Azithromycin Toxnet

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The following information was generated from the

Hazardous Substances Data Bank (HSDB),
a database of the National Library of Medicine's TOXNET system
(http://toxnet.nlm.nih.gov) on December 5, 2012.
Query: The chemical name azithromycin was identified.
The following terms were added from ChemIDplus:
zmax
zithromax
azasite
CAS Registry Number: 83905-01-5
1
NAME: AZITHROMYCIN
HSN: 7205
RN: 83905-01-5
HUMAN HEALTH EFFECTS:
HUMAN TOXICITY EXCERPTS:
/SIGNS AND SYMPTOMS/ Serious allergic (i.e., angioedema, anaphylaxis,
bronchospasm) and dermatologic (i.e., erythema multiforme, Stevens-Johnson
syndrome, toxic epidermal necrolysis) reactions, sometimes resulting in
death, have been reported rarely in patients receiving azithromycin.
...[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug
Information 2003. Bethesda, MD: American Society of Health-System
Pharmacists, Inc. 2003 (Plus Supplements)., p. 298] **PEER REVIEWED**
/CASE REPORTS/ We report the case of a 25-year-old female patient with
severe aggravation of myasthenia gravis due to azithromycin which was
prescribed for an influenza syndrome. One hour after the intake of 500 mg
azithromycin the patient developed weakness of the legs and respiratory
distress due to respiratory muscle failure. She was hospitalized in a
comatose state and required intubation and mechanical ventilation for six
days. Acute worsening of myasthenia gravis was observed in this patient in
1986 after parenteral administration of erythromycin. Erythromycin causing
aggravation of myasthenia gravis by interfering with neuromuscular
transmission is reported in the literature. The close temporal
relationship between the intake of azithromycin and severe worsening of
myasthenia gravis in our patient suggests that azithromycin, a new
azalid-antibiotic of the macrolid group, can exacerbate myasthenia gravis.
We conclude that azithromycin should be added to the list of drugs to be
used with caution in patients with myasthenia gravis.[Cadisch R et al;
Schweiz Med Wochenschr 126 (8): 308-10 (1996)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/pubmed/8701248?dopt=Abstract"
target=new>PubMed Abstract
DRUG WARNINGS:
Pregnancy risk category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well
controlled studies in pregnant women have not shown increased risk of
fetal abnormalities despite adverse findings in animals, or, in the
absents of adequate human studies, animal studies show no fetal risk. The
chance of fetal harm is remote but remains a possibility./[Physicians Desk
Reference. 58th ed. Thomson PDR. Montvale, NJ 2004., p. 2684] **PEER
REVIEWED**
http://toxnet.nlm.nih.gov/cgi-bin/sis/download.txt
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The most frequent adverse effects of azithromycin involve the GI tract

(i.e., diarrhea/loose stools, nausea, abdominal pain). While these adverse
effects generally are mild to moderate in severity and occur less
frequently than with oral erythromycin therapy, adverse GI effects are the
most frequent reason for discontinuing azithromycin therapy.[McEvoy, G.K.
(ed.). American Hospital Formulary Service - Drug Information 2003.
Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003
(Plus Supplements)., p. 298] **PEER REVIEWED**
Azithromycin has been detected in human milk. The drug should be used with
caution in nursing women.[McEvoy, G.K. (ed.). American Hospital Formulary
Service - Drug Information 2003. Bethesda, MD: American Society of
Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 300] **PEER
REVIEWED**
Serious allergic (i.e., angioedema, anaphylaxis, bronchospasm) and
dermatologic (i.e., erythema multiforme, Stevens-Johnson syndrome, toxic
epidermal necrolysis) reactions, sometimes resulting in death, have been
reported rarely in patients receiving azithromycin. ...[McEvoy, G.K.
Approximately 12% of patients experienced an adverse effect related to IV
infusion of azithromycin. Pain at the injection site or local inflammation
occurred in 6.5 or 3.1%, respectively, of patients receiving IV
azithromycin. ...[McEvoy, G.K. (ed.). American Hospital Formulary Service
- Drug Information 2003. Bethesda, MD: American Society of Health-System
Elevation in serum potassium concentration has been reported in 1-2% of
adults receiving azithromycin in clinical trials. Elevation in BUN, serum
creatinine, or serum phosphate concentration has been reported in less
than 1% of adults receiving oral azithromycin, while elevated serum
creatinine concentration has been reported in 4-6% of patients receiving
IV azithromycin. ...[McEvoy, G.K. (ed.). American Hospital Formulary
REVIEWED**
Palpitations, chest pain, edema hypotension, or syncope has been reported
in 1% or less of patients receiving oral azithromycin. While not directly
attributed to azithromycin therapy, arrhythmia (including ventricular
tachycardia)has been reported in at least one person receiving the drug.
In one patient with a history of arrhythmia, torsades de pointes with
subsequent myocardial infarction occurred following completion of
azithromycin therapy.[McEvoy, G.K. (ed.). American Hospital Formulary
REVIEWED**
Azithromycin, a semi-synthetic azalide antibiotic, is a macrolide that
thus far has not shared the neuropsychiatric side effects of other
macrolides such as erythromycin and clarithromycin. We now report
significant delirium associated with conventional dosing of azithromycin
in two geriatric patients who were being treated for lower respiratory
tract infection. The onset of delirium was apparent within 72 hours of
initiating azithromycin therapy and lasted 48 to 72 hours after
discontinuing treatment with the drug. In contrast to the adverse central
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nervous system symptoms associated with clarithromycin, those induced by

azithromycin seem to take longer to resolve, perhaps based upon the longer
elimination half-life of the latter antimicrobial, particularly in
geriatric women.[Cone LA et al; Surg Neurol 59 (6): 509-11 (2003)] **PEER
REVIEWED** <a
Intravenous azithromycin is increasingly administered for treatment of
hospitalized patients with community-acquired pneumonia. Macrolide
antibiotics cause ototoxicity, which occurs most frequently when high
serum concentrations are achieved. Current dosing guidelines for
intravenous azithromycin can result in much higher serum concentrations
than is seen with oral administration. We describe a 47-year-old woman who
developed complete deafness after receiving 8 days of intravenous
azithromycin.[Bizjak ED et al; Pharmacotherapy 19 (2): 245-8 (1999)]
**PEER REVIEWED** <a
Azithromycin (Zithromax), an erythromycin derivative that belongs to a
subgroup of the macrolides known as azolides, has generally been
considered to be a very safe medication. Hepatic side effects are uncommon
but may include jaundice, fever, and right upper quadrant pain. Herein we
describe a patient who developed azithromycin-induced cholestatic
hepatitis that resolved upon discontinuation of the drug. Lack of other
known causes for liver disease, the temporal relationship with this drug,
and the typical changes of liver histology have established the diagnosis.
Clinicians should be aware of this side effect of azithromycin, which is
widely prescribed.[Chandrupatla S et al; Dig Dis Sci 47 (10): 2186-8
(2002)] **PEER REVIEWED** <a
We report the case of a 25-year-old female patient with severe aggravation
of myasthenia gravis due to azithromycin which was prescribed for an
influenza syndrome. One hour after the intake of 500 mg azithromycin the
patient developed weakness of the legs and respiratory distress due to
respiratory muscle failure. She was hospitalized in a comatose state and
required intubation and mechanical ventilation for six days. Acute
worsening of myasthenia gravis was observed in this patient in 1986 after
parenteral administration of erythromycin. Erythromycin causing
Azithromycin, an azalide antibiotic, rarely causes ototoxicity. According
to the few reports in existence, azithromycin-induced ototoxicity occurred
following prolonged high-dose therapy in patients with acquired
immunodeficiency syndrome and resulted in a reversible sensorineural
hearing loss. We present a case of irreversible sensorineural hearing loss
due to azithromycin ototoxicity in an otherwise healthy woman following
low-dose exposure to azithromycin.[Ress BD, Gross EM; Ann Otol Rhinol
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Laryngol 109 (4): 435-7 (2000)] **PEER REVIEWED** <a

