Can Diphenhydramine Be Given Intramuscularly?
Yes, diphenhydramine can be safely administered intramuscularly (IM) and is FDA-approved for this route of administration. 1
FDA-Approved Routes and Dosing
Diphenhydramine hydrochloride injection is explicitly indicated for both intravenous and intramuscular administration when the oral form is impractical. 1
Adult IM Dosing:
- 10-50 mg deep intramuscularly, up to 100 mg if required 1
- Maximum daily dosage: 400 mg 1
- The injection should be given deep into the muscle 1
Pediatric IM Dosing:
- 5 mg/kg/24 hours or 150 mg/m²/24 hours divided into four doses 1
- Maximum daily dosage: 300 mg 1
- Not recommended for premature infants and neonates 1
Clinical Context for IM Administration
Anaphylaxis Management:
- 1-2 mg/kg or 25-50 mg per dose administered intramuscularly or intravenously 2
- The American Academy of Allergy, Asthma, and Immunology recommends this dosing for anaphylaxis 2
- Combination with H2-blockers (ranitidine) is superior to diphenhydramine alone in managing anaphylactic reactions 3, 2
Pretreatment for Radiocontrast Media Reactions:
- 50 mg intramuscularly 1 hour before radiocontrast media administration in patients with prior anaphylactoid reactions 3
- For emergency procedures: 50 mg IM 1 hour before contrast administration (combined with IV hydrocortisone) 3
Important Safety Considerations
Onset and Duration:
Adverse Effects to Monitor:
- Anticholinergic effects: confusion, delirium (especially in elderly), dry mouth, blurred vision, urinary retention 3, 2
- Cardiovascular effects: hypotension, tachycardia 3
- Respiratory depression (particularly when combined with other CNS depressants) 3
- QT prolongation has been reported with chronic use 4
Critical Pitfalls:
Avoid rapid IV administration - when given intravenously, the rate should generally not exceed 25 mg/min to minimize hypotension risk 1. While IM administration avoids this specific concern, it's important to distinguish between routes.
Risk of myonecrosis with repeated deep IM injections - one case report documented severe myonecrosis at injection sites with chronic IM diphenhydramine abuse 4. This is distinct from subcutaneous administration, which has been shown safe in hospice settings (648 injections without adverse cutaneous reactions) 5.
Pediatric cardiovascular risk - one case report documented cardiac arrest in a 3-month-old infant following 1.25 mg/kg IV diphenhydramine, highlighting the need for caution in vulnerable populations 6.
Not recommended for elderly patients due to high anticholinergic burden and increased risk of confusion, falls, and delirium 2.
Alternative Routes When IM is Impractical
If IM access is difficult but parenteral administration is needed, subcutaneous administration has been demonstrated safe in hospice settings with no reported skin necrosis in 648 injections 5. This contradicts older case reports from the 1990s that described necrosis with subcutaneous use for local anesthesia 5.