Fluoxetine Canon 20 mg 30 capsules

- major depressive episodes;
- nervous bulimia: as an adjunct to psychotherapy for reducing uncontrolled eating;
- obsessive-compulsive disorder.

For oral administration.
Fluoxetine can be taken once a day or several times a day in divided doses - during or between meals (regardless of food intake).
Major depressive episodes
Adults and elderly patients: the recommended daily dose is 20 mg. If necessary, within 3-4 weeks after starting therapy and subsequently based on clinical indications, the dose may be reviewed and adjusted. Despite the potential risk of increased frequency of adverse effects with dose escalation, in some patients who show insufficient response to therapy at a dose of 20 mg, the dose may be gradually increased to 60 mg (maximum dose). Dose adjustment should be done cautiously based on the needs of each individual patient - ensuring that the patient continues to receive the minimum effective dose.
To achieve sustained remission, the duration of therapy for patients suffering from depression should be at least 6 months.
Bulimia nervosa
Adults and elderly patients: the recommended daily dose is 60 mg. The efficacy in the long term (beyond 3 months) for bulimia nervosa has not been demonstrated.
Obsessive-compulsive disorder
Adults and elderly patients: the recommended daily dose is 20 mg. In some patients, if there is insufficient response at a dose of 20 mg after two weeks, the dose may be gradually increased to a maximum of 60 mg. If there is no improvement within 10 weeks, the therapy with fluoxetine should be reconsidered. Upon achieving a good therapeutic response, therapy may be extended using a dose adjusted based on the individual needs of the patient. Despite the lack of systematic studies addressing the duration of fluoxetine therapy, it should be noted that obsessive-compulsive disorder (OCD) is a chronic condition, and in patients responding to therapy, it makes sense to continue treatment for more than 10 weeks. Dose adjustment should be done cautiously, based on the individual needs of the patient, ensuring that the patient continues to receive the minimum effective dosage. Periodic reassessment of the need for therapy should be conducted. For patients who show a good response to pharmacotherapy, some physicians recommend concurrent behavioral psychotherapy. The efficacy of fluoxetine in the long term (beyond 24 weeks) for the treatment of OCD has not been demonstrated.
All indications
The recommended dose may be decreased or increased. Systematic study of doses exceeding 80 mg/day has not been conducted.
Elderly patients
Dose increases should be done with caution; in general, daily doses should not exceed 40 mg. The maximum recommended dose is 60 mg/day.
Liver insufficiency
In patients with liver insufficiency, the drug is prescribed at a reduced dose or with reduced frequency (e.g., 20 mg every other day). These recommendations also apply to patients taking concomitant medications that may interact with fluoxetine.
Withdrawal symptoms observed upon discontinuation of fluoxetine therapy
Abrupt discontinuation of the drug should be avoided. To reduce the risk of developing "withdrawal syndrome," the dose of fluoxetine should be gradually decreased over at least one to two weeks when discontinuing therapy. If intolerable symptoms develop after dose reduction or after stopping treatment, the drug should be resumed at the previously prescribed dose. Subsequently, the physician may prescribe a more gradual dose reduction.
After discontinuation of the drug, the active substance remains in the body for several weeks. This fact should be considered when initiating or terminating therapy.

1 capsule contains:
active ingredient: fluoxetine hydrochloride 22.36 mg, equivalent to fluoxetine 20.00 mg;
excipients: corn starch 24.84 mg, lactose monohydrate 51.80 mg, magnesium stearate 1.00 mg;
hard gelatin capsule No. 3 48 mg, including: body: gelatin 28.2043 mg, indigo carmine dye 0.0197 mg, titanium dioxide 0.5760 mg; cap: gelatin 18.8029 mg, indigo carmine dye 0.0131 mg, titanium dioxide 0.3840 mg.

Hard gelatin capsules No. 3, with a blue body and cap. The contents of the capsules are a mixture of granules and powder that is white or white with a yellowish tint. The presence of individual clumps that break apart with light pressure from a glass rod is permissible.

