Can Levofloxacin cause pyrexia?

ADVERSE REACTIONS The most common reactions (≥3%) were nausea, headache, diarrhea, insomnia, constipation and dizziness ( 6.2 ). To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Serious and Otherwise Important Adverse Reactions The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling: • Disabling and Potentially Irreversible Serious Adverse Reactions [ 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)] • Other Serious and Sometimes Fatal Reactions [see Warnings and Precautions ( 5.6)] • Hypersensitivity Reactions [see Warnings and Precautions (5.7)] • Hepatotoxicity [see Warnings and Precautions ( 5.8)] • Risk of Aortic Aneurysm and Dissection [see Warnings and Precautions ( 5.9 )] • Clostridium difficile-Associated Diarrhea [see Warnings and Precautions ( 5.10 )] • Prolongation of the QT Interval [see Warnings and Precautions ( 5.11 )] • Musculoskeletal Disorders in Pediatric Patients [see Warnings and Precautions ( 5.12 )] • Blood Glucose Disturbances [see Warnings and Precautions ( 5.13 )] • Photosensitivity/Phototoxicity [see Warnings and Precautions ( 5.14 )] • Development of Drug Resistant Bacteria [see Warnings and Precautions ( 5.15 )] Crystalluria and cylindruria have been reported with quinolones, including levofloxacin. Therefore, adequate hydration of patients receiving levofloxacin should be maintained to prevent the formation of a highly concentrated urine [see Dosage and Administration ( 2.5 )]. 6.2 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to levofloxacin in 7537 patients in 29 pooled Phase 3 clinical trials. The population studied had a mean age of 50 years (approximately 74% of the population was < 65 years of age), 50% were male, 71% were Caucasian, 19% were Black. Patients were treated with levofloxacin for a wide variety of infectious diseases [see Indications and Usage (1)]. Patients received levofloxacin doses of 750 mg once daily, 250 mg once daily, or 500 mg once or twice daily. Treatment duration was usually 3 to 14 days, and the mean number of days on therapy was 10 days. The overall incidence, type and distribution of adverse reactions was similar in patients receiving levofloxacin doses of 750 mg once daily, 250 mg once daily, and 500 mg once or twice daily. Discontinuation of levofloxacin due to adverse drug reactions occurred in 4.3% of patients overall, 3.8% of patients treated with the 250 mg and 500 mg doses and 5.4% of patients treated with the 750 mg dose. The most common adverse drug reactions leading to discontinuation with the 250 and 500 mg doses were gastrointestinal (1.4%), primarily nausea (0.6%); vomiting (0.4%); dizziness (0.3%); and headache (0.2%). The most common adverse drug reactions leading to discontinuation with the 750 mg dose were gastrointestinal (1.2%), primarily nausea (0.6%), vomiting (0.5%); dizziness (0.3%); and headache (0.3%). Adverse reactions occurring in ≥1% of levofloxacin-treated patients and less common adverse reactions, occurring in 0.1 to <1% of levofloxacin-treated patients, are shown in Table 4 and Table 5, respectively. The most common adverse drug reactions (≥3%) are nausea, headache, diarrhea, insomnia, constipation, and dizziness. Table 4:Common (≥1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin System/Organ Class Adverse Reaction % (N=7537) Infections and Infestations moniliasis 1 Psychiatric Disorders insomnia * [see Warnings and Precautions ( 5.4 )] 4 Nervous System Disorders headache dizziness [see Warnings and Precautions ( 5.4 )] 6 3 Respiratory, Thoracic and Mediastinal Disorders dyspnea [see Warnings and Precautions ( 5.7 )] 1 Gastrointestinal Disorders nausea diarrhea constipation abdominal pain vomiting dyspepsia 7 5 3 2 2 2 Skin and Subcutaneous Tissue Disorders rash [see Warnings and Precautions ( 5.7 )] pruritus 2 1 Reproductive System and Breast Disorders vaginitis 1 † General Disorders and Administration Site Conditions edema injection site reaction chest pain 1 1 1 * N = 7274 † N=3758 (women) # pool of studies included IV and oral administration Table 5: Less Common (0.1 to 1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin (N=7537) System/Organ Class Adverse Reaction Infections and Infestations genital moniliasis Blood and Lymphatic System Disorders anemiathrombocytopenia granulocytopenia [see Warnings and Precautions ( 5.6 )] Immune System Disorders allergic reaction [see Warnings and Precautions ( 5.6 , 5.7 )] Metabolism and Nutrition Disorders hyperglycemia hypoglycemia [see Warnings and Precautions ( 5.13 )] hyperkalemia Psychiatric Disorders anxiety agitation confusion depression hallucination nightmare * [see Warnings and Precautions ( 5.4 )] sleep disorder * anorexia abnormal dreaming * Nervous System Disorders tremorconvulsions [see Warnings and Precautions ( 5.4 )] paresthesia [see Warnings and Precautions ( 5.3 )] vertigo hypertonia hyperkinesias abnormal gait somnolence * syncope Respiratory, Thoraic and Mediastinal Disorders epistaxis Cardiac Disorders cardiac arrestpalpitation ventricular tachycardia ventricular arrhythmia Vascular Disorders phlebitis Gastrointestinal Disorders gastritisstomatitis pancreatitis esophagitis gastroenteritis glossitis pseudomembranous/ C. difficile colitis [see Warnings and Precautions ( 5.10 )] Hepatobiliary Disorders abnormal hepatic functionincreased hepatic enzymes increased alkaline phosphatase Skin and Subcutaneous Tissue Disorders urticaria [see Warnings and Precautions ( 5.7 )] Musculoskeletal and Connective Tissue Disorders arthralgiatendinitis [see Warnings and Precautions ( 5.2 )] myalgia skeletal pain Renal and Urinary Disorders abnormal renal functionacute renal failure [see Warnings and Precautions ( 5.6 )] * N = 7274 In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been noted in patients undergoing treatment with quinolones, including levofloxacin. The relationship of the drugs to these events is not presently established. 