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

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

AVELOX IV

• AVELOX IV is available in ready-to-use 250 mL latex-free flexibags as a sterile, preservative free, 0.8% sodium chloride aqueous solution of moxifloxacin hydrochloride (containing 400 mg moxifloxacin) with pH ranging from 4.1 to 4.6.
• The appearance of the intravenous solution is yellow. The color does not affect, nor is it indicative of, product stability.
• The inactive ingredients are sodium chloride, USP, Water for Injection, USP, and may include hydrochloric acid and/or sodium hydroxide for pH adjustment.
• AVELOX IV contains approximately 34.2 mEq (787 mg) of sodium in 250 mL.

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Serious and Otherwise Important Adverse Reactions The following serious and otherwise important adverse reactions are discussed in greater detail in the WARNINGS AND PRECAUTIONS section of the label:

• Tendinopathy and Tendon Rupture [see WARNINGS AND PRECAUTIONS]
• QT Prolongation [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Other Serious and Sometimes Fatal Reactions [see WARNINGS AND PRECAUTIONS]
• Central Nervous System Effects [see WARNINGS AND PRECAUTIONS]
• Clostridium Difficile-Associated Diarrhea [see WARNINGS AND PRECAUTIONS]
• Peripheral Neuropathy that may be irreversible [see WARNINGS AND PRECAUTIONS]
• Photosensitivity/Phototoxicity [see WARNINGS AND PRECAUTIONS]
• Development of Drug Resistant Bacteria [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to AVELOX in 14981 patients in 71 active controlled Phase II-IV clinical trials in different indications [see INDICATIONS AND USAGE]. The population studied had a mean age of 50 years (approximately 73% of the population was <65 years of age), 50% were male, 63% were Caucasian, 12% were Asian and 9% were Black. Patients received AVELOX 400 mg once daily PO, IV, or sequentially (IV followed by PO). Treatment duration was usually 6-10 days, and the mean number of days on therapy was 9 days. Discontinuation of AVELOX due to adverse events occurred in 5.0% of patients overall, 4.1% of patients treated with 400 mg PO, 3.9% with 400 mg IV and 8.2% with sequential therapy 400 mg PO/IV. The most common adverse events leading to discontinuation with the 400 mg PO doses were nausea (0.8%), diarrhea (0.5%), dizziness (0.5%), and vomiting (0.4%). The most common adverse event leading to discontinuation with the 400 mg IV dose was rash (0.5%). The most common adverse events leading to discontinuation with the 400 mg IV/PO sequential dose were diarrhea (0.5%), pyrexia (0.4%). Adverse reactions occurring in ≥1% of AVELOX-treated patients and less common adverse reactions, occurring in 0.1 to <1% of AVELOX-treated patients, are shown in Tables 2 and Table 3, respectively. The most common adverse drug reactions (≥3%) are nausea, diarrhea, headache, and dizziness. Table 2 : Common (≥ 1.0%) Adverse Reactions Reported in Active-Controlled Clinical Trials with AVELOX
System Organ Class Adverse Reactionsa %
(N=14,981) Blood and Lymphatic System Disorders Anemia 1.1 Gastrointestinal Disorders Nausea 6.9 Diarrhea 6.0 Vomiting 2.4 Constipation 1.9 Abdominal pain 1.5 Abdominal pain upper 1.1 Dyspepsia 1.0 General Disorders and Administration Site Conditions Pyrexia 1.1 Investigations Alanine aminotransferase increased 1.1 Metabolism and Nutritional Disorder Hypokalemia 1 Nervous System Disorders Headache 4.2 Dizziness 3.0 Psychiatric Disorders Insomnia 1.9 a MedDRA Version 12.0 Table 3 : Less Common (0.1 to <1.0%) Adverse Reactions Reported in Active-Controlled Clinical Trials with AVELOX (N=14,981)
System Organ Class Adverse Reactionsa Blood and Lymphatic System Disorders Thrombocythemia
Eosinophilia
Neutropenia
Thrombocytopenia
Leukopenia
Leukocytosis Cardiac Disorders Atrial fibrillation Palpitations Tachycardia Cardiac failure congestive Angina pectoris Cardiac failure Cardiac arrest Bradycardia Ear and Labyrinth Disorders Vertigo
Tinnitus Eye Disorders Vision blurred Gastrointestinal Disorders Dry mouth
Abdominal discomfort
Flatulence
Abdominal distention
Gastritis
Gastroesophageal reflux disease General Disorders and Administration Site Conditions Fatigue
Chest pain
Asthenia
Edema peripheral
Pain
Malaise
Infusion site extravasation
Edema
Chills
Chest discomfort
Facial pain Hepatobiliary disorders Hepatic function abnormal Infections and Infestations Vulvovaginal candidiasis
Oral candidiasis
Vulvovaginal mycotic infection
Candidiasis
Vaginal infection
Oral fungal infection
Fungal infection
Gastroenteritis Investigations Aspartate aminotransferase increased
Gamma-glutamyltransferase increased
Blood alkaline phosphatase increased
Hepatic enzyme increased
Electrocardiogram QT prolonged
Blood lactate dehydrogenase increased
Platelet count increased
Blood amylase increased
Blood glucose increased
Lipase increased
Hemoglobin decreased
Blood creatinine increased
Transaminases increased
White blood cell count increased
Blood urea increased
Liver function test abnormal
Hematocrit decreased
Prothrombin time prolonged
Eosinophil count increased
Activated partial thromboplastin time prolonged
Blood bilirubin increased
Blood triglycerides increased
Blood uric acid increased
Blood pressure increased Metabolism and Nutrition Disorders Hyperglycemia
Anorexia
Hypoglycemia
Hyperlipidemia
Decreased appetite
Dehydration Musculoskeletal and Connective Tissue Disorders Back pain
Pain in extremity
Arthralgia
Myalgia
Muscle spasms
Musculoskeletal chest pain
Musculoskeletal pain Nervous System Disorders Dysgeusia
Somnolence
Tremor
Lethargy
Paresthesia
Tension headache
Hypoesthesia
Syncope Psychiatric Disorders Anxiety
Confusional state
Agitation
Depression
Nervousness
Restlessness
Hallucination
Disorientation Renal and Urinary Disorders Renal failure
Dysuria
Renal failure acute Reproductive System and Breast Disorders Vulvovaginal pruritus Respiratory, Thoracic, and Mediastinal Disorders Dyspnea
Asthma
Wheezing
Bronchospasm Skin and Subcutaneous Tissue Disorders Rash
Pruritus
Hyperhidrosis
Erythema
Urticaria
Dermatitis allergic
Night sweats Vascular disorders Hypertension
Hypotension
Phlebitis a MedDRA Version 12.0 Laboratory Changes Changes in laboratory parameters, without regard to drug relationship, which are not listed above and which occurred in ≥ 2% of patients and at an incidence greater than in controls included: increases in MCH, neutrophils, WBCs, PT ratio, ionized calcium, chloride, albumin, globulin, bilirubin; decreases in hemoglobin, RBCs, neutrophils, eosinophils, basophils, PT ratio, glucose, pO2, bilirubin, and amylase. It cannot be determined if any of the above laboratory abnormalities were caused by the drug or the underlying condition being treated. Postmarketing Experience Table 4 lists adverse reactions that have been identified during post-approval use of AVELOX. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Table 4: Postmarketing Reports of Adverse Drug Reactions
System/Organ Class Adverse Reaction Blood and Lymphatic System Disorders Agranulocytosis Pancytopenia [see WARNINGS AND PRECAUTIONS] Cardiac Disorders Ventricular tachyarrhythmias (including in very rare cases cardiac arrest and torsade de pointes, and usually in patients with concurrent severe underlying proarrhythmic conditions) Ear and Labyrinth Disorders Hearing impairment, including deafness (reversible in majority of cases) Eye Disorders Vision loss (especially in the course of CNS reactions, transient in majority of cases) Hepatobiliary Disorders Hepatitis (predominantly cholestatic) Hepatic failure (including fatal cases) Jaundice Acute hepatic necrosis [see WARNINGS AND PRECAUTIONS] Immune System Disorders Anaphylactic reaction Anaphylactic shock Angioedema (including laryngeal edema) [see WARNINGS AND PRECAUTIONS] Musculoskeletal and Connective Tissue Disorders Tendon rupture [see WARNINGS AND PRECAUTIONS] Nervous System Disorders Altered coordination Abnormal gait [see WARNINGS AND PRECAUTIONS] Myasthenia gravis (exacerbation of) [see WARNINGS AND PRECAUTIONS] Muscle weakness Peripheral neuropathy (that may be irreversible), polyneuropathy [see WARNINGS AND PRECAUTIONS] Psychiatric Disorders Psychotic reaction (very rarely culminating in self-injurious behavior, such as suicidal ideation/thoughts or suicide attempts [see WARNINGS AND PRECAUTIONS] Renal and Urinary Disorders Renal dysfunction Interstitial nephritis [see WARNINGS AND PRECAUTIONS] Respiratory, Thoracic and Mediastinal Disorders Allergic pneumonitis [see WARNINGS AND PRECAUTIONS] Skin and Subcutaneous Tissue Disorders Photosensitivity/phototoxicity reaction [see WARNINGS AND PRECAUTIONS] Stevens-Johnson syndrome Toxic epidermal necrolysis [see WARNINGS AND PRECAUTIONS] Read the Avelox (moxifloxacin hcl) Side Effects Center for a complete guide to possible side effectsLearn More »

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Dosage in Adult Patients The dose of AVELOX is 400 mg (orally or as an intravenous infusion) 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 Infectiona Dose Every 24 hours Durationb (days) Acute Bacterial Sinusitis (1.1) 400 mg 10 Acute Bacterial Exacerbation of Chronic Bronchitis (1.2) 400 mg 5 Community Acquired Pneumonia 400 mg 7-14 Uncomplicated Skin and Skin Structure Infections (SSSI ) (1.4) 400 mg 7 Complicated SSSI (1.5) 400 mg 7-21 Complicated Intra-Abdominal Infections (1.6) 400 mg 5-14 aDue to the designated pathogens [see INDICATIONS AND USAGE, for IV use, see Use In Specific Populations].
b Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician 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 AVELOX IV may be switched to AVELOX Tablets when clinically indicated at the discretion of the physician. Drug interactions with Multivalent Cations Oral doses of AVELOX should be administered at least 4 hours before or 8 hours after products containing magnesium, aluminum, iron or zinc, including antacids, sucralfate, multivitamins and VIDEX® (didanosine) chewable/buffered tablets or the pediatric powder for oral solution [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY]. Administration Instructions AVELOX Film-Coated Tablets AVELOX Tablets can be taken with or without food, drink fluids liberally. AVELOX IV Solution for Infusion Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. AVELOX IV should be administered by INTRAVENOUS infusion only. It is not intended for intra-arterial, intramuscular, intrathecal, intraperitoneal, or subcutaneous administration. AVELOX IV should be administered by intravenous infusion over a period of 60 minutes by direct infusion or through a Y-type intravenous infusion set which may already be in place. Caution: rapid or bolus intravenous infusion must be avoided. Because only limited data are available on the compatibility of AVELOX intravenous injection with other intravenous substances, additives or other medications should not be added to AVELOX IV or infused simultaneously through the same intravenous line. If the same intravenous line or a Y-type line is used for sequential infusion of other drugs, or if the “piggyback” method of administration is used, the line should be flushed before and after infusion of AVELOX IV with an infusion solution compatible with AVELOX IV as well as with other drug(s) administered via this common line. AVELOX IV is compatible with the following intravenous solutions at ratios from 1:10 to 10:1
0.9% Sodium Chloride Injection, USP Sterile Water for Injection, USP 1M Sodium Chloride Injection 10% Dextrose for Injection, USP 5% Dextrose Injection, USP Lactated Ringer’s for Injection Preparation for Administration of AVELOX IV To prepare AVELOX IV injection premix in flexible containers:

1. Close flow control clamp of administration set.
2. Remove cover from port at bottom of container.
3. Insert piercing pin from an appropriate transfer set (for example, one that does not require excessive force, such as ISO compatible administration set) into port with a gentle twisting motion until pin is firmly seated.

NOTE: Refer to complete directions that have been provided with the administration set.

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Antacids, Sucralfate, Multivitamins and other products containing Multivalent Cations Quinolones form chelates with alkaline earth and transition metal cations. Oral administration of quinolones 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 VIDEX® (didanosine) chewable/buffered tablets or the pediatric powder for oral solution, may substantially interfere with the absorption of quinolones, resulting in systemic concentrations considerably lower than desired. Therefore, AVELOX should be taken at least 4 hours before or 8 hours after these agents. [see DOSAGE AND ADMINISTRATION, Pharmacokinetics, and PATIENT INFORMATION] Warfarin Quinolones, including AVELOX, 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 a quinolone is administered concomitantly with warfarin or its derivatives. [see ADVERSE REACTIONS, Pharmacokinetics, and PATIENT INFORMATION] Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Although not observed with AVELOX in preclinical and clinical trials, the concomitant administration of a nonsteroidal anti-inflammatory drug with a quinolone may increase the risks of CNS stimulation and convulsions [see WARNINGS AND PRECAUTIONS, and PATIENT INFORMATION]. Drugs that Prolong QT There is limited information available on the potential for a pharmacodynamic interaction in humans between AVELOX 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 (IV) AVELOX in dogs. Therefore, AVELOX should be avoided with Class IA and Class III antiarrhythmics. [see WARNINGS AND PRECAUTIONS, Nonclinical Toxicology, and PATIENT INFORMATION] Read the Avelox Drug Interactions Center for a complete guide to possible interactions Learn More »

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To reduce the development of drug-resistant bacteria and maintain the effectiveness of AVELOX® and other antibacterial drugs, AVELOX should be used only to treat or prevent infections that are proven or strongly suspected to be caused by 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. AVELOX® Tablets and IV are indicated for the treatment of adults (≥ 18 years of age) with infections caused by susceptible isolates of the designated microorganisms in the conditions listed below [see DOSAGE AND ADMINISTRATION and Use In Specific Populations]. Culture and Susceptibility Testing Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to moxifloxacin [see CLINICAL PHARMACOLOGY]. Therapy with AVELOX may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued. Acute Bacterial Sinusitis AVELOX is indicated for the treatment of Acute Bacterial Sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see Clinical Studies]. Acute Bacterial Exacerbation of Chronic Bronchitis AVELOX is indicated for the treatment of Acute Bacterial Exacerbation of Chronic Bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus, or Moraxella catarrhalis [see Clinical Studies]. Community Acquired Pneumonia AVELOX is indicated for the treatment of Community Acquired Pneumonia caused by Streptococcus pneumoniae (including multi-drug resistant isolates*), Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae. * MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates previously known as PRSP (Penicillinresistant S. pneumoniae), and are isolates resistant to two or more of the following antibiotics: penicillin (minimum inhibitory concentrations [MIC] ≥ 2 mcg/mL), 2nd generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole [see Clinical Studies]. Uncomplicated Skin and Skin Structure Infections AVELOX is indicated for the treatment of Uncomplicated Skin and Skin Structure Infections caused by methicillinsusceptible Staphylococcus aureus or Streptococcus pyogenes [see Clinical Studies]. Complicated Skin and Skin Structure Infections AVELOX is indicated for the treatment of Complicated Skin and Skin Structure Infections caused by methicillinsusceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae [see Clinical Studies]. Complicated Intra-Abdominal Infections AVELOX is indicated for the treatment of Complicated Intra-Abdominal Infections including polymicrobial infections such as abscess caused by Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron, or Peptostreptococcus species [see Clinical Studies ].

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AVELOX is contraindicated in persons with a history of hypersensitivity to moxifloxacin or any member of the quinolone class of antimicrobial agents. Last reviewed on RxList: 8/29/2013
This monograph has been modified to include the generic and brand name in many instances.

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Single oral overdoses up to 2.8 g were not associated with any serious adverse events. In the event of acute overdose, the stomach should be emptied and adequate hydration maintained. ECG monitoring is recommended due to the possibility of QT interval prolongation. The patient should be carefully observed and given 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. Single oral AVELOX doses of 2000, 500, and 1500 mg/kg were lethal to rats, mice, and cynomolgus monkeys, respectively. The minimum lethal intravenous dose in mice and rats was 100 mg/kg. Adverse clinical signs included CNS and gastrointestinal effects such as decreased activity, somnolence, tremor, convulsions, vomiting and diarrhea.

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Dosage Forms And Strengths AVELOX Tablets

• Containing moxifloxacin hydrochloride (equivalent to 400 mg moxifloxacin)
• Oblong, dull red film-coated tablets
• Imprinted with BAYER on one side and M400 on the other

AVELOX IV

• Containing 400 mg moxifloxacin in 0.8% saline (moxifloxacin hydrochloride in sodium chloride injection) with pH ranging from 4.1 to 4.6.
• Ready-to-use 250 mL latex-free flexibags. No further dilution is necessary  
• Sterile, preservative free, 0.8% sodium chloride aqueous solution of moxifloxacin hydrochloride

Storage And Handling AVELOX Tablets AVELOX (moxifloxacin) hydrochloride tablets are available as oblong, dull red film-coated tablets containing 400 mg moxifloxacin. The tablet is coded with the word “BAYER” on one side and “M400” on the reverse side. Package NDC Code Bottles of 30: 0085-1733-01 Unit Dose Pack of 50: 0085-1733-02 ABC Pack of 5: 0085-1733-03 Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Avoid high humidity AVELOX Intravenous Solution – Premix Bags AVELOX IV (moxifloxacin) hydrochloride in sodium chloride injection is available in ready-to-use 250 mL latex-free flexible bags containing 400 mg of moxifloxacin in 0.8% saline. NO FURTHER DILUTION OF THIS PREPARATION IS NECESSARY. Package NDC Code 250 mL flexible container 0085-1737-01 Parenteral drug products should be inspected visually for particulate matter prior to administration. Samples containing visible particulates should not be used. Because the premix flexible containers are for single-use only, any unused portion should be discarded. Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. DO NOT REFRIGERATE – PRODUCT PRECIPITATES UPON REFRIGERATION. Revised 07 2013. Manufactured for: Bayer HealthCare Pharmaceuticals Inc. Wayne, NJ 07470, AVELOX Tablets manufactured in Germany AVELOX IV manufactured in Germany or AVELOX IV manufactured in Norway by Fresenius Kabi Norge AS NO-1753 Halden, Norway. Distributed by: Merck Sharp & Dohme Corp., a subsidiary of Whitehouse Station, NJ 08889, USA AVELOX® is a registered trademark of Bayer Aktiengesellschaft and is used under license by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Last reviewed on RxList: 8/29/2013
This monograph has been modified to include the generic and brand name in many instances.

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Tendinopathy and Tendon Rupture Fluoroquinolones, including AVELOX, are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Factors, in addition to age and corticosteroid use, 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. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. AVELOX should be discontinued 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. [see ADVERSE REACTIONS and PATIENT INFORMATION] Exacerbation of Myasthenia Gravis Fluoroquinolones, including AVELOX, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid AVELOX in patients with known history of myasthenia gravis [see PATIENT INFORMATION]. QT Prolongation AVELOX has been shown to prolong the QT interval of the electrocardiogram in some patients. Following oral dosing with 400 mg of AVELOX 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). The drug should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia and patients receiving Class IA (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic agents, due to the lack of clinical experience with the drug in these patient populations. Pharmacokinetic studies between AVELOX and other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. An additive effect of AVELOX and these drugs cannot be excluded; therefore caution should be exercised when AVELOX is given concurrently with these drugs. In premarketing clinical trials, the rate of cardiovascular adverse events was similar in 798 AVELOX and 702 comparator treated patients who received concomitant therapy with drugs known to prolong the QTc interval. AVELOX should be used with caution in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia, acute myocardial ischemia. 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. QT prolongation may lead to an increased risk for ventricular arrhythmias including torsade de pointes. No excess in cardiovascular morbidity or mortality attributable to QTc prolongation occurred with AVELOX 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 AVELOX tablet treated patients in a postmarketing observational study in which ECGs were not performed. Elderly patients using IV AVELOX may be more susceptible to drug-associated QT prolongation. [see Use In Specific Populations] In addition, AVELOX should be used with caution in patients with mild, moderate, or severe liver cirrhosis. [see CLINICAL PHARMACOLOGY and PATIENT INFORMATION] Hypersensitivity Reactions Serious anaphylactic reactions, some following the first dose, have been reported in patients receiving quinolone therapy, including AVELOX . Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. AVELOX should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Oxygen, intravenous steroids, and airway management, including intubation, may be administered as indicated. [see ADVERSE REACTIONS and PATIENT INFORMATION] Other Serious and Sometimes Fatal Reactions Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including AVELOX. These events 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

The drug should be discontinued immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted [see PATIENT INFORMATION and ADVERSE REACTIONS. ] Central Nervous System Effects Fluoroquinolones, including AVELOX, may cause central nervous system (CNS) events, including: nervousness, agitation, insomnia, anxiety, nightmares or paranoia. [See ADVERSE REACTIONS] Convulsions and increased intracranial pressure (including pseudotumor cerebri) have been reported in patients receiving fluoroquinolones. Fluoroquinolones may also cause central nervous system (CNS) events including: dizziness, confusion, tremors, hallucinations, depression, and, rarely, suicidal thoughts or acts. These reactions may occur following the first dose. If these reactions occur in patients receiving AVELOX, the drug should be discontinued and appropriate measures instituted. As with all fluoroquinolones, AVELOX should be used 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. [see DRUG INTERACTIONS , ADVERSE REACTIONS and PATIENT INFORMATION.] Clostridium Difficile-Associated Diarrhea Clostridium Difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including AVELOX, 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 antibiotic 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 [see ADVERSE REACTIONS and PATIENT INFORMATION]. 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 AVELOX. Symptoms may occur soon after initiation of AVELOX and may be irreversible. AVELOX should be discontinued 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 [see ADVERSE REACTIONS and PATIENT INFORMATION]. Arthropathic Effects in Animals The oral administration of AVELOX caused lameness in immature dogs. 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 Animal Toxicology and/or Pharmacology.] 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 quinolone antibiotics after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if phototoxicity occurs. [see ADVERSE REACTIONS and Pharmacokinetics] Development of Drug Resistant Bacteria Prescribing AVELOX 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 [see PATIENT INFORMATION]. Patient Counseling Information See FDA-Approved Medication Guide Antibacterial Resistance Antibacterial drugs including AVELOX should only be used to treat bacterial infections. They do not treat viral infections (for example, the common cold). When AVELOX 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 AVELOX or other antibacterial drugs in the future. Administration With Food, Fluids, and Drug Products Containing Multivalent Cations Patients should be informed that AVELOX tablets may be taken with or without food. Patients should be advised to drink fluids liberally. AVELOX 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. Serious and Potentially Serious Adverse Reactions To assure safe and effective use of AVELOX, patients should be informed of the following serious adverse reactions that have been associated with AVELOX 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 AVELOX 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 AVELOX 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: AVELOX may produce changes in the electrocardiogram (QTc interval prolongation). AVELOX should be avoided in patients receiving Class IA (for example quinidine, procainamide) or Class III (for example amiodarone, sotalol) antiarrhythmic agents. AVELOX 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 AVELOX.
• Hypersensitivity Reactions: Patients should be advised that AVELOX may be associated with hypersensitivity reactions, including anaphylactic reactions, even following a single dose. Patients should discontinue AVELOX 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 AVELOX if there is a history of this condition. Patients should also inform their physician if they are taking NSAIDs concurrently with AVELOX.
• Neurologic Adverse Effects (for example, dizziness, lightheadedness): AVELOX 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 AVELOX.
• Peripheral Neuropathies: Patients should be informed that peripheral neuropathy has been associated with AVELOX 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 AVELOX 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.

Nonclinical Toxicology 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. Use In Specific Populations Pregnancy Pregnancy Category C Because no adequate or well-controlled studies have been conducted in pregnant women, AVELOX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Moxifloxacin was not teratogenic when administered to pregnant rats during organogenesis 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 (indicative of fetotoxicity) were observed. Intravenous administration of 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area (mg/m²) to pregnant rats resulted in maternal toxicity and a marginal effect on fetal and placental weights and the appearance of the placenta. There was no evidence of teratogenicity at intravenous doses as high as 80 mg/kg/day. 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 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. 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. There was no evidence of teratogenicity when pregnant cynomolgus monkeys were given oral doses as high as 100 mg/kg/day (2.5 times the maximum recommended human dose based upon systemic exposure). An increased incidence of smaller fetuses was observed at 100 mg/kg/day. In an oral pre-and postnatal development study conducted in rats, effects observed at 500 mg/kg/day 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. Nursing Mothers Moxifloxacin is excreted in the breast milk of rats. Moxifloxacin may also be excreted in human milk. Because of the potential for serious adverse reactions in infants who are nursing from mothers taking AVELOX, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness in pediatric patients and adolescents less than 18 years of age have not been established. AVELOX causes arthropathy in juvenile animals [see BOXED WARNING, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY]. Geriatric Use Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as AVELOX. 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 AVELOX to elderly patients especially those on corticosteroids. Patients should be informed of this potential side effect and advised to discontinue AVELOX and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur. [see BOXED WARNING, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS] In controlled multiple-dose clinical trials, 23% of patients receiving oral AVELOX 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 AVELOX in patients aged 65 or older compared to younger adults. In trials of intravenous use, 42% of AVELOX 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 AVELOX 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, AVELOX 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, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY] Renal Impairment 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) [see DOSAGE AND ADMINISTRATION, and CLINICAL PHARMACOLOGY] Hepatic Impairment 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, AVELOX should be used with caution in these patients [see WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY]. Last reviewed on RxList: 8/29/2013
This monograph has been modified to include the generic and brand name in many instances.

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