fluoxetine-prozac

Fluoxetine (Prozac)

Pharmacological group: Antidepressants
Pharmacological action: Antidepressant, propylamine derivative. The mechanism of action is associated with selective blockade of neuronal reuptake of serotonin in the CNS. Fluoxetine is a weak antagonist of cholino-, adreno- and histamine receptors. Unlike most antidepressants, fluoxetine does not appear to cause a decrease in the functional activity of postsynaptic β-adrenergic receptors. Helps improve mood, reduces feelings of fear and tension, eliminates dysphoria. Does not cause sedation. When taken in average therapeutic doses, it practically does not affect the functions of the cardiovascular and other systems.
Systematic (IUPAC) name: (RS)-N-methyl-3-phenyl-3- propane-1-amine
Trade names: Prozac, among others
Consumption: orally
Bioavailability: 72% (peak - after 6-8 hours)
Protein binding: 94.5%
Metabolism: liver
Half-life: 1-3 days (fast), 4-6 days (slow)
Excretion: renal (80%), fecal (15%)
Formula: C 17 H 18 F 3 NO
Mol. mass: 309.33 g mol-1
Melting point: 179-182°C (354-360°F)
Boiling point: 395°C (743°F)
Solubility in water: 14 mg/ml (20°C)

Fluoxetine (also known under the trade names Prozac, Sarafem, Fontex, etc.) is an antidepressant in the selective serotonin reuptake inhibitor (SSRI) class of antidepressants. Fluoxetine was first registered in 1974 by scientists from Eli Lilly and Company. In February 1977, the drug was submitted to the US FDA, and in December 1987, Eli Lilly received final approval to bring the drug to market. In August 2001, the patent for fluoxetine expired. Fluoxetine is approved for the treatment of major depressive disorder (including childhood depression), obsessive-compulsive disorder (in both adults and children), bulimia nervosa, panic disorder, and dysphoric disorder. In addition, fluoxetine is used to treat trichotillomania, in case of unsatisfactory results of cognitive-behavioral therapy. It is marketed in combination with olanzapine under the name Symbyax. Despite the availability of new drugs, the popularity of Fluoxetine is not declining. In 2010, over 24.4 million generic prescriptions for fluoxetine were filled in the United States alone. Fluoxetine is the third most prescribed antidepressant after (SSRI; became generic in 2006) and Citalopram (SSRI; became generic in 2003). In 2011, there were 6 million prescriptions for fluoxetine in the UK.

Application

Action

Selective serotonin reuptake inhibitor (SSRI), antidepressant. The chemical structure is not similar to classical antidepressants (tricyclic, tetracyclic). Does not show affinity for adrenergic receptors a1, a2 i β, serotonergic, muscarinic, histamine H1, dopaminergic receptors and GABA. After oral administration, it is well absorbed; food intake does not affect the bioavailability of the drug; tmax is 6-8 hours, steady state is reached after a few weeks of use. Contacts proteins of plasma approximately for 95%. In the liver, it is demethylated with the participation of the CYP2D6 isoenzyme, and one of the active metabolites is norfluoxetine. t1 / 2 fluoxetine is about 4-6 days, and norfluoxetine - about 4-16 days. Determined plasma concentrations are detected several weeks after discontinuation of the drug. Excreted as metabolites - 60% in the urine, 16% in the feces.

Indications

Depressive disorders in adults. Depression of varying severity in children and adolescents over the age of 8 in cases where psychotherapy does not bring the expected effect. Obsessive-compulsive disorder. Bulimia.

Contraindications

Hypersensitivity to any of the components of the drug, the parallel use of MAO inhibitors. Fluoxetine can be started 14 days after stopping an irreversible MAO inhibitor and at least 24 hours after stopping a reversible MAO inhibitor (eg, moclobemide). Therapy with an MAO inhibitor can be started no earlier than 5 weeks after stopping the use of fluoxetine (if fluoxetine has been used for a long time and / or in high doses, a longer interval should be considered). With extreme caution should be used in patients with pharmacologically controlled epilepsy, as well as with a history of seizures; should not be used in patients with refractory epilepsy. The drug should be discontinued if seizures develop. Caution should be used in patients with a history of mania or hypomania; in the case of the development of a manic phase, the drug should be discontinued. Patients with diabetes may need to adjust the dose of antidiabetic drugs. During the course of therapy (especially during the first week), patients with depression should be carefully monitored for worsening symptoms of depression and the appearance of suicidal thoughts and / or suicide attempts. Due to the possibility of developing abnormal skin hemorrhages, it should be used with caution in patients taking SSRIs, especially in the case of concomitant use of oral anticoagulants, drugs that affect platelet function, and in patients with a history of bleeding disorders. During the first weeks of taking the drug, psychomotor agitation may develop (increasing the dose in this case may be harmful). Care must be taken when using electroconvulsive therapy - there is evidence of the development of prolonged epileptic seizures against its background. There have been cases of hyponatremia, usually in the elderly or in people taking diuretics. Due to the lack of sufficient clinical data, it should be used with caution in patients with concomitant cardiovascular diseases. Abrupt discontinuation of the drug may lead to the development of a withdrawal syndrome; it is recommended to reduce the dose gradually. Drugs containing lactose should not be administered to patients with congenital galactose intolerance, primary lactase deficiency or malabsorption syndrome of glucose-galactose absorption.

drug interaction

When considering the need to use a drug that interacts with fluoxetine, one should always take into account the long period of elimination of fluoxetine and its pharmacologically active metabolite from the body. Should not be used in combination with MAO-A inhibitors due to the risk of developing serotonin syndrome. During therapy in combination with an MAO-B inhibitor (eg, selegiline), or serotonergic drugs (eg, tramadol, triptans), care must be taken due to the possibility of developing serotonin syndrome. Lithium salts and tryptophan may enhance the effect of drugs from the SSRI group. With the parallel use of drugs that affect the central nervous system, there is the possibility of changing the concentration in the blood of such drugs as: carbamazepine, haloperidol, clozapine, diazepam, phenytoin, alprazolam, imipramine, desipramine; care should be taken to consider changing the dosing regimen and observe the patient for the development of side effects. In the case of simultaneous use or use within 5 weeks after stopping taking fluoxetine, drugs metabolized by CYP2D6 with a narrow therapeutic index (for example, encainide, flecainide, vinblastine, carbamazepine, tricyclic antidepressants), the minimum effective dose should be used. Preparations containing the herb St. John's wort can lead to aggravation of side effects. There is a possibility of interaction of fluoxetine with drugs that bind strongly to plasma proteins; the concentration of concomitantly used digoxin should be monitored. In patients taking anticoagulants, coagulation parameters should be monitored. Therapy in combination with ritonavir, saquinavir or efavirenz may be associated with an increased risk of serotonin syndrome. No drug interactions of fluoxetine with chlorthiazide, secobarbital and tolbutamide were found. There is no information on cases of drug interactions with alcohol, but it is not recommended to use it while taking fluoxetine. Fluoxetine and norfluoxetine inhibit many isoenzymes of the cytochrome P450 system, which makes drug metabolism possible. Both substances are potent inhibitors of CYP2D6 (the main enzyme responsible for their metabolism) and mild to moderate inhibitors of CYP1A2, CYP2B6, CYP2C9/2C19, and CYP3A4. In addition, they inhibit the activity of P-glycoprotein, a type of membrane transport protein that plays an important role in drug transport and metabolism. This extensive effect on drug metabolism pathways in the body provides a wide potential for interactions with many commonly used drugs. The concomitant use of fluoxetine with triptans, tramadol, or other serotonergic drugs can lead to the development of a rare but potentially life-threatening adverse reaction called "serotonin syndrome". Fluoxetine has been shown to have antimicrobial activity against several groups of microorganisms, mainly Gram-positive microorganisms. The drug also shows a synergistic effect in combination with certain antibiotics against a number of bacteria.

Side effects

Often: headache, dizziness, restlessness, drowsiness or insomnia, abnormal dreams, asthenia, fatigue, agitation, euphoria, nausea, vomiting, dyspepsia, diarrhea, dry mouth, taste disturbances, rash, itching, increased sweating, blurred vision, frequent urination, urinary retention, sexual dysfunction, priapism, galactorrhea. Not very common: difficulty concentrating and thinking, mania, panic attacks, confusion, self-perception disorder, tremor, ataxia, tics, convulsions, psychomotor agitation, yawning, vasodilation, orthostatic hypotension, pharyngitis, shortness of breath, urticaria, alopecia, hypersensitivity reactions, chills, hypersensitivity to light. Rare: bleeding, bruising, hyponatremia, abnormal antidiuretic hormone secretion, pulmonary symptoms (including inflammation with variable histopathology and/or fibrosis), hepatic dysfunction, idiosyncratic hepatitis. Very rare: hallucinations, serotonin syndrome, arthralgia, myalgia, toxic epidermal necrolysis. After discontinuation of fluoxetine - withdrawal syndrome (weakness, paresthesia, headache, anxiety, nausea). In the first weeks of treatment, the risk of suicide increases. Symptomatic and supportive therapy is recommended; there is no specific antidote.

