Moxifloxacin Injection: Indications, Dosage, Precautions, Adverse Effects
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Moxifloxacin Injection - Product Information

Manufacture: Fresenius Kabi USA, LLC
Country: United States
Condition: Bacterial Infection, Bronchitis, Cutaneous Bacillus anthracis, Intraabdominal Infection, Plague, Plague Prophylaxis, Pneumonia, Sinusitis, Skin and Structure Infection, Skin or Soft Tissue Infection, Tuberculosis, Active
Class: Quinolones
Form: Intravenous (IV)
Ingredients: Moxifloxacin, sodium acetate-trihydrate, disodium sulfate, sulfuric acid, water for injection

Indications and Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of moxifloxacin injection and other antibacterial drugs, moxifloxacin injection 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.

Moxifloxacin injection is indicated for the treatment of adults (18 years of age or older) 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 moxifloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.

Acute Bacterial Sinusitis

Moxifloxacin 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

Moxifloxacin 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

Moxifloxacin 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 (Penicillin-resistant 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

Moxifloxacin 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

Moxifloxacin 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

Moxifloxacin 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 moxifloxacin injection is 400 mg intravenously once every 24 hours. The duration of therapy depends on the type of infection as described in Table 1.

Table 1: Dos age and Duration of Therapy in Adult Patients
Type of InfectionaDose Every 24
hours
Durationb
(days)
Acute Bacterial Sinusitis400 mg10
Acute Bacterial Exacerbation of Chronic Bronchitis400 mg5
Community Acquired Pneumonia400 mg7 to 14
Uncomplicated Skin and Skin Structure Infections (SSSI)400 mg7
Complicated SSSI400 mg7 to 21
Complicated Intra-Abdominal Infections400 mg5 to 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.

When switching from intravenous to oral formulation, no dosage adjustment is necessary [see Clinical Pharmacology]. Patients whose therapy is started with moxifloxacin injection may be switched to moxifloxacin tablets when clinically indicated at the discretion of the physician.

Administration Instructions

Moxifloxacin Injection Solution for Infusion

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Moxifloxacin injection should be administered by intravenous infusion only. It is not intended for intra- arterial, intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.

Moxifloxacin injection 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 moxifloxacin intravenous injection with other intravenous substances, additives or other medications should not be added to moxifloxacin injection 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 moxifloxacin injection with an infusion solution compatible with moxifloxacin injection as well as with other drug(s) administered via this common line.

Moxifloxacin Injection 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

1 molar Sodium Chloride Injection                 10% Dextrose for Injection, USP

5% Dextrose Injection, USP                          Lactated Ringer’s for Injection

Preparation for Administration of Moxifloxacin Injection

To prepare moxifloxacin injection premix in flexible plastic containers:

  1. Close flow control clamp of administration
  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

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

Dosage Forms and Strengths

Moxifloxacin Injection

Each bag contains 400 mg of moxifloxacin in 250 mL, each mL contains 1.6 mg of moxifloxacin.

Contraindications

Moxifloxacin is contraindicated in persons with a history of hypersensitivity to moxifloxacin or any member of the quinolone class of antimicrobial agents.

Warnings and Precautions

WARNING: TENDON EFFECTS and MYASTHENIA GRAVIS

Fluoroquinolones, including moxifloxacin, 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 cortico steroid drugs, and in patients with kidney, heart or lung transplants. Disco ntinue if pain or inflammation in a tendon occurs.

Fluoroquinolones, including moxifloxacin, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid moxifloxacin in patients with known history of myasthenia gravis.

Tendinopathy and Tendon Rupture

Fluoroquinolones, including moxifloxacin, 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. Moxifloxacin 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 Counseling Information].

Exacerbation of Myasthenia Gravis

Fluoroquinolones, including moxifloxacin, 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 moxifloxacin in patients with known history of myasthenia gravis [see Patient Counseling Information].

QT Prolongation

Moxifloxacin has been shown to prolong the QT interval of the electrocardiogram in some patients.

Following oral dosing with 400 mg of moxifloxacin the mean (± SD) change in QTc from the pre-dose value at the time of maximum drug concentration was 6 msec (± 26) (n = 787). Following a course of daily intravenous dosing (400 mg; 1 hour infusion each day) the mean change in QTc from the Day 1 pre-dose value was 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 moxifloxacin and other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. An additive effect of moxifloxacin and these drugs cannot be excluded; therefore caution should be exercised when moxifloxacin is given concurrently with these drugs. In premarketing clinical trials, the rate of cardiovascular adverse events was similar in 798 moxifloxacin and 702 comparator treated patients who received concomitant therapy with drugs known to prolong the QTc interval.

