Fluoxetine (Capsules) Instructions for Use

ATC Code

N06AB03 (Fluoxetine)

Active Substance

Fluoxetine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antidepressant

Pharmacotherapeutic Group

Antidepressant

Pharmacological Action

An antidepressant from the group of selective serotonin reuptake inhibitors. It has thymoanaleptic and stimulating effects.

It selectively blocks the neuronal reuptake of serotonin (5HT) in the synapses of the central nervous system neurons. Inhibition of serotonin reuptake leads to an increase in the concentration of this neurotransmitter in the synaptic cleft, enhancing and prolonging its action on postsynaptic receptor sites. By increasing serotonergic transmission, Fluoxetine inhibits neurotransmitter metabolism via the negative membrane feedback mechanism. With prolonged use, Fluoxetine suppresses the activity of 5-HT1 receptors. It has a weak effect on the reuptake of norepinephrine and dopamine. It does not have a direct effect on serotonin, m-cholinergic, H1-histaminergic, and alpha-adrenergic receptors. Unlike most antidepressants, it does not cause a reduction in the activity of postsynaptic beta-adrenergic receptors.

It is effective in endogenous depressions and obsessive-compulsive disorders. It has an anorexigenic effect and may cause weight loss. It does not cause orthostatic hypotension, a sedative effect, and is not 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 administered dose); administration with food slightly slows the absorption of fluoxetine. C_max 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, and plasma protein binding is more than 90%. It is metabolized in the liver by demethylation to the active metabolite norfluoxetine and a number of unidentified metabolites. It is excreted by the kidneys as metabolites (80%) and through the intestines (15%), mainly in the form of glucuronides. T_1/2 of fluoxetine after reaching a steady-state plasma concentration is about 4-6 days. T_1/2 of the active metabolite norfluoxetine after a single dose and after reaching a steady-state plasma concentration ranges from 4 to 16 days. In patients with hepatic insufficiency, the half-life of fluoxetine and norfluoxetine is prolonged.

Indications

• Depressions of various origins;
• Obsessive-compulsive disorders;
• Bulimic neurosis.

ICD codes

Dosage Regimen

Capsules

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

Depressive state

The initial dose is 20 mg once a day in the first half of the day, regardless of meals. If necessary, the dose can be increased to 40-60 mg/day, divided into 2-3 doses (by 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 may be achieved later.

Obsessive-compulsive disorders

The recommended dose is 20-60 mg/day.

Bulimic neurosis

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

Use of the drug in patients of different ages

There is no data on dose changes depending on age. Starting treatment for elderly patients should be with a dose of 20 mg/day.

Concomitant diseases

It is recommended to prescribe Fluoxetine to patients with impaired liver or kidney function using low doses and extending the interval between doses.

Adverse Reactions

When using fluoxetine, as in cases of using drugs of the selective serotonin reuptake inhibitor group, the following undesirable phenomena are noted.

From the cardiovascular system: common (≥ 1% – ≤10%) – atrial flutter, hot flashes; uncommon (≥ 0.1% – ≤1%) – hypotension; rare (≤ 0.1%) – vasculitis, vasodilation.

From the digestive system: very common (≥ 10%) – diarrhea, nausea; common (≥ 1% – ≤10%) – dry mouth, dyspepsia, vomiting; uncommon (≥ 0.1% – ≤1%) – dysphagia, taste perversion; rare (≤ 0.1%) – pain along the esophagus.

From the hepatobiliary system: rare (≤ 0.1%) – idiosyncratic hepatitis.

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

Metabolism and nutrition disorders: common (≥ 1% – ≤10%) – anorexia (including weight loss).

From the musculoskeletal system: uncommon (≥ 0.1% – ≤1%) – muscle twitching.

From the CNS: very common (≥ 10%) – headache; common (≥ 1% – ≤10%) – attention disturbance, dizziness, lethargy, drowsiness (including hypersomnolence, sedation), tremor; uncommon (≥ 0.1% – ≤1%) – psychomotor agitation, hyperactivity, ataxia, coordination impairment, bruxism, dyskinesia, myoclonus; rare (≤ 0.1%) – buccoglossal syndrome, seizures, serotonin syndrome.

Mental disorders: very common (≥ 10%) – insomnia (including early morning awakening, initial and middle insomnia); common (≥ 1% – ≤ 10%) – unusual dreams (including nightmares), nervousness, tension, decreased libido (including absence of libido), euphoria, sleep disorder; uncommon (≥ 0.1% – ≤1%) – depersonalization, hyperthymia, orgasm disorder (including anorgasmia), thinking disturbances; rare (≤ 0.1%) – manic disorders.

From the skin: common (≥ 1% – ≤10%) – hyperhidrosis, skin itching, polymorphic skin rash, urticaria; uncommon (≥ 0.1% – ≤1%) – ecchymosis, tendency to bruise, alopecia, cold sweat; rare (≤ 0.1%) – angioedema, photosensitivity reactions.

From the sense organs: common (≥ 1% – ≤10%) – blurred vision; uncommon (≥ 0.1% – ≤1%) – mydriasis.

From the genitourinary system: common (≥ 1% – ≤10%) – frequent urination (including pollakiuria), ejaculation disorder (including absence of ejaculation, dysfunctional ejaculation, premature ejaculation, delayed ejaculation, retrograde ejaculation), erectile dysfunction, gynecological bleeding (including cervical bleeding, dysfunctional uterine bleeding, genital tract bleeding, menometrorrhagia, menorrhagia, metrorrhagia, polymenorrhea, postmenopausal bleeding, uterine bleeding, vaginal bleeding); uncommon (≥ 0.1% – ≤1%) – dysuria; rare (≤ 0.1%) – sexual dysfunction, priapism.

