Moxifloxacin Hydrochloride

11.1 Moxifloxacin Hydrochloride Tablets

• •Moxifloxacin hydrochloride tablets are available as film-coated tablets containing moxifloxacin hydrochloride USP (equivalent to 400 mg moxifloxacin).
• •The inactive ingredients are hypromellose, iron oxide red, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium starch glycolate, and titanium dioxide.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Moxifloxacin hydrochloride is a member of the fluoroquinolone class of antibacterial agents [see Microbiology (12.4)].

12.3 Pharmacokinetics

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 (that is, 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).

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.

Mean Steady-State Plasma Concentrations of Moxifloxacin Obtained With Once Daily Dosing of 400 mg Either Orally (n=10) or by IV Infusion (n=12)
Table 7: Moxifloxacin Concentrations (mean ± SD) in Tissues and the Corresponding Plasma Concentrations After a Single 400 mg Oral or Intravenous Dose^a
Distribution

Moxifloxacin is approximately 30 to 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 IV dose are summarized in Table 7. The rates of elimination of moxifloxacin from tissues generally parallel the elimination from plasma. 

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 L/hr and 2.6 ± 0.5 L/hr, respectively.

Pharmacokinetics in Specific 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 C_max) 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. [see Use In Specific Populations (8.5).] 

Pediatric

The pharmacokinetics of moxifloxacin in pediatric subjects has not been studied [see Use in Specific Populations (8.4)].

Gender

Following oral administration of 400 mg moxifloxacin daily for 10 days to 23 healthy males (19 to 75 years) and 24 healthy females (19 to 70 years), the mean AUC and C_max 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 C_max 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 C_max of 4.1 mcg/mL, an AUC₂₄ of 47 mcg•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 (C_max) of moxifloxacin were reduced by 21% and 28% in the patients with moderate (CL_CR≥30 and ≤ 60 mL/min) and severe (CL_CR<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 C_max 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. [See Use in Specific Populations (8.6).]

The pharmacokinetics of single dose and multiple dose moxifloxacin were studied in patients with CL_CR<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. C_max 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 C_max 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 (AUC_ss) to moxifloxacin similar to that generally seen in healthy volunteers. Steady-state C_max 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

No dosage adjustment is recommended for mild, moderate, or severe hepatic insufficiency (Child-Pugh Classes A, B, or C). However, due to metabolic disturbances associated with hepatic insufficiency, which may lead to QT prolongation, moxifloxacin hydrochloride should be used with caution in these patients [see Warnings and Precautions ( 5.3), Use in Specific Populations (8.7)].

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 (C_max) 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-fold) in the mild and moderate groups, respectively. The mean C_max 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 C_max 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. In a subset of patients participating in a clinical trial, the plasma concentrations of moxifloxacin and metabolites determined approximately at the moxifloxacin T_max following the first intravenous or oral moxifloxacin dose in the Child-Pugh Class C patients (n=10) were similar to those in the Child-Pugh Class A/B patients (n=5), and also similar to those observed in healthy volunteer studies.

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 hydrochloride 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.

It is difficult to ascribe relative photosensitivity/phototoxicity among various fluoroquinolones during actual patient use because other factors play a role in determining a subject’s susceptibility to this adverse event such as: a patient’s skin pigmentation, frequency and duration of sun and artificial ultraviolet light (UV) exposure, wearing of sunscreen and protective clothing, the use of other concomitant drugs and the dosage and duration of fluoroquinolone therapy [see Warnings and Precautions (5.10), Adverse Reactions ( 6.3), and Patient Counseling Information (17.3)].

Drug-Drug Interactions

The following drug interactions were studied in healthy volunteers or patients.

Antacids and iron significantly reduced bioavailability of moxifloxacin, as observed with other quinolones [see Drug Interactions (7.1)].

Calcium, digoxin, itraconazole, morphine, probenecid, ranitidine, theophylline, and warfarin 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.

Moxifloxacin had no clinically significant effect on the pharmacokinetics of atenolol, digoxin, glyburide, itraconazole, oral contraceptives, theophylline, and warfarin [see Drug Interactions (7.2)].

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 Dosage and Administration (2.2), Drug Interactions (7.1).]

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 C_max of single dose atenolol decreased by about 10% following co-administration with a single dose of moxifloxacin.

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 C_max 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.

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 C_max increased by about 50% during the distribution phase of digoxin. This transient increase in digoxin C_max 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.

Glyburide

In diabetics, glyburide (2.5 mg once daily for two weeks pretreatment and for five days concurrently) mean AUC and C_max 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.

