A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Zithromax Side Effects, and Drug Interactions - Azithromycin
Zithromax Side Effects, and Drug Interactions - Azithromycin
SIDE EFFECTS
In clinical trials, most
of the reported side effects
were mild to moderate in severity and were reversible
upon discontinuation of the drug. Approximately 0.7% of the patients (adults
and children) from the multiple-dose clinical trials discontinued azithromycin
therapy because of treatment-related side effects. Most of the side
effects leading to discontinuation were related to the gastrointestinal
tract, e.g., nausea, vomiting, diarrhea, or abdominal
pain. Potentially serious side
effects of angioedema and
cholestatic jaundice were reported rarely.
Clinical
Adults
Multiple-Dose Regimen: Overall, the most common side
effects in adult patients receiving
a multiple-dose regimen of
azithromycin were related
to the gastrointestinal
system with diarrhea/loose
stools (5%), nausea (3%), and abdominal
pain (3%) being the most frequently
reported.
No other side effects occurred
in patients on the multiple-dose regimen of azithromycin
with a frequency greater than 1%. Side effects that occurred with a frequency
of 1% or less included the following:
Cardiovascular: Palpitations, chest
pain.
Gastrointestinal: Dyspepsia, flatulence, vomiting, melena,
and cholestatic jaundice.
Genitourinary: Monilia, vaginitis, and nephritis.
Nervous System: Dizziness, headache, vertigo, and somnolence.
General: Fatigue.
Allergic: Rash, photosensitivity, and angioedema.
Single 1-gram Dose Regimen: Overall, the most common side
effects in patients receiving a single-dose regimen
of 1 gram of azithromycin were
related to the gastrointestinal
system and were more frequently
reported than in patients receiving the multiple-dose regimen.
Side effects that occurred in patients on the single one-gram dosing
regimen of azithromycin
with a frequency of 1% or greater included diarrhea/loose stools (7%),
nausea (5%), abdominal
pain (5%), vomiting
(2%), dyspepsia (1%), and vaginitis
(1%).
Single 2-gram Dose Regimen: Overall, the most common side
effects in patients receiving a single 2-gram dose
of azithromycin were
related to the gastrointestinal
system. Side effects that occurred in patients in this study with a frequency
of 1% or greater included nausea
(18%), diarrhea/loose stools (14%), vomiting
(7%), abdominal pain
(7%), vaginitis (2%), dyspepsia
(1%), and dizziness (1%).
The majority of these complaints were mild in nature.
Pediatric Patients
Multiple-Dose Regimens: The types of side
effects in children were comparable to those seen in adults, with different
incidence rates for the
two dosage regimens recommended
in children.
Acute Otitis Media: For the recommended dosage
regimen of 10 mg/kg on day 1 followed by 5 mg/kg on days 2-5, the most
frequent side effects attributed to treatment
were diarrhea/loose stools (2%), abdominal pain (2%), vomiting
(1%), and nausea (1%).
Community-Acquired Pneumonia: For the recommended dosage
regimen of 10 mg/kg on day 1 followed by 5 mg/kg on days 2-5, the most
frequent side effects attributed
to treatment were diarrhea/loose
stools (5.8%), abdominal
pain, vomiting, and nausea
(1.9% each), and rash (1.6%).
Pharyngitis/Tonsillitis: For the recommended dosage
regimen of 12 mg/kg on days 1-5, the most frequent side
effects attributed to treatment were diarrhea/loose stools (6%), vomiting
(5%), abdominal pain
(3%), nausea (2%), and headache
(1%).
With either treatment regimen,
no other side effects occurred
in children treated with azithromycin
with a frequency greater than 1%. Side effects that occurred with a frequency
of 1% or less included the following:
Cardiovascular: Chest pain.
Gastrointestinal: Dyspepsia, constipation, anorexia, flatulence,
and gastritis.
Nervous System: Headache (otitis media
dosage), hyperkinesia, dizziness, agitation, nervousness, insomnia.
General: Fever, fatigue, malaise.
