Zithromax 250 MG Oral Tablet
WARNINGS
Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Stevens Johnson Syndrome and toxic epidermal necrolysis have been reported rarely in patients on azithromycin therapy.
Although rare, fatalities have been reported.
(See CONTRAINDICATIONS .) Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms recurred soon thereafter in some patients without further azithromycin exposure .
These patients required prolonged periods of observation and symptomatic treatment.
The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is unknown at present.
If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted.
Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death.
Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.
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 associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ZITHROMAX, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C.
difficile .
C.
difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin producing strains of C.
difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibiotic use.
Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.
difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C.
difficile , and surgical evaluation should be instituted as clinically indicated.
DESCRIPTION
ZITHROMAX (azithromycin tablets and azithromycin for oral suspension) contain the active ingredient azithromycin, 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.
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 C 38 H 72 N 2 O 12 , and its molecular weight is 749.00.
Azithromycin has the following structural formula: Azithromycin, as the dihydrate, is a white crystalline powder with a molecular formula of C 38 H 72 N 2 O 12 •2H 2 O and a molecular weight of 785.0.
ZITHROMAX is supplied for oral administration as film-coated, modified capsular shaped tablets containing azithromycin dihydrate equivalent to either 250 mg or 500 mg azithromycin and the following inactive ingredients: dibasic calcium phosphate anhydrous, pregelatinized starch, sodium croscarmellose, magnesium stearate, sodium lauryl sulfate, hypromellose, lactose, titanium dioxide, triacetin and D&C Red #30 aluminum lake.
ZITHROMAX for oral suspension is supplied in bottles containing azithromycin dihydrate powder equivalent to 300 mg, 600 mg, 900 mg, or 1200 mg azithromycin per bottle and the following inactive ingredients: sucrose; sodium phosphate, tribasic, anhydrous; hydroxypropyl cellulose; xanthan gum; FD&C Red #40; and spray dried artificial cherry, creme de vanilla and banana flavors.
After constitution, each 5 mL of suspension contains 100 mg or 200 mg of azithromycin.
MM1
CLINICAL STUDIES
(See INDICATIONS AND USAGE and Pediatric Use .
) 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.
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).
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 Day 30 Azithromycin 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%).
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).
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 20.0% 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 (0.0% azithromycin vs.
4.3% control).
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).
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%) In the safety analysis of this study, the incidence of treatment-related adverse events, primarily gastrointestinal, in all the subjects treated was 12.1%.
The most common side effects were vomiting (5.6%), diarrhea (3.2%), and abdominal pain (1.6%).
In three double-blind controlled studies, conducted in the United States, azithromycin (12 mg/kg once a day for 5 days) was compared to penicillin V (250 mg three times a day for 10 days) in the treatment of pharyngitis due to documented Group A β-hemolytic streptococci (GABHS or S.
pyogenes ).
Azithromycin was clinically and microbiologically statistically superior to penicillin at Day 14 and Day 30 with the following clinical success (i.e., cure and improvement) and bacteriologic efficacy rates (for the combined evaluable patient with documented GABHS): 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%) Approximately 1% of azithromycin-susceptible S.
pyogenes isolates were resistant to azithromycin following therapy.
The incidence of treatment-related adverse events, primarily gastrointestinal, in all patients treated was 18% on azithromycin and 13% on penicillin.
The most common side effects were diarrhea/loose stools (6% azithromycin vs.
2% penicillin), vomiting (6% azithromycin vs.
4% penicillin), and abdominal pain (3% azithromycin vs.
1% penicillin).
In a randomized, double-blind controlled clinical trial of acute exacerbation of chronic bronchitis (AECB), azithromycin (500 mg once daily for 3 days) was compared with clarithromycin (500 mg twice daily for 10 days).
The primary endpoint of this trial was the clinical cure rate at Day 21– 24.
For the 304 patients analyzed in the modified intent to treat analysis at the Day 21–24 visit, the clinical cure rate for 3 days of azithromycin was 85% (125/147) compared to 82% (129/157) for 10 days of clarithromycin.
The following outcomes were the clinical cure rates at the Day 21–24 visit for the bacteriologically evaluable patients by pathogen: 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%) In the safety analysis of this study, the incidence of treatment-related adverse events, primarily gastrointestinal, were comparable between treatment arms (25% with azithromycin and 29% with clarithromycin).
The most common side effects were diarrhea, nausea and abdominal pain with comparable incidence rates for each symptom of 5–9% between the two treatment arms.
(See ADVERSE REACTIONS .
) In a randomized, double blind, double-dummy controlled clinical trial of acute bacterial sinusitis, azithromycin (500 mg once daily for 3 days) was compared with amoxicillin/clavulanate (500/125 mg tid for 10 days).
Clinical response assessments were made at Day 10 and Day 28.
The primary endpoint of this trial was prospectively defined as the clinical cure rate at Day 28.
