Prochlorperazine

Generic Name: Prochlorperazine
Brand Names: Stemetil, Compazine (US), Buccastem, Phenotil

Drug Class: Typical antipsychotic (first-generation); Phenothiazine derivative
Therapeutic Category: Antiemetic, Antipsychotic, Vestibular suppressant
Formulations: Oral tablets, rectal suppositories, buccal tablets, intramuscular (IM) injection, intravenous (IV) injection
Routes of Administration: Oral, rectal, buccal, IM, IV (rare and only in monitored settings)

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1. Pharmacological Classification

Prochlorperazine is a first-generation (typical) antipsychotic from the phenothiazine subclass, closely related to drugs like chlorpromazine. Although initially developed as an antipsychotic, it is more commonly used today for antiemetic purposes due to its potent dopamine (D2) receptor antagonism in the chemoreceptor trigger zone (CTZ) of the brain.

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2. Mechanism of Action

Prochlorperazine acts primarily as a dopamine D2 receptor antagonist in the following brain regions:

• Chemoreceptor Trigger Zone (CTZ): Blocking D2 receptors prevents nausea and vomiting.

• Basal ganglia and nigrostriatal pathways: Leads to extrapyramidal side effects when used at high doses or long term.

• Limbic system and cerebral cortex: Antipsychotic effects stem from D2 antagonism in these areas.

Additionally, it has moderate antagonism at:

• Alpha-1 adrenergic receptors → orthostatic hypotension

• Histamine H1 receptors → sedation

• Muscarinic (M1) receptors → anticholinergic effects

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3. Clinical Uses

A. Antiemetic Indications

• Nausea and vomiting from various causes: postoperative, chemotherapy, radiotherapy, migraine-associated, and drug-induced

• Vestibular disorders (e.g., Meniere's disease, labyrinthitis, vertigo)

• Migraine-related nausea

B. Antipsychotic Indications

• Short-term treatment of schizophrenia, acute psychosis, and mania

• Agitation and severe anxiety (as an adjunct in resistant cases)

C. Other Off-label Uses

• Adjunct for acute migraine attacks (especially IV/IM)

• Management of persistent hiccups

• Cyclic vomiting syndrome in children (used cautiously)

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4. Dosage and Administration

Antiemetic Use (Adults)

• Oral tablets: 5–10 mg three or four times daily

• Buccal tablets (Buccastem M): 3–6 mg twice daily

• Rectal suppositories: 25 mg twice daily

• IM/IV injection: 12.5–25 mg every 4–6 hours as needed

Antipsychotic Use

• Initial dose: 12.5–25 mg 2–3 times daily

• Maintenance dose: up to 100 mg/day in divided doses (rare today)

Elderly

• Start with lower doses due to increased sensitivity to extrapyramidal and sedative effects.

Children (over 2 years, with caution)

• Dosing based on weight; only for severe nausea/vomiting unresponsive to other treatments

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5. Pharmacokinetics

• Absorption: Well absorbed orally and via buccal mucosa

• Onset of Action: 30–60 minutes (oral), 10–20 minutes (IM), faster IV

• Duration: 3–6 hours

• Distribution: Crosses blood-brain barrier and placenta; enters breast milk

• Metabolism: Hepatic (CYP450 system)

• Elimination: Primarily via kidneys and feces

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6. Contraindications

• Comatose states or CNS depression

• Bone marrow depression

• Pheochromocytoma

• Hypersensitivity to prochlorperazine or phenothiazines

• Children under 2 years or under 10 kg (risk of respiratory depression)

• Severe liver disease

• Parkinson’s disease (may worsen symptoms)

• Narrow-angle glaucoma

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7. Warnings and Precautions

• Extrapyramidal Symptoms (EPS): Dystonia, akathisia, parkinsonism, tardive dyskinesia (particularly in children and elderly)

• Neuroleptic Malignant Syndrome (NMS): Rare, life-threatening syndrome with fever, rigidity, altered mental status

• QT Prolongation: Risk of torsades de pointes, especially IV use or in patients with cardiac conditions

• Anticholinergic Effects: Dry mouth, urinary retention, blurred vision

• Hypotension: Especially with parenteral use or in the elderly

• Photosensitivity: Risk of sunburn or rashes with prolonged sun exposure

• Hematologic Toxicity: Rare risk of leukopenia, agranulocytosis

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8. Adverse Effects

Common:

• Sedation, drowsiness

• Dizziness, orthostatic hypotension

• Dry mouth, constipation

• Blurred vision

• Restlessness or agitation (akathisia)

Extrapyramidal Symptoms (EPS):

• Acute dystonic reactions (facial grimacing, oculogyric crisis)

• Parkinsonian symptoms (tremor, rigidity)

• Tardive dyskinesia (involuntary repetitive movements—often irreversible)

• Akathisia (urge to move constantly)

Serious:

• Neuroleptic Malignant Syndrome

• Seizures (rare)

• Jaundice (cholestatic)

• Agranulocytosis

• QT prolongation and arrhythmia

• Severe hypotension

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9. Drug Interactions

CNS Depressants

• Enhanced sedative and respiratory depressive effects with alcohol, opioids, benzodiazepines, antihistamines.

Anticholinergics

• Additive effects → dry mouth, urinary retention, confusion.

Antipsychotics and Dopamine Antagonists

• Increased risk of EPS and NMS.

QT-Prolonging Drugs

• Additive QT prolongation with amiodarone, sotalol, macrolides (erythromycin), and quinolones.

Antihypertensives

• Potentiation of hypotensive effects (e.g., with beta-blockers, ACE inhibitors).

Lithium

• Increased risk of neurotoxicity, encephalopathy, EPS when combined.

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10. Special Populations

Pregnancy

• Category C (old classification); not recommended unless clearly necessary.

• Use only under medical supervision in the first trimester (risk of congenital anomalies is controversial).

Lactation

• Excreted in breast milk; may cause sedation or irritability in the infant. Use with caution.

Elderly

• Greater sensitivity to orthostatic hypotension, EPS, and cognitive side effects.

• Avoid prolonged use due to risk of tardive dyskinesia.

Pediatrics

• Not recommended for children <2 years

• Higher risk of dystonic reactions

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11. Overdose

Symptoms:

• Profound sedation, hypotension

• Seizures, extrapyramidal symptoms

• Respiratory depression

• QT prolongation, arrhythmia

Management:

• Supportive care, airway management

• Activated charcoal (if early ingestion)

• IV fluids, vasopressors if needed

• Benzodiazepines for seizures

• Antiparkinsonian drugs (e.g., benztropine) for EPS

• Cardiac monitoring for arrhythmias

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12. Formulations and Brands

• Tablets: 5 mg, 10 mg

• Buccal tablets (Buccastem M): 3 mg

• Rectal suppositories: 25 mg

• Injectable: 12.5 mg/mL, 25 mg/mL (IM/IV)

• Available Brands:

  • Stemetil (UK and global)

  • Compazine (US)

  • Buccastem

  • Phenotil

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13. Clinical Pearls

• First-line antiemetic for migraine-associated nausea, especially in emergency departments.

• IV use must be slow and carefully monitored due to arrhythmia risk.

• Buccal route is preferred for outpatient nausea control when oral route is not tolerated.

• Monitor for movement disorders with even short-term use in children.

• Low-dose prochlorperazine (e.g., 5–10 mg) is often effective for nausea without requiring high antipsychotic-level dosing.