Antidepressant. It is a selective serotonin reuptake inhibitor, which determines its mechanism of action. Fluoxetine has almost no affinity for other receptors, for example, α1, α2, and β-adrenergic receptors, serotonin receptors, dopamine receptors, histamine H1 receptors, m-cholinergic receptors, and GABA receptors.
After ingestion is well absorbed from the gastrointestinal tract. Cmax is reached in 6-8 hours.
Bioavailability by ingestion - more than 60%. Fluoxetine oral dosage forms are bioequivalent.
Binding to plasma proteins - more than 90%. Distributed throughout the body. Css in plasma is achieved after taking the drug for several weeks. Css after prolonged use of the drug is similar to the concentrations observed at 4-5 weeks of taking the drug.
Intensively metabolized in the liver to norfluoxetine and a number of other unidentified metabolites.
Excreted in the urine as metabolites. T1 / 2 fluoxetine is 4-6 days, and its main active metabolite is 4-16 days.
Indications for use
- depression of various etiologies;
- bulimia nervosa;
- obsessive compulsive disorder;
- premenstrual dysphoric disorder.
- established hypersensitivity to fluoxetine
Dosage and administration
- For depression, the initial recommended dose is 20 mg / day.
- For bulimia nervosa, the recommended dose is 60 mg / day.
- In obsessive compulsive disorders, the recommended dose is 20-60 mg / day.
- For premenstrual dysphoric disorders, the recommended dose is 20 mg / day.
- The recommended dose can be increased or decreased, but the use of the drug in a dose of more than 80 mg / day has not been studied.
- The drug can be taken regardless of the meal.
- There is no data on the need to change the dose depending on age.
- In patients with impaired liver function, concomitant diseases or taking other drugs, reduce the dose and reduce the frequency of intake.
Use during pregnancy and lactation
In experimental animal studies, no direct or indirect adverse effect of fluoxetine on the development of the embryo or fetus or on the course of pregnancy was detected. In vitro and animal studies, no evidence of mutagenicity or fertility impairment has been obtained. Since animal reproduction studies do not always make it possible to predict the response of a person, Prozac should be used during pregnancy only in cases of extreme necessity.
Fluoxetine is excreted in breast milk, so the drug should be prescribed with caution to nursing mothers.
The effect of fluoxetine on the process of childbirth in humans is unknown.
On the part of the digestive system: diarrhea, nausea, vomiting, dysphagia, dyspepsia, taste perversion; in rare cases - idiosyncratic hepatitis.
From the side of the central nervous system and peripheral nervous system: convulsions, ataxia, buccal-global syndrome, myoclonus, tremor, anorexia (up to loss of body weight), anxiety accompanied by heartbeat, anxiety, nervousness, agitation, dizziness, fatigue (drowsiness, asthenia), violation of the process of concentration and thinking, manic reaction, sleep disorders (unusual dreams, insomnia); visual impairment (mydriasis, blurred vision); disorders of the autonomic nervous system (dry mouth, sweating, vasodilation, chills), serotonin syndrome (a complex of clinical manifestations of changes in mental state and neuromuscular activity in combination with autonomic disorders of the nervous system).
On the part of the genitourinary system: urination disorders (including frequent urination), priapism / prolonged erection, sexual disorders (decreased libido, delay or absence of ejaculation, lack of orgasm, impotence).
On the part of the endocrine system: impaired secretion of ADH.
Allergic reactions: itching, skin rash, urticaria, anaphylactic reactions, vasculitis, reactions similar to manifestations of serum sickness.
Dermatological reactions: photosensitivity, alopecia.
Others: yawning, ecchymosis.
As in the case of the use of other drugs of the Selective Serotonin Reuptake Inhibitors, the following undesirable effects are noted against the use of fluoxetine.
- Often (≥1% - <10%): atrial flutter, hot flashes ("hot flushes" of heat).
- Infrequently (≥0.1% - <1%): hypotension.
- Rarely (<0.1%): vasculitis, vasodilation.
- Very often (≥10%): diarrhea, nausea.
- Often (≥1% - <10%): dry mouth, dyspepsia, vomiting, anorexia (including weight loss).
- Infrequently (≥0.1% - <1%): dysphagia, taste perversion.
- Rarely (<0.1%): pain along the esophagus.
- Very often (≥10%): weakness (including asthenia).
- Often (≥1% - <10%): chills, anxiety, anxiety, yawning.
- Rarely (≥0.1% - <1%): feeling of heat, feeling of cold, indisposition, discomfort.
- Very rarely (<0.1%): anaphylactic reactions, serum sickness.
