Active ingredients: Fluoxetine
FLUOXETINA Sandoz GmbH 20 mg hard capsules
Why is Fluoxetine used - Generic Drug? What is it for?
Fluoxetine Sandoz GmbH contains fluoxetine which belongs to a group of medicines called selective serotonin reuptake inhibitor (SSRI) antidepressants. This medicine is used to treat the following conditions:
Adults:
- Major depressive episodes
- Obsessive Compulsive Disorder
- Bulimia nervosa: Fluoxetina Sandoz GmbH is used together with psychotherapy for the reduction of binges and elimination behaviors.
Children and adolescents aged 8 years and over
- Moderate to severe major depressive disorder, if the depression does not respond to psychotherapy after 4-6 sessions. Fluoxetina Sandoz GmbH should only be offered to a child or young person with moderate to severe major depressive disorder in association with psychotherapy.
Contraindications When Fluoxetine - Generic Drug should not be used
Do not take Fluoxetine Sandoz Gmbh if:
- You are allergic (hypersensitive) to fluoxetine or any of the other ingredients of this medicine (listed in section 6). If you get a skin rash or other allergic reactions (such as itching, swollen lips or face and wheezing), stop take the capsules immediately and contact your doctor immediately.
- You are taking other medicines known as irreversible non-selective monoamine oxidase inhibitors (MAOIs), as serious or even life-threatening reactions can occur (see section "Other medicines and Fluoxetine Sandoz Gmbh"). Examples of such MAOIs include medicines used for the treatment of depression such as nialamide, hyproniazid, phenelzine, tranylcypromine, isocarboxazid.
- You are taking metoprolol to treat heart failure
Precautions for use What you need to know before taking Fluoxetine - Generic Drug
Tell your doctor if any of the following apply to you:
- epilepsy or seizures. If you have a seizure (fits) or an increase in the frequency of seizures, contact your doctor immediately; it may be necessary to stop taking Fluoxetine Sandoz Gmbh;
- if you have or have had in the past episodes of mania; if you have an episode of mania, contact your doctor immediately as it may be necessary to stop taking Fluoxetine Sandoz Gmbh;
- diabetes (your doctor may need to adjust your insulin dose or other diabetes treatment);
- liver problems (your doctor may need to adjust your dose);
- heart problems;
- low heart rate at rest and / or if you are aware that you may have a salt deficiency as a result of severe and prolonged diarrhea and vomiting (feeling sick) or following the use of diuretics (urinating tablets);
- glaucoma (increased pressure inside the eye);
- ongoing treatment with diuretics (urinating tablets), especially if you are elderly;
- treatment with ECT (electroconvulsive therapy);
- history of bleeding disorders or bruising or unusual bleeding;
- ongoing treatment with medicines that increase blood fluidity (see "Other medicines and Fluoxetine Sandoz Gmbh");
- current treatment with tamoxifen (used to treat breast cancer) (see "Other medicines and Fluoxetine Sandoz Gmbh");
- begins to feel restless and cannot sit or stand still (akathisia). Increasing the dose of Fluoxetine Sandoz Gmbh can make the situation worse;
- onset of fever, muscle stiffness or tremor, changes in mental status such as confusion, irritability and extreme agitation; you may be affected by the so-called "serotonin syndrome" or "neuroleptic malignant syndrome". Although this syndrome occurs rarely, it can give rise to potentially life-threatening conditions; contact your doctor immediately, as it may be necessary to stop taking Fluoxetine Sandoz Gmbh.
Thoughts of suicide and worsening of depression and anxiety disorder.
If you are depressed and / or have anxiety you may sometimes have thoughts of harming or killing yourself. These thoughts may be increased when you first start treatment with antidepressants, as these medicines take a period of time to be effective, usually about 2 weeks but sometimes even longer.
You may be more likely to think like this:
- If you have previously had thoughts about killing or harming yourself.
- If you are a young adult. Data from clinical trials have shown an increased risk of suicidal behavior in adults aged less than 25 years with psychiatric disorders who were treated with an antidepressant.
If at any time you have thoughts of harming or killing yourself, contact your doctor or go to a hospital immediately.
You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder and ask them to read this leaflet. You can ask them if they think your depression or anxiety is getting worse, or if they are worried. due to variations in its behavior.
Children and adolescents (under the age of 18)
When taking this type of medicine, patients under 18 have an increased risk of side effects such as suicide attempt, suicidal thoughts and hostile attitude (especially aggressive, oppositional and anger behavior). Fluoxetine Sandoz Gmbh is for use in children and adolescents aged 8 to 18 years only for the treatment of moderate to severe major depressive episodes (in combination with psychotherapy) and must not be used to treat other situations.
Furthermore, only limited information is available in this age group regarding the long-term safety of Fluoxetine Sandoz Gmbh on growth, puberty, mental, emotional and behavioral development.
Despite this, and in patients under the age of 18, the doctor may prescribe Fluoxetine Sandoz Gmbh for the treatment of moderate to severe major depressive episodes in combination with psychotherapy if this is the best solution for them. . If your doctor has prescribed Fluoxetine Sandoz Gmbh for a patient under 18 and you want clarification, please go back to your doctor.
You should inform your doctor if any of the above symptoms appear or worsen while patients under 18 are taking Fluoxetine Sandoz Gmbh.
Fluoxetine Sandoz Gmbh should not be used in the treatment of children under 8 years of age.
Interactions Which drugs or foods can modify the effect of Fluoxetine - Generic Drug
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines (up to 5 weeks before).
Fluoxetine Sandoz Gmbh can affect the way some other medicines work (interaction).
In particular, you must not take Fluoxetine Sandoz Gmbh in combination with the following medicines (see section "Do not take Fluoxetine Sandoz Gmbh if"):
- irreversible non-selective monoamine oxidase inhibitors (MAOIs) (e.g. iproniazid), as severe or even life-threatening reactions (serotonin syndrome) may occur, including fever, muscle stiffness or tremor, mental status changes such as confusion, irritability and extreme agitation. Treatment with Fluoxetine Sandoz Gmbh must be started strictly at least 2 weeks after the discontinuation of an irreversible non-selective MAOI (such as tranylcypromine). Similarly, you must not take any irreversible non-selective MAOIs for at least 5 weeks after you stop taking Fluoxetine Sandoz Gmbh. If Fluoxetine Sandoz Gmbh has been prescribed for you
- for a long period of time and / or at high doses it is necessary for the doctor to keep in mind a longer time interval.
