Azithromycin (Powder, For Suspension)
(See INDICATIONS AND USAGE and CLINICAL PHARMACOLOGY.)<br/>Adults: Azithromycin tablets can be taken with or without food.<br/>Renal Insufficiency: No dosage adjustment is recommended for subjects with renal impairment (GFR���80 mL/min). The mean AUCwas similar in subjects with GFR 10 to 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).<br/>Hepatic 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).<br/>Pediatric Patients: Azithromycin for oral suspension can be taken with or without food.<br/>Acute Otitis Media: The recommended dose of azithromycin 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).<br/>Acute Bacterial Sinusitis: The recommended dose of azithromycin 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).<br/>Community-Acquired Pneumonia: The recommended dose of azithromycin 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). 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 thesame total dose.<br/>Pharyngitis/Tonsillitis: The recommended dose of azithromycin for pediatric patients with pharyngitis/tonsillitis is 12 mg/kg once daily for 5 days (see chart below). Constituting instructions for azithromycin for oral suspension USP, 300, 600, 900, 1200 mg bottles. The table below indicates the volume of water to be used for constitution: 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.
Azithromycin for oral suspension, USP contains 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-��-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)-��-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. Azithromycin has the following structural formula: CHNOM. W. 749.00 Azithromycin, as the monohydrate, is a white to off-white crystalline powder with a molecular formula of CHNO���HO and a molecular weight of 767.02. 5 mL of constituted suspension of azithromycin for oral suspension, 100 mg/5 mL and 200 mg/5 mL, contains 6 mg of sodium. Azithromycin for oral suspension, USP 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: arabic gum, artificial aromatic substances, ethyl vanillin, FD&C Red #40, hydroxypropyl cellulose, maltodextrin, nature aromatic substances, nature identical aromatic substances, sucrose, tribasic sodium phosphate dodecahydrate, vanillin, and xanthan gum. After constitution, each 5 mL of suspension contains 100 mg or 200 mg of azithromycin. The dry powder before constitution is off-white to pinkish in color. The suspension after constitution is pink to red in color.
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 AUC= 4.3 (1.2) mcg���h/mL; C= 0.5 (0.2) mcg/mL; T= 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. Cand Cremained essentially unchanged from day 2 through day 5 of therapy. 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 AUCfor the fitted concentration profile was comparable between the 5 day and 3 day regimens. Median azithromycin exposure (AUC) 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.<br/>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 Cby 23% but had no effect on AUC. When azithromycin suspension was administered with food to 28 adult healthy male subjects, Cincreased by 56% and AUC was unchanged. The AUC of azithromycin was unaffected by coadministration of an antacid containing aluminum and magnesium hydroxide with azithromycin capsules; however, the Cwas reduced by 24%. Administration of cimetidine (800 mg) two hours prior to azithromycin had no effect on azithromycin absorption.<br/>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 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.<br/>Metabolism: In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed.<br/>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.<br/>Special Populations:<br/>Drug-Drug Interactions: Drug interaction studies were performed with azithromycin and other drugs likely to be coadministered. The effects of coadministration 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. Coadministration 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 coadministered with azithromycin. Coadministration of azithromycin with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. Nelfinavir significantly increased the Cand AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2 (see PRECAUTIONS, Drug Interactions).<br/>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 USAGE section. 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<br/>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 couldaid the physician in selecting the most effective antimicrobial.<br/>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 4. 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.
Azithromycin for oral suspension is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic.
Azithromycin for oral suspension, USP after constitution contains a cherry flavored suspension. The dry powder before constitution is off-white to pinkish in color. The suspension after constitution is pink to red in color. Azithromycin for oral suspension, USP is supplied to provide 100 mg/5 mL or 200 mg/5 mL suspension in bottles as follows: 5 mL of constituted suspension of azithromycin for oral suspension USP, 100 mg/5 mL and 200 mg/5 mL, contains 6 mg of sodium. 100 mg/5 mL Bottle of 300 mg azithromycin contains 15 mL suspension when constituted with 9 mL of water. Each 5 mL suspension contains azithromycin monohydrate equivalent to 100 mg of azithromycin. 200 mg/5 mL Bottle of 600 mg azithromycin contains 15 mL suspension when constituted with 9 mL of water. Each 5 mL suspension contains azithromycin monohydrate equivalent to 200 mg of azithromycin. Bottle of 900 mg azithromycin contains 22.5 mL suspension when constituted with 12 mL of water. Each 5 mL suspension contains azithromycin monohydrate equivalent to 200 mg of azithromycin. Bottle of 1200 mg azithromycin contains 30 mL suspension when constituted with 15 mL of water. Each 5 mL suspension contains azithromycin monohydrate equivalent to 200 mg of azithromycin. See DOSAGE AND ADMINISTRATION for constitution instructions with each bottle type. Store dry powder at 20��to 25��C (68��to 77��F) [See USP Controlled Room Temperature]. Store constituted suspension at 5��to 30��C (41��to 86��F) and discard when full dosing is completed.
