Instructions Fluoxetine film-coated tablets 20 mg No. 20
Composition
active ingredient: fluoxetine;
1 tablet contains fluoxetine hydrochloride 20 mg;
excipients: lactose, monohydrate; corn starch; sugar; talc; calcium stearate; gelatin; Opadry II white, containing: titanium dioxide (E 171), talc, polyethylene glycol, polyvinyl alcohol; Sepispers dry yellow R.
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, light yellow to dark yellow in color.
Pharmacotherapeutic group
Antidepressants. ATX code N06A B03.
Pharmacological properties
Pharmacodynamics
Antidepressant, the mechanism of action of which is due to the selective inhibition of the neuronal reuptake of serotonin in the central nervous system. Fluoxetine is also a weak antagonist of muscarinic, histamine and a-adrenoceptors. Unlike other antidepressants, it does not reduce the functional activity of b-adrenoceptors, has little effect on the neuronal uptake of noradrenaline and dopamine. Helps improve mood, eliminates feelings of fear and tension, dysphoria. Has stimulating and analgesic effects, does not have a sedative and cardiotoxic effect when taken in medium therapeutic doses.
A sustained therapeutic effect develops after 1–2 weeks of continuous use of the drug and lasts for at least 1 week after its discontinuation.
Pharmacokinetics
Absorbed from the digestive tract. Slightly metabolized during the first pass through the liver. Food intake does not affect the extent of absorption, although it may slow down its rate. Maximum plasma concentration is reached after 6–8 hours. Equilibrium plasma concentration is reached only after continuous administration for several weeks. Binding to plasma proteins is 94.5%. Easily penetrates the blood-brain barrier. Metabolized in the liver by demethylation with the formation of the main active metabolite, norfluoxetine. The half-life of fluoxetine is 2–3 days, norfluoxetine is 7–9 days. Excreted by the kidneys (80%) and through the intestines – approximately 15%.
Indication
Major depressive episodes/disorders.
Obsessive-compulsive disorders.
Bulimia nervosa: as part of comprehensive psychotherapy to reduce uncontrolled eating and to cleanse the intestines.
Contraindication
Hypersensitivity to fluoxetine or to any other components of the drug.
Severe hepatic and renal failure, epilepsy, history of convulsions, suicidal thoughts, glaucoma, bladder atony, benign prostatic hyperplasia.
Concomitant use with monoamine oxidase inhibitors (selective, non-selective), including linezolid. The interval between the end of therapy with MAO inhibitors and the start of treatment with fluoxetine should be at least 14 days. The interval between the end of treatment with fluoxetine and the start of treatment with MAO inhibitors should be at least 5 weeks.
Interaction with other medicinal products and other types of interactions
The period between discontinuation of MAO inhibitors and initiation of treatment with the drug should be at least 14 days. After discontinuation of fluoxetine, at least 5 weeks should elapse before initiation of therapy with MAO inhibitors. Severe, sometimes fatal reactions (hyperthermia, rigidity, myoclonus, autonomic instability, rapid changes in vital signs and impaired brain function, including severe agitation, delirium and coma) have been observed in patients taking fluoxetine in combination with MAO inhibitors, as well as in those who stopped taking it and then started therapy with MAO inhibitors. The simultaneous use of fluoxetine with MAO inhibitors is contraindicated.
The long half-lives of both fluoxetine and norfluoxetine should be taken into account when considering pharmacodynamic and pharmacokinetic drug interactions (e.g., when switching from fluoxetine to other antidepressants).
Phenytoin. With the combined use of fluoxetine and phenytoin, changes in their blood levels are observed. In some cases, toxicity has occurred. The doses of the drugs should be titrated and the clinical condition of the patients should be monitored.
Serotonergic drugs: Concomitant use with other serotonergic drugs (e.g. tramadol, triptans) may increase the risk of serotonin syndrome. There is an additional increased risk of coronary vasoconstriction and hypertension with triptans.
CYP2D6 isoenzyme. Since the metabolism of fluoxetine (as well as tricyclic antidepressants and other selective serotonin antidepressants) is included in the hepatic cytochrome system CYP2D6 isoenzyme, simultaneous use with drugs that are also metabolized by these enzymes may lead to interaction reactions. Therefore, treatment with drugs that are metabolized by this system and have a narrow therapeutic index (such as flecainide, encainide, carbamazepine and tricyclic antidepressants) should be started with the lowest doses if the patient is simultaneously receiving fluoxetine or has taken it within the previous 5 weeks. In the case of including fluoxetine in the treatment regimen of a patient already taking a similar drug, a dose reduction of the first drug should be considered.
