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AZITHROMYCIN

Dispensing Solutions, Inc.

FULL PRESCRIBING INFORMATION: CONTENTS*

AZITHROMYCIN DESCRIPTION
CLINICAL PHARMACOLOGY
AZITHROMYCIN INDICATIONS AND USAGE
- Adults:
- Pediatric Patients:
AZITHROMYCIN CONTRAINDICATIONS
WARNINGS
PRECAUTIONS
AZITHROMYCIN ADVERSE REACTIONS
AZITHROMYCIN DOSAGE AND ADMINISTRATION
- Adults:
HOW SUPPLIED
CLINICAL STUDIES
Adult Patients
ANIMAL TOXICOLOGY
PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

AZITHROMYCIN DESCRIPTION

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CLINICAL PHARMACOLOGY

Pharmacokinetics

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Day 1Day 5
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AZITHROMYCIN CONCENTRATIONS FOLLOWING A 500 mg DOSE (TWO 250 mg CAPSULES) IN ADULTS¹

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
SKIN	72-96	0.4	0.012	35
LUNG	72-96	4	0.012	>100
SPUTUM*	2-4	1	0.64	2
SPUTUM**	10-12	2.9	0.1	30
TONSIL***	9-18	4.5	0.03	>100
TONSIL***	180	0.9	0.006	>100
CERVIX****	19	2.8	0.04	70

¹

_max_0-120_max_0-120DOSAGE AND ADMINISTRATION

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Pharmacokinetic Parameter [mean (SD)]	3-Day Regimen (20 mg/kg x 3 days)	5-Day Regimen (12 mg/kg x 5 days)
n	11	17
C_max (mcg/mL)	1.1 (0.4)	0.5 (0.4)
T_max (hr)	2.7 (1.9)	2.2 (0.8)
Auc_0-24 mcg•hr/mL	7.9 (2.9)	3.9 (1.9)

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DOSAGE AND ADMINISTRATION

Drug-Drug Interactions

_max PRECAUTIONS - Drug Interactions

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
				Mean C_max	Mean 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)
Didanosine	200 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 7	14	1.04*	0.95*
Fluconazole	200 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)
Midazolam	15 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)
Nelfinavir	750 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)
Rifabutin	300 mg/day x 10 days	500 mg PO on day 1, then 250 mg/day on days 2-10	6	See footnote below	NA
Sildenafil	100 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)
Theophylline	300 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)
Triazolam	0.125 mg on day 2	500 mg PO on day 1, then 250 mg/day on day 2	12	1.06*	1.02*
Trimethoprim/ Sulfamethoxazole	160 mg/800mg/day PO x 7 days	1,200 mg PO on day 7	12	0.85 (0.75 to 0.97)/	0.87 (0.80 to 0.95/ 0.96 (0.88 to 1.03)
Zidovudine	500 mg/day PO x 21 days	600 mg/day PO x 14 days	5	1.12 (0.42 to 3.02)	0.94 (0.52 to 1.70)
Zidovudine	500 mg/day PO x 21 days	1,200 mg/day PO x 14 days	4	1.31 (0.43 to 3.97)	1.30 (0.69 to 2.43)

PRECAUTIONS - Drug Interactions.

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
				Mean C_max	Mean AUC
Efavirenz	400 mg/day x 7 days	600 mg PO on day 7	14	1.22 (1.04 to 1.42)	0.92*
Fluconazole	200 mg PO single dose	1,200 mg PO single dose	18	0.82 (0.66 to 1.02)	1.07 (0.94 to1.22)
Nelfinavir	750 mg TID x 11 days	1,200 mg PO on day 9	14	2.36 (1.77 to 3.15)	2.12 (1.80 to 2.50)
Rifabutin	300 mg/day x 10 days	500 mg PO on day 1, then 250 mg/day on days 2-10	6	See footnote below	NA

Microbiology:

in vitroIn vivo

in vitroINDICATIONS AND USAGE

Aerobic and facultative gram-positive microorganisms
                Staphylococcus aureus
                Streptococcus agalactiae
                Streptococcus pneumoniae
                Streptococcus pyogenes

Enterococcus faecalis

Aerobic and facultative gram-negative microorganisms
                Haemophilus ducreyi
                Haemophilus influenzae
                Moraxella catarrhalis
                Neisseria gonorrhoeae

“Other” microorganisms
                Chlamydia pneumoniae
                Chlamydia trachomatis
                Mycoplasma pneumoniae

in vitro but their clinical significance is unknown.