Iron

When moxifloxacin tablets were administered concomitantly with iron (ferrous sulfate 100 mg once daily for two days), the mean AUC and C_max 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 Dosage and Administration (2.2), Drug Interactions (7.1).]

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 7^th day of itraconazole dosing). In addition, moxifloxacin was shown not to affect the pharmacokinetics of itraconazole.

Morphine

No significant effect of morphine sulfate (a single 10 mg intramuscular dose) on the mean AUC and C_max 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.

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 Adverse Reactions (6.2), Drug Interactions (7.2).]

12.4 Microbiology

Mechanism of Action

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.

Mechanism of Resistance

The mechanism of action for fluoroquinolones, 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. Resistance to fluoroquinolones occurs primarily by a mutation in topoisomerase II (DNA gyrase) or topoisomerase IV genes, decreased outer membrane permeability or drug efflux. 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

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. There is no known cross-resistance between moxifloxacin and other classes of antimicrobials.

Moxifloxacin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections [see Indications and Usage (1)].

Gram-positive bacteria

• • Enterococcus faecalis
• • Staphylococcus aureus
• • Streptococcus anginosus
• • Streptococcus constellatus
• • Streptococcus pneumoniae (including multi-drug resistant isolates [MDRSP]**)
• • Streptococcus pyogenes

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

Gram-negative bacteria

• • Enterobacter cloacae
• • Escherichia coli
• • Haemophilus influenzae
• • Haemophilus parainfluenzae
• • Klebsiella pneumoniae
• • Moraxella catarrhalis
• • Proteus mirabilis

Anaerobic bacteria

• • Bacteroides fragilis
• • Bacteroides thetaiotaomicron
• • Clostridium perfringens
• • Peptostreptococcus species

Other microorganisms

• • Chlamydophila pneumoniae
• • Mycoplasma pneumoniae

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for moxifloxacin. However, the efficacy of moxifloxacin hydrochloride in treating clinical infections due to these bacteria has not been established in adequate and well controlled clinical trials.

Gram-positive bacteria

• • Staphylococcus epidermidis
• • Streptococcus agalactiae
• • Streptococcus viridans group

Gram-negative bacteria

• • Citrobacter freundii
• • Klebsiella oxytoca
• • Legionella pneumophila

Anaerobic bacteria

• • Fusobacterium species
• • Prevotella species

Susceptibility Tests Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals 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 an antibacterial drug product for treatment.

• • 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 method (broth and/or agar).¹ The MIC values should be interpreted according to the criteria in Table 8.

• • Diffusion Techniques:

Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size prove should be determined using a standardized test method. ^2,3 This procedure uses paper disks impregnated with 5 mcg moxifloxacin to test the susceptibility of bacteria to moxifloxacin. The disc diffusion interpretive criteria are provided in Table 8.

• • Anaerobic Techniques:

For anaerobic bacteria, the susceptibility to moxifloxacin can be determined by a standardized test method.⁴ The MIC values obtained should be interpreted according to the criteria provided in Table 8.

A report of “Susceptible” indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the infection site necessary to inhibit growth of the pathogen. 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 the drug product can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.

• • Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay and the techniques of the individuals performing the test. ^1,2,3,4 Standard moxifloxacin powder should provide the following range of MIC values noted in Table 9. For the diffusion technique using the 5 mcg moxifloxacin disk, the criteria in Table 9 should be achieved.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals to determine the carcinogenic potential of moxifloxacin have not been performed.

Moxifloxacin was not mutagenic in 4 bacterial strains (TA 98, TA 100, TA 1535, TA 1537) used in the Ames Salmonella reversion assay. As with other quinolones, the positive response observed with moxifloxacin in strain TA 102 using the same assay may be due to the inhibition of DNA gyrase. Moxifloxacin was not mutagenic in the CHO/HGPRT mammalian cell gene mutation assay. An equivocal result was obtained in the same assay when v79 cells were used. Moxifloxacin was clastogenic in the v79 chromosome aberration assay, but it did not induce unscheduled DNA synthesis in cultured rat hepatocytes. There was no evidence of genotoxicity in vivo in a micronucleus test or a dominant lethal test in mice.

Moxifloxacin had no effect on fertility in male and female rats at oral doses as high as 500 mg/kg/day, approximately 12 times the maximum recommended human dose based on body surface area (mg/m²), or at intravenous doses as high as 45 mg/kg/day, approximately equal to the maximum recommended human dose based on body surface area (mg/m²). At 500 mg/kg orally there were slight effects on sperm morphology (head-tail separation) in male rats and on the estrous cycle in female rats.

