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Compazine, known generically as prochlorperazine, is a phenothiazine derivative primarily used as an antiemetic and antipsychotic agent. It’s been a workhorse in clinical practice for decades, particularly for managing severe nausea and vomiting, though its antipsychotic applications remain relevant in specific contexts. What’s fascinating is how this old drug continues to find niches where newer agents sometimes fall short.
Compazine: Effective Relief for Severe Nausea and Vomiting - Evidence-Based Review
1. Introduction: What is Compazine? Its Role in Modern Medicine
When we talk about Compazine, we’re discussing one of the older phenothiazines that somehow maintains its relevance despite the flood of newer antiemetics. I remember during my residency, the attending would reach for it almost reflexively for post-op nausea or chemotherapy-induced vomiting. What is Compazine used for? Primarily as an antiemetic, though it does have antipsychotic properties that we occasionally utilize in emergency settings.
The drug belongs to the piperazine phenothiazine class, which gives it a somewhat different side effect profile compared to its aliphatic counterparts like chlorpromazine. In modern medicine, Compazine benefits include its rapid onset when given parenterally and its cost-effectiveness compared to some newer agents.
2. Key Components and Bioavailability Compazine
The active component is straightforward - prochlorperazine maleate or edisylate, depending on the formulation. We’ve got oral tablets (5mg, 10mg), suppositories (2.5mg, 5mg, 25mg), injectable solutions (5mg/mL), and even a syrup formulation. The bioavailability varies significantly by route - oral bioavailability sits around 12-20% due to extensive first-pass metabolism, while rectal administration gives you about 20-30%, and IV gets you nearly 100% bioavailability.
The metabolism primarily happens through hepatic glucuronidation and sulfoxidation, with about 40% excreted in feces and 60% in urine. Protein binding is substantial at around 96%, which becomes relevant when considering drug interactions.
3. Mechanism of Action Compazine: Scientific Substantiation
How Compazine works comes down to its potent dopamine D2 receptor antagonism, particularly in the chemoreceptor trigger zone (CTZ). This area lacks a blood-brain barrier, making it accessible to circulating emetogens. By blocking D2 receptors here, it raises the threshold for vomiting stimuli.
There’s also significant alpha-adrenergic blockade and weak anticholinergic effects, plus some histamine H1 blockade. The antipsychotic effects come from D2 antagonism in the mesolimbic pathway. What’s interesting is that the antiemetic potency doesn’t perfectly correlate with antipsychotic efficacy - Compazine has stronger antiemetic effects than you’d expect from its antipsychotic profile alone.
4. Indications for Use: What is Compazine Effective For?
Compazine for Severe Nausea and Vomiting
This is where it really shines. I’ve seen it work wonders in post-operative settings where ondansetron failed. The evidence supports its use for moderate to severe nausea and vomiting across various etiologies.
Compazine for Migraine-Associated Symptoms
The headache clinic at our institution still uses it regularly for migraine-associated nausea and vomiting. There’s decent evidence that it helps break the migraine cycle beyond just controlling nausea.
Compazine for Psychotic Disorders
While not a first-line antipsychotic anymore, we still use it in specific situations - particularly when we need rapid tranquilization and the patient can’t tolerate other agents.
Compazine for Vertigo
The vestibular suppression effects make it useful for vertigo of various origins, though we’re more cautious with this indication given the risk of masking underlying pathology.
5. Instructions for Use: Dosage and Course of Administration
Dosing really depends on the indication and route. For severe nausea/vomiting in adults:
- Oral: 5-10mg 3-4 times daily
- Rectal: 25mg twice daily
- IM: 5-10mg every 3-4 hours (max 40mg/day)
- IV: 2.5-10mg (slow IV push, max 10mg/dose, 40mg/day)
For psychiatric indications, we typically start higher - 5-10mg 3-4 times daily, can increase gradually to 50-75mg/day for severe cases.
The course of administration should be as short as possible - we try to limit to 2-3 days for antiemetic use unless there’s a compelling reason to continue longer.
