Azithromycin (Azithromycin) tablets, USP contain the active ingredient Azithromycin (Azithromycin) , an azalide, a subclass of macrolide antibiotics, for oral administration. Azithromycin (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 (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. Azithromycin (Azithromycin) has the following structural formula:

Azithromycin (Azithromycin) , as the monohydrate, is a white crystalline powder with a molecular formula of CHNO•HO and a molecular weight of 767.02.

Each Azithromycin (Azithromycin) tablet, USP, intended for oral administration, contains Azithromycin (Azithromycin) monohydrate equivalent to 600 mg of Azithromycin (Azithromycin) . In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, lecithin, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, pregelatinized starch, sodium lauryl sulfate, sodium starch glycolate, talc, titanium dioxide and xanthan gum.

Following oral administration, Azithromycin (Azithromycin) is rapidly absorbed and widely distributed throughout the body. Rapid distribution of Azithromycin (Azithromycin) into tissues and high concentration within cells result in significantly higher Azithromycin (Azithromycin) concentrations in tissues than in plasma or serum.

The pharmacokinetic parameters of Azithromycin (Azithromycin) in plasma after dosing as per labeled recommendations in healthy young adults and asymptomatic HIV-seropositive adults (age 18 to 40 years old) are portrayed in the following chart:

In these studies (500 mg Day 1, 250 mg Days 2 to 5), there was no significant difference in the disposition of Azithromycin (Azithromycin) between male and female subjects. Plasma concentrations of Azithromycin (Azithromycin) following single 500 mg oral and i.v. doses declined in a polyphasic pattern resulting in an average terminal half-life of 68 hours. With a regimen of 500 mg on Day 1 and 250 mg/day on Days 2 to 5, C and C remained essentially unchanged from Day 2 through Day 5 of therapy. However, without a loading dose, Azithromycin (Azithromycin) C levels required 5 to 7 days to reach steady-state.

In asymptomatic HIV-seropositive adult subjects receiving Azithromycin (Azithromycin) tablets 600 mg once daily for 22 days, steady state Azithromycin (Azithromycin) serum levels were achieved by Day 15 of dosing.

When Azithromycin (Azithromycin) capsules were administered with food, the rate of absorption (C) of Azithromycin (Azithromycin) was reduced by 52% and the extent of absorption (AUC) by 43%.

When the oral suspension of Azithromycin (Azithromycin) was administered with food, the C increased by 46% and the AUC by 14%.

The absolute bioavailability of two 600 mg tablets was 34% (CV=56%). Administration of two 600 mg tablets with food increased C by 31% (CV=43%) while the extent of absorption (AUC) was unchanged (mean ratio of AUCs=1.00; CV=55%).

The AUC of Azithromycin (Azithromycin) in 250 mg capsules was unaffected by coadministration of an antacid containing aluminum and magnesium hydroxide with Azithromycin (Azithromycin) ; however, the C was reduced by 24%. Administration of cimetidine (800 mg) two hours prior to Azithromycin (Azithromycin) had no effect on Azithromycin (Azithromycin) absorption.

When studied in healthy elderly subjects from age 65 to 85 years, the pharmacokinetic parameters of Azithromycin (Azithromycin) (500 mg Day 1, 250 mg Days 2 to 5) 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.

The high values in adults for apparent steady-state volume of distribution (31.1 L/kg) and plasma clearance (630 mL/min) suggest that the prolonged half-life is due to extensive uptake and subsequent release of drug from tissues. Selected tissue (or fluid) concentration and tissue (or fluid) to plasma/serum concentration ratios are shown in the following table:

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 (Azithromycin) treatment of infections in these additional body sites, the clinical significance 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.

Following oral administration of a single 1200 mg dose (two tablets of 600 mg), the mean maximum concentration in peripheral leukocytes was 140 mcg/mL. Concentrations remained above 32 mcg/mL for approximately 60 hr. The mean half-lives for 6 males and 6 females were 34 hr and 57 hr, respectively. Leukocyte to plasma C ratios for males and females were 258 (± 77%) and 175 (± 60%), respectively, and the AUC ratios were 804 (± 31%) and 541 (± 28%), respectively. The clinical relevance of these findings is unknown.