Aerobic and facultative gram-positive microorganisms

Aerobic and facultative gram-negative microorganisms
                Bordetella pertussis
                Legionella pneumophila

Anaerobic microorganisms
                Peptostreptococcus species
                Prevotella bivia

“Other” microorganisms
                Ureaplasma urealyticum

Susceptibility Testing Methods:
in vitro

Dilution techniques:
_1,3

Diffusion techniques:
_2,3

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

                                                        Minimum Inhibitory                                            Disk Diffusion
Pathogen                                   Concentrations (mcg/mL)                                (zone diameters in mm)
                                                   S                I              R^a                            S                        I                       R^a
Haemophilus
Staphylococcus aureus

S. pneumoniae^b

^a
^bS. pneumoniae

Neisseria gonorrhoeae

QUALITY CONTROL:

Table 2. Acceptable Quality Control Ranges for Azithromycin

QC Strain                                                       Minimum Inhibitory                                            Disk Diffusion
                                                                    Concentrations (mcg/mL)                            (zone diameters in mm)
Haemophilus influenzae

Staphylococcus aureus

Staphylococcus aureus

Streptococcus pneumoniae

AZITHROMYCIN INDICATIONS AND USAGE

WARNINGSAs recommended dosages, durations of therapy and applicable patient populations vary among these infections, please see DOSAGE AND ADMINISTRATION for specific dosing recommendations.

Adults:

Acute bacterial exacerbations of chronic obstructive pulmonary diseaseHaemophilus influenzaeMoraxella catarrhalis or Streptococcus pneumoniae.

Acute bacterial sinusitisHaemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Community-acquired pneumonia Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate

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 functional asplenia).

Pharyngitis/tonsillitisStreptococcus pyogenes

Streptococcus pyogenesStreptococcus pyogenes

Uncomplicated skin and skin structure infectionsStaphylococcus aureus, Streptococcus pyogenes,Streptococcus agalactiae

Urethritis and cervicitisChlamydia trachomatisNeisseria gonorrhoeae.

Genital ulcer diseaseHaemophilus ducreyi

Pediatric Patients:

PRECAUTIONS—Pediatric Use CLINICAL STUDIES IN PEDIATRIC PATIENTS

Acute otitis media Haemophilus influenzae, Moraxella catarrhalisStreptococcus pneumoniaeDOSAGE AND ADMINISTRATION

Community-acquired pneumoniaChlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniaeStreptococcus pneumoniae DOSAGE AND ADMINISTRATION.

NOTE: Azithromycin should not be used in pediatric 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, or
            patients with significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).

Pharyngitis/tonsillitis Streptococcus pyogenesDOSAGE AND ADMINISTRATION

Streptococcus pyogenes

AZITHROMYCIN CONTRAINDICATIONS

WARNINGS

CONTRAINDICATIONSrecurred soon thereafter in some patients without further azithromycin exposure

In the treatment of pneumonia, azithromycin has only been shown to be safe and effective in the treatment of community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate for oral therapy. Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors such as any of the following: patients with cystic fibrosis, patients with nosocomially acquired infections, patients with known or suspected bacteremia, patients requiring hospitalization, elderly or debilitated patients, or patients with significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).

Clostridium difficile C. difficile.

C. difficileC. difficile

C. difficileC. difficile

PRECAUTIONS

General: CLINICAL PHARMACOLOGY - Special Populations - Renal Insufficiency.

Information for Patients:

Drug Interactions:

ADVERSE REACTIONS

CLINICAL PHARMACOLOGY-Drug-Drug Interactions.

Laboratory Test Interactions:

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Pregnancy:

Nursing Mothers:

Pediatric Use:

CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE,DOSAGE AND ADMINISTRATION

DOSAGE AND ADMINISTRATION

Chlamydia pneumoniaeMycoplasma pneumoniaeHaemophilus influenzaeStreptococcus pneumoniae

Studies evaluating the use of repeated courses of therapy have not been conducted.CLINICAL PHARMACOLOGYANIMAL TOXICOLOGY.

Geriatric Use:

CLINICAL PHARMACOLOGY.

AZITHROMYCIN ADVERSE REACTIONS

DOSAGE AND ADMINISTRATION.CLINICAL STUDIES IN PEDIATRIC PATIENTS.

