
Prescription Drug Name:
AZITHROMYCIN 250MG AND 500MG TAB 6 PCK AND 3 PCK FOR WOCKHARDT
ID:
335dec43-2c8b-4432-81e1-f9284a7a834f
Code:
34391-3
DESCRIPTION
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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
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 , and its molecular weight is 749. Azithromycin has the following structural formula:
Azithromycin tablet is supplied for oral administration as white, film-coated, oval shaped biconvex tablets containing anhydrous azithromycin 250 mg or 500 mg and the following inactive ingredients: microcrystalline cellulose, corn starch, croscarmellose sodium, magnesium trisilicate, magnesium stearate, colloidal silicon dioxide, hydroxypropyl cellulose, sodium lauryl sulfate, hypromellose, titanium dioxide and polyethylene glycol.
CLINICAL PHARMACOLOGY
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displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
INDICATIONS AND USAGE
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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
CONTRAINDICATIONS
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displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
WARNINGS
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displayName: WARNINGS SECTION
FDA Article Code: 34071-1
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.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against
PRECAUTIONS
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displayName: PRECAUTIONS SECTION
FDA Article Code: 42232-9
Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with other macrolides. A similar effect with azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarization.
Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.
Prescribing azithromycin tablet in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
ADVERSE REACTIONS
id: 4febcc98-c2dd-4f17-9118-4dcc84f17446
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
DOSAGE AND ADMINISTRATION
id: b30ea8e9-4bde-4e90-a492-2d29ffe367b4
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
HOW SUPPLIED
id: 0f5ec8d5-251d-419a-8c13-79781080c889
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
CLINICAL STUDIES
id: 71ebbad3-6b87-492a-8445-6bfe79b97a09
displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7
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.
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
Day 11 Azithromycin |
Day 30 Azithromycin |
|
|
61/74 (82%) | 40/56 (71%) |
|
43/54 (80%) | 30/47 (64%) |
|
28/35 (80%) | 19/26 (73%) |
|
11/11 (100%) | 7/7 |
Overall | 177/217 (82%) | 97/137 (73%) |
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
Day 11 | |
||||
---|---|---|---|---|---|
Azithromycin | Control | Azithromycin | Control | ||
|
25/29 (86%) | 26/26 (100%) | 22/28 (79%) | 18/22 (82%) | |
|
9/11 (82%) | 9/9 | 8/10 (80%) | 6/8 | |
|
7/7 | 5/5 | 5/5 | 2/3 | |
|
2/2 | 5/5 | 2/2 | 4/4 | |
Overall | 43/49 (88%) | 45/45 (100%) | 37/45 (82%) | 30/37 (81%) | |
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).
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%
Day 10 | Day 24-28 | |
|
70/76 (92%) | 67/76 (88%) |
|
30/42 (71%) | 28/44 (64%) |
|
10/10 (100%) | 10/10 (100%) |
Overall | 110/128 (86%) | 105/130 (81%) |
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 -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)
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%) |
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).
Adult Patients
id: 6bf42539-9b34-43a6-a554-bd1f827d7748
displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7
The following outcomes were the clinical cure rates at the Day 21-24 visit for the bacteriologically evaluable patients by pathogen
|
(3 Days) |
(10 Days) |
|
29/32 (91%) | 21/27 (78%) |
|
12/14 (86%) | 14/16 (88%) |
|
11/12 (92%) | 12/15 (80%) |
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
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:
|
Azithromycin (500 mg per day for 3 Days) |
|
---|---|---|
|
|
|
|
23/26 (88%) | 21/25 (84%) |
|
28/32 (87%) | 24/32 (75%) |
|
14/15 (93%) | 13/15 (87%) |
ANIMAL TOXICOLOGY
id: 52511a49-b1d7-4333-9235-c410f8f5f240
displayName: ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION
FDA Article Code: 34091-9
Wockhardt Limited
Mumbai, India
Wockhardt USA LLC.
20 Waterview Blvd.
Parsippany, NJ 07054
USA
Aidarex Pharmaceuticals LLC,
Corona, CA 92880
PACKAGE LABEL PRINCIPAL DISPLAY PANEL
id: fc7fb509-900d-4a85-8270-d26b1a6acee5
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4