Sexual dysfunction is a common side effect of SSRIs. In particular, side effects often include difficulty becoming aroused, erectile dysfunction, lack of interest in sex, and anorgasmia (inability to achieve orgasm). Other possible side effects include: genital anesthesia, loss or decreased response to sexual stimuli, and ejaculatory anhedonia. While these sexual side effects are usually reversible, they can last for months, years, or a lifetime after the drug is completely stopped. This phenomenon is known as "post-SSRI sexual dysfunction". Eli Lilly, maker of Prozac brand name Fluoxetine, says the drug is contraindicated in people taking monoamine oxidase inhibitors, pimozide (Orap) or Thioridazine (Mellaril). The recommendations for the use of the drug indicate that the treatment of patients with liver failure "should be approached with caution." In these patients, fluoxetine and its metabolite norfluoxetine are eliminated approximately twice as fast, resulting in a proportional increase in drug exposure. The use of Ibuprofen in combination with fluoxetine can cause serious intestinal bleeding. Among the common side effects associated with fluoxetine and listed in the annotation to the drug, the largest difference with placebo are: nausea (22% vs. 9% in the placebo group), insomnia (19% vs. 10% in the placebo group), drowsiness (12% vs. 5% placebo), anorexia (10% vs 3% placebo), anxiety (12% vs 6% placebo), nervousness (13% vs 8% placebo), asthenia (11% vs 6% in the placebo group) and tremor (9% vs. 2% in the placebo group). The side effects most commonly leading to treatment interruption are anxiety, insomnia, and nervousness (1-2% each), and in pediatric trials, mania (2%). Fluoxetine shares sexual side effects with other SSRIs, including anorgasmia and decreased libido. In addition, rash or urticaria, sometimes severe, was observed in 7% of patients in clinical trials, and treatment was discontinued in a third of these cases. In post-marketing reports, there are several cases of complications that developed in patients with a rash. Symptoms included vasculitis and a lupus-like syndrome. In addition, in some cases, these side effects have been fatal. Akathisia, that is, internal tension, restlessness and inability to stand still, often accompanied by "constant aimless movements of the feet and legs, and marked restlessness", is a common side effect of fluoxetine. Akathisia usually begins to manifest after the start of treatment or increase in dose and disappears after discontinuation of fluoxetine, dose reduction or after treatment with propranolol. There are reports of a direct link between akathisia and suicidal attempts, with patients feeling better after stopping fluoxetine; and with repeated use of fluoxetine, they experienced the re-development of severe akathisia. These patients reported that "the development of akathisia provoked suicidal thoughts in them and their previous suicide attempts were associated with this." The experts note that because of the association of akathisia with suicide and the distress it creates for the patient, “raising awareness among staff and patients about the symptoms of this disease is vital.” More rarely, fluoxetine has been associated with movement disorders, acute dystonia, and tardive dyskinesia. The use of fluoxetine during pregnancy is also associated with an increase in the number of newborns with a poor compensatory-adaptive response. Since fluoxetine is excreted in mother's milk, the use of the drug during lactation is not recommended. When studying the effects of fluoxetine on neonatal mice, it was shown that with early postnatal administration of the drug in adult mice, depression and anxiety behavior are subsequently developed, similar to induced depression, for the treatment of which fluoxetine is used. The American Pediatrics Association classifies fluoxetine as a drug whose effect on the nursing infant is unknown and may be of concern.

Pregnancy and lactation

Caution should be exercised when used during pregnancy, especially in the third trimester and before childbirth due to the serotonergic effect of the drug or the possibility of developing withdrawal symptoms in newborns (irritability, tremor, hypotension, constant crying, difficulty sucking, poor sleep). Fluoxetine passes into breast milk; consideration should be given to stopping breastfeeding; if breastfeeding is continued, the lowest effective dose should be used.

Dosage and administration

Inside, regardless of the meal. Adults. depressive disorders. 20 mg per day in the morning. Clinical improvement is achieved after 1-4 weeks of taking the drug. If no improvement occurs after 3-4 weeks, consideration should be given to increasing the dose to max. 60 mg per day. After the disappearance of symptoms, it is necessary to continue treatment for at least 6 months. Obsessive-compulsive disorders. The initial dose is 20 mg per day in the morning; if improvement does not occur after a few weeks of therapy, the dose should be increased to max. 60 mg per day. Bulimia. 60 mg per day. Doses > 20 mg daily given in 2 divided doses (morning and afternoon). The maximum dose for syndromes that are difficult to treat is 80 mg per day. Episodes of severe depression with a moderate or severe course in children and adolescents over the age of 8 years, if psychotherapy does not work. The initial dose is 10 mg per day. After 1-2 weeks, the dose can be increased to 20 mg per day. The dose is selected individually; the lowest effective dose should be used. Treatment must be carried out in combination with psychotherapy. In elderly patients, the maximum dose is 60 mg per day. In patients with impaired liver function or taking other drugs that may interact with fluoxetine, the dose should be reduced or the intervals between doses should be increased. The drug should be stopped gradually (for at least 1-2 weeks.).

Notes

Fluoxetine does not affect intellectual or psychomotor functions, but, like other psychotropic drugs, it can cause impaired concentration, both in connection with the disease itself and in connection with the drug. For this reason, patients should be informed that the drug adversely affects the ability to drive vehicles and maintain mechanical equipment.

Medical use

Fluoxetine is often used to treat depression, obsessive-compulsive disorder, post-traumatic stress disorder, bulimia nervosa, panic disorder, body dysmorphia , dysphoric disorder and trichotillomania. Caution should be exercised when taking any SSRI for bipolar disorder, as it may increase the chance of mania; however, in bipolar disorder, fluoxetine may be used in conjunction with antipsychotics (eg, quetiapine). The drug has also been used to treat cataplexy, obesity and alcohol addiction, and compulsive overeating.

Depression

In a six-week, double-blind, controlled trial, fluoxetine was shown to be effective in treating depression, as well as reducing anxiety and improving sleep. Fluoxetine was shown to be superior to placebo in preventing relapse of depression when patients who initially responded positively to fluoxetine were given it for an additional 38 weeks. Placebo-controlled studies have also demonstrated the effectiveness of fluoxetine in the treatment of depression in the elderly and in children. However, two meta-analyses of randomized placebo-controlled trials suggest that in patients with mild or moderate symptoms, the clinical efficacy of the drug is not very significant. Studies show that much of the resistance to SSRIs such as (Paxil) and (Celexa) can be explained by genetic variation in the glycoprotein transporter. Paroxetine and Citalopram, glycoprotein substrates, are actively transported by this protein from the brain. Fluoxetine is not a glycoprotein substrate, and thus taking fluoxetine instead of paroxetine or citalopram may be beneficial in patients who are resistant to SSRIs.

Obsessive Compulsive Disorder

In two adults and one child, a placebo-controlled 13-week study demonstrated the effectiveness of fluoxetine in the treatment of. When taking higher doses of fluoxetine, an improvement in response was observed, while an inverse relationship was observed with the treatment of depression. In two controlled studies of patients with panic disorder, fluoxetine has been shown to cause a dramatic 40-50% reduction in the frequency of panic attacks. Three double-blind studies have shown that fluoxetine causes a significant reduction in binge eating and bulimic episodes. In long-term treatment for one year in patients who showed an initial response to fluoxetine, the drug was shown to be superior to placebo in the prevention of bulimic episodes.

Antiviral agent

In 2012, researchers at the University of California, Los Angeles found that fluoxetine and various other SSRIs could act as antivirals in therapy against enteroviruses such as polio. The American Society for Microbiology called this discovery a "major breakthrough" because there are currently no drugs used against enteroviruses.

withdrawal syndrome

Several cases of severe withdrawal symptoms have been reported in the literature following abrupt discontinuation of fluoxetine. However, various studies have shown that side effects upon discontinuation of fluoxetine are rare and usually quite mild, especially when compared with paroxetine, venlafaxine and fluvoxamine, which may be due to the relatively long pharmacological half-life of fluoxetine. One of the recommended strategies for controlling withdrawal from other SSRIs, in cases where dose reduction of the original SSRI is not effective, is to replace the original drug with fluoxetine. The effectiveness of this strategy is confirmed by data from double-blind controlled studies. Several studies have not shown that the drug causes any increase in side effects when fluoxetine treatment is interrupted for a short time (4-8 days) and then resumed, and this result is not consistent with the slow elimination of the drug from organism. When treatment was interrupted (Zoloft), more side effects were observed, and when treatment with Paroxetine was interrupted, significantly more. In a longer duration, 6-week, blinded discontinuation study, there was a non-significant increase (32% vs. 27%) in the overall rate of new or worsened adverse events in the fluoxetine stop group compared to the continued treatment group. However, in patients who stopped treatment, there was a significant increase (4.2%) in sleepiness at week 2 and an increase in the number of dizziness by 5-7% at weeks 4-6. This long period of withdrawal symptoms and dizziness, which persisted until the very end of the study, is also consistent with the long half-life of fluoxetine in the body. According to a 2007 summary report of available data, fluoxetine had the lowest rate of withdrawal among the antidepressants studied, including paroxetine and venlafaxine.

Suicide

The FDA has now required all manufacturers of antidepressants to display a black box warning on their products stating that antidepressants may increase the risk of suicide in people under 25 years of age. This warning is based on statistical analyzes conducted by two independent FDA panels that showed a 2-fold increase in suicidal thoughts and behaviors in children and adolescents, and a 1.5-fold increase in suicidal ideation in individuals in aged 18-24 years. These rates were slightly lower in the 24+ group, and much lower in the 65+ group. Donald Klein criticized this analysis, noting that suicidal tendencies, that is, suicidal thoughts and behavior, do not necessarily lead to suicide, and that the possibility that antidepressants may prevent the possibility of actual suicide, despite an increase in suicidal thoughts, cannot be denied. Fluoxetine, compared with antidepressants in general, has relatively little data. To carry out the above analysis of antidepressants, the FDA pooled the results of 295 trials of 11 antidepressants. When considered separately, the use of fluoxetine in children caused a 50% increase in the risk of suicide, while in adults this risk was reduced by about 30%. In addition, an analysis by the UK Medicines and Healthcare Products Regulatory Agency (MHRA) showed a 50% increase in the number of suicidal thoughts and behaviors in children and adolescents when taking fluoxetine compared with placebo. According to the MHRA, in adults, fluoxetine does not change the number of self-harm and statistically significantly reduces the number of suicidal thoughts by 50%.

