RECENT MAJOR CHANGES SECTION

RECENT MAJOR CHANGES

Dosage and Administration (2.2) 5/2020

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DOSAGE FORMS & STRENGTHS SECTION

Highlight: •

Tablets: 400 mg moxifloxacin (3.1)

3 DOSAGE FORMS AND STRENGTHS

3.1 Moxifloxacin Tablets, USP

•

Modified capsule shaped, dull red, film-coated tablets debossed with E-18 on one side and plain on the other side containing 400 mg moxifloxacin.

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CONTRAINDICATIONS SECTION

Highlight: Known hypersensitivity to moxifloxacin tablets or other quinolones (4, 5.8)

4 CONTRAINDICATIONS

Moxifloxacin tablets are contraindicated in persons with a history of hypersensitivity to moxifloxacin or any member of the quinolone class of antibacterials [see Warnings and Precautions (5.8)].

Boxed Warning section

Highlight: Most common reactions (3% or greater) were nausea, diarrhea, headache, and dizziness. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE,

PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS AND EXACERBATION OF MYASTHENIA GRAVIS

WARNINGS AND PRECAUTIONS SECTION

Highlight: •

Prolongation of the QT interval and isolated cases of torsade de pointes has been reported. Avoid use in patients with known prolongation, proarrhythmic conditions such as clinically significant bradycardia or acute myocardial ischemia, hypokalemia, hypomagnesemia, and with drugs that prolong the QT interval. (5.6, 7.5, 8.5) 

•

Hypersensitivity and other serious reactions: Serious and sometimes fatal reactions, including anaphylactic reactions, may occur after first or subsequent doses of moxifloxacin hydrochloride. Discontinue moxifloxacin hydrochloride at first sign of skin rash, jaundice or any other sign of hypersensitivity. (5.7, 5.8) 

•

 Clostridioides difficile-Associated Diarrhea: Evaluate if diarrhea occurs. (5.10)

5 WARNINGS AND PRECAUTIONS

5.1 Disabling and Potentially Irreversible Serious Adverse Reactions

Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting moxifloxacin hydrochloride. Patients of any age or without pre-existing risk factors have experienced these adverse reactions [see Warnings and Precautions (5.2, 5.3, 5.4)].

Discontinue moxifloxacin hydrochloride immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including moxifloxacin hydrochloride, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.

5.2 Tendinitis and Tendon Rupture

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of tendinitis and tendon rupture in all ages [see Warnings and Precautions (5.1) and Adverse Reactions (6.2)]. This adverse reaction most frequently involves the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur within hours or days of starting moxifloxacin or as long as several months after completion of therapy. Tendinitis and tendon rupture can occur bilaterally.

The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Discontinue moxifloxacin hydrochloride immediately if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non- quinolone antimicrobial drug. Avoid fluoroquinolones, including moxifloxacin hydrochloride, in patients who have a history of tendon disorders or who have experienced tendinitis or tendon rupture [see Adverse Reactions (6.2)].

5.3 Peripheral Neuropathy

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of peripheral neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones including moxifloxacin hydrochloride. Symptoms may occur soon after initiation of moxifloxacin hydrochloride and may be irreversible in some patients [see Warnings and Precautions (5.1) and Adverse Reactions (6.1, 6.2)].

Discontinue moxifloxacin hydrochloride immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation. Avoid fluoroquinolones, including moxifloxacin hydrochloride, in patients who have previously experienced peripheral neuropathy.

5.4 Central Nervous System Effects

Psychiatric Adverse Reactions

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of psychiatric adverse reactions, including: toxic psychosis, hallucinations, or paranoia; depression or suicidal thoughts or acts; anxiety, agitation, or nervousness; confusion, delirium, disorientation, or disturbances in attention; insomnia or nightmares; memory impairment. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin hydrochloride, discontinue moxifloxacin hydrochloride immediately and institute appropriate measures [see Adverse Reactions (6.1, 6.2)].

Central Nervous System Adverse Reactions

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremors. As with all fluoroquinolones, use moxifloxacin hydrochloride with caution in patients with known or suspected CNS disorders (for example, severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin hydrochloride, discontinue moxifloxacin hydrochloride immediately and institute appropriate measures [see Drug Interactions (7.4) Adverse Reactions (6.1, 6.2), and Patient Counseling Information (17)].

5.5 Exacerbation of Myasthenia Gravis

Fluoroquinolones, including moxifloxacin hydrochloride, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Avoid moxifloxacin hydrochloride in patients with known history of myasthenia gravis.

5.6 QT Prolongation

Moxifloxacin hydrochloride has been shown to prolong the QT interval of the electrocardiogram in some patients. Following oral dosing with 400 mg of moxifloxacin hydrochloride the mean (± SD) change in QTc from the pre-dose value at the time of maximum drug concentration was 6 msec (± 26) (n = 787). Following a course of daily intravenous dosing (400 mg; 1 hour infusion each day) the mean change in QTc from the Day 1 pre-dose value was 10 msec (±22) on Day 1 (n=667) and 7 msec (± 24) on Day 3 (n = 667).

Avoid moxifloxacin hydrochloride in patients with the following risk factors due to the lack of clinical experience with the drug in these patient populations:

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Known prolongation of the QT interval 

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Ventricular arrhythmias including torsade de pointes because QT prolongation may lead to an increased risk for these conditions 

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Ongoing proarrhythmic conditions, such as clinically significant bradycardia and acute myocardial ischemia, 

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Uncorrected hypokalemia or hypomagnesemia 

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Class IA (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic agents 

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Other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants

Elderly patients using intravenous moxifloxacin hydrochloride may be more susceptible to drug-associated QT prolongation [see Use In Specific Populations (8.5)].

In patients with mild, moderate, or severe liver cirrhosis, metabolic disturbances associated with hepatic insufficiency may lead to QT prolongation. Monitor ECG in patients with liver cirrhosis treated with moxifloxacin hydrochloride [see Clinical Pharmacology (12.3)].

The magnitude of QT prolongation may increase with increasing concentrations of the drug or increasing rates of infusion of the intravenous formulation. Therefore, the recommended dose or infusion rate should not be exceeded.

In premarketing clinical trials, the rate of cardiovascular adverse reactions was similar in 798 moxifloxacin hydrochloride and 702 comparator treated patients who received concomitant therapy with drugs known to prolong the QTc interval. No excess in cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin hydrochloride treatment in over 15,500 patients in controlled clinical studies, including 759 patients who were hypokalemic at the start of treatment, and there was no increase in mortality in over 18,000 moxifloxacin tablet treated patients in a postmarketing observational study in which ECGs were not performed.

