Fluoxeren

Italy
Brand name Fluoxeren
Form solution, oral
Active substance / Dosage
FLUOXETINE HYDROCHLORIDE
Prescription type Prescription only
ATC code
N06AB03
Registration number 025959
Manufacturer A. MENARINI INDUSTRIE FARMACEUTICHE RIUNITE S.R.L.

Table of Contents

Patient Information Leaflet: Information for the User

FLUOXEREN 20 mg hard capsules, 20 mg/5 ml oral solution, 20 mg dispersible tablets

fluoxetine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

  • Keep this leaflet. 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 other people, even if their symptoms are the same as yours, because it could be harmful.
  • If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What FLUOXEREN is and what it is used for

FLUOXEREN contains the active substance fluoxetine, a compound belonging to the class of antidepressant drugs known as selective serotonin reuptake inhibitors (SSRIs).
This medicine is used in adults and elderly patients for the treatment of:

  • Major depressive episodes.
  • A psychiatric disorder that manifests in a wide variety of forms, but is primarily characterized by recurrent thoughts, images, or impulses causing alarm or fear, leading the individual to perform repetitive behaviors or mental acts aimed at reducing anxiety and distress (obsessive-compulsive disorder).
  • An eating disorder characterized by alternating episodes of uncontrolled food intake and restrictive eating (bulimia nervosa).

Consult your doctor if you do not feel better or if you feel worse.

2. What you should know before taking FLUOXEREN

Do not take FLUOXEREN

  • If you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
  • In combination with:
  • Antidepressant medicines containing non-selective, irreversible monoamine oxidase inhibitors (e.g. iproniazide) (see sections “Warnings and precautions” and “Other medicines and FLUOXEREN”).
  • Metoprolol used in conditions where the heart fails to pump sufficient blood to all organs (heart failure) (see section “Other medicines and FLUOXEREN”).

Warnings and precautions
Talk to your doctor before taking FLUOXEREN, especially if you have a tendency to
bleed or bruise easily, if you are pregnant (see section “Pregnancy,
breast-feeding and fertility”), or if you are taking medicines containing buprenorphine (with or without
naloxone), as concomitant use with fluoxetine may lead to serotonin syndrome, a condition that may be fatal (see “Other medicines and FLUOXEREN”). Medicines such as
FLUOXEREN (so-called selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs)) may cause symptoms of sexual dysfunction (see
section 4). In some cases, persistence of these symptoms after discontinuation of
treatment has been observed.
Use in patients with concomitant diseases
Exercise caution when taking FLUOXEREN if:

  • you have heart disease;
  • you have kidney disease;
  • you have liver diseases (hepatic diseases); if you have significant liver dysfunction, take a lower dose (e.g. follow a regimen with alternate-day dosing);
  • you have a chronic metabolic disorder characterized by high blood glucose levels due to insufficient insulin production by the pancreas and/or insulin action abnormalities (diabetes);
  • you are elderly and have concomitant systemic diseases.

