Azithromycin

Adverse reactions experienced in higher than recommended doses were similar to those seen at normal doses. In the event of overdosage, general symptomatic and supportive measures are indicated as required.

Mechanism Of Action

Azithromycin is a macrolide antibacterial drug. [see Microbiology]

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 hr of incubation. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Pharmacodynamics

Based on animal models of infection, the antibacterial activity of azithromycin appears to correlate with the ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) for certain pathogens (S. pneumoniae and S. aureus). The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in clinical trials with azithromycin.

QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1000 mg) alone or in combination with oral azithromycin (500 mg, 1000 mg, and 1500 mg once daily). Coadministration of azithromycin increased the QTc interval in a dose- and concentration- dependent manner. In comparison to chloroquine alone, the maximum mean (95% upper confidence bound) increases in QTcF were 5 (10) ms, 7 (12) ms and 9 (14) ms with the co-administration of 500 mg, 1000 mg and 1500 mg azithromycin, respectively.

Pharmacokinetics

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

MEAN (CV%) PK PARAMETER

With a regimen of 500 mg on Day 1 and 250 mg/day on Days 2-5, Cmin and Cmax remained essentially unchanged from Day 2 through Day 5 of therapy. However, without a loading dose, azithromycin Cmin levels required 5 to 7 days to reach steady state.

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

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.

The 1 gram single-dose packet is bioequivalent to four 250 mg azithromycin capsule

When the oral suspension of azithromycin was administered with food, the Cmax 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 Cmax by 31% (CV=43%) while the extent of absorption (AUC) was unchanged (mean ratio of AUCs=1.00; CV=55%).

The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 μg/mL to 7% at 2 μg/mL.

The antibacterial 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.

Azithromycin has been shown to penetrate into tissues in humans, including skin, lung, tonsil, and cervix. 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 oral administration of a single 1200 mg dose (two 600 mg tablets), the mean maximum concentration in peripheral leukocytes was 140 μg/mL. Concentration remained above 32 μg/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 Cmax 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-positive adults, mean maximum concentration in peripheral leukocytes was 252 μg/mL (±49%). Trough concentrations in peripheral leukocytes at steady-state averaged 146 μg/mL (±33%). The mean leukocyte-to-serum Cmax ratio was 456 (±38%) and the mean leukocyte to serum AUC ratio was 816 (±31%). The clinical relevance of these findings is unknown.

In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed.

Plasma concentrations of azithromycin following single 500 mg oral and IV doses declined in a polyphasic pattern resulting in an average terminal half-life of 68 hr. 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.

Specific Populations

Azithromycin pharmacokinetics was investigated in 42 adults (21 to 85 years of age) with varying degrees of renal impairment. Following the oral administration of a single 1.0 g dose of azithromycin (4 x 250 mg capsules), the mean Cmax and AUC0-120 increased by 5.1% and 4.2%, respectively, in subjects with GFR 10 to 80 mL/min compared to subjects with normal renal function (GFR > 80 mL/min). The mean Cmax and AUC0-120 increased 61% and 35%, respectively, in subjects with end-stage renal disease (GFR < 10 mL/min) compared to subjects with normal renal function (GFR > 80 mL/min).

The pharmacokinetics of azithromycin in subjects with hepatic impairment has not been established.

There are no significant differences in the disposition of azithromycin between male and female subjects. No dosage adjustment is recommended on the basis of gender.

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 Geriatric Use]

For information regarding the pharmacokinetics of ZITHROMAX (azithromycin for oral suspension) in pediatric patients, see the prescribing information for ZITHROMAX (azithromycin for oral suspension) 100 mg/5 mL and 200 mg/5 mL bottles.

Drug-drug Interactions

Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered. The effects of coadministration of azithromycin on the pharmacokinetics of other drugs are shown in Table 1 and the effects 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 Cmax and AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2. [see DRUG INTERACTIONS]

Table 1: Drug Interactions: Pharmacokinetic Parameters for Co-administered Drugs in the Presence of Azithromycin

Table 2: Drug Interactions: Pharmacokinetic Parameters for Azithromycin in the Presence of Co-administered Drugs. [see DRUG INTERACTIONS]

Microbiology

Azithromycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in [see INDICATIONS AND USAGE].

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.

Haemophilus influenzae
Moraxella catarrhalis
Other Microorganisms
Chlamydia trachomatis

Beta-lactamase production should have no effect on azithromycin activity.

Azithromycin has been shown to be active in vitro and in the prevention and treatment of disease caused by the following microorganisms:

Mycobacterium avium complex (MAC) consisting of:
Mycobacterium avium
Mycobacterium intracellulare

The following in vitro data are available, but their clinical significance is unknown.

Azithromycin exhibits in vitro minimal inhibitory concentrations (MICs) of 2.0 μg/mL or less against most ( ≥ 90%) strains of the following microorganisms; 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.

Streptococci (Groups C, F, G)
Viridans group streptococci

Bordetella pertussis
Campylobacter jejuni
Haemophilus ducreyi
Legionella pneumophila

Bacteroides bivius
Clostridium perfringens
Peptostreptococcus species

Borrelia burgdorferi
Mycoplasma pneumoniae
Treponema pallidum
Ureaplasma urealyticum

Susceptibility Testing of Bacteria Excluding Mycobacteria

The in vitro potency of azithromycin is markedly affected by the pH of the microbiological growth medium during incubation. Incubation in a 10% CO2 atmosphere will result in lowering of media pH (7.2 to 6.6) within 18 hr and in an apparent reduction of the in vitro potency of azithromycin. Thus, the initial pH of the growth medium should be 7.2-7.4, and the CO2 content of the incubation atmosphere should be as low as practical.

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

Quantitative methods are used to determine minimal inhibitory concentrations that provide reproducible estimates of the susceptibility of bacteria to antibacterial compounds. One such standardized procedure uses a standardized dilution method1 (broth, agar or microdilution) or equivalent with azithromycin powder. The MIC values should be interpreted according to the following criteria:

A report of “Susceptible” indicates that the pathogen is likely to respond to monotherapy with azithromycin. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that usually achievable drug concentrations are unlikely to be inhibitory and that other therapy should be selected.

Measurement of MIC or minimum bacterial concentration (MBC) and achieved antibacterial compound concentrations may be appropriate to guide therapy in some infections. [see CLINICAL PHARMACOLOGY] section for further information on drug concentrations achieved in infected body sites and other pharmacokinetic properties of this antibacterial drug product.)

Standardized susceptibility test procedures require the use of laboratory control microorganisms. Standard azithromycin powder should provide the following MIC values:

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antibacterial compounds. One such standardized procedure2 that has been recommended for use with disks to test the susceptibility of microorganisms to azithromycin uses the 15 μg azithromycin disk. Interpretation involves the correlation of the diameter obtained in the disk test with the MIC for azithromycin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 15 μg azithromycin disk should be interpreted according to the following criteria:

Interpretation should be as stated above for results using dilution techniques.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms. The 15 μg azithromycin disk should provide the following zone diameters in these laboratory test quality control strains:

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

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

The ability to correlate MIC values and plasma drug levels is difficult as azithromycin concentrates in macrophages and tissues. [see CLINICAL PHARMACOLOGY]

Complete cross-resistance between azithromycin and clarithromycin has been observed with MAC isolates. In most isolates, a singlepoint mutation at a position that is homologous to the Escherichia coli positions 2058 or 2059 on the 23S rRNA gene is the mechanism producing this cross-resistance pattern.3,4 MAC isolates exhibiting cross-resistance show an increase in azithromycin MICs to ≥ 128 μg/mL with clarithromycin MICs increasing to ≥ 32 μg/mL. These MIC values were determined employing the radiometric broth dilution susceptibility testing method with Middlebrook 7H12 medium. The clinical significance of azithromycin and clarithromycin cross-resistance is not fully understood at this time but preclinical data suggest that reduced activity to both agents will occur after MAC strains produce the 23S rRNA mutation.

