Leaflet: information for the user

Duloxetina Combix 30 mg hard gastro-resistant capsules EFG

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, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must 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, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

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

2. What you need to know before starting to take Duloxetina Combix

3. How to take Duloxetina Combix

4. Possible side effects

5. Storage of Duloxetina Combix

6. Contents of the pack and additional information

Duloxetina Combix contains the active ingredient duloxetine. Duloxetina Combix increases the levels of serotonin and noradrenaline in the nervous system.

Duloxetina Combix is used in adults to treat:

• depression

• generalized anxiety disorder (chronic feeling of anxiety or nervousness)

• diabetic neuropathic pain (often described as burning, stabbing, pinching, stinging, or electric shock-like pain. There may be a loss of sensation in the affected area, or pain may occur when touching the area or exposing it to heat, cold, or pressure).

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

In people with diabetic neuropathic pain, it may take several weeks to start feeling better. You should consult a doctor if you worsen or do not improve within 2 months.

Do not takeDuloxetine:

• if you are allergic to duloxetine or any of the other ingredients in this medicine (listed in section 6)
• if you have liver failure
• if you have severe kidney failure
• if you are taking or have taken in the last 14 days another medicine known as a monoamine oxidase inhibitor (MAOI) (see “Duloxetine use with other medicines”)
• if you are taking fluvoxamine, which is usually used to treat depression, ciprofloxacin or enoxacin, which are used to treat some infections
• if you are taking other medicines that contain duloxetine (see “Duloxetine use 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 for the following reasons:

• if you are taking other medicines to treat depression (see “Duloxetine use with other medicines”)
• if you are taking St. John's Wort, a herbal treatment (Hypericum perforatum)
• if you have any kidney disease
• if you have had seizures (epileptic fits)
• if you have had mania
• if you have bipolar disorder
• if you have eye problems, such as some types of glaucoma (increased eye pressure)
• if you have a tendency to develop haematomas (bleeding)
• if you have a risk of low sodium levels (for example if you are taking diuretics, especially if you are an elderly person)
• if you are taking other medicines that can cause liver damage
• if you are taking other medicines that contain duloxetine (see “Duloxetine use with other medicines”)

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

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

Thoughts of suicide and worsening of depression or anxiety

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

It is more likely that you will have these thoughts if:

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

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

It may be helpful to tell a close friend or family member that you are depressed or have an anxiety disorder, and ask them to read this leaflet. They may be able to tell if your depression or anxiety is getting worse, or if they are concerned about changes in your behaviour.

You should also contact your doctor:

if you experience signs and symptoms of restlessness, hallucinations, loss of coordination, rapid heartbeat, increased body temperature, rapid changes in blood pressure, hyperactive reflexes, diarrhoea, coma, nausea, vomiting, as you may be suffering from a serotonin syndrome.

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

Children and adolescents

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

Use ofDuloxetinewith other medicines

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine.

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

You should avoid using 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 consulting your doctor.

You should also inform 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 known as a monoamine oxidase inhibitor (MAOI). For example, 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 treatment with an MAOI before taking Duloxetine. Similarly, you should wait at least 5 days after stopping treatment with Duloxetine before starting treatment with an MAOI.

Medicines that cause drowsiness:This includes prescription medicines prescribed by your doctor, such as benzodiazepines, powerful analgesics, 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 and amitriptyline), petidina, 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 inform 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 taking Duloxetine.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy

Inform your doctor if you become pregnant or if you are trying to become pregnant while taking Duloxetine. You should only use Duloxetine after discussing the potential benefits and any potential risks to the fetus with your doctor.

Make sure your midwife and/or doctor know that 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 more rapidly and turn blue. These symptoms usually start within the first 24 hours after the baby's birth. If this happens to your baby, you should contact your midwife and/or doctor immediately.

If you take Duloxetine towards the end of your pregnancy, your baby may have some symptoms when born. These usually start at birth or within the first few days after birth. These symptoms may include weak muscles, trembling, nervousness, difficulty feeding, breathing problems, and seizures. If your baby has any of these symptoms when born or if you are concerned about your baby's health, contact your doctor or midwife, who can advise you.

Breastfeeding

Inform your doctor if you are breastfeeding. Duloxetine is not recommended during breastfeeding. Ask your doctor or pharmacist for advice.

Driving and operating machinery

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

Duloxetine contains saccharose

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

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Duloxetina Combix should be taken orally. Swallow the capsule whole with water.

For depression and diabetic neuropathic pain:

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

For generalized anxiety disorder:

The initial normal dose of Duloxetina 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 to 120 mg per day depending on your response to Duloxetina Combix.

To avoid forgetting to take Duloxetina Combix, it may be helpful to take it at the same time every day.

Discuss with your doctor for how long you should take Duloxetina Combix. Do not stop taking Duloxetina Combix or change your dose without consulting your doctor. It is essential 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 harder to treat.

