Prescription Drug Information: Levofloxacin (Page 3 of 12)

5.3 Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with fluoroquinolones, including levofloxacin. These reactions often occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat, or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), dyspnea, urticaria, itching, and other serious skin reactions. Levofloxacinshould be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity. Serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated [see ADVERSE REACTIONS (6); PATIENT COUNSELING INFORMATION (17.3)].

5.4 Other Serious and Sometimes Fatal Reactions

Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with 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:

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fever, rash, or severe dermatologic reactions (e.g., 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.

The drug should be discontinued immediately at the first appearance of skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted [see ADVERSE REACTIONS (6); PATIENT COUNSELING INFORMATION (17.3)].

5.5 Hepatotoxicity

Post-marketing reports of severe hepatotoxicity (including acute hepatitis and fatal events) have been received for patients treated with levofloxacin. No evidence of serious drug-associated hepatotoxicity was detected in clinical trials of over 7,000 patients. Severe hepatotoxicity generally occurred within 14 days of initiation of therapy and most cases occurred within 6 days. Most cases of severe hepatotoxicity were not associated with hypersensitivity [see WARNINGS AND PRECAUTIONS (5.4)]. The majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. Levofloxacin should be discontinued immediately if the patient develops signs and symptoms of hepatitis [see ADVERSE REACTIONS (6); PATIENT COUNSELING INFORMATION (17.3)].

5.6 Central Nervous System Effects

Convulsions, toxic psychoses, increased intracranial pressure (including pseudotumor cerebri) have been reported in patients receiving fluoroquinolones, including levofloxacin. Fluoroquinolones may also cause central nervous system stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, insomnia, and, rarely, suicidal thoughts or acts. These reactions may occur following the first dose. If these reactions occur in patients receiving levofloxacin, the drug should be discontinued and appropriate measures instituted. As with other fluoroquinolones, levofloxacinshould be used with caution in patients with a known or 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 seizure threshold (e.g., certain drug therapy, renal dysfunction) [see ADVERSE REACTIONS (6); DRUG INTERACTIONS (7.4, 7.5); PATIENT COUNSELING INFORMATION (17.3)].

5.7 Clostridium difficile- Associated Diarrhea

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

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

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated [see ADVERSE REACTIONS (6.2); PATIENT COUNSELING INFORMATION (17.3)].

5.8 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. Levofloxacin should be discontinued 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 [see ADVERSE REACTIONS (6); PATIENT COUNSELING INFORMATION (17.3)].

5.9 Prolongation of the QT Interval

Some fluoroquinolones, including levofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. Rare cases of torsade de pointes have been spontaneously reported during postmarketing surveillance in patients receiving fluoroquinolones, including levofloxacin. Levofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval [see ADVERSE REACTIONS (6.3), USE IN SPECIFIC POPULATIONS (8.5), and PATIENT COUNSELING INFORMATION (17.3)].

5.10 Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals

Levofloxacin is indicated in pediatric patients (6 months of age and older) only for the prevention of inhalational anthrax (post-exposure) and for plague [see INDICATIONS AND USAGE (1.13, 1.14)]. An increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, and gait abnormality) compared to controls has been observed in pediatric patients receiving levofloxacin[see USE IN SPECIFIC POPULATIONS (8.4)].

In immature rats and dogs, the oral and intravenous administration of levofloxacin resulted in increased osteochondrosis. Histopathological examination of the weight-bearing joints of immature dogs dosed with levofloxacin revealed persistent lesions of the cartilage. Other fluoroquinolones also produce similar erosions in the weight-bearing joints and other signs of arthropathy in immature animals of various species [see Animal Toxicology and/or Pharmacology (13.2)].

5.11 Blood Glucose Disturbances

As with other fluoroquinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported with levofloxacin, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glyburide) or with insulin. In these patients, careful monitoring of blood glucose is recommended. If a hypoglycemic reaction occurs in a patient being treated with levofloxacin, levofloxacin should be discontinued and appropriate therapy should be initiated immediately [see ADVERSE REACTIONS (6.2); DRUG INTERACTIONS (7.3); PATIENT COUNSELING INFORMATION (17.4)].

5.12 Photosensitivity/Phototoxicity

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., 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 after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if photosensitivity/phototoxicity occurs [see ADVERSE REACTIONS (6.3); PATIENT COUNSELING INFORMATION (17.3)].

5.13 Development of Drug Resistant Bacteria

Prescribing levofloxacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria [see PATIENT COUNSELING INFORMATION (17.1)].

6 ADVERSE REACTIONS

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:

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Tendon Effects [see WARNINGS AND PRECAUTIONS (5.1)]

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Exacerbation of Myasthenia Gravis [see WARNINGS AND PRECAUTIONS (5.2)]

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Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS (5.3)]

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Other Serious and Sometimes Fatal Reactions [see WARNINGS AND PRECAUTIONS (5.4)]

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Hepatotoxicity [see WARNINGS AND PRECAUTIONS (5.5)]

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Central Nervous System Effects [see WARNINGS AND PRECAUTIONS (5.6)]

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Clostridium difficile -Associated Diarrhea [see WARNINGS AND PRECAUTIONS (5.7)]

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Peripheral Neuropathy that may be irreversible [see WARNINGS AND PRECAUTIONS (5.8)]

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Prolongation of the QT Interval [see WARNINGS AND PRECAUTIONS (5.9)]

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Musculoskeletal Disorders in Pediatric Patients [see WARNINGS AND PRECAUTIONS (5.10)]

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Blood Glucose Disturbances [see WARNINGS AND PRECAUTIONS (5.11)]

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Photosensitivity/Phototoxicity [see WARNINGS AND PRECAUTIONS (5.12)]

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Development of Drug Resistant Bacteria [see WARNINGS AND PRECAUTIONS (5.13)]

Hypotension has been associated with rapid or bolus intravenous infusion of levofloxacin. Levofloxacinshould be infused slowly over 60 to 90 minutes, depending on dosage [see DOSAGE AND ADMINISTRATION (2.5)].

Crystalluria and cylindruria have been reported with quinolones, including levofloxacin. Therefore, adequate hydration of patients receiving levofloxacinshould be maintained to prevent the formation of a highly concentrated urine [see DOSAGE AND ADMINISTRATION (2.5)].