Active ingredients: Fluoxetine
FLUOXEREN 20 MG HARD CAPSULES
FLUOXEREN 20 MG / 5 ML ORAL SOLUTION
FLUOXEREN 20 MG DISPERSIBLE TABLETS
Indications Why is Fluoxeren used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antidepressants. Selective serotonin reuptake inhibitors.
THERAPEUTIC INDICATIONS
Treatment of major depressive episodes, obsessive compulsive disorder and bulimia nervosa.
Contraindications When Fluoxeren should not be used
Hypersensitivity to the active substance or to any of the excipients listed in the "Composition" section.
Fluoxetine is contraindicated in combination with:
- irreversible and non-selective monoamine oxidase inhibitors (eg iproniazid) (see sections "Precautions for use" and "Interactions");
- metoprolol used in heart failure (see section "Interactions").
Precautions for use What you need to know before taking Fluoxeren
Pediatric population - Children and adolescents under the age of 18
Suicide-related behaviors (suicide attempts and suicidal thoughts) and hostility (essentially aggression, oppositional behavior and anger) were observed more frequently in clinical trials in children and adolescents treated with antidepressants than in those treated with placebo.
Fluoxeren is only for use in children and adolescents aged 8 to 18 years for the treatment of moderate to severe major depressive episodes and should not be used in other indications. If, based on medical needs, a decision is made for treatment, the patient should be carefully monitored for the appearance of suicidal symptoms. Furthermore, only limited long-term safety data are available in children and adolescents, including effects on growth, sexual maturation and cognitive, emotional and behavioral development (see section 5.3).
In a 19-week clinical study, a reduction in height and weight gain was observed in children and adolescents treated with fluoxetine. It has not been established whether there is an effect on achieving normal height in adulthood. It cannot be excluded. the possibility of delayed puberty (see section "Undesirable effects"). Therefore, pubertal growth and development (height, weight and staging according to TANNER) should be monitored during and after treatment with fluoxetine. , a pediatric consultation should be considered.
In studies performed in the pediatric population, mania and hypomania were commonly reported (see section "Undesirable effects"). Therefore, regular monitoring for the occurrence of mania / hypomania is recommended. Fluoxetine should be discontinued in any patient entering a manic phase.
It is important that the doctor carefully discusses the risks and benefits of treatment with the child / young adult and / or his / her parents.
Convulsions
Seizures pose a potential risk with antidepressant medications. Therefore, as with other antidepressants, fluoxetine should be administered with caution to patients with a history of seizures. Treatment should be discontinued in any patient who experiences seizures or in whom an increase in seizure frequency is observed. Administration of fluoxetine should be avoided in patients with unstable seizure disorders / epilepsy and patients with controlled epilepsy should be closely monitored (see section "Interactions").
Electroconvulsive therapy (TEC)
Rare cases of prolonged seizures have been reported in fluoxetine-treated patients receiving TEC treatment, therefore caution is advised.
Mania
Antidepressants should be used with caution in patients with a history of mania / hypomania.
In a person suffering from depression, the appearance of an abnormally and persistently elevated mood, that is, euphoric, unusually good and joyful and expansive, or irritable, should prompt the patient to consult their doctor. As with all antidepressant medications, fluoxetine should be discontinued as soon as the patient begins to have manic symptoms.
Hepatic / renal function
Fluoxetine is extensively metabolised by the liver and eliminated by the kidneys. In patients with significant hepatic dysfunction, a lower dose is recommended, e.g. one administration every other day. When fluoxetine was administered in doses of 20 mg per day for 2 months, patients with severe renal impairment (GFR dialysis showed no difference in plasma levels of fluoxetine or norfluoxetine compared to control subjects with normal renal function.
Tamoxifen
Fluoxetine, a potent inhibitor of CYP2D6, may cause decreased concentrations of endoxifen, one of the most important active metabolites of tamoxifen. Whenever possible, the administration of fluoxetine should therefore be avoided during treatment with tamoxifen (see section "Interactions").
Cardiovascular effects
Clinical experience in acute heart disease is limited, therefore caution is advised in the use of fluoxetine. Fluoxetine should also be used with caution in patients with conditions such as congenital long QT syndrome, family history of QT prolongation or other clinical conditions predisposing to arrhythmias (e.g. hypokalaemia, hypomagnesaemia, bradycardia, acute myocardial infarction or decompensated heart failure) or increased exposure to fluoxetine (e.g. liver failure).
In patients with stable heart disease, an ECG (Electrocardiogram) should be considered before starting treatment.
If signs of cardiac arrhythmia appear during treatment with fluoxetine, the treatment should be discontinued and an ECG performed.
Diabetes
In diabetic patients, treatment with an SSRI can alter glycemic control. Hypoglycaemia occurred during fluoxetine therapy, while hyperglycaemia developed after drug discontinuation. Dosage adjustment of the insulin and / or oral hypoglycemic agent may be required.
Suicide / suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events) and this risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until improvement occurs. It is common clinical experience that the risk of suicide can increase early in the healing process.
Other psychiatric conditions for which Fluoxeren is prescribed may also be associated with an increased risk of suicidal behavior. Additionally, these conditions can be associated with major depressive disorder. Consequently, the same precautions followed when treating patients with major depressive disorder should be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide-related events, or who exhibit a significant degree of suicidal ideation prior to initiation of treatment, are at increased risk for suicidal thoughts or suicide attempts and should be closely monitored during treatment. Clinical trials, placebo-controlled and performed in adult patients with psychiatric disorders receiving antidepressants, have shown an increased risk of suicidal behavior in patients less than 25 years of age treated with antidepressants compared to those treated with placebo.
Careful monitoring of patients, particularly those at high risk, is required during therapy, especially at the start of treatment and following dose changes. Patients (and their carers) should be advised of the need for check for any clinical worsening, the appearance of suicidal behavior or thoughts, and unusual changes in behavior, and to consult your doctor immediately if these symptoms occur.
Akathisia / psychomotor restlessness
The use of fluoxetine has been associated with the development of akathisia, characterized by a subjectively unpleasant or painful feeling of restlessness and psychomotor agitation often accompanied by the inability to sit still. This is most likely to happen within the first few weeks of treatment. In patients with these symptoms, increasing the dose may be harmful.
Withdrawal symptoms observed following discontinuation of SSRI treatment
Discontinuation symptoms observed are common when treatment is stopped, particularly if it is stopped abruptly (see section "Undesirable effects").
In clinical trials, adverse events observed with treatment discontinuation occurred in 60% of patients in both the fluoxetine and placebo groups. Of these adverse events, 17% in the fluoxetine group and 12% in the fluoxetine group. of placebo were severe.
The risk of withdrawal symptoms may depend on several factors, including the duration of therapy, the dosage and how quickly the dosage is reduced.
The most commonly reported reactions are dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), asthenia, agitation or anxiety, nausea and / or vomiting, tremor and headache. Generally the intensity of these symptoms is mild to moderate, however in some patients they may be severe. They usually appear within the first few days of stopping treatment. Generally these symptoms are self-limiting, and usually resolve within two weeks. although in some individuals they may last longer (2-3 months or more). It is therefore recommended to gradually reduce the dose of Fluoxeren when treatment is stopped, over a period of at least 1 to 2 weeks, depending on the patient needs (see section "Dose, method of administration", Discontinuation symptoms observed on discontinuation of Fluoxeren therapy).
Hemorrhage
Manifestations of cutaneous bleeding, such as ecchymosis and purpura, have been reported with the use of SSRIs. Ecchymosis has been reported as an infrequent event during treatment with fluoxetine. Other haemorrhagic manifestations (eg gynecological haemorrhages, gastrointestinal bleeding and other cutaneous or mucosal bleeding) have been reported rarely. In patients who taking SSRIs, caution is advised, especially during concomitant use of oral anticoagulants, drugs known to affect platelet function or other drugs that may increase the risk of bleeding, (eg. atypical antipsychotics such as clozapine, phenothiazines, most part of the tricyclic antidepressants, aspirin, NSAIDs) as well as in patients with a history of pathological manifestations characterized by bleeding (see section "Interactions").
Mydriasis
Mydriasis has been reported in association with fluoxetine; Therefore, caution should be exercised when prescribing fluoxetine in patients with elevated intraocular pressure or in patients at risk of acute narrow-angle glaucoma.
St. John's wort
When selective serotonin reuptake inhibitors and herbal preparations containing St. John's wort (Hypericum perforatum) are used together, increased serotonin-like effects, such as serotonin syndrome, may occur.