Skin rash and allergic reactions
Cases of sudden changes in skin color and consistency (skin rash) and other allergic events, sometimes severe, affecting the skin, kidneys, liver or lungs have been reported (see section 4 “Possible side effects”). Therefore, inform your doctor immediately if you notice the appearance of such manifestations. Fluoxetine administration must be discontinued if a skin rash or other allergic phenomena occur for which no alternative cause can be identified.
Seizures
Uncontrolled and involuntary movements of striated muscles (seizures) represent a potential risk with antidepressant medicines.
Avoid taking fluoxetine if you suffer from unstable seizure disorders or a known neurological brain disease called epilepsy. If you have controlled epilepsy, careful monitoring is required during fluoxetine treatment.
Take FLUOXEREN cautiously, as with other antidepressants, if you have had seizure episodes or other manifestations described as such.
In any case, discontinue FLUOXEREN therapy immediately if seizures occur or if the frequency of seizure episodes increases.
Electroconvulsive therapy (electroshock)
Use caution when taking fluoxetine if you are receiving therapy that induces a seizure through electrical stimulation of the brain while under general anesthesia (electroconvulsive therapy), as prolonged seizures have rarely been observed (see “Other medicines and FLUOXEREN”).
Mania
Exercise caution when taking antidepressant medicines if you have previously experienced episodes characterized by elevated mood, increased expansiveness or irritability (mania/hypomania episodes).
Consult your doctor if you suffer from depression and notice the onset of persistently and abnormally elevated mood, i.e. euphoric, unusually good and joyful, expansive, or alternatively irritable.
Discontinue fluoxetine, as with all antidepressant medicines, immediately if symptoms of mania develop.
Hepatic/renal function
Fluoxetine is extensively metabolized by the liver and eliminated by the kidneys. In patients with significant hepatic dysfunction, a lower dose is recommended, for example alternate-day administration. Administration of fluoxetine at doses of 20 mg/day for 2 months in patients with severe renal impairment (GFR < 10 ml/min) requiring dialysis did not result in any difference in plasma levels of fluoxetine or norfluoxetine compared to control subjects with normal renal function.
Tamoxifen
Avoid, whenever possible, the administration of fluoxetine during treatment with tamoxifen (see section “Other medicines and FLUOXEREN”); fluoxetine, a potent inhibitor of one of the enzymes involved in the metabolism of certain substances (CYP2D6), may cause reduced concentrations of endoxifen, one of the most important active metabolites of tamoxifen.
Cardiovascular effects
No abnormalities in conduction leading to cardiac arrest were observed on ECG in 312 patients who received fluoxetine during double-blind clinical trials.
However, clinical experience in acute heart disease is limited; therefore caution is advised.
During post-marketing surveillance, cases of QT interval prolongation and ventricular arrhythmia, including torsade de pointes, have been reported.
Take fluoxetine with caution if you have conditions involving irregular and uncontrolled heartbeat in response to physical exertion or stress (congenital long QT syndrome), family history of QT prolongation, or other clinical conditions predisposing to heart rhythm disturbances (arrhythmias), e.g. low blood potassium and magnesium levels (hypokalaemia and hypomagnesaemia), slowed heart rate (bradycardia), acute myocardial infarction, or conditions of inability of the heart to deliver sufficient blood to all body organs (decompensated heart failure), or increased exposure to fluoxetine (e.g. hepatic impairment).
If you have heart disease related to physical exertion (stable), an electrocardiogram (ECG) should be considered before starting treatment.
Discontinue treatment and undergo an ECG if signs of cardiac arrhythmia occur during fluoxetine treatment.
Weight loss
Weight loss may occur when taking fluoxetine, although this decrease is usually proportional to initial body weight.
Diabetes
If you have diabetes, FLUOXEREN therapy may alter glycaemic control. Cases of hypoglycaemia (low blood glucose levels) have occurred during fluoxetine treatment, while cases of hyperglycaemia (high blood glucose levels) have occurred following discontinuation of fluoxetine treatment. Therefore, adjustment of insulin or oral antidiabetic drug dosage may be necessary.
Suicide/Suicidal ideation (having suicidal thoughts)
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission or disappearance of disease symptoms occurs. Since improvement may not occur during the first weeks or more of treatment, patients should be closely monitored until improvement occurs. It is common clinical experience that suicide risk may increase in the early phases of recovery.
Other psychiatric disorders for which FLUOXEREN is prescribed may also be associated with an increased risk of suicidal behaviour. Furthermore, these disorders may be associated with major depressive disorder. Therefore, when treating patients with other psychiatric disorders, the same precautions observed during treatment of patients with major depressive disorder should be followed.
Patients who have previously experienced suicide-related events, or who exhibit significant suicidal ideation before starting treatment, are at higher risk of suicidal thoughts or suicide attempts and should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical studies in adult patients with psychiatric disorders treated with antidepressants showed an increased risk of suicidal behaviour in patients under 25 years of age treated with antidepressants compared to those treated with placebo.
