Thioridazine hydrochloride

Indications

Thioridazine hydrochloride is used for: Depression, Schizophrenia

Adult Dose

Oral Schizophrenia Adult: Initially, 50-100 mg tid, gradually increased if necessary in increments of not more than 100 mg wkly. Usual daily dose: 200-800 mg in 2-4 divided doses. Max: 800 mg daily. Depressive Disorders Adult: Initially, 25 mg tid, titrated to 20-200 mg daily. Hepatic impairment: Lower initial doses and more gradual dosage increase.

Child Dose

Oral Schizophrenia Child: 2-12 yr: Initially, 0.5 mg/kg daily in divided doses, increased gradually until optimum effect obtained. Max: 3 mg/kg daily. >12 years: Initial 50-100 mg PO q8hr; titrate to 200-800 mg/day PO divided q6-12hr

Renal Dose

Renal impairment: Lower initial doses and more gradual dosage increase.

Administration

Should be taken with food.

Contra Indications

Hypersensitivity to phenothiazines, comatose states, pre-exisitng CNS depression, severe CVS disorders, uncorrected hypokalaemia or any electrolyte imbalance, known or suspected QT prolongation, history of ventricular arrhythmias including torsades de pointes and porphyria. Bone-marrow suppression, phaeochromocytoma, or prolactin-dependent tumours, angle-closure glaucoma, history of jaundice, parkinsonism, DM, hypothyroidism, myasthenia gravis, paralytic ileus, prostatic hyperplasia, or urinary retention. Patients with reduced activity of cytochrome P450 isoenzyme CYP2D6.

Precautions

Patient w/ severe CV disease, narrow-angle glaucoma, Parkinson's disease, seizure disorder. Avoid abrupt withdrawal. Hepatic and renal impairment. Elderly w/ dementia-related psychosis. Pregnancy and lactation. Patient Counselling May impair ability to drive or operate machinery. Monitoring Parameters Determine ECG and serum K concentrations at baseline and periodically thereafter.

Pregnancy-Lactation

Interactions

Potentiates adverse effects of anticholinergics. Concurrent use of TCAs leads to raised blood levels of both drugs. May antagonise effects of levodopa, bromocriptine and other dopamine agonists. Avoid co-admin with drugs that cause electrolyte imbalance. Monitor phenytoin therapy due to inconsistent effects of thioridazine on phenytoin levels. Potentially Fatal: Increased risk of QT prolongation with class IA and class II antiarrhythmics, astemizole, cisapride, pimozide, droperidol, erythromycin IV, sparfloxacin, terfenadine, clarithromycin and other drugs that may prolong QT interval. Potentiates CNS depression with opioids. Increased risk of arrhythmias with ephedrine-like drugs e.g. phenylpropanolamine. Increased thioridazone levels with fluovoxamine, pindolol, propranolol, ritonavir and other CYP2D6 isoenzymes inhibitors (e.g. fluoxetine, paroxetine).

Adverse Effects

Side effects of Thioridazine hydrochloride : Tardive dyskinesia; leucopenia, neutropenia, agranulocytosis; drowsiness, pseudoparkinsonism and other extrapyramidal symptoms 60%; Dry mouth, blurred vision, constipation, nausea, vomiting, diarrhoea, nasal stuffiness, pallor; galactorrhoea, breast engorgement, amenorrhoea, inhibition of ejaculation, peripheral oedema; dermatitis, skin eruptions. Rarely, nocturnal confusion, hyperactivity, lethargy, psychotic reactions, restlessness, headache, photosensitivity, parotid swelling. Potentially Fatal: Prolongation of QTc interval resulting to torsades de pointes type arrhythmias and polymorphic ventricular tachycardia.

Mechanism of Action

Thioridazine, a phenothiazine antipsychotic, exhibits strong beta-adrenergic blocking effects and depresses the release of hypothalamic and hypophyseal hormones by blocking postsynaptic mesolimbic, dopaminergic receptors in the brain.