19 . July , 2018 - Thursday
Check todays hot topics or new products

Find a Drug: Advanced

Please Sign in or Register

All about: Avelox

Big Image
Generic Name: moxifloxacin hydrochloride
Dosage Form: Tablets

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

Avelox Description

Avelox (moxifloxacin hydrochloride) is a synthetic broad spectrum antibacterial agent and is available as Avelox Tablets for oral administration and as Avelox I.V. for intravenous administration. Moxifloxacin, a fluoroquinolone, is available as the monohydrochloride salt of 1-cyclopropyl-7-[(S,S)-2,8-diazabicyclo[4.3.0]non-8-yl]-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3 quinoline carboxylic acid. It is a slightly yellow to yellow crystalline substance with a molecular weight of 437.9. Its empirical formula is C21H24FN3O4*HCl and its chemical structure is as follows:

Avelox Tablets are available as film-coated tablets containing moxifloxacin hydrochloride (equivalent to 400 mg moxifloxacin). The inactive ingredients are microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, polyethylene glycol and ferric oxide.

Avelox I.V. is available in ready-to-use 250 mL latex-free flexibags as a sterile, preservative free, 0.8% sodium chloride aqueous solution of moxifloxacin hydrochloride (containing 400 mg moxifloxacin) with pH ranging from 4.1 to 4.6. The appearance of the intravenous solution is yellow. The color does not affect, nor is it indicative of, product stability. The inactive ingredients are sodium chloride, USP, Water for Injection, USP, and may include hydrochloric acid and/or sodium hydroxide for pH adjustment.

Avelox - Clinical Pharmacology

Absorption

Moxifloxacin, given as an oral tablet, is well absorbed from the gastrointestinal tract. The absolute bioavailability of moxifloxacin is approximately 90 percent. Co-administration with a high fat meal (i.e., 500 calories from fat) does not affect the absorption of moxifloxacin.

Consumption of 1 cup of yogurt with moxifloxacin does not significantly affect the extent or rate of systemic absorption (AUC).

The mean (± SD) Cmax and AUC values following single and multiple doses of 400 mg moxifloxacin given orally are summarized below.

Cmax
(mg/L)
AUC
(mg•h/L)
Half-life
(hr)
* Range of means from different studies
Single Dose Oral
  Healthy (n = 372)
3.1 ± 1.0 36.1 ± 9.1 11.5 - 15.6*
Multiple Dose Oral
  Healthy young male/female (n = 15) 4.5 ± 0.5 48.0 ± 2.7 12.7 ± 1.9
  Healthy elderly male (n = 8) 3.8 ± 0.3 51.8 ± 6.7
  Healthy elderly female (n = 8) 4.6 ± 0.6 54.6 ± 6.7
  Healthy young male (n = 8) 3.6 ± 0.5 48.2 ± 9.0
  Healthy young female (n = 9) 4.2 ± 0.5 49.3 ± 9.5

The mean (± SD) Cmax and AUC values following single and multiple doses of 400 mg moxifloxacin given by 1 hour I.V. infusion are summarized below.

Cmax
(mg/L)
AUC
(mg•h/L)
Half-life
(hr)
* Range of means from different studies
** Expected Cmax (concentration obtained around the time of the end of the infusion)
Plasma concentrations increase proportionately with dose up to the highest dose tested (1200 mg single oral dose). The mean (± SD) elimination half-life from plasma is 12 ± 1.3 hours; steady-state is achieved after at least three days with a 400 mg once daily regimen.
Single Dose I.V.
  Healthy young male/female (n = 56) 3.9 ± 0.9 39.3 ± 8.6 8.2 - 15.4*
  Patients (n = 118)
    Male (n = 64) 4.4 ± 3.7
    Female (n = 54) 4.5 ± 2.0
    < 65 years (n = 58) 4.6 ± 4.2
    ≥ 65 years (n = 60) 4.3 ± 1.3
Multiple Dose I.V.
  Healthy young male (n = 8) 4.2 ± 0.8 38.0 ± 4.7 14.8 ± 2.2
  Healthy elderly (n =12; 8 male, 4 female) 6.1 ± 1.3 48.2 ± 0.9 10.1 ± 1.6
  Patients** (n = 107)
    Male (n = 58) 4.2 ± 2.6
    Female (n = 49) 4.6 ± 1.5
    <65 years (n = 52) 4.1 ± 1.4
    ≥65 years (n = 55) 4.7 ± 2.7