A pharmacokinetic interaction between CYP2D6 inhibitors and tamoxifen has been described in the literature, with a 65–75% decrease in one of the more active forms of tamoxifen, e.g. endoxifen. Several studies have reported a decrease in the efficacy of tamoxifen when coadministered with some serotonin reuptake inhibitors. A decrease in the efficacy of tamoxifen cannot be ruled out, and concomitant use of potent CYP2D6 inhibitors, including fluoxetine, should be avoided if possible.
Fluoxetine may potentiate the effects of alprazolam and diazepam, so they should be used with caution.
When used simultaneously with fluoxetine, changes in blood concentrations of clozapine, diazepam, alprazolam, imipramine and desipramine are noted, and in some cases, manifestations of toxic effects are observed. When taking fluoxetine with these drugs, conservative selection of the dose of the drug should be reviewed and the patient's condition monitored.
Fluoxetine is highly bound to plasma proteins, so when fluoxetine is prescribed with another drug that is highly bound to plasma proteins, changes in the plasma concentrations of both drugs are possible.
Oral anticoagulants. With simultaneous use of fluoxetine with warfarin, an increase in bleeding time was noted. Changes in anticoagulant activity (laboratory parameters and/or clinical symptoms) were inconsistent. As in the case of treatment with warfarin together with other drugs, before the start of use or in the case of discontinuation of fluoxetine, careful monitoring of blood coagulation parameters should be carried out during warfarin therapy. If it is necessary to prescribe other drugs after discontinuation of fluoxetine, the long half-life of fluoxetine and its active metabolite norfluoxetine and, in this regard, the possibility of drug interactions should be taken into account.
Electroconvulsive therapy: Rare cases of increased seizure duration have been reported in patients taking fluoxetine during electroconvulsive therapy. Therefore, caution should be exercised in these patients.
QT prolongation. No pharmacokinetic or pharmacodynamic studies have been conducted with fluoxetine and other drugs that prolong the QT interval. The addictive effect of fluoxetine and these drugs cannot be excluded. Therefore, caution should be exercised when fluoxetine is co-administered with drugs that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobials (e.g. sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine), antimalarials, especially halofantrine, some antihistamines (astemizole, mizolastine).
Alcohol: Fluoxetine did not increase blood alcohol levels or enhance the effects of alcohol in studies. However, concomitant use of serotonin reuptake inhibitors and alcohol is not recommended.
St. John's wort. As with other serotonin reuptake inhibitors, pharmacodynamic interactions between fluoxetine and St. John's wort may occur, and the risk of adverse reactions may be increased when the drug is used with St. John's wort.
Fluoxetine enhances the effect of blood sugar-lowering drugs.
Application features
Skin rashes and allergic reactions. Cases of skin rashes, anaphylactic reactions and progressive systemic disorders involving the skin, lungs and liver have been reported with fluoxetine. If skin rashes or other allergic reactions of undetermined etiology occur, fluoxetine should be discontinued.
Convulsions: There is a potential risk of seizures with antidepressants. Fluoxetine should be discontinued in patients who have experienced seizures or are at increased risk of seizures. Fluoxetine should be avoided in patients with unstable seizure disorders/epilepsy.
Liver/kidney function. Fluoxetine is extensively metabolized in the liver and excreted by the kidneys. Low doses are recommended as alternative daily doses in patients with hepatic impairment. When administered at 20 mg daily for 2 months in patients with renal insufficiency (creatinine clearance < 10 ml/min) and patients requiring hemodialysis, plasma levels of fluoxetine or norfluoxetine are similar to those in patients with normal renal function. Contraindicated in severe hepatic and renal insufficiency.
Tamoxifen: Fluoxetine, a potent CYP2D6 inhibitor, may decrease the concentration of endoxifen, one of the major active metabolites of tamoxifen. Therefore, concomitant use of tamoxifen and fluoxetine should be avoided if possible.
Cardiovascular disorders: Cases of QT prolongation and ventricular arrhythmia have been reported. Use with caution in patients with conditions such as congenital long QT interval, history of QT prolongation, or other clinical conditions that may predispose to arrhythmia (e.g., hypokalemia and hypomagnesemia, bradycardia, acute myocardial infarction, or decompensated heart failure) or in cases of increased fluoxetine concentrations (e.g., hepatic failure). An ECG should be performed before starting fluoxetine. If symptoms of cardiac arrhythmia occur during treatment with fluoxetine, fluoxetine should be discontinued and an ECG should be performed.
