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Azithromycin (Systemic)


VA CLASSIFICATION
Primary: AM200

Commonly used brand name(s): Zithromax.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antibacterial (systemic)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

General considerations
Azithromycin is an azalide antibiotic, part of the macrolide family of antibacterials. It has in vitro activity against many gram-positive and gram-negative aerobic and anaerobic bacteria {11}. It also has greater stability than erythromycin in the presence of acid {05}.

Azithromycin is active against staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis , as well as streptococci, such as Streptococcus pyogenes and Streptococcus pneumoniae . The minimum inhibitory concentration (MIC) of azithromycin is two to four times greater than that of erythromycin against staphylococcus and streptococcus {11} {12} {13}. Most erythromycin-resistant strains of staphylococcus, enterococcus, and streptococcus, including methicillin-resistant S. aureus , are also resistant to azithromycin {11} {13}. Also, azithromycin is less potent than erythromycin and clarithromycin against erythromycin-sensitive enterococci {12}.

Azithromycin has excellent activity against Haemophilus influenzae , being two to eight times more active than erythromycin and four to eight times more active than clarithromycin in vitro {11}. MICs of 4 to 16 mcg per mL inhibit most Escherichia coli , Salmonella , Shigella , and Aeromonas species {11} {13}. Pseudomonas aeruginosa , Klebsiella , Enterobacter , Citrobacter , Proteus , Providencia , Morganella , and Serratia species are resistant to azithromycin {11}.

Azithromycin is two- to fourfold more active than erythromycin against Moraxella (Branhamella) catarrhalis {12}. Inhibition of anaerobes, such as Clostridium perfringens , is slightly better with azithromycin than with erythromycin, and azithromycin"s inhibition of Bacteroides fragilis and other Bacteroides species is comparable to that of erythromycin {11} {12}. Azithromycin also has good in vitro activity against Chlamydia trachomatis , Chlamydia pneumoniae , Mycoplasma pneumoniae , Legionella species, Borrelia burgdorferi , Ureaplasma urealyticum , and Gardnerella vaginalis {11}. Azithromycin has eightfold more activity than erythromycin against Neisseria gonorrhoeae and tenfold more activity against Haemophilus ducreyi {12}. It has also been shown to inhibit Toxoplasma gondii in vitro and in animal models. However, no potentiation against T. gondii could be demonstrated when azithromycin was combined with pyrimethamine {11} {12}. Also, when azithromycin was administered as a single agent in the treatment of cerebral toxoplasmosis in two patients, it failed, although the patients responded to conventional treatment {15}.

Accepted

Bronchitis, bacterial exacerbations (treatment) or
Otitis media, acute (treatment)—Azithromycin is indicated in the treatment of bacterial exacerbations of chronic bronchitis or acute otitis media due to Haemophilus influenzae , Moraxella catarrhalis , or Streptococcus pneumoniae {01}. However, azithromycin is not recommended as the first line of therapy for otitis media {18}.

Cervicitis, gonococcal (treatment)
Cervicitis, nongonococcal (treatment)
Urethritis, gonococcal (treatment) or
Urethritis, nongonococcal (treatment)—Azithromycin is indicated in the treatment of cervicitis or urethritis due to Chlamydia trachomatis or Neisseria gonorrhoeae .

Chancroid (treatment)—Azithromycin is indicated in the treatment of genital ulcer disease in men due to Haemophilus ducreyi {01}.

Mycobacterium avium complex (MAC) disease, disseminated (prophylaxis)1— Azithromycin is indicated in the prevention of disseminated MAC disease in patients with advanced human immunodeficiency virus (HIV) infection {01}.

Pelvic inflammatory disease (treatment)1—Azithromycin is indicated in the treatment of pelvic inflammatory disease due to Chlamydia trachomatis , Mycoplasma hominis , or Neisseria gonorrhoeae {01}.

Pharyngitis (treatment) or
Tonsillitis (treatment)—Azithromycin is indicated in the treatment of pharyngitis or tonsillitis due to Streptococcus pyogenes {01}.