Mean Steady-State Plasma Concentrations of Moxifloxacin Obtained With Once Daily Dosing of 400 mg Either Orally (n=10) or by I.V. Infusion (n=12)

Distribution

Moxifloxacin is approximately 30-50% bound to serum proteins, independent of drug concentration. The volume of distribution of moxifloxacin ranges from 1.7 to 2.7 L/kg. Moxifloxacin is widely distributed throughout the body, with tissue concentrations often exceeding plasma concentrations. Moxifloxacin has been detected in the saliva, nasal and bronchial secretions, mucosa of the sinuses, skin blister fluid, subcutaneous tissue, skeletal muscle, and abdominal tissues and fluids following oral or intravenous administration of 400 mg. Moxifloxacin concentrations measured post-dose in various tissues and fluids following a 400 mg oral or I.V. dose are summarized in the following table. The rates of elimination of moxifloxacin from tissues generally parallel the elimination from plasma.

Moxifloxacin Concentrations (mean ± SD) in Tissues and the Corresponding Plasma Concentrations After a Single 400 mg Oral or Intravenous Dose §
Tissue or Fluid N Plasma
Concentration
(µg/mL)
Tissue or Fluid
Concentration
(µg/mL or µg/g)
Tissue
Plasma
Ratio
§all moxifloxacin concentrations were measured 3 hours after a single 400 mg dose, except the abdominal tissue and exudate concentrations which were measured at 2 hours post-dose and the sinus concentrations which were measured after 5 days of dosing.
† N = 5
‡ N = 7
# N = 12
* Reflects only non-protein bound concentrations of drug.
Respiratory
Alveolar Macrophages 5 3.3 ± 0.7 61.8 ± 27.3 21.2 ± 10.0
Bronchial Mucosa 8 3.3 ± 0.7 5.5 ± 1.3 1.7 ± 0.3
Epithelial Lining Fluid 5 3.3 ± 0.7 24.4 ± 14.7 8.7 ± 6.1
Sinus
Maxillary Sinus Mucosa 4 3.7 ± 1.1 7.6 ± 1.7 2.0 ± 0.3
Anterior Ethmoid Mucosa 3 3.7 ± 1.1 8.8 ± 4.3 2.2 ± 0.6
Nasal Polyps 4 3.7 ± 1.1 9.8 ± 4.5 2.6 ± 0.6
Skin, Musculoskeletal
Blister Fluid 5 3.0 ± 0.5 2.6 ± 0.9 0.9 ± 0.2
Subcutaneous Tissue 6 2.3 ± 0.4# 0.9 ± 0.3* 0.4 ± 0.6
Skeletal Muscle 6 2.3 ± 0.4# 0.9 ± 0.2* 0.4 ± 0.1
Intra-Abdominal
Abdominal tissue 8 2.9 ± 0.5 7.6 ± 2.0 2.7 ± 0.8
Abdominal exudate 10 2.34 ± 0.5 3.5 ±1.2 1.6 ± 0.7
Abscess fluid 6 2.7 ± 0.7 2.3 ±1.5 0.8±0.4

Metabolism

Approximately 52% of an oral or intravenous dose of moxifloxacin is metabolized via glucuronide and sulfate conjugation. The cytochrome P450 system is not involved in moxifloxacin metabolism, and is not affected by moxifloxacin. The sulfate conjugate (M1) accounts for approximately 38% of the dose, and is eliminated primarily in the feces. Approximately 14% of an oral or intravenous dose is converted to a glucuronide conjugate (M2), which is excreted exclusively in the urine. Peak plasma concentrations of M2 are approximately 40% those of the parent drug, while plasma concentrations of M1 are generally less than 10% those of moxifloxacin.

In vitro studies with cytochrome (CYP) P450 enzymes indicate that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2, suggesting that moxifloxacin is unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes.