- metoprolol (used to treat heart failure): as there is a risk of an increase in side effects including an excessive decrease in heart rate (bradycardia).
Also tell your doctor if you are taking any of the following medicines:
- Monoamine oxidase inhibitors (MAOIs) type A (eg linezolid and methylene blue): when these medicines are taken with Fluoxetine Sandoz Gmbh there is an increased risk of developing serotonin syndrome. If the combination cannot be avoided. , your doctor may need to lower their dosage when given with Fluoxetine Sandoz Gmbh and will carry out more checks.
- lithium, tryptophan, tramadol, triptans, selegilline (MAOI-B), St. John's wort (Hypericum perforatum): when these medicines are taken with Fluoxetina Sandoz Gmbh c "there is an increased risk of developing serotonin syndrome. The doctor will carry out checks with greater attention and greater frequency.
- phenytoin (for epilepsy); as Fluoxetine Sandoz GmbH may affect the blood levels of this medicine, your doctor may need to administer phenytoin more carefully and monitor when given with Fluoxetine Sandoz GmbH.
- medicines that can alter the heart rhythm, eg. class lA and III antiarrhythmics, antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antibacterial agents (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine), medicines used in the treatment of malaria and in particular halofantrine , some antihistamines (astemizole, mizolastine, cyproheptadine).
- flecainide, encainide or propafenone (for heart disorders), mequitazine (antihistamine), nebivolol (for high blood pressure), carbamazepine (for epilepsy), tricyclic antidepressants (for example imipramine, desipramine and amitriptyline), atomoxetine (used for attention deficit in children) and risperidone (for psychosis); as Fluoxetine Sandoz Gmbh can somehow change the blood levels of these medicines, your doctor may need to lower their dosage when given with Fluoxetine Sandoz Gmbh (although Fluoxetine Sandoz Gmbh was temporarily taken in the previous five weeks).
- medicines that lower the seizure threshold, eg tricylic antidepressants, other antidepressants (SSRIs), antipsychotic medicines (eg. butyrophenones, phenothiazines), mefloquine, chloroquine, bupropion and tramadol (analgesic): the use in combination of these medicines with Fluoxetine Sandoz Gmb increases the risk of seizures.
- medicines that can lower the level of sodium in the blood (diuretics, desmopressin, tricyclic antidepressants): the use of these medicines in combination with Fluoxetine Sandoz Gmb increases the risk of a reduced level of sodium in the blood.
- tamoxifen (used to treat breast cancer), as Fluoxetine Sandoz Gmbh may change the levels of this medicine in the blood and a decrease in the effect of tamoxifen cannot be ruled out, your doctor may need to consider other antidepressant treatments.
- oral anticoagulants, antiplatelet agents, NSAIDs (non-steroidal anti-inflammatory drugs) or other medicines that can increase blood fluidity (including clozapine, used to treat some mental disorders); Fluoxetine Sandoz Gmbh may change the effect of these medicines on the blood. If treatment with Fluoxetine Sandoz GmbH is started or stopped while you are taking these medicines, your doctor will need to perform some checks.
Fluoxetina Sandoz Gmbh with food, drink and alcohol
- You can take Fluoxetina Sandoz Gmbh regardless of meals, as you prefer.
- You should avoid drinking alcohol while you are taking this medicine.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Tell your doctor as soon as possible if you are or might be pregnant, or planning to become pregnant. In infants whose mothers took fluoxetine during the first months of pregnancy, there have been some studies that suggest an increased risk of birth defects affecting the heart. In the general population, approximately 1 in 100 newborns is born with a heart defect. This increased to about 2 in 100 newborns in mothers who took fluoxetine. Together with your doctor, you may decide to gradually stop taking Fluoxetine Sandoz Gmbh during your pregnancy.
However, depending on the circumstances, your doctor may suggest that it is better for you to continue taking Fluoxetine Sandoz Gmbh.
When taken during pregnancy, especially in the last 3 months of pregnancy, medicines such as Fluoxetine Sandoz Gmbh may increase the risk of a serious condition in newborns, called persistent pulmonary hypertension of the newborn (PPHN), which causes the newborn to breathe faster. and a bluish tint. These symptoms usually occur during the first 24 hours after birth.
If this happens to your newborn, contact your midwife and / or doctor immediately.
Caution is recommended when taken during pregnancy, especially during the terminal period of pregnancy or just before delivery as the following effects have been reported in newborns: irritability, tremor, muscle weakness, persistent crying, difficulty in sucking or sleeping.
Feeding time
Fluoxetine is excreted in breast milk and can cause unwanted effects in babies. Breastfeeding should only be done if clearly necessary. If breastfeeding is continued, your doctor may prescribe a lower dose of fluoxetine.
Fertility
Fluoxetine, in animal studies, has been shown to reduce sperm quality. In theory, this could affect fertility, but the impact on human fertility has not yet been observed.
Driving and using machines
Fluoxetine Sandoz Gmbh has no or negligible influence on the ability to drive and use machines. However, patients should be advised to avoid driving vehicles or using machines without the consent of the doctor or pharmacist and until they are sure that their ability is not impaired. .
Dose, Method and Time of Administration How to use Fluoxetine - Generic Drug: Posology
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist. The instructions are also on the package label. Do not take more capsules than your doctor has prescribed.
Swallow the capsules with a sip of water. Do not chew the capsules.
Adults:
The recommended dose is:
Depression: The recommended dose is 1 capsule (20 mg) per day. If necessary, your doctor will review and adjust the dosage within 3-4 weeks of starting treatment. If required, the dosage can be gradually increased to a maximum of 3 capsules (60 mg) per day. The dose should be increased with caution to make sure you get the lowest effective dose. You may not feel immediate improvement when you start treatment with your depression medicine. This is normal as an improvement in your depression symptoms may only occur after the first few weeks Patients with depression should be treated for a period of at least 6 months.