5.7 Other Serious and Sometimes Fatal Adverse Reactions

Other serious and sometimes fatal adverse reactions, some due to hypersensitivity, and some due to uncertain etiology, have been reported in patients receiving therapy with fluoroquinolones, including moxifloxacin hydrochloride. These reactions may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:

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Fever, rash, or severe dermatologic reactions (for example, toxic epidermal necrolysis, Stevens-Johnson syndrome) 

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Vasculitis; arthralgia; myalgia; serum sickness 

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Allergic pneumonitis 

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Interstitial nephritis; acute renal insufficiency or failure 

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Hepatitis; jaundice; acute hepatic necrosis or failure 

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Anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities

Discontinue moxifloxacin hydrochloride immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and institute supportive measures.

5.8 Hypersensitivity Reactions

Serious anaphylactic reactions, some following the first dose, have been reported in patients receiving fluoroquinolone therapy, including moxifloxacin hydrochloride. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Discontinue moxifloxacin hydrochloride at the first appearance of a skin rash or any other sign of hypersensitivity [see Warnings and Precautions (5.7)].

5.9 Risk of Aortic Aneurysm and Dissection

Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients. The cause for the increased risk has not been identified. In patients with a known aortic aneurysm or patients who are at greater risk for aortic aneurysms, reserve moxifloxacin hydrochloride for use only when there are no alternative antibacterial treatments available.

5.10 Clostridioides difficile-Associated Diarrhea

Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including moxifloxacin hydrochloride, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

5.11 Arthropathic Effects in Animals

In immature dogs, oral administration of moxifloxacin hydrochloride caused lameness. Histopathological examination of the weight-bearing joints of these dogs revealed permanent lesions of the cartilage. Related quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature animals of various species [see Nonclinical Toxicology (13.2)].

5.12 Blood Glucose Disturbances

As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with moxifloxacin hydrochloride. In moxifloxacin hydrochloride-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (for example, sulfonylurea) or with insulin. Severe cases of hypoglycemia resulting in coma or death have been reported. In diabetic patients, careful monitoring of blood glucose is recommended. If a hypoglycemic reaction occurs, discontinue moxifloxacin hydrochloride and initiate appropriate therapy immediately [see Adverse Reactions (6.1), Drug Interactions (7.3)] and Patient Counseling Information (17).

5.13 Photosensitivity/Phototoxicity

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (for example, burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of fluoroquinolones, including moxifloxacin hydrochloride, after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Moxifloxacin hydrochloride should be discontinued if phototoxicity occurs [see Clinical Pharmacology (12.2)].

5.14 Development of Drug Resistant Bacteria

Prescribing moxifloxacin hydrochloride in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

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DRUG INTERACTIONS SECTION

Highlight:

Interacting Drug	Interaction
Multivalent cation-containing products including: antacids, sucralfate, multivitamins	Decreased moxifloxacin hydrochloride absorption. Take moxifloxacin tablet at least 4 hours before or 8 hours after these products. (2.2, 7.1, 12.3)
Warfarin	Anticoagulant effect enhanced. Monitor prothrombin time/INR, and bleeding. (6, 7.2, 12.3)
Class IA and Class III antiarrhythmics:	Proarrhythmic effect may be enhanced. Avoid concomitant use. (5.6, 7.5)
Antidiabetic agents	Carefully monitor blood glucose. (5.12, 7.3)

7 DRUG INTERACTIONS

7.1 Antacids, Sucralfate, Multivitamins and Other Products Containing

Multivalent Cations

Fluoroquinolones, including moxifloxacin hydrochloride, form chelates with alkaline earth and transition metal cations. Oral administration of moxifloxacin hydrochloride with antacids containing aluminum or magnesium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as didanosine buffered tablets for oral suspension or the pediatric powder for oral solution, may substantially interfere with the absorption of moxifloxacin hydrochloride, resulting in systemic concentrations considerably lower than desired. Therefore, moxifloxacin hydrochloride should be taken at least 4 hours before or 8 hours after these agents [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

7.2 Warfarin

Fluoroquinolones, including moxifloxacin hydrochloride, have been reported to enhance the anticoagulant effects of warfarin or its derivatives in the patient population. In addition, infectious disease and its accompanying inflammatory process, age, and general status of the patient are risk factors for increased anticoagulant activity. Therefore the prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if moxifloxacin hydrochloride is administered concomitantly with warfarin or its derivatives [see Adverse Reactions (6.2) and Clinical Pharmacology (12.3)].

7.3 Antidiabetic Agents

Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones, including moxifloxacin hydrochloride, and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co- administered. If a hypoglycemic reaction occurs, moxifloxacin hydrochloride should be discontinued and appropriate therapy should be initiated immediately [see Warnings and Precautions (5.12) and Adverse Reactions (6.1)].

7.4 Nonsteroidal Anti-Inflammatory Drugs

The concomitant administration of a nonsteroidal anti-inflammatory drug (NSAID) with a fluoroquinolone, including moxifloxacin hydrochloride, may increase the risks of CNS stimulation and convulsions [see Warnings and Precautions (5.4)].

7.5 Drugs that Prolong QT

There is limited information available on the potential for a pharmacodynamic interaction in humans between moxifloxacin hydrochloride and other drugs that prolong the QTc interval of the electrocardiogram. Sotalol, a Class III antiarrhythmic, has been shown to further increase the QTc interval when combined with high doses of intravenous moxifloxacin hydrochloride in dogs. Therefore, moxifloxacin hydrochloride should be avoided with Class IA and Class III antiarrhythmics [see Warnings and Precautions (5.6), and Nonclinical Toxicology (13.2)].

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ADVERSE REACTIONS SECTION

Highlight: Most common reactions (3% or greater) were nausea, diarrhea, headache, and dizziness. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6 ADVERSE REACTIONS

The following serious and otherwise important adverse reactions are discussed in greater detail in the warnings and precautions section of the label:

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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)] 

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

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Peripheral Neuropathy [see Warnings and Precautions (5.3)]

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

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

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QT Prolongation [see Warnings and Precautions (5.6)] 

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Other Serious and Sometimes Fatal Adverse Reactions [see Warnings and Precautions (5.7)] 

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Risk of Aortic Aneurysm and Dissection [see Warnings and Precautions (5.9)]

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Hypersensitivity Reactions [see Warnings and Precautions (5.8)] 

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 Clostridioides difficile-Associated Diarrhea [see Warnings and Precautions (5.10)] 

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

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

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

6.1 Clinical Trials 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 hydrochloride in 14981 patients in 71 active controlled Phase II to IV clinical trials in different indications [see Indications and Usage (1)]. The population studied had a mean age of 50 years (approximately 73% of the population was less than 65 years of age), 50% were male, 63% were Caucasian, 12% were Asian and 9% were Black. Patients received moxifloxacin 400 mg once daily oral, intravenous, or sequentially (intravenous followed by oral). 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 reactions occurred in 5% of patients overall, 4% of patients treated with 400 mg PO, 4% with 400 mg intravenous and 8% with sequential therapy 400 mg oral/intravenous. The most common adverse reactions (>0.3%) leading to discontinuation with the 400 mg oral doses were nausea, diarrhea, dizziness, and vomiting. The most common adverse reaction leading to discontinuation with the 400 mg intravenous dose was rash. The most common adverse reactions leading to discontinuation with the 400 mg intravenous/oral sequential dose were diarrhea, pyrexia.

