DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Zmax (Azithromycin) - Description and Clinical Pharmacology

 
 



To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zmax and other antibacterial drugs, Zmax should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

DESCRIPTION

Zmax (azithromycin extended release) for oral suspension contains the active ingredient azithromycin (as azithromycin dihydrate), an azalide, a subclass of macrolide antibiotics. 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 -hexopyranosyl) 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.

CLINICAL PHARMACOLOGY

Mechanism of Action

Azithromycin is an antimicrobial agent [See Clinical Pharmacology]

Pharmacodynamics

Based on animal models of infection, the antimicrobial 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 Zmax.

Pharmacokinetics

Zmax is an extended release microsphere formulation. Based on data obtained from studies evaluating the pharmacokinetics of azithromycin in healthy adult subjects a higher peak serum concentration (Cmax) and greater systemic exposure (AUC 0–24) of azithromycin are achieved on the day of dosing following a single 2 g dose of Zmax versus 1.5 g of azithromycin tablets administered over 3 days (500 mg/day) or 5 days (500 mg on day 1, 250 mg/day on days 2–5) [Table 2]. Consequently, due to these different pharmacokinetic profiles, Zmax is not interchangeable with azithromycin tablet 3-day and 5-day dosing regimens.

Table 2. Mean (SD) Pharmacokinetic Parameters for Azithromycin on Day 1 Following the Administration of a Single Dose of 2 g Zmax or 1.5 g of Azithromycin Tablets Given over 3 Days (500 mg/day) or 5 Days (500 mg on Day 1 and 250 mg on Days 2–5) to Healthy Adult Subjects
Pharmacokinetic ParameterZmax, 3-day and 5-day regimen parameters obtained from separate pharmacokinetic studiesAzithromycin Regimen
Zmax
[N=41]N = 21 for AUC0–∞ and t1/2
3-day 1
[N=12]
5-day
[N=12]
SD = standard deviation
Cmax = maximum serum concentration
Tmax = time to Cmax
AUC = area under concentration vs. time curve
t1/2 = terminal serum half-life
Cmax (µg/mL) 0.821
(0.281)
0.441
(0.223)
0.434
(0.202)
TmaxMedian (range) (hr) 5.0
(2.0–8.0)
2.5
(1.0–4.0)
2.5
(1.0–6.0)
AUC0–24 (µg∙hr/mL) 8.62
(2.34)
2.58
(0.84)
2.60
(0.71)
AUC0–∞Total AUC for the 1-day, 3-day and 5-day regimens (µg∙hr/mL) 20.0
(6.66)
17.4
(6.2)
14.9
(3.1)
t1/2 (hr) 58.8
(6.91)
71.8
(14.7)
68.9
(13.8)

1 Cmax, Tmax and AUC0–24 values for Day 1 only

Absorption

The bioavailability of Zmax relative to azithromycin immediate release (IR) (powder for oral suspension) was 83%. On average, peak serum concentrations were achieved approximately 2.5 hours later following Zmax administration and were lower by 57%, compared to 2 g azithromycin IR. Thus, single 2 g doses of Zmax and azithromycin IR are not bioequivalent and are not interchangeable.

Effect of food on absorption: A high-fat meal increased the rate and extent of absorption of a 2 g dose of Zmax (115% increase in Cmax, and 23% increase in AUC0–72) compared to the fasted state. A standard meal also increased the rate of absorption (119% increase in Cmax) and with less effect on the extent of absorption (12% increase in AUC0–72) compared to administration of a 2 g Zmax dose in the fasted state.

Effect of antacids: Following the administration of Zmax with an aluminum and magnesium hydroxide antacid, the rate and extent of azithromycin absorption were not altered.

Distribution

The serum protein binding of azithromycin is concentration dependent, decreasing from 51% at 0.02 µg/mL to 7% at 2 µg/mL. Following oral administration, azithromycin is widely distributed throughout the body with an apparent steady-state volume of distribution of 31.1 L/kg.

Azithromycin concentrates in fibroblasts, epithelial cells, macrophages, and circulating neutrophils and monocytes. Higher azithromycin concentrations in tissues than in plasma or serum have been observed. White blood cell and lung exposure data in humans following a single 2 g dose of Zmax in adults are shown in Table 3. Following a 2 g single dose of Zmax, azithromycin achieved higher exposure (AUC0–120) in mononuclear leukocytes (MNL) and polymorphonuclear leukocytes (PMNL) than in serum. The azithromycin exposure (AUC0–72) in lung tissue and alveolar cells (AC) was approximately 100 times that in serum; and the exposure in epithelial lining fluid (ELF) was also higher (approximately 2–3 times) than in serum. The clinical significance of this distribution data is unknown.