Adverse CNS effects reported in 1% or less of adults receiving
azithromycin include dizziness, headache, vertigo, or somnolence, and
those reported in 1% or less of children include headache, hyperkinesia,
dizziness, agitation, nervousness, fatigue, malaise, and insomnia.[McEvoy,
G.K. (ed.). American Hospital Formulary Service - Drug Information 2003.
... Oral azithromycin should not be used for the treatment of pneumonia
that is considered unsuitable for outpatient oral therapy because of the
severity of the infection (e.g., moderate to severe) or when risk factors
such as nosocomially acquired infection, known or suspected bacteremia,
cystic fibrosis, or any clinically important underlying health problem
that might compromise the patient's ability to respond adequately (e.g.,
immunodeficiency, functional asplenia) are present. In addition, ... the
drug should not be used for the treatment of pneumonia in patients
requiring hospitalization or in geriatric or debilitated patients.[McEvoy,
Because azithromycin is eliminated principally via the liver, the drug
should be used with caution in patients with impaired hepatic function.
The cases of 3 patients, who presented with hearing loss after receiving a
combination of clofazimine, ethambutol, and 500 mg of oral azithromycin
daily for 30-90 days as therapy for Mycobacterium avium infection are
reported. Hearing loss was resolved 2-4 wk after cessation of azithromycin
therapy. Patients who received another macrolide in place of azithromycin
did not develop hearing loss. One patient was rechallenged with
azithromycin after his hearing returned to baseline, and within 14 days he
noted a marked decline in his auditory acuity. He again discontinued the
drug and noted a return to normal hearing over 10-15 days.[Wallace MR et
al; Lancet; 343 (Jan 22): 241 (1994)] **PEER REVIEWED**
EMERGENCY MEDICAL TREATMENT:
EMERGENCY MEDICAL TREATMENT:
EMT COPYRIGHT DISCLAIMER:
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EXCLUDED. Micromedex does not assume any responsibility or risk for your use of
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the POISINDEX(R) or MEDITEXT(R) databases. Copyright 1974-2012 Thomson

MICROMEDEX. All Rights Reserved. Any duplication, replication, "downloading,"
sale, redistribution or other use for commercial purposes is a violation of
Micromedex' rights and is strictly prohibited.<p>The following Overview, ***
MACROLIDE ANTIBIOTICS ***, is relevant for this HSDB record chemical.
LIFE SUPPORT:
o
This overview assumes that basic life support measures
have been instituted.
CLINICAL EFFECTS:
0.2.1 SUMMARY OF EXPOSURE
A) In general, macrolide antibiotics are considered to have
fewer, less severe toxic effects than most other
antimicrobial agents.
B) The more common toxic effects of the macrolides include
gastrointestinal irritation, cholestasis, ototoxicity,
and thrombophlebitis (after IV administration).
Ventricular dysrhythmias may occur with erythromycin
administration (usually intravenous), but are not
common. In general, the risk of dysrhythmias is
increased when erythromycin is administered in
combination with other drugs that prolong the QT
interval.
C) These effects are usually reversible upon
discontinuation of the drug.
0.2.3 VITAL SIGNS
A) Vital sign changes, while rare, may include hypothermia
and hypotension.
0.2.5 CARDIOVASCULAR
A) Thrombophlebitis and ventricular dysrhythmias may occur
following the intravenous administration of
erythromycin.
B) Hypovolemic shock and hypotension are extremely unusual
reactions that have been reported with the use of
erythromycin.
0.2.7 NEUROLOGIC
A) Sensorineural hearing loss may occur in patients
receiving treatment with large doses of macrolide
antibiotics, especially in patients suffering from
concomitant liver and/or kidney disease. The hearing
loss is usually reversible upon discontinuation of the
drug.
B) Exacerbation of myasthenia gravis may occur infrequently
following erythromycin administration.
0.2.8 GASTROINTESTINAL
A) Nausea, vomiting and abdominal pain are common adverse
effects of the macrolide antibiotics, particularly
erythromycin. The incidence of GI reactions may vary
with the erythromycin salt preparation, and/or dosing
regimen. Diarrhea may occur due to increased
gastrointestinal motility caused by erythromycin.
B) Pancreatitis, pyloric stenosis, dynamic ileus, and
pseudomembranous colitis occur less frequently.
0.2.9 HEPATIC
A) Cholestasis, cholestatic hepatitis, acute hepatitis and
hepatic failure may occur. The incidence of such
reactions may vary with the salt preparation used.
Discontinuation of the drug usually results in
resolution of hepatotoxic effects.
0.2.10 GENITOURINARY
A) Interstitial nephritis and glomerulonephritis have been
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reported with the administration of erythromycin, but

are uncommon.
0.2.13 HEMATOLOGIC
A) Agranulocytosis, thrombocytopenia, or hemolytic anemia
may occur with the administration of the macrolide
antibiotics, but these are rare adverse effects.
0.2.14 DERMATOLOGIC
A) Contact dermatitis, fixed drug eruptions, toxic
pustuloderma, and toxic epidermal necrolysis are
uncommon side effects which may occur with macrolide
use.
0.2.18 PSYCHIATRIC
A) Personality changes and nightmares are uncommon, but may
occur with therapeutic use.
0.2.19 IMMUNOLOGIC
A) Leukocytoclastic vasculitis, acute respiratory distress
following an allergic reaction, and the Schonlein-Henoch
syndrome are uncommon toxic effects that may occur.
0.2.20 REPRODUCTIVE
A) Azithromycin, erythromycin, and fidaxomicin are
classified by manufacturers as FDA category B.
Clarithromycin is classified by manufacturers as FDA
category C. Early prenatal exposure to erythromycin has
been associated with pyloric stenosis and cardiovascular
anomalies. Clarithromycin administered to pregnant women
during the first and early second trimesters of
pregnancy resulted in 4 spontaneous abortions, 4
voluntary terminations of pregnancy, 1 infant death due
to prematurity, and 20 physically normal newborns in 34
exposures; however, the spontaneous abortion rate was
not greater than expected. In animals, clarithromycin
has resulted in cleft palate, fetal growth retardation,
and a low incidence of cardiovascular anomalies when
given to pregnant mice, monkeys, and rats, respectively.
In a prospective study of mother-infant pairs in which
17 mothers were treated with erythromycin while
breast-feeding, 2 nursing infants experienced minor
diarrhea and 2 mothers reported irritability in their
infants. In a case report of erythromycin use during
breast-feeding, hypertrophic pyloric stenosis occurred
in a 3-week-old nursing infant following erythromycin
administration to the mother for mastitis.
0.2.21 CARCINOGENICITY
A) At the time of this review, the manufacturers of
azithromycin, clarithromycin, erythromycin, and
fidaxomicin do not report any carcinogenic potentials in
humans.
0.2.22 OTHER
A) The macrolide antibiotics may increase serum
concentrations of a number of hepatically metabolized
drugs, possibly by inhibiting cytochrome P450 isozyme
activities or by altering hepatic drug metabolism in
other ways. Some macrolide antibiotics may increase the
toxicity of certain drugs by altering intestinal flora
which are involved in the metabolism of these drugs.
LABORATORY:
A) Blood levels of the macrolide antibiotics are not
clinically useful.
B) CBC, electrolytes, and urinalysis are not generally
needed unless the development of hematological
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disturbances (rare) or nephritis (rare) is suspected, or

