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ZITHROMAX™
Pfizer
Azithromycin Dihydrate
Antibiotic
 
Action And Clinical Pharmacology: Azithromycin, a macrolide antibiotic of the azalide subclass, exerts its antibacterial action by binding to the 50s ribosomal subunits of susceptible bacteria and suppressing protein synthesis.

Following oral administration, azithromycin is rapidly absorbed (Tmax = 2 to 3 hours) and distributed widely throughout the body. Rapid movement of azithromycin from blood into tissue results in significantly higher azithromycin concentrations in tissue than in plasma (up to 50 times the maximum observed concentration in plasma). The absolute bioavailability is approximately 37%.

When azithromycin capsules were administered with food to 11 adult healthy male subjects, the rate of absorption (Cmax) of azithromycin from the capsule formulation was reduced by 52% and the extent of absorption (AUC) by 43%. However, when azithromycin suspension was administered with food to 28 adult healthy male subjects, the rate of absorption (Cmax) was increased by 56% while the extent of absorption (AUC) was unchanged. Therefore, azithromycin capsules and powder for oral suspension should be given 1 hour before or 2 hours after a meal.

Food does not affect the absorption of azithromycin in the tablet and the Single Dose 1 g Packet dosage forms. Unlike the capsule and powder for oral suspension, azithromycin tablets and the azithromycin Single Dose 1 g Packet can be taken without regard to meals. Azithromycin tablets are bioequivalent to the capsule formulation; the azithromycin oral suspension as a Single Dose 1 g Packet is bioequivalent to four 250 mg capsules or tablets.

Pharmacokinetics: Adults: Plasma concentrations of azithromycin decline in a polyphasic pattern, resulting in an average terminal half-life of 68 hours. The prolonged half-life is likely due to extensive uptake and subsequent release of drug from tissues. Over the dose range of 250 to 1 000 mg orally, the serum concentrations are related to dose. The long tissue half-life and large volume of distribution result from intracytoplasmic uptake and storage in lysosomal phospholipid complexes.

When studied in healthy elderly subjects from age 65 to 85 years, the pharmacokinetic parameters of azithromycin capsules in elderly men were similar to those in young adults; however, in elderly women, although higher peak concentrations (increased by 30 to 50%) were observed, no significant accumulation occurred. There are no pharmacokinetic data available from studies in hepatically or renally impaired individuals.

Biliary excretion of azithromycin, predominantly as unchanged drug, is a main route of elimination.

Children: Table II shows mean pharmacokinetic parameters on day 5 in children 1 to 5 years and 5 to 15 years of age when azithromycin oral suspension was dosed in the absence of food at 10 mg/kg on day 1 and 5 mg/kg on days 2 to 5.

There are no pharmacokinetic data on azithromycin suspension when administered at a dose of 12 mg/kg/day in the presence or absence of food.

Indications And Clinical Uses: For treatment of mild to moderate infections caused by susceptible strains of the designated microorganisms in the following diseases and specific conditions. As recommended dosages, durations of therapy, and applicable patient populations vary among these infections, see Dosage for specific dosing recommendations.

Adults: Upper Respiratory Tract: Pharyngitis and tonsillitis caused by S. pyogenes (group A beta-hemolytic streptococci) occurring in individuals who cannot use first line therapy.

Note: Penicillin is the usual drug of choice in the treatment of S. pyogenes pharyngitis, including the prophylaxis of rheumatic fever. Azithromycin is often effective in the eradication of susceptible strains of streptococci from the oropharynx. However, data establishing the efficacy of azithromycin in the subsequent prevention of rheumatic fever are not available at present.

Lower Respiratory Tract: Acute bacterial exacerbations of chronic obstructive pulmonary diseases caused by H. influenzae, M. catarrhalis, or S. pneumoniae. Community-acquired pneumonia caused by S. pneumoniae, H. influenzae, M. pneumoniae or C. pneumoniae in patients for whom oral therapy is appropriate.