Clinical:

Adults:
Multiple-dose regimens:

Cardiovascular:
Gastrointestinal:
Genitourinary:
Nervous System:
General:
Allergic:

Single 1-gramdose regimen:

Single 2-gram dose regimen:

Pediatric Patients:
Single and Multiple-dose regimens:

DOSAGE AND ADMINISTRATIONCLINICAL STUDIES IN PEDIATRIC PATIENTS

Dosage Regimen	Diarrhea, %	Abdominal Pain, %	Vomiting, %	Nausea, %	Rash, %
1-day	4.3%	1.4%	4.9%	1.0%	1.0%
3-day	2.6%	1.7%	2.3%	0.4%	0.6%
5-day	1.8%	1.2%	1.1%	0.5%	0.4%

Dosage Regimen	Diarrhea/Loose stools, %	Abdominal Pain, %	Vomiting, %	Nausea, %	Rash, %

5-day	5.8%	1.9%	1.9%	1.9%	1.6%

Dosage Regimen	Diarrhea, %	Abdominal Pain, %	Vomiting, %	Nausea, %	Rash, %	Headache%

5-day	5.4%	3.4%	5.6%	1.8%	0.7%	1.1%

Cardiovascular:
Gastrointestinal:
Hematologic and Lymphatic:
Nervous System:
General:
Allergic:
Respiratory:
Skin and Appendages:
Special Senses:

Post-Marketing Experience:

Allergic:
Cardiovascular:torsades de pointes
Gastrointestinal:
General:
Genitourinary:
Hematopoietic:
Liver/Biliary:
Nervous System:
Psychiatric:
Skin/Appendages:
Special Senses:

Laboratory Abnormalities:

Adults:

Pediatric Patients:
One, Three and Five Day Regimens
³³DOSAGE AND ADMINISTRATION

DOSAGE AND ADMINISTRATION

INDICATIONS AND USAGE CLINICAL PHARMACOLOGY

Adults:

Infection*	Recommended Dose/Duration of Therapy
Community-acquired pneumonia (mild severity) Pharyngitis/tonsillitis (second line therapy) Skin/skin structure (uncomplicated)	500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5.
Acute bacterial exacerbations of chronic obstructive pulmonary disease (mild to moderate)	500 mg QD x 3 days OR 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5.
Acute bacterial sinusitis	500 mg QD x 3 days
Genital ulcer disease (chancroid)	One single 1 gram dose
Non-gonoccocal urethritis and cervicitis	One single 1 gram dose
Gonococcal urethritis and cervicitis	One single 2 gram dose

* DUE TO THE INDICATED ORGANISMS (See INDICATIONS AND USAGE.)

_0-120CLINICAL PHARMACOLOGY, Special Populations, Renal Insufficiency.

CLINICAL PHARMACOLOGY, Special Populations, Hepatic Insufficiency.

CLINICAL PHARMACOLOGY, Special Populations.

Pediatric Patients:

Acute Otitis Media:

Acute bacterial Sinusitis:

Community-Acquired Pneumonia:

PEDIATRIC DOSAGE GUIDELINES FOR OTITIS MEDIA,ACUTE BACTERIAL SINUSITIS AND COMMUNITY-ACQUIRED PNEUMONIA (Age 6 months and above, see PRECAUTIONS-Pediatric Use.) Based on Body Weight
OTITIS MEDIA AND COMMUNITY-ACQUIRED PNEUMONIA: (5-Day Regimen)* Dosing Calculated on 10 mg/kg/day Day 1 and 5 mg/kg/day Days 2 to 5.
Weight		100 mg/5 mL		200 mg/5 mL		Total mL per Treatment Course	Total mg per Treatment Course
Kg	Lbs.	Day 1	Days 2-5	Day 1	Days 2-5
5	11	2.5 mL (½ tsp)	1.25 mL (¼ tsp)			7.5 mL	150 mg
10	22	5 mL (1 tsp)	2.5 mL (½ tsp)			15 mL	300 mg
20	44			5 mL (1 tsp)	2.5 mL (½ tsp)	15 mL	600 mg
30	66			7.5 mL (1½ tsp)	3.75 mL (3/4tsp)	22.5 mL	900 mg
40	88			10 mL (2 tsp)	5 mL (1tsp)	30 mL	1200 mg
50 and above				12.5 mL (2 ½ tsp)	6.25 mL (1¼ tsp)	37.5 mL	1500 mg