Bulimia nervosa: The recommended dose is 3 capsules (60 mg) per day.
Obsessive Compulsive Disorder: The recommended dose is 1 capsule (20 mg) per day. If necessary, your doctor will review and adjust your dosage after 2 weeks of therapy. If required, the dosage can be gradually increased to a maximum of 3 capsules (60 mg) per day. If no improvement is seen within the first 10 weeks, your doctor will reevaluate your treatment.
Use in children and adolescents
Children and adolescents aged 8 to 18 with depression:
Treatment must be initiated and supervised by a specialist. The starting dose is 10 mg per day.After 1-2 weeks, your doctor may increase the dose to 20 mg per day. The dose should be increased cautiously to make sure you are receiving the lowest effective dose. Children with low body weight may need lower doses. If there is a satisfactory response to treatment, the doctor will re-evaluate the need to continue treatment beyond 6 months. If there has been no improvement within the first 9 weeks, your doctor will need to reconsider your treatment.
Senior citizens:
Your doctor will take more caution in increasing the dose and the daily dosage should generally not exceed 2 capsules (40 mg). The maximum dose is 3 capsules (60 mg) per day.
Hepatic impairment:
If you have a liver disorder or are taking another medicine that could interfere with Fluoxetine Sandoz Gmbh, your doctor may decide to prescribe a lower dose or advise you to take Fluoxetine Sandoz Gmbh every other day.
Overdose What to do if you have taken an overdose of Fluoxetine - Generic Drug
If you take more Fluoxetine Sandoz Gmbh than you should
- If you take too many capsules, go to the nearest hospital emergency department or tell your doctor right away.
- If possible, take the Fluoxetine Sandoz Gmbh pack with you.Symptoms of overdose include: nausea, vomiting, seizures, heart disturbances (such as "irregular heartbeat and" cardiac arrest), breathing disturbances and changes in mental status ranging from agitation to coma.
If you forget to take Fluoxetine Sandoz Gmbh
- If you forget to take a dose, don't worry. Take your next dose at the usual time the following day. Do not take a double dose to make up for a forgotten dose.
- Taking the medicine at the same time each day can help you remember to take it regularly.
If you stop taking Fluoxetine Sandoz Gmbh
- Do not stop taking Fluoxetine Sandoz Gmbh without asking your doctor first, even when you start to feel better. It is important that you take this medicine continuously.
- Make sure you don't run out of capsules.
When you stop taking Fluoxetine Sandoz Gmbh you may notice the following effects (withdrawal effects): dizziness; tingling like feelings of pricks from pins and needles; sleep disturbances (realistic dreams, nightmares, inability to fall asleep); feeling restless or agitated; unusual tiredness or weakness; feeling anxious; nausea / vomiting; tremor; headache.
Most people report that any symptoms that occur when they stop taking Fluoxetine Sandoz Gmbh are mild and disappear within a few weeks. If you notice symptoms when stopping treatment, please contact your doctor.
When you stop taking Fluoxetine Sandoz Gmbh, your doctor will help you reduce your dose gradually over a week or two - this should help reduce the possibility of withdrawal effects.
If you have any further questions on the use of Fluoxetina Sandoz Gmbh, ask your doctor or pharmacist.
Side Effects What are the side effects of Fluoxetine - Generic Drug
Like all medicines, Fluoxetina Sandoz Gmbh can cause side effects, although not everybody gets them.
- If at any time you have thoughts of harming or killing yourself, contact your doctor or go to a hospital immediately (see section 2).
- If you experience a rash or allergic reaction such as itching, swelling of the lips or tongue, difficulty in breathing, wheezing, stop taking the capsules immediately and tell your doctor immediately.
- If you feel restless and cannot sit or stand still, you may have a disorder called akathisia; an increase in the dose of Fluoxetine Sandoz Gmbh could make you feel worse. If you experience these sensations, contact your doctor.
- Tell your doctor immediately if your skin starts to redden or develops a different one
- skin reaction or if the skin begins to blister or peel. This occurrence is rare.
Some patients presented:
- a set of symptoms (known as "serotonin syndrome") including unexplained fever with rapid breathing and heart rate, sweating, muscle stiffness or tremors, confusion, extreme agitation or sleepiness (only rarely);
- feeling weak, drowsy or confused especially in older people and in people (elderly) who are taking diuretics (urinating tablets):
- prolonged and painful erection;
- irritability and extreme agitation;
- heart problems, such as fast or irregular heart rate, fainting, collapse or dizziness on standing which may indicate abnormal heart rate functioning.
If you get any of the side effects listed above, please tell your doctor immediately.
The following side effects have also been reported in patients taking Fluoxetine Sandoz Gmbh:
- Very common (may affect more than 1 in 1 0 patients)
- insomnia
- headache
- diarrhea, feeling sick (nausea)
- fatigue
Common (affects 1 to 10 users in 100)
- lack of appetite, weight loss
- nervousness, anxiety
- restlessness, poor concentration
- feeling tense
- reduced sexual desire and sexual problems (including difficulty in maintaining an "erection for sexual activity)
- sleep problems, unusual dreams, tiredness or sleepiness
- dizziness
- change in taste
- tremor
- blurred vision
- feeling of fast and irregular heartbeat
- redness
- yawn
- indigestion, vomiting
- dry mouth
- rash, hives, itching
- excessive sweating
- joint pain
- urinalysis more frequently
- unexplained vaginal bleeding
- feeling of being unable to stand or shivering
Uncommon (affects 1 to 10 users in 1,000)
- feeling of detachment from oneself
- strange thoughts
- excessively high or euphoric mood
- orgasm problems and sexual dysfunction
- teeth grinding
- hyperactivity, muscle contraction, involuntary movements or problems with balance or coordination
- enlarged (dilated) pupils
- low blood pressure
- wheezing
- difficulty swallowing
- Gastrointestinal bleeding
- hair loss
- increased tendency to bruise
- cold sweats
- difficulty in passing urine
- feeling hot or cold
- nosebleeds
- ringing in the ears
- memory impairment
- thoughts of suicide or harming yourself
- malaise
Rare (affects 1 to 10 users in 10,000)
- reduced levels of sodium in the blood
- uncontrolled non-habitual behavior
- hallucinations
- agitation
- panic attacks
- seizures
- restlessness, inability to sit still
- vasculitis (inflammation of a blood vessel), dilation of blood vessels
- rapid swelling of tissues
- pain in the tube that allows food and water to pass through the stomach, pharyngitis
- sensitivity to sunlight
- breast milk secretion
- increases in blood levels of some liver enzymes (transaminases and gammaglutamyltransferases)
- Prolonged and painful erection
- problems urinating
- muscular pain
- lung problems
- hepatitis
- confusional state
- stuttering
- aggression
- decrease in blood platelets, which increases the risk of bleeding or bruising
- decrease in white blood cells
- severe reactions of the skin and / or mucous membranes which may include painful blisters, with detachment of large areas of skin
- anaphylactic reaction
- problems with the secretion of a hormone called antidiuretic hormone
- changes in heart rhythm
- bleeding from the mucous membranes
Not known (frequency cannot be estimated from the available data)
- abnormal liver function tests
Bone fractures - an increased risk of bone fractures has been observed in patients taking this type of medicine.
