Wednesday, 7 September 2016

Azithromycin Oral Suspension





Dosage Form: powder, for oral suspension
Azithromycin for Oral Suspension, USP

Rx only


To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin and other antibacterial drugs, azithromycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.



Azithromycin Oral Suspension Description


Azithromycin for Oral Suspension, USP contains the active ingredient azithromycin monohydrate, an azalide, a subclass of macrolide antibiotics, for oral administration. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R) - 13 - [(2,6 - dideoxy - 3 - C - methyl - 3 - O - methyl - α - 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) - β - D - xylo - hexopyranosyl]oxy] - 1 - oxa - 6 - azacyclopentadecan - 15 - one monohydrate. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring.


Its molecular formula is C38H72N2O12•H2O, and its molecular weight is 767.00.


Azithromycin monohydrate has the following structural formula:



Azithromycin, as the monohydrate, is a white crystalline powder.


Azithromycin for Oral Suspension USP, off-white to light pink dry powder, is supplied in bottles containing azithromycin monohydrate powder equivalent to 300 mg, 600 mg, 900 mg, or 1200 mg azithromycin per bottle and the following inactive ingredients: xanthan gum; spray dried artificial cherry flavors; sodium carbonate monohydrate; FD&C Red No. 40; Dehydrated Alcohol; sucrose and compressible sugar. After constitution, each 5 mL of suspension contains 100 mg or 200 mg of azithromycin.



Azithromycin Oral Suspension - Clinical Pharmacology



Pharmacokinetics


Following oral administration of a single 500 mg dose (two 250 mg tablets) to 36 fasted healthy male volunteers, the mean (SD) pharmacokinetic parameters were AUC0-72 = 4.3 (1.2) mcg·h/mL; Cmax = 0.5 (0.2) mcg /mL; Tmax = 2.2 (0.9) hours.


With a regimen of 500 mg (two 250 mg capsules*) on day 1, followed by 250 mg daily (one 250 mg capsule) on days 2 through 5, the pharmacokinetic parameters of azithromycin in plasma in healthy young adults (18 to 40 years of age) are portrayed in the chart below. Cmin and Cmax remained essentially unchanged from day 2 through day 5 of therapy.
























Pharmacokinetic Parameters


(Mean)
Total n=12
Day 1Day 5 
Cmax (mcg/mL)0.410.24
Tmax (h)2.53.2
AUC0-24 (mcg·h/mL)2.62.1
Cmin (mcg/mL)0.050.05
Urinary Excret. (% dose)4.56.5

*Azithromycin 250 mg tablets are bioequivalent to 250 mg capsules in the fasted state.


Azithromycin 250 mg capsules are no longer commercially available.


In a two-way crossover study, 12 adult healthy volunteers (6 males, 6 females) received 1,500 mg of azithromycin administered in single daily doses over either 5 days (two 250 mg tablets on day 1, followed by one 250 mg tablet on days 2 to 5) or 3 days (500 mg per day for days 1 to 3). Due to limited serum samples on day 2 (3-day regimen) and days 2 to 4 (5-day regimen), the serum concentration-time profile of each subject was fit to a 3-compartment model and the AUC0-∞ for the fitted concentration profile was comparable between the 5-day and 3-day regimens.
























*

Total AUC for the entire 3-day and 5-day regimens

3-Day Regimen5-Day Regimen
Pharmacokinetic Parameter [mean (SD)]Day 1Day 3Day 1Day 5
Cmax (serum, mcg/mL)0.44 (0.22)0.54 (0.25)0.43 (0.20)0.24 (0.06)
Serum AUC0-∞ (mcg.hr/mL)17.4 (6.2)*14.9 (3.1)*
Serum T½71.8 hr68.9 hr

Median azithromycin exposure (AUC0-288) in mononuclear (MN) and polymorphonuclear (PMN) leukocytes following either the 5-day or 3-day regimen was more than a 1000-fold and 800-fold greater than in serum, respectively. Administration of the same total dose with either the 5-day or 3-day regimen may be expected to provide comparable concentrations of azithromycin within MN and PMN leukocytes.


Two azithromycin 250 mg tablets are bioequivalent to a single 500 mg tablet.


Absorption:   The absolute bioavailability of azithromycin 250 mg capsules is 38%.


In a two-way crossover study in which 12 healthy subjects received a single 500 mg dose of azithromycin (two 250 mg tablets) with or without a high fat meal, food was shown to increase Cmax by 23% but had no effect on AUC.