Violence

Psychiatrist David Healy and some active patient groups have reported cases of violent acts committed by individuals taking fluoxetine or other SSRIs. The report says that taking these drugs can lead susceptible individuals to commit violent acts. Serial reviews of this type have been criticized because disease effects are often mistaken for treatment effects. Other studies, including randomized clinical trials and observational studies, have shown that fluoxetine and other SSRIs may reduce violence. A randomized clinical trial from the American National Institute of Mental Health showed that fluoxetine caused a reduction in acts of domestic violence in alcoholics with a history of such behavior. A second clinical trial at the University of Chicago showed that fluoxetine caused a reduction in aggressive behavior in patients with intermittent aggression disorder. In a clinical trial, fluoxetine was found to reduce aggressive behavior in patients with borderline personality disorder. These results are indirectly supported by studies demonstrating that other SSRIs may reduce the risk of violence and aggressive behavior. An NBER study examining international trends in antidepressant benefit and crime rates in the 1990s found that an increase in antidepressant prescriptions was associated with a decrease in violent crime.

Pharmacokinetics

Fluoxetine has a relatively high bioavailability (72%), and peak plasma concentrations after administration are reached within 6 to 8 hours. It binds well to plasma proteins, mainly to. Fluoxetine is metabolized in the liver by cytochrome P450 isoenzymes, including CYP2D6. The role of CYP2D6 in fluoxetine metabolism may be clinically important as there is great genetic variability in the functioning of this enzyme among individuals. Only one fluoxetine metabolite, norfluoxetine (N-demethylated fluoxetine), is biologically active. Fluoxetine and its active metabolite norfluoxetine are distinguished from other antidepressants by extremely slow excretion from the body. Over time, fluoxetine and norfluoxetine inhibit their own metabolism, so that the half-life of fluoxetine, instead of 1 day, begins to be up to 3 days after a single dose, and from 4 to 6 days after long-term use. In addition, after prolonged use, the half-life of norfluoxetine increases (16 days). Thus, during the first few weeks of treatment, the concentration of the drug and its active metabolite in the blood continues to increase. Steady-state blood levels are reached after four weeks of use. In addition, at least during the first five weeks of treatment, the concentration of fluoxetine and its metabolites in the brain continues to increase. This means that after the current dose, the drug will have its effect after at least a month. For example, in one 6-week study, the median time to achieve a consistent response was 29 days. In addition, the complete elimination of the drug from the body can take several weeks. During the first week after stopping treatment, the concentration of fluoxetine in the brain decreases only by 50%, the level of norfluoxetine in the blood 4 weeks after stopping treatment is about 80% of the level at the end of the first week of treatment, and 7 weeks after stopping taking norfluoxetine is still can be found in the blood. The PET study compared the effects of a single dose of fluoxetine on exclusively heterosexual and exclusively homosexual men who reported that their past and present sexual behaviors, desires and fantasies were directed exclusively at women or at men, respectively. The study showed that in some areas of the brain, the metabolic response in these two groups proceeded differently. "Both groups, however, show similar broadly lateralized metabolic responses to fluoxetine (compared to placebo), with most brain areas in these groups responding similarly." These groups "did not differ in behavioral characteristics or blood levels of fluoxetine." Fluoxetine is a selective serotonin reuptake inhibitor and to some extent inhibits the reuptake of norepinephrine and dopamine. However, Eli Lilly researchers found that a single high dose of fluoxetine in rats also showed a significant increase in norepinephrine and dopamine concentrations in the brain. This effect may be mediated by 5HT2a and in particular 5HT2 receptors, which are inhibited by higher concentrations of fluoxetine. Scientists at Eli Lilly also suggested that the effects on dopamine and norepinephrine receptors may contribute to enhancing the antidepressant effects of fluoxetine. According to other researchers, the strength of this effect, however, remains undetermined. When taking fluoxetine in smaller, more clinically significant doses, no increase in dopamine and norepinephrine levels was observed. In addition, in electrophysiological studies, it was shown that only when taking high doses of fluoxetine, changes in the activity of norepinephrine neurons in rats were observed. Some authors, however, argue that these data may still be of clinical relevance for the treatment of severe illness when fluoxetine is taken at doses higher than therapeutic (60-80 mg). Compared to other SSRIs, "Fluoxetine is the least selective," and exhibits a 10-fold difference in binding capacity between first and second neural targets (eg, to the serotonin and norepinephrine pumps, respectively). All values ​​greater than 10-fold difference result in insignificant activation of secondary neural targets. In addition to its known effects on serotonin, fluoxetine also increases the density of endogenous opioid receptors in the rat brain. It's not yet clear if the same thing happens in humans, but if it does, it could explain some of the antidepressant or side effects of fluoxetine.

Measurements in body fluids

For monitoring during treatment, confirming the diagnosis of poisoning in hospitalized patients, or assisting in the course of a forensic examination, the amount of fluoxetine and norfluoxetine can be quantified in blood, plasma or serum. Fluoxetine concentrations in blood or plasma are typically 50-500 µg/L in individuals taking the drug as an antidepressant, 900-3000 µg/L in acute overdose survivors, and 1000-7000 µg/L in fatal overdose victims. Norfluoxetine concentrations are approximately equal to those of the parent drug in long-term therapy, but may be significantly lower in acute overdose, as it takes at least 1-2 weeks for the metabolite to reach equilibrium.

Mechanism of action

Fluoxetine acts primarily as a serotonin reuptake inhibitor. Fluoxetine inhibits the reuptake of serotonin, causing serotonin to be released for a longer time when released. Some of the effects of fluoxetine also depend on its weak 5-HT2C receptor antagonism. In addition, fluoxetine acts as a sigma-1 receptor agonist, stronger than citalopram, but weaker than fluvoxamine. However, the meaning of this property is not entirely clear.

Story

In 1970, Eli Lilly and Company began the work that eventually led to the discovery of fluoxetine as part of a collaboration between Brian Molloy and Robert Rathbun. At the time, the antihistamine drug Diphenhydramine was known to have some antidepressant properties. The compound 3-phenoxy-3-phenylpropylamine, structurally similar to diphenhydramine, was taken as the basis. Molloy synthesized dozens of derivatives of this compound. Testing the physiological effects of these compounds in mice led to the discovery of nisoxetine, a selective norepinephrine reuptake inhibitor currently widely used in biochemical experiments. Later, hoping to find a derivative that only inhibits serotonin reuptake, another Eli Lilly scientist, David T. Wong, proposed retesting the compounds in the laboratory for serotonin, norepinephrine, and dopamine reuptake. This test by Jong-Sir Horng in May 1972 showed that the compound later named Fluoxetine was the most potent and selective serotonin reuptake inhibitor of all the compounds tested. In 1974, Wong published the first paper on fluoxetine. A year later, the compound was given the official chemical name "Fluoxetine", and Eli Lilly and Company launched it under the trade name "Prozac". In February 1977, Dista Products Company, a division of Eli Lilly and Co, submitted a new request to the US FDA for fluoxetine. In May 1984, the German Regulatory Agency (BGA) rejected Prozac as "completely unsuitable for the treatment of depression." In May 1985, the FDA's then Chief Safety Investigator, Dr. Richard Karit, wrote: "In contrast to the profile of a traditional tricyclic antidepressant, fluoxetine's side effects are more akin to stimulants than to sedatives." According to him, “fluoxetine’s specific adverse side effect profile may in the future lead to great clinical interference in the use of this drug for the treatment of depression.” Fluoxetine entered the Belgian market in 1986. More than ten years later, in December 1987, the FDA finally approved Fluoxetine, and a month later Eli Lilly began marketing Prozac, which reached $350 million in annual sales in the United States within a year. Shortly after publication Researchers from a Lilly paper titled "Prozac (Fluoxetine, Lilly 110140), the first selective serotonin reuptake inhibitor and antidepressant", which claimed that fluoxetine was the first selective serotonin reuptake inhibitor (SSRI), controversy ensued. Two years later, the authors were forced to publish an amendment acknowledging that the first SSRI, called Zimelidine, had been developed by Arvid Karlsson and colleagues. Eli Lilly's US patent on Prozac (Fluoxetine) expired in August 2001, prompting an influx of generics into the market. In an attempt to stem the declining sales of Fluoxetine by Eli Lilly after the patent expired, Prozac was rebranded as "Sarafem" for the treatment of PMS. A meta-analysis published in February 2008 collected data from 35 clinical trials of four new antidepressants (fluoxetine, paroxetine (Paxil), nefazodone (Serzone), and venlafaxine (Effexor)). These antidepressants, belonging to three different pharmacological groups, were considered together, that is, the authors did not analyze them separately. The authors concluded that "although the difference [between placebo and antidepressants] easily reaches statistical significance", it does not meet the UK National Institutes of Health and Clinical Standards criteria for clinical significance "in all but the most severely depressed patients". . Articles began to appear in the press under the titles "Myth-Making Prozac" and "Prozac Doesn't Help Most Depressed Patients" in which the authors concluded that fluoxetine was ineffective from general conclusions about the relative effectiveness of antidepressants and placebo. In the following article, the authors of the meta-analysis noted that "unfortunately, the media often portrays the results of our work in the form of such headlines as" antidepressants do not work "and the like, which fundamentally distorts the more subtle structural conclusions of our report." As of April 2, 2010, fluoxetine is one of four antidepressants that the FAA (US Federal Aviation Administration) allows pilots to carry on board a ship. The other three include sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro).