Table 3. Azithromycin Exposure Data in White Blood Cells and Lung Following a 2 g Single Dose of Zmax in Adults
A single 2 g dose of Zmax
Abbreviation: WBC: white blood cells; MNL: mononuclear leukocytes; PMNL: polymorphonuclear leukocytes; ELF: Epithelial lining fluid
WBCCmax (µg/mL)AUC0–24 (µg∙hr/mL)AUC0–120 (µg∙hr/mL)Ct=120Azithromycin concentration at 120 hours after the start of dosing (µg/mL)
  MNL 1 116 1790 (540)4710 (1100)16.2 (5.51)
PMNL146 (66.0)2080 (650)10000 (2690)81.7 (23.3)
 
LUNGCmax (µg/mL)AUC0–24 (µg∙hr/mL)AUC0–72 (µg∙hr/mL)
ALVEOLAR CELL 2 669702820403-
  ELF3.217.6131-
 
Cmax (µg/g)AUC0–24 (µg∙hr/g)AUC0–72 (µg∙hr/g)
  LUNG TISSUE37.95051693-

1 Data are presented as mean (standard deviation)
2 Cmax and AUC were calculated based on composite profile (n = 4 subjects/time point/formulation).

Following a regimen of 500 mg of azithromycin tablets on the first day and 250 mg daily for 4 days, only very low concentrations were noted in cerebrospinal fluid (less than 0.01 µg/mL) in the presence of non-inflamed meninges.

Metabolism

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

Excretion

Serum azithromycin concentrations following a single 2 g dose of Zmax declined in a polyphasic pattern with a terminal elimination half-life of 59 hours. The prolonged terminal half-life is thought to be due to a large apparent volume of distribution.

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.

Special Populations

Renal Impairment

Azithromycin pharmacokinetics were 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 × 250 mg capsules), the mean Cmax and AUC0–120 were 5.1% and 4.2% higher, 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 were 61% and 35% higher, respectively in subjects with GFR <10 mL/min compared to subjects with normal renal function. (See Renal Impairment.)

Hepatic Impairment

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

Pediatric Patients

The pharmacokinetics of azithromycin were characterized following a single 60 mg/kg dose of Zmax in pediatric patients aged 3 months to 16 years. Although there was high inter-patient variability in systemic exposure (AUC and Cmax) across the age groups studied, individual azithromycin AUC and Cmax values in pediatric patients were comparable to or higher than those following administration of 2 g Zmax in adults (Table 4). (See Pediatric Use.)

Table 4. Mean (SD) Pharmacokinetic Parameters for Azithromycin Following Administration of a Single Dose of Zmax (60 mg/kg, maximum dose of 2 g) to Pediatric Subjects Aged 3 Months to 16 Years
Treatment GroupPharmacokinetic Parameters
Cmax
(µg/mL)
TmaxMedian (range) presented only for Tmax
(hr)
AUC(0–24)
(µg∙hr/mL)
AUC(0–∞)
(µg∙hr/mL)
Empty stomach = dosed with Zmax at least 1 hour before or 2 hours after a meal (Groups I–VI)
Fed = dosed with Zmax within 5 minutes of consuming an age-appropriate high-fat breakfast (Group VII)
Group 1 (N = 6)
[3 to 18 months]
0.74 (0.20)3 (3–3)6.29 (1.17)14.1 (2.16)
(n = 3)
Group 2 1 (N = 6)
[>18 to 36 months]
1.88 (0.50)3 (3–3)19.7 (5.35)37.3 (12.9)
(n = 5)
Group 3 (N = 6)
[>36 to 48 months]
1.23 (0.42)3 (3–6)12.9 (3.79)22.4 (5.96)
Group 4 (N = 6)
[>48 months to 8 years]
1.13 (0.34)3 (3–6)13.0 (4.21)22.2 (6.89)
Group 5 (N = 6)
[>8 to 12 years]
1.65 (0.38)3 (3–6)16.0 (4.99)30.1 (10.7)
Group 6 (N = 6)
[>12 to 16 years]
0.98 (0.35)3 (3–6)11.0 (4.78)21.3 (9.37)
Pooled 1–6 (N = 36)
[On an empty stomach]
1.27 (0.53)3 (3–6)13.1 (5.78)25.2 (10.7)
(n = 32)
Group 7One subject vomited immediately after dosing and discontinued from the study (N = 7)
[Fed; 18 months to 8 years]
1.41 (0.62)3 (1.5–3.1)7.43 (3.00)18.9 (3.57)
(n = 3)

1 High mean values were driven by 2 subjects with high exposure

Gender

The impact of gender on the pharmacokinetics of azithromycin has not been evaluated for Zmax. However, previous studies have demonstrated no significant differences in the disposition of azithromycin between male and female subjects.

