FLUOXETINE COMBIX 20 mg DISPERSIBLE TABLETS

Introduction

Package Leaflet: Information for the Patient

Fluoxetine Combix 20 mg Dispersible Tablets 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

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

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

Fluoxetine Combix contains the active substance fluoxetine hydrochloride, which belongs to a group of medicines called selective serotonin reuptake inhibitors (SSRIs).

This medicine is indicated for the treatment of:

Adults:

• Major depressive episodes
• Obsessive-compulsive disorder
• Bulimia nervosa: fluoxetine is indicated as a complement to psychotherapy for the reduction of binge-eating and purging.

Children over 8 years and adolescents:

• For moderate to severe depressive episodes, if there is no response to psychological therapy after 4 to 6 sessions. Fluoxetine should be offered to children or young people with moderate to severe depression only in combination with psychological therapy.

How Fluoxetine Combix works

Everyone has a substance in their brain called serotonin. People who are depressed or have obsessive-compulsive disorder or bulimia nervosa have lower levels of serotonin than others. It is not fully understood how fluoxetine and other SSRIs work, but they may help by increasing the levels of serotonin in the brain.

Treating these conditions is important to help you improve. If left untreated, your illness may not disappear and may become more severe and more difficult to treat.

You may need to be treated for a few weeks or months to make sure you are free of symptoms.

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

Do not take Fluoxetine Combix

• if you are allergic to fluoxetine or any of the other ingredients of this medicine (listed in section 6). If you experience a rash or other type of allergic reaction (such as itching, swelling of the face or lips or shortness of breath), stop taking the tablets immediately and contact your doctor as soon as possible
• if you are taking other medicines, known as irreversible non-selective monoamine oxidase inhibitors (MAOIs), as a severe or life-threatening reaction may occur (e.g. iproniazide, which is used to treat depression).

Treatment with fluoxetine may only be started at least 2 weeks after stopping treatment with an irreversible non-selective MAOI.

Do not takeany irreversible non-selective MAOI for at least 5 weeks after stopping fluoxetine medication. If you have been prescribed fluoxetine for a long period and/or at a high dose, your doctor may consider the need for a longer interval before taking an MAOI.

• if you are taking metoprolol (for heart failure) as it increases the risk of excessive slowing of heartbeats.

Warnings and precautions

Consult your doctor or pharmacist before starting to take fluoxetine if you have any of the following:

• If you have heart disease;
• If you start to experience fever, muscle stiffness or tremors, changes in your mental state such as confusion, irritability and extreme agitation, you may be suffering from a condition called “serotonin syndrome” or “neuroleptic malignant syndrome”. Although this syndrome is rare, it can be life-threatening, contact your doctor immediately,as you may need to stop treatment with fluoxetine;
• If you suffer from mania or have suffered from mania in the past; if you have a manic episode, contact your doctor immediately, as you may need to stop treatment with fluoxetine;
• If you have a history of bleeding disorders or if you develop bruising or unusual bleeding, or if you are pregnant (see “Pregnancy”);
• If you are taking medicines that affect blood clotting (see “Other medicines and Fluoxetine Combix”);
• If you have epilepsy or convulsions. If you have had convulsions or experience an increase in the frequency of them, contact your doctor immediately; you may need to stop treatment with fluoxetine;
• If you are receiving electroconvulsive therapy (ECT);
• If you are being treated with tamoxifen (used to treat breast cancer) (see “Other medicines and Fluoxetine Combix”);
• If you start to feel restless and cannot sit or stand still (akathisia). Increasing your dose of fluoxetine may worsen it;
• If you have diabetes (your doctor may need to adjust your insulin or other antidiabetic treatment);
• If you have liver problems (your doctor may need to adjust your dose);
• If you have a low resting heart rate and/or if you know you may have salt loss as a result of severe prolonged diarrhea and vomiting or the use of diuretics (water pills);
• If you are taking diuretics (water pills), especially if you are an elderly patient;
• Glaucoma (increased eye pressure).

Suicidal thoughts and worsening of your depression or anxiety disorder

If you are depressed and/or have an anxiety disorder, you may sometimes have thoughts of harming or killing yourself. These may increase when you first start taking antidepressants, as all these medicines need time to start working, usually around 2 weeks, although sometimes a little longer.