• hypersensitivity to the drug and to any of the excipients;

• age under 18 years;

• simultaneous use of monoamine oxidase inhibitors (MAOIs) and the period of 14 days after their discontinuation. A minimum 5-week interval should be maintained between stopping fluoxetine and starting MAO. If fluoxetine is prescribed for long-term use and/or in high doses, the interval before using MAO should be extended;

• simultaneous use of metoprolol, used for the treatment of heart failure.
Pregnancy and lactation:
Pregnancy
Some epidemiological studies have suggested that the use of fluoxetine during the first trimester of pregnancy may increase the risk of developing cardiovascular defects. The mechanism is unknown. Overall, according to available data, the risk of giving birth to a child with a cardiovascular defect after maternal exposure to fluoxetine is approximately 2/100 compared to the expected frequency of such defects in the population of about 1/100.
According to epidemiological data, the use of SSRIs during pregnancy, especially in the later stages, may increase the risk of developing persistent pulmonary hypertension in newborns (approximately 5 cases per 1000 pregnancies, whereas in the general population, there are 1-2 cases of persistent pulmonary hypertension in newborns per 1000 pregnancies).
Fluoxetine should not be prescribed during pregnancy except in cases where the clinical condition of the woman necessitates fluoxetine therapy and justifies the potential risk to the fetus. Abrupt discontinuation of therapy during pregnancy should be avoided. Caution should be exercised when using fluoxetine during pregnancy, especially in the later stages or just before delivery, as newborns have been reported to exhibit effects such as irritability, tremor, hypotonia, persistent crying, difficulty feeding or sleeping. These symptoms may indicate a serotonergic effect or withdrawal syndrome. The timing and duration of these symptoms may be related to the long half-life of fluoxetine (4-6 days) and its active metabolite, norfluoxetine (4-16 days).
Breastfeeding
Fluoxetine and its metabolite norfluoxetine are found in breast milk. Adverse events have been reported in breastfed infants. If fluoxetine is necessary, breastfeeding should be discontinued, or consideration should be given to administering lower doses of fluoxetine.

Suicidal Risk
Depression is associated with an increased risk of suicidal thoughts, self-harm (self-injury), and suicidal behavior. This risk persists until a stable remission is achieved. Since improvement may not occur during the first few weeks of treatment, careful monitoring by the treating physician is necessary until the patient's condition improves. Clinical practice shows that the risk of suicide may increase in the early stages of recovery. Other psychiatric disorders for which fluoxetine is prescribed may also be associated with an increased risk of suicidal behavior. Additionally, these disorders may co-occur with major depressive disorder. Therefore, the same caution should be exercised when treating patients with other psychiatric disorders as with those with major depressive disorder.
Patients with a history of suicidal behavior, who exhibit suicidal thoughts prior to the start of therapy, are considered at increased risk for suicidal thoughts or behavior. These patients should be closely monitored during therapy.
A meta-analysis of placebo-controlled clinical trials of antidepressants used to treat psychiatric disorders in adult patients showed that among patients under 25 years of age, the use of antidepressants is associated with an increased risk of suicidal behavior compared to patients receiving placebo.
Careful monitoring of patients, particularly those at high risk for developing suicidal behavior, is essential, especially in the early stages of treatment and during subsequent dose adjustments. Patients (as well as their caregivers) should be warned to monitor for any clinical deterioration, signs of suicidal behavior or thoughts, and unusual changes in behavior, and should immediately contact their physician if these symptoms occur.

Cardiovascular Effects
Fluoxetine may cause QT interval prolongation, as well as the potential development of ventricular arrhythmias or Torsades de Pointes, as reported in post-marketing studies of fluoxetine. Fluoxetine should be used with caution in patients with congenital long QT syndrome, acquired long QT syndrome (e.g., when fluoxetine is taken with drugs that prolong the QT interval), a family history of prolonged QT interval, other clinical conditions predisposing to arrhythmias (e.g., hypokalemia, hypomagnesemia, bradycardia, acute myocardial infarction, decompensated heart failure), and in cases of increased fluoxetine exposure (e.g., in patients with reduced liver function). Patients with stable heart disease should undergo an ECG before starting fluoxetine therapy. If signs of arrhythmia develop during therapy, fluoxetine should be discontinued and an ECG performed.