Close monitoring of patients is necessary during antidepressant therapy, particularly high-risk patients, especially at the beginning of treatment and following dose changes. Patients (and caregivers) should be warned to monitor any clinical worsening, emergence of suicidal thoughts or behaviours, and unusual changes in behaviour, and to consult their doctor if these symptoms occur.
Akathisia/Psychomotor restlessness
The use of FLUOXEREN has been associated, particularly within the first weeks of treatment, with the development of akathisia, a syndrome characterized by a subjective unpleasant and distressing sensation of restlessness and psychomotor agitation accompanied by inability to sit still or remain motionless.
If these symptoms occur, increasing the dosage may be harmful.
Withdrawal symptoms observed following discontinuation of SSRI treatment
Withdrawal symptoms when treatment is stopped are common, especially if stopped abruptly (see section 4 “Possible side effects”).
The risk of withdrawal symptoms may depend on several factors, including duration of treatment, dosage, and speed of dose reduction.
The most commonly reported reactions are dizziness, sensory disturbances (including altered perception of stimuli, known as paresthesia), sleep disturbances (including insomnia and vivid dreams), asthenia, agitation or anxiety, nausea and/or vomiting, tremor, and headache. Generally, the intensity of such symptoms is mild to moderate; however, in some patients, it may be severe. They usually appear within the first days after stopping treatment and are self-limiting, resolving usually within two weeks, although in some individuals they may last longer (2–3 months or more). Therefore, when stopping treatment, it is recommended to gradually reduce the dose of FLUOXEREN over a period of at least 1 or 2 weeks, depending on the patient's needs (see “If you stop taking FLUOXEREN”).
Bleeding (haemorrhage)
Medicines belonging to the class of serotonin reuptake inhibitor antidepressants, such as fluoxetine, may cause bleeding manifestations at the skin level (e.g.
bruising, i.e. bruises, and purpura, the appearance of haemorrhagic spots that do not disappear with pressure) and, more rarely, at gynaecological and gastrointestinal tract sites (see section 4 “Possible side effects”).
Exercise caution when taking fluoxetine if you are simultaneously taking oral anticoagulants, drugs affecting platelet aggregation, or other drugs that may increase the risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazines, most tricyclic antidepressants, aspirin, NSAIDs) (see “Other
medicines and FLUOXEREN”).
Take FLUOXEREN cautiously if you have previously experienced pathological conditions characterized by bleeding episodes.
Dilation of the eye's pupil (mydriasis)
Mydriasis has been reported in association with fluoxetine; therefore caution should be exercised when prescribing fluoxetine to patients with high intraocular pressure or patients at risk of narrow-angle acute glaucoma (a particular form of glaucoma induced by mechanical problems causing closure of the iridocorneal angle).
St. John's Wort
When selective serotonin reuptake inhibitors (SSRIs) and herbal preparations containing St. John's Wort (Hypericum perforatum) are used together, an increase in serotoninergic effects, such as serotonin syndrome, may occur (see “Other
medicines and FLUOXEREN”).
Serotonin syndrome or neuroleptic malignant syndrome-like events
Rarely, the development of serotonin syndrome or neuroleptic malignant syndrome (NMS)-like events has been reported in association with fluoxetine treatment, particularly when fluoxetine is administered in combination with other serotoninergic drugs (such as L-tryptophan) and/or neuroleptics, i.e. drugs used to treat certain depressive conditions and psychoses, e.g. schizophrenia and bipolar disorder (see “Other
medicines and FLUOXEREN”).
Since these syndromes may lead to potentially life-threatening conditions, discontinue fluoxetine treatment and receive supportive symptomatic treatment if such events occur, characterized by symptoms such as increased body temperature (hyperthermia), rigidity, rapid involuntary muscle twitching (myoclonus), autonomic instability with possible rapid fluctuations in vital signs, and mental status changes including confusion, irritability, and extreme agitation up to delirium and coma.
Irreversible non-selective monoamine oxidase inhibitors (e.g. iproniazide)
Concomitant intake of FLUOXEREN with an irreversible non-selective MAO inhibitor is
contraindicated (see section “Do not take FLUOXEREN”). Since the effect of MAO inhibitors lasts 2 weeks, fluoxetine treatment should be started only 2 weeks after discontinuation of an irreversible non-selective MAO inhibitor. Similarly, at least 5 weeks must elapse after stopping fluoxetine treatment before starting therapy with an irreversible non-selective MAO inhibitor.
Cases of serious and sometimes fatal reactions have been reported in patients taking an SSRI medicine in combination with an irreversible non-selective monoamine oxidase inhibitor (MAOI).
These cases present characteristics similar to serotonin syndrome and may be confused with (or diagnosed as) neuroleptic malignant syndrome. Cyproheptadine or dantrolene may benefit patients experiencing such reactions. Symptoms of a pharmacological interaction with an MAOI include: hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs, and mental status changes including confusion, irritability, and extreme agitation up to delirium and coma (see section “Other medicines and FLUOXEREN”).
Children and adolescents under 18 years of age
