What is an alternative to Alprazolam (Xanax) for a hospice patient who cannot swallow and is allergic to Ativan (Lorazepam)?

Alternative to Alprazolam for Hospice Patients Unable to Swallow and Allergic to Lorazepam

Midazolam administered subcutaneously is the preferred alternative for this patient, starting at 2.5-5 mg every 2-4 hours as needed for anxiety or agitation. 1

Primary Recommendation: Subcutaneous Midazolam

For hospice patients who cannot swallow and have a lorazepam allergy, midazolam via subcutaneous route is the optimal benzodiazepine alternative. 1 This recommendation is based on:

• Route compatibility: Midazolam can be administered subcutaneously, intravenously, or intramuscularly, making it ideal for patients unable to take oral medications 2, 3
• Rapid onset: Midazolam has faster onset and shorter duration than other benzodiazepines, allowing for flexible dosing adjustments in the dying patient 4
• Established palliative care use: Midazolam is considered one of the four essential drugs for quality end-of-life care and is one of the three most frequently administered drugs in palliative care 5, 4

Dosing Strategy

• Initial dose: Start with 2.5-5 mg subcutaneously every 2-4 hours as needed for anxiety or agitation 1
• Continuous infusion option: For refractory symptoms, the European Society for Medical Oncology recommends continuous subcutaneous infusion starting at 0.5-1 mg/hour 6
• Dose reduction: Elderly or debilitated patients require lower starting doses due to increased sensitivity and slower elimination 2, 3

Alternative Non-Benzodiazepine Options

If benzodiazepines are contraindicated or ineffective, consider phenothiazines as alternatives:

Levomepromazine (Methotrimeprazine)

• Dosing: 12.5-25 mg subcutaneously for refractory anxiety or agitation 7, 8
• Advantages: Has analgesic properties in addition to anxiolytic effects 8

Chlorpromazine

• Dosing: 12.5 mg IV or IM every 4-12 hours 7, 8
• Route options: Can be administered parenterally (IV or IM) and rectally 8
• Monitoring requirement: Blood pressure must be monitored continuously during IV administration due to hypotension risk 8

Phenobarbital

• Listed as an alternative sedative option for palliative care, though specific dosing for anxiety is not detailed in the guidelines 7

Critical Safety Considerations

Respiratory Monitoring

• Concomitant opioid use: The combination of midazolam with opioids (common in hospice) may result in profound sedation and respiratory depression 2, 3
• Close monitoring: If using midazolam with opioids, monitor closely for respiratory depression and sedation 2, 3
• Imminently dying patients: For patients actively dying, routine vital sign monitoring is not performed; only comfort parameters are assessed 7

Dosing Precautions

• Individualization is mandatory: Midazolam must never be used without dose individualization, particularly with other CNS depressants 2, 3
• Titration approach: Start low and titrate to the least amount necessary to provide adequate relief of suffering 7
• Breakthrough dosing: Provision for emergency bolus therapy to manage breakthrough symptoms should be available 7

Common Clinical Pitfalls to Avoid

• Do not confuse anxiety with delirium: Benzodiazepines can worsen delirium if given as initial treatment when the underlying problem is delirium rather than anxiety 1
• Avoid rapid injection: In any patient, but especially those on opioids, rapid administration increases risk of severe hypotension and respiratory depression 3
• Consider paradoxical reactions: Agitation, involuntary movements, hyperactivity, and combativeness can occur with midazolam and may represent paradoxical reactions or inadequate dosing 2, 3

Cross-Sensitivity Consideration

While you mention lorazepam allergy, note that cross-reactivity between benzodiazepines is possible but not universal. If the lorazepam allergy was a true IgE-mediated reaction (anaphylaxis, angioedema), midazolam should be used with extreme caution or avoided entirely, favoring the non-benzodiazepine phenothiazine alternatives listed above. 2, 3

Administration Routes Available

The guidelines emphasize multiple parenteral routes for patients unable to swallow 7:

• Subcutaneous (preferred for hospice home care)
• Intravenous
• Intramuscular
• Rectal
• Via stoma or gastrostomy (if present)