Adverse reactions occurring in 1% of moxifloxacin hydrochloride-treated patients and less common adverse reactions, occurring in 0.1 to 1% of moxifloxacin hydrochloride-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% or more) Adverse Reactions Reported in Active- Controlled Clinical Trials with Moxifloxacin Hydrochloride

System Organ Class	Adverse Reactions	% (N=14,981)
Blood and Lymphatic System Disorders	Anemia	1
Gastrointestinal Disorders	Nausea	7
Diarrhea	6
Vomiting	2
Constipation	2
Abdominal pain	2
Dyspepsia	1
General Disorders and Administration Site Conditions	Pyrexia	1
Investigations	Alanine aminotransferase increased	1
Metabolism and Nutritional Disorder	Hypokalemia	1
Nervous System Disorders	Headache	4
Dizziness	3
Psychiatric Disorders	Insomnia	2

Table 3: Less Common (0.1 to less than 1%) Adverse Reactions Reported in Active-Controlled Clinical Trials with Moxifloxacin Hydrochloride (N=14,981)

System Organ Class	Adverse Reactions
Blood and Lymphatic System Disorders	Thrombocythemia
Eosinophilia
Neutropenia
Thrombocytopenia
Leukopenia
Leukocytosis
Cardiac Disorders	Atrial fibrillation
Palpitations
Tachycardia
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
Pain
Malaise
Infusion site extravasation
Edema
Chills
Chest discomfort
Facial pain
Hepatobiliary disorders	Hepatic function abnormal
Infections and Infestations	Candidiasis
Vaginal infection
Fungal infection
Gastroenteritis
Investigations	Aspartate aminotransferase increased
Gamma-glutamyltransferase increased
Blood alkaline phosphatase increased
Electrocardiogram QT prolonged
Blood lactate dehydrogenase increased
Blood amylase increased
Lipase increased
Blood creatinine increased
Blood urea increased
Hematocrit decreased
Prothrombin time prolonged
Eosinophil count increased
Activated partial thromboplastin time prolonged
Blood triglycerides increased
Blood uric acid increased
Metabolism and Nutrition Disorders	Hyperglycemia
Anorexia
Hyperlipidemia
Decreased appetite
Dehydration
Musculoskeletal and Connective Tissue Disorders	Back pain
Pain in extremity
Arthralgia
Muscle spasms
Musculoskeletal pain
Nervous System Disorders	Dysgeusia
Somnolence
Tremor
Lethargy
Paresthesia
Hypoesthesia
Syncope
Psychiatric Disorders	Anxiety
Confusional state
Agitation
Depression
Nervousness
Restlessness
Hallucination
Disorientation
Renal and Urinary Disorders	Renal failure
Dysuria
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

Laboratory Changes

Changes in laboratory parameters, which are not listed above and which occurred in 2% or more of patients and at an incidence greater than in controls included: increases in mean corpuscular hemoglobin (MCH), neutrophils, white blood cells (WBCs), prothrombin time (PT) ratio, ionized calcium, chloride, albumin, globulin, bilirubin; decreases in hemoglobin, red blood cells (RBCs), neutrophils, eosinophils, basophils, glucose, oxygen partial pressure (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.

6.2 Postmarketing Experience

Table 4 below lists adverse reactions that have been identified during post- approval use of moxifloxacin hydrochloride. 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 Class	Adverse Reactions
Blood and Lymphatic System Disorders	Agranulocytosis
Pancytopenia [see Warnings and Precautions (5.7)]
Cardiac Disorders	Ventricular tachyarrhythmias (including in very rare cases cardiac arrest and torsade de pointes, and usually in patients with concurrent severe underlying proarrhythmic conditions)
Ear and Labyrinth Disorders	Hearing impairment, including deafness (reversible in majority of cases)
Eye Disorders	Vision loss (especially in the course of CNS reactions, transient in majority of cases)
Hepatobiliary Disorders	Hepatitis (predominantly cholestatic)
Hepatic failure (including fatal cases)
Jaundice Acute hepatic necrosis [see Warnings and Precautions (5.7)]
Immune System Disorders	Anaphylactic reaction
Anaphylactic shock
Angioedema (including laryngeal edema) [see Warnings and Precautions (5.7, 5.8)]
Musculoskeletal and Connective Tissue Disorders	Tendon rupture [see Warnings and Precautions (5.2)]
Nervous System Disorders	Altered coordination Abnormal gait [see Warnings and Precautions (5.3)] Myasthenia gravis (exacerbation of) [see Warnings and Precautions (5.5)] Muscle weakness Peripheral neuropathy (that may be irreversible), polyneuropathy [see Warnings and Precautions (5.3)]
Psychiatric Disorders	Psychotic reaction (very rarely culminating in self-injurious behavior, such as suicidal ideation/thoughts or suicide attempts [see Warnings and Precautions (5.4)]
Renal and Urinary Disorders	Interstitial nephritis [see Warnings and Precautions (5.7)]
Respiratory, Thoracic and Mediastinal Disorders	Allergic pneumonitis [see Warnings and Precautions (5.7)]
Skin and Subcutaneous Tissue Disorders	Photosensitivity/phototoxicity reaction [see Warnings and Precautions (5.13)]
Stevens-Johnson syndrome
Toxic epidermal necrolysis [see Warnings and Precautions (5.7)]

CLINICAL STUDIES SECTION

14 CLINICAL STUDIES

14.1 Acute Bacterial Sinusitis

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

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

14.2 Acute Bacterial Exacerbation of Chronic Bronchitis

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

Table 10: Clinical Success Rates at Follow-Up Visit for Clinically Evaluable Patients by Pathogen (Acute Bacterial Exacerbation of Chronic Bronchitis)