FLUOXEREN should only be used in children and adolescents aged 8 to 18 years for the treatment of moderate to severe major depressive episodes and should not be used for other indications. If treatment is decided based on medical needs, the patient must be carefully monitored for the emergence of suicidal symptoms. Furthermore, there is limited long-term safety data in children and adolescents, including effects on growth, sexual maturation, and cognitive, emotional, and behavioural development.
In clinical studies conducted in children and adolescents treated with antidepressants compared to those treated with placebo, suicidal behaviours (suicide attempts and suicidal thoughts) and hostility (mainly aggression, oppositional behaviour, and anger) occurred more frequently.
In a 19-week clinical study, reduced increases in both height and weight were observed in children and adolescents treated with fluoxetine. It has not been established whether there is an effect on achieving normal adult height. Delayed puberty cannot be excluded. Therefore, growth and pubertal development (height, weight, and Tanner staging) must be monitored during and after fluoxetine treatment. If any of these are delayed, a paediatric consultation should be considered.
In studies conducted in the paediatric population, mania and hypomania have commonly been reported (see section 4 “Possible side effects”). Therefore, regular monitoring for the occurrence of mania/hypomania is recommended. Fluoxetine must be discontinued in any patient who enters a manic phase.
It is important that the doctor carefully discusses the risks and benefits of treatment with the child/young person and/or their parents.
Other medicines and FLUOXEREN
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Interaction studies have been conducted only in adults.
Combinations contraindicated
Irreversible non-selective Monoamine Oxidase Inhibitors (e.g. iproniazide)
Do not take fluoxetine simultaneously with medicines containing drugs belonging to the class of antidepressants such as irreversible non-selective MAO inhibitors. Since these have an effect lasting 2 weeks, start fluoxetine treatment only 2 weeks after discontinuation of an irreversible non-selective MAOI. Similarly, at least 5 weeks must elapse after stopping fluoxetine treatment before starting therapy with an irreversible non-selective MAOI (see “Do not take FLUOXEREN”).
Following concomitant administration of SSRIs and an irreversible non-selective monoamine oxidase inhibitor, serious, sometimes fatal reactions have been observed, including marked increase in body temperature (hyperthermia), rigidity, rapid involuntary muscle twitching (myoclonus), autonomic instability with possible rapid fluctuations in vital signs, and mental status changes including confusion, irritability, and extreme agitation up to delirium and coma. Cyproheptadine or dantrolene may benefit patients experiencing such reactions.
These cases present characteristics similar to serotonin syndrome and may be confused with (or diagnosed as) neuroleptic malignant syndrome.
Metoprolol (used in heart failure)
The risk of metoprolol adverse events, including excessive reduction in heart rate (bradycardia), may increase due to inhibition of its metabolism (degradation) by fluoxetine (see “Do not take FLUOXEREN”).
Combinations not recommended
Tamoxifene
Avoid, when possible, the administration of fluoxetine during treatment with tamoxifen; fluoxetine, a potent CYP2D6 inhibitor, may cause reduced concentrations of endoxifen, one of the most important active metabolites of tamoxifen (see section “Warnings and precautions”).
MAOI-type A, including linezolid and methylene blue (methylthioninium chloride)
Avoid concomitant intake of MAOI-type A medicines and FLUOXEREN as serotonin syndrome may occur, including diarrhoea, tachycardia, sweating, tremor, confusion or coma. If such combination cannot be avoided, strict clinical monitoring is required and concomitant agents should be initiated at the lowest recommended doses.
Mequitazine
Concomitant administration of mequitazine and fluoxetine may lead to an increased risk of mequitazine adverse effects (such as QT prolongation) due to inhibition of its metabolism by fluoxetine.
Combinations requiring caution
Phenytoin (antiepileptic drug)
Changes in blood phenytoin concentration (plasma phenytoin concentration) have been observed when administered together with fluoxetine. In some cases, toxicity manifestations have occurred. Therefore, it is recommended to administer the concomitant drug according to conservative therapeutic regimens and to closely monitor the patient's clinical condition.
Serotoninergic drugs [lithium, tramadol, triptans, tryptophan, selegiline (MAOI-type B), St. John's Wort (Hypericum perforatum), buprenorphine (an opioid), with or without naloxone]
Take with caution and undergo more targeted and frequent clinical monitoring during concomitant use of fluoxetine with serotoninergic drugs.
Following such co-administration, reports of moderate serotonin syndrome have been reported, and symptoms such as rhythmic involuntary contractions of muscles, including muscles controlling eye movement, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle contraction, fever above 38°C may occur. Contact your doctor if you experience such symptoms.
Combination with medicines used in migraine therapy containing triptans adds further risk of reduced diameter of blood vessels supplying the heart (coronary vasoconstriction) and high blood pressure (hypertension).
Medicines causing QT interval prolongation