13.2 Animal Toxicology and/or Pharmacology

Quinolones have been shown to cause arthropathy in immature animals. In studies in juvenile dogs oral doses of moxifloxacin ≥ 30 mg/kg/day (approximately 1.5 times the maximum recommended human dose based upon systemic exposure) for 28 days resulted in arthropathy. There was no evidence of arthropathy in mature monkeys and rats at oral doses up to 135 and 500 mg/kg/day, respectively.

Moxifloxacin at an oral dose of 300 mg/kg did not show an increase in acute toxicity or potential for CNS toxicity (for example, seizures) in mice when used in combination with NSAIDs such as diclofenac, ibuprofen, or fenbufen. Some quinolones have been reported to have proconvulsant activity that is exacerbated with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs).

A QT-prolonging effect of moxifloxacin was found in dog studies, at plasma concentrations about five times the human therapeutic level. The combined infusion of sotalol, a Class III antiarrhythmic agent, with moxifloxacin induced a higher degree of QTc prolongation in dogs than that induced by the same dose (30 mg/kg) of moxifloxacin alone. Electrophysiological in vitro studies suggested an inhibition of the rapid activating component of the delayed rectifier potassium current (I_Kr) as an underlying mechanism.

No signs of local intolerability were observed in dogs when moxifloxacin was administered intravenously. After intra‑arterial injection, inflammatory changes involving the peri-arterial soft tissue were observed suggesting that intra-arterial administration of moxifloxacin hydrochloride should be avoided.

14 CLINICAL STUDIES

14.1 Acute Bacterial Exacerbation of Chronic Bronchitis

Moxifloxacin hydrochloride tablets (400 mg once daily for five days) were evaluated for the treatment of acute bacterial exacerbation of chronic bronchitis in a randomized, double-blind, controlled clinical trial conducted in the U.S. This study compared moxifloxacin hydrochloride with clarithromycin (500 mg twice daily for 10 days) and enrolled 629 patients. Clinical success was assessed at 7 to 17 days post-therapy. The clinical success for moxifloxacin hydrochloride was 89% (222/250) compared to 89% (224/251) for clarithromycin.

The microbiological eradication rates (eradication plus presumed eradication) in moxifloxacin hydrochloride treated patients were Streptococcus pneumoniae 100%, Haemophilus influenzae 89%, Haemophilus parainfluenzae 100%, Moraxella catarrhalis 85%, Staphylococcus aureus 94%, and Klebsiella pneumoniae 85%.

14.2 Community Acquired Pneumonia

A randomized, double-blind, controlled clinical trial was conducted in the U.S. to compare the efficacy of moxifloxacin hydrochloride tablets (400 mg once daily) to that of high-dose clarithromycin (500 mg twice daily) in the treatment of patients with clinically and radiologically documented community acquired pneumonia. This study enrolled 474 patients (382 of whom were valid for the efficacy analysis conducted at the 14 to 35 day follow-up visit). Clinical success for clinically evaluable patients was 95% (184/194) for moxifloxacin hydrochloride and 95% (178/188) for high dose clarithromycin.

A randomized, double-blind, controlled trial was conducted in the U.S. and Canada to compare the efficacy of sequential IV/PO moxifloxacin 400 mg QD for 7 to 14 days to an IV/PO fluoroquinolone control (trovafloxacin or levofloxacin) in the treatment of patients with clinically and radiologically documented community acquired pneumonia. This study enrolled 516 patients, 362 of whom were valid for the efficacy analysis conducted at the 7 to 30 day post-therapy visit. The clinical success rate was 86% (157/182) for moxifloxacin hydrochloride therapy and 89% (161/180) for the fluoroquinolone comparators.

An open-label ex-U.S. study that enrolled 628 patients compared moxifloxacin hydrochloride to sequential IV/PO amoxicillin/clavulanate (1.2 g IV q 8 h/625 mg PO q 8 h) with or without high-dose IV/PO clarithromycin (500 mg BID). The intravenous formulations of the comparators are not FDA approved. The clinical success rate at Day 5 to 7 for moxifloxacin hydrochloride therapy was 93% (241/258) and demonstrated superiority to amoxicillin/clavulanate ± clarithromycin (85%, 239/280) [95% C.I. of difference in success rates between moxifloxacin and comparator (2.9%, 13.2%)]. The clinical success rate at the 21 to 28 days post-therapy visit for moxifloxacin hydrochloride was 84% (216/258), which also demonstrated superiority to the comparators (74%, 208/280) [95% C.I. of difference in success rates between moxifloxacin and comparator (2.6%, 16.3%)].