Excretion

Approximately 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces). A total of 96% ± 4% of an oral dose is excreted as either unchanged drug or known metabolites. The mean (± SD) apparent total body clearance and renal clearance are 12 ± 2.0 L/hr and 2.6 ± 0.5 L/hr, respectively.

Special Populations

Geriatric

Following oral administration of 400 mg moxifloxacin for 10 days in 16 elderly (8 male; 8 female) and 17 young (8 male; 9 female) healthy volunteers, there were no age-related changes in moxifloxacin pharmacokinetics. In 16 healthy male volunteers (8 young; 8 elderly) given a single 200 mg dose of oral moxifloxacin, the extent of systemic exposure (AUC and Cmax) was not statistically different between young and elderly males and elimination half-life was unchanged. No dosage adjustment is necessary based on age. In large phase III studies, the concentrations around the time of the end of the infusion in elderly patients following intravenous infusion of 400 mg were similar to those observed in young patients.

Pediatric

The pharmacokinetics of moxifloxacin in pediatric subjects have not been studied.

Gender

Following oral administration of 400 mg moxifloxacin daily for 10 days to 23 healthy males (19-75 years) and 24 healthy females (19-70 years), the mean AUC and Cmax were 8% and 16% higher, respectively, in females compared to males. There are no significant differences in moxifloxacin pharmacokinetics between male and female subjects when differences in body weight are taken into consideration.

A 400 mg single dose study was conducted in 18 young males and females. The comparison of moxifloxacin pharmacokinetics in this study (9 young females and 9 young males) showed no differences in AUC or Cmax due to gender. Dosage adjustments based on gender are not necessary.

Race

Steady-state moxifloxacin pharmacokinetics in male Japanese subjects were similar to those determined in Caucasians, with a mean Cmax of 4.1 µg/mL, an AUC24 of 47 µg•h/mL, and an elimination half-life of 14 hours, following 400 mg p.o. daily.

Renal Insufficiency

The pharmacokinetic parameters of moxifloxacin are not significantly altered in mild, moderate, severe, or end-stage renal disease. No dosage adjustment is necessary in patients with renal impairment, including those patients requiring hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).

In a single oral dose study of 24 patients with varying degrees of renal function from normal to severely impaired, the mean peak concentrations (Cmax) of moxifloxacin were reduced by 21% and 28% in the patients with moderate (CLCR≥ 30 and ≤ 60 mL/min) and severe (CLCR<30 mL/min) renal impairment, respectively. The mean systemic exposure (AUC) in these patients was increased by 13%. In the moderate and severe renally impaired patients, the mean AUC for the sulfate conjugate (M1) increased by 1.7-fold (ranging up to 2.8-fold) and mean AUC and Cmax for the glucuronide conjugate (M2) increased by 2.8-fold (ranging up to 4.8-fold) and 1.4-fold (ranging up to 2.5-fold), respectively.

The pharmacokinetics of single dose and multiple dose moxifloxacin were studied in patients with CLCR< 20 mL/min on either hemodialysis or continuous ambulatory peritoneal dialysis (8 HD, 8 CAPD). Following a single 400 mg oral dose, the AUC of moxifloxacin in these HD and CAPD patients did not vary significantly from the AUC generally found in healthy volunteers. Cmax values of moxifloxacin were reduced by about 45% and 33% in HD and CAPD patients, respectively, compared to healthy, historical controls. The exposure (AUC) to the sulfate conjugate (M1) increased by 1.4- to 1.5-fold in these patients. The mean AUC of the glucuronide conjugate (M2) increased by a factor of 7.5, whereas the mean Cmax values of the glucuronide conjugate (M2) increased by a factor of 2.5 to 3, compared to healthy subjects. The sulfate and the glucuronide conjugates of moxifloxacin are not microbiologically active, and the clinical implication of increased exposure to these metabolites in patients with renal disease including those undergoing HD and CAPD has not been studied.

Oral administration of 400 mg QD moxifloxacin for 7 days to patients on HD or CAPD produced mean systemic exposure (AUCss) to moxifloxacin similar to that generally seen in healthy volunteers. Steady-state Cmax values were about 22% lower in HD patients but were comparable between CAPD patients and healthy volunteers. Both HD and CAPD removed only small amounts of moxifloxacin from the body (approximately 9% by HD, and 3% by CAPD). HD and CAPD also removed about 4% and 2% of the glucuronide metabolite (M2), respectively.