PATHOGEN	Moxifloxacin Hydrochloride	Clarithromycin
Streptococcus pneumoniae	16/16 (100%)	20/23 (87%)
Haemophilus influenzae	33/37 (89%)	36/41 (88%)
Haemophilus parainfluenzae	16/16 (100%)	14/14 (100%)
Moraxella catarrhalis	29/34 (85%)	24/24 (100%)
Staphylococcus aureus	15/16 (94%)	6/8 (75%)
Klebsiella pneumoniae	17/20 (85%)	10/11 (91%)

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

14.3 Community Acquired Pneumonia

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

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

An open-label ex-U.S. study that enrolled 628 patients compared moxifloxacin tablets to sequential intravenous/oral amoxicillin/clavulanate (1.2 gram intravenously every 8 hours/625 mg orally every 8 hours) with or without high- dose intravenous/oral clarithromycin (500 mg twice a day). The intravenous formulations of the comparators are not FDA approved. The clinical success rate at Day 5 to 7 for moxifloxacin hydrochloride therapy was 93% (241/258) and demonstrated superiority to amoxicillin/clavulanate ± clarithromycin (85%, 239/280) [95% C.I. of difference in success rates between moxifloxacin and comparator (2.9%, 13.2%)]. The clinical success rate at the 21 to 28 days post-therapy visit for moxifloxacin hydrochloride was 84% (216/258), which also demonstrated superiority to the comparators (74%, 208/280) [95% C.I. of difference in success rates between moxifloxacin and comparator (2.6%, 16.3%)].

The clinical success rates by pathogen across four CAP studies are presented in Table 11.

Table 11: Clinical Success Rates By Pathogen (Pooled CAP Studies)

PATHOGEN	Moxifloxacin Hydrochloride
Streptococcus pneumoniae	80/85	(94%)
Staphylococcus aureus	17/20	(85%)
Klebsiella pneumoniae	11/12	(92%)
Haemophilus influenzae	56/61	(92%)
Chlamydophila pneumoniae	119/128	(93%)
Mycoplasma pneumoniae	73/76	(96%)
Moraxella catarrhalis	11/12	(92%)

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

Moxifloxacin hydrochloride was effective in the treatment of community acquired pneumonia (CAP) caused by multi-drug resistant Streptococcus pneumoniae MDRSP* isolates. Of 37 microbiologically evaluable patients with MDRSP isolates, 35 patients (95%) achieved clinical and bacteriological success post-therapy. The clinical and bacteriological success rates based on the number of patients treated are shown in Table 12.

• 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 12: Clinical and Bacteriological Success Rates for Moxifloxacin Hydrochloride-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.
Screening Susceptibility	Clinical Success	Bacteriological Success
n/N****a	%	n/N****b	%
Penicillin-resistant	21/21	100%c	21/21	100%c
2nd generation cephalosporin-resistant	25/26	96%c	25/26	96%c
Macrolide-resistantd	22/23	96%	22/23	96%
Trimethoprim/sulfamethoxazole-resistant	28/30	93%	28/30	93%
Tetracycline-resistant	17/18	94%	17/18	94%

Not all isolates were resistant to all antimicrobial classes tested. Success and eradication rates are summarized in Table 13.

Table 13: Clinical Success Rates and Microbiological Eradication Rates for Resistant Streptococcus pneumoniae (Community Acquired Pneumonia)

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.
S. pneumoniae** with** MDRSP	Clinical Success	Bacteriological Eradication Rate
Resistant to 2 antimicrobials	12/13 (92.3%)	12/13 (92.3%)
Resistant to 3 antimicrobials	10/11 (90.9%)a	10/11 (90.9%)a
Resistant to 4 antimicrobials	6/6 (100%)	6/6 (100%)
Resistant to 5 antimicrobials	7/7 (100%)a	7/7 (100%)a
Bacteremia with MDRSP	9/9 (100%)	9/9 (100%)

14.4 Uncomplicated Skin and Skin Structure Infections

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

14.5 Complicated Skin and Skin Structure Infections

Two randomized, active controlled trials of cSSSI were performed. A double- blind trial was conducted primarily in North America to compare the efficacy of sequential intravenous/oral moxifloxacin 400 mg once a day for 7 to 14 days to an intravenous/oral beta-lactam/beta‑-lactamase inhibitor control in the treatment of patients with cSSSI. This study enrolled 617 patients, 335 of which were valid for the efficacy analysis. A second open-label International study compared moxifloxacin 400 mg once a day for 7 to 21 days to sequential intravenous/oral beta-lactam/beta-lactamase inhibitor control in the treatment of patients with cSSSI. This study enrolled 804 patients, 632 of which were valid for the efficacy analysis. Surgical incision and drainage or debridement was performed on 55% of the moxifloxacin hydrochloride treated and 53% of the comparator treated patients in these studies and formed an integral part of therapy for this indication. Success rates varied with the type of diagnosis ranging from 61% in patients with infected ulcers to 90% in patients with complicated erysipelas. These rates were similar to those seen with comparator drugs. The overall success rates in the evaluable patients and the clinical success by pathogen are shown in Tables 14 and 15.

Table 14: Overall Clinical Success Rates in Patients with Complicated Skin and Skin Structure Infections

a) of difference in success rates between Moxifloxacin and comparator (Moxifloxacin – comparator)
Study	Moxifloxacin Hydrochloride n/N (%)	Comparator n/N (%)	95% Confidence Interval****a
North America	125/162 (77.2%)	141/173 (81.5%)	(-14.4%, 2%)
International	254/315 (80.6%)	268/317 (84.5%)	(-9.4%, 2.2%)

Table 15: Clinical Success Rates by Pathogen in Patients with Complicated Skin and Skin Structure Infections

a) methicillin susceptibility was only determined in the North American Study
Pathogen	Moxifloxacin Hydrochloride n/N (%)	Comparator n/N (%)
Staphylococcus aureus (methicillin-susceptible isolates)a	106/129 (82.2%)	120/137 (87.6%)
Escherichia coli	31/38 (81.6%)	28/33 (84.8%)
Klebsiella pneumoniae	11/12 (91.7% )	7/10 (70%)
Enterobacter cloacae	9/11 (81.8%)	4/7 (57.1%)

14.6 Complicated Intra-Abdominal Infections

Two randomized, active controlled trials of cIAI were performed. A double- blind trial was conducted primarily in North America to compare the efficacy of sequential intravenous/oral moxifloxacin 400 mg once a day for 5 to 14 days to intravenous/piperacillin/tazobactam followed by oral amoxicillin/clavulanic acid in the treatment of patients with cIAI, including peritonitis, abscesses, appendicitis with perforation, and bowel perforation. This study enrolled 681 patients, 379 of which were considered clinically evaluable. A second open- label international study compared moxifloxacin 400 mg once a day for 5 to 14 days to intravenous ceftriaxone plus intravenous metronidazole followed by oral amoxicillin/clavulanic acid in the treatment of patients with cIAI. This study enrolled 595 patients, 511 of which were considered clinically evaluable. The clinically evaluable population consisted of subjects with a surgically confirmed complicated infection, at least 5 days of treatment and a 25 to 50 day follow-up assessment for patients at the Test of Cure visit. The overall clinical success rates in the clinically evaluable patients are shown in Table 16.