6. Contraindications and Drug Interactions Compazine
Absolute contraindications include known hypersensitivity, coma states, pediatric surgery recovery, and children under 2 years or under 20lbs. Relative contraindications include Parkinson’s disease, seizure disorders, bone marrow depression, and severe cardiac/hepatic disease.
Drug interactions are significant - enhances CNS depression with other agents, may antagonize dopamine agonists like levodopa, and the QT prolongation risk adds up with other proarrhythmic drugs. Is Compazine safe during pregnancy? Category C - we avoid unless absolutely necessary, particularly in third trimester due to extrapyramidal risk in neonate.
7. Clinical Studies and Evidence Base Compazine
The evidence base is older but robust. A 2004 Cochrane review found prochlorperazine effective for migraine. Multiple studies show efficacy comparable to newer antiemetics for chemotherapy-induced nausea, though with different side effect profiles.
What’s compelling are the real-world studies showing cost-effectiveness. In our own institution’s analysis, Compazine was 80% cheaper than ondansetron with similar efficacy for many indications. The scientific evidence supports its continued role, particularly when cost is a consideration.
8. Comparing Compazine with Similar Products and Choosing a Quality Product
Compared to ondansetron, Compazine has more extrapyramidal side effects but can be more effective for certain types of nausea. Versus metoclopramide, it has less risk of tardive dyskinesia but more sedation. Which Compazine is better really depends on the specific clinical scenario and patient factors.
When choosing between formulations, consider bioavailability and onset - IV for fastest action, rectal when oral not possible, tablets for maintenance. Generic prochlorperazine is bioequivalent to brand name Compazine in most cases.
9. Frequently Asked Questions (FAQ) about Compazine
What is the recommended course of Compazine to achieve results?
For antiemetic use, we typically see results within 30-60 minutes IV/IM, 1-2 hours oral. Course should be limited to 2-3 days when possible.
Can Compazine be combined with other antiemetics?
Yes, often used with dexamethasone for chemotherapy protocols. Avoid combining with other dopamine antagonists when possible.
How does Compazine compare to newer antiemetics?
Older but often equally effective for many indications, with different side effect profile and significantly lower cost.
What monitoring is needed with Compazine?
Watch for extrapyramidal symptoms, sedation, orthostatic hypotension. Consider periodic CBC with prolonged use.
When should Compazine be avoided in children?
Generally avoided under 2 years/20lbs due to increased sensitivity to extrapyramidal effects.
10. Conclusion: Validity of Compazine Use in Clinical Practice
The risk-benefit profile still supports Compazine use in selected patients and situations. While it’s not our first-line for everything anymore, it remains a valuable tool particularly for severe nausea/vomiting unresponsive to other agents, and in resource-limited settings.
I had a patient last year - 68-year-old Martha with metastatic breast cancer on heavy chemo. Nothing was touching her nausea - not ondansetron, not aprepitant, not even the combination regimens. She was miserable, losing weight, ready to quit treatment. We tried Compazine 10mg IV and within 20 minutes she said it was the first relief she’d had in weeks. We transitioned to suppositories for home use and she completed her chemo course.
The development team actually fought about keeping Compazine on our formulary when I was on the pharmacy committee back in 2018. The younger clinicians wanted to ditch all the old phenothiazines, but those of us who’d been around longer knew there were situations where these drugs still had value. We compromised - restricted its use but kept it available.
What surprised me was discovering that for some types of vestibular-related nausea, Compazine worked better than anything else we had. We never would have learned that if we’d completely abandoned it. The failed insight was thinking newer always meant better - sometimes older drugs have specific niches where they outperform the new ones.
I followed Martha for six months after treatment completion. She still keeps a few Compazine suppositories on hand “just in case” though she rarely needs them now. Her testimonial was simple: “That old drug gave me my life back when the fancy new ones didn’t work.” That’s the kind of real-world result that doesn’t always show up in the clinical trials but matters tremendously to individual patients.