if the patient has experienced prolonged vomiting and
diarrhea. Monitor ECG, vital signs, and fluid and
electrolyte balances in massive overdoses.
C) Liver enzyme levels may aid in diagnosing or following a
patient with evidence of cholestasis or hepatitis.
D) Monitor pancreatic enzyme levels if the patient presents
with severe epigastric pain or other clinical evidence of
pancreatitis.
TREATMENT OVERVIEW:
0.4.2 ORAL/PARENTERAL EXPOSURE
A) GASTRIC LAVAGE: Consider after ingestion of a
potentially life-threatening amount of poison if it can
be performed soon after ingestion (generally within 1
hour). Protect airway by placement in the head down left
lateral decubitus position or by endotracheal
intubation. Control any seizures first.
1) CONTRAINDICATIONS: Loss of airway protective reflexes
or decreased level of consciousness in unintubated
patients; following ingestion of corrosives;
hydrocarbons (high aspiration potential); patients at
risk of hemorrhage or gastrointestinal perforation; and
trivial or non-toxic ingestion.
B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240
mL water/30 g charcoal). Usual dose: 25 to 100 g in
adults/adolescents, 25 to 50 g in children (1 to 12
years), and 1 g/kg in infants less than 1 year old.
C) Toxicity following acute overdose is uncommon. Food,
milk or an antacid may be administered orally to help
relieve gastrointestinal discomfort.
D) The toxic effects of macrolide antibiotics usually
reverse upon discontinuation of the drug.
1) Discontinue the macrolide antibiotic if there is
evidence of drug-induced hepatotoxicity, nephritis,
hypersensitivity, pancreatitis, arrhythmias,
hematologic disturbances, or enhanced toxicity from
other drugs which may be administered concomitantly
with the macrolide antibiotic.
RANGE OF TOXICITY:
A) In general, the macrolide antibiotics are of a low order
of toxicity. However, side effects can occur even within
the therapeutic range of dosing.
ANTIDOTE AND EMERGENCY TREATMENT:
Treatment of an overdose is largely supportive and symptomatic.[Ellenhorn,
M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical
Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore,
MD: Williams and Wilkins, 1997., p. 229] **PEER REVIEWED**
/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary.
Watch for signs of respiratory insufficiency and assist ventilations if
needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor
for pulmonary edema and treat if necessary ... . Monitor for shock and
treat if necessary ... . Anticipate seizures and treat if necessary ... .
For eye contamination, flush eyes immediately with water. Irrigate each
eye continuously with normal saline during transport ... . Do not use
emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of
water for dilution if the patient can swallow, has a strong gag reflex,
and does not drool ... . Cover skin burns with dry sterile dressings after
decontamination ... . /Poison A and B/[Bronstein, A.C., P.L. Currance;
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Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO.
Mosby Lifeline. 1994., p. 139] **PEER REVIEWED**
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation
for airway control in the patient who is unconscious, has severe pulmonary
edema, or is in respiratory arrest. Positive pressure ventilation
techniques with a bag valve mask device may be beneficial. Monitor cardiac
rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP:
"To keep open", minimal flow rate/. Use lactated Ringer's if signs of
hypovolemia are present. Watch for signs of fluid overload. Consider drug
therapy for pulmonary edema ... . For hypotension with signs of
hypovolemia, administer fluid cautiously. Watch for signs of fluid
overload ... . Treat seizures with diazepam (Valium) ... . Use
proparacaine hydrochloride to assist eye irrigation ... . /Poison A and
B/[Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials
Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 139] **PEER
REVIEWED**
ANIMAL TOXICITY STUDIES:
NON-HUMAN TOXICITY EXCERPTS:
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The
potential reproductive toxicity and teratogenicity of azithromycin, an
azalide antibiotic, was assessed in the rat and mouse. Reproduction and
fertility studies were performed in the Long-Evans rat at oral doses of
10, 20 and 30 mg/kg/day. Males were treated for nine weeks prior to and
during mating, and females for two weeks prior to mating and throughout
mating, gestation and lactation. Half of the females were sacrificed and
evaluated on day 14 of gestation, and the remaining females were killed on
day 21 post-partum. Postnatal development testing on F1 pups was performed
during lactation. F1 pups were raised to maturity and mated to produce an
F2 generation, and all animals were sacrificed at weaning. Pregnancy rate
was decreased at the 20 mg/kg/day level but no other azithromycin related
effects were detected upon reproductive parameters in F0 dams or in the F1
or F2 generation. Two additional fertility studies suggested that
azithromycin may cause a minimal reduction in fertility at 20 and 30 mg/kg
compared to controls and that both male and female rats must be
simultaneously treated to affect pregnancy rate. These pregnancy rates
were, however, still within the range of our historical control data.
Embryotoxicity and teratogenicity of azithromycin were evaluated in female
Sprague-Dawley rats at oral doses of 10, 20, 40, 50, 100 and 200 mg/kg/day
administered from days 6 to 15 post-insemination. A slight delay in
ossification was noted in fetuses at the 200 mg/kg dose level and was
related to evidence of maternal toxicity. Azithromycin was not teratogenic
at any dose level. Similar studies in albino mice at the same dose level
did not produce embryotoxic, fetotoxic, or teratogenic effects, and fetal
tissue concentrations were higher than in maternal plasma or amniotic
fluid. Azithromycin was tested in Sprague-Dawley rats to evaluate
peri-natal effects on dams and on postnatal development of their pups.
Dose levels were 10, 20, 40, 50, 100 or 200 mg/kg/day administered from
day 15 post-insemination through day 20 post-partum. Effects noted at
doses of 50 mg/kg and higher included decreased pup body weight, decreased
pup viability and delayed development which correlated with greater litter
size. There were no malformations or severe lesions in any of the
pups.[Stadnicki SW et al; Oyo Yakuri 51 (2): 85-95 (1996)] **PEER
REVIEWED**
/GENOTOXICITY/
Azithromycin was subjected to a series of three in vitro
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and one in vivo genetic toxicology assays for the detection of

drug-associated gene or chromosomal effects. In the Ames Salmonella
typhimurium tester strains TA1535, TA1537, TA98 and TA100, the presence of
azithromycin was not associated with any increase in the number of hisrevertants. Urine from mice dosed with up to 200 mg/kg of azithromycin
also had no effect on the number of revertants in these same strains
suggesting the absence of mutagenic excretory products following oral
exposure. When tested up to the cytotoxic level of 240 ug/ml, azithromycin
caused no increase in the mutant frequency at the thymidine kinase locus
of L5178Y/TK cells. Both the mammalian and microbial gene mutation assays
included the presence of rat-liver postmitochondrial (S9) fraction for the
detection of mutagenic biotransformation products. Mitogen-stimulated
human lymphocytes cultured in the presence of 2.5-7.5 micrograms/ml
azithromycin for 24 hr or 30.0-40.0 micrograms/ml azithromycin for 3 hr in
the presence of rat S9 had chromosomal aberration frequencies that were no
different than negative control cells even though slight to moderate
mitotic suppression was associated with these concentrations. In vivo
assessment of this compound was completed in male and female mice with a
single oral dose of 200 mg/kg followed by sacrifice at 6, 24 or 48 hr
later and metaphase analysis of bone marrow for chromosomal aberrations.
No statistically significant elevations of chromosomally aberrant cells
were found. We conclude that azithromycin does not cause gene mutations in
microbial or mammalian cells, or chromosomal aberrations in cultured human
lymphocytes or in mouse bone marrow in vivo.[Amacher DE et al; Mutat Res
300 (2): 79-90 (1993)] **PEER REVIEWED** <a
NON-HUMAN TOXICITY VALUES:
LD50 Mice oral 3000-4000 mg/kg[McEvoy, G.K. (ed.). American Hospital
Formulary Service - Drug Information 2003. Bethesda, MD: American Society
of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 301]
**PEER REVIEWED**
METABOLISM/PHARMACOKINETICS:
METABOLISM/METABOLITES:
The principal route of biotransformation involves N-demethylation of the
desosamine sugar or at the 9a position on the macrolide ring. Other
metabolic pathways include O-demethylation and hydrolysis and/or
hydroxylation of the cladinose and desosamine sugar moieties and the
macrolide ring. Up to 10 metabolites of azithromycin have been identified,
and all are microbiologically inactive. While short-term administration of
azithromycin produces hepatic accumulation of the drug and increases
azithromycin demethylase activity, current evidence indicates that hepatic
cytochrome p450 induction of inactivation via cytochrome-metabolite
complex formation does not occur. In contrast to erythromycin,
azithromycin does not inhibit its own metabolism via this pathway.[McEvoy,
ABSORPTION, DISTRIBUTION & EXCRETION:
Biliary excretion of azithromycin, predominantly as unchanged drug is a
major route of elimination following oral administration.[McEvoy, G.K.
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Azithromycin is rapidly absorbed from the GI tract after oral