Table 16: Clinical Success Rates in Patients with Complicated Intra- Abdominal Infections

Study	Moxifloxacin Hydrochloride n/N (%)	Comparator n/N (%)	95% Confidence Interval****a
a) of difference in success rates between moxifloxacin hydrochloride and comparator (moxifloxacin hydrochloride – comparator) b) Excludes 2 patients who required additional surgery within the first 48 hours. c) NA - not applicable
North America (overall)	146/183 (79.8%)	153/196 (78.1%)	(-7.4%, 9.3%)
Abscess	40/57 (70.2%)	49/63 (77.8%)b	NAc
Non-abscess	106/126 (84.1%)	104/133 (78.2%)	NA
International (overall)	199/246 (80.9%)	218/265 (82.3%)	(-8.9%, 4.2%)
Abscess	73/93 (78.5%)	86/99 (86.9%)	NA
Non-abscess	126/153 (82.4%)	132/166 (79.5%)	NA

14.7 Plague

Efficacy studies of moxifloxacin hydrochloride could not be conducted in humans with pneumonic plague for ethical and feasibility reasons. Therefore, approval of this indication was based on an efficacy study conducted in animals and supportive pharmacokinetic data in adult humans and animals.

A randomized, blinded, placebo-controlled study was conducted in an African Green Monkey (AGM) animal model of pneumonic plague. Twenty AGM (10 males and 10 females) were exposed to an inhaled mean (± SD) dose of 100 ± 50 LD50 (range 92 to 127 LD50) of Yersinia pestis (CO92 strain) aerosol. The minimal inhibitory concentration (MIC) of moxifloxacin for the Y. pestis strain used in this study was 0.06 mcg/mL. Development of sustained fever for at least 4 hours duration was used as the trigger for the initiation of 10 days of treatment with either a humanized regimen of moxifloxacin or placebo. All study animals were febrile and bacteremic with Y. pestis prior to the initiation of study treatment. Ten of 10 (100%) of the animals receiving the placebo succumbed to disease between 83 to 139 h (mean 115 ± 19 hours) post treatment. Ten of 10 (100%) moxifloxacin-treated animals survived for the 30-day period after completion of the study treatment. Compared to the placebo group, mortality in the moxifloxacin group was significantly lower (difference in survival: 100% with a two-sided 95% exact confidence interval [66.3%, 100%], p-value<0.0001).

The mean plasma concentrations of moxifloxacin associated with a statistically significant improvement in survival over placebo in an AGM model of pneumonic plague are reached or exceeded in human adults receiving the recommended oral and intravenous dosage regimens. The mean (± SD) peak plasma concentration (Cmax) and total plasma exposure defined as the area under the plasma concentration-time curve (AUC) in human adults receiving 400 mg intravenously were 3.9 ± 0.9 mcg/mL and 39.3 ± 8.6 mcg•h/mL, respectively [see Clinical Pharmacology (12.3)]. The mean (± SD) peak plasma concentration and AUC0-24 in AGM following one- day administration of a humanized dosing regimen simulating the human AUC0-24 at a 400 mg dose were 4.4 ± 1.5 mcg/mL and 22 ± 8.0 mcg·h/mL, respectively.

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OVERDOSAGE SECTION

10 OVERDOSAGE

Single oral overdoses up to 2.8 g were not associated with any serious adverse events. In the event of acute overdose, empty the stomach and maintain adequate hydration. Monitor ECG due to the possibility of QT interval prolongation. Carefully observe the patient and give supportive treatment. The administration of activated charcoal as soon as possible after oral overdose may prevent excessive increase of systemic moxifloxacin exposure. About 3% and 9% of the dose of moxifloxacin, as well as about 2% and 4.5% of its glucuronide metabolite are removed by continuous ambulatory peritoneal dialysis and hemodialysis, respectively.

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NONCLINICAL TOXICOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals to determine the carcinogenic potential of moxifloxacin have not been performed.

Moxifloxacin was not mutagenic in 4 bacterial strains (TA 98, TA 100, TA 1535, TA 1537) used in the Ames Salmonella reversion assay. As with other fluoroquinolones, the positive response observed with moxifloxacin in strain TA 102 using the same assay may be due to the inhibition of DNA gyrase. Moxifloxacin was not mutagenic in the CHO/HGPRT mammalian cell gene mutation assay. An equivocal result was obtained in the same assay when v79 cells were used. Moxifloxacin was clastogenic in the v79 chromosome aberration assay, but it did not induce unscheduled DNA synthesis in cultured rat hepatocytes. There was no evidence of genotoxicity in vivo in a micronucleus test or a dominant lethal test in mice.

Moxifloxacin had no effect on fertility in male and female rats at oral doses as high as 500 mg/kg/day, approximately 12 times the maximum recommended human dose based on body surface area) or at intravenous doses as high as 45 mg/kg/day, approximately equal to the maximum recommended human dose based on body surface area). At 500 mg/kg orally there were slight effects on sperm morphology (head-tail separation) in male rats and on the estrous cycle in female rats.

13.2 Animal Toxicology and/or Pharmacology

Fluoroquinolones have been shown to cause arthropathy in immature animals. In studies in juvenile dogs oral doses of moxifloxacin 30 mg/kg/day or more (approximately 1.5 times the maximum recommended human dose based upon systemic exposure) for 28 days resulted in arthropathy. There was no evidence of arthropathy in mature monkeys and rats at oral doses up to 135 and 500 mg/kg/day, respectively.

Moxifloxacin at an oral dose of 300 mg/kg did not show an increase in acute toxicity or potential for CNS toxicity (for example, seizures) in mice when used in combination with NSAIDs such as diclofenac, ibuprofen, or fenbufen. Some fluoroquinolones have been reported to have proconvulsant activity that is exacerbated with concomitant use of NSAIDs.

