Azix 500 Actions

Was this medicine useful for you?

Actions of Azix 500 in details


Pharmacology: Like other macrolides, Azix 500 inhibits RNA-dependent protein synthesis by binding to the 50S ribosomal sub unit of the 70S ribosome of susceptible bacteria. The site of action appears to be the same as that of the macrolides, clindamycin, lincomycin, and chloramphenicol. Azix 500 is bactericidal for Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae. It is bacteriostatic for staphylococci and most aerobic gram-negative species. The spectrum of activity of Azix 500 is broader than erythromycin, clarithromycin, or clarithromycin. Azix 500 generally is more active in vitro against gram-negative organism than erythromycin or clarithromycin and has activity comparable to erythromycin against most gram-positive organisms. Beta-lactamases produced by Haemophilus influenzae or Moraxella catarrhalis do not inactivate Azix 500.

Pharmacokinetics: Following oral intake, Azix 500 is widely distributed throughout the body except to cerebrospinal fluid. Bioavailability ranges from 34-52% and was generally maintained when Azix 500 tablets were administered with a meal. Peak plasma levels are reached in 2-3 hours. Plasma terminal elimination half-life closely reflects the tissue depletion half-life of 2-4 days.

After oral administration, Azix 500 is rapidly and widely distributed throughout the body. Unique properties of Azix 500 include extensive tissue distribution and high drug concentrations, within cells (including phagocytes) resulting in much tissue concentrations. Azix 500 concentrates intracellularly, resulting in tissue concentrations 10 to 100 times higher than those found in plasma or serum. Azix 500 is high concentrated in fibroblasts and phagocytic cells, contributing to the distribution of the drug into inflamed and infected tissues. Because of extensive tissue sequestration and binding, the usual elimination half-life of 40-68 hours is prolonged. Penetration of the drug into phagocytic cells is necessary for activity against intracellular pathogens (e.g. Staphylococcus aureus). Only very low concentrations of Azix 500 have been detected in cerebrospinal fluid in patients with non-inflamed meninges.

Following a single oral dose, plasma concentrations of Azix 500 declined with a polyphasic pattern. Azix 500 undergoes some hepatic metabolism to inactive metabolites but more than 50% of Azix 500 is eliminated through biliary secretion as unchanged drug. Azix 500 is excreted in feces primarily as unchanged drug. Approximately 4.5-6% of a dose is eliminated in urine as unchanged drug within 72 hours.

How should I take Azix 500?

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended. The dose and length of treatment with Azix 500 may not be the same for every type of infection.

You may take most forms of Azix 500 with or without food.

Take Zmax extended release liquid (oral suspension) on an empty stomach, at least 1 hour before or 2 hours after a meal.

To use the oral suspension single dose packet: Open the packet and pour the medicine into 2 ounces of water. Stir this mixture and drink all of it right away. Do not save for later use. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

Throw away any mixed Zmax oral suspension that has not been used within 12 hours.

Shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Azix 500 will not treat a viral infection such as the common cold or flu.

Store at room temperature away from moisture and heat. Throw away any unused liquid medicine after 10 days.

Azix 500 administration


IV: Infuse over 1 hour (2 mg/ml infusion) or over 3 hours (1 mg/ml infusion). Not for IM or IV bolus administration.

Oral: Immediate release suspension and tablet may be taken without regard to food; extended release suspension should be taken on an empty stomach (at least 1 hour before or 2 hours following a meal), within 12 hours of reconstitution.

Azix 500 pharmacology

Mechanism of Action

Azix 500 is a macrolide antibacterial drug.

Azix 500 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.


Based on animal models of infection, the antibacterial activity of Azix 500 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 Azix 500.

Cardiac Electrophysiology

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 Azix 500 (500 mg, 1000 mg, and 1500 mg once daily). Coadministration of Azix 500 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 coadministration of 500 mg, 1000 mg and 1500 mg Azix 500, respectively.


The pharmacokinetic parameters of Azix 500 in plasma after dosing as per labeled recommendations in healthy young adults and asymptomatic HIV-positive adults (age 18 to 40 years old) are portrayed in the following chart:


DOSE/DOSAGE FORM (serum, except as indicated)


Day No.

Cmax (mcg/mL)

Tmax (hr)

C24 (mcg/mL)

AUC (mcg•hr/mL)

T1/2 (hr)

Urinary Excretion (% of dose)

500 mg/250 mg capsule








and 250 mg on Days 2 to 5








1200 mg/600 mg tablets














600 mg tablet/day
























600 mg tablet/day (leukocytes)













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

In asymptomatic HIV-positive adult subjects receiving 600 mg Azix 500 Tablets once daily for 22 days, steady state Azix 500 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 Azix 500 capsule

When the oral suspension of Azix 500 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 Azix 500 is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL.

The antibacterial activity of Azix 500 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.

