PIMOZIDE

brands

Class

• Neuroscience-based Nomenclature: dopamine receptor antagonist (D-RAn)
• Tourette’s syndrome/tic suppressant; conventional antipsychotic (neuroleptic, dopamine 2 antagonist)

PIMOZIDE commonly prescribed for

(Bold for FDA approved)

How PIMOZIDE works

• Blocks dopamine 2 receptors in the nigrostriatal dopamine pathway, reducing tics in Tourette’s syndrome

• When used for psychosis, can block dopamine 2 receptors in the mesolimbic dopamine pathway, reducing positive symptoms of psychosis

How long until PIMOZIDE works

• Relief from tics may occur more rapidly than antipsychotic actions

• 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

• Drug-induced parkinsonism

• Tardive dyskinesia

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

• Hypotension

• Sedation, akinesia

• Galactorrhea, amenorrhea

• Dry mouth, constipation, blurred vision

• Sexual dysfunction

• 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 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

not usual

sedation

not usual

What to do about PIMOZIDE side effects

• Wait

• Wait

• Wait

• Anticholinergics may reduce drug-induced parkinsonism when present

• 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

• Less than 10 mg/day

Dosage Forms

• Tablet 1 mg scored, 2 mg scored

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

• Pimozide 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 pimozide

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

Elderly

• Some patients may tolerate lower doses better

• 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 established for patients over age 12

• Preliminary data show similar safety for patients ages 2–12 as for patients over 12

• Generally use second-line after atypical antipsychotics and other conventional antipsychotics

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

• Renal papillary abnormalities have been seen in rats during pregnancy

• 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

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

• Atypical antipsychotics 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 required during pregnancy

Breast Feeding

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

• Not recommended for use because of potential for tumorigenicity or cardiovascular effects on infant

• Recommended either to discontinue drug or bottle feed