If you have any of the symptoms listed and they are bothering you, or last for a certain period of time, please tell your doctor or pharmacist.
Most of these side effects are likely to go away with continued treatment.
Children and Adolescents (8-18 years) - In addition to the possible side effects listed above, Fluoxetine Sandoz Gmbh can slow growth and possibly delay sexual maturation. Nosebleeds have also been commonly reported in children.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https: // www. .aifa.gov.it / content / reports-adverse-reactions
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the package label. The expiry date refers to the last day of the month.
If you have any other questions, ask your doctor or pharmacist.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Fluoxetine Sandoz Gmbh contains
The active ingredient is fluoxetine hydrochloride. Each capsule contains fluoxetine hydrochloride equivalent to 20 milligrams (mg) of fluoxetine.
The other ingredients are: dimethicone 350, pregelatinised maize starch. The capsule shell consists of gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), patent blue V (E 131).
What Fluoxetine Sandoz Gmbh hard capsules look like and contents of the pack
Fluoxetina Sandoz Gmbh is a hard capsule.
The capsules are light green
The capsules are available in PP / aluminum blisters of 12, 28, 50 capsules.
Not all pack sizes may be marketed.
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
FLUOXETINA SANDOZ GMBH 20 MG HARD CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains:
Active principle: fluoxetine hydrochloride 22.4 mg equal to fluoxetine 20 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Hard capsules.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Adults:
Major Depressive Episodes, Obsessive Compulsive Disorder
Bulimia nervosa: Fluoxetina Sandoz Gmbh is indicated in association with psychotherapy for the reduction of binge eating and elimination behaviors.
Children and adolescents aged 8 years and over:
Moderate to severe major depressive episode, if the depression does not respond to psychotherapy after 4-6 sessions. Antidepressant therapy should be offered to a child or young person with moderate to severe depression only in association with concomitant psychotherapy.
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 corrected within 3-4 weeks of initiation of therapy and then evaluated if clinically appropriate. Although at higher doses there may be a potential for increased side effects, in some patients with insufficient therapeutic response to 20 mg, the dose may be gradually increased up to a maximum of 60 mg (see section 5.1) Dosage adjustments should be made carefully for each individual to keep the patient 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 at higher doses there may be a potential for increased side effects in some patients, if after two weeks there is "insufficient" therapeutic response to 20 mg, the dose may be gradually increased up to a maximum of 60 mg.
If no improvement is observed within 10 weeks, fluoxetine treatment should be resumed. If a good therapeutic response has been achieved, treatment can be continued at an individually adjusted dosage. Although there are no systematic studies to establish 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 on each individual to keep the patient at the lowest effective dose. The need for treatment should be reassessed periodically. In patients who have responded well to pharmacotherapy, some clinicians find simultaneous behavioral psychotherapy useful.
Long-term efficacy (beyond 24 weeks) has not been demonstrated in OCD.
Bulimia nervosa
Adults and the elderly: A dose of 60 mg per day is recommended. Long-term efficacy (beyond 3 months) has not been demonstrated in bulimia nervosa.
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 in single or divided doses, with or without meals.
When dosing is stopped, the pharmacologically active substances will persist in the body for weeks. This should be borne in mind when starting or stopping treatment.
Children and adolescents aged 8 years and over (Moderate to severe major depressive episode)
Treatment should be initiated and monitored under the supervision of the specialist. The starting dose is 10 mg per day. Dose adjustments should be made carefully, on an individual basis, to maintain the patient at the lowest effective dose.
After one to two weeks, the dose can be increased to 20 mg per day. Clinical experience with daily doses above 20 mg is minimal. There is only limited data on treatment beyond 9 weeks.
Children of low body weight
Due to the higher plasma levels that are achieved in children of low body weight, the therapeutic effect can be achieved with lower doses (see section 5.2).
In pediatric patients who respond to treatment, the need to continue treatment after 6 months should be re-evaluated. If no clinical benefit has been achieved within 9 weeks, treatment should be reconsidered.
Elderly: Caution is recommended when increasing the dose and the daily dose should generally not exceed 40 mg. The maximum recommended dose is 60 mg per 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 in whom there is the possibility of an "interaction between Fluoxetine Sandoz GmbH. and medicinal products taken in combination (see section 4.5).
Withdrawal symptoms observed on discontinuation of Fluoxetine Sandoz GmbH:
Abrupt discontinuation should be avoided. When discontinuing treatment with Fluoxetine Sandoz, the dose should be gradually reduced over a period of at least 1-2 weeks in order to reduce the risk of withdrawal reactions (see sections 4.4 and section 4.8. If intolerable symptoms occur following a dose reduction or discontinuation of treatment, resuming the previously prescribed dose may be considered. Thereafter, the doctor may continue to reduce the dose, but more gradually. .
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 an irreversible non-selective monoamine oxidase inhibitor (e.g. iproniazid) (see sections 4.4. And 4.5).
