Sertindole
When ATH:
N05AE03
Pharmacological action
Antipsychotics, atypical neuroleptic, phenylindole derivative. It has antipsychotic effect, due to the selective blockade of mesolimbic dopaminergic neurons and balanced inhibitory effect on central dopamine D2-receptors and serotonin 5HT2-receptors, as well as α1-adrenoreceptory.
Sertindole has no effect on muscarinic and histamine H1-receptors, as evidenced by the absence of anticholinergic and sedative effects, associated with exposure to these receptors. No effect on prolactin levels.
Pharmacokinetics
After oral sertindole is well absorbed from the gastrointestinal tract. Cmax plasma levels achieved after 10 hours after ingestion. Plasma protein binding – 99.5%. It is metabolized in the liver with the participation isozymes CYP2D6 and CYP3A. The metabolites have no antipsychotic activity. T1/2 is about 3 d.
Sertindole and its metabolites are excreted mainly in the feces and partially – urine.
Testimony
Schizophrenia (with the exception of acute psychotic disorders), intolerance to at least one antipsychotic agent.
Dosage regimen
Is the inside 1 time / day.
The initial dose – 4 mg / day. Depending on the individual response the dose can be gradually increased to 20 mg / day. In case of excess doses 20 mg / day significantly increased the risk of prolonging the QT interval.
In patients with mild or moderate hepatic insufficiency, as well as in elderly patients sertindole should be used in low doses and for a more slow increase in dose.
Side effect
The respiratory system: often – rhinitis, obstruction of nasal breathing; rarely – breathlessness.
From the central and peripheral nervous system: rarely – dizziness, paresthesia, syncope, convulsive disorders, movement disorders (including tardive dyskinesia), neuroleptic malignant syndrome.
From the digestive system: rarely – dry mouth.
Cardio-vascular system: rarely – postural hypotension, QT prolongation, paroxysms of ventricular arrhythmia (type “pirouette”).
From the urinary system: rarely – leucocyturia, hematuria.
Metabolism: rarely – weight gain, giperglikemiâ.
Other: peripheral edema, decrease in the volume of ejaculate.
Contraindications
Kaliopenia, gipomagniemiya; severe cardiovascular diseases (incl. history), including congestive heart failure, myocardial hypertrophy, arrhythmia, or bradycardia (less 50 u. / min), congenital long QT syndrome, or the syndrome in the patient's relatives, acquired QT prolongation (more 450 ms in men and 470 msec in women); concomitant use of drugs, prolonging the QT interval (incl. антиаритмиков классов I A и III, Some antipsychotics, macrolide antibiotics, fluoroquinolones, antihistamines, cisapride, lithium preparations); concomitant use of drugs, ингибирующих изоферменты CYP3A (incl. antifungal azole derivatives, macrolide antibiotics, HIV protease inhibitors, cimetidine); severe liver failure; inhibition of the central nervous system of various etiology; pregnancy, lactation; childhood and adolescence up 18 years; Hypersensitivity to sertindole.
Cautions
To use caution in patients with epilepsy, Parkinson's disease, hepatic failure, in elderly patients.
Not recommended for use in emergencies for the relief of acute psychotic disorders.
Upon receipt of a number of drugs QT prolongation associated with the development of paroxysmal ventricular tachycardia (type “pirouette”)
Because of the potential hazard of QT prolongation sertindole should be used in cases, when intolerance already have at least one antipsychotic drug.
ECG monitoring should be performed prior to treatment, when the equilibrium concentration (approximately 3 Sun. after starting) or when the dose 16 mg / day. During maintenance therapy ECG study should be conducted before and after a change in dose or after joining sertindole / increase in dose, which can increase the concentration of sertindole in plasma. With an increase in the QT interval more 500 ms sertindole should be discontinued.
Blood pressure monitoring is required during the dose titration period at the beginning of a maintenance therapy.
When symptoms during treatment, pointing to the possibility of arrhythmia (incl. heartbeat, convulsions, fainting) should immediately begin examination of the patient, including an electrocardiogram.
Before the start of the application of sertindole should carry out the correction of hypokalemia, gipomagniemii. Vomiting, diarrhea, during treatment with diuretics, which can cause hypokalemia, when electrolyte abnormalities is recommended to control the concentration of potassium in the blood.
At low to moderate liver dysfunction should be carefully monitored for clinical condition of the patient.
With prolonged use of antipsychotic drugs, especially in high doses, It increases the risk of tardive dyskinesia. When symptoms of tardive dyskinesia or neuroleptic malignant syndrome sertindole should be discontinued.
The safety and efficacy of sertindole in children and adolescents under the age of 18 s is not installed.
Effects on ability to drive vehicles and management mechanisms
We do not recommend driving and occupation of other potentially hazardous activities until determining the individual patient's response to treatment.
Drug Interactions
In an application with drugs, увеличивающими интервал QT, It increases the risk of this effect.
Since sertindole metabolized with the participation of isoenzymes CYP2D6 and CYP3A, while receiving inhibitors of CYP2D6 isoenzyme (incl. fluoxetine, paroxetine, xinidinom) may increase the concentration of sertindole in plasma. Sertindole and its main metabolites are weak inhibitors of CYP2D6 isoenzyme activity, with the participation of which are metabolized by beta-blockers, antiaritmiki, Some antihypertensives, Many antipsychotic drugs and antidepressants.
Ингибиторы изоферментов CYP3A (incl. cimetidine, antifungals pyrrole derivatives, HIV protease inhibitors, macrolide antibiotics) can greatly increase the concentration of sertindole in plasma.
Under the influence of carbamazepine, phenytoin may significantly accelerate the metabolism of sertindole, which leads to a decrease of its concentration in plasma and reduce antipsychotic action.