dailymed-ingredient:FD&C_Red_#40, dailymed-ingredient:arabic_gum, dailymed-ingredient:ethyl_vanillin, dailymed-ingredient:hydroxypropyl_cellulose, dailymed-ingredient:maltodextrin, dailymed-ingredient:sucrose, dailymed-ingredient:tribasic_sodium_phosphate_dodecahydrate, dailymed-ingredient:vanillin, dailymed-ingredient:xanthan_gum
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 torsade 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. Prescribing azithromycin for oral suspension 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.<br/>Information for Patients: Azithromycin tablets and azithromycin for oral suspension can be taken with or without food. Patients should also be cautioned not to take aluminum- and magnesium-containing antacids and azithromycin simultaneously. The patient should be directed to discontinue azithromycin immediately and contact a physician if any signs of an allergic reaction occur. Patients should be counseled that antibacterial drugs including azithromycin for oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When azithromycin for oral suspension is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by azithromycin for oral suspension or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.<br/>Drug Interactions: Coadministration of nelfinavir at steady state with a single oral dose of azithromycin resulted in increased azithromycin serum concentrations. Although a dose adjustment of azithromycin is not recommended when administered in combination with nelfinavir, close monitoring for known side effects of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted (see ADVERSE REACTIONS). Azithromycin did not affect the prothrombin time response to a single dose of warfarin. However, prudent medical practice dictates careful monitoring of prothrombin time in all patients treated with azithromycin and warfarin concomitantly. Concurrent use of macrolides and warfarin in clinical practice has been associated with increased anticoagulant effects. Drug interaction studies were performed with azithromycin and other drugs likely to be coadministered (see CLINICAL PHARMACOLOGY, Drug-Drug Interactions). When used in therapeutic doses, azithromycin had a modest effect on the pharmacokinetics of atorvastatin, carbamazepine, cetirizine, didanosine, efavirenz, fluconazole, indinavir, midazolam, rifabutin, sildenafil, theophylline (intravenous and oral), triazolam, trimethoprim/sulfamethoxazole or zidovudine. Coadministration with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. No dosage adjustment of either drug is recommended when azithromycin is coadministered with any of the above agents. Interactions with the drugs listed below have not been reported in clinical trials with azithromycin; however, no specific drug interaction studies have been performed to evaluate potential drug-drug interaction. Nonetheless, they have been observed with macrolide products. Until further data are developed regarding drug interactions when azithromycin and these drugs areused concomitantly, careful monitoring of patients is advised: Digoxin���elevated digoxin concentrations. Ergotamine or dihydroergotamine���acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia. Terfenadine, cyclosporine, hexobarbital and phenytoin concentrations.<br/>Laboratory Test Interactions: There are no reported laboratory test interactions.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. No evidence of impaired fertility due to azithromycin was found.<br/>Pregnancy:<br/>Teratogenic Effects:<br/>Nursing Mothers: It is not known whether azithromycin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when azithromycin is administered to a nursing woman.<br/>Pediatric Use: (See CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE, and DOSAGE AND ADMINISTRATION.)<br/>Acute Otitis Media (total dosage regimen: 30 mg/kg, see DOSAGE AND ADMINISTRATION): Safety and effectiveness in the treatment of pediatric patients with otitis media under 6 months of age have not been established.<br/>Acute Bacterial Sinusitis (dosage regimen: 10 mg/kg on Days 1 to 3): Safety and effectiveness in the treatment of pediatric patients with acute bacterial sinusitis under 6 months of age have not been established. Use of azithromycin for the treatment of acute bacterial sinusitis in pediatric patients (6 months of age or greater) is supported by adequate and well-controlled studies in adults,similar pathophysiology of acute sinusitis in adults and pediatric patients, and studies of acute otitis media in pediatric patients.<br/>Community-Acquired Pneumonia (dosage regimen: 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5): Safety and effectiveness in the treatment of pediatric patients with community-acquired pneumonia under 6 months of age have not been established. Safety and effectiveness for pneumonia due to Chlamydia pneumoniae and Mycoplasma pneumoniae were documented in pediatric clinical trials. Safety and effectiveness for pneumonia due to Haemophilus influenzae and Streptococcus pneumoniae were not documented bacteriologicallyin the pediatric clinical trial due to difficulty in obtaining specimens. Use of azithromycin for these two microorganisms is supported, however, by evidence from adequate and well-controlled studies in adults.