Hepatic Insufficiency

In 400 mg single oral dose studies in 6 patients with mild (Child Pugh Class A), and 10 patients with moderate (Child Pugh Class B), hepatic insufficiency, moxifloxacin mean systemic exposure (AUC) was 78% and 102%, respectively, of 18 healthy controls and mean peak concentration (Cmax) was 79% and 84% of controls.

The mean AUC of the sulfate conjugate of moxifloxacin (M1) increased by 3.9-fold (ranging up to 5.9-fold) and 5.7-fold (ranging up to 8.0-fold) in the mild and moderate groups, respectively. The mean Cmax of M1 increased by approximately 3-fold in both groups (ranging up to 4.7- and 3.9-fold). The mean AUC of the glucuronide conjugate of moxifloxacin (M2) increased by 1.5-fold (ranging up to 2.5-fold) in both groups. The mean Cmax of M2 increased by 1.6- and 1.3-fold (ranging up to 2.7- and 2.1-fold), respectively. The clinical significance of increased exposure to the sulfate and glucuronide conjugates has not been studied. Moxifloxacin plasma concentrations of patients with mild to severe hepatic impairment (Child Pugh A to C) did not reveal clinically relevant differences compared to healthy volunteers or patients with normal hepatic function, respectively. No dosage adjustment is recommended for mild or moderate hepatic insufficiency (Child Pugh Classes A and B). (See DOSAGE AND ADMINISTRATION.)

Photosensitivity Potential

A study of the skin response to ultraviolet (UVA and UVB) and visible radiation conducted in 32 healthy volunteers (8 per group) demonstrated that moxifloxacin does not show phototoxicity in comparison to placebo. The minimum erythematous dose (MED) was measured before and after treatment with moxifloxacin (200 mg or 400 mg once daily), lomefloxacin (400 mg once daily), or placebo. In this study, the MED measured for both doses of moxifloxacin were not significantly different from placebo, while lomefloxacin significantly lowered the MED. (See PRECAUTIONS, Information for Patients.)

Drug-drug Interactions

The potential for pharmacokinetic drug interactions between moxifloxacin and itraconazole, theophylline, warfarin, digoxin, atenolol, probenecid, morphine, oral contraceptives, ranitidine, glyburide, calcium, iron, and antacids has been evaluated. There was no clinically significant effect of moxifloxacin on itraconazole, theophylline, warfarin, digoxin, atenolol, oral contraceptives, or glyburide kinetics. Itraconazole, theophylline, warfarin, digoxin, probenecid, morphine, ranitidine, and calcium did not significantly affect the pharmacokinetics of moxifloxacin. These results and the data from in vitro studies suggest that moxifloxacin is unlikely to significantly alter the metabolic clearance of drugs metabolized by CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2 enzymes.

As with all other quinolones, iron and antacids significantly reduced bioavailability of moxifloxacin.

Itraconazole: In a study involving 11 healthy volunteers, there was no significant effect of itraconazole (200 mg once daily for 9 days), a potent inhibitor of cytochrome P4503A4, on the pharmacokinetics of moxifloxacin (a single 400 mg dose given on the 7th day of itraconazole dosing). In addition, moxifloxacin was shown not to affect the pharmacokinetics of itraconazole.

Theophylline: No significant effect of moxifloxacin (200 mg every twelve hours for 3 days) on the pharmacokinetics of theophylline (400 mg every twelve hours for 3 days) was detected in a study involving 12 healthy volunteers. In addition, theophylline was not shown to affect the pharmacokinetics of moxifloxacin. The effect of co-administration of a 400 mg dose of moxifloxacin with theophylline has not been studied, but it is not expected to be clinically significant based on in vitro metabolic data showing that moxifloxacin does not inhibit the CYP1A2 isoenzyme.

Warfarin: No significant effect of moxifloxacin (400 mg once daily for eight days) on the pharmacokinetics of R- and S-warfarin (25 mg single dose of warfarin sodium on the fifth day) was detected in a study involving 24 healthy volunteers. No significant change in prothrombin time was observed. (See PRECAUTIONS, Drug Interactions.)