Susceptibility Testing for MAC

The disk diffusion techniques and dilution methods for susceptibility testing against gram-positive and gram-negative bacteria should not be used for determining azithromycin MIC values against mycobacteria. In vitro susceptibility testing methods and diagnostic products currently available for determining MIC values against MAC organisms have not been standardized or validated. 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 M. avium or M. intracellulare are susceptible or resistant to azithromycin have not been established.

The clinical relevance of azithromycin in vitro susceptibility test results for other mycobacterial species, including Mycobacterium tuberculosis, using any susceptibility testing method has not been determined.

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/or pancreas) in dogs and rats treated with azithromycin at doses which, expressed on the basis of body surface area, are similar to or less than the highest recommended adult human dose. This effect has been shown to be reversible after cessation of azithromycin treatment. Based on the pharmacokinetic data, phospholipidosis has been seen in the rat (50 mg/kg/day dose) at the observed maximal plasma concentration of 1.3 mcg/mL (1.6 times the observed Cmax of 0.821 mcg/mL at the adult dose of 2 g.) Similarly, it has been shown in the dog (10 mg/kg/day dose) at the observed maximal serum concentration of 1 mcg/mL (1.2 times the observed Cmax of 0.821 mcg/mL at the adult dose of 2 g).

Phospholipidosis was also observed in neonatal rats dosed for 18 days at 30 mg/kg/day, which is less than the pediatric dose of 60 mg/kg based on the surface area. It was not observed in neonatal rats treated for 10 days at 40 mg/kg/day with mean maximal serum concentrations of 1.86 mcg/mL, approximately 1.5 times the Cmax of 1.27 mcg/mL at the pediatric dose. Phospholipidosis has been observed in neonatal dogs (10 mg/kg/day) at maximum mean whole blood concentrations of 3.54 mcg/mL, approximately 3 times the pediatric dose Cmax. The significance of the finding for animals and for humans is unknown.

Clinical Studies

Clinical Studies In Patients With Advanced HIV Infection For The Prevention And Treatment Of Disease Due To Disseminated Mycobacterium avium Complex (MAC)

[see INDICATIONS AND USAGE]

Two randomized, double-blind clinical trials were performed in patients with CD4 counts < 100 cells/μL. The first trial (Study 155) compared azithromycin (1200 mg once weekly) to placebo and enrolled 182 patients with a mean CD4 count of 35 cells/mcgL. The second trial (Study 174) randomized 723 patients to either azithromycin (1200 mg once weekly), rifabutin (300 mg daily), or the combination of both. The mean CD4 count was 51 cells/mcgL. The primary endpoint in these trials was disseminated MAC disease. Other endpoints included the incidence of clinically significant MAC disease and discontinuations from therapy for drug-related side effects.

In Study 155, 85 patients randomized to receive azithromycin and 89 patients randomized to receive placebo met the entrance criteria. Cumulative incidences at 6, 12, and 18 months of the possible outcomes are in the following table:

The difference in the one-year cumulative incidence rates of disseminated MAC disease (placebo – azithromycin) is 10.9%. This difference is statistically significant (p=0.037) with a 95% confidence interval for this difference of 0.8%, 20.9%. The comparable number of patients experiencing adverse events and the fewer number of patients lost to follow-up on azithromycin should be taken into account when interpreting the significance of this difference.

In Study 174, 223 patients randomized to receive rifabutin, 223 patients randomized to receive azithromycin, and 218 patients randomized to receive both rifabutin and azithromycin met the entrance criteria. Cumulative incidences at 6, 12, and 18 months of the possible outcomes are recorded in the following table:

Comparing the cumulative one-year incidence rates, azithromycin monotherapy is at least as effective as rifabutin monotherapy. The difference (rifabutin – azithromycin) in the one-year rates (7.6%) is statistically significant (p=0.022) with an adjusted 95% confidence interval (0.9%, 14.3%). Additionally, azithromycin/rifabutin combination therapy is more effective than rifabutin alone. The difference (rifabutin – azithromycin/rifabutin) in the cumulative one-year incidence rates (12.5%) is statistically significant (p < 0.001) with an adjusted 95% confidence interval of 6.6%, 18.4%. The comparable number of patients experiencing adverse events and the fewer number of patients lost to follow-up on rifabutin should be taken into account when interpreting the significance of this difference.

In Study 174, sensitivity testing5 was performed on all available MAC isolates from subjects randomized to either azithromycin, rifabutin, or the combination. The distribution of MIC values for azithromycin from susceptibility testing of the breakthrough isolates was similar between trial arms. As the efficacy of azithromycin in the treatment of disseminated MAC has not been established, the clinical relevance of these in vitro MICs as an indicator of susceptibility or resistance is not known.

In association with the decreased incidence of bacteremia, patients in the groups randomized to either azithromycin alone or azithromycin in combination with rifabutin showed reductions in the signs and symptoms of disseminated MAC disease, including fever or night sweats, weight loss, and anemia.

In Study 155, discontinuations for drug-related toxicity occurred in 8.2% of subjects treated with azithromycin and 2.3% of those given placebo (p=0.121). In Study 174, more subjects discontinued from the combination of azithromycin and rifabutin (22.7%) than from azithromycin alone (13.5%; p=0.026) or rifabutin alone (15.9%; p=0.209).

As these patients with advanced HIV disease were taking multiple concomitant medications and experienced a variety of intercurrent illnesses, it was often difficult to attribute adverse reactions to study medication. Overall, the nature of adverse reactions seen on the weekly dosage regimen of azithromycin over a period of approximately one year in patients with advanced HIV disease were similar to that previously reported for shorter course therapies.

INCIDENCE OF ONE OR MORE TREATMENT-RELATEDa ADVERSE REACTIONSb IN HIV INFECTED PATIENTS RECEIVING PROPHYLAXIS FOR DISSEMINATED MAC OVER APPROXIMATELY 1 YEAR

Adverse reactions related to the gastrointestinal tract were seen more frequently in patients receiving azithromycin than in those receiving placebo or rifabutin. In Study 174, 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.

In these immunocompromised patients with advanced HIV infection, it was necessary to assess laboratory abnormalities developing on trial with additional criteria if baseline values were outside the relevant normal range.

PROPHYLAXIS AGAINST DISSEMINATED MAC ABNORMAL LABORATORY VALUESa

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 250 mg daily (N=65), azithromycin 600 mg daily (N=91), or clarithromycin 500 mg twice a day (N=90), each administered with ethambutol 15 mg/kg daily, for 24 weeks. Blood cultures and clinical assessments were performed 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 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 250 mg arm was discontinued after an interim analysis at 12 weeks showed a significantly lower clearance of bacteremia compared to clarithromycin 500 mg twice a day . Efficacy results for the azithromycin 600 mg daily and clarithromycin 500 mg twice a day treatment regimens are described in the following table:

RESPONSE TO THERAPY OF PATIENTS TAKING ETHAMBUTOL AND EITHER AZITHROMYCIN 600 MG DAILY OR CLARITHROMYCIN 500 MG TWICE A DAY

The primary endpoint, rate of sterilization of blood cultures (two consecutive negative cultures) at 24 weeks, was lower in the azithromycin 600 mg daily group than in the clarithromycin 500 mg twice a day group.

Within both treatment groups, the sterilization rates at week 24 decreased as the range of MAC cfu/mL increased.

Susceptibility testing was performed on MAC isolates recovered at baseline, at the time of breakthrough on therapy or during posttherapy follow-up. The T100 radiometric broth method was employed to determine azithromycin and clarithromycin MIC values. Azithromycin MIC values ranged from < 4 to > 256 μg/mL and clarithromycin MICs ranged from < 1 to > 32 μg/mL. The individual MAC susceptibility results demonstrated that azithromycin MIC values could be 4 to 32-fold higher than clarithromycin MIC values.