Moxifloxacin 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 torsades de pointes. No excess in cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin 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. Elderly patients using moxifloxacin injection may be more susceptible to drug-associated QT prolongation [see Use in Specific Populations]. In addition, moxifloxacin should be used with caution in patients with mild, moderate, or severe liver cirrhosis [see Clinical Pharmacology and Patient Counseling Information].

Hypersensitivity Reactions

Serious anaphylactic reactions, some following the first dose, have been reported in patients receiving quinolone therapy, including moxifloxacin. 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. Moxifloxacin 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 Counseling 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 moxifloxacin. 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 Counseling Information and Adverse Reactions].

Central Nervous System Effects

Fluoroquinolones, including moxifloxacin, 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 moxifloxacin, the drug should be discontinued and appropriate measures instituted. As with all fluoroquinolones, moxifloxacin 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 Counseling Information].

Clostridium Difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including moxifloxacin, 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 Counseling 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 moxifloxacin. Symptoms may occur soon after initiation of moxifloxacin and may be irreversible. Moxifloxacin 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 Counseling Information].

High Sodium Load

Each unit dose of moxifloxacin injection contains 52.5 mEq (1,207 mg) of sodium. Avoid use of moxifloxacin injection in patients with congestive heart failure, elderly, and those with restricted sodium intake [see Use in Specific Populations, Description].

Arthropathic Effects in Animals

The oral administration of moxifloxacin 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 Nonclinical Toxicology].

Blood Glucose Disturbances

As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with moxifloxacin. In moxifloxacin-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (for example, sulfonylurea) or with insulin. In diabetic patients, careful monitoring of blood glucose is recommended [see Adverse Reactions] . If a hypoglycemic reaction occurs, moxifloxacin should be discontinued and appropriate therapy should be initiated immediately [see Adverse Reactions and Patient Counseling Information].

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 Clinical Pharmacology].

Development of Drug Resistant Bacteria

Prescribing moxifloxacin 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 Counseling Information].

Adverse Reactions

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]
  • Blood Glucose Disturbances [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 moxifloxacin in 14,981 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 moxifloxacin 400 mg once daily PO, IV, or sequentially (IV followed by PO). Treatment duration was usually 6 to 10 days, and the mean number of days on therapy was 9 days.

Discontinuation of moxifloxacin due to adverse events occurred in 5% 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%) and pyrexia (0.4%).

Adverse reactions occurring in ≥ 1% of moxifloxacin-treated patients and less common adverse reactions, occurring in 0.1 to < 1% of moxifloxacin-treated patients, are shown in Table 2 and Table 3, respectively. The most common adverse drug reactions (≥ 3%) are nausea, diarrhea, headache, and dizziness.

Table 2: Common (≥ 1%) Adverse Reactions Reported in Active-Controlled Clinical Trials with Moxifloxacin
System Organ ClassAdverse Reactionsa%
(N=14,981)
Blood and Lymphatic  System DisordersAnemia1.1
Gastrointestinal DisordersNausea6.9
Diarrhea6
Vomiting2.4
Constipation1.9
Abdominal pain1.5
Abdominal  pain upper1.1
Dyspepsia1
General Disorders and Administration Site ConditionsPyrexia1.1
InvestigationsAlanine aminotransferase increased1.1
Metabolism  and Nutritional DisorderHypokalemia1
Nervous  System DisordersHeadache Dizziness4.23
Psychiatric DisordersInsomnia1.9