Serotonin syndrome or neuroleptic malignant syndrome-like events
On rare occasions, the development of a serotonin syndrome or neuroleptic malignant syndrome-like events have been reported in association with fluoxetine treatment, particularly when fluoxetine is administered in combination with other serotonergic drugs (among others L-tryptophan) and / or neuroleptics (see "Interactions"). Since these syndromes can give rise to potentially life-threatening conditions for the patient, if such events occur (characterized by a set of symptoms such as hyperthermia, rigidity, myoclonus, autonomic nervous system instability with possible rapid fluctuations in vital signs, changes in the mental status including confusion, irritability and extreme agitation up to delirium and coma) fluoxetine treatment should be discontinued and symptomatic supportive treatment initiated.
Irreversible non-selective monoamine oxidase inhibitors (e.g. iproniazid)
There have been reports of serious and sometimes fatal reactions in patients taking an SSRI in combination with a non-selective irreversible monoamine oxidase inhibitor (MAOI).
These cases exhibit features similar to serotonin syndrome and can be confused with (or diagnosed as) a neuroleptic malignant syndrome. Cyproheptadine or dantrolene may be of benefit to patients with such reactions. Symptoms of a drug interaction with a MAOI include: hyperthermia, rigidity, myoclonus, autonomic nervous system instability with possible rapid fluctuations in vital signs, mental status changes including confusion, irritability and extreme agitation up to delirium and coma.
Therefore, fluoxetine is contraindicated in combination with an irreversible non-selective MAOI (see section "Contraindications"). Since the latter has an effect that lasts 2 weeks, fluoxetine treatment should only be started 2 weeks after stopping an irreversible non-selective MAOI. Similarly, at least 5 weeks should elapse after stopping fluoxetine treatment before starting initiation of therapy with an irreversible non-selective MAOI.
Interactions Which drugs or foods can modify the effect of Fluoxeren
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Interaction studies have only been performed in adults.
Contraindicated associations
Irreversible non-selective monoamine oxidase inhibitors (e.g. iproniazid)
There have been reports of serious and sometimes fatal reactions in patients taking an SSRI in combination with an irreversible non-selective monoamine oxidase inhibitor (MAOI).
These cases exhibit features similar to serotonin syndrome and can be confused with (or diagnosed as) a neuroleptic malignant syndrome.
Cyproheptadine or dantrolene may be of benefit to patients with such reactions. Symptoms of a drug interaction with a MAOI include: hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs, mental status changes including confusion, irritability and extreme agitation up to delirium and coma.
Therefore, fluoxetine is contraindicated in combination with an irreversible non-selective MAOI (see section "Contraindications"). Since the latter has an effect that lasts 2 weeks, fluoxetine treatment should only be started 2 weeks after stopping an irreversible non-selective MAOI. Similarly, at least 5 weeks should elapse after stopping fluoxetine treatment before starting initiation of therapy with an irreversible non-selective MAOI.
Metoprolol used in heart failure: the risk of adverse events from metoprolol, including excessive bradycardia, may be increased due to inhibition of its metabolism by fluoxetine (see section "Contraindications").
Combinations not recommended
Tamoxifen: Pharmacokinetic interaction between CYP2D6 inhibitors and tamoxifen has been reported in the literature, with a 65-75% reduction in plasma levels of one of the most active forms of tamoxifen, ie endoxifen. A reduction in the efficacy of tamoxifen administered concomitantly with some SSRI antidepressants has been reported in some studies. Since this reduction in the effect of tamoxifen cannot be ruled out, concomitant administration of potent CYP2D6 inhibitors should be avoided whenever possible ( including fluoxetine) (see section "Precautions for use").
Alcohol: In routine testing, fluoxetine does not cause an increase in blood alcohol levels or potentiate the effects of alcohol. However, the combination of SSRI and alcohol treatment is not recommended.
MAOI-type A, including linezolid and methylthioninium chloride (methylene blue): risk of serotonin syndrome including diarrhea, tachycardia, sweating, tremor, confusion or coma. If concomitant use of these active substances together with fluoxetine cannot be avoided, strict clinical monitoring should be performed and administration of the concomitant agents initiated at the lowest possible recommended doses (see section 4.4).
Mequitazine: There may be an increased risk of adverse events from mequitazine (such as QT prolongation) due to inhibition of its metabolism by fluoxetine.
Associations requiring caution
Phenytoin: Changes in blood levels have been observed when combined with fluoxetine. In some cases, manifestations of toxicity have occurred. It is therefore advisable to administer the concomitant drug according to conservative therapeutic schemes and to carefully follow the patient's clinical conditions.
Serotonergic drugs (lithium, tramadol, triptans, tryptophan, selegiline (MAOI-type B), St. John's wort (Hypericum perforatum): there have been reports of a mild serotonin syndrome following the administration of SSRIs in combination with drugs also having " a serotonergic effect. Concomitant use of fluoxetine with these drugs should therefore be carried out with caution, with more targeted and more frequent clinical monitoring (see section "Precautions for use"). The combination with triptans adds an additional risk of coronary vasoconstriction and hypertension.
QT prolongation: Although no clinical studies have been performed on the combination of fluoxetine and other medicinal products that prolong the QT interval, an additive effect of fluoxetine and these medicinal products cannot be excluded. Consequently, concomitant administration of fluoxetine and medicines that prolong the QT interval - such as class IA and III antiarrhythmics, antipsychotics (eg phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents (eg sparfloxacin, moxifloxacin, erythromycin IV, pentamidine), antimalarials, especially halofantrine, some antihistamines (astemizole, mizolastine) - requires caution (see sections "Precautions for use", "Undesirable effects" and "Overdose").
Medicinal products affecting haemostasis (oral anticoagulants, whatever their mechanism of action, antiplatelet agents, including aspirin and NSAIDs): risk of increased bleeding. Clinical monitoring and more frequent INR monitoring should be performed with oral anticoagulants. A dose adjustment may be appropriate during fluoxetine treatment and after its discontinuation (see sections "Precautions for use" and "Undesirable effects").
Cyproheptadine: Single cases of decreased antidepressant activity of fluoxetine have been reported when used in combination with cyproheptadine.
Medicinal products inducing hyponatremia: Hyponatremia is an undesirable effect of fluoxetine.
Use together with other agents associated with hyponatraemia (eg diuretics, desmopressin, carbamazepine and oxcarbazepine) may lead to an increased risk (see section "Undesirable effects").
Medicines that lower the seizure threshold seizures are an undesirable effect of fluoxetine. The risk may be increased by use in combination with other agents capable of lowering the seizure threshold (eg TCA, other SSRIs, phenothiazines, butyrophenones, mefloquine, chloroquine, buproprion, tramadol).
Other drugs metabolised by CYP2D6: fluoxetine is a strong inhibitor of the CYP2D6 enzyme, therefore concomitant therapy with drugs also metabolised by this enzyme system can cause drug interactions, especially in the case of drugs with a narrow therapeutic index (flecainide, encainide , propafenone and nebivolol) and titrated drugs, but also with atomoxetine, carbamazepine, tricyclic antidepressants and risperidone. Their administration should be initiated or adjusted from the lowest value of the dosage range. This will also need to be done when you have been taking fluoxetine in the previous 5 weeks.
Warnings It is important to know that:
Weight loss
Weight loss may occur in patients taking fluoxetine, although this decrease is usually proportional to baseline body weight.
Skin rash and allergic reactions
Rash, anaphylactoid events and progressive systemic events, sometimes serious (involving skin, kidney, liver and lung) have been reported. The patient should immediately notify their doctor of any skin rash and / or hives or other allergic events that may occur with difficulty in breathing (see "Undesirable Effects"). Fluoxetine administration should be discontinued in case of skin rash or other allergic phenomena for which a different etiology cannot be identified.
Fertility, pregnancy and breastfeeding
Pregnancy
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
Some epidemiological studies suggest an increased risk of cardiovascular defects associated with the use of fluoxetine during the first trimester. The mechanism is unknown. Overall, the data suggest that the risk of having a newborn with a cardiovascular defect following maternal exposure to fluoxetine .
In the general population, about one in a hundred children is born with a heart defect; this percentage increases to 2 in 100 babies in mothers taking fluoxetine.
Epidemiological data have suggested that the use of SSRIs in pregnancy, especially in the late stages of pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN).