During 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 600 mg daily and clarithromycin 500 mg twice a day respectively, developed MAC blood culture isolates that had a sharp increase in MIC values. All twelve MAC isolates had azithromycin MICs ≥ 256 μg/mL and clarithromycin MICs > 32 μg/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.

REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Ninth Edition. CLSI document M07-A9, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.

2. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Eleventh Edition CLSI document M02-A11, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.

3. Dunne MW, Foulds G, Retsema JA. Rationale for the use of azithromycin as Mycobacterium avium chemoprophylaxis. Am J Med 1997;102(5C):37-49.

4. Meier A, Kirshner P, Springer B, et al. Identification of mutations in 23S rRNA gene of clarithromycin-resistant Mycobacterium intracellulare. Antimicrob Agents Chemother. 1994;38:381-384.

5. Methodology per Inderlied CB, et al. Determination of In Vitro Susceptibility of Mycobacterium avium Complex Isolates to Antimicrobial Agents by Various Methods. Antimicrob Agents Chemother. 1987;31:1697-1702.

Zmax (azithromycin extended-release) for oral suspension contains the active ingredient azithromycin (as azithromycin dihydrate), an azalide, a subclass of macrolide antibacterial drug. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)13-[(2,6-Dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyra nosyl) oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C38H72N2O12, and its molecular weight is 749.0. Azithromycin has the following structural formula:

Azithromycin, as the dihydrate, is a white crystalline powder with a molecular formula of C38H72N2O12•2H2O and a molecular weight of 785.0.

Zmax is a single-dose, extended-release formulation of microspheres for oral suspension containing azithromycin (as azithromycin dihydrate) and the following excipients: glyceryl behenate, poloxamer 407, sucrose, sodium phosphate tribasic anhydrous, magnesium hydroxide, hydroxypropyl cellulose, xanthan gum, colloidal silicon dioxide, titanium dioxide, artificial cherry flavor, and artificial banana flavor.

Note: Each bottle of Zmax 2 g for oral suspension contains approximately 148 mg of sodium and 19 g of sucrose. Constituted Zmax oral suspension contains approximately 2 mg/mL of sodium and 0.26 g/mL of sucrose.

Acute Bacterial Sinusitis In Adults And Community-Acquired Pneumonia

Zmax (azithromycin) is a macrolide antibacterial drug indicated for the treatment with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below. [See Clinical Studies]

Acute bacterial sinusitis in adults due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Community-acquired pneumonia in adults and pediatric patients six months of age or older due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae, in patients appropriate for oral therapy. Pediatric use in this indication is based on extrapolation of adult efficacy. [See Use in Specific Populations]

Limitations Of Use

Zmax is not recommended for use 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 nosocomial 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).

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zmax (azithromycin) and other antibacterial drugs, Zmax (azithromycin) should be used only to treat 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.

The injectable form of azithromycin is given directly into the vein (IV) by a healthcare professional.

Take all other forms of azithromycin exactly as prescribed.

For the tablets and regular suspensions (liquid):

• Take once a day, with a glass of water and with or without food.
• Take with food if azithromycin upsets your stomach.

For the extended release suspension (liquid):

• Take one dose only on an empty stomach (at least 1 hour before or 2 hours following a meal).

For the eye drops:

• One drop is instilled in the affected eye twice a day for the first 2 days.
• One drop is instilled in the affected eye once a day for the next 5 days.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of azithromycin at the same time.

The injectable form of azithromycin is given directly in the vein (IV) by a healthcare professional.

Take all other forms of azithromycin exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

Your doctor will determine the best dose for you or your child based on the type of infection and the patient's age.

For the tablets and regular suspension:

• Adults: The recommended azithromycin dosage for most infections is 250, 500, and 600 mg once daily in this dosage form. Azithromycin is usually taken for 3 to 5 days, or longer for more serious infections. For some infections a single 1 or 2 g dose is prescribed.

• Children: The recommended azithromycin dose in this dosage form in children is based on weight and ranges from 5 mg to 20 mg per kilogram of body weight per day. Azithromycin is usually taken for 3 to 5 days.

For the extended release suspensions:

• Adults: Azithromycin in this form should be taken as a single 2 g dose.

• Children: For children 6 months and older, azithromycin in this form should be taken as a single dose of 60 mg/kg (equivalent to 27 mg/lb) body weight. Children weighing 75 lb (34 kg) or more should receive the adult dose of 2 grams.

For the eye drops:

• The recommended azithromycin eye drop dosage is one drop in the affected eye(s) twice daily, eight to twelve hours apart, for the first two days. Then, instill one drop in the affected eye(s) once daily for the next five days.

Do not take antacids that contain aluminum or magnesium within 2 hours before or after you take azithromycin. This includes Acid Gone, Aldroxicon, Alternagel, Di-Gel, Gaviscon, Gelusil, Genaton, Maalox, Maldroxal, Milk of Magnesia, Mintox, Mylagen, Mylanta, Pepcid Complete, Rolaids, Rulox, and others. These antacids can make azithromycin less effective when taken at the same time.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, stop taking azithromycin and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Avoid exposure to sunlight or tanning beds. Azithromycin can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Acute Otitis Media (AOM)

Treatment of AOM caused by H. influenzae, M. catarrhalis, or S. pneumoniae.1 94 106 139 174 175 176 177 179 203 211 294

Not a drug of first choice; considered an alternative for patients with type I penicillin hypersensitivity.203 294 S. pneumoniae resistant to amoxicillin may also be resistant to azithromycin and the drug may not be effective for AOM that fails to respond to amoxicillin.282

Pharyngitis and Tonsillitis

Treatment of pharyngitis or tonsillitis caused by susceptible Streptococcus pyogenes (group A β-hemolytic streptococci) when first-line therapy cannot be used.1 15 29 203 211 Often effective in eradicating susceptible S. pyogenes from the nasopharynx, but efficacy in the prevention of subsequent rheumatic fever has not been established to date.1

CDC, AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;1 6 15 136 137 203 oral cephalosporins and oral macrolides are considered alternatives.6 15 136 137 203 Amoxicillin sometimes used instead of penicillin V, especially for young children.136 203

Consider that strains of S. pyogenes resistant to macrolides are common is some areas of the world (e.g., Japan, Finland) and azithromycin-resistant strains have been reported in the US.1 202 203 309 (See Selection and Use of Anti-infectives under Cautions),

GI Infections

Treatment of symptomatic enteric infections caused by Campylobacter jejuni†.308 Recommended by CDC, NIH,308 IDSA,308 AAP, and others as a drug of choice for empiric treatment.15 142 203 308

Treatment of cryptosporidiosis† in HIV-infected adults, adolescents, or children.256 307 308 Anti-infectives may suppress the infection, but none found to reliably eradicate Cryptosporidium.203 290 307 308 CDC, NIH, IDSA, and others state the most appropriate treatment for cryptosporidiosis in HIV-infected individuals is use of potent antiretroviral agents (to restore immune function) and symptomatic treatment of diarrhea.290 307 308

Treatment of shigellosis† caused by susceptible strains of Shigella dysenteriae, S. boydii, S. flexneri, or S. sonnei.15 142 203 307 316 317 318 Usual drugs of choice are fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin); alternatives are azithromycin, ampicillin, ceftriaxone, or co-trimoxazole.15 142 203 307 Because of increasing resistance, select anti-infective based on susceptibility patterns of locally circulating Shigella.203 317

Treatment of travelers’ diarrhea†.319 320 359 360 372 Generally self-limited and may resolve within 3–4 days without anti-infective treatment;319 320 336 if diarrhea is moderate or severe, persists >3 days, or is associated with fever or bloody stools, short-term anti-infective therapy (1–3 days) may be indicated.203 319 336 372 Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually recommended.319 320 336 372 Azithromycin is an alternative for those who should not receive fluoroquinolones (children, pregnant women) and may be drug of choice for travelers in areas with high prevalence of fluoroquinolone-resistant Campylobacter (e.g., Thailand, Nepal) or those who have not responded after 48 hours of fluoroquinolone therapy.203 319 320 359 360 372