Skin and Skin Structure: Uncomplicated skin and skin structure infections caused by S. aureus, S. pyogenes or S. agalactiae.

Genitourinary Tract: Urethritis and cervicitis due to N. gonorrhoeae or C. trachomatis. Genital ulcer disease in men due to H. 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.

Patients 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 initiated 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, antibiotic treatment should be adjusted accordingly.

Prevention of Disseminated M. Avium Complex (MAC) Disease: Azithromycin, taken at a dose of 1 200 mg weekly, alone or in combination with rifabutin at its approved dose, is indicated for the prevention of disseminated M. avium complex (MAC) disease in persons with advanced HIV infections.

Children (see Precautions and Dosage): Acute otitis media caused by H. influenzae (beta-lactamase positive and negative strains), M. catarrhalis or S. pneumoniae. (For specific dosage recommendation, see Dosage.)

Pharyngitis and tonsillitis caused by S. pyogenes (group A beta-hemolytic streptococci) occurring in individuals who cannot use first line therapy. (For specific dosage recommendation, see Dosage.)

Note: Penicillin is the usual drug of choice in the treatment of S. pyogenes pharyngitis, including the prophylaxis of rheumatic fever. Azithromycin is often effective in the eradication of susceptible strains of streptococci from the oropharynx. However, data establishing the efficacy of azithromycin in the subsequent prevention of rheumatic fever are not available at present.

Community-acquired pneumonia caused by Haemophilus influenzae, S. pneumoniae, M. pneumoniae or C. pneumoniae. (For specific dosage recommendation, see Dosage.)

Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for outpatient oral therapy because of moderate to severe illness.

Safety and effectiveness for pneumonia due to H. influenzae and S. pneumoniae were not documented bacteriologically in 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.

Clinical Studies in Pediatric Patients: From the perspective of evaluating pediatric clinical trials, because of the extended half-life of azithromycin, days 11 to 14 were considered on-therapy evaluations and are provided for clinical guidance. Day 30 evaluations were considered the primary test of cure endpoint. For patients with community-acquired pneumonia, Days 15 to 19 were considered as on-therapy evaluations. Days 28 to 42 were the cure endpoint.

Otitis Media: Efficacy Protocol 1: In a double-blind, controlled clinical study of acute otitis media performed in North America, azithromycin (10 mg/kg on day 1 followed by 5 mg/kg on days 2 to 5) was compared to an antimicrobial/beta-lactamase inhibitor. 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 528 patients who were evaluated at the day 30 visit, the clinical success rate was 76% for azithromycin and 76% for the control agent.

Efficacy Protocol 2: In a noncomparative clinical and microbiologic trial performed in North America, and in which significant numbers of beta-lactamase producing organisms were identified (35%), the combined clinical success rate (i.e., cure plus improvement) was 84% at the day 11 visit (n=131) and 70% at the day 30 visit (n=122).

Microbiologic determinations were made at the pretreatment 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 (see Table III).

Pharyngitis and Tonsillitis: In 3 double-blind North American controlled studies, 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 beta-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 patients with documented GABHS). See Table IV.

Approximately 1% of azithromycin-susceptible S. pyogenes isolates were resistant to azithromycin following therapy.

Note: Penicillin is the usual drug of choice in the treatment of S. pyogenes pharyngitis, including the prophylaxis of rheumatic fever. Azithromycin is often effective in the eradication of susceptible strains of streptococci from the oropharynx. However, data establishing the efficacy of azithromycin in the subsequent prevention of rheumatic fever are not available at present.

Appropriate culture and susceptibility tests should be initiated 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, antibiotic treatment should be adjusted accordingly.