In addition, although fluoxetine can be used during pregnancy, caution should be used, especially in late pregnancy or just before the onset of labor, as the following effects have been reported in newborns: irritability, tremor, hypotonia , persistent crying, difficulty in sucking or sleeping. These symptoms may indicate both serotonergic effects and a withdrawal syndrome. The time of onset and duration of these symptoms may be related to the long half-life of fluoxetine (4-6 days) and its active metabolite, norfluoxetine (4-16 days).
Feeding time
Fluoxetine and its active metabolite norfluoxetine are known to be excreted in human breast milk. Adverse events have been reported in breastfed infants. If treatment with fluoxetine is deemed necessary, discontinuation of breastfeeding should be considered; however, if breastfeeding is continued, the lowest effective dose of fluoxetine should be prescribed.
Fertility
Animal data have shown that fluoxetine can affect sperm quality. Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. An impact on human fertility has not been observed so far.
Effects on ability to drive and use machines
Fluoxeren has no or negligible influence on the ability to drive or use machines. Patients should avoid driving a vehicle or operating hazardous machinery until they are reasonably certain that their abilities are not impaired.
Important information about some of the excipients
FLUOXEREN 20 mg / 5 ml oral solution contains sucrose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
FLUOXEREN 20 mg dispersible tablets contain sorbitol. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Fluoxeren: Dosage
For oral administration.
Major depressive episodes
Adults and the elderly: the recommended dose is 20 mg per day (1 hard capsule, or 1 dispersible tablet, or 5 ml of oral solution). If necessary, the dosage should be revised or adjusted within 3 to 4 weeks of initiation of therapy and thereafter as clinically appropriate. Although at higher doses there may be a potential increased risk of undesirable effects in some patients with insufficient therapeutic response at 20 mg, the dose may be gradually increased up to a maximum of 60 mg Dose adjustments should be made with caution for each individual patient to maintain patients at the lowest effective dose.
Patients with depression should be treated for a sufficient period of at least 6 months to ensure they are symptom-free.
Obsessive Compulsive Disorder
Adults and the elderly: the recommended dose is 20 mg per day (1 hard capsule, or 1 dispersible tablet, or 5 ml of oral solution). Although at higher doses there may be a potential for increased occurrence of undesirable effects, in case of insufficient therapeutic response after 2 weeks of treatment at 20 mg, it can be increased to a maximum of 60 mg. If no improvement is observed within 10 weeks, treatment with fluoxetine should be reconsidered. If a good therapeutic response has been achieved, treatment can be continued at an individually adjusted dosage. Although no systematic studies have been conducted to determine how long to continue fluoxetine treatment, OCD is a chronic condition and it is reasonable to consider prolonging therapy beyond 10 weeks in responding patients. Variations in dosage should be made carefully for each individual to keep the patient at the lowest effective dose.The need for treatment should be periodically reassessed. Some physicians find concomitant behavioral psychotherapy useful in patients who have responded well to drug therapy.
Long-term efficacy (beyond 24 weeks) has not been demonstrated in OCD.
Bulimia nervosa
Adults and the elderly: the recommended dose is 60 mg per day in a single oral administration in the morning (3 hard capsules, or 3 dispersible tablets, or 15 ml of oral solution). Efficacy has not been demonstrated in bulimia nervosa. long-term (beyond 3 months).
Adults - In all indications
The recommended dose can be increased or decreased. Doses above 80 mg per day have not been systematically evaluated.
Fluoxetine can be administered as a single or divided dose, with or without meals.
If the daily dose exceeds 20 mg it is recommended to administer FLUOXEREN twice a day, at breakfast and lunch.
When dosing is stopped, the 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 forms are bioequivalent.
Children and adolescents 8 years and older (moderate to severe major depressive episode)
Treatment should be initiated and monitored under the supervision of a specialist. The starting dose is 10 mg per day given as 2.5 ml of the Fluoxeren oral solution. Dose adjustments should be made with caution, on an individual basis, to maintain the patient at the lowest effective dose.
After 1 to 2 weeks the dose can be increased to 20 mg per day. Clinical experience with daily doses above 20 mg is minimal. There are only limited data on treatment beyond 9 weeks.
Children with low body weight
Due to higher plasma levels in children with reduced weight, the therapeutic effect can be achieved with lower doses.
For pediatric patients who respond to treatment, the need for continued treatment after 6 months should be re-evaluated. If no clinical benefit is achieved within 9 weeks, treatment should be reconsidered.
Senior citizens
Caution is advised when increasing the dose and, in general, the daily dose should not exceed 40 mg. The maximum recommended dose is 60 mg per day. Caution is advised in elderly patients with concomitant systemic diseases or taking other medications.
In patients with hepatic insufficiency, or in patients where there is a possibility of an "interaction between Fluoxeren and concomitant medicinal products, a lower or less frequent dose (eg 20 mg every other day) should be considered (see paragraph "Interactions").
In subjects with reduced hepatic or renal function and in the elderly, in subjects with intercurrent illnesses or who are taking other drugs, the dose of FLUOXEREN should be appropriately reduced or the interval between dosing increased (eg 20 mg every other day).
Withdrawal symptoms observed following discontinuation of Fluoxeren treatment
Abrupt discontinuation of treatment should be avoided. When discontinuing treatment with Fluoxeren the dose should be gradually reduced over a period of at least 1-2 weeks to reduce the risk of withdrawal reactions (see "Precautions for use" sections). and "Undesirable Effects").
If intolerable symptoms occur following a dose reduction or upon discontinuation of treatment, resuming the previously prescribed dose may be considered. Thereafter, the doctor may continue to reduce the dose, but more gradually. .
The exact dose of FLUOXEREN solution recommended by the doctor can be easily taken by following the instructions below:
- Introduce the dosing pipette into the bottle making sure that the plunger is fully inserted as far as it will go;
- Pull the plunger upwards until the dosage recommended by the doctor is reached;
- Pour the contents into a glass and dilute to taste with water.
FLUOXEREN dispersible tablets can be swallowed without chewing, or dissolved in water diluting as desired.
Overdose What to do if you have taken too much Fluoxeren
In case of accidental ingestion / intake of an excessive dose of FLUOXEREN, notify your doctor immediately or go to the nearest hospital. If you have any further questions on the use of FLUOXEREN, ask your doctor or pharmacist.
Symptoms
Cases of overdose due to fluoxetine generally have a mild course. Symptoms of overdose include nausea, vomiting, seizures, variable cardiovascular dysfunction from asymptomatic arrhythmias (including nodal rhythm arrhythmias and ventricular arrhythmias) or ECG changes indicative of QT prolongation up to cardiac arrest, pulmonary dysfunction and signs of a condition altered central nervous system ranging from excitation to coma. Fatal outcome attributed to fluoxetine overdose has been extremely rare.
Treatment
Monitoring of cardiac function and vital signs is advised, as well as general symptomatic and supportive measures. No specific antidotes are known.
Forced diuresis, dialysis, hemoperfusion and replacement transfusion are unlikely to offer benefits. Activated charcoal, which can be used in combination with sorbitol, may be an even more effective treatment than emesis or gastric lavage. When treating an overdose, consider the possibility of multiple drug involvement. Patients who have taken excessive amounts of a tricyclic antidepressant may need a longer period of time for close medical observation if they are also taking, or have recently taken, fluoxetine.
OMITTED ADMINISTRATION: WITHDRAWAL SYNDROME. In case of accidental failure to take one or more doses, the risk of the onset of a withdrawal syndrome is minimal.
Side Effects What are the side effects of Fluoxeren
Like all medicines, FLUOXEREN can cause side effects, although not everybody gets them.
Summary of the safety profile
The most commonly reported adverse reactions in fluoxetine-treated patients were headache, nausea, insomnia, fatigue and diarrhea. Undesirable effects may decrease in intensity and frequency with continued treatment and generally do not require cessation of therapy.
Table of adverse reactions
The table below presents the adverse reactions observed during fluexetine treatment in adult and pediatric populations. Some of these adverse reactions are also common to other SSRIs.
The frequencies reported below were calculated based on data from adult clinical studies (n = 9297) and spontaneous reports.