Following oral administration of multiple daily doses of 600 mg (1 tablet/day) to asymptomatic HIV-seropositive adults, mean maximum concentration in peripheral leukocytes was 252 mcg/mL (± 49%). Trough concentrations in peripheral leukocytes at steady-state averaged 146 mcg/mL (± 33%). The mean leukocyte to serum C ratio was 456 (± 38%) and the mean leukocyte to serum AUC ratio was 816 (± 31%). The clinical relevance of these findings is unknown.

The serum protein binding of Azithromycin (Azithromycin) is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL. Biliary excretion of Azithromycin (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.

The pharmacokinetics of Azithromycin (Azithromycin) in subjects with hepatic impairment has not been established.

The effect of Azithromycin (Azithromycin) on the plasma levels or pharmacokinetics of theophylline administered in multiple doses adequate to reach therapeutic steady-state plasma levels is not known. (See .)

Azithromycin (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 (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.

The potency of Azithromycin (Azithromycin) is markedly affected by the pH of the microbiological growth medium during incubation. Incubation in a 10% CO atmosphere will result in lowering of media pH (7.2 to 6.6) within 18 hours and in an apparent reduction of the potency of Azithromycin (Azithromycin) . Thus, the initial pH of the growth medium should be 7.2 to 7.4, and the CO content of the incubation atmosphere should be as low as practical.

Azithromycin (Azithromycin) can be solubilized for susceptibility testing by dissolving in a minimum amount of 95% ethanol and diluting to working concentration with water.

Azithromycin (Azithromycin) has demonstrated activity against complex (MAC) organisms. While gene probe techniques may be used to distinguish between and many studies only reported results on complex (MAC) isolates. Azithromycin (Azithromycin) has also been shown to be active against phagocytized complex (MAC) organisms in mouse and human macrophage cell cultures as well as in the beige mouse infection model.

Various methodologies employing broth or solid media at different pHs, with and without oleic acid-albumin dextrose-catalase (OADC), have been used to determine Azithromycin (Azithromycin) MIC values for complex strains. In general, Azithromycin (Azithromycin) MIC values decreased 4 to 8 fold as the pH of Middlebrook 7H11 agar media increased from 6.6 to 7.4. At pH 7.4, Azithromycin (Azithromycin) MIC values determined with Mueller-Hinton agar were 4 fold higher than that observed with Middlebrook 7H12 media at the same pH. Utilization of oleic acid-albumin-dextrose-catalase (OADC) in these assays has been shown to further alter MIC values. The relationship between Azithromycin (Azithromycin) and clarithromycin MIC values has not been established. In general, Azithromycin (Azithromycin) MIC values were observed to be 2 to 32 fold higher than clarithromycin independent of the susceptibility method employed.

The ability to correlate MIC values and plasma drug levels is difficult as Azithromycin (Azithromycin) concentrates in macrophages and tissues. (See .)

The disk diffusion techniques and dilution methods for susceptibility testing against Gram-positive and Gram-negative bacteria should not be used for determining Azithromycin (Azithromycin) MIC values against mycobacteria. susceptibility testing methods and diagnostic products currently available for determining minimal inhibitory concentration (MIC) values against complex (MAC) organisms have not been standardized or validated. Azithromycin (Azithromycin) MIC values will vary depending on the susceptibility testing method employed, composition and pH of media and the utilization of nutritional supplements. Breakpoints to determine whether clinical isolates of or are susceptible or resistant to Azithromycin (Azithromycin) have not been established.

The clinical relevance of Azithromycin (Azithromycin) susceptibility test results for other mycobacterial species, including using any susceptibility testing method has not been determined.

Azithromycin (Azithromycin) tablets, USP are 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.

Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its susceptibility to Azithromycin (Azithromycin) . Therapy with Azithromycin (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 (Azithromycin) and other antibacterial drugs, Azithromycin (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.

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

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 (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 (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.

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.

Because Azithromycin (Azithromycin) is principally eliminated via the liver, caution should be exercised when Azithromycin (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 (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 (Azithromycin) therapy.

Prescribing Azithromycin (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.

Azithromycin (Azithromycin) tablets may be taken with or without food. However, increased tolerability has been observed when tablets are taken with food.

Patients should also be cautioned not to take aluminum- and magnesium-containing antacids and Azithromycin (Azithromycin) simultaneously.

