Zithromax Information
Zithromax (Azithromycin)
Zithromax (Azithromycin) Description
Zithromax (Azithromycin) (azithromycin tablets and azithromycin for oral suspension) contain the active ingredient azithromycin, an azalide, a subclass of macrolide antibiotics, for oral administration. Azithromycin has the chemical name ()-13-[(2,6-dideoxy-3--methyl-3--methyl-α---hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β--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 CHNO, and its molecular weight is 749.00. Azithromycin has the following structural formula:
Azithromycin, as the dihydrate, is a white crystalline powder with a molecular formula of CHNO•2HO and a molecular weight of 785.0.
Zithromax (Azithromycin) is supplied for oral administration as film-coated, modified capsular shaped tablets containing azithromycin dihydrate equivalent to either 250 mg or 500 mg azithromycin and the following inactive ingredients: dibasic calcium phosphate anhydrous, pregelatinized starch, sodium croscarmellose, magnesium stearate, sodium lauryl sulfate, hypromellose, lactose, titanium dioxide, triacetin and D&C Red #30 aluminum lake.
Zithromax (Azithromycin) for oral suspension is supplied in bottles containing azithromycin dihydrate powder equivalent to 300 mg, 600 mg, 900 mg, or 1200 mg azithromycin per bottle and the following inactive ingredients: sucrose; sodium phosphate, tribasic, anhydrous; hydroxypropyl cellulose; xanthan gum; FD&C Red #40; and spray dried artificial cherry, creme de vanilla and banana flavors. After constitution, each 5 mL of suspension contains 100 mg or 200 mg of azithromycin.
Zithromax (Azithromycin) Clinical Pharmacology
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) µg∙h/mL; C= 0.5 (0.2) µg/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 (18–40 years of age) are portrayed in the chart below. C and C remained 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 2–5) or 3 days (500 mg per day for days 1–3). Due to limited serum samples on day 2 (3-day regimen) and days 2–4 (5-day regimen), the serum concentration-time profile of each subject was fit to a 3-compartment model and the AUC for 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.
Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered. The effects of co-administration 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.
Co-administration 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 co-administered with azithromycin.
Co-administration of azithromycin with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. Nelfinavir significantly increased the C and AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2. (See )
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 incubation techniques. Using such methodology, the ratio of intracellular to extracellular concentration was >30 after one hour incubation. 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 and in clinical infections as described in the section.
NOTE: Azithromycin demonstrates cross-resistance with erythromycin-resistant gram-positive strains. Most strains of and methicillin-resistant staphylococci are resistant to azithromycin.
Beta-lactamase production should have no effect on azithromycin activity.
The following data are available, .
At least 90% of the following microorganisms exhibit an 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
Zithromax (Azithromycin) Indications And Usage
Zithromax (Azithromycin) is indicated for the treatment of patients with mild to moderate infections (pneumonia: see ) caused by susceptible strains of the designated microorganisms in the specific conditions listed below. .
Community due to , , or 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:
Zithromax (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 Zithromax (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 Zithromax (Azithromycin) and other antibacterial drugs, Zithromax (Azithromycin) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
(See and .)
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:
Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its susceptibility to azithromycin. Therapy with Zithromax (Azithromycin) may be initiated before results of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly.
Zithromax (Azithromycin) Contraindications
Zithromax (Azithromycin) is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic. Zithromax (Azithromycin) is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.
Zithromax (Azithromycin) Warnings
Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Stevens Johnson Syndrome and toxic epidermal necrolysis have been reported rarely in patients on azithromycin therapy. Although rare, fatalities have been reported. (See .) Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms . 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 or 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).
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of , and surgical evaluation should be instituted as clinically indicated.
Zithromax (Azithromycin) Precautions
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
Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and , 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 Zithromax (Azithromycin) 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.
Zithromax (Azithromycin) tablets and 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 Zithromax (Azithromycin) should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Zithromax (Azithromycin) 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 Zithromax (Azithromycin) 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.
Co-administration 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 .)
Although, in a study of 22 healthy men, a 5-day course of azithromycin did not affect the prothrombin time from a subsequently administered dose of warfarin, spontaneous post-marketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants. Prothrombin times should be carefully monitored while patients are receiving azithromycin and oral anticoagulants concomitantly.
Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered. (See .) 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. Co-administration 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 are used concomitantly, careful monitoring of patients is advised:
(See and .)
Acute Otitis Media (total dosage regimen: 30 mg/kg, see ): Safety and effectiveness in the treatment of pediatric patients with otitis media under 6 months of age have not been established.