Skin Rash
Patients taking fluoxetine have reported skin rash, anaphylactic reactions, and progressive systemic disorders, sometimes serious, involving the skin, kidneys, liver, and lungs. If a skin rash or other possible allergic reactions of unknown etiology occur, fluoxetine should be discontinued.

Epileptic Seizures
As with other antidepressants, fluoxetine should be prescribed with caution to patients with a history of epileptic seizures. Fluoxetine therapy should be discontinued if any patient develops epileptic seizures. Fluoxetine should not be prescribed to patients with unstable epilepsy; patients with controlled epilepsy require careful monitoring.

Electroconvulsive Therapy
In patients receiving electroconvulsive therapy, prolonged seizures have been rarely reported with fluoxetine use. Caution is advised when treating such patients with fluoxetine.

Mania
Antidepressants should be used with caution in patients with a history of mania/hypomania. Fluoxetine, like any antidepressant, should be discontinued if the patient is in a manic state.

Akathisia/Psychomotor Agitation
Fluoxetine use can lead to the development of akathisia, which manifests as subjective feelings of discomfort or restlessness, a need for constant movement, often with an inability to sit or stand still. These phenomena are most commonly observed during the first few weeks of treatment. In patients with these symptoms, increasing the dose of fluoxetine may have negative consequences.

Withdrawal Symptoms
Withdrawal symptoms have often been noted upon discontinuation of fluoxetine therapy, especially with abrupt cessation. In clinical studies, approximately 60% of patients experienced various withdrawal phenomena upon discontinuation of therapy, both in the fluoxetine group and the placebo group. In the fluoxetine group, 17% of these phenomena were severe, while in the placebo group, 12% were severe.
The risk of developing withdrawal symptoms depends on several factors, including the duration of therapy, dosage, and rate of dose reduction. The most commonly reported symptoms include dizziness, sensory disturbances (including paresthesia), sleep disturbances (including insomnia and vivid dreams), asthenia, anxiety or agitation, nausea and/or vomiting, tremor, and headache. These episodes were usually mild to moderate in severity, but some patients may experience more pronounced symptoms. In most cases, these phenomena resolve spontaneously within two weeks, but they may sometimes last longer (2-3 months or more). Therefore, fluoxetine therapy should be discontinued gradually over one to two weeks, depending on the patient's needs.

Tamoxifen
Fluoxetine, as a potent inhibitor of the CYP2D6 isoenzyme, may lead to decreased concentrations of endoxifen, one of the most important active metabolites of tamoxifen.
Therefore, fluoxetine should be avoided during tamoxifen therapy.

Weight Loss
Weight loss may occur in patients taking fluoxetine; however, it is usually proportional to the initial average body weight.

Hyponatremia
Cases of hyponatremia have been reported (in some cases, serum sodium levels were less than 110 mmol/L). Such cases primarily occurred in elderly patients, patients receiving diuretics, and patients with reduced circulating blood volume.

Diabetes Mellitus
In patients with diabetes mellitus during fluoxetine treatment, hypoglycemia was noted, and after discontinuation of the drug, hyperglycemia developed. Dose adjustments of insulin and/or oral hypoglycemic agents may be required at the beginning or after the end of fluoxetine treatment.