When azithromycin suspension was administered with food to 28 adult healthy male subjects, Cmax increased by 56% and AUC was unchanged.


The AUC of azithromycin was unaffected by co-administration of an antacid containing


aluminum and magnesium hydroxide with azithromycin capsules; however, the Cmax was reduced by 24%. Administration of cimetidine (800 mg) two hours prior to azithromycin had no effect on azithromycin absorption.


Distribution:   The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL.


Following oral administration, azithromycin is widely distributed throughout the body with an apparent steady-state volume of distribution of 31.1 L/kg. Greater azithromycin concentrations in tissues than in plasma or serum were observed. High tissue concentrations should not be interpreted to be quantitatively related to clinical efficacy.


The antimicrobial activity of azithromycin is pH related and appears to be reduced with decreasing pH. However, the extensive distribution of drug to tissues may be relevant to clinical activity.


Selected tissue (or fluid) concentration and tissue (or fluid) to plasma/serum concentration ratios are shown in the following table:













































Azithromycin Concentrations Following a 500 mg Dose (Two 250 mg Capsules) in Adults*

*

Azithromycin tissue concentrations were originally determined using 250 mg capsules.


Sample was obtained 2-4 hours after the first dose.


Sample was obtained 10-12 hours after the first dose.

§

Dosing regimen of two doses of 250 mg each, separated by 12 hours.


Sample was obtained 19 hours after a single 500 mg dose.

Tissue or Fluid

Time After Dose (h)



Tissue or Fluid


Concentration


(mcg/g or mcg/mL)

Corresponding Plasma or Serum Level (mcg/mL)



Tissue (Fluid) Plasma (Serum) Ratio


Skin72-960.40.01235
Lung72-964.00.012>100
Sputum2-41.00.642
Sputum10-122.90.130
Tonsil§9-184.50.03>100
Tonsil§1800.90.006>100
Cervix192.80.0470

The extensive tissue distribution was confirmed by examination of additional tissues and fluids (bone, ejaculum, prostate, ovary, uterus, salpinx, stomach, liver, and gallbladder). As there are no data from adequate and well-controlled studies of azithromycin treatment of infections in these additional body sites, the clinical importance of these tissue concentration data is unknown.


Following a regimen of 500 mg on the first day and 250 mg daily for 4 days, only very low concentrations were noted in cerebrospinal fluid (less than 0.01 mcg/mL) in the presence of non-inflamed meninges.


Metabolism: In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed.


Elimination:   Plasma concentrations of azithromycin following single 500 mg oral and i.v. doses declined in a polyphasic pattern with a mean apparent plasma clearance of 630 mL/min and terminal elimination half-life of 68 hours. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues.


Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine.



Special Populations


Renal Insufficiency

  Azithromycin pharmacokinetics were investigated in 42 adults (21 to 85 years of age) with varying degrees of renal impairment. Following the oral administration of a single 1000 mg dose of azithromycin, mean Cmax and AUC0-120 increased by 5.1% and 4.2%, respectively in subjects with mild to moderate renal impairment (GFR 10 mL/min to 80 mL/min) compared to subjects with normal renal function (GFR >80 mL/min). The mean Cmax and AUC0-120 increased 61% and 35%, respectively in subjects with severe renal impairment (GFR <10 mL/min) compared to subjects with normal renal function (GFR >80 mL/min) (see DOSAGE AND ADMINISTRATION).


Hepatic Insufficiency

The pharmacokinetics of azithromycin in subjects with hepatic impairment have not been established.



Gender


There are no significant differences in the disposition of azithromycin between male and female subjects. No dosage adjustment is recommended based on gender.


Geriatric Patients

   When studied in healthy elderly subjects aged 65 to 85 years, the pharmacokinetic parameters of azithromycin in elderly men were similar to those in young adults; however, in elderly women, although higher peak concentrations (increased by 30 to 50%) were observed, no significant accumulation occurred.


Pediatric Patients

  In two clinical studies, azithromycin for oral suspension was dosed at 10 mg/kg on day 1, followed by 5 mg/kg on days 2 through 5 to two groups of pediatric patients (aged 1 to 5 years and 5 to 15 years, respectively). The mean pharmacokinetic parameters on day 5 were Cmax=0.216 mcg/mL, Tmax=1.9 hours, and AUC0-24=1.822 mcg·hr/mL for the 1- to 5-year-old group and were Cmax=0.383 mcg/mL, Tmax=2.4 hours, and AUC0-24=3.109 mcg·hr/mL for the 5- to 15-year-old group.


