What are the guidelines for using Stemitil (prochlorperazine) and metoclopramide together?

Concurrent Use of Prochlorperazine (Stemitil) and Metoclopramide

The concurrent use of prochlorperazine (Stemitil) and metoclopramide should be avoided due to the significantly increased risk of severe extrapyramidal symptoms, including persistent dystonia and rigidity that may be more severe than with either agent alone.

Pharmacological Considerations

Both medications are dopamine antagonists that work through similar mechanisms:

• Prochlorperazine (Stemitil): A phenothiazine antiemetic that blocks dopamine receptors in the chemoreceptor trigger zone
• Metoclopramide (Reglan): A prokinetic agent and antiemetic that also antagonizes dopamine receptors

When used together, these medications can cause additive dopaminergic blockade, significantly increasing the risk of adverse effects.

Evidence Against Combination Use

The combination of these medications has been documented to cause severe adverse effects:

• A case report showed a persistent, generalized syndrome of dystonia and rigidity (tardive dystonia-parkinsonism) in a patient treated with this combination that was more severe than typically seen with either drug alone and may have contributed to the patient's death 1

• The extreme severity of extrapyramidal disorders with this combination is particularly concerning in patients with pre-existing cerebral dysfunction 1

Appropriate Antiemetic Selection

Guidelines suggest using these agents individually rather than in combination:

For Nausea and Vomiting Management:

1. First-line options (choose ONE):

   • Metoclopramide: 10-20 mg PO/IV every 6 hours 2, 3
   • Prochlorperazine: 5-10 mg PO/IV every 6-8 hours 2
   • Ondansetron: 8 mg PO/IV every 8-12 hours 2

2. For refractory nausea:

   • Add a second agent with a different mechanism of action (e.g., add ondansetron if using metoclopramide) 2
   • Consider dexamethasone as an adjunct 2
   • Consider opioid rotation if nausea is opioid-induced 2

Specific Clinical Scenarios

For Pregnancy-Related Nausea:

• Metoclopramide is preferred over prochlorperazine 2
• Ondansetron should be used as a second-line therapy after metoclopramide 2

For Cancer-Related Nausea:

• Either agent can be used individually, but not together 2
• For persistent symptoms, adding a serotonin antagonist (ondansetron) is preferred over combining dopamine antagonists 2

For Post-operative Nausea:

• Either metoclopramide (0.1-0.2 mg/kg) or prochlorperazine (0.1-0.2 mg/kg) can be used individually 4
• Comparative studies show similar efficacy when used separately 4

High-Risk Populations

Exercise particular caution with either medication (and absolutely avoid the combination) in:

• Elderly patients (especially females)
• Patients with cerebral palsy or other neurological disorders
• Patients with renal or hepatic impairment
• Patients already taking other antipsychotic medications

Management of Extrapyramidal Symptoms

If extrapyramidal symptoms occur with either agent:

• Immediately discontinue the medication
• Consider diphenhydramine 25-50 mg IV/PO for acute dystonic reactions 3
• Monitor closely for resolution of symptoms

Conclusion

While both prochlorperazine and metoclopramide are effective antiemetics individually, their concurrent use significantly increases the risk of severe extrapyramidal symptoms and should be avoided. When antiemetic therapy is required, select one agent based on the clinical scenario and patient characteristics, and if additional therapy is needed, choose an agent with a different mechanism of action.