pharmachologic effect
Antipsychotic drug, atypical neuroleptic, phenylindole derivative.
It has an antipsychotic effect due to the selective blockade of mesolimbic dopaminergic neurons and a balanced inhibitory effect on central dopamine D2 receptors and serotonin 5HT2 receptors, as well as on α1 adrenergic receptors. Sertindole does not affect muscarinic and histamine H1 receptors, which is confirmed by the lack of anticholinergic and sedative effects associated with effects on these receptors. Does not affect prolactin levels.
Contraindications
Hypokalemia, hypomagnesemia; severe cardiovascular diseases (including a history), including congestive heart failure, myocardial hypertrophy, arrhythmia or bradycardia (less than 50 beats/min), congenital long QT syndrome or the presence of this syndrome in the patient’s relatives, acquired long QT interval QT interval (more than 450 ms in men and 470 ms in women); simultaneous use of drugs that prolong the QT interval (including antiarrhythmics of classes IA and III, some antipsychotics, macrolide antibiotics, fluoroquinolones, antihistamines, cisapride, lithium preparations); simultaneous use of drugs that inhibit CYP3A isoenzymes (including antifungal agents of azole derivatives, macrolide antibiotics, HIV protease inhibitors, cimetidine); severe liver failure; inhibition of central nervous system function of various etiologies; pregnancy, lactation period; children and adolescents up to 18 years of age; hypersensitivity to sertindole.
Serdolect®
The cardiovascular system
Clinical studies have shown that sertindole prolongs the QT interval to a greater extent than some other antipsychotics. The mean prolongation of the QT interval is greater at the upper end of the recommended dose range (20 mg and 24 mg). Prolongation of the QTc interval with certain drugs is associated with the possibility of torsades de pointes (TdP) (potentially fatal torsade de pointes) and sudden death. However, clinical and non-clinical trial data have failed to confirm whether sertindole is more arrhythmogenic than other antipsychotics. Therefore, sertindole should only be used in patients intolerant to at least one antipsychotic drug.
Doctors prescribing sertindole should observe the following safety precautions.
ECG monitoring:
— An ECG study must be performed before prescribing the drug Serdolect.
— When the QT interval exceeds 450 ms in men and 470 ms in women, the use of the drug Serdolect is contraindicated.
- An ECG study should be carried out before prescribing the drug, then when equilibrium concentration is reached approximately 3 weeks after the start of treatment or when the daily dose of 16 mg is reached, and also 3 months after the start of treatment.
— During maintenance therapy, an ECG study must be performed every 3 months.
- During maintenance therapy, an ECG study should be performed before and after any increase in the dose of sertindole.
— An ECG is recommended after adding/increasing the dose of a drug that can increase the concentration of sertindole in the blood (see section “Interaction with other drugs”).
— If the QTc interval prolongs beyond 500 ms, sertindole should be discontinued.
— If a patient develops symptoms such as palpitations, convulsions, fainting, which may indicate the possibility of developing arrhythmias, the attending physician should immediately begin examining the patient, including an ECG.
— It is preferable to conduct an ECG study in the morning; to calculate the QTc interval, it is preferable to use the Bazetta or Friederichia formulas.
The risk of QT prolongation is increased in patients receiving concomitant therapy with drugs that prolong the QTc interval or drugs that inhibit the metabolism of sertindole (see section "Contraindications").
In patients at risk of significant electrolyte imbalances, baseline plasma potassium and magnesium levels should be determined before initiating treatment with sertindole. Low potassium and magnesium levels should be corrected before starting treatment. Monitoring serum potassium levels is recommended for patients experiencing vomiting, diarrhea, patients taking potassium-sparing diuretics, or other electrolyte imbalances.
During the initial dose titration, due to the α1-blocking properties of sertindole, symptoms of postural hypotension may appear.
Antipsychotic drugs may inhibit the effects of dopamine agonists. Sertindole should be used with caution in patients with Parkinson's disease.
Some selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine and paroxetine (potent CYP2D6 inhibitors), can increase plasma levels of sertindole by 2-3 times. Therefore, sertindole should only be used with these drugs with extreme caution and only if the potential benefits outweigh the risks. In this case, a lower maintenance dose of sertindole may be required; in addition, a thorough ECG study should be performed before and after any dose adjustment of these drugs (see Section “Interaction with other drugs”). Sertindole should be used with caution in patients with known low activity of the CYP2D6 isoenzyme (see section "Interaction with other drugs").
