Fluoxetine - instructions for use, dose, side effects, contraindications

Selectively inhibits the reuptake of serotonin, which leads to an increase in the concentration of serotonin in the synaptic cleft, enhancing and prolonging its effect on the postsynaptic receptors. Increasing serotonergic transmission by the mechanism of negative feedback, inhibits the exchange of the neurotransmitter.With prolonged use lowers the activity of 5-HT1-receptors. It also blocks the reuptake of serotonin in platelets. Poorly affects the re-uptake of norepinephrine and dopamine. It has no direct effect on serotonin, m-cholinergic, H1-histamine and alpha-adrenergic receptors. Unlike most antidepressants, does not cause a decrease in the activity of postsynaptic beta-adrenoreceptors.

Effective with endogenous depression and obsessive-compulsive disorders. Improves mood, reduces tension, anxiety and fear, eliminates dysphoria. Has an anorexigenic effect, can cause weight loss. In patients with diabetes mellitus can cause hypoglycemia, with the abolition of fluoxetine - hyperglycemia. The expressed clinical effect at depression comes in 1-4 weeks of treatment, at obsessive-compulsive disorders - in 5 weeks and more.

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

Pharmacokinetics:Well absorbed from the digestive tract. The effect of the first passage through the liver is mild. Capsules and an aqueous solution of fluoxetine are equivalent in effectiveness. After a single dose of 40 mg, the maximum concentration of fluoxetine is reached after 4-8 hours and is 15-55 ng / ml, when taken in the same dose for 30 days maximum concentration fluoxetine is 91-302 ng / ml, norfluoxetine is 72-258 ng / ml. At a concentration of up to 200-1000 ng / ml fluoxetine on 94,5% binds to blood proteins, including albumin and alpha1-glycoproteein. Enantiomers are equally effective, but S-fluoxetine is more slowly excreted and predominates over the R-form at equilibrium concentration. Easily penetrates the blood-brain barrier. In the liver, the enantiomers are demethylated with the participation of cytochrome P450 isoenzyme CYP2D6 to norfluoxetine and other unidentifiedand S-norfluoxetine in activity is equal to R- and S-fluoxetine and is superior to R-norfluoxetine. The half-life of fluoxetine is 1-3 days after a single dose and 4-6 days with prolonged administration. Half-life norfluoxetine - 4-16 days in both cases, which causes significant cumulation of substances, slow achievement of their equilibrium level in plasma and prolonged presence in the body after cancellation. In patients with cirrhosis of the liver half-life Fluoxetine and its metabolites are lengthened. It is excreted for 1 week mainly with kidneys (80%): in unchanged form - 11,6%, in the form of fluoxetine glucuronide - 7,4%, norfluoxetine - 6,8%, norfluoxetine glucuronide - 8.2%, more than 20% - hippuric acid, 46% - other compounds; 15% is excreted by the intestine. If the renal function is impaired, the excretion of fluoxetine and its metabolites slows down. When dialysis is not withdrawn (due to the large volume of distribution and a high degree of binding to plasma proteins).

Indications:Depression of various genesis, obsessive-comp.losive disorders, bulimic neurosis.

ICD-10

V.F30-F39.F31 Bipolar affective disorder

V.F30-F39.F32 Depressive episode

V.F30-F39.F33 Recurrent depressive disorder

V.F40-F48.F41.2 Mixed anxiety and depressive disorder

V.F40-F48.F42 Obsessive-compulsive disorder

V.F50-F59.F50.3 Atypical bulimia nervosa

Contraindications:Glaucoma, atony of the bladder, severe renal dysfunction (creatinine clearance less than 10 ml / min), benignI have hyperplasia of the prostate, simultaneous administration of MAO inhibitors, convulsive syndrome of various genesis, epilepsy, pregnancy, lactation, hypersensitivity to fluoxetine.

Carefully:

Children's age (safety and efficacy not established), myocardial infarction, including history, cirrhosis of the liver, diabetes, Parkinson's disease, excessive weight loss, suicidal mood.

With caution appoint in the elderly, with cardiovascular disease, compensated failure of the liver and / or kidney function.

Pregnancy and lactation:

Recommendations for FDA - Category C. Application during pregnancy and lactation period is contraindicated.

When fluoxetine was used during pregnancy, there was an increased risk of premature birth, developmental abnormalities, and low adaptation of newborns (including difficulty breathing, cyanosis, excitability).

Dosing and Administration:

Inside while eating.

The initial dose is 20 mg once a day in the morning; if necessary, the dose may be increased after 3-4 weeks. The frequency of reception is 2-3 times a day.

The maximum daily intake for adults is 80 mg.

The course of treatment - 3-4 weeks, with obsessive-compulsive states - 5 weeks or more, with bulimia nervosa - 1 week.