For the 594 patients analyzed in the modified intent to treat analysis at the Day 10 visit, the clinical cure rate for 3 days of azithromycin was 88% (268/303) compared to 85% (248/291) for 10 days of amoxicillin/clavulanate.
For the 586 patients analyzed in the modified intent to treat analysis at the Day 28 visit, the clinical cure rate for 3 days of azithromycin was 71.5% (213/298) compared to 71.5% (206/288), with a 97.5% confidence interval of −8.4 to 8.3, for 10 days of amoxicillin/clavulanate.
In the safety analysis of this study, the overall incidence of treatment-related adverse events, primarily gastrointestinal, was lower in the azithromycin treatment arm (31%) than in the amoxicillin/clavulanate arm (51%).
The most common side effects were diarrhea (17% in the azithromycin arm vs.
32% in the amoxicillin/clavulanate arm), and nausea (7% in the azithromycin arm vs.
12% in the amoxicillin/clavulanate arm).
(See ADVERSE REACTIONS ).
In an open label, noncomparative study requiring baseline transantral sinus punctures the following outcomes were the clinical success rates at the Day 7 and Day 28 visits for the modified intent to treat patients administered 500 mg of azithromycin once daily for 3 days with the following pathogens: Pathogen Azithromycin (500 mg per day for 3 Days) Day 7 Day28 S.
pneumoniae 23/26 (88%) 21/25 (84%) H.
influenzae 28/32 (87%) 24/32 (75%) M.
catarrhalis 14/15 (93%) 13/15 (87%) The overall incidence of treatment-related adverse events in the noncomparative study was 21% in modified intent to treat patients treated with azithromycin at 500 mg once daily for 3 days with the most common side effects being diarrhea (9%), abdominal pain (4%) and nausea (3%).
(See ADVERSE REACTIONS ).
HOW SUPPLIED
ZITHROMAX 250 mg tablets are supplied as pink modified capsular shaped, engraved, film-coated tablets containing azithromycin dihydrate equivalent to 250 mg of azithromycin.
ZITHROMAX 250 mg tablets are engraved with “PFIZER” on one side and “306” on the other.
These are packaged in bottles and blister cards of 6 tablets (Z-PAKS ® ) as follows: Bottles of 30 NDC 0069-3060-30 Boxes of 3 (Z-PAKS ® of 6) NDC 0069-3060-75 Unit Dose package of 50 NDC 0069-3060-86 ZITHROMAX 500 mg tablets are supplied as pink modified capsular shaped, engraved, film-coated tablets containing azithromycin dihydrate equivalent to 500 mg of azithromycin.
ZITHROMAX 500 mg tablets are engraved with “Pfizer” on one side and “ZTM500” on the other.
These are packaged in bottles and blister cards of 3 tablets (TRI-PAKS™) as follows: Bottles of 30 NDC 0069-3070-30 Boxes of 3 (TRI-PAKS™ of 3 tablets) NDC 0069-3070-75 Unit Dose package of 50 NDC 0069-3070-86 ZITHROMAX tablets should be stored between 15° to 30°C (59° to 86°F).
ZITHROMAX for oral suspension after constitution contains a flavored suspension.
ZITHROMAX ® for oral suspension is supplied to provide 100 mg/5 mL or 200 mg/5 mL suspension in bottles as follows: Azithromycin contents per bottle NDC 300 mg 0069-3110-19 600 mg 0069-3120-19 900 mg 0069-3130-19 1200 mg 0069-3140-19 See DOSAGE AND ADMINISTRATION for constitution instructions with each bottle type.
Store dry powder below 30°C (86°F).
Store constituted suspension between 5° to 30°C (41° to 86°F) and discard when full dosing is completed.
INDICATIONS AND USAGE
INDICATIONS & USAGE ZITHROMAX (azithromycin) 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 ADMINISTRATION for specific dosing recommendations .
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 functional asplenia).
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.
ZITHROMAX is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx.
Because some strains are resistant to ZITHROMAX, susceptibility tests should be performed when patients are treated with ZITHROMAX.
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.
ZITHROMAX, 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 ZITHROMAX 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 ZITHROMAX (azithromycin) and other antibacterial drugs, ZITHROMAX (azithromycin) 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.
(See PRECAUTIONS—Pediatric Use and CLINICAL STUDIES IN PEDIATRIC PATIENTS Acute otitis media caused by Haemophilus influenzae , Moraxella catarrhalis or Streptococcus pneumoniae .
(For specific dosage recommendation, see DOSAGE AND ADMINISTRATION .) Community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate for oral therapy.
(For specific dosage recommendation, see 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 caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy.
(For specific dosage recommendation, see DOSAGE AND ADMINISTRATION .) 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.
ZITHROMAX is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx.
Because some strains are resistant to ZITHROMAX, susceptibility tests should be performed when patients are treated with ZITHROMAX.
Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available.
Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its susceptibility to azithromycin.
Therapy with ZITHROMAX may be initiated before results of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly.
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION ( See INDICATIONS AND USAGE and CLINICAL PHARMACOLOGY .
) Infection * Recommended Dose/Duration of Therapy Community-aquired 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 × 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 × 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 See ZITHROMAX tablets can be taken with or without food.
No dosage adjustment is recommended for subjects with renal impairment (GFR ≤80 mL/min).
The mean AUC 0–120 was similar in subjects with GFR 10–80 mL/min compared to subjects with normal renal function, whereas it increased 35% in subjects with GFR <10 mL/min compared to subjects with normal renal function.
Caution should be exercised when azithromycin is administered to subjects with severe renal impairment.
(See CLINICAL PHARMACOLOGY, Special Populations, Renal Insufficiency .
) The pharmacokinetics of azithromycin in subjects with hepatic impairment have not been established.
No dose adjustment recommendations can be made in patients with impaired hepatic function (See CLINICAL PHARMACOLOGY, Special Populations, Hepatic Insufficiency.
) No dosage adjustment is recommended based on age or gender.
(See CLINICAL PHARMACOLOGY, Special Populations .
) ZITHROMAX for oral suspension can be taken with or without food.
The recommended dose of ZITHROMAX for oral suspension for the treatment of pediatric patients with acute otitis media is 30 mg/kg given as a single dose or 10 mg/kg once daily for 3 days or 10 mg/kg as a single dose on the first day followed by 5 mg/kg/day on Days 2 through 5.
(See chart below.) The recommended dose of ZITHROMAX for oral suspension for the treatment of pediatric patients with acute bacterial sinusitis is 10 mg/kg once daily for 3 days.
(See chart below.) The recommended dose of ZITHROMAX for oral suspension for the treatment of pediatric patients with community-acquired pneumonia is 10 mg/kg as a single dose on the first day followed by 5 mg/kg on Days 2 through 5.
(See chart below.) 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 (¾ tsp) 22.5 mL 900 mg 40 88 10 mL (2 tsp) 5 mL (1 tsp) 30 mL 1200 mg 50 and above 110 and above 12.5 mL (2½ tsp) 6.25 mL (1¼ tsp) 37.5 mL 1500 mg Effectiveness of the 3-day or 1-day regimen in pediatric patients with community-acquired pneumonia has not been established.
OTITIS MEDIA AND ACUTE BACTERIAL SINUSITIS: (3-Day Regimen) * Dosing Calculated on 10 mg/kg/day 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 (1/2 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 (1 ½ 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 Effectiveness of the 5-day or 1-day regimen in pediatric patients with acute bacterial sinusitis has not been established.
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.
Day 1 5 11 3.75 mL (3/4 tsp) 3.75 mL 150 mg 10 22 7.5 mL (1 ½ 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 (6 tsp) 30 mL 1200 mg 50 and above 110 and above 37.5 mL (7 ½ tsp) 37.5 mL 1500 mg The safety of re-dosing azithromycin in pediatric patients who vomit after receiving 30 mg/kg as a single dose has not been established.
In clinical studies involving 487 patients with acute otitis media given a single 30 mg/kg dose of azithromycin, eight patients who vomited within 30 minutes of dosing were re-dosed at the same total dose.
The recommended dose of ZITHROMAX for children with pharyngitis/tonsillitis is 12 mg/kg once daily for 5 days.
(See chart below.) PEDIATRIC DOSAGE GUIDELINES FOR PHARYNGITIS/TONSILLITIS (Age 2 years and above, see PRECAUTIONS—Pediatric Use .) Based on Body Weight PHARYNGITIS/TONSILLITIS: (5-Day Regimen) Dosing Calculated on 12 mg/kg/day for 5 days.
Weight 200 mg/5 mL 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 (1½ tsp) 37.5 mL 1500 mg 33 73 10 mL (2 tsp) 50 mL 2000 mg 40 88 12.5 mL (2½ tsp) 62.5 mL 2500 mg Constituting instructions for ZITHROMAX Oral Suspension, 300, 600, 900, 1200 mg bottles.
The table below indicates the volume of water to be used for constitution: Amount of water to be added Total volume after constitution (azithromycin content) Azithromycin concentration after constitution 9 mL (300 mg) 15 mL (300 mg) 100 mg/5 mL 9 mL (600 mg) 15 mL (600 mg) 200 mg/5 mL 12 mL (900 mg) 22.5 mL (900 mg) 200 mg/5 mL 15 mL (1200 mg) 30 mL (1200 mg) 200 mg/5 mL Shake well before each use.
Oversized bottle provides shake space.
Keep tightly closed.
After mixing, store suspension at 5° to 30°C (41° to 86°F) and use within 10 days.
Discard after full dosing is completed.