Azithromycin and drug reaction with eosinophilia and systemic symptoms (DRESS)

HSA would like to highlight to healthcare professionals overseas cases of drug reaction with eosinophilia and systemic symptoms (DRESS) associated with the use of azithromycin.

Azithromycin (Zithromax®, Pfizer Pte Ltd) is an azalide, a subclass of macrolide antibiotics that has been registered in Singapore since 1999 for the treatment of upper and lower respiratory tract infections and other infections involving susceptible organisms. It is also licensed under 11 other generic brands and is available under various dosage forms ranging from oral tablets to intravenous formulations.

DRESS is a severe drug reaction characterised by rash, fever, lymphadenopathy, and single or multiple organ involvement (e.g., liver, kidney) that typically occurs within eight weeks of drug initiation.¹ Haematologic abnormalities, including eosinophilia and atypical lymphocytosis, are also key characteristics of this syndrome.

Review by Health Canada2

In April 2014, Health Canada highlighted in its Canadian Adverse Reaction Newsletter that the package inserts (PI) for azithromycin-containing products have been updated with information on DRESS. This followed the receipt of a domestic report of DRESS suspected to be associated with azithromycin, as well as review of published literature on DRESS in patients treated with azithromycin.

The Canadian adverse reaction report described a 60-year-old female who experienced DRESS 18 days after taking azithromycin to treat pharyngitis. Of the four DRESS cases that were published in literature,^1,3-5 two cases involved children (aged two and eight) while the other two involved adults (aged 48 and 79). Two cases stated the time to onset, which was a few hours and 22 days. Two patients recovered while the other two died. In the first fatal case which occurred in the 2-year-old child, co-amoxiclav was an additional suspected causative drug and severe liver involvement led to death. Another fatal case occurred in the 48-year-old patient who developed DRESS and subsequent hypersensitivity myocarditis.

Local situation and HSA’s advisory

To date, HSA has not received any reports of DRESS associated with the use of azithromycin. The company has initiated a labelling update for the Zithromax® range of products to warn of reports of DRESS.

Healthcare professionals are encouraged to be vigilant to the signs and symptoms of DRESS in patients who are prescribed azithromycin. These may include rash, fever, lymphadenopathy, haematological abnormalities and multiorgan involvement. Early and prompt discontinuation of the offending drug is important to achieve the best outcome in patients with DRESS.

References

1. Ann Intern Med 2009; 150: 225-6

2. http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v24n2-eng.php#article2 ↗ (opens in new tab)

3. Br J Dermatol 2013; 168: 391-401

4. Am J Med 2001; 110: 330-1

5. Pediatr Dermatol 2011; 28: 741-3