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Drug Reference

prochlorperazine

Phenothiazine antipsychotic· Brands: Compazine, Stemetil, BuccastemIMIVPOPR

Mechanism of action
Prochlorperazine is a phenothiazine that acts primarily by antagonising dopamine D2 receptors in the chemoreceptor trigger zone and the vomiting centre, which underpins its antiemetic action. It also blocks central dopamine receptors in the mesolimbic pathway, contributing to its antipsychotic effect, and has weak antimuscarinic and antihistaminic properties. The dopaminergic blockade in the basal ganglia is responsible for the extrapyramidal side effects.
Pharmacokinetics
Prochlorperazine is well absorbed from the gastrointestinal tract after oral administration, but undergoes extensive first-pass metabolism in the liver, giving a bioavailability of approximately 25 to 50%. It is widely distributed and crosses the blood-brain barrier. Metabolism is primarily hepatic, involving oxidation and conjugation, and the drug is eliminated in urine and faeces. The plasma half-life is in the range of 6 to 8 hours, with significant interindividual variation. Injected formulations achieve higher and more predictable plasma concentrations.
Indications & dosing

Nausea and vomiting

Alternatively: 10 mg IM (max 40 mg/day) or 25 mg PR twice daily.

  • adult · PO: 5–10 mg 3 times daily · Alternatively: 10 mg IM (max 40 mg/day) or 25 mg PR twice daily.

Schizophrenia

Initial dose; titrate as needed. Higher doses (up to 75 mg/day) may be used.

  • adult · PO: 15–30 mg 2-3 times daily · Initial dose; titrate as needed. Higher doses (up to 75 mg/day) may be used.

Short-term anxiety

Short-term use for severe anxiety.

  • adult · PO: 5 mg 3 times daily · Short-term use for severe anxiety.
Contraindications & precautions
  • Hypersensitivity to prochlorperazine or other phenothiazines · Cross-sensitivity among phenothiazines may occur.
  • Bone marrow depression or blood dyscrasias · Prochlorperazine may exacerbate these conditions.
  • Comatose or severely depressed CNS states · Avoid in patients with drug-induced or other CNS depression.
  • Parkinson's disease · Dopamine blockade may worsen symptoms.
  • Severe hepatic impairment · Reduced metabolism may increase toxicity.
  • Pheochromocytoma · Risk of severe hypertension.
  • Monitor closely for extrapyramidal symptoms, especially in children and the elderly.
  • Use with caution in the elderly due to increased risk of falls and drug-induced parkinsonism.
  • Advise patients about sedation and avoid driving or operating machinery.
  • Avoid concurrent use of alcohol and other CNS depressants.
  • Titrate gradually and withdraw slowly after prolonged use to avoid discontinuation symptoms.
  • Caution in patients with hepatic or renal impairment; consider dose reduction.
Adverse effects
  • Extrapyramidal symptoms (dystonia, akathisia, parkinsonism)
  • Neuroleptic malignant syndromeserious
  • Tardive dyskinesiaserious
  • Hypotension (orthostatic)
  • Anticholinergic effects (dry mouth, blurred vision, constipation)
  • Prolactin elevation (hyperprolactinaemia)
  • QT interval prolongationserious
  • Agranulocytosisserious
  • Seizuresserious
Interactions
  • co-beneldopacontraindicatedAvoid co-prescription. If an antiemetic is needed, choose a non-dopamine antagonist such as ondansetron or domperidone. For Parkinson's patients, consider specialist advice. Do not use prochlorperazine in patients receiving levodopa-containing products.
Renal & hepatic adjustment
  • eGFR 0+: No specific dose adjustment required in renal impairment; use with caution in severe renal impairment and consider dose reduction.
  • Hepatic impairment (mild): Use with caution; dose reduction may be necessary.
  • Hepatic impairment (moderate): Reduce dose; start with a lower dose and titrate cautiously.
  • Hepatic impairment (severe): Avoid in severe hepatic impairment. (avoid)
Monitoring, pregnancy & toxicity
  • Extrapyramidal symptoms (e.g., acute dystonia, akathisia, parkinsonism) · During treatment, especially early and with dose changes
  • Blood pressure · At baseline and during dose titration
  • Neuroleptic malignant syndrome (NMS) · Monitor for fever, rigidity, altered mental status; immediate evaluation if suspected
  • Serum prolactin · In patients with symptoms of hyperprolactinaemia
  • ECG · In patients with risk factors for QT prolongation
  • Liver function tests · In patients with hepatic disease or long-term therapy
  • Pregnancy: Prochlorperazine may be used during pregnancy when treatment is necessary, especially for severe nausea and vomiting. Limited data suggest no increased risk of congenital abnormalities; however, use caution in the third trimester due to potential extrapyramidal symptoms in the newborn. Advise on the basis of the individual clinical situation.
  • Toxicity: Extrapyramidal reactions (e.g., dystonia, parkinsonism) · Administer anticholinergic (e.g., procyclidine, benztropine) if severe; monitor and adjust dose.
  • Toxicity: Hypotension · Supportive measures; consider intravenous fluids; if severe, use appropriate vasopressors (e.g., norepinephrine).
  • Toxicity: CNS depression (drowsiness, coma) · Airway and respiratory monitoring; supportive care.
  • Toxicity: QT prolongation · Monitor ECG; correct electrolyte abnormalities; avoid other QT-prolonging drugs.
Clinical notes
Prochlorperazine is used for the treatment of nausea and vomiting, including in migraine and palliative care, and for schizophrenia and other psychoses. It is less commonly used now due to its high liability for extrapyramidal reactions, which are more frequent in children, adolescents, and the elderly. These include acute dystonia, akathisia, and tardive dyskinesia. It should be used with caution in epilepsy, Parkinson's disease, hypothyroidism, and myasthenia gravis. It may prolong the QT interval and cause hypotension; avoid in patients with significant cardiovascular disease or electrolyte disturbances. In pregnancy, use only if clearly indicated. It is not recommended for children under 2 years. The buccal tablets are a common formulation in some regions for nausea.

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BNF; local formulary