Treatment of severe diarrhea caused by enterotoxigenic Escherichia coli† (ETEC).203 356 ETEC diarrhea generally is of moderate severity and self-limited, but may be severe.187 203 356 Anti-infectives not usually indicated, but AAP, CDC, and others suggest an anti-infective (e.g., azithromycin, co-trimoxazole, a fluoroquinolone, rifamycin) can be considered in addition to supportive care if diarrhea is severe or intractable and causative organism is susceptible.187 203 356

Treatment of dysentery caused by enteroinvasive E. coli† (EIEC).203 AAP suggests that an oral anti-infective (e.g., azithromycin, ciprofloxacin, co-trimoxazole) can be used; whenever possible, select anti-infective based on in vitro susceptibility testing.203

Treatment of diarrhea associated with enteroaggregative E. coli† (EAEC).331 A drug of choice, especially in children with severe or persistent illness.331

Role of anti-infectives in treatment of hemorrhagic colitis caused by shiga toxin-producing E. coli† (STEC; formerly known as enterohemorrhagic E. coli [EHEC] or verotoxin-producing E. coli) unclear; most experts do not recommend use of anti-infectives in the treatment of enteritis caused by E. coli 0157:H7 since there is no evidence of benefit from such therapy.142 187 203

Respiratory Tract Infections

Treatment of acute bacterial sinusitis caused by susceptible Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae.1 3 103 179 210 211 302

Treatment of mild to moderate acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) caused by H. influenzae, M. catarrhalis, or S. pneumoniae.1 3 15 96 97 98 179 210 211

Treatment of mild to moderate community-acquired pneumonia (CAP) caused by susceptible S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae (formerly Chlamydia pneumoniae) when oral therapy is indicated.1 3 15 29 91 99 100 101 159 179 203 210 211 302 329

Treatment of CAP caused by susceptible C. pneumoniae, H. influenzae, M. catarrhalis, Legionella pneumophila, M. pneumoniae, Staphylococcus aureus, or S. pneumoniae when initial IV therapy is indicated.196

Select regimen for empiric treatment of CAP based on most likely pathogens and local susceptibility patterns; after pathogen is identified, modify to provide more specific therapy (pathogen-directed therapy).329 Do not use a macrolide alone for empiric treatment of CAP in hospitalized patients.329

For empiric outpatient treatment of CAP in previously healthy adults without risk factors for drug-resistant S. pneumoniae (DRSP), IDSA and ATS recommend monotherapy with a macrolide (azithromycin, clarithromycin, erythromycin) or, alternatively, doxycycline.329 If risk factors for DRSP are present (e.g., chronic heart, lung, liver, or renal disease, diabetes mellitus, alcoholism, malignancy, asplenia, immunosuppression, history of anti-infective treatment within the last 3 months), IDSA and ATS recommend monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam active against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.329

For empiric inpatient treatment of CAP when treatment in an intensive care unit (ICU) is not necessary, IDSA and ATS recommend adults receive monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, or moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.329 For empiric inpatient treatment of CAP in ICU patients when Pseudomonas and oxacillin-resistant (methicillin-resistant) S. aureus are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or a fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin).329

For empiric treatment of CAP in adults with risk factors for Ps. aeruginosa, IDSA and ATS recommend a combination regimen that includes an antipneumococcal, antipseudomonal β-lactam (cefepime, imipenem, meropenem, fixed combination of piperacillin and tazobactam) and ciprofloxacin or levofloxacin; one of these β-lactams, an aminoglycoside, and azithromycin; or one of these β-lactams, an aminoglycoside, and an antipneumococcal fluoroquinolone.329

Treatment of infections caused by L. pneumophila (Legionnaires’ disease).15 130 168 196 203 232 250 311 312 314 329 330 Drugs of choice are macrolides (usually azithromycin) or fluoroquinolones with or without rifampin.15 203 232 311 312 329 330

Treatment and postexposure prophylaxis of pertussis† caused by Bordetella pertussis.15 28 138 203 324 325 326 329 333 334 (See Pertussis under Uses.)

Skin and Skin Structure Infections

Treatment of uncomplicated skin and skin structure infections caused by susceptible S. aureus, S. pyogenes, or S. agalactiae (group B streptococci).1 3 210 211

Babesiosis

Treatment of babesiosis† caused by Babesia microti.125 203 288 337

Regimens of choice for babesiosis are atovaquone in conjunction with azithromycin or quinine in conjunction with clindamycin.125 288 337 The clindamycin and quinine regimen may be preferred for severe babesiosis;288 in those with mild or moderate illness, the atovaquone and azithromycin regimen may be as effective and better tolerated than the quinine and clindamycin regimen.125 337 Also consider exchange transfusions in severely ill patients with high levels of parasitemia (>10%), substantial hemolysis, or compromised renal, hepatic, or pulmonary function.125 203 288

Bartonella Infections

Treatment of infections caused by B. henselae† (e.g., cat scratch disease, bacillary angiomatosis, peliosis hepatitis).15 203 261 310 Cat scratch disease generally self-limited in immunocompetent individuals and may resolve spontaneously in 2–4 months; some clinicians suggest that anti-infectives be considered for acutely or severely ill patients with systemic symptoms, particularly those with hepatosplenomegaly or painful lymphadenopathy, and such therapy probably is indicated in immunocompromised patients.203 261 310 Anti-infectives also indicated in patients with B. henselae infections who develop bacillary angiomatosis, neuroretinitis, or Parinaud’s oculoglandular syndrome.203 Optimum regimens have not been identified; some clinicians recommend azithromycin, ciprofloxacin, erythromycin, doxycycline, rifampin, co-trimoxazole, gentamicin, or third generation cephalosporins.15 203 261 310

Treatment of bacteremia caused by Bartonella quintana†;15 257 261 used in conjunction with ceftriaxone.257 261 307 Optimum anti-infective regimens have not been identified.257 259 260 307 310

Chancroid

Treatment of chancroid (genital ulcers caused by Haemophilus ducreyi).1 8 10 15 157 159 181 203 242

CDC and others recommend azithromycin, ceftriaxone, ciprofloxacin, or erythromycin for treatment of chancroid.8 15 159 181 203 242

Safety and efficacy of azithromycin established in men (not women),1 but has been effective for and is recommended by CDC for treatment of chancroid in women†.8 157 159 181 203 262

HIV-infected patients and uncircumcised males may not respond to treatment as well as those who are HIV-negative or circumcised.242 CDC recommends that single-dose azithromycin or ceftriaxone regimens be used in HIV patients only if follow-up can be ensured.242

Chlamydial Infections

Treatment of uncomplicated urethritis or cervicitis caused by C. trachomatis.1 7 8 10 15 92 109 110 111 112 114 179 184 185 203 211 242 CDC and others recommend azithromycin or doxycycline as drug of choice for nongonococcal urethritis (NGU) or cervicitis.8 242 For recurrent or persistent urethritis in patients with NGU who have already been treated with a recommended regimen, CDC recommends metronidazole or tinidazole used in conjunction with azithromycin.242

A drug of choice for presumptive treatment of coexisting chlamydial infection in patients being treated for gonorrhea.8 242

A drug of choice for treatment of urogenital chlamydial infections in pregnant women.8 203 242

Treatment of ocular trachoma† caused by C. trachomatis.15 29 112 114 189 203 217 301 354 370 373 374 375 376 A drug of choice;15 353 354 370 376 recommended for use in mass treatment programs.354 370 375 376

Treatment of chlamydial pneumonia in infants203 or chlamydial conjunctivitis in neonates (ophthalmia neonatorum caused by C. trachomatis).8 203 242