Very rare cases of hyperglycemia or exacerbation of existing diabetes have been reported during treatment with sertindole. It is advisable to establish appropriate clinical monitoring of patients with diabetes and patients with risk factors for developing diabetes.
Increased mortality among older people with dementia
Data from two large observational studies showed that older people with dementia taking antipsychotic drugs had a small increased risk of death compared with patients not taking antipsychotic drugs. There is no sufficient data to accurately assess the magnitude of the risk and the reasons for its increase. Sertindole is not registered for the treatment of behavioral disorders associated with dementia.
Risk of developing cerebrovascular adverse events
In randomized, placebo-controlled clinical trials of certain atypical antipsychotics in patients with dementia, a 3-fold increase in the risk of cerebrovascular adverse events was observed. The mechanism for this increased risk is unknown. An increased risk cannot be ruled out when using other antipsychotics in other groups of patients. Serdolect should be used with caution in patients at risk of stroke.
Given the increased risk of developing significant cardiovascular disease in the elderly, sertindole should be used with caution in patients over the age of 65 years. Treatment should be started only after a thorough examination of the cardiovascular system.
Venous thromboembolism (VTE)
Cases of venous thromboembolism (VTE) have been reported while taking antipsychotics. Due to the fact that patients treated with antipsychotics are often at risk for developing venous thromboembolism, all possible risk factors for developing venous thromboembolism should be identified before and during treatment with sertindole and precautions taken.
Decreased liver function
With a slight or moderate degree of liver dysfunction, careful monitoring of the patient's condition is necessary. Slower dosage titration and a lower maintenance dose are recommended.
Tardive dyskinesia
Tardive dyskinesia is thought to be caused by increased sensitivity of dopamine receptors in the basal ganglia as a result of chronic receptor blockade by antipsychotic drugs. In clinical studies, a low incidence (comparable to the placebo group) of extrapyramidal symptoms was observed during treatment with sertindole. However, long-term use of antipsychotic drugs, especially in high doses, is associated with the risk of developing tardive dyskinesia.
If symptoms appear while taking sertindole, you should consider reducing the dose or discontinuing the drug.
Seizures
Serdolect should be prescribed with caution in patients with a history of seizures.
Neuroleptic malignant syndrome (NMS)
The use of antipsychotic drugs has been reported to be associated with the development of a potentially fatal symptom complex called Neuroleptic Malignant Syndrome (NMS). Therapeutic tactics for managing patients with NMS should include immediate withdrawal of antipsychotic drugs.
Withdrawal syndrome
If antipsychotics are abruptly stopped, withdrawal symptoms may occur, including nausea, vomiting, increased sweating, and insomnia. The return of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia) are also possible. Therefore, gradual withdrawal of the drug is necessary.
Excipients
The tablets contain lactose monohydrate. Patients with rare hereditary galactose intolerance, lactase deficiency or impaired absorption of glucose and galactose should not be prescribed the drug.
Side effects
From the respiratory system:
often - rhinitis, difficulty in nasal breathing; rarely - shortness of breath.
From the central nervous system 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.
From the cardiovascular system:
rarely - postural hypotension, increased QT interval, ventricular paroxysms).
From the urinary system:
rarely - leukocyturia, hematuria.
From the side of metabolism:
rarely - weight gain, hyperglycemia.
Other:
peripheral edema, decreased ejaculate volume.
Drug interactions
When used simultaneously with drugs that increase the QT interval, the risk of developing this effect increases.
Since sertindole is metabolized with the participation of the CYP2D6 and CYP3A isoenzymes, when taken simultaneously with inhibitors of the CYP2D6 isoenzyme (including fluoxetine, paroxetine, quinidine), an increase in the concentration of sertindole in the blood plasma is possible. Sertindole and its main metabolites are weak inhibitors of the activity of the CYP2D6 isoenzyme, with the participation of which beta-blockers, antiarrhythmics, some antihypertensive drugs, many antipsychotic drugs and antidepressants are metabolized.
Inhibitors of CYP3A isoenzymes (including cimetidine, pyrrole derivative antifungals, HIV protease inhibitors, macrolide antibiotics) can significantly increase the concentration of sertindole in the blood plasma.
Under the influence of carbamazepine and phenytoin, a significant acceleration of the metabolism of sertindole is possible, which leads to a decrease in its concentration in the blood plasma and a decrease in the antipsychotic effect.