administration; absorption of the drug is incomplete but exceeds that of
erythromycin. The absolute oral bioavailability of azithromycin is
reported to be approximately 34-52% with single doses of 500 mg to 1.2 g
administered as various oral dosage forms. Limited evidence indicates that
the low bioavailability of zithromycin results from incomplete GI
absorption rather acid degradation of the drug or extensive first-pss
metabolism.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug
Azithromycin appears to be distributed into most body tissues and fluids
after oral or IV administration. The extensive tissue uptake of
azithromycin has been attributed to cellular uptake of this basic
antibiotic into relatively acidic lysosomes as a result of iron trapping
and to an energy-dependent pathway associated with the nucleoside
transport system.[McEvoy, G.K. (ed.). American Hospital Formulary Service
Because of rapid distribution into tissues and high intracellular
concentrations of azithromycin, tissue concentrations of the drug
generally exceed plasma concentrations by 10- to 100-fold following single
dose administration; with multiple dosing, the tissue-to-plasma ratio
increases.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug
Administration of a single 500 mg oral dose of azithromycin generally
produces drug concentrations of 1-9 ug/g in various tissues, including
lung, gastric, prostatic, and gynecologic tissue.[McEvoy, G.K. (ed.).
American Hospital Formulary Service - Drug Information 2003. Bethesda, MD:
American Society of Health-System Pharmacists, Inc. 2003 (Plus
Supplements)., p. 303] **PEER REVIEWED**
Azithromycin has been detected in human milk.[McEvoy, G.K. (ed.). American
Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American
Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p.
300] **PEER REVIEWED**
In an open-label study, the concentrations of azithromycin in middle ear
effusions and plasma were determined in 29 children between 1 and 8 years
of age with a diagnosis of either secretory otitis media of at least 1
month's duration or acute otitis media. Azithromycin (10 mg/kg) was
administered as a single dose 12, 24 or 48 hr before the insertion of
tympanostomy tubes to 17 children with secretory otitis media and once
daily for 5 days (10 mg/kg on day 1, 5 mg/kg on days 2-5) to 12 children
with acute otitis media. In the 16 evaluable patients with secretory
otitis media, azithromycin penetrated middle ear effusions, with group
mean concentrations approximately two orders of magnitude greater than the
concurrent plasma concentrations 12, 24 and 48 hr after administration.
Similar plasma:effusion ratios were found 24 and 48 hr after starting
once-daily therapy in 10 evaluable patients with acute otitis
media.[Pukander J, Rautianen M; J Antimicrob Chemother 37 Suppl C: 53-61
(1996)] **PEER REVIEWED**
BIOLOGICAL HALF-LIFE:
An elimination half-life of 54.5 hours has been reported in children 4
months to 15 years of age receiving single or multiple oral doses of
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azithromycin.[McEvoy, G.K. (ed.). American Hospital Formulary Service Drug Information 2003. Bethesda, MD: American Society of Health-System
The average tissue half life of azithromycin is estimated to be 1-4 days.
The half life of the drug in peripheral leukocytes ranges from 34-57
hours.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug
Serum: 11 to 14 hours when measured between 8 and 24 hours after a single,
oral dose of 500 mg; however, after several doses, the half-life is
approximately the same as the half-life in tissues. Tissue: 2 to 4
days.[MICROMEDEX Thomson Health Care. USPDI - Drug Information for the
Health Care Professional. 23rd ed. Volume 1. MICROMEDEX Thomson Health
Care, Greenwood Village, CO. 2003. Content Reviewed and Approved by the
U.S. Pharmacopeial Convention, Inc., p. 459] **PEER REVIEWED**
MECHANISM OF ACTION:
Azithromycin binds to the 50S ribosomal subunit of the 70S ribosome of
susceptible organisms, thereby inhibiting RNA-dependent protein
synthesis.[MICROMEDEX Thomson Health Care. USPDI - Drug Information for
the Health Care Professional. 23rd ed. Volume 1. MICROMEDEX Thomson Health
Azithromycin inhibits protein synthesis in susceptible organisms by
penetrating the cell wall and binding to 50S ribosomal subunits, thereby
inhibiting translocation of aminoacyl transfer-RNA and inhibiting
polypeptide synthesis. ... The antimicrobial activity of azithromycin is
reduced at low pH. Azithromycin concentrates in phagocytes, including
polymorphonuclear leukocytes, monocytes, macrophages, and fibroblasts.
Penetration of the drug into phagocytic cells is necessary for activity
against intracellular pathogens (e.g., Staphylococcus aureus, Legionella
pneumophila, Chlamydia trachomatis, Salmonella typhi).[McEvoy, G.K. (ed.).
American Hospital Formulary Service - Drug Information 2003. Bethesda, MD:
American Society of Health-System Pharmacists, Inc. 2003 (Plus
Supplements)., p. 301] **PEER REVIEWED**
INTERACTIONS:
Concurrent use with macrolide antibiotics has been associated with
increased serum concentrations of carbamazepine, cyclosporine, digoxin,
hexobarbital, phenytoin, and terfenadine; patients concurrently receiving
azithromycin and any of these medications should be monitored
carefully.[MICROMEDEX Thomson Health Care. USPDI - Drug Information for
Concurrent use with /aluminum- and magnesium-containing/ antacids
decreases the peak serum concentration (Cmax) of azithromycin by
approximately 24%, but has not effect on the area under the plasma
concentration-time (AUC); oral azithromycin should be administered at
least 1 hour before or 2 hours after aluminum- and magnesium-containing
antacids.[MICROMEDEX Thomson Health Care. USPDI - Drug Information for
Concurrent use with macrolide antibiotics has been associated with acute
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ergot toxicity characterized by severe peripheral vasospasm and

dysesthesia; patients concurrently receiving azithromycin and any of these
medications /dihydroergotamine or ergotamine/ should be monitored
increased serum concentrations of theophylline; pending further
investigation, plasma concentrations of theophylline should be monitored
in patients concurrently receiving azithromycin and
theophylline.[MICROMEDEX Thomson Health Care. USPDI - Drug Information
for the Health Care Professional. 23rd ed. Volume 1. MICROMEDEX Thomson
Health Care, Greenwood Village, CO. 2003. Content Reviewed and Approved by
the U.S. Pharmacopeial Convention, Inc., p. 460] **PEER REVIEWED**
Concurrent use with macrolide antibiotics has been associated with a
decrease in the clearance of triazolam, which may increase its effects;
patients concurrently receiving azithromycin and triazolam should be
monitored carefully.[MICROMEDEX Thomson Health Care. USPDI - Drug
Information for the Health Care Professional. 23rd ed. Volume 1.
MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2003. Content
Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 460]
**PEER REVIEWED**
increased anticoagulant effects; prothrombin time should be monitored
carefully in patients concurrently receiving azithromycin and
warfarin.[MICROMEDEX Thomson Health Care. USPDI - Drug Information for
A patient on disopyramide developed disopyramide toxicity when treated
concurrently with azithromycin. Evidence of toxicity included an elevated
serum disopyramide level and ventricular tachycardia requiring
cardioversion. The azalide antibiotic presumably inhibited dealkylation of
disopyramide to its major metabolite, mono-N-dealkyldisopyramide.
Physicians should avoid using azithromycin in patients on disopyramide. If
this drug combination is unavoidable, disopyramide levels must be closely
monitored.[Granowitz EV et al; Pacing Clin Electrophysiol 23 (9): 1433-5
PHARMACOLOGY:
THERAPEUTIC USES:
Azithromycin is indicated in the treatment of cervicitis or urethritis due
to Chlamydia trachomatis or Neisseria gonorrhea. /Included in US product
labeling/[MICROMEDEX Thomson Health Care. USPDI - Drug Information for
Azithromycin is indicated in the treatment of bacterial exacerbations of
chronic bronchitis or acute otitis media due to Hemophilus influenza,
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Moraxella catarrhalis, or Streptococcus pneumonia. However, azithromycin

is not recommended as the first line of therapy for otitis media.
/Included in US product labeling/[MICROMEDEX Thomson Health Care. USPDI Drug Information for the Health Care Professional. 23rd ed. Volume 1.
**PEER REVIEWED**
Azithromycin is indicated in the treatment of genital ulcer disease in men
due to Hemophilus ducreyi. /Included in US product labeling/[MICROMEDEX
Thomson Health Care. USPDI - Drug Information for the Health Care
Professional. 23rd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood
Village, CO. 2003. Content Reviewed and Approved by the U.S. Pharmacopeial
Convention, Inc., p. 459] **PEER REVIEWED**
Azithromycin is indicated in the prevention of disseminated Mycobacterium
avium complex (MAC) disease in patients with advanced human
immunodeficiency virus (HIV) infection. /Included in US product
Azithromycin is indicated in the treatment of pelvic inflammatory disease
due to Chlamydia trachomatis, Mycoplasma hominis, or Neisseria gonorrhea.
/Included in US product labeling/[MICROMEDEX Thomson Health Care. USPDI Drug Information for the Health Care Professional. 23rd ed. Volume 1.
**PEER REVIEWED**
Azithromycin is indicated in the treatment of pharyngitis or tonsillitis
due to Streptococcus pyogenes. /Included in US product
Azithromycin is indicated in the treatment of community-acquired pneumonia
due to Chlamydia pneumonia, Hemophilus influenza, Legionella pneumophila,
Moraxella catarrhalis, Mycoplasma pneumonia, Staphylococcus aureus, or
Streptococcus pneumonia. /Included in US product labeling/[MICROMEDEX
Azithromycin is indicated in the treatment of uncomplicated skin and soft
tissue infections due to Staphylococcus aureus, Streptococcus agalactia,
or Streptococcus pyogenes. /Included in US product labeling/[MICROMEDEX
Azithromycin is indicated in the treatment of trachoma due to Chlamydia
trachomatis. /NOT included in US product labeling/[MICROMEDEX Thomson
Health Care. USPDI - Drug Information for the Health Care Professional.
23rd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO.
2003. Content Reviewed and Approved by the U.S. Pharmacopeial Convention,
05/12/2012
Pgina 14 de 25
Inc., p. 459] **PEER REVIEWED**