Alternative to tetracyclines for treatment of psittacosis† caused by Chlamydophila psittaci (formerly Chlamydia psittaci),15 203 329 especially in children <8 years of age who should not receive tetracyclines.203

Treatment of lymphogranuloma venereum caused by C. trachomatis.203 242 CDC recommends doxycycline as drug of choice and erythromycin as an alternative; some experts suggest that azithromycin may be effective, but clinical data are lacking.203 242

Has been used to treat adults with CAD who have elevated anti-C. pneumoniae antibody titers† (a possible risk factor for MI or CAD) in an attempt to reduce recurrent ischemic events;231 297 298 efficacy not proven to date.297 298

Cholera

Treatment of cholera† caused by Vibrio cholerae 01 or 0139.350 351 352

A tetracycline or, alternatively, a fluoroquinolone or co-trimoxazole generally used for treatment of cholera in conjunction with fluid and electrolyte replacement therapy.15 142 203 Although further study is needed, azithromycin may be an alternative, especially for treatment of cholera in children or infections caused by V. cholerae resistant to tetracyclines and fluoroquinolones.350 351 352

Gonorrhea

Treatment of uncomplicated urethritis or cervicitis caused by susceptible Neisseria gonorrhoeae.1 179 182 183 190 191 242 303 305

Not recommended for routine treatment of gonorrhea.179 182 183 242 250 CDC and others state azithromycin can be used as an alternative for treatment of uncomplicated gonorrhea when preferred drugs cannot be used (e.g., in patients hypersensitive to cephalosporins when spectinomycin is unavailable and desensitization to cephalosporins is not an option).303 306 371 Although azithromycin is effective, CDC recommends the drug be used only when necessary because of concerns related to emerging resistance to macrolides.371

Granuloma Inguinale (Donovanosis)

Alternative for treatment of granuloma inguinale† (donovanosis) caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis).221 242 CDC recommends doxycycline as the drug of choice and azithromycin, ciprofloxacin, erythromycin, or co-trimoxazole as alternatives.242

Leptospirosis

Alternative for treatment of leptospirosis caused by Leptospira†.363 365 Penicillin G is drug of choice for severe infections; tetracyclines (usually doxycycline) or ceftriaxone are recommended as alternatives for less severe infections.15 203 Azithromycin also has been effective.363 365

Lyme Disease

Alternative for treatment of early disseminated Lyme disease† associated with erythema migrans, in the absence of neurologic involvement or third-degree AV heart block, when first-line agents cannot be used.15 124 179 211 226 227 288 IDSA, AAP, and others recommend oral doxycycline, oral amoxicillin, or oral cefuroxime as first-line therapy for treatment of early localized or early disseminated Lyme disease when oral therapy is appropriate;15 203 289 226 288 macrolides generally have been less effective than first-line agents.203 226 288 289

Malaria

Although further study is needed, has been used in conjunction with an antimalarial (e.g., chloroquine, quinine, artesunate [not commercially available in the US]) for treatment of uncomplicated malaria† caused by Plasmodium falciparum, including multidrug-resistant strains.341 342 343 Should not be used alone as monotherapy for treatment of malaria.341 342

Although further study is needed, has been used for treatment or prevention of P. vivax malaria†.344 345 When used for treatment, the rate of resolution of parasitemia reported for azithromycin was considerably slower than that reported for chloroquine.345

Mycobacterium avium Complex (MAC) Infections

Primary prevention (primary prophylaxis) of disseminated MAC infection in adults, adolescents, and children† with advanced HIV infection.10 12 203 234 Recommended as a drug of choice for primary prevention of MAC in HIV-infected patients;234 usually used alone but has been used in conjunction with rifabutin.10 234

Treatment of disseminated MAC disease, including in HIV-infected adults, adolescents, and children.10 117 203 233 234 307 308 ATS, IDSA, CDC, NIH, and others recommend a regimen of clarithromycin (or azithromycin) and ethambutol with or without rifabutin.233 234 307 308 Clarithromycin usually the preferred macrolide for initial treatment; azithromycin can be substituted if clarithromycin cannot be used because of drug interactions or intolerance and is preferred in pregnant women.233 307 308

Prevention of recurrence (secondary prophylaxis) of disseminated MAC infection in HIV-infected adults, adolescents, and children†.10 117 203 233 234 ATS, CDC, NIH, and IDSA recommend a macrolide (clarithromycin or azithromycin) given with ethambutol (with or without rifabutin).233 234 307 308

Treatment of pulmonary MAC infections† in conjunction with other antimycobacterials.233 313 315 For initial treatment of nodular/bronchiectatic pulmonary disease caused by macrolide-susceptible MAC, ATS and IDSA recommend a 3-times-weekly regimen of clarithromycin (or azithromycin), ethambutol, and rifampin in most patients.233 For initial treatment of fibrocavitary or severe nodular/bronchiectatic pulmonary disease caused by macrolide-susceptible MAC, ATS and IDSA recommend a daily regimen of clarithromycin (or azithromycin), ethambutol, and rifampin (or rifabutin) and state that consideration can be given to adding amikacin or streptomycin during the first 2–3 months of treatment for extensive (especially fibrocavitary) disease or when previous therapy has failed.233 Although a 2-drug regimen of clarithromycin (or azithromycin) and ethambutol may be adequate for treatment of nodular/bronchiectatic MAC disease in some patients, such regimens should not be used in fibrocavitary disease because of the risk of emergence of macrolide resistance.233

Treatment of MAC infections is complicated and should be directed by clinicians familiar with mycobacterial diseases; consultation with a specialist is particularly important when the patient cannot tolerate first-line drugs or when the infection has not responded to prior therapy or is caused by macrolide-resistant MAC.233

Mycobacterium abscessus, M. kansasii, and M. marinum Infections

Treatment of infections caused by M. abscessus†.233 For serious skin, soft tissue, and bone infections, ATS and IDSA recommend a multiple-drug regimen of clarithromycin (or azithromycin) used in conjunction with a parenteral anti-infective (e.g., amikacin, cefoxitin, imipenem);233 surgery usually indicated for extensive disease, abscess formation, and when drug therapy is difficult.233 This multiple-drug regimen also has been used in the treatment of M. abscessus lung disease; anti-infectives may control symptoms and disease progression, but generally cannot produce long-term sputum conversion.233 Curative therapy may be possible in those with focal infections and limited lung disease if surgical resection is used in conjunction with a multiple-drug treatment regimen.233

Treatment of rifampin-resistant M. kansasii† infections in conjunction with other antimycobacterials.233 ATS and IDSA recommend a 3-drug regimen based on results of in vitro susceptibility testing, including clarithromycin (or azithromycin), moxifloxacin, ethambutol, sulfamethoxazole, or streptomycin.233

Treatment of M. marinum† infections.233 A regimen of clarithromycin and ethambutol has been used; based on experience in other mycobacterial infections, a regimen of azithromycin and ethambutol may be an alternative.233

Neisseria meningitidis Infections

Elimination of nasopharyngeal carriage of N. meningitidis†.346 347 349

CDC and AAP consider rifampin, ceftriaxone, or ciprofloxacin the drugs of choice to eliminate nasopharyngeal carriage of N. meningitidis and for postexposure prophylaxis in household or other close contacts of patients with invasive meningococcal disease.203 349 Although further study is needed,349 CDC suggests azithromycin can be used as an alternative in areas where ciprofloxacin-resistant N. meningitidis have been reported (e.g., Minnesota, North Dakota).347

Pelvic Inflammatory Disease

Treatment of acute pelvic inflammatory disease (PID) caused by C. trachomatis, Mycoplasma hominis, or N. gonorrhoeae when initial IV therapy is considered necessary.196 197 If anaerobic bacteria are suspected, an anti-infective active against anaerobes should be used in conjunction with azithromycin.196 Although azithromycin is not included in CDC’s recommended or alternative regimens for treatment of PID,242 371 CDC states a regimen of amoxicillin and clavulanic acid, azithromycin, and metronidazole has demonstrated short-term clinical cure when used in outpatients.371