The patient should be directed to discontinue Azithromycin (Azithromycin) immediately and contact a physician if any signs of an allergic reaction occur.

Patients should be counseled that antibacterial drugs including Azithromycin (Azithromycin) should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Azithromycin (Azithromycin) is prescribed to treat bacterial infection, patients should be told that although it is common to feel better early in the course of 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 (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.

Aluminum- and magnesium-containing antacids reduce the peak serum levels (rate) but not the AUC (extent) of Azithromycin (Azithromycin) (500 mg) absorption.

Administration of cimetidine (800 mg) two hours prior to Azithromycin (Azithromycin) had no effect on Azithromycin (Azithromycin) (500 mg) absorption.

A single oral dose of 1200 mg Azithromycin (Azithromycin) (2 tablets of Azithromycin (Azithromycin) 600 mg) did not alter the pharmacokinetics of a single 800 mg oral dose of fluconazole in healthy adult subjects.

Total exposure (AUC) and half-life of Azithromycin (Azithromycin) following the single oral tablet dose of 1200 mg were unchanged and the reduction in C was not significant (mean decrease of 18%) by coadministration with 800 mg fluconazole.

A single oral dose of 1200 mg Azithromycin (Azithromycin) (2 tablets of Azithromycin (Azithromycin) 600 mg) had no significant effect on the pharmacokinetics of indinavir (800 mg indinavir t.i.d. for 5 days) in healthy adult subjects.

Coadministration of a single oral dose of 1200 mg Azithromycin (Azithromycin) (2 tablets of Azithromycin (Azithromycin) 600 mg) with steady-state nelfinavir (750 mg t.i.d.) to healthy adult subjects produced a decrease of approximately 15% in mean AUC of nelfinavir and its M8 metabolite. Mean C of nelfinavir and its M8 metabolite were not significantly affected. No dosage adjustment of nelfinavir is required when nelfinavir is coadministered with Azithromycin (Azithromycin) .

Coadministration of nelfinavir (750 mg t.i.d.) at steady state with a single oral dose of 1200 mg Azithromycin (Azithromycin) increased the mean AUC of Azithromycin (Azithromycin) by approximately a factor of 2-times (range of up to 4 times) of that when Azithromycin (Azithromycin) was given alone. The mean C of Azithromycin (Azithromycin) was also increased by approximately a factor of 2-times (range of up to 5 times) of that when Azithromycin (Azithromycin) was given alone. Dose adjustment of Azithromycin (Azithromycin) is not recommended. However, when administered in conjunction with nelfinavir, close monitoring for known side effects of Azithromycin (Azithromycin) , such as liver enzyme abnormalities and hearing impairment, is warranted. (See .)

Following administration of trimethoprim/sulfamethoxazole DS (160 mg/800 mg) for 7 days to healthy adult subjects, coadministration of 1200 mg Azithromycin (Azithromycin) (2 tablets of Azithromycin (Azithromycin) 600 mg) on the 7th day had no significant effects on peak concentrations (C), total exposure (AUC), and the urinary excretion of either trimethoprim or sulfamethoxazole.

Coadministration of trimethoprim/sulfamethoxazole DS for 7 days had no significant effect on the peak concentration (C) and total exposure (AUC) of Azithromycin (Azithromycin) following administration of the single 1200 mg tablet dose to healthy adult subjects.

Administration of a 600 mg single oral dose of Azithromycin (Azithromycin) had no effect on the pharmacokinetics of efavirenz given at 400 mg doses for 7 days to healthy adult subjects.

Efavirenz, when administered at a dose of 400 mg for seven days produced a 22% increase in the C of Azithromycin (Azithromycin) administered as a 600 mg single oral dose, while the AUC of Azithromycin (Azithromycin) was not affected.

Azithromycin (Azithromycin) (500 mg Day 1, 250 mg Days 2 to 5) did not affect the plasma levels or pharmacokinetics of theophylline administered as a single intravenous dose. The effect of Azithromycin (Azithromycin) on the plasma levels or pharmacokinetics of theophylline administered in multiple doses resulting in therapeutic steady-state levels of theophylline is not known. However, concurrent use of macrolides and theophylline has been associated with increases in the serum concentrations of theophylline. Therefore, until further data are available, prudent medical practice dictates careful monitoring of plasma theophylline levels in patients receiving Azithromycin (Azithromycin) and theophylline concomitantly.

