What are the adverse effects of prochlorperazine?

Adverse Effects of Prochlorperazine

Prochlorperazine is associated with significant adverse effects including extrapyramidal symptoms, neuroleptic malignant syndrome, and cardiovascular complications that can significantly impact morbidity and mortality. 1

Neurological Adverse Effects

Extrapyramidal Symptoms (EPS)

• Acute dystonia: Involves sudden spastic contractions of muscle groups (neck, eyes, torso), which can be distressing and potentially life-threatening in the case of laryngospasm. Risk factors include young age, male gender, and high-potency agents. 2, 1
• Parkinsonism: Symptoms include bradykinesia, tremors, and rigidity, which may be difficult to differentiate from negative symptoms of psychosis. 2, 1
• Akathisia: A sense of severe restlessness manifesting as pacing or physical agitation, commonly occurring within hours to days of treatment initiation. Studies show this occurs in 44% of patients receiving IV prochlorperazine within one hour of administration. 2, 3
• Tardive dyskinesia: Characterized by involuntary facial movements (blinking, grimacing, chewing, tongue movements) and extremity/truncal movements. Occurs in approximately 5% of young patients per year and is more common with typical antipsychotics like prochlorperazine. 2, 1
• Tardive dystonia: Characterized by slow movements along the body axis culminating in spasms, often associated with tardive dyskinesia and can be quite disabling. 2

Neuroleptic Malignant Syndrome (NMS)

• A potentially lethal syndrome consisting of mental status changes, fever, muscle rigidity, and autonomic dysfunction. 2
• Mortality from NMS has decreased from 76% in the 1960s to <10-15% more recently. 2
• Risk factors include dehydration, physical exhaustion, preexisting brain disease, and concomitant psychotropic medications. 2

Cardiovascular Adverse Effects

• Orthostatic hypotension, particularly after parenteral administration. 1
• QT interval prolongation that can lead to potentially dangerous arrhythmias including torsades de pointes. 2
• Tachycardia and other cardiac dysrhythmias. 1
• Rare reports of sudden death, possibly due to cardiac arrest. 1

Hematological Adverse Effects

• Leukopenia, neutropenia, and agranulocytosis have been reported. 1
• Other blood dyscrasias include pancytopenia, thrombocytopenic purpura, and hemolytic anemia. 1
• Patients with pre-existing low white blood cell counts or history of drug-induced leukopenia/neutropenia should have their complete blood count monitored frequently. 1

Endocrine and Metabolic Effects

• Hyperprolactinemia leading to galactorrhea, amenorrhea, gynecomastia, and sexual dysfunction. 1
• Hyperglycemia or hypoglycemia. 1
• Weight gain. 2, 1

Cognitive Effects

• Sedation and cognitive blunting. 2
• Memory deficits, especially with agents having greater anticholinergic activity. 2
• Apathy. 2

Anticholinergic Effects

• Dry mouth, nasal congestion, constipation, urinary retention. 1
• Blurred vision. 1

Hepatic Effects

• Jaundice and biliary stasis. 1
• Elevated liver enzyme levels. 1

Dermatological Effects

• Photosensitivity, itching, erythema, urticaria. 1
• With prolonged administration of substantial doses: skin pigmentation. 1

Special Considerations

Pregnancy and Nursing

• Safety during pregnancy has not been established. 1
• Reports of prolonged jaundice, extrapyramidal signs, and abnormal reflexes in newborns whose mothers received phenothiazines. 1
• Neonates exposed during the third trimester are at risk for extrapyramidal and withdrawal symptoms following delivery. 1
• Phenothiazines are excreted in breast milk. 1

Age-Related Considerations

• Children and adolescents may be at higher risk for extrapyramidal side effects than adults. 2
• Young patients (under 20 years) appear at particular risk of acute extrapyramidal reactions. 4
• Elderly patients, especially women, have higher prevalence of tardive dyskinesia. 1

Monitoring and Management

• Clinical monitoring of both efficacy and side effects is necessary, with frequency varying according to the stage of treatment. 2
• For acute extrapyramidal symptoms, anticholinergic or antihistaminic medications can be helpful. 2
• For akathisia, lowering the dose should be attempted if clinically feasible. Beta-blockers and benzodiazepines may provide relief. 2
• For NMS, immediate discontinuation of the drug, intensive symptomatic treatment, and medical monitoring are essential. 1
• Regular assessment for tardive dyskinesia should occur at least every 3-6 months using standardized measures like the Abnormal Involuntary Movement Scale. 2
• Patients receiving prochlorperazine should be monitored with close clinical observation, cardiorespiratory monitoring, pulse oximetry, and/or electrocardiogram when tolerated. 2

Incidence of Adverse Effects

• Studies show that 16% of patients develop akathisia and 4% develop dystonia after receiving prochlorperazine in the emergency department. 5
• Another study found akathisia in 44% of patients receiving IV prochlorperazine within one hour of administration. 3
• When used as an antiemetic in cancer patients, prochlorperazine caused extrapyramidal symptoms (specifically akathisia) in 14% of patients within one week. 6

Understanding these adverse effects is crucial for appropriate patient selection, monitoring, and management when using prochlorperazine.