Post-marketing reports

From the endocrine system cases of antidiuretic hormone deficiency have been reported.

The indicated side effects occur more often at the beginning of fluoxetine therapy or when increasing the dose of the drug.

Contraindications

• Concomitant use with MAO inhibitors (and within 14 days after their discontinuation);
• Concomitant use of thioridazine (and within 5 weeks after discontinuation of fluoxetine), pimozide;
• Pregnancy;
• Breastfeeding period;
• Severe renal impairment (creatinine clearance less than 10 ml/min);
• Hepatic insufficiency;
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• Age under 18 years;
• Hypersensitivity to the drug.

With caution

Suicidal risk : in depressions, there is a possibility of suicide attempts, which may persist until stable remission occurs. Isolated 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 similar pharmacological action (antidepressants). Careful monitoring of patients belonging to the risk group is necessary. Doctors should convince patients to immediately report any thoughts and feelings that cause concern.

Epileptic seizures : Fluoxetine should be prescribed with caution to patients who have had epileptic seizures.

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

Diabetes mellitus : glycemic control in diabetic patients during treatment with fluoxetine showed hypoglycemia; after drug withdrawal, hyperglycemia developed. At the beginning or after treatment with fluoxetine, adjustment of insulin and/or oral hypoglycemic drug doses may be required.

Renal/hepatic insufficiency : Fluoxetine is metabolized in the liver and excreted by the kidneys and through the gastrointestinal tract. It is recommended to prescribe lower doses of fluoxetine to patients with significant liver function impairment, or to prescribe the drug every other day. When taking fluoxetine at a dose of 20 mg/day for two months, no differences were found in the plasma concentrations of fluoxetine and norfluoxetine between healthy individuals with normal renal function and patients with significant renal impairment (creatinine clearance 10 ml/min) requiring hemodialysis.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

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

Use in Renal Impairment

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, no differences were found in the plasma concentrations of fluoxetine and norfluoxetine between healthy individuals with normal renal function and patients with significant renal impairment (creatinine clearance 10 ml/min) requiring hemodialysis.

Pediatric Use

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

Geriatric Use

There is no data on dose changes depending on age. Starting treatment for elderly patients should be with a dose of 20 mg/day.

Special 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 motor restlessness during treatment with fluoxetine. Until significant improvement in treatment occurs, such patients should be under medical supervision.

In children, adolescents, and young people (under 24 years) with depression and other mental disorders, antidepressants, compared to placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing fluoxetine or any other antidepressants to children, adolescents, and young people (under 24 years), the risk of suicide and the benefit of their use should be weighed. In short-term studies in people over 24 years, the risk of suicide was not increased, and in people over 65 years it was somewhat reduced. Any depressive disorder itself increases the risk of suicide. Therefore, during treatment with antidepressants, all patients should be monitored for early detection of behavioral disturbances or changes, as well as suicidal tendencies.

During electroconvulsive therapy, prolonged epileptic seizures may develop.

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

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

In patients with diabetes mellitus, hypoglycemia may develop during fluoxetine therapy and hyperglycemia after its withdrawal. At the beginning or after treatment with fluoxetine, adjustment of insulin and/or oral hypoglycemic drug doses may be required.

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

During fluoxetine intake, alcohol consumption should be avoided, as the drug enhances the effect of alcohol.

Effect on ability to drive vehicles and operate machinery

Taking fluoxetine may negatively affect the performance of work requiring high speed of mental and physical reactions (operating machinery

Overdose

Symptoms: psychomotor agitation, convulsive seizures, drowsiness, heart rhythm disturbances, tachycardia, nausea, vomiting.

Other serious symptoms of fluoxetine overdose (both with isolated fluoxetine intake and with simultaneous intake with other drugs) included coma, delirium, QT interval prolongation and ventricular tachyarrhythmia, including ventricular fibrillation – flutter and cardiac arrest, decreased blood pressure, fainting, mania, pyrexia, stupor, and a condition similar to neuroleptic malignant syndrome.

Treatment: specific antagonists to fluoxetine have not been found. Symptomatic therapy is carried out, gastric lavage with the administration of activated charcoal, for convulsions – diazepam, maintaining respiration, cardiac activity, and body temperature.

Drug Interactions

Fluoxetine and its main metabolite norfluoxetine have long half-lives, which must be taken into account when combining fluoxetine with other drugs, as well as when replacing it with another antidepressant.

The drug should not be used simultaneously with MAO inhibitors, including antidepressant MAO inhibitors; furazolidone, procarbazine, selegiline, as well as tryptophan (a serotonin precursor), as the development of serotonergic syndrome is possible, manifested in confusion, hypomanic state, psychomotor agitation, convulsions, dysarthria, hypertensive crises, chills, tremor, nausea, vomiting, diarrhea.

After using MAO inhibitors, fluoxetine should be prescribed no earlier than 14 days later. MAO inhibitors should not be used earlier than 5 weeks after discontinuation of fluoxetine.

Concomitant use 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 serum concentration, enhancing their action and increasing the frequency of complications.

In patients stably taking maintenance doses of phenytoin , phenytoin plasma concentrations increased significantly and symptoms of phenytoin intoxication (nystagmus, diplopia, ataxia, and CNS depression) appeared after starting concomitant treatment with fluoxetine.

Combined use of fluoxetine and lithium salts requires careful monitoring of lithium blood concentration, as its increase is possible.

Fluoxetine enhances the effect of hypoglycemic drugs .

When used concomitantly with drugs that have a high degree of protein binding, especially with anticoagulants and digitoxin , an increase in the plasma concentration of free (unbound) drugs and an increased risk of adverse effects are possible.

Storage Conditions

In a dry place, protected from light, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.