Contra-Indications: In patients with known hypersensitivity to azithromycin, erythromycin, or other macrolide antibacterial agents. tag_WarningWarnings

Manufacturers' Warnings In Clinical States: Rare serious allergic reactions, including angioedema and anaphylaxis (with rare reports of fatalities) have been reported in patients on azithromycin therapy (see Contraindications). Allergic reactions may occur during and soon after treatment with azithromycin. 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. 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 C. pneumoniae, H. influenzae, M. pneumoniae, or S. 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).

Pseudomembranous colitis has been reported with nearly all antibacterial agents including azithromycin and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by C. difficile is a primary cause of "antibiotic-associated colitis". After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile.

In the absence of data on the metabolism and pharmacokinetics in patients with lysosomal lipid storage diseases (e.g., Tay-Sachs disease, Niemann-Pick disease) the use of azithromycin in these patients is not recommended.

Precautions: General: Since liver is the major route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic disease.

No dose adjustment is needed in patients with mild renal impairment (creatinine clearance >40 mL/min), but there are no data regarding azithromycin usage in patients with more severe renal impairment. Thus caution should be exercised before prescribing azithromycin in these patients.

The following adverse events have been reported with macrolide products: ventricular arrhythmias, including ventricular tachycardia and torsades de pointes, in individuals with prolonged QT intervals. Although these adverse events have not been reported in clinical trials with azithromycin, one AIDS patient dosed at 750 mg to 1 g daily experienced prolonged QT interval and torsades de pointes.

Pregnancy: Animal studies have demonstrated that azithromycin crosses the placenta. Safety of azithromycin for use in human pregnancy has not been established.

Lactation: There are no data on secretion in breast milk. Safety of azithromycin for use in human lactation has not been established.

Children: Acute Otitis Media or Community-Acquired Pneumonia: Safety and efficacy of azithromycin in the treatment of children with acute otitis media or community-acquired pneumonia (dosage regimen: 10 mg/kg on day 1 followed by 5 mg/kg on days 2 to 5) under 6 months of age have not been established.

Pharyngitis and Tonsillitis: Safety and efficacy of azithromycin in the treatment of children with pharyngitis and tonsillitis (dosage regimen: 12 mg/kg on days 1 to 5) under 2 years of age have not been established.

Studies evaluating the use of repeated courses of therapy have not been conducted. Safety data with the use of azithromycin at doses higher than proposed and for durations longer than recommended are limited to a small number of immunocompromised children who underwent chronic treatment.

In animal studies, treatment with azithromycin is associated with accumulation in various tissues, including the extracranial neural ganglia (i.e., retina and sympathetic nervous system). Tissue accumulation is both dose and time dependent, and is associated microscopically with the development of phospholipidosis (intra-lysosomal drug phospholipid complexes). The only evidence in animals that azithromycin is associated with alterations of intracellular phospholipid metabolism has been the documentation of small increases in phospholipid content after prolonged treatment (6 months) or exaggerated doses. Phospholipidosis has been observed at total cumulative doses only 2 multiples of the clinical dose. One month after withdrawal of treatment the concentration of azithromycin and the presence of phospholipidosis in tissue, including the retina, is at or near predose levels.

No data exist in humans in regard to the extent of accumulation, duration of exposure, metabolism or excretory mechanisms of azithromycin in neural tissue such as the retina and the cochlea. Rare cases of hearing loss have been reported (see Adverse Effects).

No data are available on the metabolism and pharmacokinetics of azithromycin in children with lysosomal lipid storage diseases (see Warnings).

Prevention of Disseminated M. Avium Complex (MAC) Disease: Safety and efficacy of azithromycin for the prevention of MAC in children have not been established. Limited safety data are available for 24 children 5 months to 14 years of age (mean 4.6 years) who received azithromycin for treatment of opportunistic infections. The mean duration of therapy was 186.7 days (range 13 to 710 days) at doses of <5 to 20 mg/kg/day. Adverse events were similar to those observed in the adult population, most of which involved the gastrointestinal tract. While none of these children prematurely discontinued treatment due to a side effect, one child discontinued due to a laboratory abnormality (eosinophilia). Based on available pediatric pharmacokinetic data, a dose of 20 mg/kg in children would provide drug exposure similar to the 1 200 mg adult dose but with a higher Cmax.