Fluoxetine is contraindicated in combination with 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 attempt and suicidal thoughts) and hostile attitude (especially aggressive, oppositional and anger behavior) were observed more frequently in clinical trials in children and adolescents treated with antidepressants than in those treated with placebo.Fluoxetine Sandoz GmbH is for use in children and adolescents aged 8 to 18 years only for the treatment of moderate to severe major depressive episodes and must not be used in other indications. If, based on medical need, a decision to treat is made, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, only limited data are available in children and adolescents regarding long-term effects on safety, including effects on growth, sexual maturation and cognitive, emotional and behavioral development (see section 5.3).
In a clinical study of 19 weeks duration, decreased height and weight gain were observed in children and adolescents treated with fluoxetine (see section 5.1). It has not been established whether there is an effect on achieving height. "normal height in adulthood. The possibility of a delay in puberty cannot be excluded (see sections 5.3 and 4.8). Pubertal growth and development (height, weight and TANNER staging) should therefore be monitored during and after treatment with fluoxetine If both are slowed, pediatric evaluation should be requested.
In pediatric clinical trials, mania and hypomania were reported frequently (see section 4.8). Therefore, regular monitoring for the onset 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 or young person and / or their parents.
Skin rash and allergic reactions
Rash, anaphylactoid events and progressive systemic events, sometimes serious (involving skin, kidney, liver or lung), have been reported. Upon the appearance of skin rash or other allergic phenomena for which a different etiology cannot be identified, the administration of fluoxetine must be discontinued.
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 carefully monitored (see section 4.5).
Electroconvulsive therapy (ECT)
Rare cases of prolonged seizures have been reported in fluoxetine-treated patients receiving ECT treatment, so caution is recommended.
Mania
Antidepressants should be used with caution in patients with a history of mania / hypomania. As with all antidepressant medicinal products, 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. an alternate day dosage. When fluoxetine 20 mg daily was administered 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 cytochrome CYP2D6, can lead to reduced plasma concentrations of endoxifen, one of the most important active metabolites of tamoxifen. Therefore, whenever possible fluoxetine should be avoided during treatment with tamoxifen (see section 4.5).
Cardiovascular effects
Cases of QT interval prolongation and ventricular arrhythmia including torsade de pointes have been reported in 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, a family history of QT interval prolongation and other clinical conditions predisposing to arrhythmias (eg, hypokalaemia and hypomagnesaemia, bradycardia, acute myocardial infarction. or decompensated heart failure) or "increased exposure to fluoxetine (eg, liver failure).
If patients with stable heart disease are being treated, a follow-up ECG should be considered before starting treatment. If signs of cardiac arrhythmia occur 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 impair 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). This risk persists until significant disease remission occurs. As improvement may not occur during the first or subsequent weeks of treatment, patients should be closely monitored until improvement occurs. It is general clinical experience that the risk of suicide can increase early in the healing process.
Other psychiatric conditions in which Fluoxetine Sandoz is prescribed may also be associated with an increased risk of suicide-related events. Furthermore, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be implemented when treating patients with other psychiatric disorders.
Among patients with a history of suicide-related events, those with a significant degree of suicidal ideation prior to initiation of treatment have an increased risk of suicidal thoughts or suicide attempts, and should be closely monitored during treatment. meta-analysis of clinical trials conducted with antidepressant medicinal products in comparison with placebo in the therapy of psychiatric disorders, showed an increased risk of suicidal behavior in patients under 25 years of age treated with antidepressants compared to placebo.
Close surveillance of patients, and particularly those at high risk, should accompany drug therapy especially in the early stages of treatment and after dose changes. Patients (or their carers) should be advised of the need to monitor and report immediately to the treating physician any worsening of the clinical picture, the onset of suicidal behavior or thoughts and unusual behavioral changes 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 distressing restlessness and need to move often accompanied by an" inability to sit or stand still. This is more likely to occur within the first few years. weeks of treatment. In patients who develop these symptoms, increasing the dose may be harmful.
Withdrawal symptoms observed on discontinuation of SSRI treatment
Discontinuation symptoms are common when treatment is stopped, especially if discontinuation occurs abruptly (see section 4.8). In clinical trials, adverse events observed with abrupt discontinuation occurred in approximately 60% of patients. patients in both fluoxetine and placebo groups. Of these adverse events, 17% in the fluoxetine group and 12% in the placebo group were severe in nature.
The risk of withdrawal symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. 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 these symptoms are mild to moderate in intensity, however in some patients they may be severe in intensity. These symptoms usually occur within the first few days of stopping treatment. Generally these symptoms are self-limiting and usually resolve within 2 weeks, although in some individuals they may be prolonged (2-3 months or more). It is therefore recommended Fluoxetine Sandoz is gradually tapered over a period of at least 1-2 weeks prior to stopping treatment, as needed by the patient (see "Withdrawal symptoms observed on discontinuation of Fluoxetine Sandoz GmbH" section 4.2).
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 (e.g. gynecological haemorrhages, gastrointestinal bleeding and other cutaneous or mucosal bleeding) have been reported rarely. Caution is advised in patients taking SSRIs, especially during concomitant use with oral anticoagulants, medicines known to affect platelet function (eg atypical antipsychotics such as clozapine, phenothiazines, most tricyclic antidepressants, aspirin , NSAIDs) or other medicinal products that may increase the risk of bleeding, as well as in patients with a history of bleeding disorders (see section 4.5).
Mydriasis
Mydriasis has been reported in association with the use of fluoxetine; therefore, caution should be used when prescribing fluoxetine to patients with increased intraocular pressure or those at risk of acute narrow-angle glaucoma.
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 medicinal products (among others L-tryptophan) and / o neuroleptic medicinal products (see section 4.5). Since these syndromes can give rise to potentially life-threatening conditions for the patient, if such events occur (characterized by groupings of symptoms such as hyperthermia, rigidity, myoclonus, autonomic nervous system instability with possible rapid fluctuations of vital signs, changes in the state including confusion, irritability and extreme agitation up to delirium and coma) treatment with fluoxetine should be discontinued and symptomatic supportive treatment initiated.
Irreversible non-selective monoamine oxidase inhibitors (e.g. iproniazid)
Some cases of severe and sometimes fatal reactions have been reported in patients taking an SSRI in combination with an irreversible non-selective monoamine oxidase inhibitor (MAOI).