A QT-prolonging effect of moxifloxacin was found in dog studies, at plasma concentrations about five times the human therapeutic level. The combined infusion of sotalol, a Class III antiarrhythmic agent, with moxifloxacin induced a higher degree of QTc prolongation in dogs than that induced by the same dose (30 mg/kg) of moxifloxacin alone. Electrophysiological in vitro studies suggested an inhibition of the rapid activating component of the delayed rectifier potassium current (IKr) as an underlying mechanism.

No signs of local intolerability were observed in dogs when moxifloxacin was administered intravenously. After intra‑-arterial injection, inflammatory changes involving the peri-arterial soft tissue were observed suggesting that intra-arterial administration of moxifloxacin hydrochloride should be avoided.

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INFORMATION FOR PATIENTS SECTION

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide)

Serious Adverse Reactions

Advise patients to stop taking moxifloxacin hydrochloride if they experience an adverse reaction and to call their healthcare provider for advice on completing the full course of treatment with another antibacterial drug.

Inform patients of the following serious adverse reactions that have been associated with moxifloxacin hydrochloride or other fluoroquinolone use:

•

**Disabling and potentially irreversible serious adverse reactions that may occur together:**Inform patients that disabling and potentially irreversible serious adverse reactions, including tendinitis and tendon rupture, peripheral neuropathies, and central nervous system effects, have been associated with use of moxifloxacin hydrochloride and may occur together in the same patient. Inform patients to stop taking moxifloxacin hydrochloride immediately if they experience an adverse reaction and to call their healthcare provider. 

•

**Tendinitis and Tendon Rupture:**Instruct patients to contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue moxifloxacin hydrochloride treatment. Symptoms may be irreversible. The risk of severe tendon disorder with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.

•

**Peripheral Neuropathies:**Inform patients that peripheral neuropathies have been associated with moxifloxacin hydrochloride use, symptoms may occur soon after initiation of therapy and may be irreversible. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness and/or weakness develop, immediately discontinue moxifloxacin hydrochloride and tell them to contact their physician.

•

**Central nervous system effects**(for example, convulsions, dizziness, lightheadedness, increased intracranial pressure)**:**Inform patients that convulsions have been reported in patients receiving fluoroquinolones, including moxifloxacin hydrochloride. Instruct patients to notify their physician before taking this drug if they have a history of convulsions. Inform patients that they should know how they react to moxifloxacin hydrochloride before they operate an automobile or machinery or engage in other activities requiring mental alertness and coordination. Instruct patients to notify their physician if persistent headache with or without blurred vision occurs. 

•

**Exacerbation of Myasthenia Gravis:**Instruct patients to inform their physician of any history of myasthenia gravis. Instruct patients to notify their physician if they experience any symptoms of muscle weakness, including respiratory difficulties. 

•

**Hypersensitivity Reactions:**Inform patients that moxifloxacin hydrochloride can cause hypersensitivity reactions, even following a single dose, and to discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (for example, swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction. 

•

**Hepatotoxicity:**Inform patients that severe hepatotoxicity (including acute hepatitis and fatal events) has been reported in patients taking moxifloxacin hydrochloride. Instruct patients to inform their physician if they experience any signs or symptoms of liver injury including: loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin and eyes, light colored bowel movements or dark colored urine. 

•

**Aortic aneurysm and dissection:**Inform patients to seek emergency medical care if they experience sudden chest, stomach, or back pain. 

•

**Diarrhea:**Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, instruct patients to contact their physician as soon as possible. 

•

**Prolongation of the QT Interval:**Instruct patients to inform their physician of any personal or family history of QT prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia; if they are taking any Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. Instruct patients to notify their physician if they have any symptoms of prolongation of the QT interval, including prolonged heart palpitations or a loss of consciousness.

•

**Blood Glucose Disturbances:**Inform the patients that if they are diabetic and are being treated with insulin or an oral hypoglycemic agent and a hypoglycemic reaction occurs, they should discontinue moxifloxacin hydrochloride and consult a physician. 

•

**Photosensitivity/Phototoxicity:**Inform patients that photosensitivity/phototoxicity has been reported in patients receiving fluoroquinolones. Inform patients to minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, instruct them to wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, instruct patients to contact their physician.

Antibacterial Resistance

Inform patients that antibacterial drugs including moxifloxacin hydrochloride should only be used to treat bacterial infections. They do not treat viral infections (for example, the common cold). When moxifloxacin hydrochloride is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by moxifloxacin hydrochloride or other antibacterial drugs in the future.

Administration Instructions

•

Inform patients that moxifloxacin tablets may be taken with or without food. Advise patients drink fluids liberally. 

•

Inform patients that moxifloxacin tablets should be taken at least 4 hours before or 8 hours after multivitamins (containing iron or zinc), antacids (containing magnesium or aluminum), sucralfate, or didanosine buffered tablets for oral suspension or the pediatric powder for oral solution. 

•

Advise patients that if a dose is missed, it should be taken anytime but not later than 8 hours prior to the next scheduled dose. If less than 8 hours remain before the next dose, the missed dose should not be taken and treatment should be continued as prescribed with the next scheduled dose. Double doses should not be taken to compensate for a missed dose. 

Plague Studies

Inform patients given moxifloxacin hydrochloride for plague that efficacy studies could not be conducted in humans for feasibility reasons. Therefore, approval for plague was based on efficacy studies conducted in animals.

**Dispense with Medication Guide available at: **www.aurobindousa.com/medication-guides

SPL MEDGUIDE SECTION

MEDICATION GUIDE

Moxifloxacin Tablets, USP

(mox'' i flox' a sin)

for oral use

Rx only

Read the Medication Guide that comes with moxifloxacin tablets before you start taking them and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about moxifloxacin tablets?

Moxifloxacin tablets is in a class of antibiotics called fluoroquinolones. Moxifloxacin tablets can cause serious side effects that can happen at the same time and could result in death. If you get any of the following serious side effects, you should stop taking moxifloxacin tablets and get medical help right away. Talk with your healthcare provider about whether you should continue to take moxifloxacin tablets.

1. Tendon rupture or swelling of the tendon (tendinitis).

•

**Tendon problems can happen in people of all ages who take moxifloxacin tablets.** Tendons are tough cords of tissue that connect muscles to bones. Symptoms of tendon problems may include: 

o

Pain, swelling, tears and inflammation of tendons including the back of the ankle (Achilles), shoulder, hand, or other tendon sites. 

•

**The risk of getting tendon problems while you take moxifloxacin tablets is higher if you:**

o

Are over 60 years of age.

o

Are taking steroids (corticosteroids).

o

Have had a kidney, heart or lung transplant.

o

**Tendon problems can happen in people who do not have the above risk factors when they take moxifloxacin tablets.**

•

**Other reasons that can increase your risk of tendon problems can include:**

o

Physical activity or exercise.

o

Kidney failure.

o

Tendon problems in the past, such as in people with rheumatoid arthritis (RA).

