Updated: January 27, 2026

Compazine Drug Interactions: What to Avoid and What to Tell Your Doctor in 2026

Author

Peter Daggett

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Contraindicated Combinations: Do Not Use Together
CNS Depressants: Serious Risk of Dangerous Sedation
QT Interval Prolonging Drugs: Cardiac Arrhythmia Risk
Dopamine-Related Interactions
Other Drug Interactions to Discuss With Your Doctor
Lab Test Interference

Learn which drugs, foods, and supplements interact with Compazine (prochlorperazine), including serious interactions to avoid and what to tell your doctor.

Compazine (prochlorperazine) is a powerful medication that works through multiple receptor systems in the body. Because of this, it has the potential to interact with a significant number of other drugs, supplements, and substances. This guide covers the most clinically important interactions — from contraindicated combinations to things you should monitor carefully.

Always give your doctor and pharmacist a complete list of everything you take, including prescription drugs, over-the-counter medications, supplements, and alcohol.

Contraindicated Combinations: Do Not Use Together

Amisulpride: Both are dopamine antagonists. Combining them significantly increases the risk of neuroleptic malignant syndrome (NMS) — a potentially fatal reaction. This combination is contraindicated.

Metrizamide (contrast dye for myelography): Prochlorperazine must be discontinued at least 24 hours before a myelogram procedure using metrizamide. The combination significantly raises the risk of seizures.

CNS Depressants: Serious Risk of Dangerous Sedation

Combining prochlorperazine with other central nervous system (CNS) depressants can cause profound sedation, respiratory depression, coma, and death. The FDA requires prescribers to limit these combinations to patients who have no adequate alternatives, at the lowest necessary doses. Avoid combining with:

Opioid pain medications (codeine, hydrocodone, oxycodone, morphine, fentanyl) — combined CNS depression with risk of life-threatening respiratory depression

Benzodiazepines (alprazolam, diazepam, lorazepam, clonazepam) — additive CNS depression

Alcohol — enhanced sedation and impaired motor coordination; avoid alcohol while taking prochlorperazine

Barbiturates (phenobarbital) — combined CNS depression

Antihistamines with sedating properties (diphenhydramine/Benadryl, hydroxyzine) — additive drowsiness; use with caution

QT Interval Prolonging Drugs: Cardiac Arrhythmia Risk

Prochlorperazine can prolong the QT interval — the electrical recovery phase of the heartbeat. When combined with other QT-prolonging drugs, the risk of a dangerous heart rhythm called Torsade de Pointes increases. Drugs to watch for include:

Dofetilide (Tikosyn) — serious arrhythmia risk; avoid combination

Erythromycin and clarithromycin (macrolide antibiotics) — additive QT prolongation; avoid or use with ECG monitoring

Fluoroquinolone antibiotics (ciprofloxacin, levofloxacin) — some have QT-prolonging effects; use caution

Antifungals (fluconazole, ketoconazole) — QT prolongation and inhibit prochlorperazine metabolism, increasing blood levels

Tricyclic antidepressants (amitriptyline, nortriptyline) — additive QT effect and anticholinergic effects

Metoclopramide (Reglan): Both block dopamine D2 receptors. Using them together significantly increases the risk of extrapyramidal symptoms (EPS) and NMS. Generally avoid combining.

Cabergoline and other dopamine agonists: Used for Parkinson's disease or hyperprolactinemia. Prochlorperazine blocks dopamine receptors and may reduce the effectiveness of these drugs. This combination may worsen Parkinson's symptoms. Discuss with your doctor.

Levodopa (Parkinson's medication): Prochlorperazine opposes the action of levodopa by blocking dopamine receptors. This can significantly reduce levodopa's effectiveness and worsen Parkinson's disease. Avoid prochlorperazine in patients with Parkinson's disease.

Other Drug Interactions to Discuss With Your Doctor

Blood pressure medications: Prochlorperazine's alpha-1 blocking effect can cause additive blood pressure lowering. Monitor for excessive hypotension.

Lithium: Some reports suggest increased risk of neurotoxicity when combined with antipsychotics including prochlorperazine. Monitor for confusion, tremor, or unusual neurological symptoms.

Anticholinergic medications (oxybutynin, scopolamine, some antidepressants): Combined anticholinergic effects may cause confusion, urinary retention, constipation, or heat stroke — particularly in elderly patients.

Lab Test Interference

Prochlorperazine can interfere with certain laboratory tests, potentially causing false results. Inform all lab personnel and healthcare providers that you take this medication before any testing. Known interferences include:

Phenylketonuria (PKU) screening tests

Certain pregnancy tests

For a full breakdown of side effects related to these mechanisms, see: Compazine Side Effects: What to Expect. If you're struggling to find prochlorperazine at your pharmacy, medfinder.com can help locate pharmacies with it in stock near you.

Frequently Asked Questions

No. You should avoid alcohol while taking prochlorperazine. Both are CNS depressants, and combining them significantly increases sedation, dizziness, and impaired coordination. In severe cases, the combination can cause dangerous respiratory depression.

This combination should be used with caution and only under a doctor's supervision. Both medications can prolong the QT interval. However, they work through different mechanisms (ondansetron blocks serotonin receptors; prochlorperazine blocks dopamine receptors), so combining them is sometimes done in clinical settings. Always check with your prescriber.

Yes, potentially. Tricyclic antidepressants (amitriptyline, nortriptyline) have additive QT prolongation and anticholinergic effects. Some SSRIs may inhibit CYP enzymes that metabolize prochlorperazine, raising its blood levels. Always tell your prescriber about any antidepressants you take before starting prochlorperazine.

No. Prochlorperazine should be avoided in patients with Parkinson's disease. It blocks dopamine receptors throughout the brain, which directly opposes the action of Parkinson's medications like levodopa and can significantly worsen motor symptoms. Talk to your neurologist about safer antiemetic options if you have Parkinson's disease.

Be cautious with sedating supplements (valerian, kava, melatonin) as they may enhance prochlorperazine's CNS depressant effects. St. John's Wort may affect liver enzyme metabolism. Always tell your pharmacist and doctor about all supplements you take, as these interactions are often overlooked.

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