Pneumonia, community-acquired (treatment)—Azithromycin is indicated in the treatment of community-acquired pneumonia due to Chlamydia pneumoniae1 , Haemophilus influenzae , Legionella pneumophila1 , Moraxella catarrhalis1 , Mycoplasma pneumoniae1 , Staphylococcus aureus1 , or Streptococcus pneumoniae {01}.

Skin and soft tissue infections (treatment)—Azithromycin is indicated in the treatment of uncomplicated skin and soft tissue infections due to Staphylococcus aureus , Streptococcus agalactiae , or Streptococcus pyogenes {01}.

[Trachoma (treatment)]1—Azithromycin is indicated in the treatment of trachoma due to Chlamydia trachomatis{19}{20}{21}.
—Trachoma is the leading cause of preventable blindness. Programs to prevent blindness due to trachoma have been based on community-wide treatment with topical tetracycline. Single-dose azithromycin has been shown to be as effective as a 6–week course of topical tetracycline ointment in the treatment of active trachoma. Therefore, azithromycin is useful in establishing high compliance in the treatment of trachoma{19}{20}{21}.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Azithromycin: 785.03 {17}

Mechanism of action/Effect:

Azithromycin binds to the 50S ribosomal subunit of the 70S ribosome of susceptible organisms, thereby inhibiting RNA-dependent protein synthesis {01} {09}.

Azithromycin is bactericidal for Streptococcus pyogenes , Streptococcus pneumoniae , and Haemophilus influenzae ; it is bacteriostatic for staphylococci and most aerobic gram-negative species {11}.

Absorption:

For oral dosage forms—

• Rapidly absorbed {01}; bioavailability is approximately 37% {05}.


• Capsule form: Food decreases peak serum concentration (C max) values by approximately 52% and area under the plasma concentration–time curve (AUC) values by approximately 43% {01}.


• Tablet form: Food increases C max values by approximately 23% and 34% for the 250- and 600-mg tablets, respectively, and has no effect on AUC values {01}.


• Oral suspension form (for adults): Food increases C max values by approximately 56% and has no effect on AUC values {01}.


Distribution:

Rapidly and widely distributed throughout the body. Concentrates intracellularly, resulting in tissue concentrations 10 to 100 times higher than those found in plasma or serum {05}. Azithromycin is highly concentrated in phagocytes and fibroblasts. Phagocytes transport the drug to the site of infection and inflammation. Release of azithromycin from phagocytes is gradual, but it is enhanced by exposure to the cell membrane of bacteria {06}. Release of azithromycin from fibroblasts is not enhanced by bacteria, but fibroblasts may act as reservoirs of the antibiotic, releasing azithromycin to phagocytes {06}. Very low concentrations (< 0.01 mcg per mL [mcg/mL]) have been detected in the cerebrospinal fluid of human subjects with noninflamed meninges {01}; however, higher concentrations were found in brain tissue in animal studies {16}.

Vol D


For oral dosage forms, approximately 31 L per kg (steady-state) {01}.


For parenteral dosage forms, approximately 33 L per kg (following 1000- to 4000-mg doses at a concentration of 1 mg/mL infused over a 2-hour period) {01}.

Protein binding:

Varies with concentration—Very low to moderate; approximately 7% at 1 mcg/mL, to 50% at 0.02 to 0.05 mcg/mL {01} {05}.

Biotransformation:

Hepatic; approximately 35% metabolized by demethylation. Up to 10 metabolites, which are thought to have no significant antimicrobial activity, may be found in the bile {06} {09}.

Half-life:

Peripheral leukocytes—34 to 57 hours (mean) after a single dose of 1200 mg (two 600-mg tablets) {01}.

Serum—11 to 14 hours when measured between 8 and 24 hours after a single, oral dose of 500 mg {05}; however, after several doses, the half-life is approximately the same as the half-life in tissues {05}.

Tissue—2 to 4 days {05} {06} {07}.

Time to peak concentration:

Adult subjects—

• For oral dosage forms: 2.1 to 3.2 hours {01} {08}.