Acne vulgaris is a common skin disease seen primarily in adolescent and
young adults. As the treatment involves long term therapy with
antibiotics, an agent with a long half life can be very useful in
increasing the compliance. To evaluate the role of a monthly dose of
azithromycin and compare it with daily doxycycline, we conducted this
randomized comparative study. Sixty patients with moderate to severe acne
were randomly assigned to two treatment groups, A & B. Patients in
group A received 100 mg doxycycline daily in addition to topical 0.05%
tretinoin cream, whereas patients in group B were given 500 mg
azithromycin once a day for four days per month along with 0.05% topical
tretinoin for a total of 12 weeks. Of the 60 patients, 22 in group A and
28 in group B were evaluated. The monthly dose of azithromycin was found
to be as effective as daily doxycycline on a pure protocol basis and
statistically significantly better than doxycycline by intention to treat
analysis.[Parsad D et al; J Dermatol 28 (1): 1-4 (2001)] **PEER REVIEWED**
<a href="http://www.ncbi.nlm.nih.gov/pubmed/11280457?dopt=Abstract"
To assess the efficacy and occurrence of severe side effects associated
with the use of a single dose of azithromycin in the treatment of
Chlamydia trachomatis in pregnant women. Patients and their sexual
partners were randomized into three treatment groups: both the patient and
her sexual partner received a single dose of azithromycin (group 1); the
patient was given a standard course of erythromycin, while her partner was
given a standard course of tetracycline (group 2); and the patient was
given a single dose of azithromycin with the sexual partner given a
standard course of tetracycline (group 3). Group 3 was included in order
to assess the relative efficacy of tetracycline with respect to the use of
azithromycin among patients and to indirectly assess possible patient
reinfection by sexual partners. With respect to the cure rate, 4.5% of
study participants given azithromycin has positive cultures vs. 21.1% of
patients given erythromycin or tetracycline (P = .018). With respect to
side effects severe enough to warrant a change in medication, 7.4% of
patients receiving azithromycin reported suffering such side effects vs.
38.8% of patients given erythromycin (P = .02). Among sexual partners,
28.6% given tetracycline reported severe side effects vs. none of those
given azithromycin (P = .03). Azithromycin in the treatment of C
trachomatis in pregnant women substantially improved the cure rates while
substantially reducing the occurrence of severe side effects associated
with the use of a standard course of erythromycin. Since both tetracycline
and erythromycin are known to be effective against C trachomatis
infection, the improved efficacy of azithromycin is probably due to
noncompliance with the multidose, multiday regimen associated with the use
of these two antibiotics.[Wehbeh HA et al; J Reprod Med 43 (6): 509-14
Cholera is a major public-health problem, with children most affected.
However, effective single-dose antimicrobial regimens have been identified
only for adults. Our aim was to compare the efficacy of azithromycin and
erythromycin regimens in the treatment of children. We did a double-blind,
randomized study of 128 severely dehydrated children (age 1-15 years) with
cholera, treated at one of two treatment centers in Bangladesh in 1999.
Children were assigned single-dose azithromycin (20 mg/kg bodyweight,
maximum individual dose 1 g; n=65) or 12.5 mg/kg erythromycin (maximum
dose 500 mg; n=63) every 6 hr for 3 days. Patients stayed in hospital for
5 days. We measured fluid balance every 6 hr, and obtained a rectal swab
05/12/2012
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or stool sample for culture daily. Our primary outcome measures were
clinical success of treatment-ie, cessation of watery diarrhea within 48
hr and bacteriological success-ie, absence of Vibrio cholerae O1 or O139
from cultures of stool or rectal swab samples after study day 2. Analysis
was per protocol. Two children in both groups withdrew from the study, and
we excluded one child in the erythromycin group. Treatment was clinically
successful in 48 (76%) patients who received azithromycin and 39 (65%) who
received erythromycin (difference 11%, 95% CI -5 to 27, p=0.244); and
bacteriologically successful in 45 (71%) and 49 (82%) patients,
respectively (10%, -5 to 25, p=0.261). Patients treated with azithromycin
had a shorter duration of diarrhea (median 24 hr vs 42 hr; difference 12
hr, 0-18 hr, p=0.019) and fewer episodes of vomiting (1 vs 4; difference 1
episode, 0-3 episodes, p=0.023). Single-dose azithromycin is as effective
for treatment of cholera in children as standard erythromycin therapy, but
is associated with less vomiting.[Khan WA et al; Lancet 360 (9347): 1722-7
Relentless chronic pulmonary inflammation is the major contributor to
morbidity and mortality in patients with cystic fibrosis (CF). While
immunomodulating therapies such as prednisolone and ibuprofen may be
beneficial, their use is limited by side effects. Macrolides have
immunomodulatory properties and long term use dramatically improves
prognosis in diffuse panbronchiolitis, a condition with features in common
with the lung disease of CF. To determine if azithromycin improves
clinical parameters and reduces inflammation in patients with CF, a 3
month prospective randomised double blind, placebo controlled study of
azithromycin (250 mg/day) was undertaken in adults with CF. Monthly
assessment included lung function, weight, and quality of life (QOL).
Blood and sputum collection assessed systemic inflammation and changes in
bacterial flora. Respiratory exacerbations were treated according to the
policy of the CF Unit. Sixty patients were recruited (29 men) of mean (SD)
age 27.9 (6.5) years and initial forced expiratory volume in 1 second
(FEV1) 56.6 (22.3)% predicted. FEV1% and forced vital capacity (FVC)%
predicted were maintained in the azithromycin group while in the placebo
group there was a mean (SE) decline of -3.62 (1.78)% (p=0.047) and -5.73
(1.66)% (p=0.001), respectively. Fewer courses of intravenous antibiotics
were used in patients on azithromycin (0.37 v 1.13, p=0.016). Median C
reactive protein (CRP) levels declined in the azithromycin group from 10
to 5.4 mg/ml but remained constant in the placebo group (p < 0.001). QOL
improved over time in patients on azithromycin and remained unchanged in
those on placebo (p=0.035). Azithromycin in adults with CF significantly
improved QOL, reduced CRP levels and the number of respiratory
exacerbations, and reduced the rate of decline in lung function. Long term
azithromycin may have a significant impact on morbidity and mortality in
patients with CF. Further studies are required to define frequency of
dosing and duration of benefit.[Wolter J et al; Thorax 57 (3): 212-6
A 4-year-old boy with acute lymphoblastic anemia in remission had a
prolonged course of diarrhea and wasting. C. parvum was identified in the
gastrointestinal tract by biopsy and in the stool using modified acid fast
staining. Improvement in the stool consistency was noted after 3 days of
therapy with azithromycin, and, after 14 days of therapy, Cryptosporidium
oocysts could no longer be identified in the stool. C. parvum should be
considered in all immunocompromised patients with severe or prolonged
diarrhea, especially if there is no blood or leukocytes in the stool.
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Because Cryptosporidium is not always tested for in a routine ova and