•

**Stop taking moxifloxacin tablets immediately and call your healthcare provider right away at the first sign of tendon pain, swelling or inflammation.** Stop taking moxifloxacin tablets until tendinitis or tendon rupture has been ruled out by your healthcare provider. Avoid exercise and using the affected area. The most common area of pain and swelling is in the Achilles tendon at the back of your ankle. This can also happen with other tendons.

•

**Talk to your healthcare provider about the risk of tendon rupture with continued use of moxifloxacin tablets.** You may need a different antibiotic that is not a fluoroquinolone to treat your infection.

•

**Tendon rupture can happen while you are taking or after you have stopped taking moxifloxacin tablets.** Tendon ruptures can happen within hours or days after taking moxifloxacin tablets and have happened up to several months after people have stopped taking their fluoroquinolone.

•

**Stop taking moxifloxacin tablets immediately and get medical help right away if you get any of the following signs or symptoms of a tendon rupture:**

o

Hear or feel a snap or pop in a tendon area. 

o

Bruising right after an injury in a tendon area. 

o

Unable to move the affected area or put weight on the area.

**2. Changes in sensation and possible nerve damage (Peripheral Neuropathy). **Damage to the nerves in arms, hands, legs, or feet can happen in people who take fluoroquinolones, including moxifloxacin tablets. Stop taking moxifloxacin tablets immediately and talk to your healthcare provider right away if you get any of the following symptoms of peripheral neuropathy in your arms, hands, legs, or feet:

•

pain 

•

tingling 

•

weakness

•

burning

•

numbness 

Moxifloxacin tablets may need to be stopped to prevent permanent nerve damage.

**3. Central Nervous System (CNS) effects.**Seizures have been reported in people who take fluoroquinolone antibiotic medicines, including moxifloxacin tablets. Tell your healthcare provider if you have a history of seizures before you start taking moxifloxacin tablets. CNS side effects may happen as soon as after taking the first dose of moxifloxacin tablets. Stop taking moxifloxacin tablets immediately and talk to your healthcare provider right away if you get any of these side effects, or other changes in mood or behavior:

•

seizures

•

hear voices, see things, or sense things that are not there (hallucinations) 

•

feel restless

•

tremors

•

feel anxious or nervous

•

confusion

•

depression

•

trouble sleeping

•

nightmares 

•

feel lightheaded or dizzy

•

feel more suspicious (paranoia)

•

suicidal thoughts or acts

•

headaches that will not go away (with or without blurred vision)

**4. Worsening of myasthenia gravis (a disease which causes muscle weakness). **Fluoroquinolones like moxifloxacin tablets may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Tell your healthcare provider if you have a history of myasthenia gravis. Moxifloxacin tablets should not be used in people who have a history of myasthenia gravis. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.

See the section**“What are the possible side effects of moxifloxacin tablets?”** for more information about side effects.

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What are moxifloxacin tablets?

Moxifloxacin tablets are a fluoroquinolone antibiotic medicine used to treat certain types of infections caused by certain germs called bacteria in adults 18 years or older. These bacterial infections include:

•

Community Acquired Pneumonia 

•

Uncomplicated Skin and Skin Structure Infections 

•

Complicated Skin and Skin Structure Infections 

•

Complicated Intra-Abdominal Infections 

•

Plague

•

Acute Bacterial Sinusitis 

•

Acute Bacterial Exacerbation of Chronic Bronchitis 

Moxifloxacin tablets should not be used in people with acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis if there are other treatment options available.

Studies of moxifloxacin tablets for use in the treatment of plague were done in animals only, because plague could not be studied in people.

It is not known if moxifloxacin tablet is safe and works in people under 18 years of age. Children have a higher chance of getting bone, joint, and tendon (musculoskeletal) problems while taking fluoroquinolone antibiotic medicines.

Sometimes infections are caused by viruses rather than by bacteria. Examples include viral infections in the sinuses and lungs, such as the common cold or flu. Antibiotics, including moxifloxacin tablets, do not kill viruses.

Call your healthcare provider if you think your condition is not getting better while you are taking moxifloxacin tablets.

Who should not take moxifloxacin tablets?

Do not take moxifloxacin tablets if you have ever had an allergic reaction to moxifloxacin, other fluoroquinolone antibiotics, or any of the ingredients in moxifloxacin tablets. Ask your healthcare provider if you are not sure. See the end of this Medication Guide for a complete list of ingredients in moxifloxacin tablets.

What should I tell my healthcare provider before taking moxifloxacin tablets?

See**“What is the most important information I should know about moxifloxacin tablets?”**

Tell your healthcare provider about all your medical conditions, including if you:

•

Have tendon problems. Moxifloxacin tablets should not be used in people who have a history of tendon problems. 

•

Have a disease that causes muscle weakness (myasthenia gravis). Moxifloxacin tablets should not be used in people who have a history of myasthenia gravis. 

•

Have central nervous system problems (such as epilepsy). 

•

Have nerve problems. Moxifloxacin tablets should not be used in people who have a history of a nerve problem called peripheral neuropathy. 

•

Have or anyone in your family has an irregular heartbeat, especially a condition called “QT prolongation”. 

•

Have low blood potassium (hypokalemia). 

•

Have a slow heartbeat (bradycardia). 

•

Have a history of seizures. 

•

Have kidney problems. 

•

Have rheumatoid arthritis (RA) or other history of joint problems. 

•

Are pregnant or plan to become pregnant. It is not known if moxifloxacin tablets will harm your unborn baby. 

•

Are breastfeeding or plan to breastfeed. It is not known if moxifloxacin hydrochloride passes into breast milk. You and your healthcare provider should decide whether you will take moxifloxacin tablets or breastfeed. 

•

Have diabetes or problems with low blood sugar (hypoglycemia).

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal and dietary supplements. Moxifloxacin tablets and other medicines can affect each other causing side effects.

** Especially tell your healthcare provider if you take:**

•

A Non-Steroidal Anti-Inflammatory Drug (NSAID). Many common medicines for pain relief are NSAIDs. Taking an NSAID while you take moxifloxacin tablets or other fluoroquinolones may increase your risk of central nervous system effects and seizures. 

•

A blood thinner (warfarin, Coumadin, Jantoven).

•

A medicine to control your heart rate or rhythm (antiarrhythmic). See**“What are the possible side effects of moxifloxacin tablets?”**

•

An anti-psychotic medicine.

•

A tricyclic antidepressant.

•

An oral anti-diabetes medicine or insulin. 

