you stop takingDuloxetine Combix

Do not stop taking your capsules without the advice of your doctor, even if you feel better.If your doctor thinks you do not need to continue taking Duloxetine Combix, they will tell you how to reduce your dose over at least 2 weeks before stopping treatment.

Some patients who have stopped taking Duloxetine Combix have experienced symptoms such as:

• dizziness, sensation of pins and needles, or electric shock-like sensations (especially in the head), sleep disturbances (vivid dreams, nightmares, inability to sleep), fatigue, drowsiness, feeling of restlessness or agitation, feeling of anxiety, nausea or vomiting, tremors, headaches, muscle pain, feeling of irritability, diarrhea, and excessive sweating or dizziness.

These symptoms are usually not serious and disappear within a few days, but if you have symptoms that are bothersome, ask your doctor for advice.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. These effects are usually mild to moderate and disappear, often, within a few weeks.

Very Common Adverse Effects (may affect more than 1 in 10 patients)

• headache, drowsiness
• discomfort (nausea), dry mouth

Common Adverse Effects (may affect up to 1 in 10 patients)

• loss of appetite
• difficulty sleeping, feeling of agitation, decreased sexual desire, anxiety, difficulty or inability to have an orgasm, unusual dreams
• dizziness, feeling of slowness, tremor, numbness, including numbness, itching, or tingling of the skin
• blurred vision
• tinnitus (perception of sounds in the ear when there is no external sound)
• feeling palpitations in the chest
• increased blood pressure, flushing
• increased yawning
• constipation, diarrhea, stomach pain, vomiting, heartburn or indigestion, gas
• increased sweating, rash (itching)
• muscle pain, muscle spasms
• difficulty urinating, frequent urination
• difficulty getting an erection, changes in ejaculation
• falls (mostly in elderly people), fatigue
• weight loss

Children and adolescents under 18 years of age with depression treated with this medicine suffered a decrease in weight when they started taking this medicine. After 6 months of treatment, the weight increased to similar levels as other children and adolescents of the same age and sex.

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

• inflammation of the throat that causes hoarseness
• suicidal thoughts, difficulty sleeping, teeth grinding, feeling of disorientation, lack of motivation
• muscle spasms and involuntary movements, feeling of restlessness or inability to remain seated or still, nervousness, difficulty concentrating, changes in taste, difficulty controlling movements, e.g., lack of coordination or involuntary muscle movements, restless legs syndrome, poor quality sleep
• dilation of the pupils (the black dot in the center of the eye), vision problems
• feeling of dizziness or vertigo, ear pain
• rapid and/or irregular heartbeats
• fainting, dizziness, feeling of dizziness or fainting when standing up, coldness in the fingers of the hands and/or feet
• throat spasms, nosebleeds
• vomiting blood, or black stools, gastroenteritis, belching, difficulty swallowing
• inflammation of the liver that can cause abdominal pain and yellowing of the skin or the white part of the eyes
• night sweats, hives, cold sweats, sensitivity to sunlight, increased tendency to bruise
• muscle stiffness, muscle spasms
• difficulty or inability to urinate, difficulty starting urination, need to urinate at night, need to urinate more than usual, decreased urine flow
• abnormal vaginal bleeding, abnormal menstrual periods, including heavy, painful, irregular, or prolonged menstruation, exceptionally light or absent menstruation, pain in the testicles or scrotum
• chest pain, feeling of cold, thirst, chills, feeling of heat, alteration in gait
• weight gain
• Duloxetine may cause effects that you may not be aware of, such as increased liver enzymes or potassium levels in the blood, creatine phosphokinase, sugar, or cholesterol.

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

• severe allergic reactions that cause difficulty breathing or dizziness with swelling of the tongue or lips, allergic reactions
• decreased activity of the thyroid gland, which can cause fatigue or weight gain
• dehydration, low sodium levels in the blood (mostly in elderly people; symptoms may include feeling of dizziness, weakness, confusion, sleepiness, or excessive tiredness, nausea, or vomiting, the most serious symptoms are fainting, convulsions, or falls), syndrome of inadequate secretion of antidiuretic hormone (SIADH)
• suicidal behavior, mania (hyperactivity, accelerated thinking, and decreased need for sleep), hallucinations, aggression, and anger
• "Serotonin syndrome" (a rare reaction that can cause feelings of intense happiness, drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating, or muscle stiffness), convulsions
• increased pressure in the eye (glaucoma)
• inflammation of the mouth, bright red blood in the stool, bad breath, inflammation of the large intestine (leading to diarrhea)
• liver failure, yellowing of the skin or the white part of the eyes (jaundice)
• Stevens-Johnson syndrome (a serious disease with blistering of the skin, mouth, eyes, and genitals), severe allergic reactions that cause swelling of the face or throat (angioedema)
• contractions of the jaw muscle
• unusual urine odor
• menopausal symptoms, abnormal milk production in men or women
• cough, wheezing, and shortness of breath, which may be accompanied by high fever

Very Rare Adverse Effects (may affect up to 1 in 10,000 patients)

• inflammation of the blood vessels in the skin (cutaneous vasculitis)

Frequency Not Known (cannot be estimated from the available data)

• signs and symptoms of a condition called "stress cardiomyopathy", which may include chest pain, difficulty breathing, dizziness, fainting, and irregular heartbeats

Reporting of Adverse Effects

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

5. Storage of Duloxetina Combix

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above 30°C. Store in the original packaging to protect it from moisture.

Medicines should not be thrown away through the sewers or in the trash. Deposit the packaging and medicines that you no longer need in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition ofDuloxetina Combix

• The active ingredientis duloxetine.

Each capsule contains 67.360 mg of duloxetine hydrochloride, which corresponds to 60 mg of duloxetine.

• The othercomponents are:

Capsule content: hypromellose (E464), succinate acetate of hypromellose, sucrose, sugar spheres, talc (E553b), titanium dioxide (E171), triethyl citrate (E1505), and red iron oxide (E172).

Capsule shell: gelatin, sodium lauryl sulfate, titanium dioxide (E171), carmine indigo (E132), and yellow iron oxide (E172).

Product Appearance and Package Contents

Duloxetina Combix 60 mg is presented in hard gelatin capsules, size 1, with a blue opaque cap and a green opaque body, containing loose pink pellets.

Duloxetina Combix 60 mg is presented in PVC/PVDC-Aluminum blisters, OPA/Alu/PVC-Aluminum blisters, and Desiccant/OPA/Al/PE-Aluminum/PE blisters in packages of 28 and 56 capsules.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/Badajoz, 2. Edificio 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Date of the Last Revision of this Prospectus: July 2024

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