Azix 500 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 Azix 500 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 mcg/mL. Concentration remained above 32 mcg/mL, for approximately 60 hr. The mean half-lives for 6 males and 6 females were 34 hr and 57 hr, respectively. Leukocyte-to-plasma 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 mcg/mL (± 49%). Trough concentrations in peripheral leukocytes at steady-state averaged 146 mcg/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 Azix 500 have not been performed.


Plasma concentrations of Azix 500 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 Azix 500, 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

Renal Insufficiency

Azix 500 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 Azix 500 (4 × 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).

Hepatic Insufficiency

The pharmacokinetics of Azix 500 in subjects with hepatic impairment has not been established.


There are no significant differences in the disposition of Azix 500 between male and female subjects. No dosage adjustment is recommended on the basis of gender.

Geriatric Patients

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.

Pediatric Patients

For information regarding the pharmacokinetics of Azix 500 for oral suspension in pediatric patients, see the prescribing information for Azix 500 for oral suspension 100 mg/5 mL and 200 mg/5 mL bottles.

Drug-drug Interactions

Drug interaction studies were performed with Azix 500 and other drugs likely to be coadministered. The effects of coadministration of Azix 500 on the pharmacokinetics of other drugs are shown in Table 1 and the effects of other drugs on the pharmacokinetics of Azix 500 are shown in Table 2.

Coadministration of Azix 500 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 coadministered with Azix 500.

Coadministration of Azix 500 with efavirenz or fluconazole had a modest effect on the pharmacokinetics of Azix 500. Nelfinavir significantly increased the Cmax and AUC of Azix 500. No dosage adjustment of Azix 500 is recommended when administered with drugs listed in Table 2.

Table 1. Drug Interactions: Pharmacokinetic Parameters for Coadministered Drugs in the Presence of Azix 500
- 90% Confidence interval not reported

Coadministered Drug

Dose of Coadministered Drug

Dose of Azix 500


Ratio (with/without Azix 500) of Coadministered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1.00

Mean Cmax

Mean AUC


10 mg/day for 8 days

500 mg/day orally on days 6 to 8



(0.63 to 1.08)


(0.81 to 1.25)


200 mg/day for 2 days, then 200 mg twice a day for 18 days

500 mg/day orally for days 16 to 18



(0.88 to 1.06)


(0.88 to 1.06)


20 mg/day for 11 days

500 mg orally on day 7, then 250 mg/day on days 8 to 11



(0.93 to 1.14)


(0.92 to 1.13)


200 mg orally twice a day for 21 days

1,200 mg/day orally on days 8 to 21



(0.85 to 2.43)


(0.83 to 1.57)


400 mg/day for 7 days

600 mg orally on day 7





200 mg orally single dose

1,200 mg orally single dose



(0.98 to 1.11)


(0.97 to 1.05)


800 mg three times a day for 5 days

1,200 mg orally on day 5



(0.86 to 1.08)


(0.81 to 1.00)


15 mg orally on day 3

500 mg/day orally for 3 days



(0.89 to 1.81)


(1.01 to 1.56)


750 mg three times a day for 11 days

1,200 mg orally on day 9



(0.81 to 1.01)


(0.78 to 0.93)


100 mg on days 1 and 4

500 mg/day orally for 3 days



(0.86 to 1.57)


(0.75 to 1.12)


4 mg/kg IV on days 1, 11, 25

500 mg orally on day 7, 250 mg/day on days 8 to 11



(1.02 to 1.40)


(0.86 to 1.22)


300 mg orally BID x 15 days

500 mg orally on day 6, then 250 mg/day on days 7 to 10



(0.92 to 1.29)


(0.89 to 1.31)


0.125 mg on day 2

500 mg orally on day 1, then 250 mg/day on day 2




Trimethoprim/ Sulfamethoxazole

160 mg/800 mg/day orally for 7 days

1,200 mg orally on day 7



(0.75 to 0.97)/


(0.80 to 0.95)/


(0.78 to 1.03)


(0.88 to 1.03)


500 mg/day orally for 21 days

600 mg/day orally for 14 days



(0.42 to 3.02)


(0.52 to 1.70)


500 mg/day orally for 21 days

1,200 mg/day orally for 14 days



(0.43 to 3.97)


(0.69 to 2.43)

Table 2. Drug Interactions: Pharmacokinetic Parameters for Azix 500 in the Presence of Coadministered Drugs.
- 90% Confidence interval not reported

Coadministered Drug

Dose of Coadministered Drug

Dose of Azix 500


Ratio (with/without coadministered drug) of Azix 500 Pharmacokinetic Parameters (90% CI); No Effect = 1.00

Mean Cmax

Mean AUC


400 mg/day for 7 days

600 mg orally on day 7



(1.04 to 1.42)



200 mg orally single dose

1,200 mg orally single dose



(0.66 to 1.02)


(0.94 to 1.22)


750 mg three times a day for 11 days

1,200 mg orally on day 9



(1.77 to 3.15)


(1.80 to 2.50)


Azix 500 has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in.