You are more likely to think this way:

• If you have previously had thoughts of self-harm or suicide.
• If you are a young adult. Information from clinical trials has shown an increased risk of suicidal behavior in adults under 25 years with psychiatric conditions, who were treated with antidepressants.

If you have thoughts of harming or killing yourself at any time, contact your doctor or go to hospital straight away.

You may find it helpful to tell a relative or close friendthat you are depressed or have an anxiety disorder and ask them to read this leaflet. You might ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behavior.

Children and adolescents aged 8 to 18 years:

Patients under 18 years have an increased risk of side effects such as suicide attempts, suicidal thoughts, and hostility (predominantly aggression, confrontational behavior, and irritability) when taking this class of medicines. Fluoxetine should only be used in children and adolescents aged 8 to 18 years for the treatment of moderate to severe depressive episodes (in combination with psychological therapy), and should not be used for other indications in this age group.

In addition, there is only limited information on the long-term safety of fluoxetine in relation to growth, puberty, and cognitive, emotional, and behavioral development in this age group. Nevertheless, if you are a patient under 18 years, your doctor may prescribe fluoxetine for the treatment of moderate to severe depressive episodes, in combination with psychological therapy, when they decide that it is the best option for you. If your doctor prescribes fluoxetine to a patient under 18 years and you wish to discuss this decision, please go back to your doctor. You should inform your doctor if any of the above symptoms appear or worsen when patients under 18 years are taking fluoxetine.

Fluoxetine should not be used in the treatment of children under 8 years of age.

Sexual dysfunction

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

Other medicines and Fluoxetine Combix

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

Do not take Fluoxetine Combix with:

• Certain irreversible non-selective monoamine oxidase inhibitors (MAOIs),some of which are used to treat depression. Irreversible non-selective MAOIs should not be used with fluoxetine as they may cause serious or life-threatening reactions (serotonin syndrome), (see section “Do not take Fluoxetine Combix”).

Treatment with fluoxetine should only be started at least 2 weeks after stopping treatment with an irreversible non-selective MAOI (e.g. tranylcypromine). Do nottake any irreversible non-selective MAOI for at least 5 weeks after stopping fluoxetine medication. If you have been prescribed fluoxetine for a long period and/or at a high dose, your doctor may consider the need for a longer interval before taking an MAOI.

• Metoprololwhen used for heart failure, as it increases the risk of excessive slowing of heartbeats.

Fluoxetine may affect the action of other medicines (interaction):

• Tamoxifen(used to treat breast cancer); your doctor may consider a different antidepressant treatment because fluoxetine may change the levels of this medicine in the blood and it cannot be ruled out that the effect of tamoxifen may be reduced.
• Monoamine oxidase A inhibitors (MAO-A)including moclobemide, linezolid (an antibiotic) and methylthioninium chloride (also known as methylthionine, used to treat conjunctivitis, itching, and mild eye irritation): due to the risk of serious and life-threatening reactions (called serotonin syndrome). Treatment with fluoxetine may be started the day after stopping treatment with reversible MAOIs, but your doctor may monitor you closely and use a lower dose of the MAOI medicine.
• Mequitazine(used to treat allergies); as taking this medicine with fluoxetine may increase the risk of changes in heart activity.
• Phenytoin(used to treat epilepsy); fluoxetine may increase the levels of this medicine in the blood, so your doctor will need to monitor you more closely and adjust the dose of phenytoin when given with fluoxetine.
• Lithium, selegiline, St. John's Wort, tramadol(for pain relief), triptans(for migraine treatment) and tryptophan; there is an increased risk of mild serotonin syndrome if these medicines are given with fluoxetine. Your doctor will monitor you more closely.
• Medicines that may affect heart rhythm, such as Class IA and III antiarrhythmics, antipsychotics(e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents(e.g. sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine), malaria treatmentparticularly halofantrine or some antihistamines(astemizole, mizolastine), as taking one or more of these medicines with fluoxetine may increase the risk of changes in heart activity.
• Anticoagulants(such as warfarin), NSAIDs (such as ibuprofen, diclofenac), aspirinand other medicines that affect blood clotting (including clozapine, used to treat certain mental disorders). Fluoxetine may alter the effect of these medicines in the blood. Your doctor will need to perform certain tests, adjust your dose, and monitor you more closely if you start or stop treatment with fluoxetine while taking warfarin.
• Cyproheptadine(used to treat allergies); as it may reduce the effect of fluoxetine.
• Medicines that lower sodium levels in the blood(including diuretics, desmopressin, carbamazepine, and oxcarbazepine); as the use of fluoxetine with these medicines may increase the risk of excessively low sodium levels in the blood.
• Antidepressantssuch as tricyclic antidepressants, other selective serotonin reuptake inhibitors (SSRIs), or bupropion, mefloquineor chloroquine(used to treat malaria), tramadol(for pain relief) or antipsychoticssuch as phenothiazines or butyrophenones; as the use of fluoxetine with these medicines may increase the risk of convulsions.
• Flecainide, propafenone, nebivololor encainide(for heart problems), carbamazepine(for epilepsy treatment), atomoxetineor tricyclic antidepressants(e.g. imipramine, desipramine, and amitriptyline) or risperidone(for schizophrenia treatment); as fluoxetine may change the levels of these medicines in the blood, your doctor may need to reduce your dose when given with fluoxetine.