parasite examination, the lab should be notified if it is in the
differential diagnosis. Azithromycin therapy may prove beneficial in the
treatment of intestinal Cryptosporidium in immunocompromised
individuals.[Russell TS et al; : J Pediatr Hematol Oncol 20 (1): 83-5
We conducted an open-label randomized controlled trial to compare the
efficacy and safety of clarithromycin (15/mg/kg/day in 2 divided doses for
7 days) with those of azithromycin (10 mg/kg/day in 1 dose for 3 days) in
the treatment of children with Mediterranean spotted fever. Until now,
there has not been a gold-standard therapy for this rickettsial disease in
children. Eighty-seven children were randomized to receive 1 of the 2
drugs. The mean time to defervescence (+/- standard deviation) was
46.2+/-36.4 hr in the clarithromycin group and 39.3+/-31.3 hr in the
azithromycin group. These differences were not statistically significant
and both drugs were equally well-tolerated. Clarithromycin and
azithromycin could be acceptable therapeutic alternatives to
chloramphenicol and tetracyclines for children aged
< or =8 years with
Mediterranean spotted fever. Azithromycin, because it has a long
half-life, offers the advantages of administration in a single daily dose
and a shorter duration of therapy, which could increase compliance in
children.[Cascio A et al; Clin Infect Dis 34 (2): 154-8 (2002)] **PEER
REVIEWED** <a
The recommended treatment for pertussis is erythromycin, 40 to 50 mg/kg
per day for 2 weeks. The newly developed macrolides, clarithromycin and
azithromycin, have been demonstrated to be superior to erythromycin
because of improved absorption and a longer half-life. As a result, we
conducted two separate comparison studies to evaluate the efficacies of
clarithromycin, 10 mg/kg per day, twice a day for 7 days, and
azithromycin, 10 mg/kg per day, once a day for 5 days, compared with the
standard erythromycin regimen. A total of 17 patients, including 10
infants 1 year of age or less, for whom pertussis had been confirmed by
culture, were allocated to receive either clarithromycin or azithromycin
treatment, and each patient was matched (age, sex, and immunization
status) with historical control subjects who had been treated with
erythromycin. Eradication rates examined at 1 week after treatment were as
follows: 9 of 9 with clarithromycin versus 16 of 18 with erythromycin (psi
M-H = 1.13), and 8 of 8 with azithromycin versus 13 of 16 with
erythromycin (psi M-H = 1.23). No bacterial relapse after treatment was
detected in either group. All isolated strains of Bordetella pertussis
were susceptible to clarithromycin, azithromycin, and erythromycin, and no
change in drug susceptibility has been confirmed for the past 20 years in
Japan. Because of the very low incidence of pertussis resulting from
widespread use of acellular pertussis vaccination, this study did not
enroll a large number of patients; however we conclude that short-term
treatment with clarithromycin or azithromycin is expected to be equal or
superior to the standard long-term erythromycin regimen for
pertussis.[Aoyama T et al; J Pediatr 129 (5): 761-4 (1996)] **PEER
REVIEWED** <a
An open, noncomparative study was performed to establish the efficacy of
azithromycin in the treatment of early syphilis. Sixteen patients were
treated with oral azithromycin: 1g the first day and then 500 mg for the
following 8 days. Two patients were excluded from the study, leaving 14
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patients for the evaluation of the efficacy. Venereal Disease Research

Laboratory (VDRL) negativity was observed in 3 out of 6 patients treated
for primary syphilis after 3 months and in all patients after 6 months.
Two of 8 patients treated for manifest or early latent secondary syphilis
had VDRL negativity after 3 months and 4 patients after 6 months. This
study demonstrates that azithromycin is effective in the treatment of
early syphilis. Two patients experienced gastrointestinal side effects
which did not require treatment interruption.[Gruber F et al; J Chemother
12 (3): 240-3 (2000)] **PEER REVIEWED** <a
The oropharyngeal barrier is an innate host defence mechanism to prevent
bacterial Lung infection. A compromised barrier function is observed in
patients with cystic fibrosis (CF) who are chronically infected with
Pseudomonas aeruginosa. Macrolides are assumed to modify host defence. We
investigated the oropharyngeal barrier function in CF patients treated
with azithromycin.
In a prospective study, eleven chronically infected
children with CF were treated with longterm low-dose azithromycin. The
oropharyngeal barrier function was assessed by adherence of P. aeruginosa
(strain PACF 12-1) to buccal epithelial cells of the patients before and
after therapy. The mean (standard deviation, SD) buccal adherence before
therapy was markedly high with 8.0 (4.8) bacteria/cell. Following therapy
with azithromycin adherence decreased in all patients by 70% or 5.6 to 2.4
(1.1) bacteria/cell (p = 0.007), representing close to normal levels (1.2
+/- 0.6). Long-term low-dose azithromycin therapy may improve the
compromised oropharyngeal barrier function in patients with CF, opening
new perspectives for early treatment of P. aeruginosa infection in
CF.[Baumann U et al; Infection 29 (1): 7-11 (2001)] **PEER REVIEWED** <a
DRUG WARNINGS:
Pregnancy risk category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well
controlled studies in pregnant women have not shown increased risk of
fetal abnormalities despite adverse findings in animals, or, in the
absents of adequate human studies, animal studies show no fetal risk. The
chance of fetal harm is remote but remains a possibility./[Physicians Desk
Reference. 58th ed. Thomson PDR. Montvale, NJ 2004., p. 2684] **PEER
REVIEWED**
The most frequent adverse effects of azithromycin involve the GI tract
(i.e., diarrhea/loose stools, nausea, abdominal pain). While these adverse
effects generally are mild to moderate in severity and occur less
frequently than with oral erythromycin therapy, adverse GI effects are the
most frequent reason for discontinuing azithromycin therapy.[McEvoy, G.K.
Azithromycin has been detected in human milk. The drug should be used with
caution in nursing women.[McEvoy, G.K. (ed.). American Hospital Formulary
REVIEWED**
Serious allergic (i.e., angioedema, anaphylaxis, bronchospasm) and
dermatologic (i.e., erythema multiforme, Stevens-Johnson syndrome, toxic
epidermal necrolysis) reactions, sometimes resulting in death, have been
reported rarely in patients receiving azithromycin. ...[McEvoy, G.K.
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Approximately 12% of patients experienced an adverse effect related to IV
infusion of azithromycin. Pain at the injection site or local inflammation
occurred in 6.5 or 3.1%, respectively, of patients receiving IV
azithromycin. ...[McEvoy, G.K. (ed.). American Hospital Formulary Service
Elevation in serum potassium concentration has been reported in 1-2% of
adults receiving azithromycin in clinical trials. Elevation in BUN, serum
creatinine, or serum phosphate concentration has been reported in less
than 1% of adults receiving oral azithromycin, while elevated serum
creatinine concentration has been reported in 4-6% of patients receiving
IV azithromycin. ...[McEvoy, G.K. (ed.). American Hospital Formulary
REVIEWED**
Palpitations, chest pain, edema hypotension, or syncope has been reported
in 1% or less of patients receiving oral azithromycin. While not directly
attributed to azithromycin therapy, arrhythmia (including ventricular
tachycardia)has been reported in at least one person receiving the drug.
In one patient with a history of arrhythmia, torsades de pointes with
subsequent myocardial infarction occurred following completion of
azithromycin therapy.[McEvoy, G.K. (ed.). American Hospital Formulary
REVIEWED**
Azithromycin, a semi-synthetic azalide antibiotic, is a macrolide that
thus far has not shared the neuropsychiatric side effects of other
macrolides such as erythromycin and clarithromycin. We now report
significant delirium associated with conventional dosing of azithromycin
in two geriatric patients who were being treated for lower respiratory
tract infection. The onset of delirium was apparent within 72 hours of
initiating azithromycin therapy and lasted 48 to 72 hours after
discontinuing treatment with the drug. In contrast to the adverse central
nervous system symptoms associated with clarithromycin, those induced by
azithromycin seem to take longer to resolve, perhaps based upon the longer
elimination half-life of the latter antimicrobial, particularly in
geriatric women.[Cone LA et al; Surg Neurol 59 (6): 509-11 (2003)] **PEER
REVIEWED** <a
Intravenous azithromycin is increasingly administered for treatment of
hospitalized patients with community-acquired pneumonia. Macrolide
antibiotics cause ototoxicity, which occurs most frequently when high
serum concentrations are achieved. Current dosing guidelines for
intravenous azithromycin can result in much higher serum concentrations
than is seen with oral administration. We describe a 47-year-old woman who
developed complete deafness after receiving 8 days of intravenous
azithromycin.[Bizjak ED et al; Pharmacotherapy 19 (2): 245-8 (1999)]
**PEER REVIEWED** <a
05/12/2012
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Azithromycin (Zithromax), an erythromycin derivative that belongs to a