The clinical success rates by pathogen across four CAP studies are presented in Table 11.

14.3 Community Acquired Pneumonia caused by Multi-Drug Resistant Streptococcus pneumoniae (MDRSP)*

Moxifloxacin hydrochloride was effective in the treatment of community acquired pneumonia (CAP) caused by multi-drug resistant Streptococcus pneumoniae MDRSP* isolates. Of 37 microbiologically evaluable patients with MDRSP isolates, 35 patients (95%) achieved clinical and bacteriological success post-therapy. The clinical and bacteriological success rates based on the number of patients treated are shown in Table 12.

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

Not all isolates were resistant to all antimicrobial classes tested. Success and eradication rates are summarized in Table 13.

14.4 Acute Bacterial Sinusitis

In a controlled double-blind study conducted in the U.S., moxifloxacin hydrochloride tablets (400 mg once daily for ten days) were compared with cefuroxime axetil (250 mg twice daily for ten days) for the treatment of acute bacterial sinusitis. The trial included 457 patients valid for the efficacy analysis. Clinical success (cure plus improvement) at the 7 to 21 day post-therapy test of cure visit was 90% for moxifloxacin hydrochloride and 89% for cefuroxime.

An additional non-comparative study was conducted to gather bacteriological data and to evaluate microbiological eradication in adult patients treated with moxifloxacin 400 mg once daily for seven days. All patients (n = 336) underwent antral puncture in this study. Clinical success rates and eradication/presumed eradication rates at the 21 to 37 day follow-up visit were 97% (29 out of 30) for Streptococcus pneumoniae, 83% (15 out of 18) for Moraxella catarrhalis, and 80% (24 out of 30) for Haemophilus influenzae.

14.5 Uncomplicated Skin and Skin Structure Infections

A randomized, double-blind, controlled clinical trial conducted in the U.S. compared the efficacy of moxifloxacin 400 mg once daily for seven days with cephalexin hydrochloride 500 mg three times daily for seven days. The percentage of patients treated for uncomplicated abscesses was 30%, furuncles 8%, cellulitis 16%, impetigo 20%, and other skin infections 26%. Adjunctive procedures (incision and drainage or debridement) were performed on 17% of the moxifloxacin hydrochloride treated patients and 14% of the comparator treated patients. Clinical success rates in evaluable patients were 89% (108/122) for moxifloxacin hydrochloride and 91% (110/121) for cephalexin hydrochloride.

14.6 Complicated Skin and Skin Structure Infections

Two randomized, active controlled trials of cSSSI were performed. A double-blind trial was conducted primarily in North America to compare the efficacy of sequential IV/PO moxifloxacin 400 mg QD for 7 to 14 days to an IV/PO beta-lactam/beta‑-lactamase inhibitor control in the treatment of patients with cSSSI. This study enrolled 617 patients, 335 of which were valid for the efficacy analysis. A second open-label International study compared moxifloxacin 400 mg QD for 7 to 21 days to sequential IV/PO beta-lactam/beta-lactamase inhibitor control in the treatment of patients with cSSSI. This study enrolled 804 patients, 632 of which were valid for the efficacy analysis. Surgical incision and drainage or debridement was performed on 55% of the moxifloxacin hydrochloride treated and 53% of the comparator treated patients in these studies and formed an integral part of therapy for this indication. Success rates varied with the type of diagnosis ranging from 61% in patients with infected ulcers to 90% in patients with complicated erysipelas. These rates were similar to those seen with comparator drugs. The overall success rates in the evaluable patients and the clinical success by pathogen are shown in Tables 14 and 15.

14.7 Complicated Intra-Abdominal Infections

Two randomized, active controlled trials of cIAI were performed. A double-blind trial was conducted primarily in North America to compare the efficacy of sequential IV/PO moxifloxacin 400 mg QD for 5 to 14 days to IV/piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of patients with cIAI, including peritonitis, abscesses, appendicitis with perforation, and bowel perforation. This study enrolled 681 patients, 379 of which were considered clinically evaluable. A second open-label international study compared moxifloxacin 400 mg QD for 5 to 14 days to IV ceftriaxone plus IV metronidazole followed by PO amoxicillin/clavulanic acid in the treatment of patients with cIAI. This study enrolled 595 patients, 511 of which were considered clinically evaluable. The clinically evaluable population consisted of subjects with a surgically confirmed complicated infection, at least 5 days of treatment and a 25 to 50 day follow-up assessment for patients at the Test of Cure visit. The overall clinical success rates in the clinically evaluable patients are shown in Table 16.