•

Erythromycin.

•

A water pill (diuretic).

•

A steroid medicine. Corticosteroids taken by mouth or by injection may increase the chance of tendon injury. See**“What is the most important information I should know about moxifloxacin tablets?”**

•

Certain medicines may keep moxifloxacin tablets from working correctly. Take moxifloxacin tablets either 4 hours before or 8 hours after taking these products:

•

An antacid, multivitamin, or other product that has magnesium, aluminum, iron, or zinc

•

Sucralfate (Carafate)

•

Didanosine oral suspension or solution 

Ask your healthcare provider if you are not sure if any of your medicines are listed above.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take moxifloxacin tablets?

•

Take moxifloxacin tablets 1 time each day exactly as prescribed by your healthcare provider.

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Take moxifloxacin tablets at about the same time each day.

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Moxifloxacin tablets can be taken with or without food.

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If you miss a dose of moxifloxacin tablets and it is: 

o

**8 hours or more**until your next scheduled dose, take your missed dose right away. Then take the next dose at your regular time.

o

**less than 8 hours**until your next scheduled dose,**do not**take the missed dose. Take the next dose at your regular time.

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Do not take 2 doses of moxifloxacin tablets to make up for a missed dose. If you are not sure about when to take moxifloxacin tablets after a missed dose, ask your doctor or pharmacist.

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Drink plenty of fluids while taking moxifloxacin tablets.

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Do not skip any doses, or stop taking moxifloxacin tablets even if you begin to feel better, until you finish your prescribed treatment, unless: 

o

You have tendon problems. See “**What is the most important information I should know about moxifloxacin tablets?”**).

o

You have nerve problems. See**“What is the most important information I should know about moxifloxacin tablets?”**

o

You have central nervous system problems. See**“What is the most important information I should know about moxifloxacin tablets?”**

o

You have a serious allergic reaction (see**“What are the possible side effects of moxifloxacin tablets?”**), or your healthcare provider tells you to stop taking moxifloxacin tablets.

•

 This will help make sure that all of the bacteria are killed and lower the chance that the bacteria will become resistant to moxifloxacin tablets. If this happens, moxifloxacin tablets and other antibiotic medicines may not work in the future.

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If you take too much moxifloxacin hydrochloride, call your healthcare provider or get medical help immediately.

What should I avoid while taking moxifloxacin tablets?

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Moxifloxacin tablets can make you feel dizzy and lightheaded. Do not drive, operate machinery, or do other activities that require mental alertness or coordination until you know how moxifloxacin tablets affect you.

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Avoid sunlamps, tanning beds, and try to limit your time in the sun. Moxifloxacin tablets can make your skin sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You could get severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while taking moxifloxacin tablets, call your healthcare provider right away. You should use a sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight.

What are the possible side effects of moxifloxacin tablets?

Moxifloxacin tablets can cause side effects that may be serious or even cause death, including:

•

See**“What is the most important information I should know about moxifloxacin tablets?”**

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**Serious heart rhythm changes**(QT prolongation and torsade de pointes). Tell your healthcare provider right away if you have a change in your heartbeat (a fast or irregular heartbeat), or if you faint. Moxifloxacin tablets may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this event are higher in people: 

o

Who are elderly 

o

With a family history of prolonged QT interval 

o

With low blood potassium (hypokalemia) 

o

Who take certain medicines to control heart rhythm (antiarrhythmics)

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**Serious allergic reactions.**Allergic reactions can happen in people taking fluoroquinolones, including moxifloxacin tablets, even after only 1 dose. Stop taking moxifloxacin tablets and get emergency medical help right away if you get any of the following symptoms of a severe allergic reaction:

o

Hives

o

Trouble breathing or swallowing

o

Swelling of the lips, tongue, face

o

Throat tightness, hoarseness

o

Fast heartbeat

o

Faint 

o

Yellowing of the skin or eyes. Stop taking moxifloxacin tablets and tell your healthcare provider right away if you get yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to moxifloxacin tablets (a liver problem).

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**Skin rash.**Skin rash may happen in people taking moxifloxacin tablets even after only 1 dose. Stop taking moxifloxacin tablets at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to moxifloxacin tablets.

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**Aortic aneurysm and dissection.**Tell your healthcare provider if you have ever been told that you have a swelling of the large artery that carries blood from the heart to the body (aortic aneurysm). Get emergency medical help right away if you have sudden chest, stomach, or back pain.

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**Intestine infection (Pseudomembranous colitis).**Pseudomembranous colitis can happen with most antibiotics, including moxifloxacin tablets. Call your healthcare provider right away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. You may have stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after you have stopped taking moxifloxacin tablets.

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**Changes in blood sugar.**People who take moxifloxacin tablets and other fluoroquinolone medicines with oral anti-diabetes medicines or with insulin can get low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia). Follow your healthcare provider's instructions for how often to check your blood sugar. If you have diabetes and you get low blood sugar while taking moxifloxacin tablets, stop taking moxifloxacin tablets and call your healthcare provider right away. Your antibiotic medicine may need to be changed.

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**Sensitivity to sunlight (photosensitivity).**See**“What should I avoid while taking moxifloxacin tablets?”**The most common side effects of moxifloxacin tablets include: 

o

nausea 

o

diarrhea 

o

headache 

o

dizziness 

These are not all the possible side effects of moxifloxacin tablets. Tell your healthcare provider about any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store moxifloxacin tablets?

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Store moxifloxacin tablets at 20° to 25°C (68° to 77°F).

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Keep moxifloxacin tablets away from moisture (humidity).

Keep moxifloxacin tablets and all medicines out of the reach of children.

General Information about the safe and effective use moxifloxacin tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use moxifloxacin tablets for a condition for which it is not prescribed. Do not give moxifloxacin tablets to other people, even if they have the same symptoms that you have. They may harm them.

This Medication Guide summarizes the most important information about moxifloxacin tablets. If you would like more information about moxifloxacin tablets, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about moxifloxacin tablets that is written for health professionals.

What are the ingredients in moxifloxacin tablets?

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**Active ingredient:** moxifloxacin hydrochloride

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**Inactive ingredients:** hypromellose, iron oxide red, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium starch glycolate, and titanium dioxide.

**Dispense with Medication Guide available at: **www.aurobindousa.com/medication-guides

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Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520

Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 038, India

Packaged and Distributed by:

MAJOR® PHARMACEUTICALS

Indianapolis, IN 46268 USA

Refer to package label for Distributor's NDC Number

All brands listed are the trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited.

For more information call Aurobindo Pharma USA, Inc. at 1-866-850-2876.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: 06/2020

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