subgroup of the macrolides known as azolides, has generally been
considered to be a very safe medication. Hepatic side effects are uncommon
but may include jaundice, fever, and right upper quadrant pain. Herein we
describe a patient who developed azithromycin-induced cholestatic
hepatitis that resolved upon discontinuation of the drug. Lack of other
known causes for liver disease, the temporal relationship with this drug,
and the typical changes of liver histology have established the diagnosis.
Clinicians should be aware of this side effect of azithromycin, which is
widely prescribed.[Chandrupatla S et al; Dig Dis Sci 47 (10): 2186-8
We report the case of a 25-year-old female patient with severe aggravation
of myasthenia gravis due to azithromycin which was prescribed for an
influenza syndrome. One hour after the intake of 500 mg azithromycin the
patient developed weakness of the legs and respiratory distress due to
respiratory muscle failure. She was hospitalized in a comatose state and
required intubation and mechanical ventilation for six days. Acute
worsening of myasthenia gravis was observed in this patient in 1986 after
parenteral administration of erythromycin. Erythromycin causing
Azithromycin, an azalide antibiotic, rarely causes ototoxicity. According
to the few reports in existence, azithromycin-induced ototoxicity occurred
following prolonged high-dose therapy in patients with acquired
immunodeficiency syndrome and resulted in a reversible sensorineural
hearing loss. We present a case of irreversible sensorineural hearing loss
due to azithromycin ototoxicity in an otherwise healthy woman following
low-dose exposure to azithromycin.[Ress BD, Gross EM; Ann Otol Rhinol
Laryngol 109 (4): 435-7 (2000)] **PEER REVIEWED** <a
Adverse CNS effects reported in 1% or less of adults receiving
azithromycin include dizziness, headache, vertigo, or somnolence, and
those reported in 1% or less of children include headache, hyperkinesia,
dizziness, agitation, nervousness, fatigue, malaise, and insomnia.[McEvoy,
... Oral azithromycin should not be used for the treatment of pneumonia
that is considered unsuitable for outpatient oral therapy because of the
severity of the infection (e.g., moderate to severe) or when risk factors
such as nosocomially acquired infection, known or suspected bacteremia,
cystic fibrosis, or any clinically important underlying health problem
that might compromise the patient's ability to respond adequately (e.g.,
immunodeficiency, functional asplenia) are present. In addition, ... the
drug should not be used for the treatment of pneumonia in patients
05/12/2012
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requiring hospitalization or in geriatric or debilitated patients.[McEvoy,

Because azithromycin is eliminated principally via the liver, the drug
should be used with caution in patients with impaired hepatic function.
The cases of 3 patients, who presented with hearing loss after receiving a
combination of clofazimine, ethambutol, and 500 mg of oral azithromycin
daily for 30-90 days as therapy for Mycobacterium avium infection are
reported. Hearing loss was resolved 2-4 wk after cessation of azithromycin
therapy. Patients who received another macrolide in place of azithromycin
did not develop hearing loss. One patient was rechallenged with
azithromycin after his hearing returned to baseline, and within 14 days he
noted a marked decline in his auditory acuity. He again discontinued the
drug and noted a return to normal hearing over 10-15 days.[Wallace MR et
al; Lancet; 343 (Jan 22): 241 (1994)] **PEER REVIEWED**
INTERACTIONS:
increased serum concentrations of carbamazepine, cyclosporine, digoxin,
hexobarbital, phenytoin, and terfenadine; patients concurrently receiving
azithromycin and any of these medications should be monitored
Concurrent use with /aluminum- and magnesium-containing/ antacids
decreases the peak serum concentration (Cmax) of azithromycin by
approximately 24%, but has not effect on the area under the plasma
concentration-time (AUC); oral azithromycin should be administered at
least 1 hour before or 2 hours after aluminum- and magnesium-containing
antacids.[MICROMEDEX Thomson Health Care. USPDI - Drug Information for
Concurrent use with macrolide antibiotics has been associated with acute
ergot toxicity characterized by severe peripheral vasospasm and
dysesthesia; patients concurrently receiving azithromycin and any of these
medications /dihydroergotamine or ergotamine/ should be monitored
increased serum concentrations of theophylline; pending further
investigation, plasma concentrations of theophylline should be monitored
in patients concurrently receiving azithromycin and
theophylline.[MICROMEDEX Thomson Health Care. USPDI - Drug Information
for the Health Care Professional. 23rd ed. Volume 1. MICROMEDEX Thomson
Health Care, Greenwood Village, CO. 2003. Content Reviewed and Approved by
the U.S. Pharmacopeial Convention, Inc., p. 460] **PEER REVIEWED**
05/12/2012
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Concurrent use with macrolide antibiotics has been associated with a

decrease in the clearance of triazolam, which may increase its effects;
patients concurrently receiving azithromycin and triazolam should be
monitored carefully.[MICROMEDEX Thomson Health Care. USPDI - Drug
Information for the Health Care Professional. 23rd ed. Volume 1.
**PEER REVIEWED**
increased anticoagulant effects; prothrombin time should be monitored
carefully in patients concurrently receiving azithromycin and
warfarin.[MICROMEDEX Thomson Health Care. USPDI - Drug Information for
A patient on disopyramide developed disopyramide toxicity when treated
concurrently with azithromycin. Evidence of toxicity included an elevated
serum disopyramide level and ventricular tachycardia requiring
cardioversion. The azalide antibiotic presumably inhibited dealkylation of
disopyramide to its major metabolite, mono-N-dealkyldisopyramide.
Physicians should avoid using azithromycin in patients on disopyramide. If
this drug combination is unavoidable, disopyramide levels must be closely
monitored.[Granowitz EV et al; Pacing Clin Electrophysiol 23 (9): 1433-5
ENVIRONMENTAL FATE & EXPOSURE:
MILK CONCENTRATIONS:
Azithromycin has been detected in human milk.[McEvoy, G.K. (ed.). American
ENVIRONMENTAL STANDARDS & REGULATIONS:
FDA REQUIREMENTS:
The Approved Drug Products with Therapeutic Equivalence Evaluations List
identifies currently marketed prescription drug products, incl
azithromycin, approved on the basis of safety and effectiveness by FDA
under sections 505 of the Federal Food, Drug, and Cosmetic Act.[DHHS/FDA;
Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence
Evaluations. Available from, as of February 10, 2004:
http://www.fda.gov/cder/ob/] **PEER REVIEWED**
CHEMICAL/PHYSICAL PROPERTIES:
MOLECULAR FORMULA:
C38-H72-N2-O12[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ:
Merck and Co., Inc., 2001., p. 159] **PEER REVIEWED**
05/12/2012
Pgina 22 de 25
MOLECULAR WEIGHT:
748.98[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
COLOR/FORM:
Crystals[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
MELTING POINT:
113-115 deg C[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
DISSOCIATION CONSTANTS:
pKa = 8.74[McFarland JW et al; J Med Chem 40: 1340-6 (1997)] **PEER
REVIEWED** <a
OCTANOL/WATER PARTITION COEFFICIENT:
log Kow = 4.02[McFarland JW et al; J Med Chem 40: 1340-6 (1997)] **PEER
REVIEWED** <a
SOLUBILITIES:
In water, 7.09 mg/L @ 25 deg C /Estimated/[US EPA; Estimation Program
Interface (EPI) Suite. Ver.3.11. June 10, 2003. Available from, as of Feb
19, 2004: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm] **PEER
REVIEWED**
VAPOR PRESSURE:
3.9X10-27 mm Hg @ 25 deg C /Estimated/[US EPA; Estimation Program
Interface (EPI) Suite. Ver.3.11. June 10, 2003. Available from, as of Feb
19, 2004: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm] **PEER
REVIEWED**
OTHER CHEMICAL/PHYSICAL PROPERTIES:
Hydroxyl radical reaction rate constant = 4.23X10-10 cu cm/molec-sec @ 25
deg C /Estimated/[US EPA; Estimation Program Interface (EPI) Suite.
Ver.3.11. June 10, 2003. Available from, as of Feb 19, 2004:
http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm] **PEER REVIEWED**
Henry's Law constant = 5.3X10-29 atm-cu m/mol @ 25 deg C /Estimated/[US
EPA; Estimation Program Interface (EPI) Suite. Ver.3.11. June 10, 2003.
Available from, as of Feb 19, 2004:
http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm] **PEER REVIEWED**
CHEMICAL SAFETY & HANDLING:
STORAGE CONDITIONS:
Commercially available azithromycin 250 mg tablets should be stored at
15-30 deg C. Azithromycin 600 mg tablets and powder for multiple dose oral
suspension should be stored at temperatures below 30 deg C. Azithromycin
powder in single dose packets for oral suspension should be stored at 5-30
05/12/2012
Pgina 23 de 25
deg C.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug

Commercially available azithromycin for injection should be stored at or
below 30 deg C. Following reconstitution with sterile water for injection,
solutions containing 100 mg of azithromycin per mL are stable for 24 hours
when stored below 30 deg C.[McEvoy, G.K. (ed.). American Hospital
Formulary Service - Drug Information 2003. Bethesda, MD: American Society
of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 304]
**PEER REVIEWED**
DISPOSAL METHODS:
SRP: The most favorable course of action is to use an alternative chemical
product with less
inherent propensity for occupational exposure or
environmental contamination. Recycle any unused portion of the material
for its approved use or return it to the manufacturer or supplier.
Ultimate disposal of the chemical must consider: the material's impact on
air quality; potential migration in soil or water; effects on animal,
aquatic, and plant life; and conformance with environmental and public
health regulations. **PEER REVIEWED**
OCCUPATIONAL EXPOSURE STANDARDS:
MANUFACTURING/USE INFORMATION:
MAJOR USES:
Antibacterial[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
MANUFACTURERS:
Pfizer Inc., 235 East 42nd St., New York, NY 10017-5755
/Dihydrate/[Physicians' Desk Reference. 57th ed. Oradell, N.J.: Medical
Economics Co., p. 104 (2003)] **PEER REVIEWED**
FORMULATIONS/PREPARATIONS:
Oral: For suspension: 100 mg (of anhydrous azithromycin) per 5 mL,
Zithromax (Pfizer); 200 mg (of anhydrous azithromycin) per 5 mL, Zithromax
(Pfizer); 1 g (of anhydrous azithromycin) per packet, Zithromax Single
Dose Packets (Pfizer); Tablets, film coated: 250 mg (of anhydrous
azithromycin), Zithromax (scored, (Pfizer), Zithromax Z-Pak (scored;
available as a 5 day mnemonic pack of 6 tablets), (Pfizer); 500 mg (of
anhydrous azithromycin), Zithromax (scored), (Pfizer), Zithromax Tri-Paks,
(scored; available as a 3 day mnemonic pack of 3 tablets), (Pfizer); 600
mg (of anhydrous azithromycin), Zithromax, (scored), (Pfizer).[McEvoy,
Parenteral: For injection, for IV infusion only: 500 mg (of anhydrous
azithromycin), (Zithromax), (Pfizer).[McEvoy, G.K. (ed.). American
05/12/2012
Pgina 24 de 25
LABORATORY METHODS:
ANALYTIC LABORATORY METHODS:
Analyte: azithromycin; matrix: chemical identification; procedure:
infrared absorption spectrophotometry with comparison to standards[U.S.
Pharmacopeia. The United States Pharmacopeia, USP 27/The National
Formulary, NF 22; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p198
Analyte: azithromycin; matrix: chemical identification; procedure:
retention time of liquid chromatogram with comparison to standards[U.S.
Pharmacopeia. The United States Pharmacopeia, USP 27/The National
Formulary, NF 22; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p198
Analyte: azithromycin; matrix: chemical purity; procedure: liquid
chromatography with amperometric electrochemical detection and comparison
to standards[U.S. Pharmacopeia. The United States Pharmacopeia, USP 27/The
National Formulary, NF 22; Rockville, MD: U.S. Pharmacopeial Convention,
Inc., p198 (2004)] **PEER REVIEWED**
Analyte: azithromycin; matrix: pharmaceutical preparation (capsules);
procedure: retention time of liquid chromatogram with comparison to
standards (chemical identification)[U.S. Pharmacopeia. The United States
Pharmacopeia, USP 27/The National Formulary, NF 22; Rockville, MD: U.S.
Pharmacopeial Convention, Inc., p199 (2004)] **PEER REVIEWED**
Analyte: azithromycin; matrix: pharmaceutical preparation (capsules);
procedure: liquid chromatography with amperometric electrochemical
detection and comparison to standards (chemical purity)[U.S. Pharmacopeia.
The United States Pharmacopeia, USP 27/The National Formulary, NF 22;
Rockville, MD: U.S. Pharmacopeial Convention, Inc., p199 (2004)] **PEER
REVIEWED**
Analyte: azithromycin; matrix: pharmaceutical preparation (oral
suspension); procedure: retention time of liquid chromatogram with
comparison to standards (chemical identification)[U.S. Pharmacopeia. The
United States Pharmacopeia, USP 27/The National Formulary, NF 22;
Rockville, MD: U.S. Pharmacopeial Convention, Inc., p200 (2004)] **PEER
REVIEWED**
Analyte: azithromycin; matrix: pharmaceutical preparation (oral
suspension); procedure: liquid chromatography with amperometric
electrochemical detection and comparison to standards (chemical
purity)[U.S. Pharmacopeia. The United States Pharmacopeia, USP 27/The
National Formulary, NF 22; Rockville, MD: U.S. Pharmacopeial Convention,
Inc., p200 (2004)] **PEER REVIEWED**
SPECIAL REFERENCES:
SPECIAL REPORTS:
Langtry HD et al; Azithromycin. A Review of its Use in Pediatric
Infectious Diseases; Drugs 56 (2): 273-97 (1998)
SYNONYMS AND IDENTIFIERS:
05/12/2012
Pgina 25 de 25
SYNONYMS:
(2R-(2R*,3S*,4R*,5R*,8R*,10R*,11R*,12S*,13S*,14R*))-13-((2,6-Dideoxy-3-Cmethyl-3-O-methyl-alpha-L-ribo-hexopyranosyl)oxy)-2-ethyl3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-((3,4,6trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl)oxy)-1oxa-6-azacyclopentadecan-15-one[O'Neil, M.J. (ed.). The Merck Index - An
Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition,
Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 159] **PEER
REVIEWED**
9-Deoxo-9a-methyl-9a-aza-9a-homoerythromycin A[O'Neil, M.J. (ed.). The
Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th
Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 159]
**PEER REVIEWED**
Zithromax[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug
ASSOCIATED CHEMICALS: Azithromycin dihydrate; 11772-70-0
FORMULATIONS/PREPARATIONS:
Oral: For suspension: 100 mg (of anhydrous azithromycin) per 5 mL,
Zithromax (Pfizer); 200 mg (of anhydrous azithromycin) per 5 mL, Zithromax
(Pfizer); 1 g (of anhydrous azithromycin) per packet, Zithromax Single
Dose Packets (Pfizer); Tablets, film coated: 250 mg (of anhydrous
azithromycin), Zithromax (scored, (Pfizer), Zithromax Z-Pak (scored;
available as a 5 day mnemonic pack of 6 tablets), (Pfizer); 500 mg (of
anhydrous azithromycin), Zithromax (scored), (Pfizer), Zithromax Tri-Paks,
(scored; available as a 3 day mnemonic pack of 3 tablets), (Pfizer); 600
mg (of anhydrous azithromycin), Zithromax, (scored), (Pfizer).[McEvoy,
Parenteral: For injection, for IV infusion only: 500 mg (of anhydrous
azithromycin), (Zithromax), (Pfizer).[McEvoy, G.K. (ed.). American
ADMINISTRATIVE INFORMATION:
HAZARDOUS SUBSTANCES DATABANK NUMBER: 7205
LAST REVISION DATE: 20040910
LAST REVIEW DATE: Reviewed by SRP on 5/13/2004
UPDATE HISTORY:
Complete Update on 2004-09-10, 28 fields added/edited/deleted
Created 20040122
05/12/2012

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The following information was generated from the

The most frequent adverse effects of azithromycin involve the GI tract

nervous system symptoms associated with clarithromycin, those induced by

Laryngol 109 (4): 435-7 (2000)] PEER REVIEWED <a

the POISINDEX(R) or MEDITEXT(R) databases. Copyright 1974-2012 Thomson

reported with the administration of erythromycin, but

disturbances (rare) or nephritis (rare) is suspected, or

Azithromycin was subjected to a series of three in vitro

and one in vivo genetic toxicology assays for the detection of

Azithromycin is rapidly absorbed from the GI tract after oral

ergot toxicity characterized by severe peripheral vasospasm and

Moraxella catarrhalis, or Streptococcus pneumonia. However, azithromycin

Inc., p. 459] PEER REVIEWED

Because Cryptosporidium is not always tested for in a routine ova and

patients for the evaluation of the efficacy. Venereal Disease Research

(ed.). American Hospital Formulary Service - Drug Information 2003.

Azithromycin (Zithromax), an erythromycin derivative that belongs to a

requiring hospitalization or in geriatric or debilitated patients.[McEvoy,

Concurrent use with macrolide antibiotics has been associated with a

deg C.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug

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