Pharmacokinetic Interaction Studies

A drug interaction study was performed with Zmax and antacids. All other drug interaction studies were performed with azithromycin immediate release (IR) formulations (capsules and tablets, doses ranging from 500 to 1200 mg) and other drugs likely to be co-administered. The effects of co-administration of azithromycin on the pharmacokinetics of other drugs are shown in Table 5 and the effects of other drugs on the pharmacokinetics of azithromycin are shown in Table 6.

When used at therapeutic doses, azithromycin IR had a minimal effect on the pharmacokinetics of atorvastatin, carbamazepine, cetirizine, didanosine, efavirenz, fluconazole, indinavir, midazolam, nelfinavir, sildenafil, theophylline (intravenous and oral), triazolam, trimethoprim/sulfamethoxazole or zidovudine (Table 5). Although the drug interaction studies were not conducted with Zmax, similar modest effect as observed with IR formulation are expected since the total exposure to azithromycin is comparable for Zmax and other azithromycin IR regimens. Therefore, no dosage adjustment of drugs listed in Table 5 is recommended when co-administered with Zmax.

Nelfinavir significantly increased the Cmax and AUC of azithromycin following co-administration with azithromycin IR 1200 mg (Table 6). However, no dose adjustment of azithromycin is recommended when Zmax is co-administered with nelfinavir.

Pharmacokinetic and/or pharmacodynamic interactions with the drugs listed below have not been reported in clinical trials with azithromycin; however, no specific drug interaction studies have been performed to evaluate potential drug-drug interaction. Nonetheless, pharmacokinetic and/or pharmacodynamic interactions with these drugs have been observed with other macrolide products. Until further data are developed, careful monitoring of patients is advised when azithromycin and these drugs are used concomitantly: digoxin, ergotamine or dihydroergotamine, cyclosporine, hexobarbital and phenytoin.

Table 5. Drug Interactions: Pharmacokinetic Parameters of Co-administered Drugs in the Presence of Azithromycin
Co-administered DrugDose of Co-administered DrugDose of AzithromycinRefers to azithromycin capsules and tablets unless specifiednRatio (with/without Azithromycin) of Co-administered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1.00
Mean CmaxMean AUC
Atorvastatin 10 mg/day × 8 days500 mg/day PO on days 6–8120.83
(0.63 to 1.08)
1.01
(0.81 to 1.25)
Carbamazepine 200 mg/day × 2 days, then 200 mg BID × 18 days500 mg/day PO for days 16–1870.97
(0.88 to 1.06)
0.96
(0.88 to 1.06)
Cetirizine 20 mg/day × 11 days500 mg PO on day 7, then 250 mg/day on days 8–11141.03
(0.93 to 1.14)
1.02
(0.92 to 1.13)
Didanosine 200 mg PO BID × 21 days1,200 mg/day PO on days 8–2161.44
(0.85 to 2.43)
1.14
(0.83 to 1.57)
Efavirenz 400 mg/day × 7 days 600 mg PO on day 7141.04 1 0.95
Fluconazole 200 mg PO single dose 1,200 mg PO single dose181.04
(0.98 to 1.11)
1.01
(0.97 to 1.05)
Indinavir 800 mg TID × 5 days1,200 mg PO on day 5180.96
(0.86 to 1.08)
0.90
(0.81 to 1.00)
Midazolam 15 mg PO on day 3500 mg/day PO × 3 days121.27
(0.89 to 1.81)
1.26
(1.01 to 1.56)
Nelfinavir 750 mg TID × 11 days1,200 mg PO on day 9140.90
(0.81 to 1.01)
0.85
(0.78 to 0.93)
Sildenafil 100 mg on days 1 and 4500 mg/day PO × 3 days121.16
(0.86 to 1.57)
0.92
(0.75 to 1.12)
Theophylline 4 mg/kg IV on days 1, 11, 25500 mg PO on day 7, then 250 mg/day on days 8–11101.19
(1.02 to 1.40)
1.02
(0.86 to 1.22)
Theophylline 300 mg PO BID × 15 days500 mg PO on day 6, then 250 mg/day on days 7–1081.09
(0.92 to 1.29)
1.08
(0.89 to 1.31)
Triazolam 0.125 mg on day 2500 mg PO on day 1, then 250 mg/day on day 2121.061.02
Trimethoprim/
Sulfamethoxazole
160 mg/800 mg/day PO × 7 days1,200 mg PO on day 7120.85
(0.75 to 0.97)/
0.90
(0.78 to 1.03)
0.87
(0.80 to 0.95)/
0.96
(0.88 to 1.03)
Zidovudine 500 mg/day PO × 21 days600 mg/day PO × 14 days51.12
(0.42 to 3.02)
0.94
(0.52 to 1.70)
Zidovudine 500 mg/day PO × 21 days1,200 mg/day PO × 14 days41.31
(0.43 to 3.97)
1.30
(0.69 to 2.43)