Philozac (Egypt)

Biozac, Deprexetin, Fluval, Biflox, Deprexit, Sofluxen, Floxet, Ranflutin - (Bulgaria)

Flunisan, Orthon, Refloksetin, Fluoxetine - (Macedonia)

Motivest (Philippines)

Seronil (Finland)

Lorien (South Africa)

Affectine (Israel)

Proxetin (Thailand)

Flow (Pakistan)

Fluxil (Singapore)

Prozac in popular culture

Mention of the drug Prozac is found in many books, films and songs of popular culture. These include: Listening to Prozac, written in 1993 by psychiatrist Peter D. Kramer. The 1994 memoir Prozac Nation by Elisabeth Werzel, as well as the 2001 film of the same name, starring Christina Ricci as Werzel. The 1995 Blur song "Country House" ("House in the Village") contains the following lines: "He" s reading Balzac and knocking back Prozac / It "s the helping hand that makes you feel wonderfully bland" ("He reads Balzac and sips Prozac in one gulp / It's like a helping hand, bringing amazing calmness"). A well-known book critical of the drug is Prozac Commentary, written by psychiatrist Peter Breggin and published in 1994 (ISBN 0312114869). Prozac is mentioned in the Superman graphic novel Red Son, where the Nerd uses it to control the mood of the people in Superman's empire. In Alison Bechdel's comic book series "Dykes to Watch Out For", Lois takes Prozac in the 1997 book "Hot, Trobbibg Dykes to Watch Out For". Prozac Diary 1998, confessional memoir by Lauren Slater. "Plato, not Prozac!" is the title of a 1999 self-help book by Lou Marinoff that proposes using classical philosophy as an alternative to the usual pro-pharmaceutical approach to psychotherapy. The song "1985" by The Bowling For Soup describes the breakdown/crisis of a suburban middle-aged housewife. It begins with "Debbie just hit the wall/she never had it all/One Prozac a day/husband"s a CPA..." - senior accountant ... ") "Pets on Prozac" is the name of an underground house band in the UK, formed in 2010. Prosac is one of the most notable works of the progressive house musician Tomcraft. The main text of the song is read from the pharmacological description and indications Bernard Sumner (musician of New Order and Joy Division) chronicled his experience with Prozac and its impact on creativity for the BBC documentary The Prozac Diaries Prozac is often referenced in the popular comedy series Ally McBeal, where 3 season, the eponymous character (played by Calista Flockheart) takes Prozac at the behest of his psychiatrist, Dr. Shirley Flott (played by Betty White).Flott describes the miraculous benefits of Prozac in honor Eucharistic proportions by telling Ellie that she "will not find happiness in love or God, happiness is in pills". Flott also claims that she herself takes Prozac in the form of suppositories. Although Ellie initially starts taking Prozac to combat her hallucinations, she is later discouraged by a friend and colleague and ends up flushing the pills down the toilet. In the HBO series The Sopranos, gangster Tony Soprano (James Gandolfini) has a tendency to have panic attacks. His psychiatrist Dr. Jennifer Melfi (Lorraine Bracco) prescribes him Prozac. Prozac takes place in the movie Love and Other Drugs, starring Jake Gyllenhaal, who plays a Pfizer drug salesman who is trying to promote Zoloft. He discards most of the Prozac shipment, which is subsequently picked up by vagrants and the drug is thus distributed throughout the country. "ProzaKc Blues" is a song by progressive rock band King Crimson from their 2000 album ConstruKction of Light. Prozac+ is the name of an Italian punk band.

Availability:

Fluoxetine is a fairly common drug on the domestic market used to treat various depressive conditions, which are accompanied by a feeling of fear and anxiety. The drug has a strong effect with many adverse reactions. Most often, people taking fluoxetine note a feeling of increased fatigue, a complete absence of an emotional factor, a lack of desire. With extreme caution, this drug can be taken by people with diabetes, as it can change the level of glucose in blood, as well as people with cardiovascular disease and people doing potentially hazardous work. Fluoxetine is available only by prescription and is in a low price category, being affordable for most citizens of the country.

Instructions for use:

Fluoxetine is a drug that belongs to the group of antidepressants.

Pharmacological action of fluoxetine

Fluoxetine is a propylamine derivative. The mechanism of its action is due to the selective (selective) ability to suppress the reuptake of serotonin in the central nervous system. In this case, the drug has a minimal effect on the metabolism of dopamine, acetylcholine and norepinephrine.

The instructions for Fluoxetine noted that this drug reduces the feeling of tension and fear, relieves anxiety, and improves mood. Fluoxetine does not cause orthostatic hypotension and does not adversely affect the myocardium.

According to reviews, fluoxetine should be taken for at least one to two weeks to achieve the full therapeutic effect.

Fluoxetine is well absorbed from the gastrointestinal tract. Food intake does not significantly affect its bioavailability.

Indications for the use of fluoxetine

The drug is taken in the following cases:

• Treatment of depressive conditions of varying severity;
• obsessive states;
• Appetite disorders (anorexia, bulimia);
• Complex therapy of alcoholism.

How to use fluoxetine

For the treatment of depressive conditions, it is usually prescribed to take the drug 1 tablet (20 mg) once a day, preferably in the morning. With insufficient effectiveness, the dose can be increased to two tablets (40 mg) per day. The maximum allowable daily dose is 4 tablets (80 mg), and for elderly patients - 3 tablets (60 mg).

According to the instructions, Fluoxetine for the treatment of bulimia is prescribed one tablet three times a day.

For the treatment of obsessive-compulsive disorders, 1 to 3 tablets (20-60 mg) per day are prescribed.

The duration of the course of treatment depends on the severity of the disease, the effectiveness of the therapy. The minimum duration of the course is at least 3 weeks, and the maximum is several years.

Side effects

Therapy with this drug can lead to the development of side effects:

• From the side of the nervous system - headache, asthenia, dizziness, weakness, irritability, mania, anxiety, increased risk of suicide;
• On the part of the digestive tract - decreased appetite, dyspepsia, dry mouth, or vice versa, increased salivation (salivation);
• On the part of other organs - decreased libido, increased sweating, weight loss, allergic reactions.

When using fluoxetine, side effects from ongoing therapy often require its withdrawal.

Contraindications

According to the instructions, Fluoxetine is contraindicated in the following cases:

• Individual intolerance to the drug;
• Bladder atony;
• Angle-closure glaucoma;
• Severe liver or kidney failure;
• Treatment with MAO inhibitors;
• Pregnancy and lactation;
• Increased suicidal tendencies;
• Prostate hypertrophy.

The use of fluoxetine in patients suffering from Parkinson's syndrome, epilepsy, diabetes mellitus or severe malnutrition requires special care.

Interaction of fluoxetine with other drugs

This drug enhances the effects of alcohol, Diazempam and medicines that lower blood glucose levels.

Fluoxetine, when taken simultaneously with tricyclic antidepressants, increases the concentration of the latter in the blood plasma by almost two times.

According to reviews, fluoxetine should not be prescribed to patients on the background of electroconvulsive therapy, tk. in this case, the severity of epileptic seizures is possible.

Overdose

In case of accidental or intentional intake of a large dose of Fluoxetine, the patient needs urgent medical attention. There is no specific antidote, so symptomatic treatment is carried out. To accelerate the excretion of the drug from the body, gastric lavage is carried out and sorbents are given inside.

Release form

Fluoxetine is available in capsules containing 20 mg of the active substance.

Storage conditions

The drug is dispensed from pharmacies only by prescription. Store at room temperature out of the reach of children. Shelf life - three years. Fluoxetine should not be used after the expiration date printed on the box.

Gross formula

C 17 H 18 F 3 NO

Pharmacological group of the substance Fluoxetine

Nosological classification (ICD-10)

CAS code

54910-89-3

Characteristics of the substance Fluoxetine

Bicyclic antidepressant, SSRI.

Fluoxetine hydrochloride is a white or off-white crystalline powder, sparingly soluble in water (14 mg/mL). Molecular weight 345.79.

Pharmacology

pharmachologic effect- antidepressant, anorexigenic.

It selectively inhibits the reuptake of serotonin, which leads to an increase in its concentration in the synaptic cleft, an increase and prolongation of its action on postsynaptic receptors. By increasing serotonergic transmission, it inhibits the metabolism of a neurotransmitter by a negative feedback mechanism. With prolonged use, it lowers the activity of 5-HT 1 receptors. It also blocks the reuptake of serotonin in platelets. Weakly affects the reuptake of norepinephrine and dopamine. It does not have a direct effect on serotonin, m-cholinergic, H 1 -histamine and alpha-adrenergic receptors. Unlike most antidepressants, it does not cause a decrease in the activity of postsynaptic beta-adrenergic receptors.

Effective in endogenous depression and obsessive-compulsive disorders. Improves mood, reduces tension, anxiety and fear, eliminates dysphoria. It has an anorexigenic effect, can cause weight loss. In patients with diabetes mellitus, it can cause hypoglycemia, with the abolition of fluoxetine - hyperglycemia. A pronounced clinical effect in depression occurs after 1-4 weeks of treatment, in obsessive-compulsive disorders - after 5 weeks or more.