Digoxin: No significant effect of moxifloxacin (400 mg once daily for two days) on digoxin (0.6 mg as a single dose) AUC was detected in a study involving 12 healthy volunteers. The mean digoxin Cmax increased by about 50% during the distribution phase of digoxin. This transient increase in digoxin Cmax is not viewed to be clinically significant. Moxifloxacin pharmacokinetics were similar in the presence or absence of digoxin. No dosage adjustment for moxifloxacin or digoxin is required when these drugs are administered concomitantly.

Atenolol: In a crossover study involving 24 healthy volunteers (12 male; 12 female), the mean atenolol AUC following a single oral dose of 50 mg atenolol with placebo was similar to that observed when atenolol was given concomitantly with a single 400 mg oral dose of moxifloxacin. The mean Cmax of single dose atenolol decreased by about 10% following co-administration with a single dose of moxifloxacin.

Morphine: No significant effect of morphine sulfate (a single 10 mg intramuscular dose) on the mean AUC and Cmax of moxifloxacin (400 mg single dose) was observed in a study of 20 healthy male and female volunteers.

Oral Contraceptives: A placebo-controlled study in 29 healthy female subjects showed that moxifloxacin 400 mg daily for 7 days did not interfere with the hormonal suppression of oral contraception with 0.15 mg levonorgestrel/0.03 mg ethinylestradiol (as measured by serum progesterone, FSH, estradiol, and LH), or with the pharmacokinetics of the administered contraceptive agents.

Probenecid: Probenecid (500 mg twice daily for two days) did not alter the renal clearance and total amount of moxifloxacin (400 mg single dose) excreted renally in a study of 12 healthy volunteers.

Ranitidine: No significant effect of ranitidine (150 mg twice daily for three days as pretreatment) on the pharmacokinetics of moxifloxacin (400 mg single dose) was detected in a study involving 10 healthy volunteers.

Antidiabetic agents: In diabetics, glyburide (2.5 mg once daily for two weeks pretreatment and for five days concurrently) mean AUC and Cmax were 12% and 21% lower, respectively, when taken with moxifloxacin (400 mg once daily for five days) in comparison to placebo. Nonetheless, blood glucose levels were decreased slightly in patients taking glyburide and moxifloxacin in comparison to those taking glyburide alone, suggesting no interference by moxifloxacin on the activity of glyburide. These interaction results are not viewed as clinically significant.

Calcium: Twelve healthy volunteers were administered concomitant moxifloxacin (single 400 mg dose) and calcium (single dose of 500 mg Ca++ dietary supplement) followed by an additional two doses of calcium 12 and 24 hours after moxifloxacin administration. Calcium had no significant effect on the mean AUC of moxifloxacin. The mean Cmax was slightly reduced and the time to maximum plasma concentration was prolonged when moxifloxacin was given with calcium compared to when moxifloxacin was given alone (2.5 hours versus 0.9 hours). These differences are not considered to be clinically significant.

Antacids: When moxifloxacin (single 400 mg tablet dose) was administered two hours before, concomitantly, or 4 hours after an aluminum/magnesium-containing antacid (900 mg aluminum hydroxide and 600 mg magnesium hydroxide as a single oral dose) to 12 healthy volunteers there was a 26%, 60% and 23% reduction in the mean AUC of moxifloxacin, respectively. Moxifloxacin should be taken at least 4 hours before or 8 hours after antacids containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc, or VIDEX® (didanosine) chewable/ buffered tablets or the pediatric powder for oral solution. (See PRECAUTIONS, Drug Interactions and DOSAGE AND ADMINISTRATION.)

Iron: When moxifloxacin tablets were administered concomitantly with iron (ferrous sulfate 100 mg once daily for two days), the mean AUC and Cmax of moxifloxacin was reduced by 39% and 59%, respectively. Moxifloxacin should only be taken more than 4 hours before or 8 hours after iron products. (See PRECAUTIONS, Drug Interactions and DOSAGE AND ADMINISTRATION.)