15 REFERENCES

• 1.Clinical and Laboratory Standards Institute (CLSI), Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically 9^th edition. Approved Standard CLSI Document M7-A9, CLSI, 950 West Valley Rd., Suite 2500, Wayne, PA 19087, 2012.
• 2.CLSI, Performance Standards for Antimicrobial Susceptibility Testing 22 Informational Supplement. CLSI Document M100-S22, 2012.
• 3.CLSI, Performance Standards for Antimicrobial Disk Susceptibility Tests 11^th edition. Approved Standard CLSI Document M2-A11, 2012.
• 4.CLSI, Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria 8^th edition; Approved Standard CLSI Document M11-A8, 2012.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 Moxifloxacin Hydrochloride Tablets

Moxifloxacin Hydrochloride Tablets are available as modified capsule shaped, dull red film-coated tablets containing 400 mg moxifloxacin. The tablet is debossed with E-18 on one side and plain on the other side.

Unit dose packages of 50 (5 x 10) NDC 68084-722-65

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Avoid high humidity.

17 PATIENT COUNSELING INFORMATION

See FDA-Approved Medication Guide.

17.1 Antibacterial Resistance

Antibacterial drugs including moxifloxacin hydrochloride should only be used to treat bacterial infections. They do not treat viral infections (for example, the common cold). When moxifloxacin hydrochloride is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by moxifloxacin hydrochloride or other antibacterial drugs in the future.

17.2 Administration With Food, Fluids, and Drug Products Containing Multivalent Cations

Patients should be informed that moxifloxacin hydrochloride tablets may be taken with or without food. Patients should be advised to drink fluids liberally.

Moxifloxacin hydrochloride tablets should be taken at least 4 hours before or 8 hours after multivitamins (containing iron or zinc), antacids (containing magnesium or aluminum), sucralfate, or VIDEX^® (didanosine) chewable/buffered tablets or the pediatric powder for oral solution.

17.3 Serious and Potentially Serious Side Effects

To assure safe and effective use of moxifloxacin hydrochloride, patients should be informed of the following serious adverse reactions that have been associated with moxifloxacin hydrochloride and other fluoroquinolone use: 

• • Tendon Disorders: Patients should contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue moxifloxacin hydrochloride treatment. The risk of severe tendon disorder with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.
• • Exacerbation of Myasthenia Gravis: Fluoroquinolones like moxifloxacin hydrochloride may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Patients should call their healthcare provider right away if they have any worsening muscle weakness or breathing problems.
• • Prolongation of the QT interval: Moxifloxacin hydrochloride may produce changes in the electrocardiogram (QTc interval prolongation). Moxifloxacin hydrochloride should be avoided in patients receiving Class IA (for example quinidine, procainamide) or Class III (for example amiodarone, sotalol) antiarrhythmic agents. Moxifloxacin hydrochloride may add to the QTc prolonging effects of other drugs such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants. The patients should inform their physician of any personal or family history of QTc prolongation or proarrhythmic conditions such as recent hypokalemia, significant bradycardia, and acute myocardial ischemia. Patients should contact their physician if they experience palpitations or fainting spells while taking moxifloxacin hydrochloride.
• • Hypersensitivity Reactions: Patients should be advised that moxifloxacin hydrochloride may be associated with hypersensitivity reactions, including anaphylactic reactions, even following a single dose. Patients should discontinue moxifloxacin hydrochloride at the first sign of a skin rash or other signs of an allergic reaction.
• • Convulsions: Convulsions have been reported in patients receiving quinolones, and they should notify their physician before taking moxifloxacin hydrochloride if there is a history of this condition. Patients should also inform their physician if they are taking NSAIDs concurrently with moxifloxacin hydrochloride.
• • Neurologic Adverse Effects (for example, dizziness, lightheadedness): Moxifloxacin hydrochloride may cause dizziness, lightheadedness, and vision disorders; therefore, patients should know how they react to this drug before they operate an automobile or machinery or engage in activities requiring mental alertness or coordination.
• • Psychotic Reaction: Psychotic reactions sometimes resulting in self-injurious behavior have been reported in patients receiving quinolones. Patients should notify their physician if they have a history of psychiatric illness before taking moxifloxacin hydrochloride.
• • Peripheral Neuropathies: Patients should be informed that peripheral neuropathy has been associated with moxifloxacin hydrochloride use. Symptoms may occur soon after initiation of therapy and may be irreversible. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness develop, patients should immediately discontinue moxifloxacin hydrochloride and contact their physician.
• • Photosensitivity/Phototoxicity: Patients should be informed that photosensitivity/ phototoxicity has been reported in patients receiving quinolones. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, patients should contact their physician.
• • Diarrhea: Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