Take fluoxetine with caution when taken simultaneously with medicines that prolong the QT interval such as class IA and III antiarrhythmics, antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents (e.g. sparfloxacin, moxifloxacin, IV erythromycin, pentamidine), antimalarials, especially halofantrine, some antihistamines (astemizole, mizolastine). An additive effect of fluoxetine and such medicines cannot be excluded.
No pharmacokinetic or pharmacodynamic studies on the combination of fluoxetine with other QT-prolonging medicines have been performed.
Medicines affecting haemostasis (oral anticoagulants, regardless of their mechanism of action, platelet aggregation inhibitors, including aspirin and NSAIDs)
Concomitant intake of fluoxetine and such medicines increases the risk of bleeding. With oral anticoagulants, clinical monitoring and more frequent INR (prothrombin time) monitoring should be performed. Dose adjustment may be appropriate during fluoxetine treatment and after its discontinuation.
Cyproheptadine
During concomitant intake of cyproheptadine and fluoxetine, isolated cases of reduced antidepressant activity of fluoxetine have been reported.
Medicines causing hyponatraemia
Low sodium concentration in the blood (hyponatraemia) is a side effect of fluoxetine. Concomitant use with other agents associated with hyponatraemia (e.g. diuretics, desmopressin, carbamazepine and oxcarbazepine) may increase the risk (see section 4 “Possible side effects”).
Medicines lowering the seizure threshold
Co-administration of drugs capable of lowering the seizure threshold (e.g. TCAs, other SSRIs, phenothiazines, butyrophenones, mefloquine, chloroquine, bupropion, tramadol) with fluoxetine may increase the risk of seizures, an adverse effect of fluoxetine.
Other medicines metabolized by CYP2D6
Fluoxetine is a strong inhibitor of the CYP2D6 enzyme; therefore, concomitant therapy with drugs also metabolized by this enzymatic system may cause pharmacological interactions, especially with drugs having a narrow therapeutic index (such as flecainide, encainide, propafenone and nebivolol) and titrated drugs, but also with atomoxetine, carbamazepine, tricyclic antidepressants and risperidone. Their administration should be initiated or adjusted starting from the lowest value in the dosage range. This should also be applied when fluoxetine has been taken within the previous 5 weeks.
FLUOXEREN with alcohol
It is important to inform your doctor about concomitant alcohol intake as interactions may occur, as with many medicines.
Although fluoxetine does not increase blood alcohol levels or enhance its effects, it is recommended to avoid alcohol intake during FLUOXEREN therapy.
Pregnancy, breast-feeding and fertility
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breast-feeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Take FLUOXEREN with particular caution if you are pregnant, especially in the late stages of pregnancy or immediately before the onset of labour, as the following effects have been reported in newborns: irritability, tremor, hypotonia (reduced muscle tone), persistent crying, difficulty sucking or sleeping. These symptoms may indicate either serotoninergic effects or withdrawal syndrome (see “If you stop treatment with FLUOXEREN”). The onset and duration of these symptoms may be related to the long half-life (persistence of the drug in the blood) of fluoxetine (4–6 days) and its active metabolite, norfluoxetine (4–16 days).
Some epidemiological studies suggest an increased risk of cardiovascular defects associated with fluoxetine use during the first trimester. The mechanism is unknown.
Overall, teratogenic data (i.e. related to abnormal fetal development during pregnancy) suggest that the risk of a newborn having a cardiovascular defect following maternal exposure to fluoxetine is 2/100 compared to an expected rate of about 1/100 in the general population.
Epidemiological data have suggested that the use of SSRIs during pregnancy, especially towards the end of pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 1000 pregnancies. In the general population, 1 to 2 cases of PPHN occur per 1000 pregnancies.
If you take FLUOXEREN close to term, there may be an increased risk of heavy vaginal bleeding shortly after delivery, especially if you have bleeding disorders (tendency to bleed). Inform your physician or midwife that you are taking FLUOXEREN so they can advise you on what to do.
Breast-feeding
If fluoxetine treatment is considered necessary, discontinuation of breast-feeding should be considered; however, if breast-feeding is continued, the lowest effective dose of fluoxetine should be prescribed. It is known that fluoxetine and its active metabolite norfluoxetine are excreted in human breast milk. Adverse effects have been reported in breastfed infants.
Fertility
No impact on human fertility has been observed so far. Animal data have shown that fluoxetine may affect sperm quality. Case reports with some SSRIs have shown that the effect on sperm quality is reversible.
Driving and using machines
FLUOXEREN does not affect or affects negligibly the ability to drive vehicles or use machines. Although it has been demonstrated that fluoxetine does not interfere with psychomotor performance in healthy volunteers, any psychoactive medicine may alter judgment or psychomotor abilities. Consequently, avoid driving a vehicle or operating dangerous machinery until you are reasonably certain that your abilities are not impaired.
FLUOXEREN 20 mg/5 ml oral solution contains sucrose.
If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.
It may be harmful to teeth.
FLUOXEREN 20 mg/5 ml oral solution contains benzoic acid
This medicine contains 2.5 mg of benzoic acid per 5 ml of oral solution.
FLUOXEREN 20 mg dispersible tablets contain sorbitol and sodium.
This medicine contains 6.71 mg of sorbitol per tablet.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially ‘sodium-free’.