Geriatrics: The pharmacokinetics in elderly volunteers (age 65 to 85) were similar to those in younger volunteers (age 18 to 40) for the 5-day therapeutic regimen. Dosage adjustment does not appear to be necessary for elderly patients with normal renal and hepatic function receiving treatment with this dosage regimen.

Drug Interactions: Antacids: Aluminum and magnesium containing antacids (Maalox) reduce the peak serum levels but not the extent of azithromycin absorption. These drugs should not be taken simultaneously.

Cimetidine: Administration of cimetidine (800 mg) 2 hours prior to azithromycin had no effect on azithromycin absorption.

Theophylline: Concurrent use of macrolides and theophylline has been associated with increases in the serum concentrations of theophylline. Azithromycin did not affect the pharmacokinetics of theophylline administered either as a single i.v. infusion or multiple oral doses at a recommended dose of 300 mg every 12 hours. There is 1 postmarketing report of supraventricular tachycardia associated with an elevated theophylline serum level that developed soon after initiation of treatment with azithromycin. Until further data are available, prudent medical practice dictates careful monitoring of plasma theophylline levels in patients receiving azithromycin and theophylline concomitantly.

Warfarin: 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.

Zidovudine: Single 1 g doses and multiple 1 200 mg or 600 mg doses of azithromycin did not affect the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentrations of phosphorylated zidovudine in peripheral blood mononuclear cells.

Didanosine: Daily doses of 1 200 mg azithromycin had no effect on the pharmacokinetics of didanosine.

Rifabutin: Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either drug.

Carbamazepine: In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of carbamazepine or its active metabolite in patients receiving concomitant azithromycin.

Concomitant Therapy: The following drug interactions have not been reported in clinical trials with azithromycin and no specific drug interaction studies have been performed to evaluate potential drug-drug interactions. Nonetheless, they have been observed with macrolide products, and there have been rare spontaneously reported cases with azithromycin and some of these drugs, in postmarketing experience. Until further data are developed regarding drug interactions, when azithromycin and these drugs are used concomitantly, careful monitoring of patients is advised both during and for a short period following therapy:

Digoxin: Elevation of digoxin levels.

Disopyramide: Increase in pharmacological effects.

Ergotamine or Dihydroergotamine: Acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.

Triazolam: Decreases in the clearance of triazolam and increases in the pharmacologic effect of triazolam.

Drugs Metabolized by the Cytochrome P450 System: Elevations of serum cyclosporine, hexobarbital, cisapride, and phenytoin levels.

Antihistamines: Prolongation of QT intervals, palpitations or cardiac arrhythmias with concomitant administration of astemizole or terfenadine.

No data are available on the concomitant clinical use of azithromycin and gentamicin or other amphophilic drugs which have been reported to alter intracellular lipid metabolism.

Adverse Reactions: The majority of side effects observed in controlled clinical trials involving patients (adults and children) treated with azithromycin were of a mild and transient nature. Approximately 0.7% of both adult patients (n=3 812) and children (n=2 878) who had multiple doses of azithromycin discontinued therapy because of drug related side effects. Most of the side effects leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea or abdominal pain. Potentially serious side effects including angioedema and cholestatic jaundice occurred in less than 1% of patients.

Clinical: Multiple-Dose Regimen (Adults and Children): In adult patients, the most common side effects in patients receiving the multiple-dose regimen of azithromycin were related to the gastrointestinal system with diarrhea (4.3%), abdominal pain (2.6%), vomiting (1.3%) and nausea (3.5%). In children (n=1 944) enrolled in North American controlled clinical trials in acute otitis media and S. pyogenes pharyngitis, the type of side effects was comparable to that seen in adults, with diarrhea/loose stools (5.3%), vomiting (3.6%), abdominal pain (2.6%), nausea (1%), rash (1%) and headache (1%) the most frequently reported.