Two clinical studies were conducted in 68 pediatric patients aged 3-16 years to determine the pharmacokinetics and safety of azithromycin for oral suspension. Azithromycin was administered following a low-fat breakfast.


The first study consisted of 35 pediatric patients treated with 20 mg/kg/day (maximum daily dose 500 mg) for 3 days of whom 34 patients were evaluated for pharmacokinetics.


In the second study, 33 pediatric patients received doses of 12 mg/kg/day (maximum daily dose 500 mg) for 5 days of whom 31 patients were evaluated for pharmacokinetics.


In both studies, azithromycin concentrations were determined over a 24-hour period following the last daily dose. Patients weighing above 25.0 kg in the 3-day study or 41.7 kg in the 5-day study received the maximum adult daily dose of 500 mg. Eleven patients (weighing 25.0 kg or less) in the first study and 17 patients (weighing 41.7 kg or less) in the second study received a total dose of 60 mg/kg. The following table shows pharmacokinetic data in the subset of pediatric patients who received a total dose of 60 mg/kg.



















Pharmacokinetic Parameter


[mean (SD)]

3-Day Regimen


(20 mg/kg x 3 days)

5-Day Regimen


(12 mg/kg x 5 days)
n1117
Cmax (mcg/mL)1.1 (0.4)0.5 (0.4)
Tmax (hr)2.7 (1.9)2.2 (0.8)
AUC0-24(mcg·hr/mL)7.9 (2.9)3.9 (1.9)

The similarity of the overall exposure (AUC0-∞) between the 3-day and 5-day regimens in pediatric patients is unknown.


Single dose pharmacokinetics in pediatric patients given doses of 30 mg/kg have not been studied (see DOSAGE AND ADMINISTRATION).



Drug-Drug Interactions


Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered. The effects of co-administration of azithromycin on the pharmacokinetics of other drugs are shown in Table 1 and the effect of other drugs on the pharmacokinetics of azithromycin are shown in Table 2.


Co-administration of azithromycin at therapeutic doses had a modest effect on the pharmacokinetics of the drugs listed in Table 1. No dosage adjustment of drugs listed in Table 1 is recommended when co-administered with azithromycin.


Co-administration of azithromycin with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. Nelfinavir significantly increased the Cmax and AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2 (see PRECAUTIONS, Drug Interactions).






















































































































Table 1: Drug Interactions: Pharmacokinetic Parameters for Co-administered Drugs in the Presence of Azithromycin

*

-90% Confidence interval not reported


NA - Not Available


Co-administered


Drug
Dose of Co-administered Drug

Dose of


Azithromycin
n

Ratio (with/without azithromycin) of


Co-administered Drug Pharmacokinetic Parameters (90% CI); No Effect=1.00
Mean CmaxMean AUC    
Atorvastatin

10 mg/day x 8


days

500 mg/day PO on


days 6-8
12

0.83


(0.63 to 1.08)

1.01


(0.81 to 1.25)
Carbamazepine

200 mg/day x 2


days, then 200 mg BID x 18 days

500 mg/day PO for


days 16-18
7

0.97


(0.88 to 1.06)

0.96


(0.88 to 1.06)
Cetirizine

20 mg/day x 11


days

500 mg PO on day


7, then 250 mg/day


on days 8-11
14

1.03


(0.93 to 1.14)

1.02


(0.92 to 1.13)
Didanosine200 mg PO BID x 21 days

1,200 mg/day PO


on days 8-21
6

1.44


(0.85 to 2.43)

1.14


(0.83 to 1.57)
Efavirenz

400 mg/day x 7


days
600 mg PO on day 7141.04*

0.95*


Fluconazole200 mg PO single dose

1,200 mg PO


single dose
18

1.04


(0.98 to 1.11)

1.01


(0.97 to 1.05)
Indinavir

800 mg TID x 5


days

1,200 mg PO on


day 5
18

0.96


(0.86 to 1.08)

0.90


(0.81 to 1.00)
Midazolam15 mg PO on day 3

500 mg/day PO x 3


days
12

1.27


(0.89 to 1.81)

1.26


(1.01 to 1.56)
Nelfinavir750 mg TID x 11 days

1,200 mg PO on


day 9
14

0.90


(0.81 to 1.01)

0.85


(0.78 to 0.93)
Rifabutin300 mg/day x 10 days

500 mg PO on day


1, then 250 mg/day


on days 2-10
6

See footnote


below
NA
Sildenafil100 mg on days 1 and 4

500 mg/day PO x 3


days
12

1.16


(0.86 to 1.57)