These cases have presented with features similar to serotonin syndrome (which may resemble and be confused (or diagnosed) as 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 leading to delirium and coma.
Therefore, fluoxetine is contraindicated in combination with an irreversible non-selective MAOI (see section 4.3). Fluoxetine treatment should only be started 2 weeks after stopping treatment with an irreversible non-selective MAOI due to its two-week duration effect.
Similarly, at least 5 weeks should elapse after discontinuation of fluoxetine treatment before starting therapy with an irreversible non-selective MAOI.
The combination of fluoxetine with a reversible MAOI [eg moclobemide, linezolid, methylthioninium chloride (also called methylene blue) is not recommended (see section 4.5).
04.5 Interactions with other medicinal products and other forms of interaction
Half-life
The long elimination half-lives of both fluoxetine and norfluoxetine (see section 5.2) should be borne in mind when considering pharmacodynamic or pharmacokinetic drug interactions (e.g. when switching from fluoxetine to other antidepressants).
Contraindicated associations
Irreversible non-selective monoamine oxidase inhibitors (e.g. iproniazid)
Some cases of severe and sometimes fatal reactions have been reported in patients taking an SSRI in combination with an irreversible non-selective monoamine oxidase inhibitor (MAOI).
These cases have presented with features similar to serotonin syndrome (which may resemble and be confused (or diagnosed) as 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 leading to delirium and coma.
Therefore, fluoxetine is contraindicated in combination with an irreversible non-selective MAOI (see section 4.3). Fluoxetine treatment should only be started 2 weeks after stopping treatment with an irreversible non-selective MAOI due to its two-week duration effect.
Similarly, at least 5 weeks should elapse after discontinuation of fluoxetine treatment before starting 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
Tamoxifen: iPharmacokinetic interactions between CYP2D6 inhibitors and tamoxifen have been reported in the literature, demonstrating a 65-75% reduction in plasma levels of one of the most active metabolites of tamoxifen, ie endoxifen. efficacy of tamoxifen during concomitant use of some SSRI antidepressants. Since a reduced effect of tamoxifen cannot be excluded, concomitant administration of potent CYP2D6 inhibitors (including fluoxetine) should be avoided whenever possible (see section 4.4 ).
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-A including linezolid and methylthioninium chloride (methylene blue): Risk of serotonin syndrome which includes diarrhea, tachycardia, sweating, tremor, confusion or coma. If concomitant use of these active substances with fluoxetine cannot be avoided, careful medical monitoring should be performed and the medicinal products should be administered at the lowest recommended dose (see section 4.4).
Mequitazine
The risk of adverse events from mequitazine (such as QT prolongation) may be increased due to inhibition of its metabolism by fluoxetine
Associations that require precautions for their use
Phenytoin
Changes in blood levels have been observed when combined with fluoxetine. In some cases, manifestations of toxicity have occurred. It is therefore recommended to administer the concomitant drug according to conservative therapeutic regimens and to carefully follow the clinical condition of the patient.
Serotonergic drugs (lithium, tramadol, triptans, tryptophan, selegiline (MAOI-B), St. John (Hypericum perforatum)
There have been reports of moderate serotonin syndrome when SSRIs have been administered in combination with medicinal products with serotonergic effects. Therefore, the concomitant use of fluoxetine with these medicinal products should be made with caution, with more careful and frequent clinical monitoring (see section 4.4).
Prolongation of the QT interval
Pharmacokinetic and pharmacodynamic studies have not been performed between fluoxetine and other medicinal products that cause QT interval prolongation. An additive effect between fluoxetine and these medicinal products cannot be excluded.Therefore, the concomitant administration of fluoxetine with medicinal products that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (eg phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antibacterial agents ( e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine), treatment against malaria and in particular halofantrine, some antihistamines (astemizole, mizolastine), should be done with caution (see sections 4.4, 4.8 and 4.9)
Medicinal products affecting haemostasis (oral anticoagulants, whatever their mechanism, antiplatelet agents including aspirin and NSAIDs)
Increased risk of bleeding. Clinical monitoring, and more frequent monitoring of INR, with oral anticoagulants should be conducted. Dose adjustment during fluoxetine treatment and after its discontinuation may be appropriate (see sections 4.4 and 4.8).
Cyprusheptadine
There have been case reports of reduced antidepressant activity of fluoxetine when used in combination with cyproheptadine.
Medicines that induce hyponatremia
Hyponatremia is an undesirable effect of fluoxetine. Use in combination with other medicinal products associated with hyponatraemia (eg, diuretics, desmopressin, carbamazepine and oxcarbazepine) may lead to an increased risk (see section 4.8).
Medicines that lower the seizure threshold
Seizures are an undesirable effect of fluoxetine. Use in combination with other medicinal products that may lower the seizure threshold (eg tricyclic antidepressants, other SSRIs, phenothiazines, butyrophenones, mefloquine, chloroquine, bupropion, tramadol) may lead to an increased risk.
Other medicinal products metabolised by CYP2D6
Fluoxetine is a strong inhibitor of the CYP2D6 enzyme, therefore concomitant therapy with medicinal products metabolised by this enzyme may lead to interactions with medicinal products, particularly with those with a narrow therapeutic index (such as flecainide, propafenone and nebivolol) and with those which are titrated, but also with atomoxetine, carbamazepine, tricyclic antidepressants and risperidone. Therapy with these medicines should be initiated or adjusted to the most recommended dose in their dosage range. This may also apply if fluoxetine has been previously taken in the previous 5 weeks.
04.6 Pregnancy and lactation
Pregnancy
Some epidemiological studies suggest an increased risk of cardiovascular defects associated with the use of fluoxetine during the first trimester of pregnancy. The mechanism is unknown. Overall, the data suggest that the risk of having a newborn with a cardiovascular defect following maternal exposure fluoxetine is in the order of 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, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 in 1,000 pregnancies. In the general population, 1 to 2 PPHN cases per 1000 pregnancies occur.
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 some other 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 breast-feeding should be considered; however, if breast-feeding is continued, the lowest effective dose of fluoxetine should be prescribed.