Well absorbed from the gastrointestinal tract. The effect of the "first pass" through the liver is weakly expressed. Capsules and an aqueous solution of fluoxetine are equivalent in effectiveness. After a single dose of 40 mg C max fluoxetine is achieved after 4-8 hours and is 15-55 ng / ml, when taken at the same dose for 30 days C max fluoxetine is 91-302 ng / ml, norfluoxetine - 72- 258 ng/ml. At concentrations up to 200-1000 ng / ml, fluoxetine is 94.5% bound to blood proteins, including albumin and alpha 1-glycoprotein. Enantiomers are equally effective, but S-fluoxetine is excreted more slowly and prevails over the R-form at equilibrium concentration. Easily penetrates through the BBB. In the liver, enantiomers are demethylated with the participation of the isoenzyme CYP2D6 cytochrome P450 to norfluoxetine and other unidentified metabolites, with S-norfluoxetine equal in activity to R- and S-fluoxetine and superior to R-norfluoxetine. T 1/2 fluoxetine is 1-3 days after a single dose and 4-6 days with prolonged administration. T 1 / 2 norfluoxetine - 4-16 days in both cases, which causes a significant cumulation of substances, the slow achievement of their equilibrium level in plasma and a long presence in the body after cancellation. In patients with cirrhosis of the liver, T 1/2 of fluoxetine and its metabolites is extended. Excreted within 1 week mainly by the kidneys (80%): unchanged - 11.6%, as fluoxetine glucuronide - 7.4%, norfluoxetine - 6.8%, norfluoxetine glucuronide - 8.2%, more than 20% - hippuric acid, 46% - other compounds; 15% is excreted by the intestines. With impaired renal function, the excretion of fluoxetine and its metabolites slows down. It is not excreted during dialysis (due to the large volume of distribution and the high degree of binding to plasma proteins).

There is evidence of the effectiveness of fluoxetine in eating disorders (anorexia nervosa), alcoholism, anxiety disorders, including social phobia; diabetic neuropathy, affective, incl. bipolar, disorders; dysthymia, autism, panic attacks, premenstrual syndrome, narcolepsy, catalepsy, obstructive sleep apnea syndrome, kleptomania, schizophrenia, schizoaffective disorders, etc.

The use of the substance Fluoxetine

Depression (especially accompanied by fear), incl. with the ineffectiveness of other antidepressants, obsessive-compulsive disorders, bulimia nervosa.

Contraindications

Hypersensitivity, the use of MAO inhibitors (in the previous 2 weeks), liver and kidney failure (creatinine clearance less than 10 ml / min), epilepsy and convulsions (history), suicidal mood, diabetes mellitus, bladder atony, angle-closure glaucoma, prostatic hypertrophy glands.

Application restrictions

Children's age (safety and efficacy have not been established), myocardial infarction, incl. history of cirrhosis of the liver.

Use during pregnancy and lactation

During pregnancy, it should be prescribed only if absolutely necessary. When using fluoxetine during pregnancy, an increased risk of preterm birth, developmental anomalies and low adaptation of newborns (including difficulty breathing, cyanosis, excitability) were noted.

At the time of treatment, breastfeeding should be abandoned (fluoxetine passes into the breast milk of lactating women).

Updating information

The use of fluoxetine in the first trimester of pregnancy

A sufficient number of controlled studies on the safety of the use of fluoxetine in women during the first trimester of pregnancy has not been conducted, and the results of some published epidemiological studies are contradictory. More than 10 cohort and case-control studies have not found an increase in the likelihood of congenital malformations. At the same time, a prospective cohort study conducted European Network of Teratology Information Services, suggests an increased risk of congenital CVD in newborns whose mothers (n=253) used fluoxetine during the first trimester of pregnancy compared with newborns whose mothers (n=1359) did not take fluoxetine. At the same time, a specific group of malformations of the cardiovascular system was not determined and it was not possible to establish a reliable causal relationship between taking fluoxetine during the first trimester of pregnancy and an increased risk of developing fetal abnormalities.

[Updated 24.02.2012 ]

The use of fluoxetine in the third trimester of pregnancy

The use of serotonin and norepinephrine reuptake inhibitors (SNRIs), as well as SSRIs, including fluoxetine, at the end of the third trimester of pregnancy led to the development of complications in newborns (the duration of hospitalization, the duration of artificial lung ventilation and tube feeding increased). There are reports of the development of such pathological conditions as neonatal respiratory distress syndrome, apnea, convulsions, body temperature lability, hypoglycemia, a decrease or increase in blood pressure, vomiting, difficulty in adequate nutrition, cyanosis, hyperreflexia, tremor, nervous irritability, excitability, constant crying. These disorders may be a manifestation of the toxic effects of SNRIs and SSRIs, or be a consequence of their withdrawal syndrome.

[Updated 24.02.2012 ]

Animal data on the teratogenicity of fluoxetine

With the introduction of fluoxetine, at doses exceeding 12.5 mg / kg per day to pregnant female rats, as well as at doses exceeding 15 mg / kg per day to pregnant female rabbits (respectively, 1.5 and 3.6 times higher than the maximum dose recommended for humans - 80 mg / m2), there were no reliable data indicating the teratogenicity of fluoxetine during the process of organogenesis. However, data from other studies in rats show an increase in stillbirths, a decrease in neonatal weight, and an increase in mortality of newborn rats within 7 days after birth with fluoxetine at a dose of 12 mg/kg per day (1.5 times the maximum dose recommended for humans) during pregnancy and at a dose of 7.5 mg / kg per day (90% of the maximum dose recommended for humans) during pregnancy and lactation. However, there were no signs of neurotoxicity in surviving newborn female rats treated during pregnancy with 12 mg/kg of fluoxetine per day. The fluoxetine dose of 5 mg/kg per day (60% of the maximum recommended human dose) has been found to not increase neonatal mortality.

[Updated 24.02.2012 ]

side effects of fluoxetine

From the nervous system and sensory organs: headache, dizziness, anxiety, nervousness, lethargy, fatigue, asthenic syndrome, emotional lability, sleep disorders (insomnia, drowsiness), nightmares, restlessness, muscle twitches, myoclonus, tremor, hyperkinesia, convulsive states, hypo- or hyperreflexia, extrapyramidal syndrome, carpal tunnel syndrome, ataxia, akathisia, dysarthria, hyper- or hypesthesia, paresthesia, neuralgia, neuropathy, neuritis, neurosis, thinking disorders, difficulty concentrating, amnesia, euphoria, mania or hypomania, hallucinations, depersonalization, paranoid reactions, psychosis, suicidal tendencies, EEG changes, stupor, coma, decreased visual acuity, amblyopia, strabismus, diplopia, exophthalmos, mydriasis, conjunctivitis, iritis, scleritis, blepharitis, xerophthalmia, photophobia, glaucoma, taste disturbance, parosmia, noise and pain in the ears, hyperacusis.

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): tachy- or bradycardia, extrasystoles, atrial or ventricular fibrillation, cardiac arrest, myocardial infarction, congestive heart failure, hyper- or hypotension, vascular dilatation, phlebitis, thrombophlebitis, vascular thrombosis, vasculitis with hemorrhagic rash, cerebral ischemia, cerebral embolism, anemia, leukocytosis or leukopenia, lymphocytosis, thrombocythemia, thrombocytopenia, pancytopenia.

From the respiratory system: nasal congestion, epistaxis, sinusitis, laryngeal edema, shortness of breath, stridor, hyper- or hypoventilation, hiccups, cough, respiratory distress syndrome, inflammatory or fibrotic lung changes, atelectasis, emphysema, pulmonary edema, hypoxia, apnea, pain in chest.

From the digestive tract: decreased (rarely increased) appetite, anorexia, dry mouth, increased salivation, enlarged salivary glands, aphthous stomatitis, glossitis, dysphagia, esophagitis, gastritis, dyspepsia, nausea, vomiting, incl. hematemesis, abdominal pain, "acute abdomen" syndrome, gastric and duodenal ulcer, gastrointestinal bleeding, flatulence, diarrhea, constipation, melena, colitis, intestinal obstruction, increased levels of hepatic transaminases, creatine phosphokinase and alkaline phosphatase in the blood, hepatitis, cholelithiasis, cholestatic jaundice, liver failure, liver necrosis, pancreatitis.

From the side of metabolism: impaired secretion of ADH, hyponatremia, hypo- or hyperkalemia, hypocalcemia, hyperuricemia, gout, hypercholesterolemia, diabetes mellitus, hypoglycemia, diabetic acidosis, hypothyroidism, edema, dehydration.

From the genitourinary system: dysuria, frequent urination, nocturia, poly- or oliguria, albumin- and proteinuria, glucosuria, hematuria, urinary tract infections, cystitis, renal failure, hyperprolactinemia, enlargement and pain in the mammary glands, decreased libido, ejaculation disorders, priapism, impotence, anorgasmia , painful menstruation, meno- and metrorrhagia.

From the musculoskeletal system: myasthenia gravis, myopathy, myalgia, myositis, arthralgia, arthritis, rheumatoid arthritis, bursitis, tendosynovitis, chondrodystrophy, osteomyelitis, osteoporosis, bone pain.

From the side of the skin: polymorphic rash, incl. hemorrhagic, ulcerative skin lesions, acne, alopecia, contact dermatitis, photosensitivity, discoloration of the skin, furunculosis, herpes zoster, hirsutism, eczema, psoriasis, seborrhea, epidermal necrosis, exfoliative dermatitis.

