azithromycin toxnet

8/18/2019 AZITHROMYCIN TOXNET

1/25

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

zithromaxazasite

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** 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**

Página 1 de 25

05/12/2012http://toxnet.nlm.nih.gov/cgi-bin/sis/download.txt


2/25

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


Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 298] **PEER 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

Página 2 de 25



3/25

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** PubMed Abstract

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** PubMed Abstract

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** PubMed Abstract

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







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

Página 3 de 25



4/25

Laryngol 109 (4): 435-7 (2000)] **PEER REVIEWED** PubMed Abstract

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. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 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,

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

Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 299] **PEER REVIEWED**

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:

Portions of the POISINDEX(R) and MEDITEXT(R) database have been provided herefor general reference. THE COMPLETE POISINDEX(R) DATABASE OR MEDITEXT(R)

DATABASE SHOULD BE CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF

SPECIFIC CASES. The use of the POISINDEX(R) and MEDITEXT(R) databases is at your

sole risk. The POISINDEX(R) and MEDITEXT(R) databases are provided "AS IS" and

"as available" for use, without warranties of any kind, either expressed or

implied. Micromedex makes no representation or warranty as to the accuracy,

reliability, timeliness, usefulness or completeness of any of the information

contained in the POISINDEX(R) and MEDITEXT(R) databases. ALL IMPLIED WARRANTIES

OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY

EXCLUDED. Micromedex does not assume any responsibility or risk for your use of

Página 4 de 25



5/25

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.

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

Página 5 de 25



6/25

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

Página 6 de 25



7/25

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;

Página 7 de 25



8/25


9/25

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 his-

revertants. 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** PubMed Abstract

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



ABSORPTION, DISTRIBUTION & EXCRETION:

Biliary excretion of azithromycin, predominantly as unchanged drug is a

major route of elimination following oral administration.[McEvoy, G.K.




Página 9 de 25



10/25

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 Information 2003. Bethesda, MD: American Society of Health-System


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

- Drug Information 2003. Bethesda, MD: American Society of Health-System


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

Página 10 de 25



11/25

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 Care, Greenwood Village, CO. 2003. Content Reviewed and Approved by the


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

the Health Care Professional. 23rd ed. Volume 1. MICROMEDEX Thomson Health



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

Página 11 de 25



12/25

ergot toxicity characterized by severe peripheral vasospasm and

dysesthesia; patients concurrently receiving azithromycin and any of these

medications /dihydroergotamine or ergotamine/ should be monitored





Concurrent use with macrolide antibiotics has been associated with 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,

Página 12 de 25



13/25


14/25


15/25

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.

Página 15 de 25



16/25

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** PubMed Abstract

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


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

Página 16 de 25



17/25

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** PubMed Abstract

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** 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**

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.

Página 17 de 25



18/25




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 Pharmacists, Inc. 2003 (Plus Supplements)., p. 298] **PEER REVIEWED**

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


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** PubMed Abstract

Página 18 de 25



19/25

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

aggravation of myasthenia gravis by interfering with neuromuscular transmission is reported in the literature. The close temporal







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** PubMed Abstract

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,


Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 298] **PEER REVIEWED**

... 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

Página 19 de 25



20/25

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.


Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 299] **PEER REVIEWED**

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: 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





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**

Página 20 de 25



21/25

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


ENVIRONMENTAL FATE & EXPOSURE:

MILK CONCENTRATIONS:

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.


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**

Página 21 de 25



22/25

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

Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ:Merck and Co., Inc., 2001., p. 159] **PEER REVIEWED**

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


OCTANOL/WATER PARTITION COEFFICIENT: log Kow = 4.02[McFarland JW et al; J Med Chem 40: 1340-6 (1997)] **PEER


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

Página 22 de 25



23/25

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



Parenteral: For injection, for IV infusion only: 500 mg (of anhydrous

azithromycin), (Zithromax), (Pfizer).[McEvoy, G.K. (ed.). American




Página 23 de 25



24/25

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 (2004)] **PEER REVIEWED**

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:

Página 24 de 25



25/25

SYNONYMS:

(2R-(2R*,3S*,4R*,5R*,8R*,10R*,11R*,12S*,13S*,14R*))-13-((2,6-Dideoxy-3-C-

methyl-3-O-methyl-alpha-L-ribo-hexopyranosyl)oxy)-2-ethyl-

3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-((3,4,6-

trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl)oxy)-1-

oxa-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

Página 25 de 25

azithromycin toxnet

Documents