Fertility
Animal data have shown that fluoxetine may affect sperm quality (see section 5.3). In humans, reports from patients treated with SSRIs have shown that the effect on sperm quality is reversible. No impact on fertility has been observed so far.
04.7 Effects on ability to drive and use machines
Fluoxetine has no or negligible influence on the ability to drive and use machines.
Although fluoxetine has been shown not to interfere with psychomotor performance in healthy volunteers, any psychoactive drug can impair judgment or professional skills. Patients should be advised to avoid driving a vehicle or operating hazardous machinery until they are reasonably aware that their performance is not impaired.
04.8 Undesirable effects
a) 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 lead to discontinuation of therapy.
b) List of adverse reactions
The table below shows the adverse reactions observed during treatment with fluoxetine in adults and the pediatric population.
Some of these adverse reactions are common to those seen with other SSRIs
The following adverse reactions were calculated from clinical studies (n = 9,297) and from spontaneous reporting.
Frequency estimate: very common (≥ 1/10), common (≥ 1/100,
1 Including anorexia.
2 Including early morning awakening, initial insomnia and central insomnia.
3 Including loss of libido.
4 Including nightmares.
5 Including anorgasmia.
6 Including complete suicide, suicidal depression, self-harm, self-harm ideation, suicidal behavior, suicidal ideation, suicide attempt, morbid thoughts, self-harm behavior. These symptoms may be due to the underlying disease
7 Including hypersomnia and sedation.
8 Including hot flash.
9 includes atelectasis, interstitial lung disease, pneumonia
10 Most frequently including gingival bleeding, haematemesis, hematochezia, rectal haemorrhage, haemorrhagic diarrhea, melaena and haemorrhagic gastric ulcer.
11 Including 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 with umbilical erythema.
12 Including pollakiuria.
13 Including cervical haemorrhage, uterine dysfunction, uterine bleeding, genital haemorrhage, menometrorrhagia, menorrhagia, metrorrhagia, polymenorrhea, postmenopausal haemorrhage, uterine haemorrhage and vaginal haemorrhage.
14 Including ejaculation failure, ejaculation dysfunction, premature ejaculation, delayed ejaculation and retrograde ejaculation.
15 Including asthenia.
Description of selected adverse reactions
Suicidal thoughts / suicide or clinical worsening:
Cases of suicidal ideation and suicidal behavior have been reported during fluoxetine therapy or early after treatment discontinuation (see section 4.4).
Bone fractures:
Epidemiological studies, conducted mainly in patients 50 years of age and older, show an increased risk of bone fractures in patients treated with SSRIs and tricyclic antidepressants (TCAs). The mechanism leading to this risk is not known.
Withdrawal symptoms observed on discontinuation of fluoxetine treatment
Discontinuation of fluoxetine treatment commonly leads to withdrawal symptoms. 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 these symptoms are mild to moderate in intensity and are self-limiting, however in some patients they may be severe and / or prolonged (see section 4.4). carry out a "gradual discontinuation by progressive dose reduction when treatment with Fluoxetine Sandoz GmbH is no longer required (see sections 4.2 and 4.4).
d) Pediatric population (see sections 4.4 and 5.1):
Adverse reactions that have been specifically observed in this patient population or with a different frequency are listed below. The frequency of these events is based on exposure to pediatric clinical studies (n = 610).
In pediatric clinical trials, suicide-related behaviors (suicide attempt and suicidal thoughts), hostile attitude (reported events are: anger, irritability, aggression, agitation, activation syndrome), manic reactions, including mania and hypomania (no previous episode had been reported) and epistaxis were commonly reported and more frequently observed in children and adolescents treated with antidepressants than in those treated with placebo.
Isolated cases of growth retardation have been reported in clinical use (see also section 5.1).
In pediatric clinical trials, fluoxetine treatment was associated with decreased 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 medicine is important, as it allows for continuous monitoring of the benefit / risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via: the national reporting system at the address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
Symptoms
Cases of overdose due to fluoxetine alone generally have a mild course. Symptoms of overdose include nausea, vomiting, convulsions, variable cardiovascular dysfunction.
From asymptomatic arrhythmia (including nodal rhythm and ventricular arrhythmia) or changes in ECG indicative of QTc prolongation to cardiac arrest (including very rare cases of torsades de pointes), pulmonary dysfunction and signs of an altered CNS condition ranging from arousal to coma. Fatal outcome attributed to overdose of fluoxetine alone has been extremely rare. Monitoring of cardiac function and vital signs is advised, as well as general symptomatic and supportive measures. No specific antidotes are known.
Treatment
Forced diuresis, dialysis, haemoperfusion 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. In patients who have taken excessive amounts of a tricyclic antidepressant, a longer period of time for close medical observation may be required if they are also taking, or have recently taken, fluoxetine.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: selective serotonin reuptake inhibitors.
ATC code: N06A B03.
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 α1-, α2- and β-adrenergics; serotonergics; dopaminergics type 1 histamine receptors (H 1); muscarinics and GABA receptors.
Major Depressive Episodes: Clinical trials comparing placebo and active substances were performed in patients with major depressive episodes. Fluoxetine Sandoz Gmbh has been shown to be significantly more effective than placebo, as shown by the Hamilton Depression Rating Scale (HAM-D). Compared to placebo, Fluoxetine Sandoz Gmbh resulted in a significantly higher rate of response (defined by a 50% reduction in HAM-D score) and remission in these studies.
Dose Response: In fixed dose studies performed in patients with major depression there is a flattening of the dose response curve, demonstrating no efficacy advantage in using higher than recommended doses. However, clinical experience shows that titration may be of benefit in some patients.
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 per day, but higher doses (40 or 60 mg per day) demonstrated a higher response rate. In long-term clinical trials (three short-term clinical trials with phase extension and a relapse prevention study) efficacy has not been demonstrated.
Bulimia nervosa: In short-term clinical studies (less than 16 weeks duration), in outpatients who fully met the DSM-III-R criteria for bulimia nervosa, fluoxetine 60 mg daily was shown to be significantly more effective 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 in the DSM-IV. Patients were included if they presented with symptoms of sufficient severity to interfere with their occupational and social function and relational life with others. Patients using oral contraceptives were excluded. In the first study with continuous dosing of 20 mg per day for 6 menstrual cycles, improvement was observed in the primary efficacy parameter (irritability, anxiety and dysphoria).In the second study, with intermittent dosing during the luteal phase (20 mg per day for 14 days) for 3 menstrual cycles, improvement was observed in the primary efficacy parameter (score based on the Daily Disorder Severity Record scale, Daily Record of Severity of Problems). However, no definitive conclusions on the efficacy and duration of treatment can be drawn from these studies.