Electrocardiogram: Prolongation of the QT interval in the ECG has been observed in some patients receiving moxifloxacin. Following oral dosing with 400 mg of moxifloxacin the mean (± SD) change in QTc from the pre-dose value at the time of maximum drug concentration was 6 msec (± 26) (n = 787). Following a course of daily intravenous dosing (400 mg; 1 hour infusion each day) the mean change in QTc from the Day 1 pre-dose value was 9 msec (± 24) on Day 1 (n = 69) and 3 msec (± 29) on Day 3 (n = 290). (See WARNINGS.)

There is limited information available on the potential for a pharmacodynamic interaction in humans between moxifloxacin and other drugs that prolong the QTc interval of the electrocardiogram. Sotalol, a Class III antiarrhythmic, has been shown to further increase the QTc interval when combined with high doses of intravenous (I.V.) moxifloxacin in dogs. Therefore, moxifloxacin should be avoided with Class IA and Class III antiarrhythmics. (See ANIMAL PHARMACOLOGY, WARNINGS, and PRECAUTIONS.)

MICROBIOLOGY

Moxifloxacin has in vitro activity against a wide range of Gram-positive and Gram-negative microorganisms. The bactericidal action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination. It appears that the C8-methoxy moiety contributes to enhanced activity and lower selection of resistant mutants of Gram-positive bacteria compared to the C8-H moiety. The presence of the bulky bicycloamine substituent at the C-7 position prevents active efflux, associated with the NorA or pmrA genes seen in certain Gram-positive bacteria.

The mechanism of action for quinolones, including moxifloxacin, is different from that of macrolides, beta-lactams, aminoglycosides, or tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to moxifloxacin and other quinolones. There is no known cross-resistance between moxifloxacin and other classes of antimicrobials.

In vitro resistance to moxifloxacin develops slowly via multiple-step mutations. Resistance to moxifloxacin occurs in vitro at a general frequency of between 1.8 x 10–9 to < 1 x 10–11 for Gram-positive bacteria.

Cross-resistance has been observed between moxifloxacin and other fluoroquinolones against Gram-negative bacteria. Gram-positive bacteria resistant to other fluoroquinolones may, however, still be susceptible to moxifloxacin.

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

Aerobic Gram-positive microorganisms
Enterococcus faecalis (many strains are only moderately susceptible)
Staphylococcus aureus (methicillin-susceptible strains only)
Streptococcus anginosus
Streptococcus constellatus
Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP]*)
Streptococcus pyogenes
* MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates previously known as PRSP (Penicillin-resistant S. pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin (MIC ≥ 2 µg/mL), 2nd generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.
Aerobic Gram-negative microorganisms
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella pneumoniae
Moraxella catarrhalis
Proteus mirabilis
Anaerobic microorganisms
Bacteroides fragilis
Bacteroides thetaiotaomicron
Clostridium perfringens
Peptostreptococcus species
Other microorganisms
Chlamydia pneumoniae
Mycoplasma pneumoniae

The following in vitro data are available, but their clinical significance is unknown.
Moxifloxacin exhibits in vitro minimum inhibitory concentrations (MICs) of 2 µg/mL or less against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of moxifloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Aerobic Gram-positive microorganisms
Staphylococcus epidermidis (methicillin-susceptible strains only)
Streptococcus agalactiae
Streptococcus viridans group
Aerobic Gram-negative microorganisms
Citrobacter freundii
Klebsiella oxytoca
Legionella pneumophila
Anaerobic microorganisms
Fusobacterium species
Prevotella species

Susceptibility Tests

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 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of moxifloxacin powder. The MIC values should be interpreted according to the following criteria:

For testing Enterobacteriaceae and methicillin-susceptible Staphylococcus aureus:

MIC (µg/mL) Interpretation
≤ 2.0 Susceptible (S)
   4.0 Intermediate (I)
≥ 8.0 Resistant (R)

For testing Haemophilus influenzae and Haemophilus parainfluenzaea:

a This interpretive standard is applicable only to broth microdilution susceptibility tests with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium1.
MIC (µg/mL) Interpretation
≤ 1.0 Susceptible (S)

The current absence of data on resistant strains precludes defining any results other than “Susceptible”. Strains yielding MIC results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing.