Different side effect incidence rates for the 2 dosage regimens recommended in children were observed:

Acute Otitis Media: For the recommended dosage regimen of 10 mg/kg on day 1 followed by 5 mg/kg on days 2 to 5, the most frequent side effects were diarrhea/loose stools (2%), abdominal pain (2%), vomiting (1%) and nausea (1%).

Community-Acquired Pneumonia: In the North American controlled clinical trial in community-acquired pneumonia in children (n=310) the following were the most frequent side effects for the recommended dosage regimen of 10 mg/kg on day 1 followed by 5 mg/kg on days 2 to 5: diarrhea/loose stools (6%), abdominal pain (2%), and vomiting (2%).

Pharyngitis/Tonsillitis: For the recommended dosage regimen of 12 mg/kg on days 1 to 5, the most frequent side effects were diarrhea/loose stools (6%), vomiting (5%), abdominal pain (3%), nausea (2%) and headache (1%).

Side effects that occurred with a frequency of 1% or less in patients included the following.

Cardiovascular: palpitations, chest pain.

Gastrointestinal: dyspepsia, flatulence, vomiting, melena, cholestatic jaundice, constipation, anorexia and gastritis.

Genitourinary: monilia, vaginitis and nephritis.

Nervous System: dizziness, headache, vertigo, somnolence, agitation, nervousness, insomnia and hyperkinesia.

General: fatigue, fever and malaise.

Allergic: rash, photosensitivity, angioedema, erythema multiforme, pruritus and urticaria.

Single 1 g Dose Regimen (Adults): In adult patients (n=904), side effects that occurred on the single 1 g dosing regimen of azithromycin with a frequency greater than 1% included diarrhea (6.1%), nausea (4.9%), abdominal pain (4.9%), vomiting (1.7%), vaginitis (1.3%), loose stools (1.2%), and dyspepsia (1.1%).

Single 2 g Dose Regimen (Adults): Overall, the most common side effects in patients receiving a single 2 g dose of azithromycin were related to the gastrointestinal system. Side effects that occurred in patients in this study with a frequency of a 1% or greater included nausea (18.2%), diarrhea/loose stools (13.8%), vomiting (6.7%), abdominal pain (6.7%), vaginitis (2.2%), dyspepsia (1.1%), and dizziness (1.3%). The majority of these complaints were mild in nature.

The following adverse experiences have been reported in patients under conditions (e.g., open trials, marketing experience) where a causal relationship is uncertain or in patients treated with significantly higher than the recommended doses for prolonged periods:

Allergic: arthralgia, edema, anaphylaxis (with rare reports of fatalities), serum sickness, urticaria, vasculitis.

Cardiovascular: cardiac arrythmias (including ventricular tachycardia), palpitations.

Gastrointestinal: anorexia, constipation, dehydration, dyspepsia, flatulence, pancreatitis, pseudomembranous colitis.

General: asthenia, paresthesia, muscle pain.

Genitourinary: interstitial nephritis, acute renal failure, nephrotic syndrome.

Liver/Biliary: abnormal liver function including drug-induced hepatitis and cholestatic jaundice, hepatic necrosis.

Nervous System: dizziness, headache, seizure, somnolence.

Skin/Appendages: serious skin reactions including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Special Senses: hearing disturbances including hearing loss, deafness and/or tinnitus, vertigo, reports of taste disturbance.

Prevention of M. Avium Complex (MAC) Disease: Chronic therapy with azithromycin 1 200 mg weekly regimen: The nature of side effects seen with the 1 200 mg weekly dosing regimen for the prevention of M. avium complex infection in severely immunocompromised HIV-infected patients were similar to those seen with short-term dosing regimens

Side effects related to the gastrointestinal tract were seen more frequently in patients receiving azithromycin than in those receiving placebo or rifabutin. In one of the studies, 86% of diarrheal episodes were mild to moderate in nature with discontinuation of therapy for this reason occurring in only 9/233 (3.8%) of patients.