1 90% confidence interval not reported

Table 6. Drug Interactions: Pharmacokinetic Parameters of Azithromycin in the Presence of Co-administered Drugs
Co-administered DrugDose of Co-administered DrugDose of AzithromycinRefers to azithromycin capsules and tablets unless specifiednRatio (with/without co-administered drug) of Azithromycin Pharmacokinetic Parameters (90% CI); No Effect = 1.00
Mean CmaxMean AUC
Efavirenz 400 mg/day × 7 days 600 mg PO on day 7141.22
(1.04 to 1.42)
0.9290% confidence interval not reported
Fluconazole 200 mg PO single dose1,200 mg PO single dose180.82
(0.66 to 1.02)
1.07
(0.94 to 1.22)
Nelfinavir 750 mg TID × 11 days1,200 mg PO on day 9142.36
(1.77 to 3.15)
2.12
(1.80 to 2.50)
Aluminum and Magnesium hydroxide 20 mL regular strength, single dose 2 g Zmax, single dose 390.99
(0.93 to 1.06)
0.99
(0.92 to 1.08)

Microbiology

Mechanism of Action

Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms, thus interfering with microbial protein synthesis. Nucleic acid synthesis is not affected.

Spectrum of Activity

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

Aerobic and facultative Gram-positive microorganisms
  Streptococcus pneumoniae

NOTE: Erythromycin- and penicillin-resistant Gram-positive isolates may demonstrate cross-resistance to azithromycin.

Aerobic and facultative Gram-negative microorganisms
  Haemophilus influenzae
  Moraxella catarrhalis

Beta-lactamase production should not affect azithromycin activity.

"Other" microorganisms
  Chlamydophila pneumoniae
  Mycoplasma pneumoniae

The following in vitro data are available, but their clinical si g nificance is unknown.

At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the azithromycin susceptible breakpoints of <4 µg/mL. However, the safety and effectiveness of azithromycin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.

Aerobic and facultative Gram-positive microorganisms
  Staphylococcus aureus
  Streptococcus agalactiae
  Streptococcus pyogenes

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

Aerobic and facultative Gram-negative microorganisms
  Bordetella pertussis
  Legionella pneumophila

Anaerobic microorganisms
  Peptostreptococcus species
   Prevotella bivia

"Other" microorganisms
  Ureaplasma urealyticum

Susceptibility Testing Methods:

When available, the clinical microbiology laboratory should provide cumulative results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.

Dilution techniques:

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1,3 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of azithromycin powder. The MIC values should be interpreted according to criteria provided in Table 7.

Diffusion techniques:

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 15-µg azithromycin to test the susceptibility of microorganisms to azithromycin. The disk diffusion interpretive criteria are provided in Table 7.

Table 7. Susceptibility Test Result Interpretive Criteria for Azithromycin
Minimum Inhibitory
Concentrations (µg/mL)
Disk Diffusion
(zone diameters in mm)
PathogenSIR 1 SIR
Haemophilus influenzae ≤ 4 -- -- ≥ 12 -- --
Streptococcus pneumoniae ≤ 0.5
1≥ 2≥ 1814–17≤ 13

1 The current absence of data on resistant strains precludes defining any category other than "susceptible." If strains yield MIC results other than susceptible, they should be submitted to a reference laboratory for further testing.

No interpretive criteria have been established for testing Moraxella catarrhalis. This species is not usually tested.

A report of "susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound reaches the concentrations usually achievable. 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 implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. 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 the pathogen is not likely to be inhibited if the antimicrobial compound reaches the concentrations usually achievable; other therapy should be selected.

Quality Control:

Standardized susceptibility test procedures require the use of quality control microorganisms to determine if the test was performed correctly. Standard azithromycin powder should provide the range of values noted in Table 8. Quality control (QC) microorganisms are specific strains of organisms with intrinsic biological properties. QC strains are very stable strains, which will give a standard and repeatable susceptibility pattern. The specific strains used for microbiological quality control are not clinically significant.

