FDA label b8dfa367-6a1b-e403-e053-2995a90a7e7e

BOXED WARNING SECTION WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAI NERVOUS SYTEM EFFECTS and EXACERBATION OF MYASTHENIA GRAVIS • Fluoroquinolones, including moxifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together [see Warnings and Precautions (5.1)], including: • 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)] Discontinue moxifloxacin, immediately and avoid the use of fluoroquinolones, including moxifloxacin, in patients who experience any of these serious adverse reactions [see Warnings and Precautions (5.1)]. • Fluoroquinolones, including moxifloxacin, may exacerbate muscle weakness in patients with myasthenia gravis. Avoid moxifloxacin, in patients with known history of myasthenia gravis [see Warnings and Precautions (5.5)]. • Because fluoroquinolones, including moxifloxacin, have been associated with serious adverse reactions [see Warnings and Precautions(5.1-5.13)], reserve moxifloxacin, for use in patients who have no alternative treatment options for the following indications: • Acute bacterial sinusitis [see Indications and Usage (1.6)] • Acute bacterial exacerbation of chronic bronchitis [see Indications and Usage (1.7)]

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, 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. Patients of any age or without pre-existing risk factors have experienced these adverse reactions [see W arnings and Precautions ( 5.2 , 5.3 , 5.4 ) ]. Discontinue moxifloxacin immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including moxifloxacin, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones. 5.2 Tendinitis and Tendon Rupture Fluoroquinolones, including moxifloxacin, 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 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, 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, 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. Symptoms may occur soon after initiation of moxifloxacin and may be irreversible in some patients [see Warnings and Precautions ( 5.1) and Adverse Reactions ( 6.1 , 6.2 ) ]. Discontinue moxifloxacin 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, in patients who have previously experienced peripheral neuropathy 5.4 Central Nervous System Effects Psychiatric Adverse Reactions Fluoroquinolones, including moxifloxacin, 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, discontinue moxifloxacin immediately and institute appropriate measures [see Adverse Reactions ( 6.1 , 6.2 )]. Central Nervous System Adverse Reactions Fluoroquinolones, including moxifloxacin, 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 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, discontinue moxifloxacin 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, 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 in patients with known history of myasthenia gravis. 5.6 QT Prolongation Moxifloxacin has been shown to prolong the QT interval of the electrocardiogram in some patients. Following oral dosing with 400 mg of moxifloxacin the mean (± SD) change in QTc from the pre-dose value at the time of maximum drug concentration was 6 msec (± 26) (n = 787). Following a course of daily intravenous dosing (400 mg; 1 hour infusion each day) the mean change in QTc from the Day 1 pre-dose value was 10 msec (±22) on Day 1 (n=667) and 7 msec (± 24) on Day 3 (n = 667). Avoid moxifloxacin in patients with the following risk factors due to the lack of clinical experience with the drug in these patient populations: • Known prolongation of the QT interval • Ventricular arrhythmias including torsade de pointes because QT prolongation may lead to an increased risk for these conditions • Ongoing proarrhythmic conditions, such as clinically significant bradycardia and acute myocardial ischemia, • Uncorrected hypokalemia or hypomagnesemia • Class IA (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic agents • Other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants Elderly patients using intravenous moxifloxacin 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. [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 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 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. These reactions may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following: • Fever, rash, or severe dermatologic reactions (for example, toxic epidermal necrolysis, Stevens-Johnson syndrome) • Vasculitis; arthralgia; myalgia; serum sickness • Allergic pneumonitis • Interstitial nephritis; acute renal insufficiency or failure • Hepatitis; jaundice; acute hepatic necrosis or failure • Anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities Discontinue moxifloxacin 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. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Discontinue moxifloxacin at the first appearance of a skin rash or any other sign of hypersensitivity. [See Warnings and Precautions ( 5.7 ) ] 5.9 Clostridium difficile -Associated Diarrhea Clostridium difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including moxifloxacin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following 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. 5.10 Arthropathic Effects in Animals In immature dogs, oral administration of moxifloxacin 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 ) ] 5.11 Blood Glucose Disturbances As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with moxifloxacin. In moxifloxacin-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (for example, sulfonylurea) or with insulin. 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 and initiate appropriate therapy immediately [see Adverse Reactions ( 6.1 ), Drug Interactions ( 7.3 ) and Patient Counseling Information ( 17 )]. 5.12 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, after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Moxifloxacin therapy should be discontinued if phototoxicity occurs. [See Clinical Pharmacology ( 12.2 ) ] 5.13 Development of Drug Resistant Bacteria Prescribing moxifloxacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

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: • 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 ) ] • Other Serious and Sometimes Fatal Adverse Reactions [see Warnings and Precautions ( 5.7 ) ] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.8 ) ] • Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.9 ) ] • Blood Glucose Disturbances [see Warnings and Precautions ( 5.11 ) ] • Photosensitivity/Phototoxicity [see Warnings and Precautions ( 5.12 ) ] • Development of Drug Resistant Bacteria [see Warnings and Precautions ( 5.13 ) ] 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 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 (0.5%). 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-treated patients and less common adverse reactions, occurring in 0.1 to 1% of moxifloxacin-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 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 HeadacheDizziness 43 Psychiatric Disorders Insomnia 2 Table 3 Less Common (0.1 to less than 1%) Adverse Reactions Reported in Active-Controlled Clinical Trials with Moxifloxacin (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 HHyperlipidemia 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 (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. 6.2 Postmarketing Experience Table 4 below lists adverse reactions that have been identified during post-approval use of moxifloxacin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Table 4: Postmarketing Reports of Adverse Drug Reactions System Organ Class Adverse Reaction s 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 ( 5.12 ) ] Stevens-Johnson syndrome Toxic epidermal necrolysis [see Warnings and Precautions ( 5.7 )]

<table border="1" cellpadding="2" width="85%"><tbody><tr><td><content styleCode="bold">System Organ Class</content></td><td><content styleCode="bold">Adverse Reactions</content></td><td><content styleCode="bold">% (N=14,981)</content></td></tr><tr><td><content styleCode="bold">Blood and Lymphatic System Disorders </content></td><td>Anemia </td><td>1</td></tr><tr><td rowspan="6"><content styleCode="bold">Gastrointestinal Disorders </content></td><td>Nausea </td><td>7</td></tr><tr><td>Diarrhea </td><td>6</td></tr><tr><td>Vomiting </td><td>2</td></tr><tr><td>Constipation </td><td>2</td></tr><tr><td>Abdominal pain </td><td>2</td></tr><tr><td>Dyspepsia </td><td>1</td></tr><tr><td><content styleCode="bold">General Disorders and Administration Site Conditions </content></td><td>Pyrexia </td><td>1</td></tr><tr><td><content styleCode="bold">Investigations </content></td><td>Alanine aminotransferase increased </td><td>1</td></tr><tr><td><content styleCode="bold">Metabolism and Nutritional Disorder </content></td><td>Hypokalemia </td><td>1</td></tr><tr><td><content styleCode="bold">Nervous System Disorders </content></td><td>HeadacheDizziness </td><td>43</td></tr><tr><td><content styleCode="bold">Psychiatric Disorders </content></td><td>Insomnia </td><td>2</td></tr></tbody></table>

