Moxifloxacin Injection

Make sure you drink plenty of water or other fluids every day during your treatment with moxifloxacin injection.

• If you have an allergy to moxifloxacin or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Long QTc on ECG or other heartbeat that is not normal, slow heartbeat, or low potassium or magnesium levels.
• If you have had a recent heart attack.
• If you have ever had any of these health problems: Nerve problems or tendon problems.
• If you have had tendons get irritated or torn when taking moxifloxacin injection or an alike drug in the past.
• If you have been taking any drugs to treat a heartbeat that is not normal.
• If you are taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take moxifloxacin injection with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Chest pain or pressure.
• Fever or chills.
• Ringing in ears.
• Shortness of breath.
• Any unexplained bruising or bleeding.
• Shakiness.
• Not able to pass urine or change in how much urine is passed.
• Not able to sleep.
• Trouble walking.
• Vaginal itching or discharge.
• White patches in mouth.
• Muscle pain or weakness.
• Very bad and sometimes deadly liver problems have happened with this medicine. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
• It is common to have diarrhea when taking moxifloxacin injection. Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking this medicine or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about moxifloxacin injection, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about moxifloxacin injection. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using moxifloxacin injection.

Review Date: October 4, 2017

Community Acquired Pneumonia

Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Community Acquired Pneumonia caused by susceptible isolates of 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 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 (14.2)] .

Uncomplicated Skin and Skin Structure Infections

Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Uncomplicated Skin and Skin Structure Infections caused by susceptible isolates of methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes [see  Clinical Studies (14.5)].

Complicated Skin and Skin Structure Infections

Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Complicated Skin and Skin Structure Infections caused by susceptible isolates of methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae [see  Clinical Studies (14.6)].

Complicated Intra-Abdominal Infections

Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Complicated Intra-Abdominal Infections including polymicrobial infections such as abscess caused by susceptible isolates of Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron, or Peptostreptococcus species [see  Clinical Studies (14.7)] .

Acute Bacterial Sinusitis

Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Acute Bacterial Sinusitis (ABS) caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see  Clinical Studies (14.4)] .

Because fluoroquinolones, including Moxifloxacin Injection, have been associated with serious adverse reactions [see  Warnings and Precautions (5.1 to 5.13)] and for some patients ABS is self-limiting, reserve Moxifloxacin Injection for treatment of ABS in patients who have no alternative treatment options.

Acute Bacterial Exacerbation of Chronic Bronchitis

Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB) caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus, or Moraxella catarrhalis [see  Clinical Studies (14.1)].

Because fluoroquinolones, including Moxifloxacin Injection, have been associated with serious adverse reactions [see  Warnings and Precautions (5.1 to 5.13)] and for some patients ABECB is self-limiting, reserve Moxifloxacin Injection for treatment of ABECB in patients who have no alternative treatment options.

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.

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 (12.4)] .  Therapy with moxifloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.

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:

• Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects [see  Warnings and Precautions (5.1)]

• Tendinitis and Tendon Rupture [see Warnings and Precautions (5.2)]

• Peripheral Neuropathy [see  Warnings and Precautions (5.3)]

• Central Nervous System Effects [see  Warnings and Precautions (5.4)]

• Exacerbation of Myasthenia Gravis [see  Warnings and Precautions (5.5)]

• QT Prolongation [see  Warnings and Precautions (5.6)]

• Hypersensitivity Reactions [see  Warnings and Precautions (5.7)]

• Other Serious and Sometimes Fatal Adverse Reactions [see  Warnings and Precautions (5.8)]

• Clostridium Difficile-Associated Diarrhea [see  Warnings and Precautions (5.9)]

• Blood Glucose Disturbances [see  Warnings and Precautions( 5.12)]

• Photosensitivity/Phototoxicity [see  Warnings and Precautions (5.13)]

• Development of Drug Resistant Bacteria [see  Warnings and Precautions (5.14)]

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 [seeIndications and Usage (1)].  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

a MedDRA Version 12.0

Table 3: Less Common (0.1 to < 1%) Adverse Reactions Reported in Active-Controlled

                                          Clinical Trials with Moxifloxacin (N=14,981)

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, pO 2, 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

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 [seeAdverse Reactions (6.2, 6.3) , Clinical Pharmacology (12.3), and Patient Counseling Information (17)].

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 (5.12),  Adverse Reactions (6.2), and  Patient Counseling Information (17)].

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 (5.4), and Patient Counseling Information (17)] .  

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 (5.6), Nonclinical Toxicology (13.2), and  Patient Counseling Information (17)].

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.  