- Often (≥1% - <10%): anorexia (including weight loss).
- Infrequently (≥0.1% - <1%): muscle twitching.
- Very often (≥10%): headache.
- Often (≥1% - <10%): impaired attention, dizziness, lethargy, drowsiness (including hyper drowsiness, sedation), tremor.
- Infrequently (≥0.1% - <1%): psychomotor hyperactivity, ataxia, impaired coordination, bruxism, dyskinesia, myoclonus.
- Seldom (<0.1%): bukko-globalny syndrome, spasms.
- Very often (≥10%): insomnia (including early morning awakening, primary 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, impaired orgasm (including anorgasmia), impaired thinking.
- Rarely (<0.1%): mania, hypomania.
- Often (≥1% - <10%): hyperhidrosis, pruritus, rash (including exfoliative, hyperthermic, erythematous, follicular, generalized, macular, pulmonary, core-like, papular, itchy, vesicular, erythema, pipital, pruritic, pruritic, pruritic, pruritus, erythema, erythema, pectular, pruritic, pruritus, erythema, prickly, pruritic, pruritus, erythema, prickly, pruritus erythema), urticaria. Infrequently (≥0.1% - <1%): ecchymosis, tendency to bruise, alopecia, cold sweat.
- Rarely (<0.1%): angioedema, photosensitivity reactions.
- Often (≥1% - <10%): blurred vision.
- Infrequently (≥0.1% - <1%): mydriasis.
- Often (≥1% - <10%): frequent urination (including pollakiuria), ejaculation disorders (including lack of ejaculation, dysfunctional ejaculation, early ejaculation, delayed ejaculation, retrograde ejaculation), erectile dysfunction, gynecological bleeding (including bleeding from the cervix, dysfunctional uterine bleeding, bleeding from the genital tract, menometer, menorrhagia, metrorrhagia, polymenorrhea, post-menopause bleeding, uterine bleeding, vaginal bleeding).
- Infrequently (≥0.1% - <1%): dysuria.
- Seldom (<0.1%): sexual dysfunction.
- Insufficient secretion of antidiuretic hormone.
- Rarely (<0.1%): Idiosyncratic hepatitis.
- Serotonin syndrome.
- Genitourinary system: priapism.
There are reports of the occurrence of skin rash, anaphylactic reactions and progressive systemic disorders involving the skin, lungs, liver, and kidneys in the pathological process in patients taking fluoxetine. If a skin rash or other possible allergic reactions appear, the etiology of which cannot be determined, Prozac should be discontinued.
As with the use of other antidepressants, Prozac should be used with caution in patients who have had epileptic seizures in history.
When fluoxetine was used, there were cases of hyponatremia (in some cases, the sodium level in the blood was less than 110 mmol / l). Mostly similar cases were observed in elderly patients and in patients who received diuretics, due to a decrease in BCC.
In patients with diabetes mellitus, hypoglycemia was observed during treatment with Prozac, and after discontinuation of the drug - hyperglycemia. At the beginning and after the end of treatment with fluoxetine, dosage adjustment of insulin and / or hypoglycemic drugs for oral administration may be required.
The results of experimental studies
In in vitro and animal studies, no evidence of carcinogenicity has been obtained.
Use in Pediatrics
The safety and efficacy of Prozac in children have not been established.
Influence on ability to drive motor transport and control mechanisms
Drugs that affect mental activity can affect decision-making ability and car driving skills. Patients should be advised to avoid driving a car or controlling dangerous machinery until it is determined that the drug does not affect the ability of these activities.
Prozac should not be prescribed simultaneously with MAO inhibitors and for at least 14 days after stopping treatment with MAO inhibitors. After discontinuation of fluoxetine and the start of treatment with MAO inhibitors, there should be an interval of at least 5 weeks. If long-term fluoxetine treatment was carried out and / or the drug was used in high doses, this interval should be increased. Among patients who had previously taken fluoxetine and started taking MAO inhibitors at a shorter interval, there were serious cases of the development of serotonin syndrome (manifestations of which may be similar to the NNS), up to death.
Fluoxetine has the ability to inhibit the CYP2D6 isoenzyme. Therefore, treatment with drugs that are metabolized by this system and which have a narrow therapeutic index should be started with the lowest doses if the patient simultaneously receives fluoxetine or has taken it during the previous 5 weeks. In the case of the inclusion of fluoxetine in the treatment regimen of a patient already taking such a drug, a dose reduction of the first drug should be provided.