Weight loss: Weight loss may occur in patients taking fluoxetine.
Diabetes mellitus. Changes in blood glucose levels have been observed in diabetic patients during treatment with fluoxetine. Hypoglycemia has occurred during treatment with fluoxetine, and hyperglycemia has occurred after discontinuation of the drug. At the beginning and after the end of treatment with fluoxetine, dose adjustment of insulin and/or oral hypoglycemic agents may be necessary.
Suicide/suicidal thoughts or clinical worsening. Depression is associated with an increased risk of suicidal thoughts, suicide attempts. The risk persists until some remission has occurred. Improvement may not occur for several weeks or more of treatment, and patients should be closely observed until improvement occurs. General clinical experience suggests that the risk of suicide may be increased in the early stages of recovery.
Patients with major depressive disorder and other psychiatric illnesses should be monitored closely, as other psychiatric disorders may develop.
Patients should be closely monitored, especially those at high risk of developing suicidal ideation or attempts, especially at the beginning of treatment or when changing the dose. Use is contraindicated in patients with suicidal thoughts.
The use of antidepressants in adult patients with psychiatric disorders has shown an increased risk of suicidal behavior in patients under 25 years of age taking antidepressants. Appropriate measures should be taken if clinical worsening, suicidal attempts, or changes in behavior occur.
Akathisia/psychomotor dysphoria. Fluoxetine has been associated with the development of akathisia, which is a subjective need to move, often with an inability to stand or sit. This is particularly noticeable in the first weeks of treatment. In patients who develop such symptoms, it is not recommended to increase the dose.
Withdrawal symptoms: Withdrawal symptoms are common if treatment is stopped abruptly. The risk of developing withdrawal symptoms depends on many factors, including duration of treatment, dose, and rate of dose reduction. Dose reduction should be titrated over 1 or 2 weeks according to patient need.
Withdrawal symptoms: dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), asthenia, agitation or agitation, nausea and/or vomiting, tremor and headache. In general, withdrawal symptoms are mild to moderate in severity, but may be severe. They usually occur within the first few days after discontinuation of fluoxetine. Symptoms usually resolve spontaneously within the first 2 weeks, although in some cases they may persist for 2–3 months or longer. Therefore, it is recommended to gradually reduce the dose of fluoxetine over a period of at least 1–2 weeks, according to the patient's needs.
Bleeding. Subcutaneous bleeding such as ecchymoses or purpura have been reported. Ecchymoses are rare with fluoxetine. Other haemorrhagic manifestations (gynecological bleeding, gastrointestinal bleeding and other cutaneous or mucous membrane bleeding) have also been reported rarely. The drug should be used with caution in patients taking concomitant oral anticoagulants and drugs that affect platelet function (atypical antipsychotics such as clozapine, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs), or other drugs that may increase the risk of bleeding, in patients with a history of bleeding.
Mydriasis: Mydriasis has been reported in patients taking fluoxetine. Therefore, caution should be exercised in patients with elevated intraocular pressure or at risk of acute angle-closure glaucoma. Contraindicated in patients with glaucoma.
Electroconvulsive therapy: Rare cases of increased seizure duration have been reported in patients receiving fluoxetine during electroconvulsive therapy. Therefore, caution should be exercised in these patients.
St. John's wort: Concomitant use of fluoxetine and St. John's wort increases the risk of serotonergic effects, such as serotonin syndrome, which can occur with the use of selective serotonin reuptake inhibitors (SSRIs) and herbal preparations containing St. John's wort.
Rare cases of serotonin syndrome or neuroleptic malignant syndrome have been reported in patients taking fluoxetine, especially in combination with other serotonergic (including L-tryptophan) and/or neuroleptic drugs. Since these symptoms can be life-threatening, treatment with fluoxetine should be discontinued and supportive and symptomatic treatment should be provided if the following symptoms occur: hyperthermia, rigidity, myoclonus, autonomic instability with possible impairment of vital functions, mental status including impaired consciousness, irritability, progressive agitation up to delirium and coma.
Hyponatremia may develop when using fluoxetine. This is mainly characteristic of elderly patients and patients receiving diuretics, due to a decrease in circulating blood volume.