• For parenteral dosage forms: 1 to 2 hours {02}.


Elderly subjects—3.8 to 4.4 hours {08}.

Peak plasma concentration


For oral dosage forms, after a 500-mg loading dose on day 1, then 250 mg once a day on days 2 through 5 {01} {08}:

Day 1: Approximately 0.41 and 0.38 mcg/mL for healthy young and elderly adults, respectively.

Day 5: Approximately 0.24 and 0.26 mcg/mL for healthy young and elderly adults, respectively.



For parenteral dosage forms:

Approximately 1.1 mcg/mL after a 3-hour intravenous infusion of 500 mg at a concentration of 1 mg/mL {02}.

Approximately 3.6 mcg/mL after a 1-hour intravenous infusion of 500 mg at a concentration of 2 mg/mL {02}.


Elimination:
    Over 50% of the dose is eliminated through biliary excretion as unchanged drug {06}.
    For oral dosage forms, approximately 4.5% of the dose is eliminated in the urine as unchanged drug within 72 hours {05}.
    For parenteral dosage forms, approximately 11 to 14% of the dose is eliminated in the urine as unchanged drug within 24 hours {02}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients who are hypersensitive to erythromycin or other macrolides may also be hypersensitive to azithromycin {01}.

Carcinogenicity

Long-term studies have not been done in animals to evaluate the carcinogenic potential of azithromycin {01}.

Mutagenicity

Azithromycin was not found to be mutagenic in the mouse lymphoma assay, the human lymphoctye clastogenic assay, or the mouse bone marrow clastogenic assay {01}.

Pregnancy/Reproduction
Fertility—
Adequate and well-controlled studies in humans have not been done {01}.

Reproduction studies done in rats and mice given azithromycin at doses of up to moderately maternally toxic levels (i.e., 200 mg per kg of body weight [mg/kg] per day) have found no evidence of impaired fertility. On a mg per square meter of body surface area (mg/m 2) basis, these doses are estimated to be four and two times the human daily dose of 500 mg in rats and mice, respectively. {01}

Pregnancy—
Adequate and well-controlled studies in humans have not been done {01}.

Reproduction studies done in rats and mice given azithromycin at doses of up to moderately maternally toxic levels (i.e., 200 mg/kg per day) have found no evidence of harm to the fetus. On a mg/m 2 basis, these doses are estimated to be four and two times the human daily dose of 500 mg in rats and mice, respectively. {01}

FDA Pregnancy Category B {01}.

Breast-feeding

It is not known if azithromycin is distributed into breast milk {01}.

Pediatrics

Appropriate studies on the relationship of age to the effects of parenteral azithromycin or of the capsule or tablet dosage form of oral azithromycin have not been performed in children up to 16 years of age. Safety and efficacy have not been established. However, the oral suspension dosage form of azithromycin is approved for use in infants and children 6 months of age and older. {01} {02}


Geriatrics


Pharmacokinetic data in healthy elderly subjects (65 to 85 years old) were similar to those for younger volunteers (18 to 40 years old). A higher peak concentration (by 30 to 50%) was found in elderly women; however, no significant accumulation occurred. Dosage adjustment does not appear to be necessary in older patients with normal renal and hepatic function. {01} {08}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Antacids, aluminum- and magnesium-containing{01}{04}{10}    (concurrent use with antacids decreases the peak serum concentration [C max] of azithromycin by approximately 24%, but has no effect on the area under the plasma concentration–time curve [AUC] {01}; oral azithromycin should be administered at least 1 hour before or 2 hours after aluminum- and magnesium-containing antacids)


Carbamazepine{01} or
Cyclosporine{01} or
Digoxin{01} or
Hexobarbital{01} or
Phenytoin{01} or
Terfenadine{01}    (concurrent use with macrolide antibiotics has been associated with increased serum concentrations of carbamazepine, cyclosporine, digoxin, hexobarbital, phenytoin, and terfenadine {01}; patients concurrently receiving azithromycin and any of these medications should be monitored carefully {01})