Taking Fluoxetine Combix with food, drinks, and alcohol

• Fluoxetine can be taken with or without food, as you prefer.
• It is not recommended to drink alcohol while taking this medicine.

Pregnancy, breastfeeding, and fertility

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

Talk to your doctor as soon as possible if you are pregnant, think you may be pregnant, or are planning to become pregnant.

In babies whose mothers took fluoxetine during the first months of pregnancy, there are studies that describe a higher risk of suffering from congenital heart defects. In the general population, about 1 in 100 babies are born with a heart defect. This probability increased to about 2 in 100 in babies whose mothers took fluoxetine.

When taken during pregnancy, particularly in the last 3 months of pregnancy, medicines like fluoxetine may increase the risk of a serious disease 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 the baby is born. If this happens to your baby, contact your midwife and/or doctor immediately.

If you take fluoxetine in the final stages of pregnancy, there may be a higher risk of heavy vaginal bleeding soon after delivery, especially if you have a history of bleeding disorders. Your doctor or midwife should know that you are taking fluoxetine so they can advise you.

It is preferable not to use this treatment during pregnancy unless the potential benefit outweighs the potential risk. Therefore, you and your doctor may decide to stop taking fluoxetine gradually during pregnancy or before becoming pregnant. However, depending on your circumstances, your doctor may suggest that it is better for you to continue taking fluoxetine.

Caution should be exercised when used during pregnancy, especially during the last stage of pregnancy or just before delivery, as the following effects have been reported in newborn babies: irritability, tremors, muscle weakness, persistent crying, and difficulty sleeping or feeding.

Breastfeeding

Fluoxetine is excreted in breast milk and may cause side effects in children. You should only continue breastfeeding if it is absolutely necessary. If you continue breastfeeding, your doctor may prescribe a lower dose of fluoxetine.

Fertility

In animal studies, fluoxetine has been shown to reduce sperm quality. This may theoretically affect fertility, but it has not yet been observed to have an impact on human fertility.

Driving and using machines

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

Fluoxetine Combix contains aspartame

This medicine contains 4 mg of aspartame in each tablet.

Aspartame is a source of phenylalanine, which may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body cannot eliminate it properly.

Fluoxetine Combix contains sodium benzoate

This medicine contains 0.02 mg of sodium benzoate in each tablet.

Fluoxetine Combix contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; this is essentially “sodium-free”.

3. How to take Fluoxetina Combix

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again. Do not take more tablets than indicated by your doctor.

Swallow the tablets with half a glass of water, or dissolved in half a glass of water that you should swallow whole immediately. Do not chew the tablets.

