How should I prescribe a compounded ABH (lorazepam, diphenhydramine, haloperidol) topical gel for hospice or palliative‑care patients with breakthrough nausea, vomiting, or terminal delirium refractory to oral anti‑emetics?

ABH Gel Should Not Be Prescribed for Hospice or Palliative Care Patients

Do not prescribe ABH (lorazepam, diphenhydramine, haloperidol) topical gel for breakthrough nausea, vomiting, or terminal delirium—the drugs are not absorbed through the skin at therapeutic levels and the formulation is ineffective. 1, 2

Evidence Against ABH Gel Efficacy

Pharmacokinetic Failure

• No lorazepam or haloperidol was detected in plasma samples from healthy volunteers who applied standard 1.0 mL doses of ABH gel, with detection limits down to 0.05 ng/mL 1
• Diphenhydramine showed only erratic, subtherapeutic absorption with maximum concentrations of 0.30 ng/mL—far below levels needed for antiemetic activity 1
• Theoretical steady-state plasma concentrations from percutaneous absorption studies were 2.30 ng/mL for lorazepam, 0.13 ng/mL for haloperidol, and 1.6 ng/mL for diphenhydramine—all substantially below therapeutic thresholds required for symptom control 2

Clinical Trial Evidence

• A randomized controlled trial comparing ABH gel to placebo in 22 participants found no significant benefit over placebo for nausea relief 3
• The continued use of ABH gel represents a "pricey placebo" that delays treatment with evidence-based modalities 4

Recommended Alternatives for Breakthrough Nausea/Vomiting

First-Line Systemic Antiemetics

• Haloperidol 0.5–1 mg orally or subcutaneously every 4–6 hours as needed is effective when given by routes that achieve systemic absorption 5, 6
• Haloperidol can be administered by multiple routes (oral, subcutaneous, intravenous) and requires no dose adjustment in renal or hepatic insufficiency 6
• Olanzapine 2.5–5 mg orally or subcutaneously is recommended as first-line for elderly patients with advanced cancer, starting at the lower end (2.5 mg) for geriatric populations 5

Alternative Antipsychotics

• Quetiapine 25 mg orally (immediate release) offers lower risk of extrapyramidal side effects and sedating properties beneficial for agitation 5
• Levomepromazine 12.5–25 mg subcutaneously can be used for patients unable to swallow 5

Adjunctive Agents

• Lorazepam is a useful adjunct to antiemetic drugs but should not be used as monotherapy 7
• For severe agitation refractory to antipsychotics, lorazepam 0.25–0.5 mg may be added, though use caution in elderly patients due to fall risk and paradoxical agitation 5
• Diphenhydramine is no longer recommended as an adjunctive antiemetic since the rationale (preventing extrapyramidal symptoms from high-dose metoclopramide) is obsolete 7

Management of Terminal Delirium

Antipsychotic Selection

• Olanzapine 2.5–5 mg is preferred for elderly patients with advanced cancer and delirium-related agitation, with dose reduction appropriate for advanced age 5
• Haloperidol 0.5–1 mg orally at night and every 2 hours as needed for patients who can swallow 5
• Short-term use at the lowest effective dose is essential, particularly when patients pose risk to themselves or others 5

Monitoring Requirements

• Monitor for drowsiness, orthostatic hypotension, and extrapyramidal symptoms 5
• Antipsychotics themselves can potentially worsen agitation and delirium, requiring careful observation 5
• Ensure well-controlled pain, as uncontrolled pain worsens delirium 5

Critical Pitfalls to Avoid

• Do not rely on topical formulations of medications that require systemic absorption for efficacy 1, 2
• Do not use benzodiazepines alone as first-line treatment for delirium in patients not already taking them 5
• Do not delay effective treatment by prescribing unproven compounded products when evidence-based alternatives exist 4
• Address reversible causes of symptoms first: hypoxia, urinary retention, constipation, medication toxicity 5

Prescription Algorithm for Refractory Symptoms

For breakthrough nausea/vomiting:

1. Start haloperidol 0.5–1 mg subcutaneously or orally every 4–6 hours PRN 5, 6
2. If inadequate response, add lorazepam 0.25–0.5 mg as adjunct 5
3. Consider olanzapine 2.5–5 mg if haloperidol ineffective or not tolerated 5

For terminal delirium with agitation:

1. Start olanzapine 2.5 mg orally/subcutaneously (elderly patients) 5
2. If severe agitation persists, add lorazepam 0.25–0.5 mg 5
3. Alternative: quetiapine 25 mg orally if olanzapine unavailable 5