Laboratory Abnormalities: Adults: Significant abnormalities (irrespective of drug relationship) occurring during the clinical trials in patients were reported as follows:

With an incidence of 1 to 2%, elevated serum creatine phosphokinase, potassium, ALT, GGT and AST.

With an incidence of less than 1%, leukopenia, neutropenia, decreased platelet count, elevated serum alkaline phosphatase, bilirubin, BUN, creatinine, blood glucose, LDH and phosphate.

When follow-up was provided, changes in laboratory tests appeared to be reversible.

In multiple-dose clinical trials involving more than 3 000 patients, 3 patients discontinued therapy because of treatment-related liver enzyme abnormalities and 1 because of a renal function abnormality.

Prevention of M. Avium Complex (MAC) Disease: In these immunocompromised patients with advanced HIV infection, it was sometimes necessary to assess laboratory abnormalities developing on study with additional criteria if baseline values were outside the normal range. See Table VI.

In a phase I drug interaction study performed in normal volunteers, 1 of 6 subjects given the combination of azithromycin and rifabutin, 1 of 7 given rifabutin alone and 0 of 6 given azithromycin alone developed a clinically significant neutropenia (<500 cells/mm.

Children: Significant abnormalities (irrespective of drug relationship) occurring during clinical trials were all reported at a frequency of less than 1%, but were similar in type to the adult pattern.

In multiple-dose clinical trials involving almost 3 000 pediatric patients, no patients discontinued therapy because of treatment-related abnormalities.

Symptoms And Treatment Of Overdose: Symptoms: There are no data on overdosage. tag_Treatment

Treatment: Gastric lavage and general supportive measures are indicated.

Up to 15 g cumulative dose of azithromycin over 10 days has been administered in clinical trials without apparent adverse effect.

Dosage And Administration: Adults: Capsules: The capsules should be given as a single daily dose at least 1 hour before or 2 hours after a meal.

Tablets: The tablets can be taken with or without food.

Single Dose 1 g Packet: The powder for oral suspension as Single Dose 1 g Packet can be taken with or without food after reconstitution.

Mixing Directions: Directions for administration of the powder for oral suspension as a Single Dose Packet (1 g): The entire contents of the Packet should be mixed thoroughly with 60 mL of water. Drink the entire contents immediately, add an additional 60 mL of water, mix, and drink to assure complete consumption of dosage.

Skin and Skin Structure Infections, Upper and Lower Respiratory Tract Infections: The recommended dose for the treatment of individuals 16 years of age and older is 500 mg as a single dose on the first day followed by 250 mg once daily on days 2 through 5 for a total dose of 1.5 g.

Genitourinary: The recommended dose for the treatment of genital ulcer disease due to H. ducreyi (chancroid) and non-gonococcal urethritis and cervicitis due to C. trachomatis is: a single 1 g (1 000 mg) oral dose. This dose can be administered as four 250 mg capsules, four 250 mg tablets, or as 1 Single Dose Packet (1 g).

The recommended dose for the treatment of urethritis and cervicitis due to N. gonorrhoeae is: a single 2 g (2 000 mg) dose. This dose can be administered as eight 250 mg capsules, eight 250 mg tablets, or as 2 Single Dose Packets (1 g each).

Prevention of Disseminated M. Avium Complex (MAC) Disease: Tablets: The tablets may be taken without regard to food. The recommended dose is 1 200 mg (two 600 mg tablets) taken once weekly. This dose may be continued with the approved dosage regimen of rifabutin.

In patients with mild to moderate hepatic impairment, there is no evidence of a marked change in serum pharmacokinetics of azithromycin compared to those with normal hepatic function. In these patients urinary recovery of azithromycin appears to increase. Hence no dose adjustment is recommended for patients with mild to moderate hepatic impairment. Nonetheless, since the liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic disease.

