Thioridazine Hydrochloride

Pronunciation

Pronunciation: THYE-oh-RID-a-zeen HYE-droe-KLOR-ide
Class: Phenothiazine derivative

Trade Names

Thioridazine Hydrochloride
- Tablets, oral 10 mg
- Tablets, oral 25 mg
- Tablets, oral 50 mg
- Tablets, oral 100 mg

Apo-Thioridazine (Canada)

Pharmacology

Effects apparently caused by dopamine receptor blocking in CNS.

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Pharmacokinetics

Absorption

More than 95% bound to plasma proteins.

Metabolism

Metabolized by CYP2D6; main active metabolite is mesoridazine.

Elimination

Plasma half-life is approximately 4 to 10 h.

Indications and Usage

Management of schizophrenia.

Contraindications

Coadministration with drugs that prolong the QTc interval; congenital long QT syndrome or a history of cardiac arrhythmias; coadministration with reduced CYP2D6 isozyme activity drugs that inhibit this isozyme (eg, fluoxetine, paroxetine) and fluvoxamine, propranolol, and pindolol; patients who have a genetic defect leading to reduced levels of activity of CYP2D6; severe CNS depression or comatose states, including drug-induced CNS depression; hypertensive or hypotensive heart disease of extreme degree.

Dosage and Administration

Adults

PO Start with 50 to 100 mg 3 times daily, increasing the dose gradually, if necessary (max, 800 mg/day). Total daily dose ranges from 200 to 800 mg divided into 2 to 4 doses.

Children

PO Start with 0.5 mg/kg/day in divided doses, increasing the dose gradually until optimal therapeutic effect is obtained (max, 3 mg/kg/day).

Storage/Stability

Store between 68° and 77°F. Protect from light.

Drug Interactions

Abiraterone

Plasma concentrations and pharmacologic effects of thioridazine may be increased by abiraterone. Avoid concurrent use.

Anorexiants (eg, dextroamphetamine)

Coadministration may decrease or abolish the pharmacologic effects of both drugs.

Anticholinergics (eg, atropine)

The antipsychotic effectiveness of thioridazine may be decreased. Additive anticholinergic toxicity may occur. Use with caution. If anticholinergics are required, it may be necessary to adjust the thioridazine dosage to produce the max therapeutic effect with minimum toxicity.

Beta-adrenergic blockers (ie, propranolol, pindolol)

Coadministration has resulted in increased thioridazine serum levels, as well as higher than expected serum pindolol levels. It is not known whether other beta-adrenergic blockers and thioridazine interact in a similar manner. Coadministration is not recommended.

CNS depressants (eg, alcohol, anesthetics, barbiturates, opioids)

Thioridazine may potentiate CNS depressants. Severe respiratory depression and respiratory arrest have been reported when a patient was given a phenothiazine and a concomitant high dose of a barbiturate.

Duloxetine

Plasma concentrations and pharmacologic effects of thioridazine may be increased. Risk for cardiac arrhythmias is increased. If coadministration cannot be avoided, monitor closely and adjust the thioridazine dosage as needed.

Epinephrine

Thioridazine may reverse the beta-adrenergic effects of epinephrine, producing hypotension and tachycardia. Concurrent use is not recommended.

Guanethidine

Thioridazine may counteract the antihypertensive effect of guanethidine and related compounds.

Levodopa

The pharmacologic effects of levodopa may be decreased. Concomitant use is not recommended. If concomitant use is necessary, monitor the patient for reduced levodopa pharmacologic effect.

Lithium

The pharmacologic effects of thioridazine may be decreased by lithium. Severe neurotoxicity has been reported. Monitor clinical status and adjust the dose of (or discontinue) either drug.

Metoclopramide

Coadministration may increase the risk of extrapyramidal reactions. Coadministration is contraindicated.

Pergolide

The pharmacologic effects of pergolide may be decreased.

QT interval–prolonging drugs (eg, antiarrhythmic agents [eg, amiodarone, bretylium, disopyramide, dofetilide, flecainide, procainamide, propafenone, quinidine, sotalol], arsenic trioxide, chloroquine, chlorpromazine, cisapride, citalopram, clozapine, crizotinib, dasatinib, dolasetron, doxepin, droperidol, erythromycin, haloperidol, iloperidone, lapatinib, mefloquine, mesoridazine, methadone, moxifloxacin, nilotinib, ondansetron, paliperidone, pentamidine, pimozide, propafenone, romidepsin, tacrolimus, tetrabenazine, toremifene, vandetanib, and ziprasidone)

The risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased.

Quetiapine

Plasma concentrations and pharmacologic effects of quetiapine may be decreased by thioridazine. Clinical significance is unknown. Monitor closely.

Risperidone

Risperidone plasma concentrations may be elevated, increasing the pharmacologic effects and adverse reactions. Monitor closely, especially during the initial stages after addition of thioridazine to a stable course of risperidone.

SSRIs (eg, fluoxetine, fluvoxamine, paroxetine)

Plasma thioridazine concentrations may be elevated, increasing the pharmacologic and adverse effects. Concomitant use of thioridazine with fluvoxamine, fluoxetine, or paroxetine is contraindicated.

Tamoxifen

Pharmacologic effects of tamoxifen may be decreased. Coadministration may increase the risk of breast cancer recurrence. If possible, avoid coadministration.