Acute Bacterial Sinusitis (dosage regimen: 10 mg/kg on Days 1–3): Safety and effectiveness in the treatment of pediatric patients with acute bacterial sinusitis under 6 months of age have not been established. Use of Zithromax (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.
Community-Acquired Pneumonia (dosage regimen: 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2–5): 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 and were documented in pediatric clinical trials. Safety and effectiveness for pneumonia due to and 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.
Pharyngitis/Tonsillitis (dosage regimen: 12 mg/kg on Days 1–5): Safety and effectiveness in the treatment of pediatric patients with pharyngitis/tonsillitis under 2 years of age have not been established.
Pharmacokinetic parameters in older volunteers (65–85 years old) were similar to those in younger volunteers (18–40 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 .)
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.
Zithromax (Azithromycin) 250 mg tablets contain 0.9 mg of sodium per tablet.
Zithromax (Azithromycin) 500 mg tablets contain 1.8 mg of sodium per tablet.
Zithromax (Azithromycin) for oral suspension 100 mg/5 mL contains 3.7 mg of sodium per 5 mL of constituted solution.
Zithromax (Azithromycin) for oral suspension 200 mg/5 mL contains 7.4 mg of sodium per 5 mL of constituted solution.
Zithromax (Azithromycin) Adverse Reactions
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 Zithromax (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 .) Most of the side effects leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. (See .)
Adverse events reported with azithromycin during the post-marketing period in adult and/or pediatric patients for which a causal relationship may not be established include:
Allergic:
Gastrointestinal:
General:
Genitourinary:
Hematopoietic:
Nervous System:
Psychiatric:
Skin/Appendages:
Special Senses:
Zithromax (Azithromycin) Dosage And Administration
Zithromax (Azithromycin) How Supplied
Zithromax (Azithromycin) 250 mg tablets are supplied as pink modified capsular shaped, engraved, film-coated tablets containing azithromycin dihydrate equivalent to 250 mg of azithromycin. Zithromax (Azithromycin) 250 mg tablets are engraved with "PFIZER" on one side and "306" on the other. These are packaged in bottles and blister cards of 6 tablets (Z-PAKS) as follows:
Zithromax (Azithromycin) 500 mg tablets are supplied as pink modified capsular shaped, engraved, film-coated tablets containing azithromycin dihydrate equivalent to 500 mg of azithromycin. Zithromax (Azithromycin) 500 mg tablets are engraved with "Pfizer" on one side and "ZTM500" on the other. These are packaged in bottles and blister cards of 3 tablets (TRI-PAKS™) as follows:
Zithromax (Azithromycin) tablets should be stored between 15° to 30°C (59° to 86°F).
Zithromax (Azithromycin) for oral suspension after constitution contains a flavored suspension. Zithromax (Azithromycin) for oral suspension is supplied to provide 100 mg/5 mL or 200 mg/5 mL suspension in bottles as follows:
See for constitution instructions with each bottle type.
Zithromax (Azithromycin) Clinical Studies
Zithromax (Azithromycin) Animal Toxicology
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/m, 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 value of 1.3 µg/mL (six times greater than the observed C of 0.216 µg/mL at the pediatric dose of 10 mg/kg). Similarly, it has been shown in the dog (10 mg/kg dose) at observed C value of 1.5 µg/mL (seven times greater than the observed same C and drug dose in the studied pediatric population). On a mg/m basis, 30 mg/kg dose in the neonatal rat (135 mg/m) and 10 mg/kg dose in the neonatal dog (79 mg/m) 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.
Zithromax (Azithromycin)
Zithromax (Azithromycin) Principal Display Panel - Mg - Tablet Bottle
Zithromax (Azithromycin) Principal Display Panel - Mg - Tablet Blister Pack
Costs less thanmost brand nameantibiotics
NDC 0069-3060-75
Z-PAK
A full course ofantibiotic therapyin 5 daily doses
Rx only
3 CARDS x 6 TABLETS
Zithromax (Azithromycin) Principal Display Panel - Mg - Tablet Unit Dose Box
For in-institution use only
Zithromax (Azithromycin) Principal Display Panel - Mg - Tablet Bottle
Zithromax (Azithromycin) Principal Display Panel - Mg - Blister Card
PFIZER LABSDIV OF PFIZER INC, NY, NY 10017
Zithromax (Azithromycin) Principal Display Panel - Mg - Tablet Unit Dose Box
For in-institution use only
Zithromax (Azithromycin) Principal Display Panel - Mg Bottle
Zithromax (Azithromycin) Principal Display Panel - Mg Bottle
Zithromax (Azithromycin) Principal Display Panel - Mg Bottle
Zithromax (Azithromycin) Principal Display Panel - Mg Bottle