Estimated frequency: very common (≥ 1/10); common (≥ 1/100 to
- Thrombocytopenia
- Neutropenia
- Leukopenia
- Anaphylactic reaction
- Serum sickness
- Inappropriate secretion of antidiuretic hormone
- Decreased appetite 1
- Hyponatremia
- Insomnia 2
- Anxiety
- Nervousness
- Restlessness
- Voltage
- Decreased libido 3
- Sleep disorders
- Abnormal dreams 4
- Depersonalization
- Elevated mood
- Euphoric mood
- Abnormal thinking
- Abnormal orgasm 5
- Bruxism
- Suicidal thinking and behavior 6
- Hypomania
- Mania
- Hallucinations
- Agitation
- Panic attacks
- Confusional state
- Dysphemia Aggression
- Headache
- Attention disturbances
- Dizziness
- Dysgeusia
- Lethargy
- Somnolence 7
- Tremor
- Psychomotor hyperactivity
- Dyskinesia
- Ataxia
- Balance disorders
- Myoclonus
- Memory impairment
- Convulsion
- Akathisia
- Buccolingual syndrome
- Serotonin syndrome
- Blurred vision
- Mydriasis
- Tinnitus
- Palpitations
- Ventricular arrhythmia, including torsades de pointes
- QT prolongation in ECG
- Redness 8
- Hypotension
- Vasculitis
- Vasodilation
- Yawn
- Dyspnea
- Epistaxis
- Pharyngitis
- Pulmonary pathologies (inflammatory processes with variable histopathology and / or fibrosis) 9
- Diarrhea
- Nausea
- He retched
- Dyspepsia
- Dry mouth
- Dysphagia
- Gastrointestinal haemorrhage 10
- Esophageal pain
- Idiosyncratic hepatitis
- Skin rash 11
- Urticaria
- Itching
- Hyperhidrosis
- Alopecia
- Increased tendency to bruise
- Cold sweat
- Angioedema
- Bruising
- Photosensitivity
- Purple
- Erythema multiforme
- Stevens-Johnson Syndrome
- Toxic epidermal necrolysis (Lyell's syndrome)
- Arthralgia
- Muscle contractions
- Myalgia
- Frequent urination 12
- Dysuria
- Urinary retention
- Disorder of urination
- Gynecological bleeding 13
- Erectile dysfunction
- Ejaculation disorder 14
- Sexual dysfunction
- Galactorrhea
- Hyperprolactinemia
- Priapism
- Fatigue 15
- Feeling nervous
- Chills
- Malaise
- Feeling strange
- Feel cold
- Feel hot
- Mucosal bleeding
- Weight loss
- Increased transaminases
- Increased gammaglutamyltransferase
1 Includes anorexia
2 Includes early awakening in the morning, initial insomnia, intermediate insomnia
3 Includes loss of libido
4 Includes nightmares
5 Includes anorgasmia
6 Includes completed suicide, suicidal depression, intentional self-harm, self-harm, suicidal behavior, suicidal ideation, suicide attempt, morbid thoughts, self-harm behavior. These symptoms may be due to underlying disease.
7 Includes hypersomnia, sedation
8 Includes hot flashes
9 Includes atelectasis, interstitial lung disease, pneumonia
10 Mostly includes gingival bleeding, haematemesis, haematochezia, rectal haemorrhage, haemorrhagic diarrhea, melaena and gastric ulcer haemorrhage
11 Includes erythema, exfoliative rash, heat rash, rash, erythematous rash, follicular rash, generalized rash, macular rash, maculo-papular rash, morbilliform rash, papular rash, itchy rash, vesicular rash, rash erythematosus
12 Includes pollakiuria
13 Includes cervical haemorrhage, uterine dysfunction, uterine bleeding, genital haemorrhage, menometrorrhagia, menorrhagia, metrorrhagia, polymenorrhea, postmenopausal haemorrhage, uterine haemorrhage, vaginal haemorrhage
14 Includes ejaculation failure, ejaculatory dysfunction, premature ejaculation, delayed ejaculation, retrograde ejaculation
15 Includes asthenia.
Taste disturbances, dizziness, euphoria, anorgasmia and hyponatremia have also been reported.
Description of selected adverse reactions
Suicide / suicidal thoughts or clinical worsening: Cases of suicidal ideation and suicidal behaviors have been reported during fluoxetine therapy or soon after treatment discontinuation (see section "Precautions for use").
Bone Fractures: Epidemiological studies, conducted mainly in patients aged 50 years and older, show an increased risk of bone fractures in patients who are given SSRIs and TCAs. The mechanism behind this increased risk is unknown.
Withdrawal symptoms observed following discontinuation of fluoxetine treatment
Discontinuation of fluoxetine treatment commonly causes withdrawal symptoms.
Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), asthenia, agitation or anxiety, nausea and / or vomiting, tremor and headache are the most commonly reported reactions.
Generally these events are mild / moderate and self-limiting, however in some patients they may be severe and / or prolonged (see section "Precautions for use"). It is therefore recommended when treatment with Fluoxeren is no longer necessary , to carry out a gradual withdrawal by tapering the dose (see "Dose, method and time of administration" and "Precautions for use").
Pediatric population (see "Precautions for use" sections)
In pediatric clinical trials, suicide-related behaviors (suicide attempt and suicidal thoughts), hostility (reported events were: 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 more frequently observed among children and adolescents treated with antidepressants than in those treated with placebo.
The safety of fluoxetine has not been systematically evaluated for chronic treatment for more than 19 weeks.
Manic reactions, including mania and hypomania (2.6% of fluoxetine-treated patients vs. 0% in placebo-controlled), have been reported in pediatric clinical trials, leading to discontinuation in most cases. These patients had not had first episodes of hypomania / mania.
After 19 weeks of treatment, pediatric subjects treated in the clinical study with fluoxetine reported an average of 1.1 cm less in height (p = 0.004) and 1.1 kg less in weight (p = 0.008) than subjects treated with placebo.
Isolated cases of growth retardation have also been reported during clinical use.
In clinical studies conducted in a pediatric population, fluoxetine treatment was associated with a decrease in alkaline phosphatase levels.
Isolated cases of adverse events potentially indicating delayed sexual maturation or sexual dysfunction have been reported in pediatric clinical use.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili
Expiry and Retention
Expiry: see the expiry date indicated on the package.
The expiry date refers to the product in intact packaging, correctly stored.
CAUTION: DO NOT USE THE MEDICINAL PRODUCT AFTER THE EXPIRY DATE INDICATED ON THE PACKAGE
FLUOXEREN 20 mg hard capsules and FLUOXEREN 20 mg / 5 ml oral solution
Store below 25 ° C.
FLUOXEREN 20 mg dispersible tablets
Store below 30 ° C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
KEEP THE MEDICINAL PRODUCT OUT OF THE SIGHT AND REACH OF CHILDREN
Deadline "> Other information
COMPOSITION
FLUOXEREN 20 mg hard capsules
Each hard capsule contains:
- active ingredient: fluoxetine hydrochloride 22.36 mg equivalent to fluoxetine 20.00 mg
- excipients: corn 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 contains:
- active ingredient: fluoxetine hydrochloride 22.36 mg equivalent to fluoxetine 20.00 mg
- excipients: benzoic acid, sucrose, glycerin, mint flavor, purified water
FLUOXEREN 20 mg dispersible tablets
Each dispersible tablet contains:
- active ingredient: fluoxetine hydrochloride 22.36 mg equivalent to fluoxetine 20.00 mg
- excipients: microcrystalline cellulose, sodium saccharin, mannitol, sorbitol, anise flavoring, peppermint flavoring, colloidal anhydrous silica, pregelatinised starch, sodium stearyl fumarate, crospovidone
PHARMACEUTICAL FORM AND CONTENT
- 12 and 28 hard capsules of 20 mg each
- 60 ml of 20 mg / 5 ml oral solution
- 12 and 28 dispersible tablets of 20 mg each
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
FLUOXEREN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
FLUOXEREN 20 mg hard capsules
Each hard capsule contains:
active principle: 22.36 mg of fluoxetine hydrochloride equivalent to 20.00 mg of fluoxetine.
FLUOXEREN 20 mg / 5ml oral solution
5 ml of oral solution contains:
active principle: 22.36 mg of fluoxetine hydrochloride equivalent to 20.00 mg of fluoxetine.
FLUOXEREN 20 mg dispersible tablets
Each dispersible tablet contains:
active principle: 22.36 mg of fluoxetine hydrochloride equivalent to 20.00 mg of fluoxetine.
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM -
Hard capsule, dispersible tablet, oral solution.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Major depressive episodes.
Obsessive Compulsive Disorder.
Bulimia nervosa: Fluoxeren is indicated in association with psychotherapy for the reduction of binge-eating and purging activity.
04.2 Posology and method of administration -
For oral administration.