Pertussis

Treatment of pertussis† caused by Bordetella pertussis and postexposure prophylaxis of pertussis† in household and other close contacts of an individual with pertussis.15 28 138 203 324 325 326 333 334

Macrolides (azithromycin, clarithromycin, erythromycin) are the drugs of choice.15 138 203 326 333 334 Although erythromycin traditionally has been considered the drug of choice for treatment and postexposure prophylaxis of pertussis,15 138 203 326 333 334 azithromycin and clarithromycin appear to be as effective and may be associated with better compliance because shorter regimens are required and the drugs are better tolerated.203 324 333 334

For treatment and postexposure prophylaxis of pertussis in adults and children ≥1 month of age, CDC and AAP recommend azithromycin, clarithromycin, or erythromycin as drug of choice;203 334 co-trimoxazole is an alternative for those ≥2 months of age when a macrolide cannot be used.203 334 AAP and CDC state azithromycin is the preferred macrolide for treatment of pertussis in infants <1 month of age; however, safety and efficacy not established in this age group and only limited data are available.203 334

If given during the catarrhal stage of pertussis (approximately 1–2 weeks of nasal congestion, runny nose, mild sore throat, nonproductive cough, minimal or no fever), anti-infectives may reduce the duration and severity of symptoms and lessen the period of communicability.203 334 After paroxysmal cough is established, anti-infectives may not affect the course of illness but are recommended to limit spread of the disease to others.203

All household and other close contacts of an individual with suspected pertussis should receive anti-infective postexposure prophylaxis, regardless of age or vaccination status.198 203 Prophylaxis should be initiated within 21 days of exposure; if >21 days have elapsed since onset of cough in the index patient, prophylaxis has limited value but should be considered for those in households with high-risk contacts (e.g., young infants, pregnant women, individuals with contact with infants).203 In addition, all close contacts who are unvaccinated or incompletely vaccinated against pertussis should receive age-appropriate vaccination with a preparation containing pertussis antigens.198 203

Scrub Typhus

Alternative for treatment of scrub typhus caused by Orientia tsutsugamushi (formerly Rickettsia tsutsugamushi).362 363 364 Drug of choice usually is doxycycline;15 362 363 364 alternatives are chloramphenicol or a fluoroquinolone.15 362 364 Azithromycin may be a preferred alternative for treatment of scrub typhus in children or pregnant women or when scrub typhus was acquired in areas where doxycycline-resistant O. tsutsugamushi have been reported (e.g., South Korea, Thailand).362 363 364

Syphilis

Alternative for treatment of primary, secondary, or early latent syphilis in nonpregnant adults and adolescents hypersensitive to penicillin†.242 292 293 358

Penicillin G is drug of choice for treatment of all stages of syphilis,8 203 242 but CDC, NIH, and IDSA state azithromycin can be considered for treatment of primary, secondary, or early latent syphilis† in nonpregnant adults and adolescents hypersensitive to penicillin if close follow-up can be ensured.203 242 293 307

Use with caution and with close follow-up; efficacy not well documented (especially in HIV-infected individuals) and resistance and treatment failures reported.8 242 293 307 327 328

Toxoplasmosis

Treatment of infections caused by Toxoplasma gondii, including toxoplasmic encephalitis† in HIV-infected patients127 128 129 296 307 and ocular toxoplasmosis†;295 usually used in conjunction with pyrimethamine.295 296

CDC, NIH, IDSA, and others usually recommend pyrimethamine in conjunction with sulfadiazine and leucovorin for treatment of toxoplasmosis in adults and children, especially immunocompromised patients (e.g., HIV-infected individuals).125 307 308 Azithromycin in conjunction with pyrimethamine and leucovorin is one of several alternative regimens that can be considered in adults and adolescents when the regimen of choice cannot be used;307 this regimen has not been evaluated in children.308

Typhoid Fever and Other Salmonella Infections

Treatment of uncomplicated typhoid fever† caused by susceptible Salmonella.15 321 322 323 332 361 Drugs of choice are fluoroquinolones (e.g., ciprofloxacin, ofloxacin), especially in areas with multidrug-resistant S. typhi (strains resistant to ampicillin, amoxicillin, chloramphenicol, co-trimoxazole); alternatives are azithromycin and third generation cephalosporins (cefotaxime, ceftriaxone, cefixime), especially for fluoroquinolone-resistant strains.15 203 332 361

Prevention of Bacterial Endocarditis

Alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in penicillin-allergic individuals with certain cardiac conditions who are undergoing certain dental procedures (i.e., procedures that involve manipulation of gingival tissue, the periapical region of teeth, or perforation of oral mucosa) or certain invasive respiratory tract procedures (i.e., procedures involving incision or biopsy of respiratory mucosa).201

Consult most recent AHA recommendations for specific information on which cardiac conditions are associated with the highest risk of adverse outcome from endocarditis and specific recommendations regarding use of prophylaxis to prevent endocarditis in these patients.201

Prophylaxis in Sexual Assault Victims

Empiric anti-infective prophylaxis in sexual assault victims†;8 242 used in conjunction with IM ceftriaxone and oral metronidazole.242

Take azithromycin only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

azithromycin comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

You may take Zithromax® oral liquid or tablets with or without food.

Shake well the bottle of Zithromax® oral liquid before each use. Measure your dose correctly with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

Measure the Zmax® extended-release oral suspension with a marked measuring spoon, syringe, or cup. You or your child must take azithromycin within 12 hours after it has been mixed with water. It is best to take the Zmax® extended-release oral suspension on an empty stomach or at least 1 hour before or 2 hours after a meal. If your child does not use all of the medicine in the bottle, throw it away after you give the dose.

If you or your child vomits within one hour of taking the Zmax® extended-release oral suspension, call your doctor right away to see if more medicine is needed.

Keep using azithromycin for the full treatment time, even if you or your child feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.

If you are taking aluminum or magnesium-containing antacids, do not take them at the same time that you take Zithromax®. These medicines may keep azithromycin from working properly. However, you can take antacids with Zmax®.

Dosing

The dose of azithromycin will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of azithromycin. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release suspension):
  • For treatment of pneumonia:
    • Adults—2 grams (g) once as a single dose.
    • Children weighing 34 kilograms (kg) or more—Dose is based on body weight and must be determined by your doctor. The dose is usually 2 grams once a day, taken as a single dose.
    • Children 6 months of age and older weighing less than 34 kg—Dose is based on body weight and must be determined by your doctor. The dose is usually 60 milligrams (mg) per kilogram (kg) of body weight once a day, taken as a single dose.
  • For treatment of sinusitis:
    • Adults—2 grams (g) once a day as a single dose.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage forms (suspension or tablets):
  • For treatment of infections:
    • Adults—500 to 2000 milligrams (mg) once a day, taken as a single dose. Depending on the type of infection, this may be followed with doses of 250 to 500 mg once a day for several days.
    • Children 6 months of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 10 to 30 milligrams (mg) per kilogram (kg) of body weight once a day, taken as a single dose. Depending on the type of infection, this may be followed with doses of 5 to 10 mg per kg of body weight once a day for several days.
    • Children younger than 6 months of age—Use and dose must be determined by your doctor.
  • For treatment of pharyngitis or tonsillitis:
    • Adults—500 milligrams (mg) on Day 1 (the first day), taken as a single dose. Then, 250 mg on Day 2 through Day 5.
    • Children 2 years of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 12 milligrams (mg) per kilogram (kg) of body weight once a day for 5 days.
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of azithromycin, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Do not refrigerate or freeze the Zmax® extended-release oral suspension. After water has been added to the powder, use the dose within 12 hours and throw away any unused liquid after your dose.

