AVELOX
(moxifloxacin hydrochloride)
WARNING
Fluoroquinolones, including AVELOX®, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk 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 [see WARNINGS AND PRECAUTIONS].
Fluoroquinolones, including AVELOX, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid AVELOX in patients with known history of myasthenia gravis [see WARNINGS AND PRECAUTIONS].
DRUG DESCRIPTION
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.
INDICATIONS
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 strains 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 strains*), 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 strains 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 methicillin-susceptible 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 methicillin-susceptible 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].
DOSAGE AND ADMINISTRATION
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 400 mg 10
Acute Bacterial Exacerbation of Chronic Bronchitis 400 mg 5
Community Acquired Pneumonia 400 mg 7-14
Uncomplicated Skin and Skin Structure Infections (SSSI ) 400 mg 7
Complicated SSSI 400 mg 7-21
Complicated Intra-Abdominal Infections 400 mg 5-14
a Due 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 Tablets
AVELOX Tablets can be taken with or without food, drink fluids liberally.
AVELOX IV
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
1. To prepare AVELOX IV injection premix in flexible containers:
2. Close flow control clamp of administration set.
3. Remove cover from port at bottom of container.
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.
HOW SUPPLIED
Dosage Forms And Strengths
AVELOX Tablets
1. Containing moxifloxacin hydrochloride (equivalent to 400 mg moxifloxacin)
2. Oblong, dull red film-coated tablets
3. 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.
SIDE EFFECTS
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 [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
aMedDRA 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
System Organ Class Adverse Reactionsa
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
System Organ Class Adverse Reactionsa
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
aMedDRA 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)
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]
Psychiatric Disorders Psychotic reaction (very rarely culminating ins elf-endangering behavior)
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]
DRUG INTERACTIONS
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.]
WARNINGS
Included as part of the PRECAUTIONS section.
tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to moxifloxa