Sexual dysfunction: SSRIs may cause symptoms of sexual dysfunction (see section 4.8). Long-term sexual dysfunction has been reported, with symptoms persisting despite discontinuation of SSRIs.
This medicine contains sugar and lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Use during pregnancy or breastfeeding
Contraindicated.
Observational data indicate an increased (almost 2-fold) risk of postpartum hemorrhage when SSRIs/NSAIDs are used during the last month of pregnancy (see sections “Special warnings and precautions for use” and “Adverse reactions”).
Ability to influence reaction speed when driving vehicles or other mechanisms
During treatment with fluoxetine, you should refrain from driving or operating other mechanisms.
Method of administration and doses
The drug is taken orally, regardless of the time of eating.
Major depressive episodes/disorders. Fluoxetine therapy should be initiated at 20 mg/day in a single morning dose, which is sufficient to achieve an antidepressant effect. If clinically indicated, the dose may be increased to 20 mg twice daily after 3–4 weeks of therapy; although dose increases may increase side effects, some patients with inadequate response to 20 mg may be gradually increased to 60 mg/day. Doses should be titrated individually and with caution, and therapy should be initiated at the lowest effective dose.
Patients with depressive disorders should be treated for a sufficient period of time, at least 6 months, to ensure that symptoms of the disease are absent.
Obsessive-compulsive disorder. The usual recommended dose is 20 mg daily. Although increasing the dose may increase side effects, in some patients who do not respond adequately to treatment with 20 mg within 2 weeks, the dose may be gradually increased to 60 mg daily.
If there is no clinical effect within 10 weeks of treatment, fluoxetine therapy should be reviewed. If a positive therapeutic effect of treatment has been obtained, fluoxetine therapy should be continued at an individually selected dose of the drug. The dose is increased individually and with caution, therapy should be carried out at the minimum maintenance dose. The patient's need for drug treatment should be periodically reviewed.
Prolonged pharmacotherapy (more than 24 weeks) in patients with obsessive-compulsive disorder has not been studied.
Bulimia nervosa: For adults and elderly patients, the dose is 20 mg per day. Prolonged pharmacotherapy (more than 3 months) in patients with bulimia has not been studied.
General recommendations. The usual recommended dose of the drug is 20 mg per day, which can be increased if necessary. The maximum daily dose is 80 mg. Doses above 80 mg per day have not been studied. If it is necessary to use a single dose of less than 20 mg, another form of the drug in the appropriate dosage should be used.
Fluoxetine can be prescribed 1–2 times a day, regardless of mealtimes.
After stopping the drug, the active substance circulates in the body for another 2 weeks, which should be taken into account when prescribing other drugs or discontinuing treatment.
The dose of the drug for patients with renal or hepatic insufficiency, for elderly patients with concomitant diseases, as well as for patients taking other medications, should be reduced.
Elderly patients: the dose should be increased with caution. Usually the daily dose does not exceed 40 mg.
The maximum daily dose is 60 mg.
A reduced dose or intermittent dosing (e.g., every other day) may be recommended for patients with liver disorders or concomitant medications that may interact with fluoxetine.
Abrupt discontinuation of fluoxetine therapy should be avoided. When discontinuing the drug, the dose should be gradually reduced over 1–2 weeks to avoid withdrawal symptoms. If symptoms worsen during dose reduction or discontinuation of treatment, treatment should be resumed at the previous effective therapeutic dose. After some time, the doctor may continue to gradually reduce the dose.
Children
The drug should not be used in children.
Overdose
Symptoms: nausea, vomiting, convulsions, cardiovascular disorders (including sinus rhythm disturbances and ventricular arrhythmias) or ECG changes indicating QT prolongation, heart attacks, including rare cases of torsades de pointes, respiratory disorders, central nervous system changes from agitation to coma, hypomania.
Treatment: induction of vomiting or gastric lavage, use of activated charcoal, sorbents, symptomatic and supportive therapy. There is no specific antidote. Forced diuresis or dialysis are ineffective in case of fluoxetine overdose.
It is recommended to monitor cardiac and respiratory activity.
Side effects
General disorders: weakness, including asthenia, feeling of trembling, chills, fatigue, malaise, feeling cold, feeling hot, abnormal sensations, neuroleptic malignant syndrome.
Blood and lymphatic system disorders: thrombocytopenia, hemorrhagic manifestations, subcutaneous or mucous hemorrhages, tendency to bruise.