Major depressive episodes
Adults and the elderly: the recommended dose is 20 mg per day. If necessary, the dosage should be reviewed and adjusted within 3 - 4 weeks of initiation of therapy and thereafter as deemed clinically appropriate. Although at higher doses there may be a potential increased risk of side effects in some patients with insufficient therapeutic response. at 20 mg, the dose may be gradually increased up to a maximum of 60 mg (see section 5.1). Dose adjustments should be made with caution for each individual patient to maintain patients at the lowest effective dose.
Patients with depression should be treated for a sufficient period of at least 6 months to be sure they are symptom free.
Obsessive Compulsive Disorder
Adults and the elderly: the recommended dose is 20 mg per day. Although there may be a potential increased risk of side effects at higher doses, in some patients, if there is insufficient therapeutic response after 2 weeks of treatment at 20 mg, the dose may be increased up to a maximum of 60 mg.
If no improvement is observed within 10 weeks, treatment with fluoxetine should be reconsidered. If a good therapeutic response has been achieved, treatment can be continued by adjusting the dosage on an individual basis. Although no systematic studies have been conducted to determine how long to continue fluoxetine treatment, OCD is a chronic condition and it is reasonable to consider prolonging therapy beyond 10 weeks in responding patients. Dosage changes should be made with caution for each individual in order to maintain the patient at the lowest effective dose. The need for treatment should be reassessed periodically. Some physicians find concomitant behavioral psychotherapy useful in patients who have responded well to drug therapy. Long-term efficacy (beyond 24 weeks) has not been demonstrated in Obsessive Compulsive Disorder.
Bulimia nervosa
Adults and the elderly: the recommended dose is 60 mg / day. Long-term efficacy (beyond 3 months) has not been demonstrated in bulimia nervosa.
Adults - All indications
The recommended dose can be increased or decreased. Doses above 80 mg / day have not been systematically evaluated.
Fluoxetine can be administered as a single or divided dose, with or without meals.
When dosing is stopped, the 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 forms are bioequivalent.
Children and adolescents 8 years and older (moderate to severe major depressive episode)
Treatment should be initiated and monitored under the supervision of a specialist. The starting dose is 10 mg / day administered as 2.5 ml of the Fluoxeren oral solution. Dose adjustments should be made with caution, on an individual basis, to maintain the patient at the lowest effective dose.
After 1 - 2 weeks, the dose can be increased to 20 mg / day. Clinical experience with daily doses above 20 mg is minimal. There are only limited data on treatment beyond 9 weeks.
Children with low body weight
Due to higher plasma levels in children with reduced weight, the therapeutic effect can be achieved with lower doses (see section 5.2).
For pediatric patients who respond to treatment, the need for continued treatment after 6 months should be re-evaluated. If no clinical benefit is achieved within 9 weeks, treatment should be reconsidered.
Senior citizens
Caution is advised when increasing the dose and, in general, the daily dose should not exceed 40 mg. The maximum recommended dose is 60 mg / day.
A lower or less frequent dose (eg 20 mg every other day) should be considered in patients with hepatic insufficiency (see section 5.2), or in patients where there is a potential for an "interaction between Fluoxeren and medicinal products. taken concomitantly (see section 4.5).
Withdrawal symptoms observed following discontinuation of Fluoxeren treatment
Abrupt discontinuation of treatment should be avoided. When discontinuing treatment with Fluoxeren the dose should be gradually reduced over a period of at least 1 - 2 weeks to reduce the risk of withdrawal reactions (see sections 4.4 and 4.8).
If intolerable symptoms occur following a dose reduction or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Thereafter, the doctor may continue to reduce the dose, but more gradual.
04.3 Contraindications -
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Fluoxetine is contraindicated in combination with:
- irreversible and non-selective monoamine oxidase inhibitors (e.g. iproniazid) (see sections 4.4 and 4.5);
- metoprolol used in heart failure (see section 4.5).
04.4 Special warnings and appropriate precautions for use -
Pediatric population - Children and adolescents under the age of 18
Suicide-related behaviors (suicide attempts and suicidal thoughts) and hostility (essentially aggression, oppositional behavior and anger) were observed more frequently in clinical trials in children and adolescents treated with antidepressants than in those treated with placebo. Fluoxeren is only for use in children and adolescents aged 8 to 18 years for the treatment of moderate to severe major depressive episodes and should not be used in other indications. If, based on medical needs, a decision is made for treatment, the patient should be carefully monitored for the appearance of suicidal symptoms. Furthermore, only limited long-term safety data are available in children and adolescents, including effects on growth, sexual maturation and cognitive, emotional and behavioral development (see section 5.3).
In a 19-week clinical study, a reduced increase in both height and weight was observed in children and adolescents treated with fluoxetine (see section 5.1). It has not been established whether there is an effect on achieving normal height in adulthood. The possibility of delayed puberty cannot be excluded (see sections 5.3 and 4.8). Therefore, pubertal growth and development (height, weight and TANNER staging) should be monitored during and after treatment with fluoxetine. of these has slowed down, a pediatric consultation should be considered.
In studies performed in the pediatric population, mania and hypomania were commonly reported (see section 4.8). Therefore, regular monitoring for the occurrence of mania / hypomania is recommended. Fluoxetine should be discontinued in any patient entering a manic phase.
It is important that the doctor carefully discusses the risks and benefits of treatment with the child / young adult and / or his / her parents.
Skin rash and allergic reactions
Rash, anaphylactoid events and progressive systemic events, sometimes serious (involving skin, kidney, liver or lung), have been reported. Fluoxetine administration should be discontinued in case of skin rash or other allergic phenomena for which a different etiology cannot be identified.
Convulsions
Seizures pose a potential risk with antidepressant medications. Therefore, as with other antidepressants, fluoxetine should be administered with caution to patients with a history of seizures. Treatment should be discontinued in any patient who experiences seizures or in whom an increase in seizure frequency is observed. Administration of fluoxetine should be avoided in patients with unstable seizure disorders / epilepsy and patients with controlled epilepsy should be closely monitored (see section 4.5).
Electroconvulsive therapy (TEC)
Rare cases of prolonged seizures have been reported in fluoxetine-treated patients receiving TEC treatment, therefore caution is advised.
Mania
Antidepressants should be used with caution in patients with a history of mania / hypomania. As with all antidepressant drugs, fluoxetine should be discontinued in any patient entering a manic phase.
Hepatic / renal function
Fluoxetine is extensively metabolised by the liver and eliminated by the kidneys. In patients with significant hepatic dysfunction, a lower dose is recommended, e.g. administration every other day. When fluoxetine was administered in doses of 20 mg / day for 2 months, patients with severe renal impairment (GFR dialysis showed no difference in plasma levels of fluoxetine or norfluoxetine compared to control subjects with normal renal function.
Tamoxifen
Fluoxetine, a potent inhibitor of CYP2D6, may cause decreased concentrations of endoxifen, one of the most important active metabolites of tamoxifen. Whenever possible, administration of fluoxetine should therefore be avoided during treatment with tamoxifen (see section 4.5).
Cardiovascular effects
No conduction disturbances leading to cardiac arrest were observed on ECG in 312 patients who received fluoxetine in double-blind clinical trials. However, clinical experience in acute heart disease is limited, therefore caution is advised. Cases of QT interval prolongation and ventricular arrhythmia including torsades de pointes have been reported during the post-marketing period (see sections 4.5, 4.8 and 4.9).
Fluoxetine should be used with caution in patients with conditions such as congenital long QT syndrome, family history of QT prolongation or other clinical conditions predisposing to arrhythmias (e.g. hypokalaemia, hypomagnesaemia, bradycardia, acute myocardial infarction or decompensated heart failure. ) or increased exposure to fluoxetine (e.g. liver failure).
If patients with stable heart disease are being treated, an ECG should be considered before starting treatment.
If signs of cardiac arrhythmia appear during treatment with fluoxetine, the treatment should be discontinued and an ECG performed.
Weight loss
Weight loss may occur in patients taking fluoxetine, but this is usually proportional to the starting body weight.
Diabetes
In diabetic patients, treatment with an SSRI can alter glycemic control. Hypoglycaemia occurred during fluoxetine therapy, while hyperglycaemia developed after drug discontinuation. Dosage adjustment of the insulin and / or oral hypoglycemic agent may be required.
Suicide / Suicidal ideation or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission of the disease occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until improvement occurs. It is common clinical experience that the risk of suicide can increase early in the healing process.
