Thioril (THIORIDAZINE)

brands

Class

• Neuroscience-based Nomenclature: dopamine, serotonin receptor antagonist (DS-RAn)
• Conventional antipsychotic (neuroleptic, phenothiazine, dopamine 2 antagonist)

Thioril commonly prescribed for

(Bold for FDA approved)

How Thioril works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis

How long until Thioril works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior

Notable Side Effects

• Neuroleptic-induced deficit syndrome

• Akathisia

• Priapism

• Drug-induced parkinsonism

• Tardive dyskinesia

• Risk of potentially irreversible involuntary dyskinetic movements may increase with cumulative dose and treatment duration

• Galactorrhea, amenorrhea

• Pigmentary retinopathy at high doses

• Dizziness, sedation

• Dry mouth, constipation, blurred vision

• Decreased sweating

• Sexual dysfunction

• Hypotension

• Weight gain

Life Threatening Side Effects

• Rare neuroleptic malignant syndrome may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability with elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure

• Rare jaundice, agranulocytosis

• Rare seizures

• Dose-dependent QTc prolongation

• Ventricular arrhythmias and sudden death

• As a class, antipsychotics are associated with an increased risk of death and cerebrovascular events in elderly patients with dementia; not approved for treatment of dementia-related psychosis

weight gain

common

sedation

common

What to do about Thioril side effects

• Wait

• Wait

• Wait

• For drug-induced parkinsonism, add an anticholinergic agent

• Reduce the dose

• For sedation, give at night

• Switch to an atypical antipsychotic

• Weight loss, exercise programs, and medical management for high BMIs, diabetes, dyslipidemia

usual dosage range

• 200–800 mg/day in divided doses

Dosage Forms

• Tablet 10 mg, 15 mg, 25 mg, 50 mg, 100 mg

• Liquid 30 mg/mL, 100 mg/mL (discontinued in USA)

• Suspension 5 mg/mL, 20 mg/mL (discontinued in USA)

long term use

• Should periodically reevaluate long-term usefulness in individual patients, but treatment may need to continue for many years

habit forming

• No

Renal Impairment

• Use with caution

Hepatic Impairment

• Use with caution

Cardiac Impairment

• Thioridazine produces a dose-dependent prolongation of QTc interval, which may be enhanced by the existence of bradycardia, hypokalemia, congenital or acquired long QTc interval, which should be evaluated prior to administering thioridazine

• Use with caution if treating concomitantly with a medication likely to produce prolonged bradycardia, hypokalemia slowing of intracardiac conduction, or prolongation of the QTc interval

• Avoid thioridazine in patients with a known history of QTc prolongation, recent acute myocardial infarction, and uncompensated heart failure

• Risk/benefit ratio may not justify use in cardiac impairment

Elderly

• Some patients may tolerate lower doses better

• Elderly patients may be more sensitive to adverse effects, including agranulocytosis and leukopenia

• Although conventional antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with behavioral symptoms of dementia such as agitation

• Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

Children and Adolescents

• Safety and efficacy not established in children under age 2

• Dose: initial 0.5 mg/kg per day in divided doses; increase gradually; maximum 3 mg/ kg per day

• Risk/benefit ratio may not justify use in children or adolescents

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• Reports of drug-induced parkinsonism, jaundice, hyperreflexia, hyporeflexia in infants whose mothers took a phenothiazine during pregnancy

• Psychotic symptoms may worsen during pregnancy and some form of treatment may be necessary

• Atypical antipsychotic may be preferable to conventional antipsychotics or anticonvulsant mood stabilizers if treatment is required during pregnancy

• Should evaluate for an antipsychotic with a better risk/benefit ratio if treatment is required during pregnancy

Breast Feeding

• Unknown if thioridazine is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or bottle feed