Liver/Kidney Insufficiency
Fluoxetine undergoes extensive metabolism in the liver and is excreted by the kidneys. Patients with significant liver dysfunction are recommended to be prescribed lower doses of fluoxetine or to take the drug every other day. In patients with severe renal insufficiency (GFR < 10 mL/min) requiring hemodialysis, no differences in plasma concentrations of fluoxetine and norfluoxetine were found when compared to patients in the control group with normal kidney function after taking fluoxetine at a dose of 20 mg/day for two months.Mydriasis Mydriasis associated with fluoxetine use has been reported. Caution should be exercised when prescribing fluoxetine to patients with increased intraocular pressure or those at risk of developing acute angle-closure glaucoma.Bleeding The use of SSRIs has been associated with ecchymosis, purpura, and other similar disorders related to increased bleeding risk. Ecchymosis has been reported rarely. Other hemorrhagic events (gynecological bleeding, gastrointestinal bleeding, etc.) have been noted infrequently. Caution should be exercised when treating with fluoxetine, particularly in patients receiving concomitant therapy with oral anticoagulants and other drugs affecting platelet function (e.g., atypical antipsychotics such as clozapine, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, non-steroidal anti-inflammatory drugs), as well as in patients with a history of bleeding.Symptoms Similar to Serotonin Syndrome or Neuroleptic Malignant Syndrome In rare cases, serotonin syndrome or neuroleptic malignant syndrome associated with fluoxetine use has been reported, especially when used in conjunction with other serotonergic agents (including those containing L-tryptophan) and/or neuroleptics. Since these syndromes can lead to life-threatening conditions, fluoxetine therapy should be discontinued if symptoms such as hyperthermia, rigidity, myoclonus, autonomic nervous system disturbances, changes in mental state including confusion, irritability, extreme agitation with possible development of delirium and coma occur, and necessary symptomatic therapy should be initiated. All patients taking antidepressants for any indication should be under appropriate supervision, with careful monitoring for signs of clinical deterioration, suicidal intentions, and unusual changes in behavior, especially during the first months of therapy or during dose changes (increases or decreases).Effects on the Ability to Drive and Operate Machinery: Fluoxetine does not have any effect or has minimal effect on the ability to drive vehicles and operate machinery. Therapy with any psychoactive drugs may affect judgment, thinking, or motor skills. Patients should be advised to avoid driving a car or operating hazardous machinery until they are sufficiently confident that the drug does not affect them.

The most commonly reported adverse reactions in patients receiving fluoxetine treatment include headache, nausea, insomnia, weakness, and diarrhea. The intensity and frequency of adverse effects may decrease as therapy continues, so their occurrence does not always lead to discontinuation of therapy.
The table below presents the adverse events observed during fluoxetine therapy. Some of these adverse reactions also occur with other SSRIs.
The information on the frequency of adverse reactions provided below was calculated based on clinical studies involving adult patients, as well as spontaneous reports.
The following criteria were used to assess the frequency of adverse effects: very common (>1/10); common (>1/100, 1/1000, 1/10000, 450 msec.)8 Ventricular arrhythmia, including Torsades de Pointes
Disorders of the blood vessels
"Hot flashes"9 Decreased blood pressure Vasculitis
Vasodilation
Disorders of the respiratory system, thoracic organs, and mediastinum
Yawning Dyspnea
Nosebleeds Pharyngitis
Inflammatory processes in the lungs of various histopathologies and/or fibrosis10
Disorders of the gastrointestinal tract
Diarrhea
Nausea Vomiting
Dyspepsia
Dry mouth Dysphagia
Gastrointestinal bleeding11 Esophageal pain
Disorders of the liver and biliary tract
Idiosyncratic hepatitis
Disorders of the skin and subcutaneous tissue
Rash12
Urticaria
Itching
Hyperhidrosis Alopecia
Tendency to bruise
Cold sweat Angioedema
Ecchymosis
Photosensitivity
Erythema multiforme
Stevens-Johnson syndrome
Toxic epidermal necrolysis (Lyell's syndrome)
Purpura
Disorders of the musculoskeletal and connective tissue
Allergy Muscle twitching Myalgia
Disorders of the kidneys and urinary tract
Frequent urges to urinate13 Dysuria Urination disorder
Urinary retention
Disorders of the genital organs and breast
Gynecological bleeding14
Erectile dysfunction
Ejaculation disorder15 Sexual dysfunction Galactorrhea
Hyperprolactinemia
Priapism
General disorders and administration site reactions
Lethargy16 Feeling of anxiety
Chills Malaise
Feeling unwell
Feeling cold
Feeling hot Mucosal hemorrhages
Laboratory and instrumental data
Weight loss Increased transaminase levels
Increased gamma-glutamyltransferase levels
1 Including anorexia
2 Including early morning awakenings, difficulty falling asleep, nighttime awakenings
3 Including loss of libido
4 Including nightmares
5 Including anorgasmia
6 Including completed suicide, suicidal depression, intentional self-harm, self-harm thoughts, suicidal behavior, suicidal thoughts, suicide attempts, dark thoughts, auto-aggressive behavior. These symptoms may be due to an underlying condition
7 Including daytime drowsiness and sedative effect
8 Based on ECG results obtained during clinical studies
9 Including hot flashes
10 Including atelectasis, interstitial lung disease, pneumonia
11 Including gum bleeding, hematochezia, bloody vomiting, bloody diarrhea, melena, rectal bleeding, hemorrhagic ulcer disease of the stomach
12 Including erythema, peeling, sweat rash, erythematous rash, follicular rash, diffuse rash, macular rash, maculopapular rash, morbilliform rash, papular rash, itchy rash, vesicular rash, umbilical rash
13 Including pollakiuria
14 Including cervical bleeding, uterine dysfunction, uterine bleeding, genital bleeding, menometrorrhagia, menorrhagia, metrorrhagia, polymenorrhea, postmenopausal bleeding, vaginal bleeding
15 Including absence of ejaculation, ejaculatory dysfunction, premature ejaculation, delayed ejaculation, retrograde ejaculation
16 Including asthenia
Description of individual adverse reactions
Cases of suicidal thoughts and suicidal behavior have been reported during fluoxetine therapy or shortly after its discontinuation.
Bone fractures: data from epidemiological studies, primarily among patients aged 50 and older, indicate an increased risk of bone fractures in patients receiving selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). The reasons for this increased risk are not established.
Withdrawal symptoms that may occur upon discontinuation of fluoxetine
Discontinuation of fluoxetine usually leads to the development of withdrawal symptoms. The most commonly reported reactions include dizziness, sensory disturbances (including paresthesias), sleep disturbances (including insomnia and vivid dreams), asthenia, agitation or anxiety, irritability, nausea and vomiting, tremor, and headache.
Generally, these phenomena are mild to moderate in severity and resolve spontaneously.
However, in some patients, they may be more pronounced and prolonged. Therefore, patients who no longer require fluoxetine therapy are advised to discontinue the medication gradually by reducing the dose.