Immune system disorders: hypersensitivity reactions, including angioedema, anaphylactic shock; anaphylactoid reactions, serum sickness.
On the part of the endocrine system: insufficient secretion of antidiuretic hormone.
Metabolic disorders: decreased appetite, including anorexia, hyponatremia.
Nervous system: headache, disturbance in attention, dizziness, dysgeusia, lethargy, drowsiness, including hypersomnia, sedation, tremor, psychomotor hyperactivity, dyskinesia, ataxia, impaired coordination of movements, myoclonus, convulsions, epileptic seizures, psychomotor agitation, disturbance in attention, anxiety, dysphemia, impaired concentration, akathisia, buccoglossal syndrome, serotonin syndrome, memory impairment, including morning awakening, insomnia when falling asleep, insomnia at night, agitation, nervousness, anxiety, tension, decreased libido, including loss of libido, sleep disorders, including pathological dreams, nightmares, insomnia, depersonalization, elevated mood, euphoric mood, thinking disorders, orgasm disorders, including anorgasmia, bruxism, hypomania, mania, hallucinations, agitation, panic attacks, suicidal thoughts and behavior (may be due to the underlying disease), confusion, speech disorders, change in taste.
From the organs of vision: blurred vision, mydriasis.
From the side of the organs of hearing and vestibular apparatus: tinnitus.
Cardiovascular system: palpitations, ventricular arrhythmia, including torsades de pointes, QT prolongation, flushing, hot flushes, hypotension, vasculitis, vasodilation.
Respiratory system: yawning, shortness of breath, pharyngitis, respiratory disorders (inflammatory processes or various histopathological changes and/or fibrosis, epistaxis.
On the part of the digestive tract: diarrhea, nausea, vomiting, dyspepsia, dry mouth, dysphagia, esophageal pain, gastrointestinal bleeding, including most often bleeding from the gums, vomiting blood, bloody stools, rectal bleeding, hemorrhagic diarrhea, melena and gastric bleeding from ulcers.
Hepatobiliary system: idiosyncratic hepatitis.
Skin and subcutaneous tissue disorders: rash, including erythema, exfoliative rash, sweating, erythematous, follicular, generalized, macular, maculo-papular, papular, crusty rash, pruritic rash, vesicular rash, periorbital rash, photosensitivity reactions, erythema multiforme, which may progress to Stevens-Johnson syndrome or toxic epidermal necrolysis (Lyell's syndrome), pruritus, urticaria, purpura, alopecia, ecchymoses.
Musculoskeletal system: arthralgia, muscle twitching, myalgia.
From the urinary system: frequent urination, dysuria, urinary retention, urination disorders, pollakiuria.
Investigations: weight loss, abnormal liver function tests.
Cases of suicidal thoughts and behavior have been reported while taking fluoxetine or shortly after stopping fluoxetine.
Bone fractures: Increased risk of bone fractures in patients receiving SSRIs and antidepressants. The mechanism of these risks is unknown.
Withdrawal symptoms. Discontinuation of fluoxetine is likely to result in withdrawal symptoms. The most common symptoms are dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), asthenia, agitation or agitation, nausea and/or vomiting, tremor and headache. Withdrawal symptoms are generally mild to moderate in severity, but may be severe and prolonged. They usually occur within the first few days after discontinuation of fluoxetine. Therefore, it is recommended that the dose of fluoxetine be gradually reduced over a period of at least 1–2 weeks, according to the patient's needs.
* This event is registered for the therapeutic class SSRIs/SNRIs (see sections “Special warnings and precautions for use” and “Use during pregnancy or lactation”).
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
Tablets No. 10, No. 10×2 in blisters in a pack.
Vacation category
According to the recipe.
Producer
Limited Liability Company "Pharmaceutical Company "Zdorovya".
Limited Liability Company "Research Plant "GNTSLS".
Limited Liability Company "PHARMEX GROUP".
Location of the manufacturer and address of its place of business.
Ukraine, 61013, Kharkiv region, Kharkiv city, Shevchenko street, building 22.
(Limited Liability Company "Pharmaceutical Company "Zdorovya")
Ukraine, 61057, Kharkiv region, Kharkiv city, Vorobyovy street, building 8.
(Limited Liability Company "Research Plant "GNTSLS")
Ukraine, 08301, Kyiv region, Boryspil city, Shevchenko street, building 100.
(Limited Liability Company "PHARMEX GROUP")
