What is the preferred route of administration, intravenous (IV) or intramuscular (IM), for Phenergan (promethazine) in adults and children?

Promethazine Administration Route: Deep Intramuscular Injection is Strongly Preferred

Deep intramuscular (IM) injection is the preferred route of administration for promethazine (Phenergan), as intravenous (IV) administration carries significant risk of severe tissue injury, gangrene, and potentially fatal complications including respiratory depression. 1

Critical Safety Considerations

Severe Tissue Injury Risk with IV Administration

The FDA explicitly warns that promethazine can cause severe chemical irritation and damage to tissues regardless of route, but IV administration poses particularly high risks including: 1

• Perivascular extravasation leading to tissue necrosis and gangrene
• Unintentional intra-arterial injection causing severe vessel spasm, gangrene, and potential amputation
• Intraneuronal or perineuronal infiltration resulting in palsies and paralysis
• Surgical intervention including fasciotomy, skin graft, and/or amputation has been required in documented cases 1

The FDA drug label explicitly states: "Because of the risks of intravenous injection, the preferred route of administration of promethazine hydrochloride injection is deep intramuscular injection." 1

Respiratory Depression Risk

Promethazine carries a black box warning for potentially fatal respiratory depression, particularly in: 1

• Pediatric patients less than 2 years of age (contraindicated)
• Pediatric patients 2 years and older (use lowest effective dose with extreme caution)
• Patients with compromised respiratory function or at risk for respiratory failure (COPD, sleep apnea)
• When combined with other respiratory depressants 1

Clinical Administration Guidelines

When IM Route Must Be Used

Deep intramuscular injection should be the default route for promethazine administration in all clinical scenarios where parenteral administration is required. 1

If IV Administration is Absolutely Necessary

If clinical circumstances make IV administration unavoidable, the following precautions are mandatory: 1

• Stop injection immediately if patient complains of pain during administration
• Use extreme care to avoid perivascular extravasation or intra-arterial injection
• Recognize that aspiration of dark blood does NOT exclude intra-arterial placement (blood discolors on contact with promethazine)
• Avoid rigid plungers or small-bore needles that may obscure arterial backflow
• There is no proven successful management of unintentional intra-arterial injection once it occurs 1

Contraindicated Route

Subcutaneous injection is absolutely contraindicated due to severe tissue injury risk. 1

Alternative Considerations

For procedural sedation in emergency settings, other agents may be safer alternatives. The combination of demerol, phenergan, and thorazine showed only 0.6% respiratory depression in pediatric patients, but this does not negate the tissue injury risks of IV promethazine. 2

For antiemetic therapy in the emergency department, prochlorperazine (10 mg IV) demonstrated superior efficacy compared to promethazine (25 mg IV) with significantly better symptom relief, fewer treatment failures (9.5% vs 31%), and less sedation (38% vs 71%). 3 This makes prochlorperazine a safer and more effective alternative when IV antiemetic therapy is required.

Common Pitfalls to Avoid

• Never assume dark blood on aspiration excludes arterial placement - promethazine discolors blood on contact 1
• Never continue IV injection if patient reports pain - this may indicate arterial injection or extravasation 1
• Never use subcutaneous route - it is contraindicated 1
• Never use in children under 2 years - risk of fatal respiratory depression 1