Symptoms
Cases of overdose with fluoxetine alone are usually characterized by a mild course. Symptoms of overdose include nausea, vomiting, seizures, cardiovascular disturbances ranging from asymptomatic arrhythmias (including atrioventricular rhythm and ventricular arrhythmia) or ECG changes typical of prolonged QTc interval to cardiac arrest (including very rare cases of torsades de pointes), respiratory system disturbances, and signs of altered CNS status ranging from agitation to coma. Fatal cases due to fluoxetine overdose have been reported very rarely.
Treatment
It is recommended to monitor the overall condition and cardiac activity, along with providing general symptomatic and supportive measures. A specific antidote is unknown. The effectiveness of forced diuresis, dialysis, hemoperfusion, and cross-transfusion is low. Activated charcoal, used in combination with sorbitol, may be as effective or more effective compared to inducing vomiting or gastric lavage.
When treating an overdose, the influence of multiple drug use should be considered. Patients who have taken a large amount of tricyclic antidepressants, if they are concurrently taking or have recently taken fluoxetine, may require a longer period of medical observation.

Fluoxetine and its main metabolite norfluoxetine have long half-lives, which should be considered when combining fluoxetine with other medications, as well as when switching fluoxetine to another antidepressant. Fluoxetine has a high affinity for plasma proteins, so combining fluoxetine with other drugs that also significantly bind to plasma proteins may lead to changes in their concentrations.