Tramadol

Concurrent use may increase the risk for seizures. Avoid concurrent use.

Trazodone

Plasma concentrations and pharmacologic effects of trazodone may be increased. If an interaction is suspected, decrease the dosage of trazodone.

Tricyclic antidepressants (eg, imipramine, nortriptyline)

Plasma concentrations of thioridazine and tricyclic antidepressants may be increased. Risk of toxicity may be increased. Monitor closely.

Laboratory Test Interactions

False-positive pregnancy test results may occur.

Adverse Reactions

Cardiovascular

ECG changes (including dose-related prolongation of the QTc interval and torsades de pointes–type arrhythmias), orthostatic hypotension.

CNS

Drowsiness, extrapyramidal symptoms, headache, hyperactivity, lethargy, nocturnal confusion, pseudoparkinsonism, psychotic reaction, restlessness, seizures, tardive dyskinesia.

Dermatologic

Dermatitis, pallor, photosensitivity, skin eruptions of urticarial type.

EENT

Blurred vision, nasal stuffiness.

GI

Constipation, diarrhea, dryness of mouth, nausea, vomiting.

Genitourinary

Amenorrhea, breast engorgement, ejaculation inhibition, galactorrhea; priapism (postmarketing).

Hematologic

Agranulocytosis, leukopenia, neutropenia.

Miscellaneous

Increased prolactin levels, NMS, parotid swelling, peripheral edema.

Precautions

Warnings

Proarrhythmic effects

QTc prolongation is dose related and has been associated with torsades de pointes–type arrhythmias and sudden death. Reserve for use in the treatment of schizophrenic patients who fail to show an acceptable response to adequate courses of treatment with other antipsychotics.

Increased mortality

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Over the course of a 10-week controlled trial, the rate of death in drug-treated patients was approximately 4.5% compared with 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Thioridazine is not approved for the treatment of patients with dementia-related psychosis.


Monitor

Monitor CBC frequently during the first few months of therapy in patients who have a preexisting low WBC or history of drug-induced leukopenia/neutropenia. Monitor patients with clinically significant neutropenia for fever or other symptoms/signs of infection. Patients requiring antipsychotic drug treatment after recovery from NMS should be monitored for recurrence of NMS if therapy is reintroduced. Periodically reassess the need for continued treatment. Periodically monitor ECGs and serum potassium during treatment, especially during periods of dose adjustments. Consider Holter monitoring for patients with symptoms that may be associated with torsades de pointes (eg, dizziness, palpitations, syncope).


Pregnancy

Category undetermined . Neonates exposed to antipsychotics during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery.

Lactation

Undetermined. However, other phenothiazines are excreted in breast milk and have caused toxicity.

Hypersensitivity

Patients who have demonstrated a hypersensitivity reaction (eg, blood dyscrasias, jaundice) to one antipsychotic drug may be more prone to react to others.

Hazardous Tasks

May impair the mental and physical abilities required for driving a car or operating machinery.

Hematologic effects

Leukopenia/neutropenia and agranulocytosis have been reported with antipsychotics.

Hyperprolactinemia

Prolactin levels may be elevated.

NMS

Has occurred with agents of this class and is potentially fatal. Signs and symptoms are altered mental status, diaphoresis, hyperpyrexia, irregular BP, irregular pulse, muscle rigidity, and tachycardia.

Ophthalmic effects

Pigmentary retinopathy has been observed, primarily in patients taking larger than recommended doses.

Orthostatic hypotension

Female patients appear to have a greater tendency for orthostatic hypotension than male patients.

Seizures

May occur.

Tardive dyskinesia

Syndrome of potentially irreversible involuntary body and facial movements may develop. Prevalence is highest in elderly patients, especially women. Use the smallest effective doses for the shortest possible time.

Overdosage

Symptoms

Cardiac toxicity.

Patient Information

  • Advise patients, families, or caregivers that dose will be adjusted periodically until max benefit has been obtained.
  • Instruct patients to not stop taking thioridazine when feeling better.
  • Instruct patients, families, or caregivers to immediately report altered mental status, dizziness, fainting or loss of consciousness, high fever, irregular pulse, muscle rigidity, palpitations, sore throat, unusual bruising, or yellowing of the skin or eyes.
  • Advise patients, families, or caregivers to notify their health care provider of the following: excessive drowsiness, increased agitation or anxiety, involuntary body or facial movements, vision problems (eg, brownish coloring, fuzzy vision, impairment of night vision).
  • Advise patients to avoid strenuous activity during periods of high temperature or humidity.
  • Instruct patients to avoid alcoholic beverages and other depressants while taking this medication.
  • Instruct patients to get up slowly from a lying or sitting position and to avoid sudden position changes to prevent postural hypotension. Advise patients to report dizziness with position changes to their health care provider. Caution patients that hot tubs and hot showers or baths may make dizziness worse.
  • Advise patients to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Advise patients that drug may cause drowsiness or impaired judgment or thinking skills, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Caution patients that medication may cause sensitivity to sunlight and to avoid unnecessary exposure to UV light (eg, sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light until tolerance is determined.
  • Inform patients in whom long-term use is contemplated of the likelihood of the development of tardive dyskinesia.

Copyright © 2009 Wolters Kluwer Health.

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