Allergic reactions: rash, itching, urticaria, Quincke's edema, serum sickness type reactions, anaphylactic and anaphylactoid reactions.

Others: weight loss, sweating, flushing of the face and neck with a feeling of heat, neuroleptic malignant syndrome, yawning, chills, fever, flu-like syndrome, hypothermia, lymphadenopathy, incl. enlarged tonsils, pharyngitis. Deaths have been described.

Interaction

Incompatible with MAO inhibitors, other antidepressants, furazolidone, procarbazine, because causes serotonergic syndrome (chills, hyperthermia, muscle rigidity, myoclonus, autonomic lability, hypertensive crisis, agitation, tremor, restlessness, convulsions, diarrhea, hypomanic state, delirium, coma; death is possible. When taken simultaneously with drugs that have a high degree binding to plasma proteins (oral anticoagulants, oral hypoglycemic agents, cardiac glycosides, etc.), mutual exclusion from the connection with the protein is possible with a change in the concentration of the free fraction in the blood, the risk of side effects increases.The risk of bleeding increases while taking warfarin.Inhibits biotransformation drugs metabolized with the participation of the isoenzyme CYP2D6 cytochrome P450 (tricyclic antidepressants, dextromethorphan, etc.). Extends T 1/2 diazepam, potentiates the effects of alprazolam. When taken simultaneously, it changes (increases or decreases) the concentration of lithium in the blood plasma, increases the content of phenytoin (up to the clinical manifestations of its overdose); the level of tricyclic antidepressants (imipramine, desipramine) increases by 2-10 times. Tryptophan enhances the serotonergic properties of fluoxetine (possible agitation, restlessness, dysfunction of the gastrointestinal tract). Incompatible with ethanol.

Updating information

Learn more about fluoxetine drug interactions

The use of fluoxetine in combination with MAO inhibitors is contraindicated, as well as within 14 days after their cancellation in order to avoid the risk of interaction. The appointment of MAO inhibitors is possible only 5 weeks after the abolition of fluoxetine.

[Updated 24.02.2012 ]

The simultaneous use of fluoxetine and pimozide is not recommended. Clinical safety studies of the use of pimozide in combination with other antidepressants have shown that their simultaneous use can lead to lengthening of the corrected QT interval (QTc). Despite the fact that special studies on the safety of the simultaneous use of pimozide and fluoxetine have not been conducted, the potential for drug interactions, mainly prolongation of the QTc interval, is sufficient reason to limit the combined use of these drugs.

[Updated 24.02.2012 ]

A study was conducted with the participation of 19 healthy volunteers - 6 slow and 13 fast metabolizers of the debrisoquine-hydroxylase enzyme, who took 25 mg of thioridazine orally once. Cmax in slow metabolizers was 2.4 times higher, AUC - 4.5 times higher compared to fast metabolizers. It is known that the activity of debrisoquine hydroxylase depends on the level of activity of the isoenzyme of the cytochrome P450 CYP2D6 system. Thus, this study demonstrated that drugs that inhibit the isoenzyme CYP2D6, such as selective serotonin reuptake inhibitors, in particular fluoxetine, can increase the concentration of thioridazine in blood plasma. Thioridazine has the ability to dose-dependently lengthen QTc, which causes the risk of developing life-threatening forms of ventricular arrhythmias, such as torsades de pointes, and sudden death, the likelihood of which increases when thioridazine is taken concomitantly with fluoxetine.

Taking into account the risk of developing life-threatening forms of ventricular arrhythmias and sudden death while taking thioridazine and fluoxetine, it should be noted that such a therapeutic combination is contraindicated, and thioridazine can be taken after 5 weeks from the last dose of fluoxetine.

[Updated 24.02.2012 ]

Fluoxetine inhibits the activity of an isoenzyme of the cytochrome P450 system CYP2D6 and thus changes the normal metabolic activity of the isoenzyme to a level similar to that of slow metabolizers. Other drugs, the metabolism of which is carried out with the participation of the isoenzyme CYP2D6, such as tricyclic antidepressants (TCAs), antipsychotics (including phenothiazines and most atypical antipsychotics), antiarrhythmics (propafenone, flecainide, etc.) should be used with caution in conjunction with fluoxetine. If the patient is taking fluoxetine or has taken it within the last 5 weeks, therapy with drugs that are mainly metabolized CYP2D6 and having a narrow therapeutic range (for example, flecainide, propafenone, vinblastine and TCA), should begin with the lowest possible doses (dose selection should occur in the same way as in the case of slow metabolizers for this isoenzyme of the cytochrome P450 system). When prescribing fluoxetine to a patient already receiving drugs metabolized by the isoenzyme CYP2D6, it is necessary to provide for the need to adjust the dose of these drugs in the direction of its reduction.

[Updated 24.02.2012 ]

In some patients, it is possible to prolong T1 / 2 diazepam while taking fluoxetine. The combined use of alprazolam and fluoxetine was accompanied by an increase in serum concentrations of alprazolam, leading to depression of psychomotor activity.

[Updated 24.02.2012 ]

Some clinical evidence suggests a possible drug interaction between antipsychotics and selective serotonin reuptake inhibitors. In particular, an increase in the concentrations of haloperidol and clozapine was observed in patients receiving fluoxetine as concomitant therapy.

[Updated 24.02.2012 ]

Both a decrease and an increase in the serum concentration of lithium have been reported with the simultaneous use of fluoxetine. In the latter case, the likelihood of developing toxic effects of both normothymic drugs and selective serotonin reuptake inhibitors increases. With the simultaneous administration of lithium and fluoxetine preparations, it is necessary to constantly monitor the concentration of lithium in the blood plasma.

[Updated 24.02.2012 ]

Fluoxetine when taken at a dose of 60 mg once or for 8 days leads to a slight (about 16%) decrease in the clearance of olanzapine and an increase in Cmax.

In patients receiving fixed doses of phenytoin and carbamazepine, there was an increase in their plasma concentrations with the development of clinical manifestations of toxic effects, with the addition of fluoxetine as concomitant therapy.

[Updated 24.02.2012 ]

In the study in vivo it has been shown that a single administration of terfenadine (a CYP3A4 substrate) during fluoxetine therapy is not accompanied by an increase in serum terfenadine concentrations.

Research in vitro data were obtained indicating that ketoconazole, an effective inhibitor of the isoenzyme of the cytochrome P450 CYP3A4 system, is at least 100 times more active than fluoxetine and norfluoxetine in preventing the metabolism of CYP3A4 substrates (such as astemizole, cisapride, midazolam). Thus, the inhibitory ability of fluoxetine in relation to the isoenzyme of the cytochrome P450 system CYP3A4 is not clinically significant.

[Updated 24.02.2012 ]

Overdose

Symptoms: nausea, vomiting, agitation, anxiety, hypomania, convulsions, grand mal seizures. Two deaths from acute overdose of fluoxetine (in combination with maprotiline, codeine, temazepam) have been described.

Treatment: gastric lavage, activated charcoal, sorbitol, ECG monitoring, symptomatic and supportive therapy, with convulsions - diazepam. There is no specific antidote. Forced diuresis, peritoneal dialysis, hemodialysis, blood transfusion are ineffective.

Routes of administration

inside.

Fluoxetine Substance Precautions

Use with caution in the elderly, with cardiovascular diseases, insufficiency of the liver and / or kidneys. Careful monitoring of patients with suicidal tendencies is required, especially at the beginning of treatment. The highest risk of suicide is in patients who have previously taken other antidepressants and in patients who experience excessive fatigue, hypersomnia, or restlessness during treatment with fluoxetine. When treating patients with low body weight, the anorexigenic properties of fluoxetine should be taken into account. When conducting electroconvulsive therapy while taking fluoxetine, prolonged epileptic seizures are possible. The interval between the withdrawal of MAO inhibitors and the start of taking fluoxetine should be more than 2 weeks, and between the withdrawal of fluoxetine and taking MAO inhibitors - at least 5 weeks.

| Fluoxetine

Analogues (generics, synonyms)

Apo-Fluoxetine, Bioxetine, Deprex, Deprenon, Portal, Prodep, Prozac, Profluzak, Floxet, Fluval, Fluxonil, Flunat, Flunisan, Fluoxetine Hexal, Fludak, Framex

Recipe (International)

Rp.: Caps. Fluoxetini 0.02 № 20
D.S. 20 mg 1 time / day.

Recipe (Russia)

Prescription form - 107-1 / y

Active substance

(Fluoxetine)

pharmachologic effect

Antidepressant, anorexigenic.

It selectively inhibits the reuptake of serotonin, which leads to an increase in its concentration in the synaptic cleft, an increase and prolongation of its action on postsynaptic receptors. By increasing serotonergic transmission, it inhibits the metabolism of a neurotransmitter by a negative feedback mechanism. With prolonged use, it lowers the activity of 5-HT1 receptors. It also blocks the reuptake of serotonin in platelets. Weakly affects the reuptake of norepinephrine and dopamine. It does not have a direct effect on serotonin, m-cholinergic, H1-histamine and alpha-adrenergic receptors. Unlike most antidepressants, it does not cause a decrease in the activity of postsynaptic beta-adrenergic receptors.

Effective in endogenous depression and obsessive-compulsive disorders. Improves mood, reduces tension, anxiety and fear, eliminates dysphoria. It has an anorexigenic effect, can cause weight loss. In patients with diabetes mellitus, it can cause hypoglycemia, with the abolition of fluoxetine - hyperglycemia. A pronounced clinical effect in depression occurs after 1-4 weeks of treatment, in obsessive-compulsive disorders - after 5 weeks or more.

