Can Zyprexa (olanzapine) be given with Haldol (haloperidol)?

Can Zyprexa (Olanzapine) Be Given With Haldol (Haloperidol)?

No, Zyprexa (olanzapine) should not be combined with Haldol (haloperidol) in the same syringe or given simultaneously, as the FDA drug label explicitly states that combining these agents results in degradation of olanzapine due to low pH. 1

Critical FDA Contraindication

The FDA-approved prescribing information for Zyprexa IntraMuscular specifically warns: "ZYPREXA IntraMuscular should not be combined in a syringe with haloperidol injection because the resulting low pH has been shown to degrade olanzapine over time." 1

Sequential Administration May Be Acceptable

While simultaneous administration is contraindicated, sequential use of these agents (switching from one to the other) is supported by clinical evidence:

• Multiple studies demonstrate safe and effective transitions from haloperidol to olanzapine when patients experience haloperidol-induced extrapyramidal symptoms 2, 3
• Direct switching from haloperidol (mean dose 12.7 mg/day) to olanzapine (mean dose 11.4 mg/day) resulted in 87.2% reduction in extrapyramidal symptoms and was successful in 90.5% of patients 2
• Transition from IM haloperidol to oral olanzapine maintained agitation control while improving the safety profile 3

Clinical Context for Combination Therapy

In emergency settings managing acute agitation, guidelines support using either agent but not both together:

• The American Academy of Pediatrics guidelines list haloperidol and olanzapine as separate treatment options for agitation, never recommending their combination 4
• Studies comparing IM olanzapine 10 mg versus IM haloperidol 7.5 mg show equivalent efficacy for acute agitation, with olanzapine demonstrating superior extrapyramidal symptom safety 5, 3

Alternative Combination Strategies

If combination therapy is needed for severe agitation, evidence-based alternatives include:

• Haloperidol + benzodiazepine (lorazepam): Can be given together in the same syringe with additive effects 4
• Olanzapine + benzodiazepine: The manufacturer advises caution, but recent evidence suggests this combination is safe in alcohol-negative patients, though it should be avoided in alcohol-intoxicated patients due to risk of oxygen desaturation 6

Practical Algorithm for Antipsychotic Selection

When choosing between haloperidol and olanzapine for acute agitation:

1. Assess cardiac risk: Check for QTc prolongation, recent MI, or concurrent QT-prolonging medications—if present, avoid both agents but particularly be cautious 4
2. Evaluate extrapyramidal symptom risk: If patient has Parkinson's disease, dementia with Lewy bodies, or prior dystonic reactions, choose olanzapine over haloperidol 4
3. Consider metabolic factors: Olanzapine is weight-neutral compared to other atypicals but still has metabolic effects with long-term use 7
4. Assess alcohol intoxication status: If patient is alcohol-positive and benzodiazepine co-administration is anticipated, haloperidol may be safer than olanzapine 6

Common Pitfall to Avoid

The most critical error is attempting to mix these medications in the same syringe for IM administration. This pharmaceutical incompatibility causes olanzapine degradation and renders the medication ineffective 1. If both agents are deemed necessary (which is rarely clinically justified), they must be administered as separate injections at different sites.