Although, in a study of 22 healthy men, a 5-day course of Azithromycin (Azithromycin) did not affect the prothrombin time from a subsequently administered dose of warfarin, spontaneous post-marketing reports suggest that concomitant administration of Azithromycin (Azithromycin) may potentiate the effects of oral anticoagulants. Prothrombin times should be carefully monitored while patients are receiving Azithromycin (Azithromycin) and oral anticoagulants concomitantly.

Dose adjustments are not indicated when Azithromycin (Azithromycin) and zidovudine are coadministered. When zidovudine (100 mg q3h x5) was coadministered with daily Azithromycin (Azithromycin) (600 mg, n=5 or 1200 mg, n=7), mean C, AUC and Clr increased by 26% (CV 54%), 10% (CV 26%) and 38% (CV 114%), respectively. The mean AUC of phosphorylated zidovudine increased by 75% (CV 95%), while zidovudine glucuronide C and AUC increased by less than 10%. In another study, addition of 1 gram Azithromycin (Azithromycin) per week to a regimen of 10 mg/kg daily zidovudine resulted in 25% (CV 70%) and 13% (CV 37%) increases in zidovudine C and AUC, respectively. Zidovudine glucuronide mean C and AUC increased by 16% (CV 61%) and 8.0% (CV 32%), respectively.

Doses of 1200 mg/day Azithromycin (Azithromycin) for 14 days in 6 subjects increased C of concurrently administered didanosine (200 mg .12h) by 44% (54% CV) and AUC by 14% (23% CV). However, none of these changes were significantly different from those produced in a parallel placebo control group of subjects.

Preliminary data suggest that coadministration of Azithromycin (Azithromycin) and rifabutin did not markedly affect the mean serum concentrations of either drug. Administration of 250 mg Azithromycin (Azithromycin) daily for 10 days (500 mg on the first day) produced mean concentrations of Azithromycin (Azithromycin) 1 day after the last dose of 53 ng/mL when coadministered with 300 mg daily rifabutin and 49 mg/mL when coadministered with placebo. Mean concentrations 5 days after the last dose were 23 ng/mL and 21 ng/mL in the two groups of subjects. Administration of 300 mg rifabutin for 10 days produced mean concentrations of rifabutin one half day after the last dose of 60 mg/mL when coadministered with daily 250 mg Azithromycin (Azithromycin) and 71 ng/mL when coadministered with placebo. Mean concentrations 5 days after the last dose were 8.1 ng/mL and 9.2 ng/mL in the two groups of subjects.

The following drug interactions have not been reported in clinical trials with Azithromycin (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 (Azithromycin) and these drugs are used concomitantly, careful monitoring of patients is advised:

Digoxin–elevated digoxin levels.

Ergotamine or dihydroergotamine–acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.

Triazolam–decrease the clearance of triazolam and thus may increase the pharmacologic effect of triazolam.

Drugs metabolized by the cytochrome P system–elevations of serum carbamazepine, cyclosporine, hexobarbital, and phenytoin levels.

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 .)

In multiple-dose clinical trials of oral Azithromycin (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 responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Azithromycin (Azithromycin) tablets 600 mg contain 0.5 mg of sodium per tablet.

In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Approximately 0.7% of the patients from the multiple-dose clinical trials discontinued Azithromycin (Azithromycin) therapy because of treatment-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. Rarely but potentially serious side effects were angioedema and cholestatic jaundice.

Significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows:

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

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 3000 patients, 3 patients discontinued therapy because of treatment-related liver enzyme abnormalities and 1 because of a renal function abnormality.

In a phase I drug interaction study performed in normal volunteers, 1 of 6 subjects given the combination of Azithromycin (Azithromycin) and rifabutin, 1 of 7 given rifabutin alone and 0 of 6 given Azithromycin (Azithromycin) alone developed a clinically significant neutropenia (
Laboratory abnormalities seen in clinical trials for the prevention of disseminated disease in severely immunocompromised HIV-infected patients are presented in the section.

Chronic therapy (median duration: 87.5 days, range: 1 to 229 days) that resulted in laboratory abnormalities in > 5% subjects with normal baseline values in the pivotal trial for treatment of disseminated MAC in severely immunocompromised HIV infected patients treated with Azithromycin (Azithromycin) 600 mg daily in combination with ethambutol include: a reduction in absolute neutrophils to

(See .)