Well absorbed from the gastrointestinal tract. The effect of the "first pass" through the liver is weakly expressed.
Capsules and an aqueous solution of fluoxetine are equivalent in effectiveness. After a single dose of 40 mg, Cmax of fluoxetine is achieved after 4-8 hours and is 15-55 ng / ml, when taken at the same dose for 30 days, Cmax of fluoxetine is 91-302 ng / ml, norfluoxetine - 72-258 ng /ml At concentrations up to 200-1000 ng / ml, fluoxetine is 94.5% bound to blood proteins, including albumin and alpha1-glycoprotein. Enantiomers are equally effective, but S-fluoxetine is excreted more slowly and prevails over the R-form at equilibrium concentration. Easily penetrates through the BBB. In the liver, enantiomers are demethylated with the participation of the CYP2D6 isoenzyme of cytochrome P450 to norfluoxetine and other unidentified metabolites, and S-norfluoxetine is equal in activity to R- and S-fluoxetine and surpasses R-norfluoxetine. T1 / 2 of fluoxetine is 1-3 days after a single dose and 4-6 days with prolonged administration. T1 / 2 norfluoxetine - 4-16 days in both cases, which causes a significant cumulation of substances, the slow achievement of their equilibrium level in plasma and a long presence in the body after cancellation. In patients with cirrhosis of the liver, T1 / 2 of fluoxetine and its metabolites is prolonged.
Excreted within 1 week mainly by the kidneys (80%): unchanged - 11.6%, as fluoxetine glucuronide - 7.4%, norfluoxetine - 6.8%, norfluoxetine glucuronide - 8.2%, more than 20% - hippuric acid, 46% - other compounds; 15% is excreted by the intestines. With impaired renal function, the excretion of fluoxetine and its metabolites slows down. It is not excreted during dialysis (due to the large volume of distribution and the high degree of binding to plasma proteins).

There is evidence of the effectiveness of fluoxetine in eating disorders (anorexia nervosa), alcoholism, anxiety disorders, including social phobia; diabetic neuropathy, affective, incl. bipolar, disorders; dysthymia, autism, panic attacks, premenstrual syndrome, narcolepsy, catalepsy, obstructive sleep apnea syndrome, kleptomania, schizophrenia, schizoaffective disorders, etc.

Mode of application

For adults: Initial dose - 20 mg 1 time / day in the morning; if necessary, the dose can be increased after 3-4 weeks. The frequency of admission is 2-3 times / day.

The maximum daily oral dose for adults is 80 mg.

Indications

Depression of various origins
- obsessive-compulsive disorders
- bulimic neurosis.

Contraindications

Glaucoma
- atony of the bladder
severe renal dysfunction
benign prostatic hyperplasia
- simultaneous appointment of MAO inhibitors
- convulsive syndrome of various origins
- epilepsy
- pregnancy, lactation
- hypersensitivity to fluoxetine.

Side effects

- From the side of the central nervous system:
anxiety, tremor, nervousness, drowsiness, headache, sleep disturbances are possible.
- From the digestive system:
possible diarrhea, nausea.
- From the side of metabolism:
possible increased sweating, hypoglycemia, hyponatremia (especially in elderly patients and with hypovolemia).
- From the reproductive system:
decreased libido.
- Allergic reactions:
possible skin rash, itching.

Other: pain in the joints and muscles, shortness of breath, fever.

Release form

Caps. 20 mg: 14, 20 or 28 pcs.

ATTENTION!

The information on the page you are viewing was created for informational purposes only and does not promote self-treatment in any way. The resource is intended to familiarize healthcare professionals with additional information about certain medicines, thereby increasing their level of professionalism. The use of the drug "" without fail provides for a consultation with a specialist, as well as his recommendations on the method of application and dosage of the medicine you have chosen.

Release form:

Capsules hard gelatin, No. 4, with a white body and a blue cap; the contents of the capsules are white or almost white granules.

Excipients: lactose monohydrate (milk sugar) - 30.8 mg, microcrystalline cellulose - 16.1 mg, colloidal silicon dioxide (aerosil) - 150 mcg, magnesium stearate - 600 mcg, talc - 1.15 mg.

The composition of the capsule shell: gelatin - 36.44 mg, titanium dioxide - 1.52 mg, indigo carmine - 40 mcg.

Capsules hard gelatin, with a white body and a blue cap; the contents of the capsules are white or almost white powder.

Excipients: lactose monohydrate (milk sugar) - 61.6 mg, microcrystalline cellulose - 32.2 mg, colloidal silicon dioxide (aerosil) - 300 mcg, magnesium stearate - 1.2 mg, talc - 2.3 mg.

The composition of the capsule shell: gelatin - 36.44 mg, titanium dioxide - 1.52 mg, azorubin dye - 30 μg, crimson dye [Ponso 4R] - 10 μg, patented blue dye - 50 μg, brilliant black dye - 60 μg.

10 pieces. - cellular contour packings (1) - packs of cardboard.
10 pieces. - cellular contour packings (2) - packs of cardboard.
10 pieces. - cellular contour packings (3) - packs of cardboard.
10 pieces. - cellular contour packings (4) - packs of cardboard.
10 pieces. - cellular contour packings (5) - packs of cardboard.

Pharmacotherapeutic group:

• Neurotropic agents

Pharmacological properties:

Pharmacodynamics

Antidepressant of the group of selective serotonin reuptake inhibitors. It has a thymoanaleptic and stimulating effect.

Selectively blocks the reverse neuronal uptake of serotonin (5HT) in the synapses of neurons of the central nervous system. Inhibition of serotonin reuptake leads to an increase in the concentration of this neurotransmitter in the synaptic cleft, enhances and prolongs its action on postsynaptic receptor sites. By increasing serotonergic transmission, fluoxetine inhibits the metabolism of the neurotransmitter by the mechanism of negative membrane communication. With prolonged use, fluoxetine inhibits the activity of 5-HT1 receptors. Weakly affects the reuptake of norepinephrine and dopamine. It does not have a direct effect on serotonin, m-cholinergic, H1-histamine and alpha-adrenergic receptors. Unlike most antidepressants, it does not cause a decrease in the activity of postsynaptic beta-adrenergic receptors.

Effective in endogenous depression and obsessive-compulsive disorders. It has an anorexigenic effect, can cause weight loss. Does not cause orthostatic hypotension, sedation, non-cardiotoxic. A stable clinical effect occurs after 1-2 weeks of treatment.

Pharmacokinetics

When taken orally, the drug is well absorbed from the gastrointestinal tract (up to 95% of the dose taken), the use with food slightly inhibits the absorption of fluoxetine. Cmax in blood plasma is reached after 6-8 hours. The bioavailability of fluoxetine after oral administration is more than 60%. The drug accumulates well in tissues, easily penetrates the blood-brain barrier, binding to plasma proteins is more than 90%. Metabolized in the liver by demethylation to the active metabolite norfluoxetine and a number of unidentified metabolites. It is excreted by the kidneys in the form of metabolites (80%) and the intestines (15%), mainly in the form of glucuronides. T 1/2 of fluoxetine after reaching an equilibrium concentration in the blood plasma is about 4-6 days. T1 / 2 of the active metabolite of norfluoxetine with a single dose and after reaching an equilibrium concentration in the blood plasma ranges from 4 to 16 days. In patients with liver failure, the half-life of fluoxetine and norfluoxetine is prolonged.

Indications for use:

Depression of various origins;

obsessive-compulsive disorders;

Bulimic neurosis.

Regarding diseases:

• Depression
• Neuritis
• neuroses

Contraindications:

Simultaneous administration with MAO inhibitors (and within 14 days after their withdrawal);

Simultaneous reception of thioridazine (and within 5 weeks after the abolition of fluoxetine), pimozide;

Pregnancy;

The period of breastfeeding;

Severe renal dysfunction (creatinine clearance less than 10 ml / min);

Liver failure;

Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

Age up to 18 years;

Hypersensitivity to the drug.

FROM caution

Suicidal risk: with depression, there is a possibility of suicidal attempts, which may persist until a stable remission occurs. Individual cases of suicidal thoughts and suicidal behavior have been described during therapy or shortly after its completion, similar to the action of other drugs of close pharmacological action (antidepressants). Careful monitoring of patients at risk is necessary. Physicians should encourage patients to promptly report any thoughts or feelings that cause concern.

epileptic seizures: Fluxetine should be used with caution in patients who have experienced epileptic seizures.

Hyponatremia: Cases of hyponatremia have been reported. Basically, such cases were observed in elderly patients and in patients taking diuretics, due to a decrease in circulating blood volume.

Diabetes: glycemic control in diabetic patients during treatment with fluoxetine showed hypoglycemia, after discontinuation of the drug, hyperglycemia developed. Doses of insulin and/or oral hypoglycemic agents may need to be adjusted at the start or after treatment with fluoxetine.

Renal/liver failure: fluoxetine is metabolized in the liver and excreted by the kidneys and through the gastrointestinal tract. In patients with severe hepatic impairment, it is recommended to prescribe lower doses of fluoxetine, or to prescribe the drug every other day. When taking fluoxetine at a dose of 20 mg / day for two months, there were no differences in the concentration of fluoxetine and norfluoxetine in the blood plasma of healthy individuals with normal renal function and patients with severely impaired renal function (creatinine clearance 10 ml / min) requiring hemodialysis.