Combinations of drugs whose use is contraindicated:
Irreversible non-selective monoamine oxidase inhibitors (e.g., phenelzine)
Patients taking SSRIs in combination with irreversible non-selective monoamine oxidase inhibitors (MAOIs) have reported serious reactions, sometimes with fatal outcomes. These cases were characterized by symptoms resembling serotonin syndrome (which can be confused with neuroleptic malignant syndrome). Patients experiencing such reactions may be prescribed cyproheptadine or dantrolene. Symptoms of drug interaction with MAOIs include: hyperthermia, muscle rigidity, myoclonus (myoclonic seizures), autonomic nervous system disturbances with possible rapid fluctuations in blood pressure and heart rate, as well as changes in mental state, including confusion, irritability, and excessive agitation, progressing to delirium and coma. Therefore, fluoxetine is contraindicated in combination with irreversible non-selective MAOIs. Since the effects of these MAOIs persist for 2 weeks, fluoxetine therapy should not be initiated earlier than 2 weeks after discontinuation of irreversible non-selective MAOIs. Similarly, therapy with irreversible non-selective MAOIs should not be started earlier than 5 weeks after discontinuation of fluoxetine.

Metoprolol, prescribed for heart failure
Due to fluoxetine inhibiting the metabolism of metoprolol, the risk of adverse effects while taking metoprolol, including severe bradycardia, may increase.

Combinations of drugs not recommended for use:
Tamoxifen
Fluoxetine, as a potent inhibitor of the CYP2D6 isoenzyme, reduces the concentration of the active metabolite of tamoxifen (endoxifen) in plasma by 65-75% when used concurrently. Therefore, fluoxetine should be avoided during tamoxifen therapy.

Alcohol
In experimental studies, fluoxetine did not increase blood alcohol concentration or enhance the effects of alcohol. However, concurrent use of SSRIs and alcohol is not recommended.

MAO-A, linezolid, and methylthioninium chloride (methylene blue)
There is a risk of developing serotonin syndrome, which includes diarrhea, tachycardia, sweating, tremor, confusion, or coma. If concurrent use of these active substances with fluoxetine is unavoidable, careful clinical monitoring is necessary, and the administration of MAO-A, linezolid, and methylthioninium chloride should start with the minimum recommended doses.

Mequitazine
Due to fluoxetine inhibiting the metabolism of mequitazine, the risk of adverse effects while taking mequitazine (e.g., QT interval prolongation) may be increased.

Combinations of drugs requiring special caution when prescribed:
Phenytoin
When prescribed in combination with fluoxetine, changes in phenytoin concentration in the blood have been observed. In some cases, signs of toxicity were noted. When these drugs are used together, the dose of the concomitant drug should be gradually increased, and clinical monitoring should be ensured.

Serotonergic drugs (lithium, tramadol, triptans, tryptophan, selegiline (MAO-B), St. John's wort (Hypericum perforatum))
When SSRIs are prescribed with serotonergic drugs, cases of mild serotonin syndrome have been reported. Therefore, concurrent use of fluoxetine with these drugs should be conducted with caution.

Drugs that prolong the QT interval
Pharmacokinetic and pharmacodynamic studies of fluoxetine's interaction with other drugs that prolong the QT interval have not been conducted. However, the additive effect of fluoxetine and these drugs cannot be excluded. Caution should be exercised when concurrently prescribing fluoxetine with drugs that prolong the QT interval (with antiarrhythmic agents of class IA and III, antipsychotic drugs (phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents (sparfloxacin, moxifloxacin, erythromycin IV, pentamidine), antimalarial agents (halofantrine), and some antihistamines (astemizole, mizolastine)).

Drugs affecting hemostasis (oral anticoagulants, regardless of their mechanism of action, drugs preventing aggregation, including aspirin and NSAIDs)
When prescribed concurrently with oral anticoagulants, clinical monitoring with more frequent INR checks is necessary due to the possible increased risk of bleeding. During fluoxetine therapy and after its discontinuation, dose adjustment of drugs affecting hemostasis may be required.

Cyproheptadine
When fluoxetine is used in combination with cyproheptadine, isolated cases of reduced antidepressant activity of fluoxetine have been reported.

Drugs causing hyponatremia
Hyponatremia is a side effect of fluoxetine. The use of fluoxetine in combination with other drugs associated with the development of hyponatremia (e.g., diuretics, desmopressin, carbamazepine, and oxcarbazepine) may lead to an increased risk of this condition.