Major Depressive Episodes (Children and Adolescents): Clinical trials comparing to placebo have been performed in children and adolescents aged 8 years and older. At a dose of 20 mg, Fluoxetine Sandoz Gmbh was shown to be significantly more effective than placebo in two short-term pilot studies, as assessed by the reduction of the revised Childhood Depression Rating Scale (CDRS-R) total score and the "Clinical Global Impression of Improvement" (CGI-I). In both studies, patients met the criteria for moderate to severe Major Depressive Disorder (according to DSMIII or DSM-IV) in three different evaluations by the child psychiatrist. Efficacy in fluoxetine studies may depend on the inclusion of a selected patient population (one that did not recover spontaneously within a 3-5 week period and whose depression persisted despite considerable attention). There are only limited data on safety and efficacy beyond 9 weeks. Overall, the efficacy of fluoxetine was modest. Response rates (primary endpoint, defined as a 30% reduction in CDRS-R score) demonstrated a statistically significant difference in one of the two pilot studies (58% with fluoxetine compared with 32% with placebo, p = 0.013 and 65% with fluoxetine compared with 54% with placebo, p = 0.093). In these two studies, the mean absolute changes in CDRS-R from baseline to end point were 20 with fluoxetine compared with 11 with placebo, p = 0.002 and 22 with fluoxetine compared with 15 with placebo, p
Effects on growth (children and adolescents), see sections 4.4 and 4.8: After 19 weeks of treatment, pediatric patients treated with fluoxetine in a clinical study reported an average of 1.1 cm less in height (p = 0.004) and 1.1 kg less weight (p = 0.008) than placebo-treated subjects.
In a retrospective cross-control observational study with a mean fluoxetine exposure of 1.8 years, there was no difference in height adjusted growth expected in pediatric patients treated with fluoxetine compared to untreated cross controls (0, 0 cm, p = 0.9673).
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. The 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 is mainly via the kidney (approximately 60%). Fluoxetine is excreted in breast milk.
Populations at risk
Elderly: Pharmacokinetic parameters are not altered in healthy elderly compared to younger subjects.
Children and adolescents: The mean concentration of fluoxetine in children is approximately 2 times higher than that seen in adolescents and the mean concentration of norfluoxetine is approximately 1.5 times higher. Equilibrium plasma concentrations are dependent on body weight and are found to be higher in children of low body weight (see section 4.2). As in adults, fluoxetine and norfluoxetine accumulate extensively following administration of multiple oral doses; with daily dosing, equilibrium concentrations are reached within 3-4 weeks.
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 single dose administration of fluoxetine in patients with mild, moderate or complete (anuria) renal insufficiency, the pharmacokinetic 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
In vitro or animal studies did not show a carcinogenic or mutagenic effect.
Studies on adult animals
In a 2-generation reproduction study in rats, fluoxetine produced no harmful effects on mating and fertility of rats, was not teratogenic, and had no effect on the growth, development and reproduction of the offspring. Fluoxetine provided in the diet were approximately equivalent doses of 1.5 - 3.9 and 9.7 mg / kg body weight.
Male mice treated for 3 months with a daily dietary intake of a dose of fluoxetine of approximately 31 mg / kg showed decreased testicular weight and hypospermatogenesis. However this dose level exceeds the maximum tolerated dose (MTD) at which significant signs of toxicity were observed.
Studies on young animals
In a toxicology study in juvenile CD rats, the administration of 30 mg / kg per day of fluoxetine hydrochloride from the 21st to the 90th day after birth resulted in irreversible testicular degeneration and necrosis, the appearance of vacuoles in the "epithelium of the" epididymis, immaturity and inactivity of the female reproductive tract and decreased fertility. Delays in sexual maturation occurred in males (10 and 30 mg / kg per day) and females (30 mg / kg per day). The significance of these findings in humans is unknown. Rats treated with 30 mg / kg also had decreased femoral length compared to controls and skeletal muscle degeneration, necrosis and regeneration. At doses of 10 mg / kg per day, plasma levels achieved in animals were approximately 0.8 to 8.8 times (fluoxetine) and 3.6 to 23.2 times (norfluoxetine) those usually observed in pediatric patients. At doses of 3 mg / kg per day , plasma levels achieved in animals were approximately 0.04 to 0.5 times (fluoxetine) and 0.3 to 2.1 times (norfluoxetine) those usually achieved in pediatric patients.
A study in young mice indicated that inhibition of the serotonin transporter hinders the development of bone formation. This finding appears to be supported by clinical evidence. The reversibility of this effect has not been established.
Another study in young mice (treated from day 4 to day 21 after birth) showed that inhibition of the serotonin transporter had long lasting effects on the behavior of the mice. It is not known whether the effect was reversible. The clinical significance of this finding has not been established.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Excipients: Dimethicone 350 - pregelatinised maize starch.
Constituents of the capsule: gelatin - titanium dioxide (E 171) - yellow iron oxide (E 172) - patent blue V (E 131).
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
PP and aluminum blisters
20 mg Capsules, hard, box of 12 capsules
PP and aluminum blisters
20 mg Capsules, hard, carton of 28 capsules
PP and aluminum blisters
20 mg Hard capsules, box of 50 capsules
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Sandoz GmbH, Biochemiestrasse 10 - 6250 Kundl, Austria
Legal Representative for Italy: Sandoz S.p.A., Largo Umberto Boccioni, 1 - 21040
Origgio (VA).
08.0 MARKETING AUTHORIZATION NUMBER
20 mg hard capsules, 12 capsules AIC n ° 033569017
20 mg hard capsules, 28 capsules AIC n ° 033569056
20 mg hard capsules, 50 capsules AIC n ° 033569068
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 21 December 1999
Date of most recent renewal: 21 December 2009
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