Clin Drug Invest 2001; 21 (3): 233-234
1173-2563/01/0003-0233/$22.00/0
CORRESPONDENCE
© Adis International Limited. All rights reserved.
found in the gut flora of an estimated 5 to 10% of
the population, metabolises digoxin to an inactive
metabolite, dihydrodigoxin. Antibiotics with an-
aerobic coverage have the potential, in susceptible
patients treated concomitantly with digoxin, to
increase the bioavailability of the parent drug by
altering the presence of E. lentum in their gut flora.
The macrolides erythromycin and clarithromycin
have been hypothesised to increase digoxin con-
centrations via this mechanism. Pharmacodynamic
properties of azithromycin, an azilide, include
activity in vitro against a wide range of bacteria
including anaerobic bacteria; however, activity
against E. lentum has not been studied.
Based on the review of potentially relevant
cases, the possibility that the 5 to 10% of the pop-
ulation with E. lentum may experience an increase
in digoxin concentrations during concurrent
azithromycin therapy, through an indirect inter-
action, cannot be entirely excluded. Current
azithromycin labelling advises prescribers that in
patients receiving azithromycin and digoxin the
possibility of raised digoxin concentrations should
be borne in mind.
Possible Digoxin-Azithromycin
Interaction in a Child
The Editor
In the July 2000 issue of Clinical Drug Investi-
gation, Ten Eick et al.[1] cited Pfizer Pharmaceuti-
cals as having received 103 spontaneous adverse
event reports concerning a possible drug-drug
interaction between azithromycin and digoxin.
This statement is not entirely correct. A review of
the company’s tolerability database identified the
spontaneous azithromycin and concomitant
digoxin cases; eight cases described a suspected
drug interaction. All cases were reviewed based on
adverse events that could have been related to
digoxin toxicity such as tachycardia, bradycardia,
nausea, vomiting, anorexia, headache, dizziness,
blurred vision and seizure.
Patients presented with concomitant medica-
tions known to increase digoxin concentrations
and/or with relevant medical histories that affect
cardiac glycoside pharmacodynamics, confound-
ing many of the cases. Thirteen cases monitoring
digoxin concentrations recorded normal, low or
elevated concentrations. Where serum digoxin
concentrations were reported, either samples were
obtained prior to the completion of the distribution
phase of digoxin or the time the sample was
obtained was not disclosed, making serum concen-
tration data hard to interpret. Only three cases
provided serum digoxin concentrations prior to
azithromycin initiation and only the case reported
by Ten Eick et al.[1] provided the point in time when
samples were retrieved.
Philip Miner, Jr, PharmD
Assistant Director
Safety Evaluation and Epidemiology
Worldwide Safety
Pfizer Pharmaceuticals Group
New York, NY, USA
Reference
1. Ten Eick AP, Sallee D, Preminger T, et al. Possible drug inter-
action between digoxin and azithromycin in a young child.
Clin Drug Invest 2000; 20: 61-4.
An anaerobic bacterium, Eubacterium lentum,
Datta