Aerobic Gram-Positive Microorganisms

Staphylococcus aureus
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes

NOTE: Azix 500 demonstrates cross-resistance with erythromycin-resistant gram-positive strains. Most strains of Enterococcus faecalis and methicillin-resistant staphylococci are resistant to Azix 500.

Aerobic Gram-Negative Microorganisms

Haemophilus influenzae
Moraxella catarrhalis

Other Microorganisms

Chlamydia trachomatis

Beta-lactamase production should have no effect on Azix 500 activity.

Azix 500 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.

Azix 500 exhibits in vitro minimal inhibitory concentrations (MICs) of 2.0 mcg/mL or less against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of Azix 500 in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.

Aerobic Gram-Positive Microorganisms

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

Aerobic Gram-Negative Microorganisms

Bordetella pertussis
Campylobacter jejuni
Haemophilus ducreyi
Legionella pneumophila

Anaerobic Microorganisms

Bacteroides bivius
Clostridium perfringens
Peptostreptococcus species

Other Microorganisms

Borrelia burgdorferi
Mycoplasma pneumoniae
Treponema pallidum
Ureaplasma urealyticum

Susceptibility Testing of Bacteria Excluding Mycobacteria

The in vitro potency of Azix 500 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 Azix 500. Thus, the initial pH of the growth medium should be 7.2 to 7.4, and the CO2 content of the incubation atmosphere should be as low as practical.

Azix 500 can be solubilized for in vitro susceptibility testing by dissolving in a minimum amount of 95% ethanol and diluting to working concentration with water.

Dilution Techniques

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 Azix 500 powder. The MIC values should be interpreted according to the following criteria:

MIC (mcg/mL)


≤ 2

Susceptible (S)


Intermediate (I)

≥ 8

Resistant (R)

A report of “Susceptible” indicates that the pathogen is likely to respond to monotherapy with Azix 500. 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. 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 Azix 500 powder should provide the following MIC values:


MIC (mcg/mL)

Escherichia coli ATCC 25922

2.0 to 8.0

Enterococcus faecalis ATCC 29212

1.0 to 4.0

Staphylococcus aureus ATCC 29213

0.25 to 1.0

Diffusion Techniques

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 Azix 500 uses the 15 mcg Azix 500 disk. Interpretation involves the correlation of the diameter obtained in the disk test with the MIC for Azix 500.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 15 mcg Azix 500 disk should be interpreted according to the following criteria:

Zone Diameter (mm)


≥ 18

Susceptible (S)

14 to 17

Intermediate (I)

≤ 13

Resistant (R)

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 mcg Azix 500 disk should provide the following zone diameters in these laboratory test quality control strains:


Zone Diameter (mm)

Staphylococcus aureus ATCC 25923

21 to 26

In Vitro Activity of Azix 500 Against Mycobacteria

Azix 500 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. Azix 500 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-albumin-dextrose-catalase (OADC), have been used to determine Azix 500 MIC values for MAC strains. In general, Azix 500 MIC values decreased 4 to 8 fold as the pH of Middlebrook 7H11 agar media increased from 6.6 to 7.4. At pH 7.4, Azix 500 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 Azix 500 and clarithromycin MIC values has not been established. In general, Azix 500 MIC values were observed to be 2 to 32 fold higher than clarithromycin independent of the susceptibility method employed.

The ability to correlate MIC values and plasma drug levels is difficult as Azix 500 concentrates in macrophages and tissues.

Drug Resistance

Complete cross-resistance between Azix 500 and clarithromycin has been observed with MAC isolates. In most isolates, a single-point 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 Azix 500 MICs to ≥ 128 mcg/mL with clarithromycin MICs increasing to ≥ 32 mcg/mL. These MIC values were determined employing the radiometric broth dilution susceptibility testing method with Middlebrook 7H12 medium. The clinical significance of Azix 500 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 Azix 500 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. Azix 500 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 Azix 500 have not been established.

The clinical relevance of Azix 500 in vitro susceptibility test results for other mycobacterial species, including Mycobacterium tuberculosis, using any susceptibility testing method has not been determined.



  1. DailyMed. "AZITHROMYCIN: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". (accessed September 17, 2018).
  2. NCIt. "Azithromycin: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". (accessed September 17, 2018).
  3. EPA DSStox. "Azithromycin: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". (accessed September 17, 2018).


The results of a survey conducted on for Azix 500 are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Azix 500. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.

User reports

Consumer reported administration

No survey data has been collected yet

Consumer reviews

There are no reviews yet. Be the first to write one!

Your name: 
Spam protection:  < Type 18 here

Information checked by Dr. Sachin Kumar, MD Pharmacology

| Privacy Policy
This site does not supply any medicines. It contains prices for information purposes only.
© 2003 - 2024 All Rights Reserved