Prochlorperazine

BRAND NAMES

• Stemetil – Most widely used brand in many countries (including India) 

• Compazine – Common brand in the US 

• Buccastem – Buccal formulation used for nausea/vertigo 

• Stemetil MD – Mouth-dissolving tablets in some regions

MECHANISM OF ACTION

Prochlorperazine works primarily by blocking dopamine D2 receptors in the brain. In thechemoreceptor trigger zone (CTZ) of the medulla, this reduces stimulation of the vomiting center, thereby controlling nausea and vomiting. In the central nervous system, dopamine blockade also produces its antipsychotic effects by reducing dopaminergic overactivity.

PHARMACOKINETICS

Absorption

Prochlorperazine is well absorbed from the gastrointestinal tract after oral administration, but it undergoes significant first-pass metabolism, which reduces its systemic bioavailability. Peak plasma levels are typically reached within a few hours depending on the formulation used.

Distribution

Prochlorperazine has a large volume of distribution, indicating extensive distribution into body tissues, including the central nervous system.

Metabolism

Prochlorperazine is extensively metabolized in the liver, mainly by cytochrome P450 enzymes, into inactive metabolites. It undergoes significant first-pass metabolism, which reduces its oral bioavailability.

Elimination

Prochlorperazine is eliminated mainly through urine and bile as metabolites, with a small amount excreted unchanged. Its elimination half-life is relatively prolonged due to extensive tissue distribution.

PHARMACODYNAMICS

Prochlorperazine acts primarily as a dopamine (D2) receptor antagonist, producing antiemetic and antipsychotic effects. By blocking D2 receptors in the chemoreceptor trigger zone, it suppresses nausea and vomiting, while central dopamine blockade reduces psychotic symptoms. It also has mild anticholinergic and sedative properties, contributing to its overall therapeutic effects.

ADMINISTRATION

Prochlorperazine can be administered orally (tablets or buccal forms), intramuscularly, or intravenously depending on the clinical situation. For nausea and vomiting, it is often given in divided doses, while buccal tablets are placed between the gum and cheek. Dosage and route depend on the severity of symptoms and patient condition.

DOSAGE AND STRENGTH

Prochlorperazine is available in 5 mg and 10 mg tablets, as well as buccal tablets and injectable forms. For nausea and vomiting, the usual adult dose is 5–10 mg taken 2–3 times daily. Buccal tablets are typically 3–6 mg twice daily, and injectable doses vary based on severity. Dosage is adjusted according to patient response and clinical condition. 

DRUG INTERACTIONS

Increases sedation with CNS depressants (alcohol, benzodiazepines), may prolong QT interval with certain drugs, enhances anticholinergic effects, and increases risk of extrapyramidal symptoms with other dopamine antagonists.

FOOD INTERACTIONS

Food has no significant effect on the absorption or action of prochlorperazine. It can be taken with or without meals, but taking it with food may help reduce stomach upset.

CONTRAINDICATIONS

Avoid in hypersensitivity, coma/severe CNS depression, Parkinson’s disease, and severe bone marrow suppression.

SIDE EFFECTS

• Drowsiness

• Dizziness

• Dry mouth

• Blurred vision

• Constipation

• Extrapyramidal symptoms (tremors, rigidity, dystonia)

• Restlessness (akathisia)

• Hypotension

• Rare: neuroleptic malignant syndrome (serious)

OVERDOSE 
May cause severe CNS depression, extrapyramidal symptoms, hypotension, and possible cardiac arrhythmias. Treatment is supportive.

TOXICITY

Prochlorperazine toxicity is mainly due to excessive dopamine blockade, leading to severe extrapyramidal symptoms, sedation, hypotension, and in rare cases neuroleptic malignant syndrome. Cardiac toxicity such as QT prolongation and arrhythmias may also occur in severe overdose. Management is supportive and symptomatic.