Vancomycin infusion reaction, formerly known as red man syndrome, is a non-IgE-mediated anaphylactoid reaction, caused by the release of histamine from direct toxicity to mast cells due to intravenous (IV), and less commonly oral or intraperitoneal, vancomycin. As early as 4 minutes after the start of a vancomycin infusion, patients may develop symptoms and signs ranging from mild pruritus to an erythematous or urticarial eruption on the trunk, face, and neck. In severe cases, angioedema, nausea and vomiting, tachycardia, dyspnea, hypotension, and altered mental status may be seen, although these are less common.

The reaction to vancomycin can occur in all age groups; however, patients 40 years of age and younger tend to have more severe reactions. Severity of reaction is also related to dose and rate of vancomycin infusion.

The majority of cases will resolve following discontinuation of the infusion, as soon as 20 minutes after infusion completion when combined with antihistamine treatment.

Other drugs that have been reported to cause a similar reaction include ciprofloxacin, cefepime, rifampin, teicoplanin, amphotericin B, and infliximab.