Thioridazine

Indications
 Oral
Schizophrenia
Adult: Initially, 50-100 tid daily and slowly titrated upwards at no more than 100 mg wkly. Max: 800 mg daily in 2-4 divided doses.
Child: 2-12 yr: Initially, 0.5 mg/kg daily in divided doses, increased gradually until optimum effect obtained. Max: 3 mg/kg daily.
Renal impairment: Lower initial doses and more gradual dosage increase.
Hepatic impairment: Lower initial doses and more gradual dosage increase.
Oral
Depression
Adult: Initially, 25 mg tid, titrated to 20-200 mg daily.
Renal impairment: Lower initial doses and more gradual dosage increase.
Hepatic impairment: Lower initial doses and more gradual dosage increase.

Incompatibility: Oral liquid thioridazine should not be admin simultaneously with carbamazepine oral suspension.
Contraindications
 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.
Warnings / Precautions
 Pregnancy, lactation; renal or hepatic impairment, epilepsy. Perform ECG screening and electrolyte measurement before therapy, after each dose increase and at 6-mthly intervals. Monitor for visual defects on long-term therapy. May impair ability to perform skilled tasks. Withdrawal of drug to be carried out gradually over 1-2 wk.
Adverse Reactions
 Drowsiness, sedation, dry mouth, nasal congestion, blurring of vision, tremor, mydriasis, constipation, urinary retention, tachycardia, postural hypotension, sexual dysfunction, pigmentary retinopathy (high doses and prolonged therapy), contact dermatitis, tardive dyskinesias.
Potentially Fatal: Neuroleptic malignant syndrome. Sudden deaths due to cardiac arrhythmias and arrest.
Overdose Reactions
 Overdosage may produce effects that are extensions of the adverse reactions. Extrapyramidal reactions, hypotension, sedation, CNS depression progressing to coma or CNS stimulation with convulsions followed by respiratory depression, shock (e.g. ECG changes and cardiac arrhythmias), increased QT and PR intervals, non-specific ST and T wave changes, torsades de pointes, myocardial depression, agitation, urinary retention, oliguria, uremia, blurring of vision, hypothermia, hyperthermia, mydriasis, miosis, tremor, muscle twitching, rigidity, seizures, muscular hypotonia, respiratory and/or vasomotor collapse and pulmonary oedema. Treatment is symptomatic and supportive with ECG monitoring for at least 24 hr or as long as QT interval is prolonged. A patent airway should be established and adequate oxygenation and ventilation maintained. Emesis (less preferable due to risk of dystonia and potential of aspiration of vomitus) or gastric lavage followed by repeated doses of activated charcoal. Management of arrhythmias include ventricular pacing, defibrillation, admin of IV magnesium sulfate, lidocaine, phenytoin or isoproterenol with correction of electrolyte abnormalities and acid-base balance. Lidocaine should be admin cautiously due to increased risk of seizures.
Drug 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).
See Below for More thioridazine Drug Interactions
Lab Interactions
 Urinary metabolites may cause urine to darken and result in false-positive test results for urobilinogen, amylase, uroporphyrins, porphobilinogens and 5-hydroxyindolacetic acid. False-positive test results for phenylketonuria and pregnancy test (e.g. frog test, Gravindex®, HCG test, Pregnosticon®, UCG test).
Mechanism of Actions
 Thioridazine, a phenothiazine antipsychotic, exhibits strong α-adrenergic blocking effects and depresses the release of hypothalamic and hypophyseal hormones by blocking postsynaptic mesolimbic, dopaminergic receptors in the brain.
Duration: 4-5 days.
Distribution: Protein-binding (Thioridazine and metabolites): >95%. Crosses the placenta and is distributed into breast milk
Metabolism: Hepatic by the cytochrome P450 isoenzyme CYP2D6; converted to active metabolites, mesoridazine and sulforidazine.
Excretion: 4-10 hr (plasma half-life).
Administration
 Should be taken with food.
Storage Conditions
 Oral: Tablet/oral concentrate: Store 15-30°C.
ATC Classification
 N05AC02 - thioridazine ; Belongs to the class of phenothiazine antipsychotics with piperidine structure.
Storage
 Oral: Tablet/oral concentrate: Store 15-30°C.
Available As
  • Thioridazine 10 mg
  • Thioridazine 100 mg
  • Thioridazine 25 mg
  • Thioridazine 5 mg
  • Thioridazine 50 mg

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