Drugs lowering the seizure threshold
Adverse effects such as epileptiform seizures may occur while taking fluoxetine. The use of fluoxetine in combination with other drugs that lower the convulsive threshold (such as tricyclic antidepressants, other SSRIs, phenothiazines, butyrophenones, mefloquine, chloroquine, bupropion, tramadol) may lead to an increased risk of this phenomenon.

Other drugs metabolized by the CYP2D6 isoenzyme
Fluoxetine is a potent inhibitor of the CYP2D6 isoenzyme; therapy in combination with drugs metabolized by this isoenzyme may lead to drug interactions, especially when used in combination with drugs that have a narrow therapeutic range (such as flecainide, propafenone, and nebivolol), with titratable drugs, as well as with atomoxetine, carbamazepine, tricyclic antidepressants, and risperidone. The use of these drugs should start at or be adjusted to the minimum dose. Similar dose adjustments should be made if fluoxetine has been used in the preceding 5 weeks.

The drug Fluoxetine is an antidepressant, a selective serotonin reuptake inhibitor (SSRI), which defines its mechanism of action. Fluoxetine has virtually no affinity for other receptors, such as α1-, α2- and β-adrenergic, serotonergic, dopaminergic, histaminergic, muscarinic, and GABA receptors.

Absorption
When taken orally, fluoxetine is well absorbed. Food intake does not affect the bioavailability of this medication.
Distribution
Fluoxetine is significantly bound to plasma proteins (about 95%) and is characterized by a large volume of distribution (20-40 L/kg). The maximum concentration in plasma is reached within 6-8 hours. Steady-state plasma concentration is achieved after several weeks of medication use. The steady-state concentration after prolonged use of the medication is similar to the concentration observed in the 4th-5th week of treatment.
Metabolism
After 30 days of taking the medication at a dose of 40 mg/day, fluoxetine plasma concentrations ranged from 91 to 302 pg/ml, and norfluoxetine concentrations ranged from 72 to 258 pg/ml. In a portion (approximately 7%) of the population, reduced activity of the cytochrome P450 2D6 isoenzyme (CYP2D6 isoenzyme), which metabolizes fluoxetine, was observed. These patients are referred to as "slow metabolizers" of medications such as debrisoquine, dextromethorphan, and tricyclic antidepressants (TCAs). In a study using labeled and unlabeled enantiomers administered as a racemic mixture, the metabolism of S-fluoxetine in these patients was slower, and consequently, their S-fluoxetine concentrations were higher. Accordingly, the steady-state concentration of S-norfluoxetine was lower. The metabolism of S-fluoxetine in these patients is equivalent to that in the entire population. When compared to normal metabolizers, the total steady-state plasma concentrations of the 4 active enantiomers in slow metabolizers were not significantly higher. Therefore, the overall pharmacological activity was virtually the same. The metabolism of fluoxetine also occurs through alternative non-CYP2D6 pathways. This explains the achievement of steady-state levels of fluoxetine instead of an unrestricted increase in concentration. Since the metabolism of fluoxetine, like that of some other compounds, including TCAs and other selective serotonin reuptake inhibitors (SSRIs), involves the CYP2D6 isoenzyme system, concomitant use with medications that are also metabolized by this enzyme system (such as TCAs) may lead to drug interactions.
Excretion
The half-life of fluoxetine is between 4 to 6 days, while the half-life of norfluoxetine is between 4 to 16 days. Therefore, the medication can be detected in plasma for 5-6 weeks after therapy is discontinued. Fluoxetine is primarily excreted by the kidneys (about 60%).
Special patient groups
Elderly patients
Pharmacokinetic parameters in healthy elderly patients are comparable to those in younger patients.
Liver insufficiency
In cases of liver insufficiency (alcoholic liver cirrhosis), the half-lives of fluoxetine and norfluoxetine increased to 7 and 12 days, respectively. In liver insufficiency, a reduction in the dose or frequency of medication administration may be required.
Renal insufficiency
After a single dose of fluoxetine in patients with mild, moderate, or severe (anuria) renal insufficiency, pharmacokinetic parameters did not change compared to those in healthy volunteers. However, after repeated administration, an extension of the plateau of steady-state plasma concentration of the medication may be observed.