0.92


(0.75 to 1.12)
Theophylline

4 mg/kg IV on


days 1, 11, 25

500 mg PO on day


7, 250 mg/day on


days 8-11
10

1.19


(1.02 to 1.40)

1.02


(0.86 to 1.22)
Theophylline300 mg PO BID x 15 days

500 mg PO on day


6, then 250 mg/day


on days 7-10
8

1.09


(0.92 to 1.29)

1.08


(0.89 to 1.31)
Triazolam0.125 mg on day 2

500 mg PO on day


1, then 250 mg/day


on day 2
121.06*1.02*

Trimethoprim/


Sulfamethoxazole

160 mg/800


mg/day PO x 7


days

1,200 mg PO on


day 7
12

0.85


(0.75 to 0.97)/


0.90


(0.78 to 1.03)

0.87


(0.80 to 0.95/


0.96


(0.88 to 1.03)
Zidovudine500 mg/day PO x 21 days600 mg/day PO x 14 days5

1.12


(0.42 to 3.02)

0.94


(0.52 to 1.70)
Zidovudine500 mg/day PO x 21 days1,200 mg/day PO x 14 days4

1.31


(0.43 to 3.97)

1.30


(0.69 to 2.43)

Mean rifabutin concentrations one-half day after the last dose of rifabutin were 60 ng/mL when co-administered with azithromycin and 71 ng/mL when co-administered with placebo.








































Table 2: Drug Interactions: Pharmacokinetic Parameters for Azithromycin in the Presence of Co-administered Drugs (see PRECAUTIONS, Drug Interactions).

*

-90% Confidence interval not reported


NA - Not available


Co- administered


Drug

Dose of Co-


administered


Drug



Dose of


Azithromycin

n



Ratio (with/without co-administered


drug) of Azithromycin Pharmacokinetic


Parameters (90% CI); No Effect = 1.00
Mean CmaxMean AUC    
Efavirenz400 mg/day x 7 days

600 mg PO on day


7
14

1.22


(1.04 to 1.42)
0.92*
Fluconazole200 mg PO single dose

1200 mg PO


single dose
18

0.82


(0.66 to 1.02)

1.07


(0.94 to 1.22)
Nelfinavir

750 mg TID x 11 days



1200 mg PO on


day 9
14

2.36


(1.77 to 3.15)

2.12


(1.80 to 2.50)
Rifabutin300 mg/day x 10 days

500 mg PO on day


1, then 250 mg/day on days 2 -10
6

See footnote


below
NA

Mean azithromycin concentrations one day after the last dose were 53 ng/mL when co-administered with 300 mg daily rifabutin and 49 ng/mL when co-administered with placebo.


Microbiology:Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and, thus, interfering with microbial protein synthesis. Nucleic acid synthesis is not affected.


Azithromycin concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. Using such methodology, the ratio of intracellular to extracellular concentration was >30 after one hour incubation. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.


Azithromycin has been shown to be active against most isolates of the following


microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGEsection.


Aerobic and facultative gram-positive microorganisms


 

Staphylococcus aureus

 

Streptococcus agalactiae

 

Streptococcus pneumoniae

 

Streptococcus pyogenes

NOTE: Azithromycin demonstrates cross-resistance with erythromycin-resistant gram-positive strains. Most strains of Enterococcus faecalis and methicillin-resistant staphylococci are resistant to azithromycin.


Aerobic and facultative gram-negative microorganisms


Haemophilus ducreyi


Haemophilus influenzae


Moraxella catarrhalis


Neisseria gonorrhoeae


“Other” microorganisms


Chlamydia pneumoniae


Chlamydia trachomatis


Mycoplasma pneumoniae


Beta-lactamase production should have no effect on azithromycin activity.


The following in vitro data are available, but their clinical significance is unknown.


At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory


concentration (MIC) less than or equal to the susceptible breakpoints for azithromycin. However, the safety and effectiveness of azithromycin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.


Aerobic and facultative gram-positive microorganisms


Streptococci (Groups C, F, G)


Viridans group streptococci


Aerobic and facultative gram-negative microorganisms


Bordetella pertussis


Legionella pneumophila


Anaerobic microorganisms


Peptostreptococcus species


Prevotella bivia


“Other” microorganisms


Ureaplasma urealyticum


Susceptibility Testing Methods: When available, the results of in vitro susceptibility test results for antimicrobial drugs used in resident hospitals should be provided to the physician as periodic reports which describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports may differ from susceptibility data obtained from outpatient use, but could aid the physician in selecting the most effective antimicrobial.