Dihydroergotamine{01} or
Ergotamine{01}    (concurrent use with macrolide antibiotics has been associated with acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia {01}; patients concurrently receiving azithromycin and either of these medications should be monitored carefully {01})


Theophylline{01}    (concurrent use with macrolide antibiotics has been associated with increased serum concentrations of theophylline {01}; pending further investigation, plasma concentrations of theophylline should be monitored in patients concurrently receiving azithromycin and theophylline {01})


Triazolam{01}    (concurrent use with macrolide antibiotics has been associated with a decrease in the clearance of triazolam, which may increase its effects {01}; patients concurrently receiving azithromycin and triazolam should be monitored carefully {01})


Warfarin{01}    (concurrent use with macrolide antibiotics has been associated with increased anticoagulant effects {01}; prothrombin time should be monitored carefully in patients concurrently receiving azithromycin and warfarin {01})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]){01} and
Aspartate aminotransferase (AST [SGOT]){01} and
Creatine kinase{01} and
Gamma-glutamyltransferase{01} and
Lactate dehydrogenase{02}    (serum values may be increased {01} {02} {04})


Bilirubin{02} and
Potassium, serum{01}    (concentrations may be increased {01} {02})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Hypersensitivity to azithromycin, erythromycins, or other macrolides{01}
Risk-benefit should be considered when the following medical problem exists
» Hepatic function impairment{01}{04}    (because biliary excretion is the major route of elimination, caution should be used in patients with hepatic function impairment {01} {04})




Side/Adverse Effects

Note: Rarely, serious allergic reactions, such as anaphylaxis and angioedema, have been reported in patients taking azithromycin. Despite discontinuation of azithromycin and successful symptomatic treatment of the allergic reactions, allergic symptoms soon recurred in some patients when the symptomatic therapy was discontinued. These patients require prolonged periods of observation and symptomatic treatment. {14}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent—for injection form only
    
Thrombophlebitis {02}(pain, redness, and swelling at site of injection)

Incidence rare
    
Acute interstitial nephritis {14}(fever; joint pain; skin rash)
    
allergic reactions {01}(difficulty in breathing; swelling of face, mouth, neck, hands, and feet; skin rash)
    
pseudomembranous colitis {01}(abdominal or stomach cramps or pain, severe; abdominal tenderness; diarrhea, watery and severe, which may also be bloody; fever)



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Gastrointestinal disturbances {01}{04}(abdominal pain; diarrhea, mild; nausea; vomiting)

Incidence rare
    
Dizziness {01}{04}
    
headache {01}{04}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Azithromycin (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to azithromycin, erythromycins, or other macrolides
Other medications, especially aluminum- and magnesium-containing antacids
Other medical problems, especially hepatic function impairment

Proper use of this medication
Azithromycin capsules and pediatric oral suspension should be given at least 1 hour before or 2 hours after meals

Azithromycin tablets and adult single dose oral suspension may be taken with or without food

Compliance with full course of therapy

» Importance of not taking more medication than prescribed; importance of not discontinuing medication without checking with physician

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Checking with physician if no improvement within a few days or if condition becomes worse


Side/adverse effects
Signs of potential side effects, especially thrombophlebitis, acute interstitial nephritis, allergic reactions, and pseudomembranous colitis


General Dosing Information
No adjustment in dose is required in patients with mild renal function impairment (creatinine clearance ³ 40 mL per minute [0.67 mL per second]). No data are available on the use of azithromycin in patients with more severe renal function impairment. {04} {09}

Diet/Nutrition
Azithromycin capsules and oral suspension in dropper bottles (for children) should be given at least 1 hour before or 2 hours after meals.

Azithromycin tablets and oral suspension in 1-gram packets (for adults) may be taken with or without food.