3. How to take FLUOXEREN

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.

Major depressive episodes
Adults and elderly
The recommended dose is 20 mg (1 hard capsule, or 1 dispersible tablet, or 5 ml of oral solution) daily. If necessary, the dosage should be reviewed and adjusted within 3–4 weeks after starting treatment and subsequently as clinically appropriate. Although higher doses may potentially increase the risk of adverse effects, in some patients who show an inadequate therapeutic response at 20 mg, the dose may be gradually increased up to a maximum of 60 mg. Dose adjustments must be made cautiously for each individual patient in order to maintain patients on the lowest effective dose.
Antidepressant treatment should continue for at least 6 months.

Obsessive-compulsive disorder
Adults and elderly
The recommended dose is 20 mg (1 hard capsule, or 1 dispersible tablet, or 5 ml of oral solution) daily. An increase in dose up to a maximum of 60 mg may be considered after 2 weeks if the therapeutic response is inadequate, although higher doses may potentially increase the risk of adverse effects. If no improvement is observed within 10 weeks, fluoxetine treatment should be reconsidered.
If a good therapeutic response is achieved, treatment may be continued with dosage adjustments on an individual basis. Although no systematic studies have been conducted to determine how long treatment with fluoxetine should continue, obsessive-compulsive disorder is a long-term condition, and it is reasonable to consider continuing therapy beyond 10 weeks in patients who respond to treatment.
Dosage adjustments must be made cautiously for each individual patient to maintain the patient on the lowest effective dose. The need for continued treatment should be periodically reassessed. Some physicians consider concomitant behavioral psychotherapy beneficial in patients who respond well to pharmacological therapy.
In obsessive-compulsive disorder, efficacy has not been demonstrated in the long term (beyond 24 weeks).

Bulimia nervosa
Adults and elderly
The recommended dose is 60 mg daily orally (3 hard capsules, or 3 dispersible tablets, or 15 ml of oral solution). In bulimia nervosa, efficacy has not been demonstrated in the long term (beyond 3 months).

In all indications
Adults
The recommended dose may be increased or decreased. Daily doses higher than 80 mg have not been evaluated.
Take fluoxetine as a single or divided dose, with or without food.
When administration is discontinued, pharmacologically active substances will persist in the body for weeks. This should be taken into account when starting or stopping treatment.
The capsule and liquid formulations are bioequivalent.

Elderly
Caution is advised when increasing the dose; the daily dose should generally not exceed 40 mg. The maximum recommended dose is 60 mg daily.

Patients with hepatic or renal impairment or patients taking other medicines
If your liver or kidney function is reduced, if you are elderly, have concomitant illnesses, or are taking other medications, the dose of FLUOXEREN should be appropriately reduced or the dosing interval increased (e.g., 20 mg every other day).

Use in children and adolescents
Children and adolescents aged 8 years and older (moderate to severe major depressive episode)
Treatment should be initiated and monitored under the supervision of a specialist. The initial dose is 10 mg daily administered as 2.5 ml of FLUOXEREN oral solution. Dose adjustments should be made cautiously on an individual basis to maintain the patient on the lowest effective dose.
After 1 or 2 weeks, the dose may be increased to 20 mg daily. Clinical experience with daily doses exceeding 20 mg is limited. There are only limited data on treatment beyond 9 weeks.
Children with low body weight
Due to higher plasma levels in children with low body weight, the therapeutic effect may be achieved with lower doses.
For pediatric patients who respond to treatment, the need to continue therapy should be reassessed after 6 months. If no clinical benefit is observed within 9 weeks, treatment should be reconsidered.

FLUOXEREN 20 mg/5 ml oral solution
The exact dose prescribed by your doctor can be easily taken following the instructions below:

Three sequential drawings show how to insert the pipette into the bottle, pull the plunger for dosing, and pour the liquid into a glass

10 mg
2.5 ml
20 mg
5 ml

FLUOXEREN 20 mg dispersible tablets
Swallow the FLUOXEREN dispersible tablets without chewing, or dissolve them in water to the desired dilution.

FLUOXEREN 20 mg hard capsules
Swallow the FLUOXEREN capsules without chewing.

If you take more FLUOXEREN than you should
If you take too much FLUOXEREN, contact your doctor immediately or go to the nearest hospital.
Cases of overdose with fluoxetine alone have generally had a mild course. Symptoms of overdose mainly include nausea, vomiting, seizures, variable cardiovascular disturbances ranging from arrhythmia (altered heart rhythm) without symptoms to cardiac arrest (including nodal and ventricular arrhythmias), or ECG changes indicative of QT prolongation up to cardiac arrest (including very rare cases of torsade de pointes), pulmonary dysfunction, and manifestations of altered nervous system function ranging from agitation to coma.
Fatal outcome following an overdose of fluoxetine is very rare.
If symptoms of overdose occur, cardiac function and vital signs should be monitored, and general symptomatic and supportive measures should be implemented. Specific antidotes are not known. Forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be beneficial. Activated charcoal, which may be used in combination with sorbitol, may represent a more effective treatment than emesis (induced vomiting) or gastric lavage (stomach emptying and washing).
When managing an overdose, consider the possibility of multiple drug involvement.
If you have taken excessive amounts of another tricyclic antidepressant while taking, or having recently taken, fluoxetine, a longer period of close medical observation may be required.

If you stop taking FLUOXEREN
Avoid abruptly stopping FLUOXEREN treatment; reduce the dose gradually over a period of at least 1–2 weeks to reduce the risk of withdrawal reactions (see “Warnings and precautions”).
If intolerable symptoms occur during dose reduction or upon discontinuation, re-institution of the previously prescribed dose may be considered. Subsequently, your doctor may continue to reduce the dose, but more gradually.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The most commonly reported side effects in patients treated with fluoxetine have been headache, nausea, insomnia, fatigue and diarrhoea; these effects may decrease in intensity and frequency with continued treatment and generally do not require discontinuation of therapy.
As with other SSRIs, the following side effects have been observed during treatment with fluoxetine:

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

  • insomnia (early morning awakening, initial and middle insomnia);
  • headache;
  • diarrhoea and nausea;
  • fatigue (asthenia).