Children: Powder for Oral Suspension: Should be given as a single daily dose at least 1 hour before or 2 hours after a meal.

Mixing Directions: Powder for Oral Suspension: Tap bottle to loosen powder. Add the directed volume of water. Shake well before each use. Oversized bottle provides shake space. Keep tightly closed. Table VII indicates the volume of water to be used for reconstitution.

Acute Otitis Media or Community-Acquired Pneumonia: The recommended dose of oral suspension for the treatment of children with acute otitis media or community-acquired pneumonia is 10 mg/kg as a single-dose on the first day (not to exceed 500 mg/day) followed by 5 mg/kg on days 2 through 5 (not to exceed 250 mg/day), for a total dose of 30 mg/kg (see Table VIII).

Pharyngitis and Tonsillitis: The recommended dose for children with pharyngitis and tonsillitis is 12 mg/kg once a day (not to exceed 500 mg/day) for 5 days for a total dose of 60 mg/kg (see Table IX).

SuppliedSupplied: Capsules: 250 mg: Each red, No. 0 hard gelatin capsule, imprinted with "Pfizer" and "ZITHROMAX" in black ink, contains: azithromycin dihydrate equivalent to azithromycin 250 mg. Nonmedicinal ingredients: cornstarch, lactose, magnesium stearate and sodium lauryl sulfate; capsule shell: FD&C Red #40, gelatin and titanium dioxide. White plastic (high density polyethylene) bottles of 30 and 100. Single treatment package (Z-Pak) of 6 blister packaged capsules per box. Store at controlled room temperature between 15 to 30°C.

Powder for Oral Suspension: After reconstitution, each bottle of cherry-flavored suspension contains: azithromycin dihydrate equivalent to: 300 mg/15 mL (100 mg/5 mL); 600 mg/15 mL (200 mg/5 mL); or 900 mg/22.5 mL (200 mg/5 mL). Nonmedicinal ingredients: artificial flavors, FD&C Red #40, sodium phosphate, sucrose, tribasic hydroxypropyl cellulose and xanthan gum. A graduated syringe is included in the package. Dry powder: Store at controlled room temperature (15 to 30°C). Reconstituted suspension: Store between 5 and 30°C. Discard unused portion after 10 days.

Tablets: 250 mg: Each pink, film-coated, modified capsular-shaped tablet engraved "Pfizer" on the upper face, and scored on the lower face, contains: azithromycin dihydrate equivalent to azithromycin 250 mg. Nonmedicinal ingredients: anhydrous calcium phosphate dibasic, D&C Red #30 aluminum lake, hydroxypropyl methylcellulose, lactose, magnesium stearate, pregelatinized starch, sodium croscarmellose, sodium lauryl sulfate, titanium dioxide and triacetin. White plastic (high density polyethylene) bottles of 30 and 100. Single treatment package (Z-pak) of 6 blister packaged tablets per box. Store at controlled room temperature between 15 and 30°C.

600 mg: Each white, film-coated, capsular-shaped tablet engraved "Pfizer" on the upper face, and scored on the lower face, contains: azithromycin dihydrate equivalent to azithromycin 600 mg. Nonmedicinal ingredients: anhydrous calcium phosphate dibasic, hydroxypropylmethylcellulose, lactose, magnesium stearate, pregelatinized starch, sodium croscarmellose, sodium lauryl sulfate, titanium dioxide and triacetin. White plastic (high density polyethylene) bottles of 30 and 100. Store at controlled room temperature between 15 and 30°C.

Single Dose 1 g Packet: Each sealed, laminated aluminum foil and polyethylene pouch contains: azithromycin dihydrate equivalent to 1 000 mg azithromycin. Nonmedicinal ingredients: artificial banana and cherry flavors, colloidal silicon dioxide, sodium phosphate tribasic and sucrose. Store at controlled room temperature between 15 and 30°C.