Oral Dosage Forms

AZITHROMYCIN CAPSULES USP

Usual adult and adolescent dose
Bronchitis, bacterial exacerbations or
Pharyngitis, streptococcal or
Pneumonia, due to Streptococcus pneumoniae or Haemophilus influenzae , or
Skin and soft tissue infections, uncomplicated, due to Staphylococcus aureus , Streptococcus agalactiae , or Streptococcus pyogenes or
Tonsillitis, streptococcal
Adults and adolescents 16 years of age and older: Oral, 500 mg as a single dose on the first day, then 250 mg once a day on days two through five {01}.

Adolescents up to 16 years of age: Safety and efficacy have not been established {01}.

Cervicitis, nongonococcal or
Urethritis, nongonococcal
Adults and adolescents 16 years of age and older: Oral, 1000 mg as a single dose {01}.

Adolescents up to 16 years of age: Safety and efficacy have not been established {01}.


Usual pediatric dose
Children up to 16 years of age—Safety and efficacy have not been established {01}.

Strength(s) usually available
U.S.—


250 mg (Rx) [Zithromax (lactose)]{01}

Canada—


250 mg (Rx) [Zithromax (lactose)]{03}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F) in a well-closed container.

Auxiliary labeling:
   • Do not take with food.
   • Continue medicine for full time of treatment.


AZITHROMYCIN FOR ORAL SUSPENSION USP

Usual adult and adolescent dose
Cervicitis, nongonococcal or
Chancroid, in men or
Urethritis, nongonococcal
Oral, 1 gram as a single dose {01}.

Cervicitis, gonococcal or
Urethritis, gonococcal
Oral, 2 grams as a single dose {01}.


Usual pediatric dose
Otitis media, acute or
Pneumonia, due to Chlamydia pneumoniae 1 , Haemophilus influenzae , Mycoplasma pneumoniae1 , or Streptococcus pneumoniae
Infants and children 6 months to 12 years of age: Oral, 10 mg per kg of body weight, up to 500 mg, on the first day, then 5 mg per kg of body weight, up to 250 mg, on days two through five {01}.

Infants up to 6 months of age: Safety and efficacy have not been established.{01}

Pharyngitis, streptococcal or
Tonsillitis, streptococcal
Children 2 to 12 years of age: Oral, 12 mg per kg of body weight, up to 500 mg, once a day for five days {01}.

Infants and children up to 2 years of age: Safety and efficacy have not been established {01}.

[Trachoma (treatment)]1
Children 2 to 10 years of age: Oral, 20 mg per kg of body weight as a single dose{19}{20}{21}.

Infants and children up to 2 years of age: Safety and efficacy have not been established{01}.

Note: Depending on the severity of the trachoma and the initial clinical response, doses of azithromycin oral suspension may be repeated once every 28 days for a total of 6 doses{19}{20}{21}.



Usual pediatric prescribing limits
500 mg per day for pharyngitis, tonsillitis, and the first day of dosing for otitis media and pneumonia.
250 mg per day for days two through five for otitis media and pneumonia {01}.

Strength(s) usually available
U.S.—


100 mg per 5 mL (when reconstituted according to manufacturer"s instructions) (available in 300-mg bottles) (Rx) [Zithromax (sucrose)]{01}


200 mg per 5 mL (when reconstituted according to manufacturer"s instructions) (available in 600-, 900-, and 1200-mg bottles) (Rx) [Zithromax ( sucrose)]{01}


1 gram (single dose packet) (Rx) [Zithromax (sucrose)]{01}

Canada—


100 mg per 5 mL (when reconstituted according to manufacturer"s instructions) (available in 300-mg bottles) (Rx) [Zithromax (sucrose)]{03}


200 mg per 5 mL (when reconstituted according to manufacturer"s instructions) (available in 600- and 900-mg bottles) (Rx) [Zithromax (sucrose )]{03}


1 gram (single dose packet) (Rx) [Zithromax (sucrose)]{03}

Packaging and storage:
Prior to reconstitution, store between 5 and 30 °C (41 and 86 °F) in a tight container.

After reconstitution, the pediatric oral suspension should be stored between 5 and 30 °C (41 and 86 °F).

Preparation of dosage form:
For the pediatric suspension—Add the indicated volume of water to the bottle and shake well {01}.


Azithromycin content  Final concentration  Total volume of water to be added 
300 mg  100 mg/5 mL  9 mL 
600 mg  200 mg/5 mL  9 mL  
900 mg   200 mg/5 mL  12 mL 
1200 mg  200 mg/5 mL  15 mL 
For the adult single dose packets—Empty the entire contents of the packet into a glass containing 2 ounces (approximately 60 mL) of water and mix thoroughly. The suspension should be consumed immediately. Add an additional 2 ounces of water to the glass, mix, and drink to assure complete consumption of the dose. This packet should not be used to administer doses other than 1000 mg of azithromycin. {01}

Auxiliary labeling:


• For the pediatric suspension—    • Refrigerate.
   • Shake well.
   • Do not take with food.
   • Continue medicine for full time of treatment.



• For the adult single dose packets—    • Reconstitute before taking.




AZITHROMYCIN TABLETS

Usual adult and adolescent dose
Bronchitis, bacterial exacerbations or
Pharyngitis, streptococcal or
Pneumonia, due to Chlamydia pneumoniae 1 , Haemophilus influenzae , Mycoplasma pneumoniae1 , or Streptococcus pneumoniae or
Skin and soft tissue infections or
Tonsillitis, streptococcal
Adults and adolescents 16 years of age and older: Oral, 500 mg as a single dose on the first day, then 250 mg once a day on days two through five {01}.

Adolescents up to 16 years of age: Safety and efficacy have not been established {01}.

Cervicitis, nongonococcal or
Urethritis, nongonococcal
Adults and adolescents 16 years of age and older: Oral, 1000 mg as a single dose {01}.

Adolescents up to 16 years of age: Safety and efficacy have not been established {01}.

Mycobacterium avium complex (MAC) disease, disseminated, prophylaxis1
Adults and adolescents 16 years of age and older: Oral, 1200 mg once a week, alone or in combination with an approved dosing regimen of rifabutin {01}.

Adolescents up to 16 years of age: Safety and efficacy have not been established {01}.


Usual pediatric dose
Children up to 16 years of age—Safety and efficacy have not been established {01}.

Strength(s) usually available
U.S.—


250 mg (Rx) [Zithromax (scored) ( lactose)]{01}


600 mg (Rx) [Zithromax (lactose)]{01}

Canada—


250 mg (Rx) [Zithromax (scored) ( lactose)]{03}

Packaging and storage:
Store between 5 and 30 °C (41 and 86 °F).

Auxiliary labeling:
   • Continue medicine for full time of treatment.



Parenteral Dosage Form

AZITHROMYCIN FOR INJECTION

Note: Azithromycin for injection should be infused at a concentration of 1 mg per mL over a 3-hour period, or 2 mg per mL over a 1-hour period {02}. Azithromycin should not be administered by bolus or intramuscular injection {02}.


Usual adult and adolescent dose
Pelvic inflammatory disease 1
Adults and adolescents 16 years of age and older: Intravenous infusion, 500 mg as a single dose once a day for the first one or two days of a seven-day course of therapy {02}.

Adolescents up to 16 years of age: Safety and efficacy have not been established {02}.

Note: After the one- or two-day infusion therapy is complete, an oral dose of 250 mg should be administered once a day to complete the seven-day course of therapy {02}.


Pneumonia1, due to Chlamydia pneumoniae , Haemophilus influenzae , Legionella pneumophila , Moraxella catarrhalis , Mycoplasma pneumoniae , Staphylococcus aureus , or Streptococcus pneumoniae
Adults and adolescents 16 years of age and older: Intravenous infusion, 500 mg as a single dose once a day for at least the first two days of a seven- to ten-day course of therapy {02}.

Adolescents up to 16 years of age: Safety and efficacy have not been established {02}.

Note: After the infusion therapy is complete, an oral dose of 500 mg should be administered once a day to complete the seven- to ten-day course of therapy {02}.



Usual pediatric dose
Children up to 16 years of age—Safety and efficacy have not been established {02}.

