CONTRAINDICATIONS
Azithromycin is contraindicated in patients with known hypersensitivity to azithromycin,
erythromycin, or any macrolide antibiotic.
WARNINGS
Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions
including Stevens Johnson Syndrome and toxic epidermal necrolysis have been reported
rarely in patients on azithromycin therapy. Although rare, fatalities have been reported.
(See CONTRAINDICATIONS.) Despite initially successful symptomatic treatment of
the allergic symptoms, when symptomatic therapy was discontinued, the allergic
symptoms recurred soon thereafter in some patients without further azithromycin
exposure. These patients required prolonged periods of observation and symptomatic
treatment. The relationship of these episodes to the long tissue half-life of azithromycin
and subsequent prolonged exposure to antigen is unknown at present.
If an allergic reaction occurs, the drug should be discontinued and appropriate therapy
should be instituted. Physicians should be aware that reappearance of the allergic
symptoms may occur when symptomatic therapy is discontinued.
In the treatment of pneumonia, azithromycin has only been shown to be safe and
effective in the treatment of community-acquired pneumonia due to Chlamydia
pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus
pneumoniae in patients appropriate for oral therapy. Azithromycin should not be
used in patients with pneumonia who are judged to be inappropriate for oral
therapy because of moderate to severe illness or risk factors such as any of the
following: patients with cystic fibrosis, patients with nosocomially acquired
infections, patients with known or suspected bacteremia, patients requiring
hospitalization, elderly or debilitated patients, or patients with significant
underlying health problems that may compromise their ability to respond to their
illness (including immunodeficiency or functional asplenia).
Pseudomembranous colitis has been reported with nearly all antibacterial agents
and may range in severity from mild to life-threatening. Therefore, it is important
to consider this diagnosis in patients who present with diarrhea subsequent to the
administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit
overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is
a primary cause of “antibiotic-associated colitis.”
After the diagnosis of pseudomembranous colitis has been established, therapeutic
measures should be initiated. Mild cases of pseudomembranous colitis usually respond to
discontinuation of the drug alone. In moderate to severe cases, consideration should be
given to management with fluids and electrolytes, protein supplementation, and treatment
with an antibacterial drug clinically effective against Clostridium difficile colitis.
PRECAUTIONS
General
Because azithromycin is principally eliminated via the liver, caution should be exercised
when azithromycin is administered to patients with impaired hepatic function. There are
no data regarding azithromycin usage in patients with renal impairment; thus, caution
should be exercised when prescribing azithromycin in these patients.
The following adverse events have not been reported in clinical trials with azithromycin,
an azalide; however, they have been reported with macrolide products: ventricular
arrhythmias, including ventricular tachycardia and torsade de pointes, in individuals with
prolonged QT intervals.
There has been a spontaneous report from the post-marketing experience of a patient
with previous history of arrhythmias who experienced torsade de pointes and subsequent
myocardial infarction following a course of azithromycin therapy.
Information for the Patient
Patients should be cautioned to take azithromycin capsules and azithromycin suspension
at least one hour prior to a meal or at least two hours after a meal. These medications
should not be taken with food.
Azithromycin tablets can be taken with or without food.
Patients should also be cautioned not to take aluminum— and magnesium-containing
antacids and azithromycin simultaneously.
The patient should be directed to discontinue azithromycin immediately and contact a
physician if any signs of an allergic reaction occur.
Laboratory Test Interactions
There are no reported laboratory test interactions.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term studies in animals have not been performed to evaluate carcinogenic potential.
Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse
lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow
clastogenic assay. No evidence of impaired fertility due to azithromycin was found.
Pregnancy, Teratogenic Effects, Pregnancy Category B
Reproduction studies have been performed in rats and mice at doses up to moderately
maternally toxic dose levels (i.e., 200 mg/kg/day). These doses, based on a mg/m2 basis,
are estimated to be 4 and 2 times, respectively, the human daily dose of 500 mg. In the
animal studies, no evidence of harm to the fetus due to azithromycin was found. There
are, however, no adequate and well-controlled studies in pregnant women. Because
animal reproduction studies are not always predictive of human response, azithromycin
should be used during pregnancy only if clearly needed.
Nursing Mothers
It is not known whether azithromycin is excreted in human milk. Because many drugs are
excreted in human milk, caution should be exercised when azithromycin is administered to
a nursing woman.
Pediatric Use
(See CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE, and
DOSAGE AND ADMINISTRATION.)
Acute Otitis Media (Dosage Regimen: 10 mg/kg on Day 1 Followed by 5 mg/kg on
Days 2-5): Safety and effectiveness in the treatment of children with otitis media under 6
months of age have not been established.
Community-Acquired Pneumonia (dosage Regimen: 10 mg/kg on Day 1 Followed by
5 mg/kg on Days 2-5): Safety and effectiveness in the treatment of children with
community—acquired pneumonia under 6 months of age have not been established.
Safety and effectiveness for pneumonia due to Chlamydia pneumoniae and Mycoplasma
pneumoniae were documented in pediatric clinical trials. Safety and effectiveness for
pneumonia due to Haemophilus influenzae and Streptococcus pneumoniae were not
documented bacteriologically in the pediatric clinical trial due to difficulty in obtaining
specimens. Use of azithromycin for these two microorganisms is supported, however, by
evidence from adequate and well-controlled studies in adults.
Pharyngitis/Tonsillitis (Dosage Regimen: 12 mg/kg on Days 1-5): Safety and
effectiveness in the treatment of children with pharyngitis/tonsillitis under 2 years of age
have not been established.
Studies evaluating the use of repeated courses of therapy have not been
conducted. (See CLINICAL PHARMACOLOGY and ANIMAL
PHARMACOLOGY.)
Geriatric Use
Pharmacokinetic parameters in older volunteers (65-85 years old) were similar to those
in younger volunteers (18-40 years old) for the 5-day therapeutic regimen. Dosage
adjustment does not appear to be necessary for older patients with normal renal and
hepatic function receiving treatment with this dosage regimen. (See CLINICAL
PHARMACOLOGY.)