With simultaneous use with Prozac, there is a change in blood concentrations of phenytoin, carbamazepine, haloperidol, clozapine, diazepam, alprazolam, lithium, imipramine and desipramine, and in some cases, toxic effects have been observed. When taking fluoxetine in combination with these drugs should provide a conservative selection of the drug dose and monitor the patient's condition.
Fluoxetine binds strongly to plasma proteins. Therefore, when fluoxetine is prescribed while using another drug that binds strongly to plasma proteins, changes in plasma concentrations of both drugs are possible.
With simultaneous use of fluoxetine with warfarin, an increase in bleeding time was noted. Changes in the anticoagulant effect (laboratory parameters and / or clinical signs and symptoms) were intermittent. As in the case of treatment with warfarin in combination with many other drugs at the beginning of use or in case of discontinuation of treatment with fluoxetine during therapy with warfarin, careful monitoring of blood coagulation parameters should be carried out.
If it is necessary to prescribe other drugs after Prozac is canceled, the long half-life of fluoxetine and its active metabolite, norfluoxetine, and, therefore, the possibility of drug interaction, should be considered.
Rarely there have been cases of an increase in the duration of seizures in patients taking fluoxetine during electroconvulsive therapy.
Interaction with other drugs
Fluoxetine and its main metabolite, norfluoxetine, have long half-life, which must be considered when combining fluoxetine with other drugs, as well as when replacing it with another antidepressant.
Phenytoin. Changes in the concentration of phenytoin in the blood were found when it was combined with fluoxetine. In some cases, there were manifestations of intoxication. Increasing the dose of phenytoin or fluoxetine with their simultaneous appointment should be carried out with caution and under the control of the clinical dynamics of the condition.
Serotonergic drugs. The simultaneous intake of serotonergic drugs (for example, tramadol and triptans) contributes to the increased likelihood of developing serotonin syndrome. The simultaneous administration of triptans also contributes to an increase in the likelihood of the development of narrowing of the coronary vessels and arterial hypertension.
Benzodiazepines. With simultaneous use of fluoxetine and benzodiazepines may increase the half-life of the latter. When alprazolam and fluoxetine were taken together, an increase in the concentration of alprazolam in the blood and an increase in its sedative effect were observed.
Lithium and tryptophan. It is known about the development of serotonin syndrome with the admission of SSRIs and lithium, or tryptophan, and therefore the simultaneous appointment of fluoxetine with these drugs should be carried out with caution. When fluoxetine and lithium are taken simultaneously, more frequent and careful monitoring of the clinical condition is necessary.
The drugs metabolized with participation of an isoenzyme of CYP2D6 (propafenone, carbamazepine, tricyclic antidepressants). It should be noted that the metabolism of fluoxetine (as well as tricyclic antidepressants, as well as selective serotonergic antidepressants) is carried out with the participation of the cytochrome of the liver cytochrome system CYP2D6. Simultaneous administration of drugs, the main route of biotransformation of which is metabolism with the participation of the CYP2D6 isoenzyme, and having a small therapeutic dose range (such as propafenone, carbamazepine, tricyclic antidepressants) should be carried out using minimal therapeutic doses. The above is also applicable if less than 5 weeks have passed since the withdrawal of fluoxetine.
Anticoagulants for oral administration and other drugs that affect the blood coagulation system (NSAIDs, acetylsalicylic acid). It is known to change the anticoagulant action (by laboratory parameters and / or clinical manifestations) without any general characteristic tendency, but with the likelihood of increased bleeding while taking fluoxetine and oral anticoagulants. The functional state of the blood coagulation system in patients receiving warfarin should be carefully monitored when fluoxetine is prescribed and discontinued.
Electroconvulsive therapy (ECT). There are rare reports of prolonged seizures in patients taking fluoxetine and receiving ECT, therefore caution is advised.
Alcohol. In experimental studies, fluoxetine did not contribute to an increase in alcohol concentration in the blood, as well as enhancing the effects of alcohol. However, simultaneous administration of SSRIs and alcohol is not recommended.
Means based on the plant Hypericum perforatum. As with other SSRIs, a pharmacodynamic interaction is possible between fluoxetine and plant-based products Hypericum perforatum, which may lead to an increase in undesirable effects.
Symptoms: nausea, vomiting, seizures, impaired function of the cardiovascular system (from asymptomatic arrhythmias to cardiac arrest), impaired function of the respiratory system and signs of changes in the central nervous system from agitation to coma.
Treatment: control of general condition and cardiac activity along with general symptomatic and maintenance therapy. The specific antidote is unknown. The effectiveness of forced diuresis, dialysis, hemoperfusion, cross-transfusion is unlikely.
In the treatment of overdose should consider the possibility of using several drugs.