AZITHROMYCIN 250MG AND 500MG TAB 6 PCK AND 3 PCK FOR WOCKHARDT

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Azithromycin tablets 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)-ß-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 C₃₈H₇₂N₂O₁₂ , and its molecular weight is 749. Azithromycin has the following structural formula: Anhydrous azithromycin is a white amorphous powder with a molecular formula of C₃₈H₇₂N₂O₁₂ and a molecular weight of 749.
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

Azithromycin tablets are 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.

CONTRAINDICATIONS

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displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Azithromycin tablets are contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic.

WARNINGS

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displayName: WARNINGS SECTION
FDA Article Code: 34071-1

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.

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 azithromycin, 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.

PRECAUTIONS

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displayName: PRECAUTIONS SECTION
FDA Article Code: 42232-9

General: Because azithromycin is principally eliminated via the liver, caution should be exercised when azithromycin is administered to patients with impaired hepatic function. Due to the limited data in subjects with GFR <10 mL/min, caution should be exercised when prescribing azithromycin in these patients. (See CLINICAL PHARMACOLOGY – Special Populations – Renal Insufficiency.)

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

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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Potentially serious side effects of angioedema and cholestatic jaundice were reported rarely. Approximately 0.7% of the patients (adults and pediatric patients) from the 5-day multiple-dose clinical trials discontinued azithromycin tablet therapy because of treatment-related side effects. In adults given 500 mg/day for 3 days, the discontinuation rate due to treatment-related side effects was 0.6%. In clinical trials in pediatric patients given 30 mg/kg, either as a single dose or over 3 days, discontinuation from the trials due to treatment-related side effects was approximately 1%. (See DOSAGE AND ADMINISTRATION.) Most of the side effects leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. (See CLINICAL STUDIES IN PEDIATRIC PATIENTS.)

DOSAGE AND ADMINISTRATION

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displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

(See INDICATIONS AND USAGE and CLINICAL PHARMACOLOGY.)

HOW SUPPLIED

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displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Azithromycin tablets 250 mg are supplied as white film-coated oval shaped biconvex tablets debossed with W961 on one side and other side plain containing anhydrous azithromycin 250 mg. These are packaged as follows: 6 tablets NDC 33261-0403-01 Azithromycin tablets 500 mg are supplied as white film-coated oval shaped biconvex tablets debossed with W964 on one side and other side plain containing anhydrous azithromycin 500 mg. These are packaged as follows: 3 tablets :  NDC 33261-879-01

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

CLINICAL STUDIES

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displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7

(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

Adult Patients

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displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7

Acute Bacterial Exacerbations of Chronic Obstructive Pulmonary Disease
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

ANIMAL TOXICOLOGY

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displayName: ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION
FDA Article Code: 34091-9

Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple doses of azithromycin. It has been demonstrated in numerous organ systems (e.g., eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and pancreas) in dogs treated with azithromycin at doses which, expressed on the basis of mg/m², are approximately equal to the recommended adult human dose, and in rats treated at doses approximately one-sixth of the recommended adult human dose. This effect has been shown to be reversible after cessation of azithromycin treatment. Phospholipidosis has been observed to a similar extent in the tissues of neonatal rats and dogs given daily doses of azithromycin ranging from 10 days to 30 days. Based on the pharmacokinetic data, phospholipidosis has been seen in the rat (30 mg/kg dose) at observed C_maxvalue of 1.3 mcg/mL (six times greater than the observed C_max of 0.216 mcg/mL at the pediatric dose of 10 mg/kg). Similarly, it has been shown in the dog (10 mg/kg dose) at observed C_max value of 1.5 mcg/mL (seven times greater than the observed same C_max and drug dose in the studied pediatric population). On a mg/m² basis, 30 mg/kg dose in the neonatal rat (135 mg/m²) and 10 mg/kg dose in the neonatal dog (79 mg/m²) are approximately 0.5 and 0.3 times, respectively, the recommended dose in the pediatric patients with an average body weight of 25 kg. Phospholipidosis, similar to that seen in the adult animals, is reversible after cessation of azithromycin treatment. The significance of these findings for animals and for humans is unknown.

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. Manufactured by

Wockhardt Limited
Mumbai, India

Distributed by:

Wockhardt USA LLC.
20 Waterview Blvd.
Parsippany, NJ 07054
USA Repackaged By :
Aidarex Pharmaceuticals LLC,
Corona, CA 92880 Rev.141010

PACKAGE LABEL PRINCIPAL DISPLAY PANEL

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4