Acute Bacterial Exacerbation of Chronic Bronchitis

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

Table 9: Clinical Success Rates at Follow-Up Visit for
Clinically Evaluable Patients by Pathogen (Acute Bacterial
                  Exacerbation of Chronic Bronchitis)

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

Community Acquired Pneumonia

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

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

An open-label ex-US study that enrolled 628 patients compared moxifloxacin to sequential IV/PO amoxicillin/clavulanate (1.2 g IV q8h/625 mg PO q8h) with or without high-dose IV/PO clarithromycin (500 mg BID).  The intravenous formulations of the comparators are not FDA approved.  The clinical success rate at Day 5 to 7 for moxifloxacin therapy was 93% (241/258) and demonstrated superiority to amoxicillin/clavulanate ± clarithromycin (85%, 239/280) [95% C.I. of difference in success rates between moxifloxacin and comparator (2.9%, 13.2%)].  The clinical success rate at the 21 to 28 days post-therapy visit for moxifloxacin was 84% (216/258), which also demonstrated superiority to the comparators (74%, 208/280) [95% C.I. of difference in success rates between moxifloxacin and comparator (2.6%, 16.3%)].

The clinical success rates by pathogen across four CAP studies are presented in Table 10. 

Table 10: Clinical Success Rates by 
    Pathogen (Pooled CAP Studies)

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

Moxifloxacin was effective in the treatment of community acquired pneumonia (CAP) caused by multi-drug resistant MDRSP* isolates.  Of 37 microbiologically evaluable patients with MDRSP isolates, 35 patients (95%) achieved clinical and bacteriological success post-therapy.  The clinical and bacteriological success rates based on the number of patients treated are shown in Table 11.

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

    Table 11: Clinical and Bacteriological Success Rates for Moxifloxacin-Treated

                    MDRSP CAP Patients (Population: Valid for Efficacy)

a n = number of patients successfully treated; N = number of patients with MDRSP (from a

  total of   37 patients)

b n = number of patients successfully treated (presumed eradication or eradication);

   N = number of patients with MDRSP (from a total of 37 patients)

c One patient had a respiratory isolate that was resistant to penicillin and cefuroxime but a

   blood isolate that was intermediate to penicillin and cefuroxime.  The patient is included in

   the database based on the respiratory isolate.

d Azithromycin, clarithromycin, and erythromycin were the macrolide antimicrobials tested.

Not all isolates were resistant to all antimicrobial classes tested.  Success and eradication rates are summarized in Table 12.

Table 12: Clinical Success Rates and Microbiological Eradication Rates for Resistant

            Streptococcus pneumoniae (Community Acquired Pneumonia)

a One patient had a respiratory isolate resistant to 5 antimicrobials and a blood isolate

  resistant to 3 antimicrobials.  The patient was included in the category resistant to 5

  antimicrobials.

Acute Bacterial Sinusitis

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

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

Uncomplicated Skin and Skin Structure Infections

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

Complicated Skin and Skin Structure Infections

Two randomized, active controlled trials of cSSSI were performed.  A double-blind trial was conducted primarily in North America to compare the efficacy of sequential IV/PO moxifloxacin 400 mg QD for 7 to 14 days to an IV/PO beta-lactam/beta-lactamase inhibitor control in the treatment of patients with cSSSI.  This study enrolled 617 patients, 335 of which were valid for the efficacy analysis.  A second open-label International study compared moxifloxacin 400 mg QD for 7 to 21 days to sequential IV/PO beta-lactam/beta-lactamase inhibitor control in the treatment of patients with cSSSI.  This study enrolled 804 patients, 632 of which were valid for the efficacy analysis.  Surgical incision and drainage or debridement was performed on 55% of the moxifloxacin-treated and 53% of the comparator treated patients in these studies and formed an integral part of therapy for this indication.  Success rates varied with the type of diagnosis ranging from 61% in patients with infected ulcers to 90% in patients with complicated erysipelas.  These rates were similar to those seen with comparator drugs.  The overall success rates in the evaluable patients and the clinical success by pathogen are shown in Tables 13 and 14.

Table 13: Overall Clinical Success Rates in Patients with Complicated

                                Skin and Skin Structure Infections

* of difference in success rates between moxifloxacin and comparator (moxifloxacin - comparator)

Table 14: Clinical Success Rates by Pathogen in Patients with Complicated

                           Skin and Skin Structure Infections

a  methicillin susceptibility was only determined in the North American Study  

Complicated Intra-Abdominal Infections

Two randomized, active controlled trials of cIAI were performed.  A double-blind trial was conducted primarily in North America to compare the efficacy of sequential IV/PO moxifloxacin 400 mg QD for 5 to 14 days to IV/piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of patients with cIAI, including peritonitis, abscesses, appendicitis with perforation, and bowel perforation.  This study enrolled 681 patients, 379 of which were considered clinically evaluable.  A second open-label international study compared moxifloxacin 400 mg QD for 5 to 14 days to IV ceftriaxone plus IV metronidazole followed by PO amoxicillin/clavulanic acid in the treatment of patients with cIAI.  This study enrolled 595 patients, 511 of which were considered clinically evaluable.  The clinically evaluable population consisted of subjects with a surgically confirmed complicated infection, at least 5 days of treatment and a 25 to 50 day follow-up assessment for patients at the Test of Cure visit.  The overall clinical success rates in the clinically evaluable patients are shown in Table 15.

Table 15: Clinical Success Rates in Patients with Complicated Intra-Abdominal Infections

a of difference in success rates between moxifloxacin and comparator (moxifloxacin –

  comparator)

b Excludes 2 patients who required additional surgery within the first 48 hours.

c NA – not applicable