6.3 Postmarketing Experience Table 6 lists adverse reactions that have been identified during post-approval use of levofloxacin. 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 6: Postmarketing Reports Of Adverse Drug Reactions System/Organ Class Adverse Reaction Blood and Lymphatic System Disorders pancytopenia aplastic anemia leukopenia hemolytic anemia [see Warnings and Precautions ( 5.6 )] eosinophilia Immune System Disorders hypersensitivity reactions, sometimes fatal including: anaphylactic/anaphylactoid reactions anaphylactic shock angioneurotic edema serum sickness [see Warnings and Precautions ( 5.6 , 5.7 )] Psychiatric Disorders psychosis paranoia isolated reports of suicide attempt and suicidal ideation [see Warnings and Precautions ( 5.4 )] Nervous System Disorders exacerbation of myasthenia gravis [see Warnings and Precautions (5.5 )] anosmia ageusia parosmia dysgeusia peripheral neuropathy (may be irreversible) [see Warnings and Precautions ( 5.3 )] isolated reports of encephalopathy abnormal electroencephalogram (EEG) dysphonia pseudotumor cerebri [see Warnings and Precautio

WARNINGS AND PRECAUTIONS Anaphylactic reactions and allergic skin reactions, serious, occasionally fatal, may occur after first dose ( 4 , 5.7 ) Hematologic (including agranulocytosis, thrombocytopenia), and renal toxicities may occur after multiple doses ( 5.6 ) Hepatotoxicity: Severe, and sometimes fatal, hepatoxicity has been reported. Discontinue immediately if signs and symptoms of hepatitis occur ( 5.8 ) Clostridium difficile -associated colitis: evaluate if diarrhea occurs ( 5.10 ) Prolongation of the QT interval and isolated cases of torsade de pointes have been reported. Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval ( 5.11 , 8.5 ) 5.1 Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects Fluoroquinolones, including levofloxacin, 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 levofloxacin. 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 levofloxacin immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including levofloxacin, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones. 5.2 Tendinopathy and Tendon Rupture Fluoroquinolones, including levofloxacin, 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 tendon sites. Tendinitis or tendon rupture can occur within hours or days of starting levofloxacin or as long as several months after completion of fluoroquinolone 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 those 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 been reported in patients taking fluoroquinolones who do not have the above risk factors. Discontinue levofloxacin 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 levofloxacin in patients who have a history of tendon disorders or tendon rupture [see Adverse Reactions ( 6.3 ) and Patient Counseling Information ( 17 )]. 5.3 Peripheral Neuropathy Fluoroquinolones, including levofloxacin, 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 levofloxacin. Symptoms may occur soon after initiation of levofloxacin and may be irreversible in some patients [see Warnings and Precautions ( 5.1) and Adverse Reactions ( 6.1, 6.2 )]. Discontinue levofloxacin immediately if the patient experiences symptoms of 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 levofloxacin, in patients who have previously experienced peripheral neuropathy [see Adverse Reactions ( 6) and Patient Counseling Information ( 17)]. 5.4 Central Nervous System Effects Psychiatric Adverse Reactions Fluoroquinolones, including levofloxacin, havebeenassociated with an increased risk of psychiatric adverse reactions, including: toxic psychoses, hallucinations, or paranoia; depression, or suicidal thoughts; anxiety,agitation, restlessness, or nervousness; confusion, delirium, disorientation, or disturbances in attention; insomnia or nightmares; memory impairment. Attempted or completed suicide have been reported, especially in patients with a medical history of depression, or an underlying risk factor for depression. These reactions may occurfollowingthe first dose. If these reactions occur in patients receiving levofloxacin, discontinue levofloxacin and institute appropriate measures. Central Nervous SystemAdverseReactions Fluoroquinolones, including levofloxacin, have beenassociated with an increased risk of seizures (convulsions), increased intracranial pressure (including pseudotumor cerebri), tremors, and lightheadedness. As with other fluoroquinolones, levofloxacin should be used with caution in patients with a knownor suspected central nervous system (CNS) disorder that may predispose them to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose them to seizures or lower the seizurethreshold (e.g., certain drug therapy, renal dysfunction). If these reactions occur in patients receiving levofloxacin discontinue levofloxacin and institute appropriatemeasures [see Adverse Reactions ( 6 ), Drug Interactions ( 7.4, 7.5), and Patient Counseling Information (17)]. 5.5 Exacerbation of Myasthenia Gravis Fluoroquinolones, including levofloxacin, 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 levofloxacin in patients with a known history of myasthenia gravis [see Adverse Reactions ( 6.3) and Patient Counseling Information ( 17 )]. 5.6 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 rarely in patients receiving therapy with fluoroquinolones, including levofloxacin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following: • fever, rash, or severe dermatologic reactions (e.g., 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 levofloxacin immediately at the first appearance of skin rash, jaundice, or any other sign of hypersensitivity and institute supportive measures [see Adverse Reactions ( 6 ) and Patient Counseling Information ( 17)]. 5.7 Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with fluoroquinolones, including levofloxa