If you take moreDuloxetina Combixthan you should

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

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

If you forgot to takeDuloxetina Combix

If you forget to take a dose, take it as soon as you remember. However, if it is time for the next dose, skip the missed dose and take a single dose as you normally do. Do not take a double dose to compensate for the missed doses. Do not take more Duloxetina Combix than prescribed for you in a day.

If you interrupt treatment withDuloxetina Combix

DO NOT stop taking your capsules without consulting your doctor, even if you feel better. If your doctor thinks you no longer need to take Duloxetina Combix, they will instruct you to reduce your dose for at least 2 weeks before stopping treatment.

Some patients who have stopped treatment with Duloxetina Combix abruptly have experienced symptoms such as:

• dizziness, feeling of pins and needles or electric shock (especially in the head), sleep disturbances (intense 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 vertigo.

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

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them. These side effects are usually mild to moderate and often disappear within a few weeks.

Very common side effects (may affect more than 1 in 10 patients)

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

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

• loss of appetite
• difficulty sleeping, feeling agitated, decreased libido, anxiety, difficulty or inability to have an orgasm, unusual dreams
• dizziness, feeling slow, tremor, numbness, including numbness, itching, or tingling in the skin
• blurred vision
• tinnitus (perception of sounds in the ear when there is no sound outside)
• 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
• painful urination, urinating frequently
• difficulty achieving an erection, changes in ejaculation
• falls (mainly in older adults), fatigue
• weight loss

Children and adolescents under 18 years of age with depression treated with this medicine experienced 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 side effects (may affect up to 1 in 100 patients)

• throat inflammation causing hoarseness
• suicidal thoughts, difficulty sleeping, bruxism, feeling disoriented, lack of motivation
• muscle spasms and involuntary muscle movements, feeling restless 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
• pupil dilation (the black center of the eye), vision problems
• feeling dizzy or vertigo, ear pain
• rapid or irregular heartbeat
• syncope, dizziness, feeling dizzy or syncope when standing up, cold hands and/or feet
• throat spasms, nasal bleeding
• vomiting blood, or black stools, gastroenteritis, belching, difficulty swallowing
• liver inflammation that can cause abdominal pain and yellowing of the skin or white part of the eyes
• night sweats, rashes, 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 periods, occasionally light or absent periods, testicular or scrotal pain
• chest pain, feeling cold, thirst, chills, feeling hot, gait alteration
• weight gain
• Duloxetine may cause effects that you may not be aware of, such as increased liver enzymes or blood levels of potassium, creatine phosphokinase, sugar, or cholesterol.

Rare side effects (may affect up to 1 in 1,000 patients)

• severe allergic reactions, which 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 (mainly in older adults; symptoms may include dizziness, weakness, confusion, sleepiness, or excessive fatigue, nausea, or vomiting, more serious symptoms are syncope, convulsions, or falls), syndrome of inappropriate antidiuretic hormone secretion (SIADH).
• suicidal behavior, mania (hyperactivity, accelerated thinking, and decreased need for sleep), hallucinations, aggression, and anger
• "serotonin syndrome" (a rare reaction that can cause intense happiness, drowsiness, clumsiness, restlessness, feeling 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 white part of the eyes (jaundice)
• Stevens-Johnson syndrome (a severe disease with blistering of the skin, mouth, eyes, and genitals), severe allergic reactions that cause swelling of the face or throat (angioedema)
• jaw muscle contractions
• unusual odor of urine
• menopausal symptoms, abnormal milk production in men or women
• cough, wheezing, and shortness of breath, which may be accompanied by high fever

Very rare side effects (may affect up to 1 in 10,000 patients)

• inflammation of the skin blood vessels (cutaneous vasculitis)

Unknown frequency (cannot be estimated from available data)

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

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 Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication 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.

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

Composition ofDuloxetina Combix

• Theactive principleis duloxetina.

Each capsule contains 33.680 mg of duloxetina hydrochloride corresponding to 30 mg of duloxetina.

• Theothercomponents are:

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

Capsule coating: gelatin, sodium lauryl sulfate, titanium dioxide (E171) and indigo carmine (E132).

Appearance of the product and content of the container

Duloxetina Combix 30 mg is presented in hard gelatin capsules of size 3, with a blue opaque cap and a white opaque body, containing loose pink pellets.

Duloxetina Combix 30 mg is presented in PVC/PVDC-Aluminum blisters, OPA/Alu/PVC-Aluminum blisters and Desiccant/OPA/Al/PE-Aluminum/PE blisters in containers of 7 and 28 capsules.

Only some sizes of containers may be commercially marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Laboratorios Combix, S.L.U.

C/Badajoz, 2. Building 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible for manufacturing

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

Last review date of this leaflet: July 2024

The detailed information of this medicine is available on the website of theSpanish Agency of Medicines and Medical Devices (AEMPS)https://www.aemps.gob.es/