OTITIS MEDIA AND ACUTE BACTERIAL SINUSITIS: (3-Day Regimen)* Dosing Calculated on 10 mg/kg/day Day 1.
Weight		100 mg/5 mL	200 mg/5 mL	Total mL per Treatment Course	Total mg per Treatment Course
Kg	Lbs.	Day 1-3	Day 1-3
5	11	2.5 mL (½ tsp)		7.5 mL	150 mg
10	22	5 mL (1 tsp)		15 mL	300 mg
20	44		5 mL (1 tsp)	15 mL	600 mg
30	66		7.5 mL (1½ tsp)	22.5 mL	900 mg
40	88		10 mL (2 tsp)	30 mL	1200 mg
50 and above	110 and above		12.5 mL (2 ½ tsp )	37.5 mL	1500 mg

OTITIS MEDIA : (1-Day Regimen) Dosing Calculated on 30 mg/kg as a single dose
Weight		200 mg/5 mL	Total mL per Treatment course	Total mg per Treatment course
Kg	Lbs.	Day1
5	11	3.75 mL (3/4 tsp)	3.75 mL	150 mg
10	22	7.5 mL (1½ tsp)	7.5 mL	300 mg
20	44	15 mL (3 tsp)	15 mL	600 mg
30	66	22.5 mL (4 ½ tsp)	22.5 mL	900 mg
40	88	30 mL (6tsp)	30 mL	1200 mg
50 and above	110 and above	37.5 mL (7½ tsp)	37.5 mL	1500 mg

Pharyngitis/Tonsillitis:

PEDIATRIC DOSAGE GUIDELINES FOR PHARYNGITIS /TONSILLITIS
(Age 2 years and above, see PRECAUTIONS-Pediatric Use.)
Based on Body weight

PHARYNGITIS/TONSILITIS: (5-Day Regimen) Dosing Calculated on 12 mg/kg/day for 5 days
Weight		200mg/5mL	Total mL per Treatment course	Total mg per Treatment course
Kg	Lbs.	Day 1-5
8	18	2.5 mL (½ tsp)	12.5 mL	500 mg
17	37	5 mL (1 tsp)	25 mL	1000 mg
25	55	7.5 mL (1 ½ tsp)	37.5 mL	1500 mg
33	73	10 mL (2 tsp)	50 mL	2000 mg
40	88	12.5 mL (2 ½ tsp)	62.5 mL	2500 mg

HOW SUPPLIED

CLINICAL STUDIES

(See INDICATIONS AND USAGE and Pediatric Use.)
Pediatric Patients
From the perspective of evaluating pediatric clinical trials, Days 11-14 were considered on-therapy evaluations because of the extended half-life of azithromycin. Day 11-14 data are provided for clinical guidance. Day 24-32 evaluations were considered the primary test of cure endpoint.

Acute Otitis Media
Safety and efficacy using azithromycin 30 mg/kg given over 5 days
Protocol 1
In a double-blind, controlled clinical study of acute otitis media performed in the United States, azithromycin (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2-5) was compared to amoxicillin/clavulanate potassium (4:1). For the 553 patients who were evaluated for clinical efficacy, the clinical success rate (i.e., cure plus improvement) at the Day 11 visit was 88% for azithromycin and 88% for the control agent. For the 521 patients who were evaluated at the Day 30 visit, the clinical success rate was 73% for azithromycin and 71% for the control agent.

In the safety analysis of the above study, the incidence of treatment-related adverse events, primarily gastrointestinal, in all patients treated was 9% with azithromycin and 31% with the control agent. The most common side effects were diarrhea/loose stools (4% azithromycin vs. 20% control), vomiting (2% azithromycin vs. 7% control), and abdominal pain (2% azithromycin vs. 5% control).

Protocol 2
In a non-comparative clinical and microbiologic trial performed in the United States, where significant rates of beta-lactamase producing organisms (35%) were found, 131 patients were evaluable for clinical efficacy. The combined clinical success rate (i.e., cure and improvement) at the Day 11 visit was 84% for azithromycin. For the 122 patients who were evaluated at the Day 30 visit, the clinical success rate was 70% for azithromycin.

Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits. The following presumptive bacterial/clinical cure outcomes (i.e., clinical success) were obtained from the evaluable group

Presumed Bacteriologic Eradication

	Day 11 Azithromycin	Day 30 Azithromycin
S. pneumoniae	61/74 (82%)	40/56 (71%)
H. influenzae	43/54 (80%)	30/47 (64%)
M. catarrhalis	28/35 (80%)	19/26 (73%)
S. pyogenes	11/11 (100%)	7/7
Overall	177/217 (82%)	97/137 (73%)

In the safety analysis of this study, the incidence of treatment-related adverse events, primarily gastrointestinal, in all patients treated was 9%. The most common side effect was diarrhea (4%).

