What is the dose of diphenhydramine (antihistamine) for preventing akathisia in children treated with prochlorperazine (antiemetic)?

Diphenhydramine Dosing for Prevention of Prochlorperazine-Induced Akathisia in Children

The recommended dose of diphenhydramine for preventing akathisia in children treated with prochlorperazine is 1-2 mg/kg per dose (maximum 50 mg) administered parenterally. 1

Dosing Guidelines

• Diphenhydramine should be administered at 1-2 mg/kg per dose with a maximum single dose of 50 mg 1
• Administration should occur prior to or concurrently with prochlorperazine to effectively prevent akathisia 2, 3
• The parenteral route (intravenous or intramuscular) is preferred for acute prevention when prochlorperazine is given intravenously 1

Evidence for Efficacy

• Diphenhydramine has been shown to rapidly reduce signs and symptoms of acute akathisia induced by prochlorperazine in clinical studies 4
• In pediatric emergency department settings, diphenhydramine is routinely co-administered with prochlorperazine for migraine treatment to prevent akathisia 2, 3
• Despite prophylactic diphenhydramine use, some studies report that akathisia remains a concern, with approximately 5% of children still developing definitive akathisia and up to 34% showing possible symptoms 3

Clinical Considerations

• Extrapyramidal symptoms (EPS), including akathisia, are among the most common adverse effects of prochlorperazine in children (9% in single-dose studies) 5
• Akathisia presents as an unpleasant symptom complex characterized by restlessness and agitation 6
• Sedation is a common side effect of diphenhydramine (10% in multiple-dose studies) and should be monitored 5
• The onset of action for intravenous diphenhydramine is several minutes, with effects lasting up to 4-6 hours 1

Pitfalls and Caveats

• Diphenhydramine may cause excessive sedation when combined with prochlorperazine, requiring careful monitoring of respiratory status and level of consciousness 1
• Other potential adverse effects of diphenhydramine include hypotension, dizziness, blurred vision, dry mouth, epigastric discomfort, and urinary retention 1
• While diphenhydramine is effective for preventing akathisia, it does not address other potential side effects of prochlorperazine such as tardive dyskinesia or neuroleptic malignant syndrome 5
• For children with a history of adverse reactions to antihistamines, alternative approaches to managing akathisia risk should be considered 1

Alternative Approaches

• In cases where diphenhydramine is contraindicated, consider using a lower dose of prochlorperazine to reduce the risk of akathisia 5
• For children with severe nausea requiring antiemetic therapy but at high risk for akathisia, alternative antiemetics such as ondansetron may be considered 1