PACKAGING INFORMATION

American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Aurobindo Pharma Limited as follows:

(400 mg / 50 UD) NDC 68084-722-65 packaged from NDC 65862-603

Packaged and Distributed by:

American Health Packaging

Columbus, OH 43217

8272265/0314

8272265/0314FDA-Approved Medication Guide

MEDICATION GUIDE

Moxifloxacin Hydrochloride Tablets
(mox" i flox' a sin hye" droe klor' ide)
Rx only

Read the Medication Guide that comes with moxifloxacin hydrochloride tablets before you start taking them and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about moxifloxacin hydrochloride tablets?
 
Moxifloxacin hydrochloride tablets belong to a class of antibiotics called fluoroquinolones. Moxifloxacin hydrochloride tablets can cause side effects that may be serious or even cause death. If you get any of the following serious side effects, get medical help right away. Talk with your healthcare provider about whether you should continue to take moxifloxacin hydrochloride tablets.

1. Tendon rupture or swelling of the tendon (tendinitis).

• • Tendon problems can happen in people of all ages who take moxifloxacin hydrochloride tablets. Tendons are tough cords of tissue that connect muscles to bones. Symptoms of tendon problems may include:
  • •Pain, swelling, tears and inflammation of tendons including the back of the ankle (Achilles), shoulder, hand, or other tendon sites.
• •The risk of getting tendon problems while you take moxifloxacin hydrochloride tablets is higher if you:
  • •Are over 60 years of age
  • •Are taking steroids (corticosteroids)
  • •Have had a kidney, heart or lung transplant
• • Tendon problems can happen in people who do not have the above risk factors when they take moxifloxacin hydrochloride tablets.
• • Other reasons that can increase your risk of tendon problems can include:
  • •Physical activity or exercise
  • •Kidney failure
  • •Tendon problems in the past, such as in people with rheumatoid arthritis (RA).
• • Call your healthcare provider right away at the first sign of tendon pain, swelling or inflammation. Stop taking moxifloxacin hydrochloride tablets until tendinitis or tendon rupture has been ruled out by your healthcare provider. Avoid exercise and using the affected area. The most common area of pain and swelling is in the Achilles tendon at the back of your ankle. This can also happen with other tendons.
• • Talk to your healthcare provider about the risk of tendon rupture with continued use of moxifloxacin hydrochloride tablets. You may need a different antibiotic that is not a fluoroquinolone to treat your infection.
• • Tendon rupture can happen while you are taking or after you have finished taking moxifloxacin hydrochloride tablets. Tendon ruptures have happened up to several months after patients have finished taking their fluoroquinolone.
• • Get medical help right away if you get any of the following signs or symptoms of a tendon rupture:
  • •Hear or feel a snap or pop in a tendon area
  • •Bruising right after an injury in a tendon area
  • •Unable to move the affected area or bear weight.

2.   Worsening of myasthenia gravis (a disease which causes muscle weakness).

Fluoroquinolones like moxifloxacin hydrochloride tablets may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.

See the section “What are the possible side effects of moxifloxacin hydrochloride tablets?” for more information about side effects.

What are moxifloxacin hydrochloride tablets?
 
Moxifloxacin hydrochloride tablets are a fluoroquinolone antibiotic medicine used to treat certain types of infections caused by certain germs called bacteria in adults 18 years or older. It is not known if moxifloxacin hydrochloride tablets are safe and work in people under 18 years of age. Children have a higher chance of getting bone, joint, and tendon (musculoskeletal) problems while taking fluoroquinolone antibiotic medicines.

Sometimes infections are caused by viruses rather than by bacteria. Examples include viral infections in the sinuses and lungs, such as the common cold or flu. Antibiotics, including moxifloxacin hydrochloride tablets, do not kill viruses.

Call your healthcare provider if you think your condition is not getting better while you are taking moxifloxacin hydrochloride tablets.

Who should not take moxifloxacin hydrochloride tablets?

Do not take moxifloxacin hydrochloride tablets if you have ever had a severe allergic reaction to an antibiotic known as a fluoroquinolone, or if you are allergic to any of the ingredients in moxifloxacin hydrochloride tablets. Ask your healthcare provider if you are not sure. See the list of ingredients in moxifloxacin hydrochloride tablets at the end of this Medication Guide.

What should I tell my healthcare provider before taking moxifloxacin hydrochloride tablets?

See “What is the most important information I should know about moxifloxacin hydrochloride tablets?”