Table 8. Acceptable Quality Control Ranges for Azithromycin
QC StrainMinimum Inhibitory Concentrations (µg/mL)Disk Diffusion
(zone diameters in mm)
Haemophilus influenzae
  ATCC 49247
1.0–4.013–21
Streptococcus pneumoniae
  ATCC 49619
0.06–0.2519–25

NONCLINICAL TOXICOLOGY

1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. No evidence of impaired fertility due to azithromycin was found in rats given daily doses up to 10 mg/kg (approximately 0.05 times the single 2 g oral adult human dose on a mg/m2 basis).

2 Animal Toxicology and/or Pharmacology

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 treated with azithromycin at doses which, expressed on the basis of mg/m2, are approximately one-sixth the recommended adult dose, and in rats treated at doses approximately one-fourth the recommended adult 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 µg/mL (1.6 times the observed Cmax of 0.821 µg/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 µg/mL (1.2 times the observed Cmax of 0.821 µg/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 on a mg/m2 basis, but was not observed in neonatal rats treated for 10 days at 40 mg/kg/day with mean maximal serum concentrations of 1.86 µg/ml, approximately 1.5 times the Cmax of 1.27 µg/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 µg/ml, approximately 3 times the pediatric dose Cmax.

The significance of the finding for animals and for humans is unknown.

CLINICAL STUDIES

Acute Bacterial Maxillary Sinusitis

Adult subjects with a diagnosis of acute bacterial maxillary sinusitis were evaluated in a randomized, double-blind, multicenter study; a maxillary sinus tap was performed on all subjects at baseline. Clinical evaluations were conducted for all subjects at the TOC visit, 7 to 14 days post-treatment. Two hundred seventy (270) subjects were treated with a single 2 g oral dose of Zmax and 268 subjects were treated with levofloxacin, 500 mg orally QD for 10 days. A subject was considered a cure if signs and symptoms related to the acute infection had resolved, or if clinical improvement was such that no additional antibiotics were deemed necessary. The clinical response for the primary population, Clinical Per Protocol Subjects, is presented below.

ZMAXLEVOFLOXACIN
RESPONSE AT TOC N = 255N = 254
   CURE 241 (94.5%)236 (92.9%)
   FAILURE 14 (5.5%)18 (7.1%)

Clinical response by pathogen in the Bacteriologic Per Protocol population is presented below.

ZmaxLevofloxacin
Pathogen NCureNCure
S. pneumoniae 3736 (97.3%)3936 (92.3%)
H. influenzae 2726 (96.3%)3030 (100.0%)
M. catarrhalis 88 (100.0%)1110 (90.9%)

Community-Acquired Pneumonia

Adult subjects with a diagnosis of mild-to-moderate community-acquired pneumonia were evaluated in two, randomized, double-blind, multicenter studies. In both studies, clinical and microbiologic evaluations were conducted for all subjects at the Test of Cure (TOC) visit, 7 to 14 days post-treatment. In the first study, 247 subjects were treated with a single 2 g oral dose of Zmax and 252 subjects were treated with clarithromycin extended release, 1 g orally QD for 7 days. In the second study, 211 subjects were treated with a single 2.0 g oral dose of Zmax and 212 subjects were treated with levofloxacin, 500 mg orally QD for 7 days. A patient was considered a cure if signs and symptoms related to the acute infection had resolved, or if clinical improvement was such that no additional antibiotics were deemed necessary; in addition, the chest x-ray performed at the TOC visit was to be either improved or stable. The clinical response at TOC for the primary population, Clinical Per Protocol Subjects, is presented in the table below.

ZMAXCOMPARATOR
ZMAX VS. CLARITHROMYCIN EXTENDED RELEASE N=202N=209
   CURE 187 (92.6%)198 (94.7%)
   FAILURE 15 (7.4%)11 (5.3%)
ZMAX VS. LEVOFLOXACIN N=174N=189
   CURE 156 (89.7%)177 (93.7%)
   FAILURE 18 (10.3%)12 (6.3%)

Clinical response by pathogen in the Bacteriologic Per Protocol population, across both studies, is presented below:

PathogenZmaxComparators
NCureNCure
S. pneumoniae 3328 (84.8%)3935 (89.7%)
H. influenzae 3028 (93.3%)3431 (91.2%)
C. pneumoniae 4037 (92.5%)5350 (94.3%)
M. pneumoniae 3330 (90.9%)3938 (97.4%)

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2014