Adults:

The recommended dose is:

• Depression: the recommended dose is 1 tablet (20 mg) daily. Your doctor may review and adjust your dose if necessary within 3 to 4 weeks after starting treatment. When necessary, the dose can be gradually increased up to a maximum of 3 tablets (60 mg) daily. The dose should be carefully increased to ensure that you receive the lowest effective dose. You may not feel better immediately after starting to take your medication for depression. This is common since there is no improvement in depressive symptoms until after the first few weeks of treatment. Patients with depression should be treated for a period of at least 6 months.
• Bulimia nervosa: the recommended dose is 3 tablets (60 mg) daily.
• Obsessive-compulsive disorder: the recommended dose is 1 tablet (20 mg) daily. Your doctor may review and adjust the dose after 2 weeks of treatment. When necessary, the dose can be gradually increased up to a maximum of 3 tablets (60 mg) daily. If no improvement is observed within 10 weeks, your doctor will reconsider your treatment.

Use in children and adolescents from 8 to 18 years with depression:

Treatment should be initiated and supervised by a specialist. The initial dose is 10 mg/day (administered as 2.5 ml of the fluoxetine oral solution presentation). After one or two weeks, your doctor may increase the dose to 20 mg/day. The dose should be carefully increased to ensure that you receive the lowest effective dose. Children with low weight may need lower doses. If there is a satisfactory response to treatment, your doctor should reassess the need to continue treatment after 6 months. If you have not improved within 9 weeks, treatment should be reconsidered.

Elderly patients:

Dose increases made by your doctor should be carried out more carefully, and the daily dose should not generally exceed 2 tablets (40 mg). The maximum dose is 3 tablets (60 mg) daily.

Hepatic impairment:

If you have a liver problem or are using other medication that may affect fluoxetine, your doctor will decide whether to prescribe a lower dose or instruct you on how to use fluoxetine on alternate days.

If you take more Fluoxetina Combix than you should

In case of overdose or accidental ingestion, go to the emergency department of the nearest hospital, 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 possible, bring the Fluoxetina Combix packaging with you.

The symptoms of overdose include: nausea, vomiting, seizures, heart problems (such as irregular heartbeats or cardiac arrest), lung problems, and changes in mental state ranging from excitement to coma.

If you forget to take Fluoxetina Combix

• Do not worry if you forget to take a dose. Take the next dose the following day at the usual time. Do not take a double dose to make up for missed doses.
• Taking your medication at the same time every day can help you remember to take it regularly.

If you stop treatment with Fluoxetina Combix

• Do notstop taking fluoxetine unless your doctor has indicated it, even if you start to feel better. It is important that you continue taking your medication.
• Make sure you do not run out of medication.

You may experience the following effects (withdrawal effects) when stopping treatment with fluoxetine: dizziness, sensation of tingling similar to pinpricks or needles, sleep disorders (intense dreams, nightmares, insomnia), feeling of restlessness or agitation, unusual fatigue or weakness, anxiety, nausea and/or vomiting (feeling sick or being sick), tremors (instability), and headache.

Most people find that the symptoms that occur when stopping treatment with fluoxetine are moderate and disappear within a few weeks. If you experience these symptoms when stopping your treatment, consult your doctor.

When stopping treatment with fluoxetine, your doctor will help you gradually reduce the dose over one to two weeks - this will help reduce the possibility of withdrawal effects.

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

4. Possible adverse effects

Like all medications, this medication can produce adverse effects, although not all people experience them.

• If you have suicidal thoughts or self-harm thoughts at any time, contact your doctor or go directly to the hospital(see section 2).
• If you experience skin rash or allergic reactions such as itching, swelling of the lips/tongue, or wheezing/shortness of breath, stop taking the tablets and inform your doctor immediately.
• If you feel restless and feel like you cannot sit still or stay still, you may be suffering from something called akathisia, and increasing your fluoxetine dose could make you feel worse. If you feel this way, consult your doctor.
• Talk to your doctor immediatelyif your skin starts to redden or presents any kind of reaction or blisters, or if your skin begins to peel. This happens very rarely.

The most frequent adverse effects (very frequent adverse effects that may affect more than 1 in 10 people) are insomnia, headache, diarrhea, discomfort (nausea), and fatigue.

Some patients have experienced:

• A combination of symptoms (known as "serotonin syndrome") that include unexplained fever with increased breathing or heart rate, sweating, muscle stiffness or tremor, confusion, extreme agitation or somnolence (only in rare cases);
• Feeling of weakness, somnolence, or confusion mainly in elderly patients and in people treated with diuretics (elderly patients);
• Prolonged and painful erection;
• Irritability and extreme agitation;
• Heart problems, such as rapid or irregular heartbeat, fainting, collapse, or dizziness when standing up, which may indicate abnormal heart rhythm.

