Posology : מינונים

4.2 Posology and method of administration
Adults:
Major Depressive Disorder
Initial Treatment
In controlled trials used to support the efficacy of fluoxetine, patients were administered morning doses ranging from 20 to 80 mg/day. Studies comparing fluoxetine 20, 40, and 60 mg/day to placebo indicate that 20 mg/day is sufficient to obtain a satisfactory response in Major Depressive Disorder in most cases. Consequently, a dose of 20 mg/day, administered in the morning, is recommended as the initial dose.
A dose increase may be considered after several weeks if insufficient clinical improvement is observed. Doses above 20 mg/day may be administered on a once-a-day (morning) or BID schedule (i.e., morning and noon) and should not exceed a maximum dose of 80 mg/day.
All patients — As with other drugs effective in the treatment of Major Depressive Disorder, the full effect may be delayed until 4 weeks of treatment or longer.
Patients with depression should be treated for a sufficient period of at least 6 months to ensure that they are free from symptoms.

Maintenance/Continuation/Extended Treatment — It is generally agreed that acute episodes of Major Depressive Disorder require several months or longer of sustained pharmacologic therapy. Whether the dose needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.
Daily Dosing — Systematic evaluation of FLUOXETINE in adult patients has shown that its efficacy in Major Depressive Disorder is maintained for periods of up to 38 weeks following 12 weeks of open-label acute treatment (50 weeks total) at a dose of 20 mg/day.
Switching Patients to a Tricyclic Antidepressant (TCA) — Dosage of a TCA may need to be reduced, and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is co- administered or has been recently discontinued.

Obsessive Compulsive Disorder
Initial Treatment
In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fixed daily doses of 20, 40, or 60 mg of fluoxetine or placebo. In one of these studies, no dose-response relationship for effectiveness was demonstrated. Consequently, a dose of 20 mg/day, administered in the morning, is recommended as the initial dose. Since there was a suggestion of a possible dose-response relationship for effectiveness in the second study, a dose increase may be considered after several weeks if insufficient clinical improvement is observed. The full therapeutic effect may be delayed until 5 weeks of treatment or longer. If no improvement is observed within 10 weeks, treatment with fluoxetine should be reconsidered.
Doses above 20 mg/day may be administered on a once daily (i.e., morning) or BID schedule (i.e., morning and noon). A dose range of 20 to 60 mg/day is recommended; however, doses of up to 80 mg/day have been well tolerated in open studies of OCD. The maximum fluoxetine dose should not exceed 80 mg/day.
Maintenance/Continuation Treatment — While there are no systematic studies that answer the question of how long to continue FLUOXETINE, OCD is a chronic condition, and it is reasonable to consider continuation for a responding patient. Although the efficacy of FLUOXETINE after 13 weeks has not been documented in controlled trials, adult patients have been continued in therapy under double-blind conditions for up to an additional 6 months without loss of benefit. However, dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for treatment.

Bulimia Nervosa
Initial Treatment — In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Bulimia Nervosa, patients were administered fixed daily fluoxetine doses of 20 or 60 mg, or placebo. Only the 60 mg dose was statistically significantly superior to placebo in reducing the frequency of binge-eating and vomiting. Consequently, the recommended dose is 60 mg/day, administered in the morning. For some patients it may be advisable to titrate up to this target dose over several days. Fluoxetine doses above 60 mg/day have not been systematically studied in patients with bulimia.
Maintenance/Continuation Treatment — Systematic evaluation of continuing FLUOXETINE 60 mg/day for periods of up to 52 weeks in patients with bulimia who have responded while taking FLUOXETINE 60 mg/day during an 8-week acute treatment phase has demonstrated a benefit of such maintenance treatment. Nevertheless, patients should be periodically reassessed to determine the need for maintenance treatment.

Pediatric population
Children and adolescents aged 8 years and above (Moderate to severe
major depressive episode)
Treatment should be initiated and monitored under specialist supervision. The starting dose is 10 mg/day fluoxetine (as hydrochloride) given as oral solution (there is a drug from another company, which comes as a solution). 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 may be increased to 20 mg/day. Clinical trial experience with daily doses greater than 20 mg is minimal. There is only limited data on treatment beyond 9 weeks.

Lower weight children
Due to higher plasma levels in lower weight children, the therapeutic effect may 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 reviewed. If no clinical benefit is achieved within 9 weeks, treatment should be reconsidered.


Elderly patients
Caution is recommended when increasing the dose and the daily dose should generally not exceed 40 mg. Maximum recommended dose is 60 mg/day.

Patients with hepatic impairment

A lower or less frequent dose (e.g. 20 mg every second day) should be considered in patients with hepatic impairment, or in patients where concomitant medication has the potential for interaction with Fluoxetine.

Dosing in Specific Populations
Treatment of Pregnant Women — When treating pregnant women with FLUOXETINE, the physician should carefully consider the potential risks and potential benefits of treatment. Neonates exposed to SSRI or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding.
Geriatric — A lower or less frequent dosage should be considered for the elderly.
Hepatic Impairment — As with many other medications, use a lower or less frequent dosage should be used in patients with hepatic impairment.
Concomitant Illness — Patients with concurrent disease or on multiple concomitant medications may require dosage adjustments.

Discontinuation of Treatment
Symptoms associated with discontinuation of fluoxetine, SNRIs, and SSRIs, have been reported.
Withdrawal symptoms seen on discontinuation of FLUOXETINE: Abrupt discontinuation should be avoided. When stopping treatment with FLUOXETINE the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions (see sections 4.4 and 4.8). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with FLUOXETINE. Conversely, at least 5 weeks should be allowed after stopping FLUOXETINE before starting an MAOI intended to treat psychiatric disorders.

Use of FLUOXETINE with Other MAOIs such as Linezolid or Methylene Blue 
Do not start FLUOXETINE in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered.
In some cases, a patient already receiving FLUOXETINE therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, FLUOXETINE should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for five weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first.
Therapy with FLUOXETINE may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with FLUOXETINE is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use.

Method of administration
For oral administration.
Fluoxetine may be administered as a single or divided dose, during or between meals.
When dosing is stopped, active drug substances will persist in the body for weeks. This should be borne in mind when starting or stopping treatment.