Dilution Techniques: Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1,3 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of azithromycin powder. The MIC values should be interpreted according to criteria provided in Table 1.


Diffusion Techniques: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 15-mcg azithromycin to test the susceptibility of microorganisms to azithromycin. The disk diffusion interpretive criteria are provided in Table 1.




































Table 1: Susceptibility Interpretive Criteria for Azithromycin Susceptibility Test Result Interpretive Criteria

*

The current absence of data on resistant strains precludes defining any category other than "susceptible." If strains yield MIC results other than susceptible, they should be submitted to a reference laboratory for further testing.


Susceptibility of streptococci including S. pneumoniae to azithromycin and other macrolides can be predicted by testing erythromycin.

Pathogen

Minimum Inhibitory


Concentrations (mcg/mL)

Disk Diffusion


(zone diameters in mm)
SIR*SIR* 
Haemophilus spp.≤4----≥12----
Staphylococcus aureus≤24≥8≥1814-17≤13

Streptococci including


S. pneumoniae
≤0.51≥2≥1814-17≤13

No interpretive criteria have been established for testing Neisseria gonorrhoeae. This species is not usually tested.


A report of “susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound reaches the concentrations usually achievable. A report of “intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test


should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small-uncontrolled technical factors from causing major discrepancies in interpretation. A report of “resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound reaches the concentrations usually achievable; other therapy should be selected.



Quality Control


Standardized susceptibility test procedures require the use of quality control microorganisms to control the technical aspects of the test procedures. Standard azithromycin powder should provide the following range of values noted in Table 2. Quality control microorganisms are specific strains of organisms with intrinsic biological properties. QC strains are very stable strains, which will give a standard and repeatable susceptibility pattern. The specific strains used for microbiological quality control are not clinically significant.



















Table 2: Acceptable Quality Control Ranges for Azithromycin
QC Strain

Minimum Inhibitory


Concentrations (mcg/mL)

Disk Diffusion


(zone diameters in mm)

Haemophilus influenzae


ATCC 49247
1.0-4.013-21

Staphylococcus aureus


ATCC 29213
0.5-2.0

Staphylococcus aureus


 ATCC 25923
21-26

Streptococcus pneumoniae


 ATCC 49619
0.06-0.2519-25

Indications and Usage for Azithromycin Oral Suspension


Azithromycin for oral suspension USP is indicated for the treatment of patients with mild to moderate infections (pneumonia: see WARNINGS) caused by susceptible strains of the designated microorganisms in the specific conditions listed below. As recommended dosages, durations of therapy and applicable patient populations vary among these infections, please see DOSAGE AND ADMINISTRATIONfor specific dosing recommendations.



Adults


 Acute bacterial exacerbations of chronic obstructive pulmonary disease due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.


Acute bacterial sinusitis due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.


Community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate for oral therapy.


NOTE: Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors such as any of the following:


  • patients with cystic fibrosis,

  • patients with nosocomially acquired infections,

  • patients with known or suspected bacteremia,

  • patients requiring hospitalization,

  • elderly or debilitated patients, or

  • patients with significant underlying health problems that may compromise their

ability to respond to their illness (including immunodeficiency or functionalasplenia).


Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy.


NOTE: Penicillin by the intramuscular route is the usual drug of choice in the treatment of Streptococcus pyogenes infection and the prophylaxis of rheumatic fever. Azithromycin for oral suspension USP is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx. Because some strains are resistant to azithromycin for oral suspension USP, susceptibility tests should be performed when patients are treated with azithromycin for oral suspension USP. Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available.


Uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae. Abscesses usually require surgical drainage.


Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae.


Genital ulcer disease in men due to Haemophilus ducreyi (chancroid). Due to the small number of women included in clinical trials, the efficacy of azithromycin in the treatment of chancroid in women has not been established.


Azithromycin for oral suspension USP, at the recommended dose, should not be relied upon to treat syphilis. Antimicrobial agents used in high doses for short periods of time to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis. All patients with sexually-transmitted urethritis or cervicitis should have a serologic test for syphilis and appropriate cultures for gonorrhea performed at the time of diagnosis.


Appropriate antimicrobial therapy and follow-up tests for these diseases should be initiated if infection is confirmed.


Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its susceptibility to azithromycin. Therapy with azithromycin for oral suspension USP may be initiated before results of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly. To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin for oral suspension USP and other antibacterial drugs, azithromycin for oral suspension USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.



Pediatric Patients


 (See PRECAUTIONS, Pediatri

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