Strength(s) usually available
U.S.—


500 mg (Rx) [Zithromax (sodium hydroxide)]{02}

Canada—
Not commercially available.

Preparation of dosage form:
To prepare the initial solution for intravenous infusion, add 4.8 mL of sterile water for injection to each 500-mg vial and shake until all of the medication is dissolved. Further dilute this solution by transferring it into 250 or 500 mL of a suitable diluent (see manufacturer"s package insert) to provide a final concentration of 2 or 1 mg per mL, respectively. {02}

Stability:
After reconstitution with sterile water for injection, the solution is stable for 24 hours when stored below 30 °C (86 °F). After dilution to 1 or 2 mg per mL in suitable diluent, solutions are stable for 24 hours at or below room temperature (30 °C [86 °F]), or for 7 days if stored at 5 °C (41 °F). {02}



Revised: 08/09/2000



References
  1. Zithromax package insert for oral dosage forms (Pfizer—US), New 2/92, Rec 3/92; Rev 10/92, Rec 10/92; Rev 6/96, Rec 3/97; Rev 12/96, Rec 3/97; Rev 6/97, Rec 8/97.
  1. Zithromax package insert for parenteral dosage forms (Pfizer—US), New 2/97, Rec 3/97.
  1. Zithromax product monograph (Pfizer—Canada), Rev 11/96, Rec 3/97.
  1. Hopkins S. Clinical toleration and safety of azithromycin. Am J Med 1991; 91 Suppl 3A: 40S-45S.
  1. Foulds G, Shepard RM, Johnson RB. The pharmacokinetics of azithromycin in human serum and tissues. J Antimicrob Chemother 1990; 25 Suppl A: 73-82.
  1. Schentag JJ, Ballow CH. Tissue-directed pharmacokinetics. Am J Med 1991; 91 Suppl 3A: 5S-11S.
  1. Lode H. The pharmacokinetics of azithromycin and their clinical significance. Eur J Clin Microbiol Infect Dis 1991; 10(10): 807-12.
  1. Coates P, et al. An open study to compare the pharmacokinetics, safety and tolerability of a multiple-dose regimen of azithromycin in young and elderly volunteers. Eur J Clin Microbiol Infect Dis 1991; 10(10): 850-2.
  1. Drew RH, Gallis HA. Azithromycin—spectrum of activity, pharmacokinetics, and clinical applications. Pharmacotherapy 1992; 12(3): 161-73.
  1. Foulds G, Hilligoss DM, Henry EB, et al. The effects of an antacid or cimetidine on the serum concentrations of azithromycin. J Clin Pharmacol 1991; 31: 164-7.
  1. Neu HC. Clinical microbiology of azithromycin. Am J Med 1991; 91 Suppl 3A: 12S-18S.
  1. Piscitelli SC, Danziger LH, Rodvold KA. Clarithromycin and azithromycin: new macrolide antibiotics. Clin Pharm 1992; 11: 137-52.
  1. Williams JD. Spectrum of activity of azithromycin. Eur J Clin Microbiol Infect Dis 1991; 10(10): 813-20.
  1. Mansoor GA, Panner BJ, Ornt DB. Azithromycin-induced acute interstitial nephritis. Ann Intern Med 1993; 119(7 Pt 1): 636-7.
  1. Wynn FR, Leen CLS, Brettle RP. Azithromycin for cerebral toxoplasmosis in AIDS. Lancet 1993; 341: 243-4.
  1. Shepard RM, Falkner FC. Pharmacokinetics of azithromycin in rats and dogs. J Antimicrob Chemother 1990; 25 Suppl A: 49-60.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1997. p. 75.
  1. Panel comment, 2/98.
  1. Panel consensus, 1/2000.
  1. Schachter J, West SK, Mabey D, et al. Azithromycin in control of trachoma. Lancet 1999; 354: 630-5.
  1. Dawson CR, Schachter J, Sallam S, et al. A comparison of oral azithromycin with topical oxytetracycline/polymyxin for the tx of trachoma in children. Clin Infect Dis 1997; 24(3): 363-8.
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