You may store the Zithromax® oral liquid at room temperature or in the refrigerator. Do not freeze the bottle. Do not keep the oral liquid for more than 10 days. Throw away any unused liquid after all doses are completed.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Diarrhea
• loose stools

• Blistering, crusting, irritation, itching, or reddening of the skin
• cracked, dry, or scaly skin
• fever
• swelling

• Abdominal or stomach pain
• blistering, peeling, or loosening of the skin
• bloody or cloudy urine
• bloody, black, or tarry stools
• body aches or pain
• burning while urinating
• chest pain
• chills
• congestion
• cough increased
• cough producing mucus
• dark urine
• difficult or labored breathing
• difficult or painful urination
• dizziness
• drowsiness
• dryness or soreness of the throat
• earache
• fainting
• fast, irregular, pounding, or racing heartbeat or pulse
• general feeling of discomfort or illness
• general feeling of tiredness or weakness
• headache
• indigestion
• irregular or slow heart rate
• itching or rash
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• loss of appetite
• muscle aches and pains
• nausea or vomiting
• noisy breathing
• passing of gas
• red skin lesions, often with a purple center
• red, irritated eyes
• redness or swelling in the ear
• runny nose
• shivering
• sneezing
• sores, ulcers, or white spots on the lips or in the mouth
• stomach pain, continuing
• stomach pain, fullness, or discomfort
• stuffy nose
• sweating
• swelling of the face, ankles, hands, feet, or lower legs
• tender, swollen glands in the neck
• tightness in the chest
• trouble with sleeping
• trouble with swallowing
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• upper right abdominal or stomach pain
• voice changes
• vomiting of blood
• yellow eyes or skin

• Abdominal or stomach cramps or tenderness
• bleeding gums
• bloating
• blood in the urine or stools
• blurred vision
• change in hearing
• clay-colored stools
• coma
• confusion
• constipation
• continuing ringing or buzzing or other unexplained noise in the ears
• decreased urine output
• depression
• diarrhea, watery and severe, which may also be bloody
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• greatly decreased frequency of urination or amount of urine
• hives
• hostility
• increased thirst
• irritability
• lethargy
• loss of hearing
• lower back or side pain
• muscle twitching
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pale skin
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain
• seizures
• stupor
• unusual weight loss

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• aggressive or angry
• bad, unusual, or unpleasant (after) taste
• belching
• burning feeling in the chest or stomach
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in taste
• changes in the color of the tongue
• crying
• depersonalization
• dry mouth
• dysphoria
• euphoria
• excess air or gas in the stomach or intestines
• feeling of constant movement of self or surroundings
• full feeling
• heartburn
• hyperventilation
• increase in body movements
• itching of the vagina or genital area
• lack or loss of strength
• mental depression
• nervousness
• pain during sexual intercourse
• paranoia
• quick to react or overreact emotionally
• rapidly changing moods
• rash with flat lesions or small raised lesions on the skin
• redness of the skin
• restlessness
• sensation of spinning
• shaking
• sleepiness or unusual drowsiness
• stomach upset
• thick, white vaginal discharge with no odor or with a mild odor
• white patches in the mouth, tongue, or throat

• Difficulty with moving
• increased sensitivity of the skin to sunlight
• muscle pain or stiffness
• pain in the joints
• redness or other discoloration of the skin
• severe sunburn
• trouble sitting still

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials, most of the reported adverse reactions 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 ZITHROMAX (azithromycin) therapy because of treatment-related adverse reactions. Serious adverse reactions included angioedema and cholestatic jaundice. Most of the adverse reactions leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. [see Clinical Studies]

Multiple-dose Regimen

Overall, the most common adverse reactions in adult patients receiving a multiple-dose regimen of ZITHROMAX were related to the gastrointestinal system with diarrhea/loose stools (5%), nausea (3%), and abdominal pain (3%) being the most frequently reported.

No other adverse reactions occurred in patients on the multiple-dose regimen of ZITHROMAX with a frequency greater than 1%. Adverse reactions that occurred with a frequency of 1% or less included the following:

Cardiovascular: Palpitations and chest pain.

Gastrointestinal: Dyspepsia, flatulence, vomiting, melena, and cholestatic jaundice.

Genitourinary: Monilia, vaginitis, and nephritis.

Nervous System: Dizziness, headache, vertigo, and somnolence.

General: Fatigue.

Allergic: Rash, photosensitivity, and angioedema.

The nature of adverse reactions seen with the 1200 mg weekly dosing regimen for the prevention of Mycobacterium avium infection in severely immunocompromised HIV-infected patients were similar to those seen with short-term dosing regimens. [see Clinical Studies]

The nature of adverse reactions seen with the 600 mg daily dosing regimen for the treatment of Mycobacterium avium complex infection in severely immunocompromised HIV-infected patients were similar to those seen with short term dosing regimens. Five percent of patients experienced reversible hearing impairment in the pivotal clinical trial for the treatment of disseminated MAC in patients with AIDS. Hearing impairment has been reported with macrolide antibiotics, especially at higher doses. Other treatment related adverse reactions occurring in > 5% of subjects and seen at any time during a median of 87.5 days of therapy include: abdominal pain (14%), nausea (14%), vomiting (13%), diarrhea (12%), flatulence (5%), headache (5%), and abnormal vision (5%). Discontinuations from treatment due to laboratory abnormalities or adverse reactions considered related to study drug occurred in 8 of 88 (9.1%) of subjects.

Single 1 Gram Dose Regimen

Overall, the most common adverse reactions in patients receiving a single-dose regimen of 1 gram of ZITHROMAX were related to the gastrointestinal system and were more frequently reported than in patients receiving the multiple-dose regimen.

Adverse reactions that occurred in patients on the single 1 gram dosing regimen of ZITHROMAX with a frequency of 1% or greater included diarrhea/loose stools (7%), nausea (5%), abdominal pain (5%), vomiting (2%), dyspepsia (1%), and vaginitis (1%).

Post-marketing Experience

The following adverse reactions have been identified during post approval use of azithromycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions 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 reports of QT prolongation and torsades de pointes.

Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea pseudomembranous colitis, pancreatitis, oral candidiasis, pyloric stenosis, and tongue discoloration.

General: Asthenia, paresthesia, fatigue, malaise, and anaphylaxis

Genitourinary: Interstitial nephritis, acute renal failure, and vaginitis.

Hematopoietic: Thrombocytopenia.

Liver/Biliary: Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure. [see WARNINGS AND PRECAUTIONS]

Nervous System: Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation, and syncope.

Psychiatric: Aggressive reaction and anxiety.

Skin/Appendages: Pruritus, and serious skin reactions including erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and DRESS.

Special Senses: Hearing disturbances including hearing loss, deafness, and/or tinnitus, and reports of taste/smell perversion and/or loss.

Laboratory Abnormalities

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

• With an incidence of 1-2%, 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 1 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/mm³).

Laboratory abnormalities seen in clinical trials for the prevention of disseminated Mycobacterium avium disease in severely immunocompromised HIV-infected patients. [see Clinical Studies]

Chronic therapy (median duration: 87.5 days, range: 1-229 days) that resulted in laboratory abnormalities in > 5% of subjects with normal baseline values in the pivotal trial for treatment of disseminated MAC in severely immunocompromised HIV-infected patients treated with azithromycin 600 mg daily in combination with ethambutol include: a reduction in absolute neutrophils to < 50% of the lower limit of normal (10/52, 19%) and an increase to five times the upper limit of normal in alkaline phosphatase (3/35, 9%). These findings in subjects with normal baseline values are similar when compared to all subjects for analyses of neutrophil reductions (22/75, 29%) and elevated alkaline phosphatase (16/80, 20%). Causality of these laboratory abnormalities due to the use of study drug has not been established.