Serdolect tablet p/o 16mg N28 (H. Lundbeck A/O)
Due to precautions related to QT prolongation and ECG monitoring, sertindole should be prescribed in cases where at least one other antipsychotic is already intolerant. The risk of QT interval prolongation is greater when taking higher doses (20-24 mg/day). Prolongation of the QT interval when taking a number of drugs can lead to the development of paroxysms of ventricular tachycardia and sudden death. Blood pressure monitoring is necessary during the dose titration period and at the beginning of the maintenance therapy period. Cardiovascular system Before prescribing Serdolect, it is necessary to conduct an ECG study. When the QT interval exceeds 450 ms in men and 470 ms in women, Serdolect should not be prescribed. An ECG study should be carried out before prescribing the drug, when equilibrium concentration is reached approximately 3 weeks after the start of administration or a daily dose of 16 mg, as well as 3 months after the start of treatment. During maintenance therapy, ECG examinations must be performed every 3 months. During maintenance treatment, an ECG study should be performed before and after increasing the dose of sertindole or after adding/increasing the dose of a drug that may increase the concentration of sertindole in the blood. If the QT interval prolongs beyond 500 ms, sertindole should be discontinued. If a patient develops symptoms such as palpitations, convulsions, fainting, indicating the possibility of an arrhythmia, the attending physician should immediately begin examining the patient, including an ECG. It is preferable to carry out an ECG study in the morning. Electrolyte disturbances In patients at risk of developing severe electrolyte disturbances, the level of potassium and magnesium in the blood serum should be measured before starting treatment with Serdolect. Hypokalemia and hypomagnesemia should be corrected before starting sertindole. It is recommended to monitor plasma potassium concentrations in patients with vomiting and diarrhea, in patients taking potassium-sparing diuretics, and in other electrolyte disturbances. Parkinson's disease Antipsychotics may inhibit the effects of dopamine agonists. Serdolect should be used with caution in patients with Parkinson's disease. Reduced liver function If liver function is slightly or moderately impaired, careful monitoring of the patient's condition is necessary. A slower dosage increase and a lower maintenance dose are recommended. Seizures Serdolect should be prescribed with caution in patients with a history of seizures. Tardive dyskinesia Long-term use of antipsychotic drugs, especially in high doses, is associated with the risk of developing tardive dyskinesia. If symptoms appear while taking sertindole, you should reduce the dosage or completely discontinue the drug. Neuroleptic malignant syndrome (NMS) In cases of NMS development, immediate discontinuation of the drug is necessary. Withdrawal syndrome When antipsychotics are abruptly discontinued, nausea, vomiting, increased sweating, and insomnia may occur. The return of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia) are also possible. Gradual withdrawal of the drug is necessary. Excipients Tablets contain lactose monohydrate. The drug should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency or impaired absorption of glucose and galactose. Pregnancy and breastfeeding Since the safety of Serdolect during pregnancy in humans has not been studied, this drug should not be prescribed to pregnant women. The safety of Serdolect in breastfeeding women has not been studied. In cases where the use of sertindole is considered necessary, breastfeeding should be stopped. Children and adolescents (up to 18 years) The safety and effectiveness of Serdolect in children and adolescents has not been studied, therefore the drug should not be used in children and adolescents. Effect on the ability to drive a car or other mechanisms Although Serdolect does not have a sedative effect, patients are not recommended to drive a car or use other mechanisms while taking it until individual tolerance to the drug has been established.
special instructions
Use with caution in patients with epilepsy, Parkinson's disease, liver failure, and elderly patients.
It is not recommended for use in emergency cases to relieve acute psychotic disorders.
When taking a number of drugs, prolongation of the QT interval is associated with the development of paroxysms of ventricular tachycardia (pirouette type)
Due to the potential for QT prolongation, sertindole should be used in cases where at least one antipsychotic drug is already intolerant.
ECG monitoring should be performed before starting treatment, when steady-state concentrations are reached (approximately 3 weeks after the start of treatment), or when the dose reaches 16 mg/day. During maintenance therapy, an ECG study should be performed before and after changing the dose of sertindole or after adding/increasing the dose of a drug that may increase the concentration of sertindole in the blood plasma. If the QT interval increases beyond 500 ms, sertindole should be discontinued.
Blood pressure monitoring is necessary during the dose titration period and at the beginning of the maintenance therapy period.
If symptoms appear during treatment that indicate the possibility of arrhythmia (including palpitations, convulsions, fainting), an examination of the patient should immediately begin, including an ECG.