<br/>Pharyngitis/Tonsillitis (dosage regimen: 12 mg/kg on Days 1 to 5): Safety and effectiveness in the treatment of pediatric patients with pharyngitis/tonsillitis under 2 years of age have not been established. Studies evaluating the use of repeated courses of therapy have not been conducted (see CLINICAL PHARMACOLOGY and ANIMAL TOXICOLOGY).<br/>Geriatric Use: Pharmacokinetic parameters in older volunteers (65 to 85 years old) were similar to those in younger volunteers (18 to 40 years old) for the 5 day therapeutic regimen. Dosage adjustment does not appear to be necessary for older patients with normal renal and hepatic function receiving treatment with this dosage regimen (see CLINICAL PHARMACOLOGY). In multiple-dose clinical trials of oral azithromycin, 9% of patients were at least 65 years of age (458/4949) and 3% of patients (144/4949) were at least 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Azithromycin for oral suspension, 100 mg/5 mL contains 6 mg of sodium per 5 mL of constituted solution. Azithromycin for oral suspension, 200 mg/5 mL contains 6 mg of sodium per 5 mL of constituted solution.
Azithromycin (Powder, For Suspension)
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 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, Pediatric Patients).<br/>Clinical:<br/>Adults:<br/>Pediatric Patients:<br/>Postmarketing Experience: Adverse events reported with azithromycin during the postmarketing period in adult and/or pediatric patients for which a causal relationship may not be established include: Allergic: Arthralgia, edema, urticaria and angioedema. Cardiovascular: Arrhythmias including ventricular tachycardia and hypotension. There have been rare reports of QT prolongation and torsade de pointes. Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea rarely resulting in dehydration, pseudomembranous colitis, pancreatitis, oral candidiasis and rare reports of tongue discoloration. General: Asthenia, paresthesia, fatigue, malaise and anaphylaxis (rarely fatal). Genitourinary: Interstitial nephritis and acute renal failure and vaginitis. Hematopoietic: Thrombocytopenia. Liver/Biliary: Abnormal liver function including hepatitis and cholestatic jaundice, as well as rare cases of hepatic necrosis and hepatic failure, some of which have resulted in death. Nervous System: Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation and syncope. Psychiatric: Aggressive reaction and anxiety. Skin/Appendages: Pruritus, rarely serious skin reactions including erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis. Special Senses: Hearing disturbances including hearing loss, deafness and/or tinnitus and reports of taste/smell perversion and/or loss.<br/>Laboratory Abnormalities:<br/>Adults: Clinically significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows: with an incidence of greater than 1%: decreased hemoglobin, hematocrit, lymphocytes, neutrophils and blood glucose; elevated serum creatine phosphokinase, potassium, ALT, GGT, AST, BUN, creatinine, blood glucose, platelet count, lymphocytes, neutrophils and eosinophils; with an incidence of less than 1%: leukopenia, neutropenia, decreased sodium, potassium, platelet count, elevated monocytes, basophils, bicarbonate, serum alkaline phosphatase, bilirubin, LDH and phosphate. The majority of subjects with elevated serum creatinine also had abnormal values at baseline. When follow-up was provided, changes in laboratory tests appeared to be reversible. In multiple-dose clinical trials involving more than 5000 patients, four patients discontinued therapy because of treatment-related liver enzyme abnormalities and one because of a renal function abnormality.<br/>Pediatric Patients:
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 isunknown 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.
Azithromycin for oral suspension 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.<br/>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 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. Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx. Because some strains are resistant to azithromycin, susceptibility tests should be performed when patients are treated with azithromycin. 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, 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 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 and other antibacterial drugs, azithromycin for oral suspension 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.<br/>Pediatric Patients: (See PRECAUTIONS, Pediatric Use and CLINICAL STUDIES, 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. Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx. Because some strains are resistant to azithromycin, susceptibility tests should be performed when patients are treated with azithromycin. 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 azithromycin may be initiated before results of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly.