moxifloxacin 400 MG Oral Tablet
Generic Name: MOXIFLOXACIN HYDROCHLORIDE
Brand Name: Moxifloxacin Hydrochloride
- Substance Name(s):
- MOXIFLOXACIN HYDROCHLORIDE
DRUG INTERACTIONS
7 Interacting Drug Interaction Multivalent cation-containing products including: antacids, sucralfate, multivitamins Decreased moxifloxacin hydrochloride absorption.
Take moxifloxacin tablet at least 4 hours before or 8 hours after these products.
(2.2 , 7.1 , 12.3) Warfarin Anticoagulant effect enhanced.
Monitor prothrombin time/INR, and bleeding.
(6 , 7.2 , 12.3) Class IA and Class III antiarrhythmics: Proarrhythmic effect may be enhanced.
Avoid concomitant use.
(5.6 , 7.5) Antidiabetic agents Carefully monitor blood glucose.
(5.12 , 7.3) 7.1 Antacids, Sucralfate, Multivitamins and Other Products Containing Multivalent Cations Fluoroquinolones, including moxifloxacin hydrochloride, form chelates with alkaline earth and transition metal cations.
Oral administration of moxifloxacin hydrochloride with antacids containing aluminum or magnesium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as didanosine buffered tablets for oral suspension or the pediatric powder for oral solution, may substantially interfere with the absorption of moxifloxacin hydrochloride, resulting in systemic concentrations considerably lower than desired.
Therefore, moxifloxacin hydrochloride should be taken at least 4 hours before or 8 hours after these agents [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3) ].
7.2 Warfarin Fluoroquinolones, including moxifloxacin hydrochloride, have been reported to enhance the anticoagulant effects of warfarin or its derivatives in the patient population.
In addition, infectious disease and its accompanying inflammatory process, age, and general status of the patient are risk factors for increased anticoagulant activity.
Therefore the prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if moxifloxacin hydrochloride is administered concomitantly with warfarin or its derivatives [see Adverse Reactions (6.2) and Clinical Pharmacology (12.3) ].
7.3 Antidiabetic Agents Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones, including moxifloxacin hydrochloride, and an antidiabetic agent.
Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered.
If a hypoglycemic reaction occurs, moxifloxacin hydrochloride should be discontinued and appropriate therapy should be initiated immediately [see Warnings and Precautions (5.12) and Adverse Reactions (6.1) ].
7.4 Nonsteroidal Anti-Inflammatory Drugs The concomitant administration of a nonsteroidal anti-inflammatory drug (NSAID) with a fluoroquinolone, including moxifloxacin hydrochloride, may increase the risks of CNS stimulation and convulsions [see Warnings and Precautions (5.4) ].
7.5 Drugs that Prolong QT There is limited information available on the potential for a pharmacodynamic interaction in humans between moxifloxacin hydrochloride 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 moxifloxacin hydrochloride in dogs.
Therefore, moxifloxacin hydrochloride should be avoided with Class IA and Class III antiarrhythmics [see Warnings and Precautions (5.6) , and Nonclinical Toxicology (13.2) ].
OVERDOSAGE
10 Single oral overdoses up to 2.8 g were not associated with any serious adverse events.
In the event of acute overdose, empty the stomach and maintain adequate hydration.
Monitor ECG due to the possibility of QT interval prolongation.
Carefully observe the patient and give supportive treatment.
The administration of activated charcoal as soon as possible after oral overdose may prevent excessive increase of systemic moxifloxacin exposure.
About 3% and 9% of the dose of moxifloxacin, as well as about 2% and 4.5% of its glucuronide metabolite are removed by continuous ambulatory peritoneal dialysis and hemodialysis, respectively.
DESCRIPTION
11 Moxifloxacin hydrochloride is a synthetic antibacterial agent for oral 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 powder or crystals, slightly hygroscopic substance with a molecular weight of 437.9.
Its molecular formula is C 21 H 24 FN 3 O 4 *HCl and its chemical structure is as follows: Structural Formula 11.1 Moxifloxacin Tablets, USP Moxifloxacin tablets, USP are available as film-coated tablets 400 mg moxifloxacin (equivalent to 436.33 mg moxifloxacin hydrochloride USP).
The inactive ingredients are hypromellose, iron oxide red, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium starch glycolate, and titanium dioxide.
CLINICAL STUDIES
14 14.1 Acute Bacterial Sinusitis In a controlled double-blind study conducted in the U.S., moxifloxacin 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 .
14.2 Acute Bacterial Exacerbation of Chronic Bronchitis Moxifloxacin 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.
Table 10: Clinical Success Rates at Follow-Up Visit for Clinically Evaluable Patients by Pathogen (Acute Bacterial Exacerbation of Chronic Bronchitis) Pathogen Moxifloxacin Hydrochloride Clarithromycin Streptococcus pneumoniae 16/16 (100%) 20/23 (87%) Haemophilus influenzae 33/37 (89%) 36/41 (88%) Haemophilus parainfluenzae 16/16 (100%) 14/14 (100%) Moraxella catarrhalis 29/34 (85%) 24/24 (100%) Staphylococcus aureus 15/16 (94%) 6/8 (75%) Klebsiella pneumoniae 17/20 (85%) 10/11 (91%) 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%.
14.3 Community Acquired Pneumonia A randomized, double-blind, controlled clinical trial was conducted in the U.S.
to compare the efficacy of moxifloxacin 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 intravenous/oral moxifloxacin 400 mg once a day for 7 to 14 days to an intravenous/oral 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 tablets to sequential intravenous/oral amoxicillin/clavulanate (1.2 gram intravenously every 8 hours/625 mg orally every 8 hours) with or without high-dose intravenous/oral clarithromycin (500 mg twice a day).
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.
Table 11: Clinical Success Rates By Pathogen (Pooled CAP Studies) Pathogen Moxifloxacin Hydrochloride Streptococcus pneumoniae 80/85 (94%) Staphylococcus aureus 17/20 (85%) Klebsiella pneumoniae 11/12 (92%) Haemophilus influenzae 56/61 (92%) Chlamydophila pneumoniae 119/128 (93%) Mycoplasma pneumoniae 73/76 (96%) Moraxella catarrhalis 11/12 (92%) 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 14.
* 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.
Table 12: Clinical and Bacteriological Success Rates for Moxifloxacin Hydrochloride-Treated MDRSP CAP Patients (Population: Valid for Efficacy) Screening Susceptibility Clinical Success Bacteriological Success n/N n = number of patients successfully treated; N = number of patients with MDRSP (from a total of 37 patients) % n/N n = number of patients successfully treated (presumed eradication or eradication); N = number of patients with MDRSP (from a total of 37 patients) % Penicillin-resistant 21/21 100% One patient had a respiratory isolate that was resistant to penicillin and cefuroxime but a blood isolate that was intermediate to penicillin and cefuroxime.
The patient is included in the database based on the respiratory isolate.
21/21 100% 2 nd generation cephalosporin-resistant 25/26 96% 25/26 96% Macrolide-resistant Azithromycin, clarithromycin, and erythromycin were the macrolide antimicrobials tested.
22/23 96% 22/23 96% Trimethoprim/sulfamethoxazole-resistant 28/30 93% 28/30 93% Tetracycline-resistant 17/18 94% 17/18 94% Not all isolates were resistant to all antimicrobial classes tested.
Success and eradication rates are summarized in Table 13.
Table 13: Clinical Success Rates and Microbiological Eradication Rates for Resistant Streptococcus pneumoniae (Community Acquired Pneumonia) S.
pneumoniae with MDRSP Clinical Success Bacteriological Eradication Rate Resistant to 2 antimicrobials 12/13 (92.3%) 12/13 (92.3%) Resistant to 3 antimicrobials 10/11 (90.9%) One patient had a respiratory isolate resistant to 5 antimicrobials and a blood isolate resistant to 3 antimicrobials.
The patient was included in the category resistant to 5 antimicrobials.
10/11 (90.9%) Resistant to 4 antimicrobials 6/6 (100%) 6/6 (100%) Resistant to 5 antimicrobials 7/7 (100%) 7/7 (100%) Bacteremia with MDRSP 9/9 (100%) 9/9 (100%) 14.4 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.
14.5 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 intravenous/oral moxifloxacin 400 mg once a day for 7 to 14 days to an intravenous/oral 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 once a day for 7 to 21 days to sequential intravenous/oral 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.
Table 14: Overall Clinical Success Rates in Patients with Complicated Skin and Skin Structure Infections Study Moxifloxacin Hydrochloride n/N (%) Comparator n/N (%) 95% Confidence Interval of difference in success rates between Moxifloxacin and comparator (Moxifloxacin – comparator) North America 125/162 (77.2%) 141/173 (81.5%) (-14.4%, 2%) International 254/315 (80.6%) 268/317 (84.5%) (-9.4%, 2.2%) Table 15: Clinical Success Rates by Pathogen in Patients with Complicated Skin and Skin Structure Infections Pathogen Moxifloxacin Hydrochloride n/N (%) Comparator n/N (%) Staphylococcus aureus (methicillin-susceptible isolates) methicillin susceptibility was only determined in the North American Study 106/129 (82.2%) 120/137 (87.6%) Escherichia coli 31/38 (81.6%) 28/33 (84.8%) Klebsiella pneumoniae 11/12 (91.7%) 7/10 (70%) Enterobacter cloacae 9/11 (81.8%) 4/7 (57.1%) 14.6 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 intravenous/oral moxifloxacin 400 mg once a day for 5 to 14 days to intravenous /piperacillin/tazobactam followed by oral 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 once a day for 5 to 14 days to intravenous ceftriaxone plus intravenous metronidazole followed by oral 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.
Table 16: Clinical Success Rates in Patients with Complicated Intra-Abdominal Infections Study Moxifloxacin Hydrochloride n/N (%) Comparator n/N (%) 95% Confidence Interval of difference in success rates between moxifloxacin hydrochloride and comparator (moxifloxacin hydrochloride – comparator) North America (overall) 146/183 (79.8%) 153/196 (78.1%) (-7.4%, 9.3%) Abscess 40/57 (70.2%) 49/63 (77.8%) Excludes 2 patients who required additional surgery within the first 48 hours.
NA NA – not applicable Non-abscess 106/126 (84.1%) 104/133 (78.2%) NA International (overall) 199/246 (80.9%) 218/265 (82.3%) (-8.9%, 4.2%) Abscess 73/93 (78.5%) 86/99 (86.9%) NA Non-abscess 126/153 (82.4%) 132/166 (79.5%) NA 14.7 Plague Efficacy studies of moxifloxacin hydrochloride could not be conducted in humans with pneumonic plague for ethical and feasibility reasons.
Therefore, approval of this indication was based on an efficacy study conducted in animals and supportive pharmacokinetic data in adult humans and animals.
A randomized, blinded, placebo-controlled study was conducted in an African Green Monkey (AGM) animal model of pneumonic plague.
Twenty AGM (10 males and 10 females) were exposed to an inhaled mean (± SD) dose of 100 ± 50 LD 50 (range 92 to 127 LD 50 ) of Yersinia pestis (CO92 strain) aerosol.
The minimal inhibitory concentration (MIC) of moxifloxacin for the Y.
pestis strain used in this study was 0.06 mcg/mL.
Development of sustained fever for at least 4 hours duration was used as the trigger for the initiation of 10 days of treatment with either a humanized regimen of moxifloxacin or placebo.
All study animals were febrile and bacteremic with Y.
pestis prior to the initiation of study treatment.
Ten of 10 (100%) of the animals receiving the placebo succumbed to disease between 83 to 139 h (mean 115 ± 19 hours) post treatment.
Ten of 10 (100%) moxifloxacin-treated animals survived for the 30-day period after completion of the study treatment.
Compared to the placebo group, mortality in the moxifloxacin group was significantly lower (difference in survival: 100% with a two-sided 95% exact confidence interval [66.3%, 100%], p-value<0.0001).
The mean plasma concentrations of moxifloxacin associated with a statistically significant improvement in survival over placebo in an AGM model of pneumonic plague are reached or exceeded in human adults receiving the recommended oral and intravenous dosage regimens.
The mean (± SD) peak plasma concentration (C max ) and total plasma exposure defined as the area under the plasma concentration-time curve (AUC) in human adults receiving 400 mg intravenously were 3.9 ± 0.9 mcg/mL and 39.3 ± 8.6 mcg•h/mL, respectively [see Clinical Pharmacology (12.3) ].
The mean (± SD) peak plasma concentration and AUC 0-24 in AGM following one-day administration of a humanized dosing regimen simulating the human AUC 0-24 at a 400 mg dose were 4.4 ± 1.5 mcg/mL and 22 ± 8.0 mcg·h/mL, respectively.
HOW SUPPLIED
16 /STORAGE AND HANDLING 16.1 Moxifloxacin Tablets, USP Moxifloxacin Tablets, USP 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.
FOR YOUR PROTECTION: Do not use if blister is torn or broken.
RECENT MAJOR CHANGES
Dosage and Administration (2.2) 5/2020
GERIATRIC USE
8.5 Geriatric Use Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as moxifloxacin hydrochloride.
This risk is further increased in patients receiving concomitant corticosteroid therapy.
Tendinitis or tendon rupture can involve the Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported.
Caution should be used when prescribing moxifloxacin hydrochloride to elderly patients especially those on corticosteroids.
Patients should be informed of this potential side effect and advised to discontinue moxifloxacin tablets and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [see Boxed Warning , and Warnings and Precautions (5.2) ].
Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients [see Warnings and Precautions (5.9) ].
In controlled multiple-dose clinical trials, 23% of patients receiving oral moxifloxacin hydrochloride were greater than or equal to 65 years of age and 9% were greater than or equal to 75 years of age.
The clinical trial data demonstrate that there is no difference in the safety and efficacy of oral moxifloxacin hydrochloride in patients aged 65 or older compared to younger adults.
In trials of intravenous use, 42% of moxifloxacin hydrochloride patients were greater than or equal to 65 years of age, and 23% were greater than or equal to 75 years of age.
The clinical trial data demonstrate that the safety of intravenous moxifloxacin hydrochloride in patients aged 65 or older was similar to that of comparator-treated patients.
In general, elderly patients may be more susceptible to drug-associated effects of the QT interval.
Therefore, moxifloxacin hydrochloride should be avoided in patients taking drugs that can result in prolongation of the QT interval (for example, class IA or class III antiarrhythmics) or in patients with risk factors for torsade de pointes (for example, known QT prolongation, uncorrected hypokalemia) [see Warnings and Precautions (5.6) , Drug Interactions (7.5) , and Clinical Pharmacology (12.3) ].
DOSAGE FORMS AND STRENGTHS
3 Tablets: 400 mg moxifloxacin (3.1) 3.1 Moxifloxacin Tablets, USP Modified capsule shaped, dull red, film-coated tablets debossed with E-18 on one side and plain on the other side containing 400 mg moxifloxacin
MECHANISM OF ACTION
12.1 Mechanism of Action Moxifloxacin hydrochloride is a member of the fluoroquinolone class of antibacterial agents [see Microbiology (12.4) ].
INDICATIONS AND USAGE
1 Moxifloxacin tablets are a fluoroquinolone antibacterial indicated for treating infections in adults 18 years of age and older caused by designated susceptible bacteria, in the conditions listed below: Community Acquired Pneumonia (1.1) Skin and Skin Structure Infections: Uncomplicated (1.2) and Complicated (1.3) Complicated Intra-Abdominal Infections (1.4) Plague (1.5) Acute Bacterial Sinusitis (1.6) Acute Bacterial Exacerbation of Chronic Bronchitis (1.7) To reduce the development of drug-resistant bacteria and maintain the effectiveness of moxifloxacin tablets and other antibacterial drugs.
Moxifloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
(1.8) 1.1 Community Acquired Pneumonia Moxifloxacin tablets are indicated in adult patients for the treatment of Community Acquired Pneumonia caused by susceptible isolates of Streptococcus pneumoniae (including multi-drug resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Clinical Studies (14.3) ].
MDRSP isolates are isolates resistant to two or more of the following antibacterial drugs: penicillin (minimum inhibitory concentrations [MIC] ≥ 2 mcg/mL), 2nd generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.
1.2 Uncomplicated Skin and Skin Structure Infections Moxifloxacin tablets are indicated in adult patients for the treatment of Uncomplicated Skin and Skin Structure Infections caused by susceptible isolates of methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes [see Clinical Studies (14.4) ].
1.3 Complicated Skin and Skin Structure Infections Moxifloxacin tablets are indicated in adult patients for the treatment of Complicated Skin and Skin Structure Infections caused by susceptible isolates of methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae [see Clinical Studies (14.5) ].
1.4 Complicated Intra-Abdominal Infections Moxifloxacin tablets are indicated in adult patients for the treatment of Complicated Intra-Abdominal Infections (cIAI) including polymicrobial infections such as abscess caused by susceptible isolates of Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron, or Peptostreptococcus species [see Clinical Studies (14.6) ].
1.5 Plague Moxifloxacin tablets are indicated in adult patients for the treatment of plague, including pneumonic and septicemic plague, due to susceptible isolates of Yersinia pestis and prophylaxis of plague in adult patients.
Efficacy studies of moxifloxacin could not be conducted in humans with plague for feasibility reasons.
Therefore, this indication is based on an efficacy study conducted in animals only [see Clinical Studies (14.7) ].
1.6 Acute Bacterial Sinusitis Moxifloxacin tablets are indicated in adult patients for the treatment of acute bacterial sinusitis (ABS) caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae , or Moraxella catarrhalis [see Clinical Studies (14.1) ].
Because fluoroquinolones, including moxifloxacin tablets, have been associated with serious adverse reactions [see Warnings and Precautions (5.1 to 5.14) ] and for some patients ABS is self-limiting, reserve moxifloxacin tablets for treatment of ABS in patients who have no alternative treatment options.
1.7 Acute Bacterial Exacerbation of Chronic Bronchitis Moxifloxacin tablets are indicated in adult patients for the treatment of Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB) caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus, or Moraxella catarrhalis [see Clinical Studies (14.2) ].
Because fluoroquinolones, including moxifloxacin tablets, have been associated with serious adverse reactions [see Warnings and Precautions (5.1 to 5.14) ] and for some patients ABECB is self-limiting, reserve moxifloxacin tablets for treatment of ABECB in patients who have no alternative treatment options.
1.8 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of moxifloxacin tablets and other antibacterial drugs, moxifloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.
In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
PEDIATRIC USE
8.4 Pediatric Use Effectiveness in pediatric patients and adolescents less than 18 years of age has not been established.
Moxifloxacin hydrochloride causes arthropathy in juvenile animals.
Limited information on the safety of moxifloxacin hydrochloride in 301 pediatric patients is available from the cIAI trial [see Boxed Warning , Warnings and Precautions (5.11) and Nonclinical Toxicology (13.2) ].
Active Controlled Trial in Complicated Intra-Abdominal Infection (cIAI) The safety and efficacy of moxifloxacin hydrochloride in pediatric patients for the treatment of cIAI has not been demonstrated.
Pediatric patients 3 months to <18 years of age (mean age of 12 ± 4 years) were enrolled in a single randomized, double-blind, active controlled trial in cIAI including appendicitis with perforation, abscesses and peritonitis.
Pediatric patients were randomized (2:1) to receive either moxifloxacin hydrochloride or comparator.
This study enrolled 451 patients who received study medication, 301 treated with moxifloxacin, and 150 with comparator.
Of the 301 pediatric patients treated with moxifloxacin hydrochloride, 15 were below the age of 6 years and 286 were between the ages of 6 to <18 years.
Patients received sequential intravenous/oral moxifloxacin hydrochloride or comparator (intravenous ertapenem followed by oral amoxicillin/clavulanate) for 5 to 14 days (mean duration was 9 days with a range of 1 to 24 days).
The overall adverse reaction profile in pediatric patients was comparable to that of adult patients.
The most frequently occurring adverse reactions in pediatric patients treated with moxifloxacin hydrochloride were QT prolongation 9.3% (28/301), vomiting, 6.6% (20/301), diarrhea 3.7% (11/301), arthralgia 3.0% (9/301), and phlebitis 2.7% (8/301) (see Table 5).
Discontinuation of study drug due to an adverse reaction was reported in 5.3% (16/301) of moxifloxacin hydrochloride-treated patients versus 1.3% (2/150) of comparator-treated patients.
The adverse reaction profile of moxifloxacin hydrochloride or comparator was similar across all age groups studied.
Musculoskeletal adverse reactions were monitored and followed up to 5 years after the end of study treatment.
The rates of musculoskeletal adverse reactions were 4.3% (13/301) in the moxifloxacin hydrochloride-treated group versus 3.3% (5/150) in the comparator-treated group.
The majority of musculoskeletal adverse reactions were reported between 12 and 53 weeks after start of study treatment with complete resolution at the end of the study [see Warnings and Precautions (5.11) and Nonclinical Toxicology (13.2) ].
Table 5 Incidence (%) of Selected Adverse Reactions in ≥2.0% of Pediatric Patients Treated with Moxifloxacin Hydrochloride in cIAI Clinical Trial System Organ Class Adverse Reactions Moxifloxacin Hydrochloride N = 301 (%) Comparator N = 150 (%) Gastrointestinal disorders Abdominal pain 8 (2.7) 3 (2.0) Diarrhea 11 (3.7) 1 (0.7) Vomiting 20 (6.6) 12 (8.0) General disorders and administration site conditions Pyrexia 6 (2.0) 4 (2.7) Investigations Aspartate aminotransferase increased 2 (0.7) 3 (2.0) Electrocardiogram QT prolonged 28 (9.3) 4 (2.7) Musculoskeletal and connective tissue disorders Arthralgia 9 (3.0) 2 (1.3) Nervous system disorders Headache 6 (2.0) 2 (1.3) Vascular disorders Phlebitis 8 (2.7) 0 (0) Clinical response was assessed at the test-of-cure visit (28 to 42 days after end of treatment).
The clinical response rates observed in the modified intent to treat population were 83.9% (208/248) for moxifloxacin hydrochloride and 95.5% (127/133) for comparator; see Table 6.
Table 6: Clinical Response Rates at 28 to 42 Days After End of Treatment in Pediatric Patients with cIAI Moxifloxacin Hydrochloride n (%) Comparator n (%) Difference Difference in clinical cure rates (moxifloxacin hydrochloride – Comparator) and 95% confidence intervals, presented as percentages, are based on stratified analysis by age group using Mantel-Haenszel methods.
(95% CI) mITT Population The modified intent-to-treat (mITT) population is defined as all subjects who were treated with at least one dose of study medication and who have at least one pre-treatment causative organism from the intra-abdominal site of infection or from blood cultures.
N=248 N=133 Cure 208 (83.9) 127 (95.5) -12.2 (-17.9, -6.4) Failure 17 (6.9) 3 (2.3) Indeterminate 21 (8.5) 3 (2.3) Missing 2 (0.8) 0
PREGNANCY
8.1 Pregnancy Risk Summary There are no available human data establishing a drug associated risk with the use of moxifloxacin.
Based on animal studies with moxifloxacin, moxifloxacin hydrochloride may cause fetal harm.
Moxifloxacin did not cause fetal malformations when administered to pregnant rats (IV and oral), rabbits (IV), and monkeys (oral) at exposures that were 0.24 to 2.5 times of those at the human clinical dose (400 mg/day moxifloxacin hydrochloride).
However, when moxifloxacin was administered to rats and rabbits during pregnancy and throughout lactation (rats only) at doses associated with maternal toxicity, decreased neonatal body weights, increased incidence of skeletal variations (rib and vertebra combined), and increased fetal loss were observed (see Data).
Advise pregnant women of the potential risk to the fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Animal Data Animal reproductive and development studies were done in rats, rabbits and cynomolgus macaques.
Moxifloxacin did not cause fetal malformations when administered to pregnant rats during organogenesis (gestation days 6 to 17) at oral doses as high as 500 mg/kg/day or 0.24 times the maximum recommended human dose based on systemic exposure (AUC), but decreased fetal body weights and slightly delayed fetal skeletal development were observed.
Intravenous administration of 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) to pregnant rats resulted in maternal toxicity and a marginal effect on fetal and placental weights and the appearance of the placenta (Gestation days 6 to 17).
Fetal malformations were not observed at intravenous doses as high as 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) in litters of pregnant rats that received moxifloxacin during organogenesis (Gestation days 6 to 17).
Intravenous administration of 20 mg/kg/day (approximately equal to the maximum recommended human oral dose based upon systemic exposure) to pregnant rabbits during organogenesis (gestation days 6 to 20) resulted in decreased fetal body weights and delayed fetal skeletal ossification.
When rib and vertebral malformations were combined, there was an increased fetal and litter incidence of these effects in rabbits.
Signs of maternal toxicity in rabbits at this dose included mortality, abortions, marked reduction of food consumption, decreased water intake, body weight loss and hypoactivity.
Fetal malformations were not observed when pregnant cynomolgus macaques were given oral doses as high as 100 mg/kg/day (2.5 times the maximum recommended human dose based upon systemic exposure) during organogenesis (gestation days 20 to 50).
An increased incidence of smaller fetuses was observed at 100 mg/kg/day in macaques.
In a pre-and postnatal development study conducted in rats given oral doses from Gestation day 6, throughout gestation and rearing to Postpartum day 21, effects observed at 500 mg/kg/day (0.24 times the maximum recommended human dose based on systemic exposure (AUC)) included slight increases in duration of pregnancy and prenatal loss, reduced pup birth weight and decreased neonatal survival.
Treatment-related maternal mortality occurred during gestation at 500 mg/kg/day in this study.
BOXED WARNING
WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS and EXACERBATION OF MYASTHENIA GRAVIS Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together [see Warnings and Precautions (5.1) ], including: Tendinitis and tendon rupture [see Warnings and Precautions (5.2) ] Peripheral neuropathy [see Warnings and Precautions (5.3) ] Central nervous system effects [see Warnings and Precautions (5.4) ] Discontinue moxifloxacin hydrochloride immediately and avoid the use of fluoroquinolones, including moxifloxacin hydrochloride, in patients who experience any of these serious adverse reactions [see Warnings and Precautions (5.1) ].
Fluoroquinolones, including moxifloxacin hydrochloride, may exacerbate muscle weakness in patients with myasthenia gravis.
Avoid moxifloxacin hydrochloride in patients with known history of myasthenia gravis [see Warnings and Precautions (5.5) ].
Because fluoroquinolones, including moxifloxacin hydrochloride, have been associated with serious adverse reactions [see Warnings and Precautions (5.1 to 5.14) ], reserve moxifloxacin hydrochloride for use in patients who have no alternative treatment options for the following indications: Acute bacterial sinusitis [see Indications and Usage (1.6) ] Acute bacterial exacerbation of chronic bronchitis [see Indications and Usage (1.7) ] WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS and EXACERBATION OF MYASTHENIA GRAVIS See full prescribing information for complete boxed warning Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together (5.1) including: Tendinitis and tendon rupture (5.2) Peripheral Neuropathy (5.3) Central nervous system effects (5.4) Discontinue moxifloxacin hydrochloride immediately and avoid the use of fluoroquinolones, including moxifloxacin hydrochloride, in patients who experience any of these serious adverse reactions (5.1) Fluoroquinolones, including moxifloxacin hydrochloride, may exacerbate muscle weakness in patients with myasthenia gravis.
Avoid moxifloxacin hydrochloride in patients with known history of myasthenia gravis (5.5) .
Because fluoroquinolones, including moxifloxacin hydrochloride, have been associated with serious adverse reactions (5.1 to 5.14) , reserve moxifloxacin hydrochloride for use in patients who have no alternative treatment options for the following indications: Acute bacterial sinusitis (1.6) Acute bacterial exacerbation of chronic bronchitis (1.7)
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS Prolongation of the QT interval and isolated cases of torsade de pointes has been reported.
Avoid use in patients with known prolongation, proarrhythmic conditions such as clinically significant bradycardia or acute myocardial ischemia, hypokalemia, hypomagnesemia, and with drugs that prolong the QT interval.
(5.6 , 7.5 , 8.5) Hypersensitivity and other serious reactions: Serious and sometimes fatal reactions, including anaphylactic reactions, may occur after first or subsequent doses of moxifloxacin hydrochloride.
Discontinue moxifloxacin hydrochloride at first sign of skin rash, jaundice or any other sign of hypersensitivity.
(5.7 , 5.8) Clostridioides difficile -Associated Diarrhea: Evaluate if diarrhea occurs.
(5.10) 5.1 Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient.
Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion).
These reactions can occur within hours to weeks after starting moxifloxacin hydrochloride.
Patients of any age or without pre-existing risk factors have experienced these adverse reactions [see Warnings and Precautions (5.2 , 5.3 , 5.4) ].
Discontinue moxifloxacin hydrochloride immediately at the first signs or symptoms of any serious adverse reaction.
In addition, avoid the use of fluoroquinolones, including moxifloxacin hydrochloride, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.
5.2 Tendinitis and Tendon Rupture Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of tendinitis and tendon rupture in all ages [see Warnings and Precautions (5.1) and Adverse Reactions (6.2) ].
This adverse reaction most frequently involves the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons.
Tendinitis or tendon rupture can occur within hours or days of starting moxifloxacin or as long as several months after completion of therapy.
Tendinitis and tendon rupture can occur bilaterally.
The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.
Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.
Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors.
Discontinue moxifloxacin hydrochloride immediately if the patient experiences pain, swelling, inflammation or rupture of a tendon.
Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug.
Avoid fluoroquinolones, including moxifloxacin hydrochloride, in patients who have a history of tendon disorders or who have experienced tendinitis or tendon rupture [see Adverse Reactions (6.2) ].
5.3 Peripheral Neuropathy Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of peripheral neuropathy.
Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones including moxifloxacin hydrochloride.
Symptoms may occur soon after initiation of moxifloxacin hydrochloride and may be irreversible in some patients [see Warnings and Precautions (5.1) and Adverse Reactions (6.1 , 6.2) ].
Discontinue moxifloxacin hydrochloride immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation.
Avoid fluoroquinolones, including moxifloxacin hydrochloride, in patients who have previously experienced peripheral neuropathy.
5.4 Central Nervous System Effects Psychiatric Adverse Reactions Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of psychiatric adverse reactions, including: toxic psychosis, hallucinations, or paranoia; depression or suicidal thoughts or acts; anxiety, agitation, or nervousness; confusion, delirium, disorientation, or disturbances in attention; insomnia or nightmares; memory impairment.
These adverse reactions may occur following the first dose.
If these reactions occur in patients receiving moxifloxacin hydrochloride, discontinue moxifloxacin hydrochloride immediately and institute appropriate measures [see Adverse Reactions (6.1 , 6.2) ].
Central Nervous System Adverse Reactions Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremors.
As with all fluoroquinolones, use moxifloxacin hydrochloride with caution in patients with known or suspected CNS disorders (for example, severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold.
These adverse reactions may occur following the first dose.
If these reactions occur in patients receiving moxifloxacin hydrochloride, discontinue moxifloxacin hydrochloride immediately and institute appropriate measures [see Drug Interactions (7.4) , Adverse Reactions (6.1 , 6.2) , and Patient Counseling Information (17) ].
5.5 Exacerbation of Myasthenia Gravis Fluoroquinolones, including moxifloxacin hydrochloride, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis.
Postmarketing serious adverse reactions, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in patients with myasthenia gravis.
Avoid moxifloxacin hydrochloride in patients with known history of myasthenia gravis.
5.6 QT Prolongation Moxifloxacin hydrochloride has been shown to prolong the QT interval of the electrocardiogram in some patients.
Following oral dosing with 400 mg of moxifloxacin hydrochloride 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 10 msec (±22) on Day 1 (n=667) and 7 msec (± 24) on Day 3 (n = 667).
Avoid moxifloxacin hydrochloride in patients with the following risk factors due to the lack of clinical experience with the drug in these patient populations: Known prolongation of the QT interval Ventricular arrhythmias including torsade de pointes because QT prolongation may lead to an increased risk for these conditions Ongoing proarrhythmic conditions, such as clinically significant bradycardia and acute myocardial ischemia, Uncorrected hypokalemia or hypomagnesemia Class IA (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic agents Other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants Elderly patients using intravenous moxifloxacin hydrochloride may be more susceptible to drug-associated QT prolongation [see Use In Specific Populations (8.5) ].
In patients with mild, moderate, or severe liver cirrhosis, metabolic disturbances associated with hepatic insufficiency may lead to QT prolongation.
Monitor ECG in patients with liver cirrhosis treated with moxifloxacin hydrochloride [see Clinical Pharmacology (12.3) ].
The magnitude of QT prolongation may increase with increasing concentrations of the drug or increasing rates of infusion of the intravenous formulation.
Therefore the recommended dose or infusion rate should not be exceeded.
In premarketing clinical trials, the rate of cardiovascular adverse reactions was similar in 798 moxifloxacin hydrochloride and 702 comparator treated patients who received concomitant therapy with drugs known to prolong the QTc interval.
No excess in cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin hydrochloride treatment in over 15,500 patients in controlled clinical studies, including 759 patients who were hypokalemic at the start of treatment, and there was no increase in mortality in over 18,000 moxifloxacin tablet treated patients in a postmarketing observational study in which ECGs were not performed.
5.7 Other Serious and Sometimes Fatal Adverse Reactions Other serious and sometimes fatal adverse reactions, some due to hypersensitivity, and some due to uncertain etiology, have been reported in patients receiving therapy with fluoroquinolones, including moxifloxacin hydrochloride.
These reactions may be severe and generally occur following the administration of multiple doses.
Clinical manifestations may include one or more of the following: Fever, rash, or severe dermatologic reactions (for example, toxic epidermal necrolysis, Stevens-Johnson syndrome) Vasculitis; arthralgia; myalgia; serum sickness Allergic pneumonitis Interstitial nephritis; acute renal insufficiency or failure Hepatitis; jaundice; acute hepatic necrosis or failure Anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities Discontinue moxifloxacin hydrochloride immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and institute supportive measures.
5.8 Hypersensitivity Reactions Serious anaphylactic reactions, some following the first dose, have been reported in patients receiving fluoroquinolone therapy, including moxifloxacin hydrochloride.
Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching.
Discontinue moxifloxacin hydrochloride at the first appearance of a skin rash or any other sign of hypersensitivity [see Warnings and Precautions (5.7) ].
5.9 Risk of Aortic Aneurysm and Dissection Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients.
The cause for the increased risk has not been identified.
In patients with a known aortic aneurysm or patients who are at greater risk for aortic aneurysms, reserve moxifloxacin hydrochloride for use only when there are no alternative antibacterial treatments available.
5.10 Clostridioides difficile -Associated Diarrhea Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including moxifloxacin hydrochloride, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C.
difficile .
C.
difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin producing strains of C.
difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibacterial use.
Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.
difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C.
difficile , and surgical evaluation should be instituted as clinically indicated.
5.11 Arthropathic Effects in Animals In immature dogs, oral administration of moxifloxacin hydrochloride caused lameness.
Histopathological examination of the weight-bearing joints of these dogs revealed permanent lesions of the cartilage.
Related quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature animals of various species [see Nonclinical Toxicology (13.2) ].
5.12 Blood Glucose Disturbances As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with moxifloxacin hydrochloride.
In moxifloxacin hydrochloride-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (for example, sulfonylurea) or with insulin.
Severe cases of hypoglycemia resulting in coma or death have been reported.
In diabetic patients, careful monitoring of blood glucose is recommended.
If a hypoglycemic reaction occurs, discontinue moxifloxacin hydrochloride and initiate appropriate therapy immediately [see Adverse Reactions (6.1) , Drug Interactions (7.3) , and Patient Counseling Information (17) ].
5.13 Photosensitivity/Phototoxicity Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (for example, burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of fluoroquinolones, including moxifloxacin hydrochloride, after sun or UV light exposure.
Therefore, excessive exposure to these sources of light should be avoided.
Moxifloxacin hydrochloride should be discontinued if phototoxicity occurs [see Clinical Pharmacology (12.2) ].
5.14 Development of Drug Resistant Bacteria Prescribing moxifloxacin hydrochloride in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide) Serious Adverse Reactions Advise patients to stop taking moxifloxacin hydrochloride if they experience an adverse reaction and to call their healthcare provider for advice on completing the full course of treatment with another antibacterial drug.
Inform patients of the following serious adverse reactions that have been associated with moxifloxacin hydrochloride or other fluoroquinolone use: Disabling and potentially irreversible serious adverse reactions that may occur together: Inform patients that disabling and potentially irreversible serious adverse reactions, including tendinitis and tendon rupture, peripheral neuropathies, and central nervous system effects, have been associated with use of moxifloxacin hydrochloride and may occur together in the same patient.
Inform patients to stop taking moxifloxacin hydrochloride immediately if they experience an adverse reaction and to call their healthcare provider.
Tendinitis and Tendon Rupture: Instruct patients to 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.
Symptoms may be irreversible.
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.
Peripheral Neuropathies: Inform patients that peripheral neuropathies have 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, immediately discontinue moxifloxacin hydrochloride and tell them to contact their physician.
Central nervous system effects (for example, convulsions, dizziness, lightheadedness, increased intracranial pressure): Inform patients that convulsions have been reported in patients receiving fluoroquinolones, including moxifloxacin hydrochloride.
Instruct patients to notify their physician before taking this drug if they have a history of convulsions.
Inform patients that they should know how they react to moxifloxacin hydrochloride before they operate an automobile or machinery or engage in other activities requiring mental alertness and coordination.
Instruct patients to notify their physician if persistent headache with or without blurred vision occurs.
Exacerbation of Myasthenia Gravis: Instruct patients to inform their physician of any history of myasthenia gravis.
Instruct patients to notify their physician if they experience any symptoms of muscle weakness, including respiratory difficulties.
Hypersensitivity Reactions: Inform patients that moxifloxacin hydrochloride can cause hypersensitivity reactions, even following a single dose, and to discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (for example, swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction.
Hepatotoxicity: Inform patients that severe hepatotoxicity (including acute hepatitis and fatal events) has been reported in patients taking moxifloxacin hydrochloride.
Instruct patients to inform their physician if they experience any signs or symptoms of liver injury including: loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin and eyes, light colored bowel movements or dark colored urine.
Aortic aneurysm and dissection: Inform patients to seek emergency medical care if they experience sudden chest, stomach, or back pain.
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, instruct patients to contact their physician as soon as possible.
Prolongation of the QT Interval: Instruct patients to inform their physician of any personal or family history of QT prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia; if they are taking any Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents.
Instruct patients to notify their physician if they have any symptoms of prolongation of the QT interval, including prolonged heart palpitations or a loss of consciousness.
Blood Glucose Disturbances: Inform the patients that if they are diabetic and are being treated with insulin or an oral hypoglycemic agent and a hypoglycemic reaction occurs, they should discontinue moxifloxacin hydrochloride and consult a physician.
Photosensitivity/Phototoxicity: Inform patients that photosensitivity/phototoxicity has been reported in patients receiving fluoroquinolones.
Inform patients to 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, instruct them to 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, instruct patients to contact their physician.
Antibacterial Resistance Inform patients that 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.
Administration Instructions Inform patients that moxifloxacin tablets may be taken with or without food.
Advise patients drink fluids liberally.
Inform patients that moxifloxacin 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 didanosine buffered tablets for oral suspension or the pediatric powder for oral solution.
Advise patients that if a dose is missed, it should be taken anytime but not later than 8 hours prior to the next scheduled dose.
If less than 8 hours remain before the next dose, the missed dose should not be taken and treatment should be continued as prescribed with the next scheduled dose.
Double doses should not be taken to compensate for a missed dose.
Plague Studies Inform patients given moxifloxacin hydrochloride for plague that efficacy studies could not be conducted in humans for feasibility reasons.
Therefore, approval for plague was based on efficacy studies conducted in animals.
Dispense with Medication Guide.
To order more Medication Guides, call American Health Packaging at 1-800-707-4621.
DOSAGE AND ADMINISTRATION
2 Type of Infection Dose Every 24 hours Duration (days) Community Acquired Pneumonia (1.1) 400 mg 7 to 14 Uncomplicated Skin and Skin Structure Infections (SSSI) (1.2) 400 mg 7 Complicated SSSI (1.3) 400 mg 7 to 21 Complicated Intra-Abdominal Infections (1.4) 400 mg 5 to 14 Plague (1.5) 400 mg 10 to 14 Acute Bacterial Sinusitis (1.6) 400 mg 10 Acute Bacterial Exacerbation of Chronic Bronchitis (1.7) 400 mg 5 No dosage adjustment in patients with renal or hepatic impairment.
(8.6 , 8.7) 2.1 Dosage in Adult Patients The dose of moxifloxacin is 400 mg (orally) once every 24 hours.
The duration of therapy depends on the type of infection as described in Table 1.
Table 1: Dosage and Duration of Therapy in Adult Patients Type of Infection Due to the designated pathogens [see Indications and Usage (1)].
Dose Every 24 hours Duration Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician (days) Community Acquired Pneumonia (1.1) 400 mg 7 to 14 Uncomplicated Skin and Skin Structure Infections (SSSI ) (1.2) 400 mg 7 Complicated SSSI (1.3) 400 mg 7 to 21 Complicated Intra-Abdominal Infections (1.4) 400 mg 5 to 14 Plague (1.5) Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis.
400 mg 10 to 14 Acute Bacterial Sinusitis (ABS) (1.6) 400 mg 10 Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB) (1.7) 400 mg 5 Conversion of Intravenous to Oral Dosing in Adults Intravenous formulation is indicated when it offers a route of administration advantageous to the patient (for example, patient cannot tolerate an oral dosage form).
When switching from intravenous to oral formulation, no dosage adjustment is necessary.
Patients whose therapy is started with moxifloxacin hydrochloride injection may be switched to moxifloxacin tablets when clinically indicated at the discretion of the physician.
2.2 Important Administration Instructions With Multivalent Cations Administer moxifloxacin tablets at least 4 hours before or 8 hours after products containing magnesium, aluminum, iron or zinc, including antacids, sucralfate, multivitamins and didanosine buffered tablets for oral suspension or the pediatric powder for oral solution [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ].
With Food Moxifloxacin tablets can be taken with or without food, drink fluids liberally.
Missed Doses If a dose is missed, it should be taken anytime but not later than 8 hours prior to the next scheduled dose.
If less than 8 hours remain before the next dose, the missed dose should not be taken and treatment should be continued as prescribed with the next scheduled dose.
Double doses should not be taken to compensate for a missed dose.