Compazine (Prochlorperazine) vs. Top Antiemetic Alternatives - 2025 Comparison

Key Takeaways

• Compazine is a phenothiazine used for nausea, but it carries a higher risk of extrapyramidal side effects than newer agents.
• Ondansetron offers the best safety profile for chemotherapy‑induced nausea, while metoclopramide is cheaper for mild to moderate cases.
• Promethazine is handy for motion sickness but can cause heavy sedation.
• Haloperidol and droperidol work well for severe refractory nausea but require careful cardiac monitoring.
• Choosing the right drug hinges on cause of nausea, patient age, comorbs, and cost considerations.

Nausea and vomiting can turn any day upside‑down. When over‑the‑counter remedies fail, doctors often turn to prescription antiemetics. One name that pops up frequently is Compazine, the brand name for prochlorperazine. But is it always the best pick? Below we break down how Compazine stacks up against the most common alternatives, so you can decide which medication fits your situation without wading through medical jargon.

What is Compazine (Prochlorperazine)?

If you’ve never heard the term, think of it as a "phenothiazine"‑type drug. Compazine is a prescription medication whose generic name is prochlorperazine, approved by the FDA for treating severe nausea, vomiting, and hiccups, as well as for short‑term control of psychotic disorders. It was first marketed in the early 1960s and remains on the WHO Essential Medicines List. The drug works by blocking dopamine D2 receptors in the brain’s chemoreceptor trigger zone, which reduces the urge to vomit.

How Compazine Works - Mechanism and Formulations

Prochlorperazine belongs to the phenothiazine class, originally designed as an antipsychotic. Its anti‑nausea action comes from dopamine antagonism, plus some antihistamine and anticholinergic activity that dampens the vestibular system.

• Available forms: 5mg tablets, 10mg tablets, and an injectable solution (5mg/mL).
• Typical adult dose for nausea: 5-10mg orally or intravenously every 6hours as needed.
• Onset of relief: 15-30minutes when given IV, 30-60minutes orally.

Because it crosses the blood‑brain barrier, it can cause central nervous system side effects that newer agents often avoid.

Pros and Cons of Compazine

Every drug has trade‑offs. Here’s a quick rundown:

• Pros: Fast onset (especially IV), inexpensive in NZ, effective for a wide range of nausea triggers (migraine, postoperative, vertigo).
• Cons: Higher incidence of extrapyramidal symptoms (e.g., dystonia, akathisia), potential for sedation, can prolong the QT interval, not ideal for pregnant women without specialist advice.

Top Alternatives - Quick Comparison Table

Alternative #1 - Metoclopramide

Metoclopramide is a dopamine‑2 receptor antagonist that also increases gastric motility, making it useful for nausea tied to delayed gastric emptying. It comes in 5mg and 10mg tablets, plus an injectable form. For most adults, 10mg taken 30minutes before a known nausea trigger works well.

• Pros: Cheap, good for gastroparesis, less likely to cause severe dystonia than Compazine.
• Cons: Can cause restlessness, and long‑term use risks tardive dyskinesia - a concern for chronic users.

Alternative #2 - Ondansetron

Ondansetron is a selective 5‑HT3 receptor antagonist, the go‑to drug for chemotherapy and radiation‑induced nausea. Available as 4mg tablets, orally disintegrating strips, and IV solution. It’s more expensive but boasts a clean side‑effect profile.

• Pros: Minimal sedation, works well for severe acute nausea, very low risk of movement disorders.
• Cons: Higher cost, occasional headache or constipation, QT‑prolongation warning in high‑dose regimens.

Alternative #3 - Promethazine

Promethazine is an H1 antihistamine with strong anticholinergic effects, traditionally used for motion sickness and allergic reactions. Comes in 25mg tablets and a syrup for children.

• Pros: Very effective for motion‑induced nausea, inexpensive, also helps with allergic itching.
• Cons: Can cause pronounced drowsiness, dry mouth, and at high doses may depress breathing - not ideal for elderly patients.

Alternative #4 - Haloperidol (and Droperidol)

Haloperidol is a high‑potency typical antipsychotic that blocks dopamine D2 receptors, sometimes repurposed for refractory nausea. Low‑dose IV (0.5mg) can calm severe vomiting after surgery.

Droperidol is a close cousin with a shorter half‑life, often used in emergency departments. Both need cardiac monitoring because they can lengthen the QT interval.

• Pros: Powerful anti‑nausea effect when other drugs fail, useful in ICU settings.
• Cons: Risk of severe extrapyramidal symptoms, QT prolongation, requires ECG monitoring.

Decision Criteria - How to Choose the Right Antiemetic

Instead of guessing, match the drug to the situation using these checkpoints:

1. Cause of nausea: Chemotherapy → ondansetron; migraine or vertigo → compazine or metoclopramide; motion sickness → promethazine.
2. Patient age: Children under 12 often need promethazine syrup; elderly patients should avoid strong dopamine blockers that cause akathisia.
3. Cardiac risk: If the patient has a history of arrhythmia, steer clear of drugs that prolong QT (compazine, ondansetron at high dose, haloperidol).
4. Interaction profile: Metoclopramide interacts with SSRIs (serotonin syndrome risk); ondansetron is metabolized by CYP3A4, watch for inhibitors like ketoconazole.
5. Cost and accessibility: In New Zealand, compazine and promethazine are subsidised under PHARMAC, while ondansetron may require private prescription.
6. Desired sedation level: If the patient wants to stay alert (e.g., surgical prep), avoid promethazine.

Best‑Fit Scenarios

• Chemo‑induced nausea: Ondansetron (first‑line), add low‑dose metoclopramide if breakthrough.
• Migraine‑related vomiting: Compazine or metoclopramide; compazine works faster IV.
• Post‑operative nausea: Ondansetron for most, but if cost is a barrier, compazine IV is a viable alternative.
• Motion sickness on a cruise: Promethazine 25mg PO 30min before boarding.
• Elderly with constipation: Avoid anticholinergic promethazine; consider low‑dose metoclopramide.

Safety Tips & Common Pitfalls

Even the right drug can cause trouble if you miss a warning:

• Never give high‑dose compazine to someone with Parkinson’s disease - dopamine blockade worsens motor symptoms.
• Watch for acute dystonic reactions with any dopamine antagonist; a single dose of benztropine can reverse the spasm.
• Check renal function before dosing ondansetron; accumulation can raise QT risk.
• Pregnant women: Promethazine is CategoryC, ondansetron is CategoryB; discuss with obstetrician.
• Never combine multiple dopamine antagonists (e.g., compazine + metoclopramide) without specialist input.

Quick Checklist for Clinicians & Patients

1. Identify nausea trigger.
2. Screen for cardiac, psychiatric, and renal issues.
3. Select first‑line drug based on efficacy‑cost‑safety balance.
4. Prescribe the lowest effective dose; monitor for side effects within 24hours.
5. Document response; switch to alternative if symptoms persist after two doses.