<table border="1" cellpadding="0" cellspacing="0" width="661"><tbody><tr><td><content styleCode="bold">System Organ Class</content></td><td><content styleCode="bold">Adverse Reactions </content></td></tr><tr><td valign="top"><content styleCode="bold">Blood and Lymphatic System Disorders </content></td><td valign="top">Thrombocythemia Eosinophilia Neutropenia Thrombocytopenia Leukopenia Leukocytosis </td></tr><tr><td valign="top"><content styleCode="bold">Cardiac Disorders </content></td><td valign="top">Atrial fibrillation Palpitations Tachycardia Angina pectoris Cardiac failure Cardiac arrest Bradycardia </td></tr><tr><td valign="top"><content styleCode="bold">Ear and Labyrinth Disorders </content></td><td valign="top">Vertigo Tinnitus </td></tr><tr><td><content styleCode="bold">Eye Disorders </content></td><td>Vision blurred </td></tr><tr><td valign="top"><content styleCode="bold">Gastrointestinal Disorders </content></td><td valign="top">Dry mouth Abdominal discomfort Flatulence Abdominal distention Gastritis Gastroesophageal reflux disease </td></tr><tr><td valign="top"><content styleCode="bold">General Disorders and Administration Site Conditions </content></td><td valign="top">Fatigue Chest pain Asthenia Pain Malaise Infusion site extravasation Edema Chills Chest discomfort Facial pain </td></tr><tr><td><content styleCode="bold">Hepatobiliary disorders </content></td><td>Hepatic function abnormal </td></tr><tr><td valign="top"><content styleCode="bold">Infections and Infestations </content></td><td valign="top">Candidiasis Vaginal infection Fungal infection Gastroenteritis </td></tr><tr><td valign="top"><content styleCode="bold">Investigations </content></td><td valign="top">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 </td></tr><tr><td valign="top"><content styleCode="bold">Metabolism and Nutrition Disorders </content></td><td valign="top">Hyperglycemia Anorexia HHyperlipidemia Decreased appetite Dehydration </td></tr><tr><td valign="top"><content styleCode="bold">Musculoskeletal and Connective Tissue Disorders </content></td><td valign="top">Back pain Pain in extremity Arthralgia Muscle spasms Musculoskeletal pain </td></tr><tr><td valign="top"><content styleCode="bold">Nervous System Disorders </content></td><td valign="top">Dysgeusia Somnolence Tremor Lethargy Paresthesia Hypoesthesia Syncope </td></tr><tr><td valign="top"><content styleCode="bold">Psychiatric Disorders </content></td><td valign="top">Anxiety Confusional state Agitation Depression Nervousness Restlessness Hallucination Disorientation </td></tr><tr><td valign="top"><content styleCode="bold">Renal and Urinary Disorders </content></td><td valign="top">Renal failure Dysuria </td></tr><tr><td><content styleCode="bold">Reproductive System and Breast Disorders </content></td><td>Vulvovaginal pruritus </td></tr><tr><td valign="top"><content styleCode="bold">Respiratory, Thoracic, and Mediastinal Disorders </content></td><td valign="top">Dyspnea Asthma Wheezing Bronchospasm </td></tr><tr><td valign="top"><content styleCode="bold">Skin and Subcutaneous Tissue Disorders </content></td><td valign="top">Rash Pruritus Hyperhidrosis Erythema Urticaria Dermatitis allergic Night sweats </td></tr><tr><td valign="top"><content styleCode="bold">Vascular Disorders </content></td><td valign="top">Hypertension Hypotension Phlebitis <footnote ID="K2840"/></td></tr></tbody></table>

