Is there a contraindication between Metoclopramide (Reglan) and Olanzapine (Zyprexa)?

Contraindication Between Metoclopramide (Reglan) and Olanzapine (Zyprexa)

Concurrent use of metoclopramide (Reglan) and olanzapine (Zyprexa) should be avoided due to the increased risk of severe extrapyramidal symptoms from their combined dopamine antagonist effects.

Mechanism of Interaction

Both medications act as dopamine (D2) receptor antagonists, though through different mechanisms:

• Metoclopramide is a prokinetic agent and antiemetic that blocks dopamine receptors
• Olanzapine is an atypical antipsychotic that also has dopamine receptor antagonist properties

When used together, their effects on dopamine receptors are additive, significantly increasing the risk of extrapyramidal symptoms (EPS).

Evidence for Contraindication

The 2022 case report by Neuropsychopharmacology Reports documents a patient who developed prolonged extrapyramidal symptoms after receiving concurrent olanzapine and metoclopramide for chemotherapy-induced nausea 1. The patient experienced:

• Persistent akathisia
• Rigidity
• Postural reflex disorder
• Mask-like facial expression

These symptoms persisted even after discontinuation of the medications and required anticholinergic treatment with biperiden 1.

Specific Extrapyramidal Risks

When these medications are combined, patients may experience:

• Acute dystonia: Involuntary muscle contractions
• Akathisia: Severe restlessness and inability to remain still
• Parkinsonism: Tremor, rigidity, and bradykinesia
• Tardive dyskinesia: Potentially irreversible involuntary movements

Risk Factors for Severe Reactions

The risk of extrapyramidal symptoms is higher in:

• Elderly patients
• Patients with prolonged use of either medication
• Those with a history of previous extrapyramidal symptoms
• Patients receiving higher doses of either medication 2, 3

Alternative Management Approaches

For patients requiring antiemetic therapy:

1. If psychiatric symptoms require olanzapine: Consider alternative antiemetics that don't antagonize dopamine receptors:

   • 5-HT3 antagonists (ondansetron)
   • NK1 antagonists (aprepitant)
   • Dexamethasone

2. If antiemetic therapy is primary need: Consider:

   • Using olanzapine alone as an antiemetic (shown to be superior to metoclopramide in some studies) 4, 5
   • Using alternative antiemetics without dopamine antagonist properties

Monitoring if Combination Cannot Be Avoided

In rare situations where the combination cannot be avoided:

1. Use the lowest effective doses of both medications
2. Monitor closely for early signs of extrapyramidal symptoms:
   • Restlessness
   • Tremor
   • Muscle rigidity
   • Changes in gait
3. Have anticholinergic rescue medication (biperiden or benztropine) immediately available
4. Discontinue one or both medications at the first sign of extrapyramidal symptoms

Conclusion

The evidence strongly suggests avoiding the concurrent use of metoclopramide and olanzapine due to the significantly increased risk of severe and potentially prolonged extrapyramidal symptoms. Alternative antiemetic strategies should be employed when patients require either medication.