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

  • decreased appetite, including anorexia;
  • anxiety, nervousness, restlessness, tension, decreased and loss of libido, sleep disturbances, abnormal dreams (nightmares);
  • attention disturbances, dizziness, dysgeusia (altered taste), lethargy (tendency to continuous sleep), somnolence (hypersomnia and sedation), tremor;
  • blurred vision;
  • palpitations;
  • flushing;
  • yawning;
  • vomiting, dyspepsia (digestive difficulties), dry mouth;
  • skin rash (skin changes such as erythema, exfoliative rash, heat rash, erythematous exanthema, follicular exanthema, generalized skin rash, macular exanthema, maculopapular exanthema, morbilliform exanthema, papular exanthema, pruritic exanthema, vesicular exanthema, erythematous umbilical exanthema), urticaria, pruritus;
  • hyperhidrosis (excessive sweating);
  • arthralgia (joint pain);
  • frequent urination (frequent passing of urine);
  • gynaecological bleeding (cervical haemorrhage, uterine dysfunction, uterine bleeding, genital haemorrhage, menometrorrhagia, menorrhagia, metrorrhagia, polymenorrhoea, postmenopausal haemorrhage, uterine haemorrhage, vaginal haemorrhage), erectile dysfunction, ejaculation disorder;
  • feeling nervous, chills;
  • weight loss.

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

  • depersonalisation, euphoric mood, abnormal thinking, abnormal orgasm (anorgasmia), bruxism (teeth grinding), suicidal thoughts and behaviour (completed suicide, suicidal depression, intentional self-injury, self-harming ideation, suicidal behaviour, suicidal ideation, suicide attempt, morbid thoughts, self-harming behaviour);
  • psychomotor hyperactivity, dyskinesia (movement disorder), ataxia (progressive loss of muscular coordination), balance disturbances, myoclonus, memory impairment;
  • mydriasis;
  • tinnitus (ringing in the ears);
  • hypotension (low blood pressure);
  • dyspnoea (difficulty breathing), epistaxis (nosebleed);
  • dysphagia (difficulty swallowing), gastrointestinal haemorrhage (more frequently gingival bleeding, haematemesis, haematochezia, rectal haemorrhage, haemorrhagic diarrhoea, melena and gastric ulcer haemorrhage);
  • alopecia (hair loss), increased tendency to bruising, cold sweats;
  • muscle contractions;
  • dysuria (difficulty passing urine);
  • sexual dysfunction;
  • malaise, feeling of abnormality, feeling cold, feeling hot.

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

  • thrombocytopenia (reduced number of platelets in the blood), neutropenia (reduced number of neutrophils, a type of white blood cells, in the blood), leucopenia (reduced number of leucocytes, white blood cells, in the blood);
  • anaphylactic reaction (severe allergic reaction), serum sickness;
  • inappropriate secretion of antidiuretic hormone;
  • hyponatraemia;
  • hypomania, mania, hallucinations, agitation, panic attacks, confusion, dysphemia (inability to pronounce sounds), aggression;
  • convulsions, akathisia (inability to remain still), buccolinguomasticatory syndrome, serotonin syndrome (see “Warnings and precautions”);
  • ventricular arrhythmia, including torsade de pointes, QT prolongation on ECG;
  • vasculitis (inflammation of blood vessels), vasodilation;
  • pharyngitis (inflammation of the pharynx), lung disorders (inflammatory processes with variable histopathology and/or fibrosis including atelectasis, interstitial lung disease, pneumonia);
  • oesophageal pain;
  • idiosyncratic hepatitis (liver damage);
  • angioedema (rapid swelling of the skin, mucosa and submucosal tissues), ecchymosis (blood infiltration into subcutaneous tissue), photosensitivity, purpura, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome);
  • myalgia (muscle pain);
  • urinary retention, micturition disorder;
  • galactorrhoea (abnormal milk secretion);
  • hyperprolactinaemia (elevated concentration of prolactin in the blood), priapism (persistent and abnormal erection, often painful);
  • mucosal haemorrhage (bleeding);
  • increased transaminases, increased gamma-glutamyl transferase (markers of liver function).

Side effects with unknown frequency (frequency cannot be estimated from the available data):

  • Profuse vaginal bleeding shortly after childbirth (postpartum haemorrhage); see section 2, Pregnancy, for further information.

An increased risk of bone fractures has been observed in patients taking this type of SSRI and TCA (tricyclic antidepressants).
Alterations in taste, dizziness, euphoria, anorgasmia and hyposodiemia have also been reported.
Cases of suicidal ideation and suicidal behaviour have been reported during treatment with fluoxetine or immediately after discontinuation of treatment.