For testing Streptococcus species including Streptococcus pneumoniae b and Enterococcus faecalis:

b These interpretive standards are applicable only to broth microdilution susceptibility tests using cation-adjusted Mueller-Hinton broth with 2 - 5% lysed horse blood.
MIC (µg/mL) Interpretation
≤ 1.0 Susceptible (S)
   2.0 Intermediate (I)
≥ 4.0 Resistant (R)

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood 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 a 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 in the blood reaches the concentrations usually achievable; other therapy should be selected.

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

c This quality control range is applicable to only H. influenzae ATCC 49247 tested by a broth microdilution procedure using Haemophilus Test Medium (HTM)1.
d This quality control range is applicable to only S. pneumoniae ATCC 49619 tested by a broth microdilution procedure using cation-adjusted Mueller-Hinton broth with 2 - 5% lysed horse blood.
Microorganism MIC (µg/mL)
Enterococcus faecalis ATCC 29212 0.06 - 0.5
Escherichia coli ATCC 25922 0.008 - 0.06
Haemophilus influenzae  ATCC 49247c 0.008 - 0.03
Staphylococcus aureus ATCC 29213 0.015 - 0.06
Streptococcus pneumoniae  ATCC 49619d 0.06 - 0.25

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 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5-µg moxifloxacin to test the susceptibility of microorganisms to moxifloxacin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5-µg moxifloxacin disk should be interpreted according to the following criteria:

The following zone diameter interpretive criteria should be used for testing Enterobacteriaceae and methicillin-susceptible Staphylococcus aureus:

Zone Diameter (mm) Interpretation
≥ 19 Susceptible (S)
16 – 18 Intermediate (I)
≤ 15 Resistant (R)

For testing Haemophilus influenzae and Haemophilus parainfluenzaee:

eThis zone diameter standard is applicable only to tests with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium (HTM)2.
Zone Diameter (mm) Interpretation
≥ 18 Susceptible (S)

The current absence of data on resistant strains precludes defining any results other than “Susceptible”. Strains yielding zone diameter results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing.

For testing Streptococcus species including Streptococcus pneumoniae f and Enterococcus faecalis :

f These interpretive standards are applicable only to disk diffusion tests using Mueller-Hinton agar supplemented with 5% sheep blood incubated in 5% CO2.
Zone Diameter (mm) Interpretation
≥ 18 Susceptible (S)
15 – 17 Intermediate (I)
≤ 14 Resistant (R)

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for moxifloxacin.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5-µg moxifloxacin disk should provide the following zone diameters in these laboratory test quality control strains:

gThese quality control limits are applicable to only H. influenzae ATCC 49247 testing using Haemophilus Test Medium (HTM)2.
h These quality control limits are applicable only to tests conducted with S. pneumoniae ATCC 49619 tested by disk diffusion procedure using Mueller-Hinton agar supplemented with 5% sheep blood and incubated in 5% CO2.
Microorganism Zone Diameter (mm)
Escherichia coli ATCC 25922 28 – 35
Haemophilus influenzae  ATCC 49247g 31 – 39
Staphylococcus aureus ATCC 25923 28 – 35
Streptococcus pneumoniae  ATCC 49619h 25 – 31

Anaerobic Techniques: For anaerobic bacteria, the susceptibility to moxifloxacin as MICs can be determined by standardized procedures3 such as reference agar dilution methodsi. The MICs obtained should be interpreted according to the following criteria:

i This interpretive standard is applicable to reference agar dilution susceptibility tests using Brucella agar supplemented with hemin, vitamin K1 and 5% laked sheep blood.
MIC (ug/mL) Interpretation
≤2.0 Susceptible (S)
4.0 Intermediate (I)
≥ 8.0 Resistant (R)

Acceptable ranges of MICs (ug/mL) for control strains for reference agar dilution testing j:

jThese quality control ranges are applicable to reference agar dilution tests using Brucella agar supplemented with hemin, vitamin K1 and 5% laked sheep blood.
Microorganism MIC (ug/mL)
Bacteroides fragilis ATCC 25285 0.12-0.5
Bacteroides thetaiotaomicron ATCC 29741 1.0-4.0
Eubacterium lentum ATCC 43055 0.12-0.5

Indications and Usage for Avelox

Avelox Tablets and I.V. are indicated for the treatment of adults (≥ 18 years of age) with infections caused by susceptible strains of the designated microorganisms in the conditions listed below. (See DOSAGE AND ADMINISTRATION for specific recommendations. In addition, for I.V. use see PRECAUTIONS, Geriatric Use.)

