Sertindole

Mild to moderate: Slower dose titration and lower maintenance dose. Severe: Contraindicated.

May be taken with or without food.

Known uncorrected hypokalaemia or hypomagnesaemia, known or family history of congenital long QT syndrome, known acquired QT interval prolongation [QTc >450 msec (male) and 470 msec (female)]; history of clinically significant CV disease, CHF, cardiac hypertrophy, arrhythmia or bradycardia (<50 beats/min). Severe hepatic impairment. Concomitant use w/ potent CYP3A4 inhibitors or drugs known to significantly prolong or increase QT interval.

Patient w/ Parkinson's disease, history of seizures, risk factors for stroke, conditions which may contribute to an elevation of core body temp (e.g. exercising strenuously). Patient at risk for aspiration pneumonia and those who are poor CYP2D6 metabolisers. Not intended for the treatment of dementia-related psychosis. Avoid abrupt withdrawal. Mild to moderate hepatic impairment. Elderly. Pregnancy and lactation.

QT interval prolongation, tardive dyskinesia, convulsions, hyperglycaemia, seizures, hyperprolactinaemia, peripheral oedema, dyspnoea, rhinitis, sexual dysfunction, dizziness, dry mouth, orthostatic hypotension, wt gain, paraesthesia, insomnia, headache, nasal congestion, constipation.
Potentially Fatal: Torsade de Pointes-type arrhythmia, neuroleptic malignant syndrome.

May impair ability to drive or operate machinery.

Monitor ECG prior to and periodically during treatment, BP (during titration and early maintenance treatment); baseline serum K and Mg screening.

Symptoms: Hypotension, tachycardia, somnolence, slurred speech, transient prolongation of QTc interval, Torsade de Pointes. Management: Supportive treatment. Establish a patent airway and maintain adequate oxygenation. Establish IV access; may consider admin of activated charcoal w/ laxative. Hypotension and circulatory collapse may be treated w/ IV fluids. Anticholinergic agents may be administered for severe extrapyramidal symptoms.

Increased plasma levels w/ potent CYP2D6 inhibitors (e.g. fluoxetine, paroxetine). Decreased plasma concentration w/ CYP inducers (e.g. rifampicin, carbamazepine, phenytoin).
Potentially Fatal: Increases in QT interval may be exacerbated by drugs known to significantly prolong or increase QT interval (e.g. quinidine, thioridazine, erythromycin, lithium). Significantly increased plasma levels w/ potent CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, indinavir, diltiazem).

Description:
Mechanism of Action: Sertindole is an atypical antipsychotic. The exact mechanism of action is unknown but it has been proposed that its efficacy is derived from its selective inhibitory effect on mesolimbic dopaminergic neurons through a combination of central dopamine D₂, serotonin 5-HT₂ and α₁-adrenergic receptor antagonism.
Pharmacokinetics:
Absorption: Slowly absorbed. Time to peak plasma concentration: Approx 10 hr.
Distribution: Readily crosses the blood-brain barrier and placenta. Volume of distribution: Approx 20 L/kg. Plasma protein binding: Approx 99.5% (primarily to albumin and α₁-acid glycoprotein).
Metabolism: Extensively metabolised in the liver by CYP2D6 and CYP3A4 isoenzymes.
Excretion: Mainly via faeces (as unchanged drug and metabolites); urine (small amount). Terminal half-life: Approx 3 days.

Source: National Center for Biotechnology Information. PubChem Database. Sertindole, CID=60149, https://pubchem.ncbi.nlm.nih.gov/compound/Sertindole (accessed on Jan. 23, 2020)

Store between 15-30°C. Protect from light and moisture.

Thuốc chống loạn thần

N05AE03 - sertindole ; Belongs to the class of indole derivatives antipsychotics.

Buckingham R (ed). Sertindole. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/03/2016.

Serdolect 4 mg Film-Coated Tablets (H. Lundbeck A/S, Denmark). MHRA. https://products.mhra.gov.uk/. Accessed 08/03/2016.

Serdolect Tablets (H. Lundbeck A/S, Denmark). U.S. FDA. http://www.fda.gov/. Accessed 08/03/2016.