What are the considerations for concomitant use of ziprasidone and Ativan (lorazepam)?

Concomitant Use of Ziprasidone and Lorazepam (Ativan)

Ziprasidone and lorazepam can be safely co-administered without adverse consequences, as demonstrated in multiple clinical trials, though caution is warranted in specific populations including alcohol-intoxicated patients and those with severe pulmonary insufficiency. 1, 2

Safety Profile of Combination Therapy

Clinical trials have specifically evaluated the safety of combining ziprasidone IM with benzodiazepines and found no safety concerns:

• No bradycardia, sinus pauses, disinhibition, confusion, excessive sedation, or respiratory depression was observed when lorazepam was co-administered with ziprasidone IM in controlled studies 2
• The combination did not adversely affect vital signs in emergency department settings, though it was associated with marginally longer ED stays 3
• Both agents can be used together for rapid control of acute agitation, with ziprasidone providing antipsychotic effects and lorazepam providing anxiolytic/sedative effects 1

Critical Contraindications and Warnings

Avoid or use extreme caution in these populations:

• Severe pulmonary insufficiency: Both agents cause central nervous system depression and can decrease respiratory drive 4
• Alcohol intoxication: Concurrent alcohol use with ziprasidone and benzodiazepines is associated with decreased oxygen saturations, requiring close monitoring 3
• Severe liver disease or myasthenia gravis: Benzodiazepines carry specific warnings in these conditions 4
• Patients with cardiac risk factors: Ziprasidone prolongs QTc interval and should be avoided in patients with recent myocardial infarction, baseline QT prolongation, or those taking other QT-prolonging medications 5, 6

Specific Dosing Considerations

When combining these agents, use lower doses than typical monotherapy:

• Lorazepam: Use 0.25-0.5 mg SC/IV q1h PRN (rather than standard 1-2 mg) when co-administered with an antipsychotic 4
• Ziprasidone IM: Standard dose of 10-20 mg can be used, with onset of action within 15-30 minutes 7, 1
• In older or frail patients, or those with COPD, further dose reduction of lorazepam is recommended 4

Clinical Decision Algorithm

Follow this approach when considering combination therapy:

1. Rule out absolute contraindications: Recent MI, baseline QT prolongation >500 msec, severe pulmonary disease, myasthenia gravis 4, 5

2. Assess alcohol/substance use: If patient is alcohol-intoxicated, monitor oxygen saturations closely and consider monotherapy with ziprasidone alone 3

3. Determine agitation severity:

   • For severe agitation requiring rapid control: Ziprasidone 10-20 mg IM can be given, with lorazepam 0.25-0.5 mg added if needed 4, 7
   • For moderate agitation in cooperative patients: Consider oral combination of lorazepam with an oral antipsychotic 4

4. Monitor vital signs: Check oxygen saturation, blood pressure, and respiratory rate, particularly in first 30-60 minutes after administration 3

Important Caveats

Be aware of these specific risks:

• The ESMO guidelines note that fatalities have been reported with concurrent use of benzodiazepines with high-dose olanzapine, suggesting general caution with combining benzodiazepines and second-generation antipsychotics at high doses 4
• Risk of oversedation and respiratory depression exists, particularly in vulnerable populations 4
• Both agents can paradoxically cause agitation or delirium in some patients 4
• No washout period is necessary when transitioning between agents or adding one to the other 5

Transition to Oral Therapy

The transition from IM to oral formulations has been well-tolerated:

• Ziprasidone oral must be administered with a 500 kcal meal to ensure adequate absorption; otherwise, bioavailability is substantially reduced 8
• Target oral ziprasidone dose of 120-160 mg/day is associated with optimal symptom control 8
• Symptoms remain controlled during the transition from IM to oral ziprasidone 2