Read the entire FDA prescribing information for Zithromax (Azithromycin)

Get emergency medical help if you have signs of an allergic reaction to azithromycin: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

In rare cases, azithromycin may cause a severe skin reaction that can be fatal if it spreads to other parts of the body. Seek medical treatment if you have a new or worsening skin rash with fever, swollen glands, flu symptoms, or severe tingling or numbness.

Call your doctor at once if you have:

• severe stomach pain, diarrhea that is watery or bloody;

• headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;

• liver problems - nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

• severe skin reaction - fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain or swelling, pus-filled pimples, red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Call your doctor right away if a baby taking azithromycin becomes irritable or vomits while eating or nursing.

Older adults may be more likely to have side effects on heart rhythm, including a life-threatening fast heart rate.

Common azithromycin side effects may include:

• diarrhea;

• nausea, vomiting, stomach pain; or

• headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Commonly reported side effects of azithromycin include: diarrhea, loose stools, and nausea. Other side effects include: abdominal pain, and vomiting. See below for a comprehensive list of adverse effects.

Community-acquired pneumonia:
Oral:
-Immediate-release: 500 mg orally as a single dose on day 1, followed by 250 mg orally once a day on days 2 to 5
-Extended-release: 2 g orally once as a single dose

Parenteral: 500 mg IV once a day as a single dose for at least 2 days, followed by 500 mg (immediate-release formulation) orally to complete a 7- to 10-day course of therapy

Comment: Extended-release formulations should be taken on an empty stomach.

Uses:
-Treatment of mild community acquired pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae in patients appropriate for oral therapy
-Treatment of community-acquired pneumonia due to C pneumoniae, H influenzae, Legionella pneumophila, Moraxella catarrhalis, M pneumoniae, or S pneumoniae in patients who require initial IV therapy

Non-gonococcal urethritis and cervicitis:
-Immediate-release: 1 g orally once

Comment: A 1 g oral dose given once a week for 3 weeks may be effective in the treatment of lymphogranuloma venereum due to Chlamydia trachomatis.

Uses:
-Treatment of mild to moderate urethritis and cervicitis due to C trachomatis
-Treatment of nongonococcal urethritis, cervicitis, and chlamydial infections

Immediate-release: 500 mg orally once a day for 3 days OR 500 mg orally as a single dose on day 1, followed by 250 mg orally once a day on days 2 to 5

Uses:
-Mild to moderate acute bacterial exacerbations of COPD
-Treatment of mild to moderate acute bacterial exacerbations of chronic bronchitis due to H influenzae, M catarrhalis, or S pneumoniae

Immediate-release:
1200 mg orally once a week

Comment: This drug may be given with rifabutin.

Use: Prevention of disseminated Mycobacterium avium-intracellulare complex (MAC) disease

NIH, IDSA, and ATS Recommendations:
Immediate-release:
Patients with AIDS and CD4 counts less than 50 cells/mcL:
-Primary prophylaxis: 1200 mg orally once a week OR 600 mg orally 2 times a week

Comment: Primary prophylaxis may be discontinued when the CD3 count is greater than 100 cells/mm3 for at least 3 months in response to antiretroviral therapy.

Use: Preventing the first episode of disseminated MAC disease

American Society for Blood and Marrow Transplantation (ASBMT) and IDSA Recommendations:
Immediate-release:
Immunization against pertussis:
-Alternative treatment: 250 mg orally once a day

Postexposure prophylaxis: 500 mg orally once on day 1, then 250 mg orally once a day for 4 days

Comments:
-Patients should receive the acellular pertussis vaccine after hematopoietic cell transplantation (HCT).
-Treatment with this drug may be given to patients with an incomplete vaccination series.

Uses:
-Immunization against pertussis for adult recipients after HCT
-Postexposure prophylaxis for HCT recipients, regardless of vaccination status
-Prophylaxis against bacterial infections

NIH Recommendations:
Immediate-release: 900 to 1200 mg orally once a day plus pyrimethamine and leucovorin
-Duration of therapy: At least 6 weeks; longer treatment may be required if clinical/radiologic disease is extensive or response is incomplete at 6 weeks

Comments:
-This drug is recommended as an alternative regimen.
-Patients should continue chronic maintenance therapy once acute treatment is complete.

Use: Treatment of Toxoplasma gondii encephalitis

NIH Recommendations:
Immediate-release:
-Alternative treatment: 2 g orally as a single dose

Comments:
-This drug may be given to patients with penicillin allergies.
-Use should be avoided in men who have sex with men or pregnant patients.

Use: Alternative therapy for the treatment of early stage syphilis, including primary, secondary, and early latent stage syphilis

US CDC Recommendations:
Immediate-release:
Adolescents: 1 g orally once

Comments:
-The efficacy of this drug in female patients with chancroid has not been established.
-The patient's sexual partner(s) during the 10 days preceding the onset of symptoms should be evaluated/treated.
-Patients should be tested for HIV infection when chancroid is diagnosed and a serologic test for HIV and syphilis should be performed 3 months after diagnosis in patients with negative initial HIV test results.

Use: Treatment of genital ulcer disease in men due to H ducreyi (chancroid)

NIH and IDSA Recommendations:
Immediate-release:
CHILDREN:
Primary prophylaxis of MAC disease:
-First choice: 20 mg/kg orally once a week (max 1200 mg/week)
-Alternative choice: 5 mg/kg orally once a day (max 250 mg/day)

Secondary prophylaxis/chronic suppressive therapy):
-Alternative choice: 5 mg/kg (maximum: 250 mg) orally once a day plus ethambutol with/without rifabutin

ADOLESCENTS:
Patients with AIDS and CD4 counts less than 50 cells/mcL:
-Primary prophylaxis: 1200 mg orally once a week OR 600 mg orally 2 times a week

Comments:
-Primary prophylaxis may be discontinued when the CD3 count is greater than 100 cells/mm3 for at least 3 months in response to antiretroviral therapy (ART).
-Secondary prophylaxis is usually continued for life; however, discontinuation may be considered in patients with sustained immune recovery in response to ART.

Use: Preventing the first episode of disseminated MAC disease

ASBMT and IDSA Recommendations:
Immediate-release:
Immunization against pertussis:
-Alternative treatment: 5 mg/kg orally once a day

Postexposure prophylaxis: 10 mg/kg orally (as a loading dose), then 5 mg/kg orally once a day for 4 days

Comments:
-Patients should receive the acellular pertussis vaccine after hematopoietic cell transplantation (HCT).
-Treatment with this drug may be given to patients with an incomplete vaccination series.

Uses:
-Immunization against pertussis for adult HCT recipients
-Postexposure prophylaxis for HCT recipients, regardless of vaccination status

US CDC Recommendations:
Immediate-release:
Adolescents: 900 to 1200 mg orally once a day plus pyrimethamine and leucovorin
-Duration of treatment: At least 6 weeks; longer treatment may be required if clinical/radiologic disease is extensive or response is incomplete at 6 weeks

Comments:
-This drug is recommended as an alternative regimen.
-Patients should be continued on chronic maintenance therapy once acute treatment ends.

Use: Treatment of T gondii encephalitis

NIH Recommendations:
Immediate-release:
Adolescents:
Campylobacteriosis:
-Mild to moderate disease: 500 mg orally once a day for 5 days

Shigellosis:
-Alternative therapy: 500 mg orally once a day for 5 days

Comment: This drug should not be used to treat Shigella or Campylobacter bacteremia.

Uses:
-Treatment of gastroenteritis caused by Shigella infection
-Treatment of mild to moderate campylobacteriosis

NIH Recommendations:
Immediate-release:
Adolescents:
-Alternative treatment: 2 g orally as a single dose

Comments:
-This drug may be given to patients with penicillin allergies.
-Use should be avoided in men who have sex with men or pregnant patients.

Use: Alternative therapy for the treatment of early stage syphilis, including primary, secondary, and early latent stage syphilis