Before starting the use of sertindole, hypokalemia and hypomagnesemia should be corrected. In case of vomiting, diarrhea, during the use of diuretics that can cause hypokalemia, in case of electrolyte disturbances, it is recommended to monitor the concentration of potassium in the blood.
With a slight or moderate degree of liver dysfunction, careful monitoring of the patient's clinical condition is necessary.
With long-term use of antipsychotic drugs, especially in high doses, the risk of developing tardive dyskinesia increases. If symptoms of tardive dyskinesia or neuroleptic malignant syndrome occur, sertindole should be discontinued.
The safety and effectiveness of sertindole in children and adolescents under 18 years of age have not been established.
Impact on the ability to drive vehicles and operate machinery
Driving and engaging in other potentially hazardous activities is not recommended until the patient's individual response to treatment is determined.
Serdolect, 20 mg, film-coated tablets, 28 pcs.
Due to precautions related to QT prolongation and ECG monitoring, Serdolect should be prescribed only in cases where there is already intolerance to at least one other antipsychotic.
The risk of QT prolongation increases with higher doses of sertindole (20–24 mg/day). Prolongation of the QT interval, which occurs when using a number of drugs, can lead to the development of paroxysmal ventricular tachycardia and sudden death.
Blood pressure control is necessary during the dose selection period and at the beginning of the maintenance therapy period.
SSS.
Before prescribing the drug Serdolect, it is necessary to conduct an ECG study. When the QT interval exceeds 450 ms in men and 470 ms in women, Serdolect should not be prescribed. An ECG study should be carried out before prescribing the drug, when Css is reached approximately 3 weeks after the start of administration or a daily dose of 16 mg, as well as 3 months after the start of treatment. During maintenance therapy, an ECG examination must be performed every 3 months.
During maintenance treatment, an ECG study should be performed before and after increasing the dose of sertindole or after adding/increasing the dose of a drug that may increase the concentration of sertindole in the blood.
If the QT interval prolongs beyond 500 ms, sertindole should be discontinued.
If a patient develops symptoms such as palpitations, convulsions, fainting, indicating the possibility of an arrhythmia, the attending physician should immediately begin examining the patient, including an ECG. It is preferable to carry out an ECG study in the morning.
Electrolyte disturbances.
In patients at risk of developing severe electrolyte disturbances, serum potassium and magnesium levels should be measured before starting treatment with Serdolect. Hypokalemia and hypomagnesemia should be corrected before starting sertindole. It is recommended to monitor the concentration of potassium in the blood plasma in patients with vomiting and diarrhea, in patients taking potassium-sparing diuretics, as well as in other electrolyte disturbances.
Parkinson's disease.
Antipsychotics may inhibit the effects of dopamine agonists. Serdolect should be used with caution in patients with Parkinson's disease.
Decreased liver function.
With a slight or moderate degree of liver dysfunction, careful monitoring of the patient's condition is necessary. A slower dosage increase and a lower maintenance dose are recommended.
Convulsive seizures.
Serdolect should be prescribed with caution in patients with a history of seizures.
Tardive dyskinesia.
Long-term use of antipsychotic drugs, especially in high doses, is associated with the risk of developing tardive dyskinesia. If symptoms appear while taking sertindole, the dosage should be reduced or the drug should be discontinued completely.
ZNS.
In cases of development of NMS, immediate discontinuation of the drug is necessary.
Withdrawal syndrome.
Abrupt withdrawal of antipsychotics may cause nausea, vomiting, increased sweating, and insomnia. The return of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia) are also possible. Gradual withdrawal of the drug is necessary.
Excipients.
The tablets contain lactose monohydrate. Patients with hereditary galactose intolerance, lactase deficiency or impaired absorption of glucose and galactose should not be prescribed the drug.
Pregnancy and breastfeeding.
Since the safety of Serdolect during pregnancy in humans has not been studied, this drug should not be prescribed to pregnant women. The safety of Serdolect in breastfeeding women has not been studied. In cases where the use of sertindole is considered necessary, breastfeeding should be discontinued.
Children and youth (up to 18 years).
The safety and effectiveness of Serdolect in children and adolescents has not been studied, so the drug should not be used in children and adolescents.
Impact on the ability to drive vehicles or operate other machinery.
Although Serdolect does not have a sedative effect, patients are not recommended to drive a car or use other machinery while taking it until individual tolerance to the drug has been established.