Withdrawal symptoms observed following discontinuation of treatment
Discontinuation of treatment with FLUOXEREN (especially if abrupt) generally leads to the withdrawal symptoms described below.
The most commonly reported symptoms are dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability and visual disturbances.
Generally, these events are mild to moderate and resolve spontaneously; however, in some patients they may be severe and/or prolonged. If treatment with FLUOXEREN is no longer required, gradually discontinue the medicine by gradually reducing the dose (see “If you stop taking FLUOXEREN”).
Following the instructions in this leaflet reduces the risk of side effects.

Additional side effects in children and adolescents
The side effects observed specifically or with different frequency in this population are described below.
In paediatric clinical trials, suicidal-related behaviours (suicide attempt and suicidal thoughts), hostility (reported events: anger, irritability, aggression, agitation, hyperactivity syndrome), manic reactions, including mania and hypomania (without previous episodes reported in these patients), and epistaxis, were commonly reported and observed more frequently in children and adolescents treated with antidepressants compared to those treated with placebo.
The safety of fluoxetine has not been systematically evaluated for chronic treatment longer than 19 weeks.
In clinical trials conducted in a paediatric population, manic reactions, including mania and hypomania (2.6% of patients treated with fluoxetine vs. 0% in placebo-controlled), were reported, leading in most cases to discontinuation of treatment. These patients had no prior episodes of hypomania/mania.
After 19 weeks of treatment, paediatric subjects treated with fluoxetine in the clinical study showed on average 1.1 cm less growth in height (p=0.004) and 1.1 kg less weight gain (p=0.008) compared to subjects treated with placebo.
During clinical use, isolated cases of growth delay have also been reported.
In paediatric clinical trials, treatment with fluoxetine has been associated with decreased levels of alkaline phosphatase.
In paediatric clinical use, isolated cases of adverse events potentially indicating delayed sexual maturation or sexual dysfunction have been reported.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store FLUOXEREN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
Storage precautions:
FLUOXEREN 20 mg hard capsules and FLUOXEREN 20 mg/5 ml oral solution
Store below 25°C.
FLUOXEREN 20 mg orodispersible tablets
Store below 30°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What FLUOXEREN contains
FLUOXEREN 20 mg hard capsules
Each capsule contains:
Active substance: Fluoxetine hydrochloride 22.36 mg, equivalent to fluoxetine 20 mg.
Other components: Maize starch, dimethicone, patent blue V E-131, yellow iron oxide E-172,
titanium dioxide E-171, gelatin.

FLUOXEREN 20 mg/5 ml oral solution
5 ml of oral solution contain:
Active substance: Fluoxetine hydrochloride 22.36 mg, equivalent to fluoxetine 20 mg.
Other components: Benzoic acid, sucrose, glycerin, peppermint flavor, purified water.

FLUOXEREN 20 mg orodispersible tablets
Each tablet contains:
Active substance: Fluoxetine hydrochloride 22.36 mg, equivalent to fluoxetine 20 mg.
Other components: Microcrystalline cellulose, sodium saccharin, mannitol, sorbitol, anise flavor,
peppermint flavor, colloidal anhydrous silica, pregelatinized starch, sodium stearyl fumarate,
crospovidone.

Description of the appearance of FLUOXEREN and contents of the pack
FLUOXEREN 20 mg hard capsules
12 and 28 hard green/white capsules containing a homogeneous white powder of 20 mg, in blister packs.

FLUOXEREN 20 mg/5 ml oral solution
60 ml of colourless oral solution in amber glass bottles closed with a plastic cap, with an accompanying dosing pipette.

FLUOXEREN 20 mg orodispersible tablets
12 and 28 white, elongated orodispersible tablets of 20 mg, in blister packs.

Marketing Authorization Holder and Manufacturer
A. Menarini Industrie Farmaceutiche Riunite s.r.l. - Via Sette Santi 3, Florence.
Marketing partner: Istituto Luso Farmaco d’Italia S.p.A., Milanofiori - Strada 6 - Edificio L - Rozzano (MI).

Manufacturer
FLUOXEREN 20 mg hard capsules
A. Menarini Manufacturing Logistics and Services s.r.l., Via Campo di Pile, L'Aquila.
Laboratorios Menarini S.A., Alfonso XII n. 587, Badalona – Barcelona (Spain).

FLUOXEREN 20 mg/5 ml oral solution
Laboratorios Menarini S.A., Alfonso XII n. 587, Badalona – Barcelona (Spain).

FLUOXEREN 20 mg orodispersible tablets
A. Menarini Manufacturing Logistics and Services s.r.l., Via Campo di Pile, L'Aquila.
Menarini Von Heyden GmbH - Leipziger Strasse 7-13 – Dresden (Germany).