Side effects:

From the side nervous system and sense organs: headaches, dizziness, anxiety, nervousness, lethargy, fatigue, asthenic syndrome, emotional lability, sleep disorders (insomnia, drowsiness), nightmares, motor anxiety, muscle twitching, myoclonus, tremor, hyperkinesia, convulsions, hypo- or hyperreflexia, extrapyramidal syndrome, carpal tunnel syndrome, ataxia, akathisia, dysarthria, hyper- or hypoesthesia, paresthesia, neuralgia, neuropathy, neuritis, neurosis, thinking disorders, difficulty concentrating, am euphoria, mania or hypomania, hallucinations, depersonalization, paranoid reactions, psychosis, suicidal tendencies, EEG changes, stupor, coma, visual acuity, amblyopia, strabismus, diplopia, exophthalmus, mydriasis, conjunctivitis, iritis, scleritis, blepharitis, xerophthalmia, photophobia, glaucoma, a taste disorder, parosmia, noise and pain in the ears, and hyperacus.

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

From the side metabolism: increased sweating, hypoglycemia, hyponatremia (especially in elderly patients and hypovolemia).

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

From the side respiratory system: nasal congestion, epistaxis, sinusitis, laryngeal edema, shortness of breath, wheezing, hyper- or hypoventilation, hiccups, cough, respiratory distress syndrome, pulmonary inflammatory changes or fibrous character, atelectasis, emphysema, pulmonary edema, hypoxia, apnea, pain thorax.

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

From the side genitourinary system: dysuria, frequent urination, nocturia, oliguria or poly-, albumin and proteinuria, glycosuria, hematuria, urinary tract infections, cystitis, renal insufficiency, hyperprolactinemia, and increase breast pain, decreased libido, ejaculatory disorders, priapism, impotence, anorgasmia , painful menstruation, meno- and metrorrhagia.

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

From the side skin integument: polymorphic rash, including hemorrhagic, ulcerative skin lesions, acne, alopecia, contact dermatitis, photosensitivity, discoloration, furunculosis, shingles, hirsutism, eczema, psoriasis, seborrhea, epidermal necrosis, exfoliative dermatitis.

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

Other: loss of body weight, sweating, hyperemia of the face and neck with a sensation of heat, malignant neuroleptic syndrome, yawning, chills, fever, flu-like syndrome, hypothermia, lymphadenopathy, including tonsillitis, pharyngitis. Lethal outcomes are described.

Overdose:

Symptoms: nausea, vomiting, agitation, anxiety, hypomania, seizures, major epileptic seizures. Two deaths from an acute fluoxetine overdose (in combination with maprotiline, codeine, temazepam) are described.

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

Interaction:

Astemizole - fluoxetine inhibits the metabolism of astemizole, increasing its concentrations and the risk of developing ventricular arrhythmias (torsades de pointes) with possible fatal outcome.

Benzodiazepines (metabolized in the cytochrome P450 system, alprazolam, diazepam) - increase in their half-life and toxicity.

Incompatible with MAO inhibitors, other antidepressants, furazolidone, procarbazine, since it causes serotonergic syndrome (chills, hyperthermia, muscle rigidity, myoclonus, vegetative lability, hypertensive crisis, agitation, tremor, motor anxiety, convulsions, diarrhea, hypomanic state, delirium, coma ; it is possible a lethal outcome. Simultaneous use is contraindicated. Between courses of treatment with these drugs, a 14-day interval is needed.

With simultaneous reception with drugs,which have a high degree of binding to plasma proteins (oral anticoagulants, oral hypoglycemic agents, cardiac glycosides, etc.), it is possible to mutually displace from the bond with the protein with a change in the concentration of free fraction in the blood, the risk of side effects increases. The risk of bleeding increases when taking warfarin.

Sumatriptan and other serotonergic drugs - the danger of developing a rare but potentially lethal serotonin syndrome (profuse sweating, diarrhea, fever, CNS excitation, hyperreflexia, impaired consciousness, myoclonus, tremor).

It will inhibit the biotransformation of drugs metabolized with the participation of the CYP2D6 isoenzyme, CYP3A4 (nifedipine), 2C9 (diclofenac), 2C19 (omeprazole) cytochrome P450 (tricyclic antidepressants, risperidone, dextromethorphan, vinblastine, carbamazepine, flecainide, metoprolol).An increase in the concentration of tricyclic antidepressants 2-10 times compared with the usual ones and within 3 weeks after stopping fluoxetine intake, the development of seizures, a possible fatal outcome is possible. It is required to reduce their doses.

Phenytoin - increasing its concentration and the risk of toxicity.

Special instructions:

With liver disease and in old age, treatment should begin with half the doses.

In patients with diabetes, blood glucose levels may change, which requires correction of the dosage regimen for hypoglycemic drugs.

It requires careful monitoring of patients with suicidal tendencies, especially at the beginning of treatment. The greatest risk of suicide in patients who have previously taken other antidepressants, and patients who have excessive fatigue, hypersomnia, or motor anxiety with fluoxetine. In the treatment of patients with low body weight, the anorexigenic properties of fluoxetine should be taken into account. When conducting electroconvulsive therapy with fluoxetine, prolonged epileptic seizures are possible. The interval between the cancellation of MAO inhibitors and the onset of fluoxetine should be more than 2 weeks, and between the abolition of fluoxetine and the intake of MAO inhibitors - at least 5 weeks.

Impact on the ability to drive vehicles and manage mechanisms.

With caution apply to drivers of vehicles and people whose activities require increased concentration and speed of psychomotor reactions. During treatment should avoid drinking alcohol.

Instructions

Fluoxetine (Fluoxetinum)