Other psychiatric conditions for which Fluoxeren is prescribed may also be associated with an increased risk of suicidal behavior. Additionally, these conditions can be associated with major depressive disorder. Consequently, the same precautions followed when treating patients with major depressive disorder should be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide-related events, or who exhibit a significant degree of suicidal ideation prior to initiation of treatment, are at increased risk for suicidal thoughts or suicide attempts, and should be closely monitored during treatment. A meta-analysis Placebo-controlled clinical trials performed in adult patients with psychiatric disorders receiving antidepressants have shown an increased risk of suicidal behavior in patients less than 25 years of age treated with antidepressants compared to those treated with placebo.
Careful monitoring of patients, particularly those at high risk, is required during therapy, especially at the start of treatment and following dose changes. Patients (and their carers) should be advised of the need for check for any clinical worsening, the appearance of suicidal behaviors or thoughts, and unusual changes in behavior, and seek immediate medical attention if these symptoms occur.
Akathisia / Psychomotor restlessness
The use of fluoxetine has been associated with the development of akathisia, characterized by a subjectively unpleasant or painful feeling of restlessness and psychomotor agitation accompanied by an inability to sit or stand still. This is most likely to happen within the first few weeks of treatment. In patients with these symptoms, increasing the dose may be harmful.
Withdrawal symptoms observed following discontinuation of SSRI treatment
Discontinuation symptoms when treatment is stopped are common, particularly in the event of abrupt discontinuation (see section 4.8).
In clinical trials, adverse events observed with treatment discontinuation occurred in 60% of patients in both the fluoxetine and placebo groups. Of these adverse events, 17% in the fluoxetine group and 12% in the fluoxetine group. of placebo were severe.
The risk of withdrawal symptoms may depend on several factors, including the duration of therapy, the dosage and how quickly the dosage is reduced.
The most commonly reported reactions are dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), asthenia, agitation or anxiety, nausea and / or vomiting, tremor and headache. Generally, the intensity of these symptoms is mild to moderate, however, in some patients, they may be severe. They usually appear within the first few days of stopping treatment. Generally these symptoms are self-limiting, and usually resolve within two days. weeks, although in some individuals they may last longer (2-3 months or more). It is therefore recommended to gradually reduce the dose of Fluoxeren when discontinuing treatment, over a period of at least 1 to 2 weeks, based on patient needs (see section 4.2, Withdrawal symptoms observed on discontinuation of Fluoxeren therapy).
Hemorrhage
Manifestations of cutaneous bleeding such as ecchymosis and purpura have been reported with the use of SSRIs.Ecchymosis has been reported as an infrequent event during treatment with fluoxetine. Other haemorrhagic manifestations (eg gynecological haemorrhages, gastrointestinal bleeding and other cutaneous or mucosal bleeding) have been reported rarely. In patients who taking SSRIs, caution is advised, especially during concomitant use of oral anticoagulants, drugs known to affect platelet function, or other drugs that may increase the risk of bleeding (eg atypical antipsychotics such as clozapine, phenothiazines, most part of the tricyclic antidepressants, aspirin, NSAIDs, as well as in patients with a history of pathological manifestations characterized by bleeding (see section 4.5).
Mydriasis
Mydriasis has been reported in association with fluoxetine; Therefore, caution should be exercised when prescribing fluoxetine in patients with elevated intraocular pressure or in patients at risk of acute narrow-angle glaucoma.
St. John's wort
When selective serotonin reuptake inhibitors and herbal preparations containing St. John's wort (Hypericum perforatum) are used together, increased serotonergic-type effects, such as serotonin syndrome, may occur.
Serotonin syndrome or neuroleptic malignant syndrome-like events
On rare occasions the development of a serotonin syndrome or neuroleptic malignant syndrome-like events have been reported in association with fluoxetine treatment, particularly when fluoxetine is administered in combination with other serotonergic drugs (among others L-tryptophan) and / or neuroleptics (see section 4.5). Since these syndromes can give rise to potentially life-threatening conditions for the patient, if such events occur (characterized by a set of symptoms such as hyperthermia, rigidity, myoclonus, autonomic nervous system instability with possible rapid fluctuations in vital signs, changes in the mental status including confusion, irritability and extreme agitation up to delirium and coma) fluoxetine treatment should be discontinued and symptomatic supportive treatment initiated.
Irreversible non-selective monoamine oxidase inhibitors (e.g. iproniazid)
There have been reports of serious and sometimes fatal reactions in patients taking an SSRI in combination with an irreversible non-selective monoamine oxidase inhibitor (MAOI).
These cases exhibit features similar to serotonin syndrome (and can be confused with (or diagnosed as) a neuroleptic malignant syndrome). Cyproheptadine or dantrolene may be of benefit to patients with such reactions. Symptoms of a drug interaction with a MAOI include: hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs, mental status changes including confusion, irritability and extreme agitation up to delirium and coma.
Therefore, fluoxetine is contraindicated in combination with an irreversible non-selective MAOI (see section 4.3). Since the latter has an effect that lasts 2 weeks, fluoxetine treatment should only be started 2 weeks after stopping an irreversible non-selective MAOI. Similarly, at least 5 weeks should elapse after stopping fluoxetine treatment before starting initiation of therapy with an irreversible non-selective MAOI.
Important information about some of the excipients
FLUOXEREN 20 mg / 5 ml oral solution contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose malabsorption, or sucrase isomaltase insufficiency should not take this medicine.
FLUOXEREN 20 mg dispersible tablets contain sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction -
Interaction studies have only been performed in adults.
Half-life: The long elimination half-lives of both fluoxetine and norfluoxetine should be borne in mind (see section 5.2) when considering pharmacodynamic or pharmacokinetic drug interactions (e.g. when switching from fluoxetine to other antidepressants).
Contraindicated associations
Irreversible non-selective inhibitors of monoamine oxidase (e.g. iproniazid)
There have been reports of serious and sometimes fatal reactions in patients taking an SSRI in combination with an irreversible non-selective monoamine oxidase inhibitor (MAOI).
These cases exhibit features similar to serotonin syndrome (and can be confused with (or diagnosed as) a neuroleptic malignant syndrome).
Cyproheptadine or dantrolene may be of benefit to patients with such reactions. Symptoms of a drug interaction with a MAOI include: hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs, mental status changes including confusion, irritability and extreme agitation up to delirium and coma.
Therefore, fluoxetine is contraindicated in combination with an irreversible non-selective MAOI (see section 4.3). Since the latter has an effect that lasts 2 weeks, fluoxetine treatment should only be started 2 weeks after stopping an irreversible non-selective MAOI. Similarly, at least 5 weeks should elapse after stopping fluoxetine treatment before starting initiation of therapy with an irreversible non-selective MAOI.
Metoprolol used in heart failure: The risk of metoprolol adverse events, including excessive bradycardia, may be increased due to inhibition of its metabolism by fluoxetine (see section 4.3).
Combinations not recommended
TamoxifenPharmacokinetic interaction between CYP2D6 inhibitors and tamoxifen has been reported in the literature, with a 65-75% reduction in plasma levels of one of the most active forms of tamoxifen, ie endoxifen. A reduction in the efficacy of tamoxifen administered concomitantly with some SSRI antidepressants has been reported in some studies. Since this reduction in the effect of tamoxifen cannot be ruled out, concomitant administration of potent CYP2D6 inhibitors should be avoided whenever possible ( including fluoxetine) (see section 4.4).
Alcohol: In routine tests, fluoxetine does not cause an increase in blood alcohol levels or potentiate the effects of alcohol. However, the combination of SSRI and alcohol treatment is not recommended.
MAO-type A including linezolid and methylthioninium chloride (methylene blue): risk of serotonin syndrome including diarrhea, tachycardia, sweating, tremor, confusion or coma. If concomitant use of these active substances together with fluoxetine cannot be avoided, strict clinical monitoring should be performed and administration of the concomitant agents initiated at the lowest possible recommended doses (see section 4.4).
Mequitazine: there may be an increased risk of adverse events from mequitazine (such as QT prolongation), due to the inhibition of its metabolism by fluoxetine.
Associations requiring caution
Fenitoina: Changes in blood levels have been observed when combined with fluoxetine. In some cases, manifestations of toxicity have occurred. It is therefore advisable to administer the concomitant drug according to conservative therapeutic schemes and to carefully follow the patient's clinical conditions.
Serotonergic drugs [lithium, tramadol, triptans, tryptophan, selegiline (MAOI-type B), St. John's wort (Hypericum perforatum)]: There have been reports of a moderate serotonin syndrome following the administration of SSRIs in combination with drugs also having a serotonergic effect. Concomitant use of fluoxetine with these drugs should therefore be carried out with caution, with more targeted clinical monitoring and more frequent (see section 4.4).