Tell your healthcare provider about all your medical conditions, including if you: 

• •Have tendon problems
•  Have a disease that causes muscle weakness (myasthenia gravis)

• •Have central nervous system problems (such as epilepsy)
• •Have nerve problems
• •Have or anyone in your family has an irregular heartbeat, especially a condition called “QT prolongation”
• •Have low blood potassium (hypokalemia)
• •Have a slow heartbeat (bradycardia)
• •Have a history of seizures
• •Have kidney problems
• •Have rheumatoid arthritis (RA) or other history of joint problems
• •Are pregnant or planning to become pregnant. It is not known if moxifloxacin hydrochloride tablets will harm your unborn child
• •Are breastfeeding or planning to breastfeed. It is not known if moxifloxacin hydrochloride passes into breast milk. You and your healthcare provider should decide whether you will take moxifloxacin hydrochloride tablets or breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, herbal, and dietary supplements. Moxifloxacin hydrochloride tablets and other medicines can affect each other causing side effects. Especially tell your healthcare provider if you take: 

• •An NSAID (Non-Steroidal Anti-Inflammatory Drug). Many common medicines for pain relief are NSAIDs. Taking an NSAID while you take moxifloxacin hydrochloride tablets or other fluoroquinolones may increase your risk of central nervous system effects and seizures. See “What are the possible side effects of moxifloxacin hydrochloride tablets?”
• •A blood thinner (warfarin, Coumadin, Jantoven).
• •A medicine to control your heart rate or rhythm (antiarrhythmic). See “What are the possible side effects of moxifloxacin hydrochloride tablets?"
• •An anti-psychotic medicine.
• •A tricyclic antidepressant.
• •Erythromycin.
• •A water pill (diuretic).
• •A steroid medicine. Corticosteroids taken by mouth or by injection may increase the chance of tendon injury. See “What is the most important information I should know about moxifloxacin hydrochloride tablets?”
• •Certain medicines may keep moxifloxacin hydrochloride tablets from working correctly. Take moxifloxacin hydrochloride tablets either 4 hours before or 8 hours after taking these products:
  • •An antacid, multivitamin, or other product that has magnesium, aluminum, iron, or zinc
  • •Sucralfate (Carafate)
  • •Didanosine (Videx^®, Videx EC^®)

Ask your healthcare provider if you are not sure if any of your medicines are listed above.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take moxifloxacin hydrochloride tablets? 

• •Take moxifloxacin hydrochloride tablets once a day exactly as prescribed by your healthcare provider.
• •Take moxifloxacin hydrochloride tablets at about the same time each day.
• •Moxifloxacin hydrochloride tablets should be swallowed.
• •Moxifloxacin hydrochloride tablets can be taken with or without food.
• •Drink plenty of fluids while taking moxifloxacin hydrochloride tablets.
• •Do not skip any doses, or stop taking moxifloxacin hydrochloride tablets even if you begin to feel better, until you finish your prescribed treatment, unless:
  • •You have tendon effects (see “What is the most important information I should know about moxifloxacin hydrochloride tablets?”).
  • •You have a serious allergic reaction (see “What are the possible side effects of moxifloxacin hydrochloride tablets?”), or your healthcare provider tells you to stop.
• •This will help make sure that all of the bacteria are killed and lower the chance that the bacteria will become resistant to moxifloxacin hydrochloride tablets. If this happens, moxifloxacin hydrochloride tablets and other antibiotic medicines may not work in the future.
• •If you miss a dose of moxifloxacin hydrochloride tablets, take it as soon as you remember. Do not take more than 1 dose of moxifloxacin hydrochloride tablets in one day.
• •If you take too much, call your healthcare provider or get medical help immediately.

What should I avoid while taking moxifloxacin hydrochloride tablets?

• •Moxifloxacin hydrochloride tablets can make you feel dizzy and lightheaded. Do not drive, operate machinery, or do other activities that require mental alertness or coordination until you know how moxifloxacin hydrochloride tablets affect you.
• •Avoid sunlamps, tanning beds, and try to limit your time in the sun. Moxifloxacin hydrochloride tablets can make your skin sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You could get severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while taking moxifloxacin hydrochloride tablets, call your healthcare provider right away. You should use a sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight.

What are the possible side effects of moxifloxacin hydrochloride tablets?

Moxifloxacin hydrochloride tablets can cause side effects that may be serious or even cause death. See “What is the most important information I should know about moxifloxacin hydrochloride tablets?”

