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Pimozide Metabolization

Pimozide is a first-generation antipsychotic with a haloperidol-like profile. It selectively blocks dopaminergic central receptors, presenting neuroleptic properties.

It is mostly used in psychotic symptoms, behavioral disorders and agitation.

CONTRAINDICATIONS

Hypersensitivity.

CNS depression, comatose state, depressive disorder and Parkinson's.

Congenital or acquired QT prolongation, history of cardiac arrhythmias or ""Torsades de pointes"" (previous ECG). Hypokalemia, hypomagnesemia, clinically significant bradycardia.

Hypokalemia, hypomagnesemia, clinically significant bradycardia.

There is limited experience in children under 3 years.

CAUTIONS

Hepatic failure, cardiovascular disease, history of seizures or conditions that reduce threshold.

Cautions should be taken in situations that favor the elevation of central body temperature because pimozide alters its regulation (intense exercise, extreme heat, concomitance with anticholinergics, risk of dehydration).

Perform ECG before starting treatment and repeat periodically during it, if there are changes in repolarization or arrhythmias appear, it is recommended to reduce doses and monitor.

Suspend treatment if: QTc> 500 msec, tardive dyskinesia or NMS (monitor). Treatment should be discontinued gradually because there is a risk of nausea, vomiting, transient dyskinesia and insomnia. Extrapyramidal symptoms may appear. Little or no activity on agitation, excitement and severe anxiety.

SIDE EFFECTS

Very common side effects developed with the intake of pimozide: drowsiness and sedation.

Anorexia, insomnia, dizziness, headache, lethargy, blurred vision, constipation, dry mouth, vomiting, hyperhidrosis, sebaceous gland hyperactivity, nocturia, polyuria, erectile dysfunction, prostration, depression, agitation, restlessness, extrapyramidal disorder, salivary hypersecretion and muscle stiffness.

PHARMACOLOGIC INTERACTIONS

Cautions should be taken when concomitancy with: QT interval prolongers such as class IA and III antiarrhythmics, amitriptyline, maprotiline, phenothiazines, sertindole, terfenadine, astemizole, cisapride, bepridil, halofantrine, sparfloxacin, CYP3A4 inhibitors (such as azole antifungals, protease inhibitors, macrolides, nefazodone) and CYP2D6 inhibitors (quinidine, SSRIs, such as sertraline, fluoxetine, paroxetine, citalopram and escitalopram).

Avoid associating with drugs causing electrolyte disturbances, diuretics (in particular hypokalemic) and grapefruit juice.

Also, pimozide may weaken antiparkinsonian effect of levodopa.

BRAND NAME

  • Orap ®

Gene or region studied

  • CYP2D6
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