a MedDRA Version 12.0

Table 3: Les s Common (0.1 to < 1%) Advers e Reactions Reported in Active-Controlled Clinical Trials with Moxifloxacin (N=14,981)
System Organ ClassAdverse Reactionsa
Blood and Lymphatic System DisordersThrombocythemia
Eosinophilia
Neutropenia
Thrombocytopenia
Leukopenia
Leukocytosis
Cardiac DisordersAtrial fibrillation
Palpitations
Tachycardia
Cardiac failure congestive
Angina pectoris
Cardiac failure
Cardiac arrest
Bradycardia
Ear and Labyrinth DisordersVertigo
Tinnitus
Eye DisordersVision blurred
Gastrointestinal DisordersDry mouth
Abdominal discomfort
Flatulence
Abdominal distention
Gastritis
Gastroesophageal reflux disease
General Disorders and Administration Site ConditionsFatigue
Chest pain
Asthenia
Edema peripheral
Pain
Malaise
Infusion site extravasation
Edema
Chills
Chest discomfort
Facial pain
Hepatobiliary DisordersHepatic function abnormal
Infections and InfestationsVulvovaginal candidiasis
Oral candidiasis
Vulvovaginal mycotic infection
Candidiasis
Vaginal infection
Oral fungal infection
Fungal infection
Gastroenteritis
InvestigationsAspartate 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 DisordersHyperglycemia
Anorexia
Hypoglycemia
Hyperlipidemia
Decreased appetite
Dehydration
Musculoskeletal and Connective Tissue DisordersBack pain
Pain in extremity
Arthralgia
Myalgia
Muscle spasms
Musculoskeletal chest pain
Musculoskeletal pain
Nervous System DisordersDysgeusia
Somnolence
Tremor
Lethargy
Paresthesia
Tension headache
Hypoesthesia
Syncope
Psychiatric DisordersAnxiety
Confusional state
Agitation
Depression
Nervousness
Restlessness
Hallucination
Disorientation
Renal and Urinary DisordersRenal failure
Dysuria
Renal failure acute
Reproductive System and Breast DisordersVulvovaginal pruritus
Respiratory, Thoracic, and Mediastinal DisordersDyspnea
Asthma
Wheezing
Bronchospasm
Skin and Subcutaneous Tissue DisordersRash
Pruritus
Hyperhidrosis
Erythema
Urticaria
Dermatitis allergic
Night sweats
Vascular DisordersHypertension
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 moxifloxacin. Because these reactions 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 ClassAdverse Reaction
Blood and Lymphatic System DisordersAgranulocytosis
Pancytopenia
[see Warnings and Precautions]
Cardiac DisordersVentricular tachyarrhythmias (including in very rare cases cardiac arrest and torsades de pointes, and usually in patients with concurrent severe underlying proarrhythmic conditions)
Ear and Labyrinth DisordersHearing impairment, including deafness (reversible in majority of cases)
Eye DisordersVision loss (especially in the course of CNS reactions, transient in majority of cases)
Hepatobiliary DisordersHepatitis (predominantly cholestatic)
Hepatic failure (including fatal cases)
Jaundice
Acute hepatic necrosis
[see Warnings and Precautions]
Immune System DisordersAnaphylactic reaction
Anaphylactic shock
Angioedema (including laryngeal edema)
[see Warnings and Precautions]
Musculoskeletal and Connective Tissue DisordersTendon rupture
[see Warnings and Precautions]
Nervous System DisordersAltered 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]
PsychiatricDisordersPsychotic reaction (very rarely culminating in self-injurious behavior, such as suicidal ideation/thoughts or suicide attempts [see Warnings and Precautions]
Renal and Urinary DisordersRenal dysfunction
Interstitial nephritis
[see Warnings and Precautions]
Respiratory, Thoracic and Mediastinal DisordersAllergic pneumonitis
[see Warnings and Precautions]
Skin and Subcutaneous Tissue DisordersPhotosensitivity/phototoxicity reaction
[see Warnings and Precautions]
Stevens-Johnson syndrome
Toxic epidermal necrolysis
[see Warnings and Precautions]

Drug Interactions

Warfarin

Quinolones, including moxifloxacin, 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 Counseling Information].

Antidiabetic Agents

Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered. If a hypoglycemic reaction occurs, moxifloxacin should be discontinued and appropriate therapy should be initiated immediately [see Warnings and Precautions, Adverse Reactions, and Patient Counseling Information].

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Although not observed with moxifloxacin 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 Counseling Information].

Drugs that Prolong QT

There is limited information available on the potential for a pharmacodynamic interaction in humans between moxifloxacin and other drugs that prolong the QTc interval of the electrocardiogram. Sotalol, a Class III antiarrhythmic, has been shown to further increase the QTc interval when combined with high doses of intravenous (IV) moxifloxacin in dogs. Therefore, moxifloxacin should be avoided with Class IA and Class III antiarrhythmics [see Warnings and Precautions, Nonclinical Toxicology, and Patient Counseling Information].

Use in Specific Populations

Pregnancy

Pregnancy Category C. Because no adequate or well-controlled studies have been conducted in pregnant women, moxifloxacin 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) 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 moxifloxacin, 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. Moxifloxacin causes arthropathy in juvenile animals [see 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 moxifloxacin. 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 to elderly patients especially those on corticosteroids. Patients should be informed of this potential side effect and advised to discontinue moxifloxacin and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [see Warnings and Precautions, and Adverse Reactions].

Moxifloxacin injection contains 1,207 mg (52.5 mEq) of sodium per unit dose. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure [see Warnings and Precautions].

In controlled multiple-dose clinical trials, 23% of patients receiving oral moxifloxacin 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 in patients aged 65 or older compared to younger adults.

In trials of intravenous use, 42% of moxifloxacin 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 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 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 torsades 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, moxifloxacin should be used with caution in these patients [see Warnings and Precautions, and Clinical Pharmacology].

Overdosage

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.

How Supplied/Storage and Handling

How Supplied

Moxifloxacin Injection 400 mg/250 mL is a sterile solution available in a single-use, ready-to-use flexible plastic container.

No further dilution is necessary.

Product
No.
NDC
No.
StrengthBag Size

850174

63323-850-74

400 mg per 250 mL
(1.6 mg  per mL)

300 mL

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 plastic containers are for single-use only, any unused portion should be discarded.

Storage and Handling

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

Do not refrigerate - Product precipitates upon refrigeration.

Use immediately once removed from the overwrap. Product is sensitive to light.

The container closure is not made with natural rubber latex, polyvinyl chloride (Non-PVC), or di-(2- ethylhexyl)phthalate (Non-DEHP).

Patient Counseling Information

See FDA-Approved Consumer Medicine Information.

Antibacterial Resistance

Antibacterial drugs including moxifloxacin should only be used to treat bacterial infections. They do not treat viral infections (for example, the common cold). When moxifloxacin 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 or other antibacterial drugs in the future.

Serious and Potentially Serious Adverse Reactions

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

  • Tendon Disorders: Patients should contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue moxifloxacin treatment. The risk of severe tendon disorder with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.
  • Exacerbation of Myasthenia Gravis: Fluoroquinolones like moxifloxacin may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Patients should call their healthcare provider right away if they have any worsening muscle weakness or breathing problems.
  • Prolongation of the QT interval: Moxifloxacin may produce changes in the electrocardiogram (QTc interval prolongation). Moxifloxacin should be avoided in patients receiving Class IA (for example quinidine, procainamide) or Class III (for example amiodarone, sotalol) antiarrhythmic agents. Moxifloxacin may add to the QTc prolonging effects of other drugs such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants. The patients should inform their physician of any personal or family history of QTc prolongation or proarrhythmic conditions such as recent hypokalemia, significant bradycardia, and acute myocardial ischemia. Patients should contact their physician if they experience palpitations or fainting spells while taking moxifloxacin.
  • Hypersensitivity Reactions: Patients should be advised that moxifloxacin may be associated with hypersensitivity reactions, including anaphylactic reactions, even following a single dose. Patients should discontinue moxifloxacin at the first sign of a skin rash or other signs of an allergic reaction.
  • Convulsions: Convulsions have been reported in patients receiving quinolones, and they should notify their physician before taking moxifloxacin if there is a history of this condition. Patients should also inform their physician if they are taking NSAIDs concurrently with moxifloxacin.
  • Neurologic Adverse Effects (for example, dizziness, lightheadedness): Moxifloxacin may cause dizziness, lightheadedness and vision disorders therefore, patients should know how they react to this drug before they operate an automobile or machinery or engage in activities requiring mental alertness or coordination.
  • Psychotic Reaction: Psychotic reactions sometimes resulting in self-injurious behavior have been reported in patients receiving quinolones. Patients should notify their physician if they have a history of psychiatric illness before taking moxifloxacin.
  • Peripheral Neuropathies: Patients should be informed that peripheral neuropathy has been associated with moxifloxacin use. Symptoms may occur soon after initiation of therapy and may be irreversible. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness develop, patients should immediately discontinue moxifloxacin and contact their physician.
  • 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 and consult a 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.

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