indication

For the treatment of schizophrenia and generalized anxiety disorder.

pharmacology

Thioridazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Thioridazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.

mechanism of action

Thioridazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; blocks alpha-adrenergic effect, depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

toxicity

LD₅₀=956-1034 mg/kg (Orally in rats); Agitation, blurred vision, coma, confusion, constipation, difficulty breathing, dilated or constricted pupils, diminished flow of urine, dry mouth, dry skin, excessively high or low body temperature, extremely low blood pressure, fluid in the lungs, heart abnormalities, inability to urinate, intestinal blockage, nasal congestion, restlessness, sedation, seizures, shock

biotransformation

Hepatic

absorption

60%

half life

21-25 hours

drug interactions

Amiodarone: Increased risk of cardiotoxicity and arrhythmias

Amitriptyline: Increased risk of cardiotoxicity and arrhythmias

Amphetamine: Decreased anorexic effect, may increase psychotic symptoms

Artemether: Additive QTc-prolongation may occur. Concomitant therapy is contraindicated.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Atomoxetine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Benzphetamine: Antipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.

Bretylium: Increased risk of cardiotoxicity and arrhythmias

Bromocriptine: The phenothiazine decreases the effect of bromocriptine

Bupropion: Bupropion may increase the effect and toxicity of thioridazine.

Chloroquine: Increased risk of cardiotoxicity and arrhythmias

Chlorpromazine: Increased risk of cardiotoxicity and arrhythmias

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Dexfenfluramine: Decreased anorexic effect, may increase psychotic symptoms

Dextroamphetamine: Decreased anorexic effect, may increase psychotic symptoms

Diethylpropion: Decreased anorexic effect, may increase psychotic symptoms

Diltiazem: Increased risk of cardiotoxicity and arrhythmias

Diphenhydramine: Increased risk of cardiotoxicity and arrhythmias

Disopyramide: Increased risk of cardiotoxicity and arrhythmias

Dofetilide: Increased risk of cardiotoxicity and arrhythmias

Donepezil: Possible antagonism of action

Doxepin: Increased risk of cardiotoxicity and arrhythmias

Duloxetine: Increased risk of cardiotoxicity and arrhythmias

Erythromycin: Increased risk of cardiotoxicity and arrhythmias

Fenfluramine: Decreased anorexic effect, may increase psychotic symptoms

Flecainide: Increased risk of cardiotoxicity and arrhythmias

Fluoxetine: Increased risk of cardiotoxicity and arrhythmias

Fluvoxamine: Increased risk of cardiotoxicity and arrhythmias

Galantamine: Possible antagonism of action

Gatifloxacin: Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Guanethidine: Thioridazine may decrease the effect of guanethidine.

Halofantrine: Increased risk of cardiotoxicity and arrhythmias

Haloperidol: Increased risk of cardiotoxicity and arrhythmias

Imipramine: Increased risk of cardiotoxicity and arrhythmias

Josamycin: Increased risk of cardiotoxicity and arrhythmias

Levofloxacin: Increased risk of cardiotoxicity and arrhythmias

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Maprotiline: Increased risk of cardiotoxicity and arrhythmias

Mazindol: Decreased anorexic effect, may increase psychotic symptoms

Methamphetamine: Decreased anorexic effect, may increase psychotic symptoms

Metrizamide: Increased risk of convulsions

Paroxetine: Increased risk of cardiotoxicity and arrhythmias

Penicillin G: Increased risk of cardiotoxicity and arrhythmias

Pentamidine: Increased risk of cardiotoxicity and arrhythmias

Phendimetrazine: Decreased anorexic effect, may increase psychotic symptoms

Phenmetrazine: Decreased anorexic effect, may increase psychotic symptoms

Phentermine: Decreased anorexic effect, may increase psychotic symptoms

Phenylpropanolamine: Decreased anorexic effect, may increase psychotic symptoms

Pimozide: Increased risk of cardiotoxicity and arrhythmias

Pindolol: Increased risk of cardiotoxicity and arrhythmias

Procainamide: Increased risk of cardiotoxicity and arrhythmias

Propafenone: Increased risk of cardiotoxicity and arrhythmias.

Propranolol: Increased risk of cardiotoxicity and arrhythmias

Quinidine: Increased risk of cardiotoxicity and arrhythmias

Quinidine barbiturate: Increased risk of cardiotoxicity and arrhythmias

Quinine: Increased risk of cardiotoxicity and arrhythmias

Ranolazine: Possible additive effect on QT prolongation

Rivastigmine: Possible antagonism of action

Sertindole: Increased risk of cardiotoxicity and arrhythmias

Sotalol: Increased risk of cardiotoxicity and arrhythmias

Sparfloxacin: Increased risk of cardiotoxicity and arrhythmias

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Thioridazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.

Tacrolimus: May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.

Tamoxifen: Thioridazine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.

Tamsulosin: Thioridazine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Thioridazine is initiated, discontinued, or dose changed.

Telithromycin: Telithromycin may increase the QTc-prolonging effect of Thioridazine. Concomitant therapy should be avoided.

Terbinafine: Terbinafine may increase serum concentrations of Thioridazine. Concomitant therapy is contraindicated.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Tetrabenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Thiothixene: May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.

Ticlopidine: Ticlopidine may decrease the metabolism of Thioridazine. Concomitant therapy is contraindicated.

Toremifene: May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.

Tramadol: Thioridazine may decrease the effect of Tramadol by decreasing active metabolite production.

Tranylcypromine: Tranylcypromine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Thioridazine. Concomitant therapy is contraindicated.

Trimethobenzamide: Trimethobenzamide and Thioridazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Trimipramine: May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.

Triprolidine: The antihistamine, Triprolidine, may increase the arrhythmogenic effect of the phenothiazine, Thioridazine. Monitor for symptoms of ventricular arrhythmias. Additive anticholinergic and CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Thioridazine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Vilazodone: Thioridazine prescribing information contraindicates the concomitant use of agents that inhibit CYP2D6 isoenzymes. Avoid combination.

Voriconazole: Additive QTc prolongation may occur. Concomitant use is contraindicated.

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.

Zuclopenthixol: Additive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy is contraindicated.