Prochlorperazine: Uses, Interactions, Mechanism of Action

LD50 and Overdose

Oral LD50 in rats is 750 mg/kg. Intraperitoneal and subcutaneous LD50 in mice are 191 mg/kg and 320 mg/kg, respectively.MSDS In placebo-controlled trials, there were increased incidences of mortality in elderly patients with dementia-related psychosis receiving antipsychotic medications. The risk of death in drug-treated patients was about 1.6 to 1.7 times that of placebo-treated patients. Deaths were largely resulting from cardiovascular, such as heart failure and sudden death, or infectious, such as pneumonia, conditions.Label Due to its antagonist action on dopamine receptors, prochlorperazine is associated with a risk for developing extrapyramidal symptoms such as tardive dyskinesia, which is a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements. This risk is also conferred on other antipsychotic agents that block dopamine receptors. It is proposed that increased duration of the drug treatment is likely thus increased total cumulative dose of antipsychotic drugs administered to the patient leads to increased risk for developing the syndrome and the likelihood that it will become irreversible. As with other antipsychotic agents, prochlorperazine is associated with a risk for causing neuroleptic malignant syndrome (NMS), which is a potentially fatal symptom complex, which is manifested as hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability.

There is no known antidote for prochlorperazine thus overdose treatment should be supportive and symptomatic. Overdose of prochlorperazine may produce dystonic reactions that involve extrapyramidal mechanism. To reduce these symptoms, antiparkinsonism drugs, barbiturates, or diphenhydramine may be used. Symptoms of central nervous system depression, such as somnolence or coma, may also be observed. Amphetamine, destroamphetamine, or caffeine and sodium benzoate may be used to induce stimulatory effects. In contrast, agitation and restlessness may also be seen in case of overdose. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever, and autonomic reactions such as hypotension, dry mouth and ileus. Hypotension can be responded with the standard measures for managing circulatory shock.Label

Nonclinical Toxicology

In a rat developmental or reproductive toxicity study, abnormalities in both the reproductive measures and neurobehavioral testing were observed following administration of 25 mg/kg of prochlorperazine.13

Use in specific populations

As the use of antipsychotic agents during the third trimester of pregnancy is associated with a risk for extrapyramidal and/or withdrawal symptoms following delivery, the use of prochlorperazine in pregnant patients is generally not recommended and it should be limited after careful consideration of the potential benefit of drug therapy justifying the potential risk to the fetus. Caution should be exercised when prochlorperazine is administered to a nursing mother. While lower doses of prochlorperazine is reported to be safe for elderly patients, caution is still advised, especially those with higher susceptibility to hypotension and neuromuscular reactions.Label