Protocol 3
In another controlled comparative clinical and microbiologic study of otitis media performed in the United States, azithromycin was compared to amoxicillin/clavulanate potassium (4:1). This study utilized two of the same investigators as Protocol 2 (above), and these two investigators enrolled 90% of the patients in Protocol 3. For this reason, Protocol 3 was not considered to be an independent study. Significant rates of beta-lactamase producing organisms (20%) were found. Ninety-two (92) patients were evaluable for clinical and microbiologic efficacy. The combined clinical success rate (i.e., cure and improvement) of those patients with a baseline pathogen at the Day 11 visit was 88% for azithromycin vs. 100% for control; at the Day 30 visit, the clinical success rate was 82% for azithromycin vs. 80% for control.
Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits. At the Day 11 and Day 30 visits, the following presumptive bacterial/clinical cure outcomes (i.e., clinical success) were obtained from the evaluable group

Presumed Bacteriologic Eradication
Day 11					Day 30
	Azithromycin	Control	Azithromycin	Control
S. pneumoniae	25/29 (86%)	26/26 (100%)	22/28 (79%)	18/22 (82%)
H. influenzae	9/11 (82%)	9/9	8/10 (80%)	6/8
M. catarrhalis	7/7	5/5	5/5	2/3
S. pyogenes	2/2	5/5	2/2	4/4
Overall	43/49 (88%)	45/45 (100%)	37/45 (82%)	30/37 (81%)

In the safety analysis of the above study, the incidence of treatment-related adverse events, primarily gastrointestinal, in all patients treated was 4% with azithromycin and 31% with the control agent. The most common side effect was diarrhea/loose stools (2% azithromycin vs. 29% control).

Safety and efficacy using azithromycin 30 mg/kg given over 3 days
Protocol 4
In a double-blind, controlled, randomized clinical study of acute otitis media in pediatric patients from 6 months to 12 years of age, azithromycin (10 mg/kg per day for 3 days) was compared to amoxicillin/clavulanate potassium (7:1) in divided doses q12h for 10 days. Each patient received active drug and placebo matched for the comparator.
For the 366 patients who were evaluated for clinical efficacy at the Day 12 visit, the clinical success rate (i.e., cure plus improvement) was 83% for azithromycin and 88% for the control agent. For the 362 patients who were evaluated at the Day 24-28 visit, the clinical success rate was 74% for azithromycin and 69% for the control agent.
In the safety analysis of the above study, the incidence of treatment-related adverse events, primarily gastrointestinal, in all patients treated was 10.6% with azithromycin and 20% with the control agent. The most common side effects were diarrhea/loose stools (5.9% azithromycin vs. 14.6% control), vomiting (2.1% azithromycin vs. 1.1% control), and rash (0% azithromycin vs. 4.3% control).

Safety and efficacy using azithromycin 30 mg/kg given as a single dose
Protocol 5
A double blind, controlled, randomized trial was performed at nine clinical centers. Pediatric patients from 6 months to 12 years of age were randomized 1:1 to treatment with either azithromycin (given at 30 mg/kg as a single dose on Day 1) or amoxicillin/clavulanate potassium (7:1), divided q12h for 10 days. Each child received active drug, and placebo matched for the comparator.
Clinical response (Cure, Improvement, Failure) was evaluated at End of Therapy (Day 12-16) and Test of Cure (Day 28-32). Safety was evaluated throughout the trial for all treated subjects. For the 321 subjects who were evaluated at End of Treatment, the clinical success rate (cure plus improvement) was 87% for azithromycin, and 88% for the comparator. For the 305 subjects who were evaluated at Test of Cure, the clinical success rate was 75% for both azithromycin and the comparator.
In the safety analysis, the incidence of treatment-related adverse events, primarily gastrointestinal, was 16.8% with azithromycin, and 22.5% with the comparator. The most common side effects were diarrhea (6.4% with azithromycin vs. 12.7% with the comparator), vomiting (4% with each agent), rash (1.7% with azithromycin vs. 5.2% with the comparator) and nausea (1.7% with azithromycin vs. 1.2% with the comparator).