If you experience any of the above adverse effects, inform your doctor immediately.

The following adverse effects have also been reported in patients taking fluoxetine:

Frequent(may affect up to 1 in 10 people)

• loss of appetite, weight loss
• nervousness, anxiety
• restlessness, lack of concentration
• feeling of nervous tension
• decreased sexual desire or sexual problems (including difficulty maintaining an erection during sexual activity)
• sleep disorders, abnormal dreams, fatigue, somnolence
• dizziness
• alteration of taste
• uncontrolled tremor movements
• blurred vision
• feeling of rapid and irregular heartbeats
• flushing
• yawning
• indigestion, vomiting
• dry mouth
• skin rash, hives, itching
• excessive sweating
• joint pain
• increased frequency of urination
• unexplained vaginal bleeding
• feeling of weakness or chills

Uncommon(may affect up to 1 in 100 people)

• feeling detached, distant from oneself
• strange thinking
• euphoria
• sexual problems, including orgasm problems, occasionally persisting after treatment discontinuation
• suicidal thoughts or self-harm thoughts
• teeth grinding
• muscle spasms, involuntary movements, or problems with balance or coordination
• memory disorders
• dilated pupils
• ringing in the ears
• low blood pressure
• breathing difficulties
• nasal bleeding
• difficulty swallowing
• hair loss
• increased tendency to bruise
• unexplained bruising or bleeding
• cold sweats
• difficulty urinating
• feeling of heat or cold
• liver test abnormalities

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

• low sodium levels in the blood
• reduction of platelets in the blood, which increases the risk of bleeding or bruising
• reduction in white blood cell count
• atypically unrestrained behavior
• hallucinations
• agitation
• panic attacks
• confusion
• stuttering
• aggressiveness
• seizures
• vasculitis (inflammation of a blood vessel)
• rapid swelling of tissues around the neck, face, mouth, and/or throat
• esophageal pain (the tube that connects the mouth to the stomach)
• hepatitis
• lung problems
• sensitivity to sunlight
• muscle pain
• urination problems
• breast milk production

Frequency not known(cannot be estimated from available data)

• Abundant vaginal bleeding shortly after childbirth (postpartum hemorrhage), see "Pregnancy"in section 2 for more information

Bone fractures:In patients taking this type of medication, an increased risk of bone fractures has been observed.

Most of these adverse effects tend to disappear with continued treatment.

In children and adolescents (8 to 18 years) –In addition to the possible adverse effects mentioned above, fluoxetine may decrease growth or delay sexual maturation. Suicidal behavior (suicide attempts and suicidal thoughts), hostility, mania, and nasal bleeding have also been frequently reported in children.

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 medication.

5. Storage of Fluoxetina Combix

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the packaging after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Fluoxetina Combix

• The active ingredient is fluoxetine in the form of hydrochloride. Each tablet contains 20 mg of fluoxetine (in the form of fluoxetine hydrochloride).
• The other components are: silicified microcrystalline cellulose (microcrystalline cellulose and anhydrous colloidal silica), alginic acid, hypromellose, aspartame (E-951), sodium lauryl sulfate, dental silica, magnesium stearate, peppermint flavor, and apricot flavor (contains sodium benzoate (E-210)).

Appearance of the product and package contents

Fluoxetina Combix 20 mg are dispersible, uncoated tablets, white or almost white, oval-shaped, biconvex, and scored on both sides. The tablet can be divided into equal doses.

The tablets are presented in blisters, available in packages of 14, 28, and 60 tablets.

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

O

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

O

Netpharmalab Consulting Services

Carretera de Fuencarral 22

28108 Alcobendas, Madrid

Spain

O

Pharmex Advanced Laboratories S.L.

Ctra. A-431 Km. 19

14720 Almodóvar del Río (Córdoba)

Spain

O

Flavine Pharma France

3 Voie d’Allemagne

13127 Vitrolles

France

Date of the last revision of this prospectus: December 2022

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