Side Effects of Compazine (Prochlorperazine)
Prochlorperazine (Compazine) commonly causes extrapyramidal symptoms, particularly akathisia, which occurs in up to 44% of patients receiving intravenous administration and can also occur with oral dosing. 1
Common Side Effects
Neurological Side Effects
Extrapyramidal symptoms (EPS):
- Akathisia (severe restlessness, often misinterpreted as anxiety)
- Dystonia (sudden muscle contractions, especially in neck, eyes, or torso)
- Parkinsonism (bradykinesia, tremors, rigidity)
- Tardive dyskinesia (with long-term use)
Central Nervous System effects:
- Drowsiness/sedation
- Dizziness
- Headache
- CNS depression
Cardiovascular Side Effects
- Hypotension (particularly orthostatic)
- Tachycardia
- Arrhythmias
- QT prolongation (rare)
Gastrointestinal Side Effects
- Dry mouth (xerostomia)
- Constipation
- Nausea
Other Common Side Effects
- Anticholinergic effects (blurred vision, urinary retention)
- Nasal congestion
- Decreased sweating
Serious Side Effects
Severe Neurological Reactions
- Neuroleptic Malignant Syndrome (NMS) - characterized by:
- Hyperpyrexia
- Muscle rigidity
- Altered mental status
- Autonomic instability 2
Hematologic Effects
- Leukopenia
- Neutropenia
- Agranulocytosis (higher risk in elderly patients) 2
Endocrine Effects
- Hyperprolactinemia
- Galactorrhea
- Amenorrhea
- Gynecomastia
Special Populations at Higher Risk for Side Effects
- Patients under 30 years of age
- Elderly patients
- Patients with AIDS
- Patients with renal disease
- Oncology patients
- Possibly women 3
Clinical Considerations
Akathisia - A Common but Often Misdiagnosed Side Effect
Akathisia is particularly problematic because:
- It can be misinterpreted as anxiety, agitation, or worsening of the primary condition 3
- It occurs in up to 44% of patients receiving IV prochlorperazine within one hour 1
- It can present as severe restlessness, pacing, or physical agitation
- It's a common reason for medication noncompliance
Management of Extrapyramidal Symptoms
- For dystonic reactions: anticholinergic medications (e.g., diphenhydramine) 4
- For akathisia: dose reduction, benzodiazepines, or β-blockers
- For severe reactions: discontinuation of the medication
Alternative Antiemetics
When prochlorperazine side effects are problematic, consider:
- Ondansetron (8 mg sublingual every 4-6 hours) 5
- Atypical antipsychotics like perospirone, which has shown similar antiemetic efficacy with significantly lower risk of extrapyramidal symptoms (0% vs 14% for prochlorperazine) 6
Contraindications
- CNS depression
- Use of adrenergic blockers
- Glaucoma
- Hepatic or renal impairment
- History of leukopenia or neutropenia
- Dementia
- Seizure disorder 5, 2
Monitoring Recommendations
- Watch for signs of akathisia within the first hour after administration
- Monitor for delayed extrapyramidal symptoms for up to 48 hours
- In long-term therapy, regularly evaluate for tardive dyskinesia
- For elderly patients, use lower doses and monitor more closely for adverse effects
Remember that extrapyramidal side effects can sometimes present as psychiatric symptoms, making diagnosis challenging. Maintaining a high index of suspicion for drug-induced symptoms is crucial, especially when patients present with new-onset anxiety, depression, or movement disorders while taking prochlorperazine.