<table border="1" cellpadding="0" cellspacing="0"><tbody><tr align="center"><td valign="top"><content styleCode="bold">System Organ Class</content></td><td valign="top"><content styleCode="bold">Adverse Reaction</content><content styleCode="bold">s</content></td></tr><tr><td valign="top"><content styleCode="bold">Blood and Lymphatic System Disorders </content></td><td valign="top">Agranulocytosis Pancytopenia [see <content styleCode="bold">Warnings and Precautions ( <linkHtml href="#_a7cc8822-aeb0-2add-2f10-5f8166a14872">5.7</linkHtml>) </content>] </td></tr><tr><td valign="top"><content styleCode="bold">Cardiac Disorders </content></td><td valign="top">Ventricular tachyarrhythmias (including in very rare cases cardiac arrest and torsade de pointes, and usually in patients with concurrent severe underlying proarrhythmic conditions) </td></tr><tr><td valign="top"><content styleCode="bold">Ear and Labyrinth Disorders</content></td><td valign="top">Hearing impairment, including deafness (reversible in majority of cases) </td></tr><tr><td valign="top"><content styleCode="bold">Eye Disorders</content></td><td valign="top">Vision loss (especially in the course of CNS reactions, transient in majority of cases) </td></tr><tr><td valign="top"><content styleCode="bold">Hepatobiliary Disorders </content></td><td valign="top">Hepatitis (predominantly cholestatic) Hepatic failure (including fatal cases) Jaundice Acute hepatic necrosis [see <content styleCode="bold">Warnings and Precautions ( <linkHtml href="#_a7cc8822-aeb0-2add-2f10-5f8166a14872">5.7</linkHtml>) </content>] </td></tr><tr><td valign="top"><content styleCode="bold">Immune System Disorders </content></td><td valign="top">Anaphylactic reaction Anaphylactic shock Angioedema (including laryngeal edema) [see <content styleCode="bold">Warnings and Precautions </content><content styleCode="bold">(</content><linkHtml href="#_a7cc8822-aeb0-2add-2f10-5f8166a14872">5.7</linkHtml><content styleCode="bold">, </content><linkHtml href="#_9323422d-dabd-4d0b-b14e-4a1863dc4f54">5.8</linkHtml><content styleCode="bold">)</content>] </td></tr><tr><td valign="top"><content styleCode="bold">Musculoskeletal and Connective Tissue Disorders </content></td><td valign="top">Tendon rupture [see <content styleCode="bold">Warnings and Precautions ( <linkHtml href="#_5d6f2491-ba63-44d6-1c1c-8c5be77a0b9a">5.2</linkHtml>) </content>] </td></tr><tr><td valign="top"><content styleCode="bold">Nervous System Disorders </content></td><td valign="top">Altered coordination Abnormal gait [see <content styleCode="bold">Warnings and Precautions ( <linkHtml href="#_7df9a780-3428-6dd7-4c1b-1908c2d39ff0">5.3</linkHtml>) </content>] Myasthenia gravis (exacerbation of) [see <content styleCode="bold">Warnings and Precautions ( <linkHtml href="#_ebd35c85-fc1d-60e0-15de-083a4ae66013">5.5</linkHtml>) </content>] Muscle weakness Peripheral neuropathy (that may be irreversible), polyneuropathy <content styleCode="bold">[</content>see <content styleCode="bold"> Warnings and Precautions ( <linkHtml href="#_7df9a780-3428-6dd7-4c1b-1908c2d39ff0">5.3</linkHtml>)] </content></td></tr><tr><td valign="top"><content styleCode="bold">Psychiatric Disorders</content></td><td valign="top">Psychotic reaction (very rarely culminating in self-injurious behavior, such as suicidal ideation/thoughts or suicide attempts [see <content styleCode="bold"> Warnings and Precautions ( <linkHtml href="#_32060965-40b1-75f8-0a3b-a1c326ab7fc7">5.4</linkHtml>)] </content><content styleCode="bold"/></td></tr><tr><td valign="top"><content styleCode="bold">Renal and Urinary Disorders </content></td><td valign="top">Interstitial nephritis [see <content styleCode="bold">Warnings and Precautions ( <linkHtml href="#_a7cc8822-aeb0-2add-2f10-5f8166a14872">5.7</linkHtml>) </content>] </td></tr><tr><td valign="top"><content styleCode="bold">Respiratory, Thoracic and Mediastinal Disorders </content></td><td valign="top">Allergic pneumonitis [see <content styleCode="bold">Warnings and Precautions ( <linkHtml href="#_a7cc8822-aeb0-2add-2f10-5f8166a14872">5.7</linkHtml>) </content>] </td></tr><tr><td valign="top"><content styleCode="bold">Skin and Subcutaneous Tissue Disorders </content></td><td valign="top">Photosensitivity/phototoxicity reaction [see <content styleCode="bold">Warnings and Precautions ( <linkHtml href="#_fbc30be2-fad3-8c4d-60f7-c27aad2103a6">5.12</linkHtml>) </content>] Stevens-Johnson syndrome Toxic epidermal necrolysis [see <content styleCode="bold">Warnings and Precautions ( <linkHtml href="#_a7cc8822-aeb0-2add-2f10-5f8166a14872">5.7</linkHtml>)] </content></td></tr></tbody></table>