Other serious side effects of moxifloxacin hydrochloride tablets include:

  

• • Central Nervous System effects. 
  Seizures have been reported in people who take fluoroquinolone antibiotics including moxifloxacin hydrochloride tablets. Tell your healthcare provider if you have a history of seizures. Ask your healthcare provider whether taking moxifloxacin hydrochloride tablets will change your risk of having a seizure.
  Central Nervous System (CNS) side effects may happen as soon as after taking the first dose of moxifloxacin hydrochloride tablets. Talk to your healthcare provider right away if you have any of these side effects, or other changes in mood or behavior:
  • •Feeling dizzy
  • •Seizures
  • •Hear voices, see things, or sense things that are not there (hallucinations)
  • •Feel restless
  • •Tremors
  • •Feel anxious or nervous
  • •Confusion
  • •Depression
  • •Trouble sleeping
  • •Feel more suspicious (paranoia)
  • •Suicidal thoughts or acts
  • •Nightmares
  • •Vision Loss
• • Serious allergic reactions 
  Allergic reactions can happen in people taking fluoroquinolones, including moxifloxacin hydrochloride tablets, even after only one dose. Stop taking moxifloxacin hydrochloride tablets and get emergency medical help right away if you get any of the following symptoms of a severe allergic reaction:
  • •Hives
  • •Trouble breathing or swallowing
  • •Swelling of the lips, tongue, face
  • •Throat tightness, hoarseness
  • •Rapid heartbeat
  • •Faint
  • •Yellowing of the skin or eyes. Stop taking moxifloxacin hydrochloride tablets and tell your healthcare provider right away if you get yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to moxifloxacin hydrochloride tablets (a liver problem).
• • Skin rash   
  Skin rash may happen in people taking moxifloxacin hydrochloride tablets even after only one dose. Stop taking moxifloxacin hydrochloride tablets at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to moxifloxacin hydrochloride tablets.
• • Serious heart rhythm changes (QT prolongation and torsade de pointes)   
  Tell your healthcare provider right away if you have a change in your heart beat (a fast or irregular heartbeat), or if you faint. Moxifloxacin hydrochloride tablets may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this event are higher in people:
  • •Who are elderly
  • •With a family history of prolonged QT interval
  • •With low blood potassium (hypokalemia)
  • •Who take certain medicines to control heart rhythm (antiarrhythmics)
• • Intestine infection (Pseudomembranous colitis)   
  Pseudomembranous colitis can happen with most antibiotics, including moxifloxacin hydrochloride tablets. Call your healthcare provider right away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. You may have stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after you have finished your antibiotic.
•   Changes in sensation and nerve damage (Peripheral Neuropathy)
•  Damage to the nerves in arms, hands, legs, or feet can happen in people taking fluoroquinolones, including moxifloxacin hydrochloride tablets. Stop moxifloxacin and talk with your healthcare provider right away if you get any of the following symptoms of peripheral neuropathy in your arms, hands, legs, or feet:
  • •Pain
  • •Burning
  • •Tingling
  • •Numbness
  • •Weakness
•  The nerve damage may be permanent.

• • Sensitivity to sunlight (photosensitivity)   
  See “What should I avoid while taking moxifloxacin hydrochloride tablets?” The most common side effects of moxifloxacin hydrochloride tablets include nausea and diarrhea.

These are not all the possible side effects of moxifloxacin hydrochloride tablets. Tell your healthcare provider about any side effect that bothers you or that does not go away.

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

How should I store moxifloxacin hydrochloride tablets? 

• •Store moxifloxacin hydrochloride tablets at 20° to 25°C (68° to 77°F).
• •Keep moxifloxacin hydrochloride tablets away from moisture (humidity).

Keep moxifloxacin hydrochloride tablets and all medicines out of the reach of children.

General information about moxifloxacin hydrochloride tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use moxifloxacin hydrochloride tablets for a condition for which it is not prescribed. Do not give moxifloxacin hydrochloride tablets to other people, even if they have the same symptoms that you have. They may harm them.

This Medication Guide summarizes the most important information about moxifloxacin hydrochloride tablets. If you would like more information about moxifloxacin hydrochloride tablets, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about moxifloxacin hydrochloride tablets that is written for healthcare professionals. For more information call  Aurobindo Pharma USA, Inc. at 1-866-850-2876.

What are the ingredients in moxifloxacin hydrochloride tablets?

Active ingredient: moxifloxacin hydrochloride

Inactive ingredients: hypromellose, iron oxide red, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium starch glycolate, and titanium dioxide.

All brands listed are the trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Packaged and Distributed by:

American Health Packaging

Columbus, OH 43217

8272265/0314

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