Serdolect^® (Tablets) Instructions for Use

ATC Code

N05AE03 (Sertindole)

Active Substance

Sertindole (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antipsychotic drug (neuroleptic)

Pharmacotherapeutic Group

Antipsychotic agent (neuroleptic)

Pharmacological Action

Antipsychotic agent, atypical neuroleptic, phenylindole derivative. It exerts an antipsychotic effect due to selective blockade of mesolimbic dopaminergic neurons and balanced inhibitory action 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 absence of anticholinergic and sedative effects associated with the impact on these receptors. It does not affect prolactin levels.

Pharmacokinetics

After oral administration, Sertindole is well absorbed from the gastrointestinal tract. C_max in plasma is reached 10 hours after oral administration. Plasma protein binding is 99.5%. It is metabolized in the liver with the participation of CYP2D6 and CYP3A isoenzymes. Metabolites do not possess neuroleptic activity. T_1/2 is about 3 days.

Sertindole and its metabolites are excreted mainly in feces and partially in urine.

Indications

Schizophrenia (except for acute psychotic disorders), in case of intolerance to at least one antipsychotic agent.

ICD codes

Dosage Regimen

Tablets

Take orally once daily.

The initial dose is 4 mg/day. Depending on the individual response, the dose can be gradually increased to 20 mg/day. If the dose exceeds 20 mg/day, the risk of QT interval prolongation significantly increases.

In patients with mild or moderate hepatic impairment, as well as in elderly patients, Sertindole should be used at low doses and the dose increase should be slower.

Adverse Reactions

From the respiratory system common – rhinitis, nasal congestion; rare – dyspnea.

From the central and peripheral nervous system rare – dizziness, paresthesia, syncope, seizure disorders, movement disorders (including tardive dyskinesia), neuroleptic malignant syndrome.

From the digestive system rare – dry mouth.

From the cardiovascular system rare – postural hypotension, QT interval prolongation, paroxysms of ventricular arrhythmia (torsades de pointes).

From the urinary system rare – leukocyturia, hematuria.

From metabolism rare – weight gain, hyperglycemia.

Other peripheral edema, decreased ejaculate volume.

Contraindications

Hypokalemia, hypomagnesemia; severe cardiovascular diseases (including in history), including congestive heart failure, myocardial hypertrophy, arrhythmia or bradycardia (less than 50 beats/min), congenital long QT syndrome or presence of this syndrome in the patient’s relatives, acquired long QT interval (more than 450 msec in men and 470 msec in women); concurrent use of drugs that prolong the QT interval (including class I A and III antiarrhythmics, some antipsychotics, macrolide antibiotics, fluoroquinolones, antihistamines, cisapride, lithium preparations); concurrent use of drugs that inhibit CYP3A isoenzymes (including azole derivative antifungals, macrolide antibiotics, HIV protease inhibitors, cimetidine); severe hepatic impairment; depression of the central nervous system of various etiologies; pregnancy, lactation period; children and adolescents under 18 years of age; hypersensitivity to sertindole.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment. In patients with mild or moderate hepatic impairment, it should be used at low doses and the dose increase should be slower.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Use with caution in patients with epilepsy, Parkinson’s disease, with hepatic impairment, in elderly patients.

It is not recommended for use in emergency cases for the relief of acute psychotic disorders.

When taking a number of drugs, QT interval prolongation is associated with the development of paroxysms of ventricular tachycardia (torsades de pointes).

Due to the potential risk of QT interval prolongation, Sertindole should be used in cases where there is already intolerance to at least one antipsychotic drug.

ECG monitoring should be performed before starting treatment, upon reaching steady-state concentration (approximately 3 weeks after starting administration) or upon reaching a dose of 16 mg/day. During maintenance therapy, ECG examination should be performed before and after changing the dose of sertindole or after adding/increasing the dose of a drug that may increase the plasma concentration of sertindole. If the QT interval increases to more than 500 msec, Sertindole should be discontinued.

Blood pressure monitoring is necessary during dose titration and at the beginning of the maintenance therapy period.

If symptoms indicating the possibility of arrhythmia (including palpitations, convulsions, fainting) appear during treatment, the patient should be immediately examined, including an ECG.

Before starting sertindole, hypokalemia and hypomagnesemia should be corrected. In case of vomiting, diarrhea, while using diuretics that can cause hypokalemia, or in case of electrolyte disturbances, it is recommended to monitor blood potassium levels.

In case of mild 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 appear, Sertindole should be discontinued.

The safety and efficacy of sertindole in children and adolescents under 18 years of age have not been established.

Effect on ability to drive vehicles and operate machinery

Driving vehicles and engaging in other potentially hazardous activities is not recommended until the individual patient response to treatment is determined.

Drug Interactions

With concurrent use with drugs that increase the QT interval, the risk of developing this effect increases.

Since Sertindole is metabolized with the participation of CYP2D6 and CYP3A isoenzymes, concurrent use with inhibitors of the CYP2D6 isoenzyme (including fluoxetine, paroxetine, quinidine) may increase the plasma concentration of sertindole. Sertindole and its main metabolites are weak inhibitors of the activity of the CYP2D6 isoenzyme, which metabolizes beta-blockers, antiarrhythmics, some antihypertensive agents, many antipsychotic drugs and antidepressants.

Inhibitors of CYP3A isoenzymes (including cimetidine, pyrrole derivative antifungals, HIV protease inhibitors, macrolide antibiotics) can significantly increase the plasma concentration of sertindole.

Under the influence of carbamazepine, phenytoin, a significant acceleration of sertindole metabolism is possible, leading to a decrease in its plasma concentration and a reduction in antipsychotic action.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.