Acute Bacterial Sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae , or Moraxella catarrhalis.

Acute Bacterial Exacerbation of Chronic Bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus, or Moraxella catarrhalis.

Community Acquired Pneumonia caused by Streptococcus pneumoniae (including multi-drug resistant strains*), Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydia pneumoniae.

* MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates previously known as PRSP (Penicillin-resistant S. pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin (MIC ≥ 2 µg/mL), 2nd generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.

Uncomplicated Skin and Skin Structure Infections caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes.

Complicated Intra-Abdominal Infections including polymicrobial infections such as abscess caused by Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron, or Peptostreptococcus species.

Complicated Skin and Skin Structure Infections caused by methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae (See Clinical Studies).

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to moxifloxacin. Therapy with Avelox may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.

Recent Drug Updates at DrugIndexOnline:





Acthar HP Gel Acthar HP Gel
Generic Name: Corticotropin Injection Gel (core-tih-koe-TROE-pin) Brand Name: Acthar HPActhar HP Gel is used for:Diagnosing adrenal gland function. It may be used to treat certain conditions caused by allergies; breathing, blood, or endocrine problems; arthritis; skin or eye problems; bowel infl more...

Amcort Amcort
Some commonly used brand names are: In the U.S.— Acetocot 9 A-hydroCort 5 Amcort 9 A-MethaPred 6 Aristocort 9 Aristocort Forte 9 Aristopak 9 Aristospan 9 Articulose-50 7 Articulose-L.A. 9 Celestone 1 Celestone Phosphate 1 Celestone Soluspan 1 Cinalone 40 9 Cinonide 40 9 Clinacort 9 Clinal more...

dexchlorpheniramine dexchlorpheniramine
Generic Name: dexchlorpheniramine (dex klor fen IR a meen) Brand Names: Polaramine What is dexchlorpheniramine? Dexchlorpheniramine is an antihistamine. It blocks the effects of the naturally occurring chemical histamine in your body. Dexchlorpheniramine is used to treat sneezing; runny more...

Doral Doral
Generic name: Quazepam Brand names: Doral Why is Doral prescribed? Doral, a sleeping medication available in tablet form, is taken as short-term treatment for insomnia. Symptoms of insomnia may include difficulty falling asleep, frequent awakenings throughout the night, or very early morning awa more...

Enteral Nutrition Formulas Enteral Nutrition Formulas
Some commonly used brand names are: In the U.S.— Accupep HPF 9 Advera 2 Alitraq 9 Amin-Aid 2 Attain 10 Carnation Instant Breakfast 7 Carnation Instant Breakfast No Sugar Added 7 Casec 8 CitriSource 10 Compleat Modified 1 Compleat Regular 1 Comply 10 Criticare HN 9 Crucial 2 Deliver 2.0 10 more...

Meprobamate Meprobamate
Some commonly used brand names are: In the U.S.— Equanil Meprospan 200 Meprospan 400 Miltown-200 Miltown-400 Miltown-600 Probate Trancot In Canada— Apo-Meprobamate Equanil Meprospan-400 Miltown Generic name product may be available in the U.S. Category Antianxiety agent D more...

Oramorph SR Oramorph SR
Note: Palladone (hydromorphone hydrochloride extended release capsules) was suspended from the U.S. market in July 2005 by the manufacturer. Serious side effects were reported when Palladone was taken with alcohol. Some commonly used brand names are: In the U.S.— Astramorph PF 10 more...

Promethazine VC w/Codeine Promethazine VC w/Codeine
Some commonly used brand names are: In the U.S.— Alka-Seltzer Plus Cold and Cough 21 Alka-Seltzer Plus Cold and Cough Medicine Liqui-Gels 34 Alka-Seltzer Plus Night-Time Cold Liqui-Gels 35 Ami-Tex LA 69 Anatuss LA 70 Benylin Expectorant 54 Bromfed-DM 17 Broncholate 68 Carbinoxamine Compou more...