Dosage and administration:

The drug is taken orally, at any time, regardless of the meal.

depressive state

The initial dose is 20 mg 1 time / day in the morning, regardless of the meal. If necessary, the dose can be increased to 40-60 mg / day, divided into 2-3 doses (20 mg / day weekly). The maximum daily dose is 80 mg in 2-3 doses.

The clinical effect develops 1-2 weeks after the start of treatment, in some patients it can be achieved later.

Obsessive Compulsive Disorders

bulimic neurosis

The drug is used in a daily dose of 60 mg, divided into 2-3 doses.

The use of the drug by patients of different ages

elderly patients followed by a dose of 20 mg/day.

Accompanying illnesses

Prescribe fluoxetine patients with impaired liver or kidney function recommended with the use of low doses and lengthening the interval between doses.

Side effect:

When using fluoxetine, as in cases of using drugs from the group of selective serotonin reuptake inhibitors, the following adverse events are noted.

From the side of the cardiovascular system: often (≥ 1% - ≤10%) - atrial flutter, hot flashes; infrequently (≥ 0.1% - ≤1%) - hypotension; rarely (≤ 0.1%) - vasculitis, vasodilation.

From the digestive system: very often (≥ 10%) - diarrhea, nausea; often (≥ 1% - ≤10%) - dry mouth, dyspepsia, vomiting; infrequently (≥ 0.1% - ≤1%) - dysphagia, taste perversion; rarely (≤ 0.1%) - pain along the esophagus.

From the hepatobiliary system: rarely (≤ 0.1%) - idiosyncratic hepatitis.

From the immune system: very rarely (≤ 0.1%) - anaphylactic reactions, serum sickness.

Metabolic and nutritional disorders: often (≥ 1% - ≤10%) - anorexia (including weight loss) of the body.

From the musculoskeletal system: infrequently (≥ 0.1% - ≤1%) - muscle twitching.

From the side of the central nervous system: very often (≥ 10%) - headache; often (≥ 1% - ≤10%) - impaired attention, dizziness, lethargy, drowsiness (including hyperdrowsiness, sedation), tremor; infrequently (≥ 0.1% - ≤1%) - psychomotor agitation, hyperactivity, ataxia, impaired coordination, bruxism, dyskinesia, myoclonus; rarely (≤ 0.1%) - bucco-glossal syndrome, convulsions, serotonin syndrome.

Mental disorders: very often (≥ 10%) - insomnia (including early morning awakening, initial and secondary insomnia); often (≥ 1% - ≤ 10%) - unusual dreams (including nightmares), nervousness, tension, decreased libido (including lack of libido), euphoria, sleep disturbance; infrequently (≥ 0.1% - ≤1%) - depersonalization, hyperthymia, orgasm disturbance (including anorgasmia), thought disorders; rarely (≤ 0.1%) - manic disorders.

From the side of the skin: often (≥ 1% - ≤10%) - hyperhidrosis, pruritus, polymorphic skin rash, urticaria; infrequently (≥ 0.1% - ≤1%) - ecchymosis, tendency to bruising, alopecia, cold sweat; rarely (≤ 0.1%) - angioedema, photosensitivity reactions.

From the sense organs: often (≥ 1% - ≤10%) - blurred vision; infrequently (≥ 0.1% - ≤1%) - mydriasis.

From the genitourinary system: often (≥ 1% - ≤10%) - frequent urination (including pollakiuria), ejaculation disorder (including lack of ejaculation, dysfunctional ejaculation, early ejaculation, delayed ejaculation, retrograde ejaculation), erectile dysfunction, gynecological bleeding (including .h bleeding from the cervix, dysfunctional uterine bleeding, bleeding from the genital tract, menometrorrhagia, menorrhagia, metrorrhagia, polymenorrhea, postmenopausal bleeding, uterine bleeding, vaginal bleeding); infrequently (≥ 0.1% - ≤1%) - dysuria; rarely (≤ 0.1%) - sexual dysfunction, priapism.

Post-marketing messages

From the endocrine system cases of insufficiency of antidiuretic hormone were noted.

These side effects often occur at the beginning of fluoxetine therapy or with an increase in the dose of the drug.

Overdose:

Symptoms: psychomotor agitation, seizures, drowsiness, cardiac arrhythmias, tachycardia, nausea, vomiting.

Other serious symptoms of fluoxetine overdose (whether fluoxetine taken alone or concomitantly with other drugs) included coma, delirium, QT interval prolongation, and ventricular tachyarrhythmia, including ventricular fibrillation and cardiac arrest, decreased blood pressure, syncope, mania, pyrexia, stupor, and a neuroleptic malignant syndrome-like condition

Treatment: specific antagonists to fluoxetine have not been found. Symptomatic therapy is carried out, gastric lavage with the appointment of activated charcoal, with convulsions - diazepam, maintenance of breathing, cardiac activity, body temperature.

Use during pregnancy and lactation:

Contraindicated in pregnancy and lactation.

Interaction with other drugs:

Fluoxetine and its main metabolite, norfluoxetine, have long half-lives, which must be considered when fluoxetine is combined with other drugs, as well as when it is replaced by another antidepressant.

You can not use the drug simultaneously with MAO inhibitors, incl. antidepressants - MAO inhibitors; furazolidone, procarbazine, selegiline, as well as tryptophan(precursor of serotonin), since it is possible to develop a serotonergic syndrome, manifested in confusion, hypomania, psychomotor agitation, convulsions, dysarthria, hypertensive crises, chills, tremors, nausea, vomiting, diarrhea.

After the use of MAO inhibitors, the appointment of fluoxetine is allowed no earlier than 14 days. MAO inhibitors should not be used earlier than 5 weeks after the abolition of fluoxetine.

Simultaneous administration of drugs metabolized with the participation of the CYP2D6 isoenzyme ( carbamazepine, diazepam, propafenone) with fluoxetine should be carried out using the minimum therapeutic doses. Fluoxetine blocks the metabolism of tricyclic and tetracyclic antidepressants trazodone, metoprolol, terfenadine, which leads to an increase in their concentration in the blood serum, enhancing their action and increasing the frequency of complications.

Patients on stable maintenance doses phenytoin, plasma concentrations of phenytoin increased significantly and symptoms of phenytoin intoxication (nystagmus, diplopia, ataxia and CNS depression) appeared after the start of concomitant treatment with fluoxetine.

The combined use of fluoxetine and lithium salts, requires careful monitoring of the concentration of lithium in the blood, tk. it is possible to increase it.

Fluoxetine enhances the effect hypoglycemic drugs.

With simultaneous use with drugs with a high degree of protein binding, especially with anticoagulants and digitoxin may increase plasma concentrations of free (unbound) drugs and increase the risk of adverse effects.

Special instructions and precautions:

Careful monitoring of patients with suicidal tendencies is required, especially at the beginning of treatment. The risk of suicide is highest in patients who have previously taken other antidepressants and in patients who experience excessive fatigue, hypersomnia, or restlessness during treatment with fluoxetine. Until a significant improvement in treatment occurs, such patients should be under the supervision of a physician.

In children, adolescents and young people (under 24 years of age) with depression, other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing fluoxetine or any other antidepressants in children, adolescents and young adults (under 24 years of age), the risk of suicide should be correlated with the benefits of their use. In short-term studies, the risk of suicide did not increase in people over 24 years of age, and slightly decreased in people over 65 years of age. Any depressive disorder in itself increases the risk of suicide. Therefore, during treatment with antidepressants, all patients should be monitored for early detection of violations or changes in behavior, as well as suicidal tendencies.

Against the background of electroconvulsive therapy, the development of prolonged epileptic seizures is possible.

The interval between the end of therapy with MAO inhibitors and the start of treatment with fluoxetine should be at least 14 days; between the end of treatment with fluoxetine and the start of therapy with MAO inhibitors - at least 5 weeks.

After discontinuation of the drug, its therapeutic concentration in the blood serum may persist for several weeks.

Patients with diabetes may develop hypoglycemia during fluoxetine therapy and hyperglycemia after its withdrawal. Doses of insulin and/or oral hypoglycemic agents may need to be adjusted at the start or after treatment with fluoxetine.

When treating patients with underweight, anorexigenic effects should be taken into account (progressive weight loss is possible).

While taking fluoxetine, you should refrain from drinking alcohol, because. the drug enhances the effect of alcohol.

Influence on the ability to drive vehicles and control mechanisms

Taking fluoxetine can adversely affect the performance of work that requires a high rate of mental and physical reactions (management of mechanical

For impaired renal function

Fluoxetine is metabolized in the liver and excreted by the kidneys and through the gastrointestinal tract. When taking fluoxetine at a dose of 20 mg / day for two months, there were no differences in the concentration of fluoxetine and norfluoxetine in the blood plasma of healthy individuals with normal renal function and patients with severely impaired renal function (creatinine clearance 10 ml / min) requiring hemodialysis.

For impaired liver function

Fluoxetine is metabolized in the liver and excreted by the kidneys and through the gastrointestinal tract. In patients with severe hepatic impairment, it is recommended to prescribe lower doses of fluoxetine, or to prescribe the drug every other day.

Use in the elderly

There are no data on changes in doses depending on age. Start treatment elderly patients followed by a dose of 20 mg/day.

Application in childhood

In children and adolescents with depression, other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing fluoxetine or any other antidepressants in this category of patients, the risk of suicide should be correlated with the benefits of their use.

Storage conditions:

In a dry, dark place at a temperature not exceeding 25°C. Keep out of the reach of children.