Prochlorperazine — Drug Monograph

Brand names: Compazine, Compro

Drug class: Supportive Care Agent

Mechanism of Action

Phenothiazine dopamine D2 receptor antagonist. Blocks dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) of the area postrema, suppressing central emetic signaling. Also has antihistamine (H1) and anticholinergic properties contributing to antiemetic and sedative effects.

FDA Indications

• Control of severe nausea and vomiting
• Management of manifestations of psychotic disorders (antipsychotic indication)
• Short-term treatment of generalized non-psychotic anxiety

Common Side Effects

• Extrapyramidal symptoms (EPS): akathisia, dystonia, parkinsonism — dose-dependent
• Sedation/drowsiness
• Orthostatic hypotension
• Dry mouth
• Constipation
• Urinary retention

Clinical Pearl

Prochlorperazine remains useful as rescue/breakthrough therapy in CINV when 5-HT3 antagonists are inadequate. The most common acute adverse event in oncology settings is akathisia (restlessness, inability to sit still) — often misinterpreted as anxiety. Diphenhydramine 25 mg IV or lorazepam 0.5 mg IV rapidly reverses acute dystonia and akathisia. Limit prochlorperazine to short-term rescue use; avoid scheduled long-term use due to tardive dyskinesia risk.

Related Therapies & Mechanisms

• Aprepitant (Emend) — Supportive Care Agent
• Avatrombopag (Doptelet) — Supportive Care Agent
• Darbepoetin Alfa (Aranesp) — Supportive Care Agent
• Defibrotide (Defitelio) — Supportive Care Agent