For pediatric suspension, please refer to the and sections of the prescribing information for Azithromycin (Azithromycin) for oral suspension 100 mg/5 mL and 200 mg/5 mL bottles.

Azithromycin (Azithromycin) tablets may be taken without regard to food. However, increased tolerability has been observed when tablets are taken with food.

Azithromycin (Azithromycin) tablets, USP, equivalent to 600 mg Azithromycin (Azithromycin) , are unscored white, oval-shaped, film-coated tablets, debossed GG D7 on one side and plain on the reverse side, and are supplied as follows:

NDC 0781-1497-31 in bottles of 30 tablets

NDC 0781-1497-01 in bottles of 100 tablets

(See .)

One randomized, double blind clinical trial (Study 189) was performed in patients with disseminated MAC. In this trial, 246 HIV infected patients with disseminated MAC received either Azithromycin (Azithromycin) 250 mg qd (N=65), Azithromycin (Azithromycin) 600 mg qd (N=91) or clarithromycin 500 mg b.i.d. (N=90), each administered with ethambutol 15 mg/kg qd, for 24 weeks. Patients were cultured and clinically assessed every 3 weeks through week 12 and monthly thereafter through week 24. After week 24, patients were switched to any open label therapy at the discretion of the investigator and followed every 3 months through the last follow up visit of the trial. Patients were followed from the baseline visit for a period of up to 3.7 years (median: 9 months). MAC isolates recovered during study treatment or post-treatment were obtained whenever possible.

The primary endpoint was sterilization by week 24. Sterilization was based on data from the central laboratory, and was defined as two consecutive observed negative blood cultures for MAC, independent of missing culture data between the two negative observations. Analyses were performed on all randomized patients who had a positive baseline culture for MAC.

The Azithromycin (Azithromycin) 250 mg arm was discontinued after an interim analysis at 12 weeks showed a significantly lower clearance of bacteremia compared to clarithromycin 500 mg b.i.d.

Efficacy results for the Azithromycin (Azithromycin) 600 mg qd and clarithromycin 500 mg b.i.d. treatment regimens are described in the following table:

The primary endpoint, rate of sterilization of blood cultures (two consecutive negative cultures) at 24 weeks, was lower in the Azithromycin (Azithromycin) 600 mg qd group than in the clarithromycin 500 mg b.i.d. group.

Susceptibility testing was performed on MAC isolates recovered at baseline, at the time of breakthrough on therapy or during post-therapy follow-up. The T100 radiometric broth method was employed to determine Azithromycin (Azithromycin) and clarithromycin MIC values. Azithromycin (Azithromycin) MIC values ranged from 256 mcg/mL and clarithromycin MICs ranged from 32 mcg/mL. The individual MAC susceptibility results demonstrated that Azithromycin (Azithromycin) MIC values could be 4 to 32 fold higher than clarithromycin MIC values.

During study treatment and post-treatment follow up for up to 3.7 years (median: 9 months) in study 189, a total of 6/68 (9%) and 6/57 (11%) of the patients randomized to Azithromycin (Azithromycin) 600 mg daily and clarithromycin 500 mg b.i.d., respectively, developed MAC blood culture isolates that had a sharp increase in MIC values. All twelve MAC isolates had Azithromycin (Azithromycin) MIC’s ≥256 mcg/mL and clarithromycin MIC’s >32 mcg/mL. These high MIC values suggest development of drug resistance. However, at this time, specific breakpoints for separating susceptible and resistant MAC isolates have not been established for either macrolide.

Phospholipidosis (intracellular phospholipid binding) has been observed in some tissues of mice, rats, and dogs given multiple doses of Azithromycin (Azithromycin) . It has been demonstrated in numerous organ systems (e.g., eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and pancreas) in dogs administered doses which, based on pharmacokinetics, are as low as 2 times greater than the recommended adult human dose and in rats at doses comparable to the recommended adult human dose. This effect has been reversible after cessation of Azithromycin (Azithromycin) treatment. The significance of these findings for humans is unknown.

NDC 0781-1497-31

Azithromycin (Azithromycin)

Tablets, USP

600 mg*

Rx only

30 Tablets

SANDOZ