Protocol 6
In a non-comparative clinical and microbiological trial, 248 patients from 6 months to 12 years of age with documented acute otitis media were dosed with a single oral dose of azithromycin (30 mg/kg on Day 1).
For the 240 patients who were evaluable for clinical modified Intent-to-Treat (MITT) analysis, the clinical success rate (i.e., cure plus improvement) at Day 10 was 89% and for the 242 patients evaluable at Day 24-28, the clinical success rate (cure) was 85%

Presumed Bacteriologic Eradication
	Day 10	Day 24-28
S. pneumoniae	70/76 (92%)	67/76 (88%)
H. influenzae	30/42 (71%)	28/44 (64%)
M. catarrhalis	10/10 (100%)	10/10 (100%)
Overall	110/128 (86%)	105/130 (81%)

Pharyngitis/Tonsillitis

Three U.S. Streptococcal Pharyngitis Studies
Azithromycin vs. Penicillin V
	EFFICACY RESULTS
	Day 14	Day 30
Bacteriologic Eradication
Azithromycin	323/340 (95%)	255/330 (77%)
Penicillin V	242/332 (73%)	206/325 (63%)
Clinical Success (Cure plus improvement)
Azithromycin	336/343 (98%)	310/330 (94%)
Penicillin V	284/338 (84%)	241/325 (74%)

Adult Patients

Acute Bacterial Exacerbations of Chronic Obstructive Pulmonary Disease

Pathogen	Azithromycin (3 Days)	Clarithromycin (10 Days)
S. pneumoniae	29/32 (91%)	21/27 (78%)
H. influenzae	12/14 (86%)	14/16 (88%)
M. catarrhalis	11/12 (92%)	12/15 (80%)

ADVERSE REACTIONS.

Acute Bacterial Sinusitis

ADVERSE REACTIONS

Pathogen	Azithromycin (500 mg per day for 3 Days)
	Day 7	Day 28
S. pneumoniae	23/26 (88%)	21/25 (84%)
H. influenzae	28/32 (87%)	24/32 (75%)
M. catarrhalis	14/15 (93%)	13/15 (87%)

ADVERSE REACTIONS

ANIMAL TOXICOLOGY

²_max_max_max_max²²²

REFERENCES:

National Committee for Clinical Laboratory Standards, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically – Fifth Edition. Approved Standard NCCLS Document M7-A5, Vol. 20, No. 2 (ISBN 1-56238-394-9). NCCLS, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898, January 2000.
National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests - Seventh Edition. Approved Standard NCCLS Document M2-A7, Vol. 20, No. 1 (ISBN 1-56238-393-0). NCCLS, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898, January 2000.
National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing – Eleventh Informational Supplement. NCCLS Document M100-S11, Vol. 21, No. 1 (ISBN 1-56238-426-0). NCCLS, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898, January 2001.

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PRINCIPAL DISPLAY PANEL

AZITHROMYCIN

NDC 66336-0168-XX

NDC 66336-0168-06
NDC 66336-0168-44

AZITHROMYCIN

AZITHROMYCIN TABLET, FILM COATED

Product Information
Product Type	Human prescription drug label	Item Code (Source)	NDC:66336-168(NDC:64679-961)
Route of Administration	ORAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
AZITHROMYCIN ANHYDROUS AZITHROMYCIN ANHYDROUS		250 mg

Product Characteristics
Color	Size	Imprint Code	Shape
white (white film-coated)	14 mm	W961	OVAL

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC:66336-168-06	6 in 1 BOTTLE
2	NDC:66336-168-44	4 in 1 BOTTLE

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA065404	2008-02-11

PLEASE, BE CAREFUL!

Be sure to consult your doctor before taking any medication!

AZITHROMYCIN description, usages, side effects, indications, overdosage, supplying and lots more!

AZITHROMYCIN

FULL PRESCRIBING INFORMATION: CONTENTS*

FULL PRESCRIBING INFORMATION

AZITHROMYCIN DESCRIPTION

CLINICAL PHARMACOLOGY

Pharmacokinetics

Drug-Drug Interactions

Microbiology:

AZITHROMYCIN INDICATIONS AND USAGE

Adults:

Pediatric Patients:

AZITHROMYCIN CONTRAINDICATIONS

WARNINGS

PRECAUTIONS

Information for Patients:

Drug Interactions:

Pregnancy:

Pediatric Use:

Geriatric Use:

AZITHROMYCIN ADVERSE REACTIONS

Clinical:

Post-Marketing Experience:

Laboratory Abnormalities:

DOSAGE AND ADMINISTRATION

Adults:

HOW SUPPLIED

CLINICAL STUDIES

Adult Patients

ANIMAL TOXICOLOGY

PRINCIPAL DISPLAY PANEL

AZITHROMYCIN

Product Information

Active Ingredient/Active Moiety

Product Characteristics

Packaging

Marketing Information