Prochlorperazine - Drug Monograph

Introduction

Prochlorperazine is a phenothiazine antipsychotic medication primarily used for the management of nausea and vomiting, as well as for the treatment of schizophrenia and anxiety. First introduced in the 1950s, it remains a clinically relevant agent with both psychiatric and non-psychiatric applications. As a typical antipsychotic, it belongs to the piperazine subgroup of phenothiazines, offering a distinct pharmacological profile from other agents in its class.

Mechanism of Action

Prochlorperazine exerts its therapeutic effects primarily through potent antagonism of dopamine D₂ receptors in the chemoreceptor trigger zone (CTZ) of the area postrema and in the mesolimbic system. This dopamine blockade is responsible for both its antiemetic and antipsychotic properties. Additionally, it demonstrates antagonism at muscarinic M₁, histamine H₁, and alpha-adrenergic receptors, contributing to both its therapeutic effects and side effect profile. The antiemetic effect specifically results from inhibition of dopamine receptors in the CTZ, which lacks a blood-brain barrier and is accessible to emetogenic substances in the blood and cerebrospinal fluid.

Indications

• Severe nausea and vomiting
• Schizophrenia
• Anxiety (short-term management)

• Migraine-associated nausea and vomiting
• Vertigo management
• Adjunctive therapy in cancer chemotherapy-induced nausea and vomiting (though largely superseded by newer agents)

Dosage and Administration

• Nausea/vomiting: 5-10 mg 3-4 times daily
• Schizophrenia: 5-10 mg 3-4 times daily, may increase to 150 mg/day
• Anxiety: 5 mg 3-4 times daily (max 20 mg/day)

• 25 mg twice daily

• 5-10 mg repeated every 3-4 hours (max 40 mg/day)

• Geriatric: Start with lower doses (2.5-5 mg)
• Hepatic impairment: Reduce dose by 50% or avoid
• Renal impairment: Caution recommended
• Pediatrics: Not recommended for children under 2 years or 20 lbs

Pharmacokinetics

Contraindications

• Hypersensitivity to phenothiazines
• Comatose states
• Significant CNS depression
• Bone marrow suppression
• Severe hepatic impairment
• Concomitant use with QT-prolonging agents
• Children under 2 years or 20 lbs

Warnings and Precautions

• Neuroleptic malignant syndrome (potentially fatal)
• Tardive dyskinesia (may be irreversible)
• QT prolongation and risk of torsades de pointes
• Orthostatic hypotension
• Seizures
• Cognitive and motor impairment
• Jaundice and hepatic dysfunction
• Blood dyscrasias
• Temperature regulation dysfunction
• Esophageal dysmotility and aspiration risk

Drug Interactions

• Other CNS depressants (enhanced sedation)
• QT-prolonging agents (increased arrhythmia risk)
• Anticholinergic agents (enhanced anticholinergic effects)
• CYP2D6 inhibitors (increased prochlorperazine levels)
• Guanethidine (reduced antihypertensive effect)
• Levodopa (reduced efficacy)
• Lithium (increased neurotoxicity risk)

Adverse Effects

• Sedation/drowsiness
• Dizziness
• Dry mouth
• Blurred vision
• Constipation
• Orthostatic hypotension

• Extrapyramidal symptoms (dystonia, akathisia, parkinsonism)
• Neuroleptic malignant syndrome
• Tardive dyskinesia
• QT prolongation and cardiac arrhythmias
• Blood dyscrasias (agranulocytosis, leukopenia)
• Seizures
• Jaundice
• Severe hypotension

Monitoring Parameters

• Efficacy assessment (nausea/vomiting control, psychiatric symptoms)
• Extrapyramidal symptoms (AIMS scale recommended periodically)
• Vital signs (especially blood pressure)
• ECG (baseline and periodic, especially with high doses)
• CBC with differential (periodic)
• Liver function tests
• Renal function
• Weight and BMI
• Mental status changes
• Signs of NMS (fever, rigidity, autonomic instability)

Patient Education

• Take with food or milk to reduce GI upset
• Avoid alcohol and other CNS depressants
• Rise slowly from sitting/lying position
• May cause drowsiness - avoid driving or operating machinery
• Report any muscle stiffness, fever, or involuntary movements immediately
• Use effective contraception (may affect fertility)
• Maintain adequate hydration
• Do not stop abruptly without medical supervision
• Sugarless gum/candy for dry mouth
• Regular follow-up appointments essential

References

1. FDA Prescribing Information: Prochlorperazine 2. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. 3. Stahl SM. Stahl's Essential Psychopharmacology. 4th ed. 4. Lexicomp Online: Prochlorperazine Monograph 5. Clinical Pharmacology [database online]: Prochlorperazine 6. Kane JM, Correll CU. Pharmacologic Treatment of Schizophrenia. Dialogues Clin Neurosci. 2010;12(3):345-357. 7. Gralla RJ et al. Recommendations for the Use of Antiemetics. J Clin Oncol. 1999;17(9):2971-2994. 8. Miller LG et al. Recognizing and Managing Antipsychotic Drug Interactions. J Clin Psychiatry. 1998;59 Suppl 20:18-22.