The association with triptans adds an additional risk of coronary vasoconstriction and hypertension.
Prolongation of the QT intervalPharmacokinetic and pharmacodynamic studies on the combination of fluoxetine and other medicinal products that prolong the QT interval have not been performed. An additive effect of fluoxetine and these medicinal products cannot be excluded. Consequently, concomitant administration of fluoxetine and drugs that prolong the QT interval - such as class IA and III antiarrhythmics, antipsychotics (eg phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents (eg sparfloxacin, moxifloxacin) , erythromycin IV, pentamidine), antimalarial therapy, especially halofantrine, some antihistamines (astemizole, mizolastine) - requires caution (see sections 4.4, 4.8 and 4.9).
Medicines that affect haemostasis (oral anticoagulants, whatever their mechanism of action, antiplatelet agents, including aspirin and NSAIDs): risk of increased bleeding. Clinical monitoring and more frequent INR monitoring should be performed with oral anticoagulants. Dose adjustment may be appropriate during fluoxetine treatment and after its discontinuation (see sections 4.4 and 4.8).
Cyprusheptadine: Single cases of decreased antidepressant activity of fluoxetine have been reported when used in combination with cyproheptadine.
Medicines that induce hyponatremia: Hyponatremia is an undesirable effect of fluoxetine. Use together with other agents associated with hyponatraemia (eg diuretics, desmopressin, carbamazepine and oxcarbazepine) may lead to an increased risk (see section 4.8).
Medicines that lower the epileptogenic threshold: Seizures are an undesirable effect of fluoxetine. The risk may be increased by use in combination with other agents capable of lowering the epileptogenic threshold (eg TCA, other SSRIs, phenothiazines, butyrophenones, mefloquine, chloroquine, buproprion, tramadol).
Other medicinal products metabolised by CYP2D6: fluoxetine is a strong inhibitor of the CYP2D6 enzyme, therefore concomitant therapy with drugs also metabolized by this enzyme system can cause drug interactions, especially in the case of drugs that have 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 from the lowest value of the dosage range. This should also be done when there has been fluoxetine in the previous 5 weeks.
04.6 Pregnancy and breastfeeding -
Pregnancy
Some epidemiological studies suggest an increased risk of cardiovascular defects associated with the use of fluoxetine during the first trimester. The mechanism is unknown. Overall, the data suggest that the risk of having a newborn with a cardiovascular defect following maternal exposure to fluoxetine it is 2/100 compared to an expected rate for such defects of about 1/100 in the general population.
Epidemiological data have suggested that the use of SSRIs in 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 in 1000 pregnancies. In the population Generally, 1 to 2 cases of PPHN occur per 1000 pregnancies.
In addition, although fluoxetine can be used during pregnancy, caution should be used, especially in the late stages of pregnancy or just before the onset of labor, as the following effects have been reported in newborns: irritability, tremor, hypotonia , persistent crying, difficulty in sucking or sleeping. These symptoms may indicate both serotonergic effects and a withdrawal syndrome. The time of onset and duration of these symptoms may be related to the long half-life of fluoxetine (4-6 days) and its active metabolite, norfluoxetine (4-16 days).
Feeding time
Fluoxetine and its active metabolite norfluoxetine are known to be excreted in human breast milk. Adverse events have been reported in breastfed infants. If treatment with fluoxetine is deemed necessary, discontinuation of breastfeeding should be considered; however, if breastfeeding is continued, the lowest effective dose of fluoxetine should be prescribed.
Fertility
Animal data have shown that fluoxetine can affect sperm quality (see section 5.3). Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. An impact on human fertility has not been observed so far.
04.7 Effects on ability to drive and use machines -
Fluoxeren has no or negligible influence on the ability to drive or use machines. Although fluoxetine has been shown not to interfere with psychomotor skills in healthy volunteers, any psychoactive drug can impair judgment or psychomotor skills. Patients should be advised to avoid driving a vehicle or operating hazardous machinery until they are reasonably certain that their abilities are not impaired.
04.8 Undesirable effects -
to) Summary of the safety profile
The most commonly reported adverse reactions in fluoxetine-treated patients were headache, nausea, insomnia, fatigue and diarrhea. Undesirable effects may decrease in intensity and frequency with continued treatment and generally do not require discontinuation of therapy.
b) Table of adverse reactions
The table below presents the adverse reactions observed during fluoxetine treatment in adult and pediatric populations. Some of these adverse reactions are also common to other SSRIs.
The frequencies reported below were calculated based on data from adult clinical studies (n = 9297) and spontaneous reports.
Estimated frequency: very common (≥ 1/10); common (≥ 1/100 to
¹ Includes anorexia
² Includes early awakening in the morning, initial insomnia, intermediate insomnia
³ Includes loss of libido
4 Includes nightmares
5 Includes anorgasmia
6 Includes completed suicide, suicidal depression, intentional self-harm, self-harm ideas, suicidal behavior, suicidal ideation, suicide attempt, morbid thoughts, self-harm behavior. These symptoms may be due to underlying disease.
7 Includes hypersomnia, sedation
8 Includes hot flashes
9 Includes atelectasis, interstitial lung disease, pneumonia
10 Most commonly includes gingival bleeding, haematemesis, haematochezia, rectal haemorrhage, haemorrhagic diarrhea, melaena and gastric ulcer haemorrhage
11 Includes erythema, exfoliative rash, heat rash, rash, erythematous rash, follicular rash, generalized rash, macular rash, maculo-papular rash, morbilliform rash, papular rash, itchy rash, vesicular rash, rash erythematosus
12 Includes pollakiuria
13 Includes cervical haemorrhage, uterine dysfunction, uterine bleeding, genital haemorrhage, menometrorrhagia, menorrhagia, metrorrhagia, polymenorrhea, postmenopausal haemorrhage, uterine haemorrhage, vaginal haemorrhage
14 Includes ejaculation failure, ejaculatory dysfunction, premature ejaculation, delayed ejaculation, retrograde ejaculation
15 Includes asthenia.
Taste disturbances, dizziness, euphoria, anorgasmia and hyponatremia have also been reported.
c) Description of selected adverse reactions
Suicide / suicidal thoughts or clinical worsening: Cases of suicidal ideation and suicidal behaviors have been reported during fluoxetine therapy or soon after treatment discontinuation (see section 4.4).
Bone fractures: Epidemiological studies, mainly conducted in patients aged 50 years and over show an increased risk of bone fractures in patients receiving SSRIs and TCAs
The mechanism behind this increased risk is unknown.
Withdrawal symptoms observed following discontinuation of fluoxetine treatment: Discontinuation of fluoxetine treatment commonly causes withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), asthenia, agitation or anxiety, nausea and / or vomiting, tremor and headache, are the most commonly reported reactions.
Generally these events are mild / moderate and self-limiting, however in some patients they may be severe and / or prolonged (see section 4.4). It is therefore recommended, when treatment with Fluoxeren is no longer necessary, to discontinue therapy by gradual dose reduction (see sections 4.2 and 4.4).
d) Pediatric population (see sections 4.4 and 5.1)
Adverse reactions that have been observed specifically or with a different frequency in this population are described below. The frequencies of these events are based on exposures during pediatric clinical trials (n = 610).
In pediatric clinical trials, suicide-related behaviors (suicide attempt and suicidal thoughts), hostility (reported events were: 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 more frequently observed among children and adolescents treated with antidepressants than in those treated with placebo.
The safety of fluoxetine has not been systematically evaluated for chronic treatment lasting longer than 19 weeks.
Manic reactions, including mania and hypomania (2.6% of fluoxetine-treated patients vs. 0% of placebo-controlled patients) have been reported in clinical trials in a pediatric population, leading in most cases to discontinuation of treatment. These patients had not previously had episodes of hypomania / mania.
After 19 weeks of treatment, pediatric subjects treated in the clinical study with fluoxetine reported an average growth of 1.1 cm less in height (p = 0.004) and 1.1 kg less in weight (p = 0.008) compared to subjects treated with placebo.
Isolated cases of growth retardation have also been reported during clinical use (see also section 5.1).
In clinical studies conducted in a pediatric population, fluoxetine treatment was associated with a decrease in alkaline phosphatase levels.
Isolated cases of adverse events potentially indicating delayed sexual maturation or sexual dysfunction have been reported in pediatric clinical use (see also section 5.3).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
Symptoms
Cases of overdose due to fluoxetine alone generally have a mild course. Symptoms of overdose include nausea, vomiting, seizures, cardiovascular dysfunction ranging from asymptomatic arrhythmias (including nodal rhythm arrhythmias 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 signs of an altered CNS condition ranging from excitation to coma. Fatal outcome attributed to fluoxetine overdose alone has been extremely rare.
