pimozide

Mechanism of action 

It is an antipsychotic drug that blocks dopamine receptors in the brain. It is primarily used to treat symptoms of schizophrenia and Tourette’s syndrome. The mechanism of action of pimozide is thought to involve the inhibition of dopamine receptors in the brain, which leads to a reduction in the symptoms of psychosis and tics associated with Tourette’s syndrome. 

Spectrum 

The drug has a relatively narrow spectrum of activity and is not typically used to treat other psychiatric conditions. 

 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency defined:  

>10% 

Drowsiness 

Sedation 

Visual disturbance 

Constipation 

Akinesia 

EPS 

Speech disorder 

Dry mouth 

impotence 

1-10% 

Increased thirst 

Dystonia 

Photosensitivity 

Orthostatic hypotension 

Nasal congestion 

Urinary retention 

Appetite increased 

Dizziness 

Nervousness 

Taste change 

Diminished sweating 

Diarrhea 

Retinitis pigmentosa 

Frequency undefined 

Heatstroke 

Seizures 

Paralytic ileus 

Disorder of hematopoietic structure 

Thrombocytopenia 

Death 

Ineffective thermoregulation 

Neuroleptic malignant syndrome  

Prolonged QT interval 

Obstipation 

Agranulocytosis 

 

Black box warning 

The use of pimozide is contraindicated in patients with a history of QT prolongation or with certain heart conditions. Additionally, the drug should be used with caution in patients with a family history of QT prolongation or other risk factors for torsades de pointes. The dose should be limited to the lowest effective dose. 

 

Contraindications 

• pimozide is contraindicated in patients with documented hypersensitivity to the drug. It should also be used with caution in patients with CNS depression (including coma), neuroleptic malignant syndrome (NMS), or poorly controlled seizure disorder. 
• It is not recommended as a first-line treatment for patients with tics not associated with Tourette’s disorder. 
• It is important to note that pimozide prolongs the QT interval, which can increase the risk of a dangerous heart rhythm called torsades de pointes.  
• Therefore, it should not be used with other drugs that prolong the QT interval or in patients with congenital long QT syndrome. 

Caution 

• The FDA has issued a warning regarding the off-label use of certain medications for dementia in the elderly. These medications may interact with grapefruit juice and increase the risk of specific side effects such as EPS (extrapyramidal symptoms) and NMS (neuroleptic malignant syndrome).  
• Additionally, there have been reports of leukopenia/neutropenia and agranulocytosis, which are severe blood disorders characterized by low levels of white blood cells. People with pre-existing low white blood cell count or a history of drug-induced leukopenia/neutropenia may be at increased risk of these blood disorders.  
• The FDA recommends closely monitoring complete blood count (CBC) during the first few months of therapy and discontinuing the medication at the first sign of a clinically significant white blood cell count decline. 

Pregnancy consideration: C 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

 

Pharmacology 

• It is an antipsychotic medication that is used to treat certain mental disorders such as schizophrenia and Tourette’s disorder. It works by blocking the action of certain neurotransmitters, specifically dopamine, in the brain. This helps to reduce symptoms such as hallucinations, delusions, and tics. 
• It is classified as a “typical” antipsychotic, meaning it is a member of the older generation of antipsychotics. It is available in tablets and is usually taken once or twice daily. 
• Common side effects of pimozide include drowsiness, dizziness, and tremors. It also can cause EPS (extrapyramidal symptoms), including stiffness, restlessness, and muscle spasms. Other side effects include weight gain, dry mouth, constipation, blurred vision, and changes in blood pressure.  

Pharmacodynamics 

• pimozide is an antipsychotic medication that works by blocking the action of dopamine in the brain. The exact mechanism of action is not fully understood, but it is thought to work by binding to dopamine receptors in the brain, specifically the D2 receptor.  
• This blocks the binding of dopamine to these receptors, which reduces the amount of dopamine activity in the brain. Dopamine is a neurotransmitter that plays a role in regulating mood, emotion, and movement, so reducing its activity can help alleviate the symptoms of certain mental disorders such as schizophrenia and Tourette’s disorder. 
• pimozide also has a weak affinity for serotonin receptors, and it can reduce the activity of other neurotransmitters, such as noradrenaline and acetylcholine. 

Pharmacokinetics 

Absorption 

The bioavailability of pimozide is approximately 85%. The elimination half-life of pimozide is approximately 20-30 hours  

Distribution 

It is highly protein bound, with approximately 98% of the drug bound to plasma proteins  

Metabolism 

It is metabolized primarily by the liver to several active and inactive metabolites  

Elimination and excretion 

It is excreted primarily in the urine, with a small amount excreted in the feces 

 

Administration 

• It is a medication that treats certain mental disorders such as schizophrenia and Tourette’s syndrome. It is typically administered orally as a tablet, and the dosage and frequency of administration will depend on the treated condition and the individual patient. 
• The usual starting dose of pimozide for the treatment of Tourette’s syndrome is 0.5 mg once daily, with the dose gradually increased as needed and tolerated. The maintenance dose is typically between 1-8 mg daily, divided into 2-4 doses. 
• For the treatment of schizophrenia, the usual starting dose is 2 mg per day, with the dose gradually increased as needed and tolerated. The maintenance dose is typically between 2-10 mg daily, divided into 2-4 doses. 

Patient information leaflet 

Generic Name: pimozide 

Pronounced: [ PIM-oh-zide ] 

Why do we use pimozide? 

It treats certain mental disorders such as schizophrenia and Tourette’s syndrome. 

In treating Tourette’s syndrome: pimozide is used to reduce the frequency and severity of motor and vocal tics. It works by blocking the action of dopamine, a neurotransmitter that is thought to be involved in developing tics. Pimozide is considered a second-line treatment for Tourette’s syndrome and is typically used when other treatments, such as alpha-2 agonists, have been ineffective or poorly tolerated. 

In treating schizophrenia: pimozide is used as an adjunct to other antipsychotic medications to treat symptoms such as hallucinations, delusions, and disordered thinking. It works by blocking the action of dopamine and other neurotransmitters in the brain, which can help to reduce the severity of these symptoms