Allergic: Rash.
Skin and Appendages: Pruritus, urticaria.
Special Senses: Conjunctivitis.
Post-Marketing Experience
Adverse events reported with azithromycin
during the post-marketing period in adult
and/or pediatric patients
for which a causal relationship may not be established include:
Allergic: Arthralgia, edema, urticaria.
Cardiovascular: Arrhythmias including ventricular
tachycardia.
Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence,
vomiting/diarrhea rarely resulting in dehydration.
General: Asthenia, paresthesia.
Genitourinary: Interstitial nephritis
and acute renal failure.
Liver/Biliary: Abnormal liver
function including hepatitis
and cholestatic jaundice.
Nervous System: Convulsions.
Skin/Appendages: Rarely serious skin
reactions including erythema multiforme, Stevens Johnson Syndrome, and
toxic epidermal necrolysis.
Special Senses: Hearing disturbances including hearing
loss, deafness, and/or tinnitus, rare reports of taste
disturbances.
Laboratory Abnormalities
Adults
Significant abnormalities (irrespective of drug
relationship) occurring during the clinical
trials were reported as follows: with an incidence of 1-2%, elevated serum
creatine phosphokinase, potassium,
ALT (SGPT), GGT, and AST
(SGOT); with an incidence
of less than 1%, leukopenia, neutropenia, decreased platelet
count, elevated serum alkaline
phosphatase, bilirubin, BUN, creatinine, blood
glucose, LDH, and phosphate.
When follow-up was provided,
changes in laboratory tests appeared to be reversible.
In multiple-dose clinical
trials involving more than 3000 patients, 3 patients discontinued therapy
because of treatment-related liver
enzyme abnormalities and 1 because of a renal
function abnormality.
Pediatric Patients
Significant abnormalities (irrespective of drug
relationship) occurring during clinical
trials were all reported at a frequency of less than 1%, but were similar
in type to the adult
pattern.
In multiple-dose clinical
trials involving almost 3300 pediatric
patients, no patients discontinued therapy because of treatment-related
laboratory abnormalities.
DRUG INTERACTIONS
Aluminum¾ and magnesium¾containing
antacids reduce the peak serum
levels (rate) but not the AUC
(extent) of azithromycin absorption.
Administration of cimetidine
(800 mg) two hours prior to azithromycin had no effect
on azithromycin absorption.
Azithromycin did not affect
the plasma levels or pharmacokinetics
of theophylline administered as a single intravenous
dose. The effect of azithromycin
on the plasma levels or pharmacokinetics
of theophylline administered
in multiple doses resulting in therapeutic
steady-state levels of theophylline is not known. However, concurrent
use of macrolides and theophylline
has been associated with increases in the serum
concentrations of theophylline. Therefore, until further data are available,
prudent medical practice
dictates careful monitoring of plasma
theophylline levels in
patients receiving azithromycin and theophylline
concomitantly.
Azithromycin did not affect
the prothrombin time
response to a single dose
of warfarin. However, prudent medical
practice dictates careful
monitoring of prothrombin
time in all patients treated
with azithromycin and
warfarin concomitantly. Concurrent use of macrolides and warfarin in clinical
practice has been associated with increased anticoagulant
effects.
The following drug interactions
have not been reported in clinical
trials with azithromycin; however, no specific
drug interaction studies have
been performed to evaluate potential
drug-drug interaction. Nonetheless, they have been observed with macrolide
products. Until further data are developed regarding drug
interactions when azithromycin
and these drugs are used concomitantly, careful monitoring of patients
is advised:
Digoxin: Elevated digoxin
levels.
Ergotamine or Dihydroergotamine: Acute ergot
toxicity characterized by severe peripheral
vasospasm and dysesthesia.
Triazolam: Decrease the clearance
of triazolam and thus may increase the pharmacologic effect
of triazolam.
Drugs Metabolized by the Cytochrome P450System:
Elevations of serum carbamazepine,
terfenadine, cyclosporine, hexobarbital, and phenytoin
levels.
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