Fluoroquinolone-associated anaphylaxis in spontaneous adverse drug reaction reports in Germany: differences in reporting rates between individual fluoroquinolones and occurrence after first-ever use.
BACKGROUND
The frequency of fluoroquinolone-associated anaphylaxis has been estimated to be 1.8-23 per 10 million days of treatment based on spontaneous reports. It is unknown whether there are differences between the reporting rates of anaphylaxis with individual fluoroquinolones. According to pathophysiology, anaphylaxis may be immune mediated (anaphylactic) or not (anaphylactoid). The latter may occur after first-ever intake since no sensitisation phase is necessary.


OBJECTIVE
To analyse spontaneous reports of fluoroquinolone-associated anaphylaxis contained in the spontaneous adverse drug reaction database of the Federal Institute for Drugs and Medical Devices in Germany with regard to differences in reporting rates between various fluoroquinolones, the previous intake and the time to onset of the reaction.


METHODS
All fluoroquinolone-associated cases of anaphylaxis, anaphylactic shock, and anaphylactic/anaphylactoid reaction spontaneously reported to the Federal Institute for Drugs and Medical Devices between 1 January 1993 and 31 December 2004 were identified and assessed with regard to the correctness of the diagnosis of anaphylaxis, the causal relationship with the drug, the previous intake of fluoroquinolones and the time to onset of the reaction.


RESULTS
In 166 of 204 cases identified, the diagnosis of anaphylaxis and a causal relationship with the drug were considered at least possible. Moxifloxacin, levofloxacin, ciprofloxacin and ofloxacin accounted for 90 (54%), 25 (15%), 21 (13%) and 16 (10%) of the 166 cases, respectively. The corresponding reporting rates per 1 million defined daily doses based on crude estimates of exposure were 3.3, 0.6, 0.2 and 0.2 for moxifloxacin, levofloxacin, ciprofloxacin and ofloxacin, respectively. The occurrence of anaphylaxis after the first dose or within the first three days was reported in 71 of 166 (43%) cases, but no information on prior exposure with this or any other fluoroquinolone was provided with these reports. In 21 of 166 (13%) cases, the reaction occurred within the first 3 days and it was stated that the particular fluoroquinolone had never been taken before.


CONCLUSIONS
Anaphylaxis appears to be associated with the fluoroquinolone class of antibacterials. Observed differences in reporting rates should be further investigated. Fluoroquinolone-associated anaphylaxis may occur after first-ever intake of the agent.
Sachs
Bernhardt
B
Division of Pharmacovigilance, Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany. sachs@bfarm.de
Riegel
Stefan
S
Seebeck
Jörg
J
Beier
Rainer
R
Schichler
Dagmar
D
Barger
Antina
A
Merk
Hans F
HF
Erdmann
Stephan
S
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000707:Anaphylaxis / Q000453:epidemiology*; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged
D024841:Fluoroquinolones