Treatment
Monitoring of cardiac function and vital signs is advised, as well as general symptomatic and supportive measures. No specific antidotes are known.
Forced diuresis, dialysis, hemoperfusion and replacement transfusion are unlikely to offer benefits. Activated charcoal, which can be used in combination with sorbitol, may be an even more effective treatment than emesis or gastric lavage. When treating an overdose, consider the possibility of multiple drug involvement. Patients who have taken excessive amounts of a tricyclic antidepressant may need a longer period of time for close medical observation if they are also taking, or have recently taken, fluoxetine.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: antidepressants; selective serotonin reuptake inhibitors.
ATC code: N06AB03.
Fluoxetine is a selective serotonin reuptake inhibitor, and this probably accounts for the mechanism of action. Fluoxetine has virtually no affinity for other receptors such as alpha1-, alpha2- and beta-adrenergics; serotonergics; dopaminergics type 1 histamine receptors; muscarinics and GABA receptors.
Major depressive episodes: Clinical studies comparing placebo and active substances were performed in patients with major depressive episodes. Fluoxetine has been shown to be significantly more effective than placebo, as shown by the Hamilton Depression Rating Scale (HAM-D). Compared to placebo, fluoxetine resulted in significantly higher rates of response (defined by a 50% reduction in HAM-D score) and remission in these studies.
Obsessive Compulsive Disorder: In short-term clinical trials (lasting less than 24 weeks), fluoxetine was shown to be significantly more effective than placebo. The therapeutic effect was observed at 20 mg / day, but higher doses (40 or 60 mg / day) demonstrated a higher response rate. In long-term clinical trials (3 short-term clinical trials with extension phase to a relapse prevention study) efficacy has not been demonstrated.
Bulimia nervosa: In short-term clinical trials (less than 16 weeks duration), in outpatients who fully met the DSM-III-R criteria for bulimia nervosa, fluoxetine 60 mg / day was shown to be significantly more effective than placebo in reducing binge eating and purging. However, as far as long-term effectiveness is concerned, it is not possible to draw a conclusion.
Two placebo-controlled clinical trials were conducted in patients who met the diagnostic criteria for Pre-Menstrual Dysphoric Disorder as reported on the DSM-IV. Patients were included if they had symptoms of sufficient severity to interfere with their occupational and social function and in their relationship life with others. Patients using oral contraceptives were excluded. In the first study with a continuous dosage of 20 mg / day for 6 menstrual cycles, the improvement was observed in the primary efficacy parameter (irritability, anxiety, dysphoria). In the second study, with intermittent dosing during the luteal phase (20 mg / day for 14 days) for 3 menstrual cycles, improvement was observed in the primary efficacy parameter (score based on the daily recording scale of the severity of the disorders, Daily Record of Severity of Problem Score). However, no definitive conclusions on the efficacy and duration of treatment can be drawn from these studies.
05.2 "Pharmacokinetic properties -
Absorption
After oral administration, fluoxetine is well absorbed from the gastrointestinal tract. Bioavailability is not affected by food intake.
Distribution
Fluoxetine is extensively bound to plasma proteins (approximately 95%) and is distributed diffusely in the body (volume of distribution: 20-40 l / kg). Equilibrium plasma concentrations are reached only after several weeks of treatment. Equilibrium concentrations after prolonged dosing are similar to those observed after 4-5 weeks.
Metabolism
Fluoxetine has a non-linear pharmacokinetic profile with a hepatic first pass effect. The maximum plasma concentration is generally reached 6 to 8 hours after administration. Fluoxetine is extensively metabolised by the polymorphic enzyme CYP2D6. Fluoxetine is predominantly metabolised by the liver to the active metabolite norfluoxetine (demethylfluoxetine) via demethylation.
Elimination
The elimination half-life of fluoxetine is 4-6 days, while that of norfluoxetine is 4-16 days. These long half-lives are responsible for the drug's persistence for 5-6 weeks after its discontinuation. Elimination occurs mainly by renal route (about 60%). Fluoxetine is excreted in breast milk.
Populations at risk
• Elderly: the kinetic parameters are not altered in healthy elderly compared to younger subjects.
• Hepatic insufficiency: in case of hepatic insufficiency (alcoholic cirrhosis), the half-lives of fluoxetine and norfluoxetine are increased to 7 and 12 days, respectively. A lower or less frequent dose should be considered.
• Renal insufficiency: after administration of a single dose of fluoxetine in patients with mild, moderate or complete (anuria) renal insufficiency, the kinetic parameters were not altered compared to healthy volunteers. However, after repeated administration, an increase in the equilibrium plateau of plasma concentrations may be observed.
05.3 Preclinical safety data -
Studies conducted in vitro or on animals did not show a carcinogenic, mutagenic effect or impaired fertility.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
FLUOXEREN 20 mg hard capsules: each hard capsule contains: corn starch, dimethicone, patent blue V E-131, yellow iron oxide E-172, titanium dioxide E-171, gelatin
FLUOXEREN 20 mg / 5ml oral solution: 5 ml of oral solution contain: benzoic acid, sucrose, glycerin, mint flavor, purified water
FLUOXEREN 20 mg dispersible tablets: each dispersible tablet contains: microcrystalline cellulose, sodium saccharin, mannitol, sorbitol, anise flavoring, peppermint flavoring, colloidal anhydrous silica, pregelatinised starch, sodium stearyl fumarate, crospovidone.
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
FLUOXEREN 20 mg hard capsules: 3 years.
FLUOXEREN 20 mg dispersible tablets: 2 years.
FLUOXEREN 20 mg / 5 ml oral solution: 2 years.
06.4 Special precautions for storage -
FLUOXEREN 20 mg hard capsules and FLUOXEREN 20 mg / 5 ml oral solution
Store below 25 ° C.
FLUOXEREN 20 mg dispersible tablets
Store below 30 ° C.
06.5 Nature of the immediate packaging and contents of the package -
FLUOXEREN 20 mg hard capsules
The product is packaged in blisters consisting of PVC (opaque) and aluminum.
Blister of 12 hard capsules
Blister of 28 hard capsules.
FLUOXEREN 20 mg dispersible tablets
The product is packaged in blisters consisting of ACLAR and Aluminum.
Blister pack of 12 dispersible tablets
Blister packs of 28 dispersible tablets.
FLUOXEREN 20 mg / 5 ml oral solution
The product is packaged in 60 ml amber glass bottles and closed with a plastic cap.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
FLUOXEREN 20 mg hard capsules:
Swallow without chewing.
FLUOXEREN 20 mg / 5 ml oral solution:
The exact recommended dose of Fluoxeren oral solution can be easily taken by following the instructions below:
- Introduce the dosing pipette into the bottle making sure that the plunger is fully inserted as far as it will go.
- Pull the plunger upwards until the dosage recommended by the doctor is reached.
- Pour the contents into a glass and dilute to taste with water.
FLUOXEREN 20 mg dispersible tablets:
Swallow without chewing or dissolve the tablet in water, diluting to taste.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
A. Menarini Industrie Farmaceutiche Riunite s.r.l. - Via Sette Santi, 3 - Florence
Dealer for sale: Istituto Luso Farmaco d "Italia S.p.A. - Milanofiori - Road 6 - Building L - Rozzano (MI)
08.0 MARKETING AUTHORIZATION NUMBER -
FLUOXEREN 20 mg hard capsules (12 capsules): AIC n. 025959014
FLUOXEREN 20 mg hard capsules (28 capsules): AIC n. 025959040
FLUOXEREN 20 mg / 5 ml oral solution: AIC n. 025959026
FLUOXEREN 20 mg dispersible tablets (12 tablets): AIC n. 025959038
FLUOXEREN 20 mg dispersible tablets (28 tablets): AIC n. 025959053
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
RENEWAL OF THE AUTHORIZATION
May 2010
FIRST AUTHORIZATION
FLUOXEREN 20 mg hard capsules (12 capsules): October 1988
FLUOXEREN 20 mg hard capsules (28 capsules): February 2000
FLUOXEREN 20 mg dispersible tablets (12 tablets): August 1999
FLUOXEREN 20 mg dispersible tablets (28 tablets): February 2000
FLUOXEREN 20 mg / 5mL oral solution: November 1994
10.0 DATE OF REVISION OF THE TEXT -
September 2015
