Levox Special Precautions

General: Patients should be adequately hydrated while on Levofloxacin therapy to prevent the formation of a highly concentrated urine.
As with other quinolones, use Levofloxacin with caution in patients with known or suspected CNS disorder that may predispose to seizures or lower seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of risk factors that may predispose to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction).
Moderate to severe phototoxicity reactions have been observed in patients exposed to direct sunlight while receiving quinolones. Avoid excessive exposure to sunlight. However, in clinical trials with Levofloxacin, phototoxicity has been observed in less than 0.1% of patients. Discontinue treatment if phototoxicity occurs.
Disturbances of blood glucose, including symptomatic hyper- and hypoglycemia usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent or with insulin, have been reported with quinolone use. Careful monitoring of blood glucose is recommended in these patients. Discontinue treatment if a hypoglycemic reaction occurs and initiate appropriate therapy. Some quinolones, including Levofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. During post-marketing surveillance, extremely rare cases of torsades de pointes, have been reported in patients taking Levofloxacin. These reports generally involve patients with concurrent medical conditions or concomitant medications that may have been contributory. Risk of arrhythmias may be reduced by avoiding concurrent use with other drugs that prolong QT interval including class Ia or class III antiarrhythmic agents. In addition, avoid Levofloxacin use in the presence of risk factors for torsaides de pointes such as hypokalemia, significant bradycardia, and cardiomyopathy.
As with any potent antimicrobial drug, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, is advisable during therapy. Adjust dose in patients with renal impairment since Levofloxacin is excreted mainly by the kidneys.
Vial: Infusion Time: Rapid or bolus intravenous infusion may result in hypotension. Administer Levofloxacin solution by slow intravenous infusion over a period of not less than 60 minutes.
Impairment of Fertility, Teratogenicity: Levofloxacin causes no impairment of fertility or reproductive performance in rats at oral doses as high as 360 mg/kg/day. Levofloxacin is not teratogenic in rats given oral doses as high as 810 mg/kg/day, or at intravenous doses of up to 160 mg/kg/day. No teratogenicity is observed in rabbits given oral doses as high as 50 mg/kg/day.
750 mg Infusion: Tendinopathy and Tendon Rupture: Fluoroquinolones including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. This risk is further increased in those over 60 years old, in kidney, heart, or lung transplant recipients, and with concomitant steroid therapy. Strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis may also increase the risk of tendon rupture. Tendinitis and tendon rupture have been reported in patients taking fluoroquinolones who do not have the above risk factors. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. Levofloxacin should be discontinued 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 doctor about changing to a non-quinolone antimicrobial drug.
Myasthenia gravis: Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Post-marketing reports of serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Levofloxacin should be avoided in patients with known history of myasthenia gravis.
Hepatotoxicity: Severe hepatotoxicity (including acute hepatitis and fatal events) has been reported in patients treated with levofloxacin. Most cases of severe hepatotoxicity occurred within 6 to 14 days of initiation of levofloxacin therapy and were not associated with hypersensitivity reactions. The majority of fatal cases occurred in patients ≥ 65 years old.
Levofloxacin should be discontinued in any patient who experiences loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin or eyes, light colored bowel movement, or dark colored urine.
Hypersensitivity: Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving fluoroquinolones, including levofloxacin. These reactions often occur after the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, larynx, throat, or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath and acute respiratory distress), dyspnea, urticaria, itching, and other serious skin reactions.
Serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, IV fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated.
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 treatment with fluoroquinolones, including levofloxacin. Clinical manifestations which may be severe and generally occur after multiple doses 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, including acute 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.
Levofloxacin should be discontinued immediately at the first appearance of skin rash or any other sign of hypersensitivity and supportive measures instituted.
Central Nervous System (CNS) Disorders: Convulsions, toxic psychoses, increased intracranial pressure (including pseudotumor cerebri) have been reported in patients receiving fluoroquinolones, including levofloxacin. Fluoroquinolones may also cause CNS stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, insomnia, anxiety, and rarely, suicidal thoughts or acts. These reactions may occur after the first dose. If these reactions occur in patients receiving levofloxacin, the drug should be discontinued and appropriate measures instituted. As with other quinolones, levofloxacin should be used with caution in patients with known or suspected CNS disorders (e.g., severe cerebral arteriosclerosis, epilepsy), or other risk factors (e.g., certain drug therapy, renal impairment) that may predispose to seizures or lower the seizure threshold. Levofloxacin should be used with caution in patients with unstable psychiatric illness.
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.
Cardiac Disorders: Prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia have been reported with some fluoroquinolones, including levofloxacin. Rare cases of torsades de pointes have been spontaneously reported during post-marketing surveillance in patients receiving levofloxacin. Levofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, significant bradycardia, cardiomyopathy, or myocardial ischemia. The risk of arrhythmias may be reduced by avoiding concomitant use with other drugs that prolong the QT interval including macrolide antibiotics, antipsychotics, tricyclic antidepressants, class IA (quinidine, procainamide) or class III (amiodarone, sotalol) antiarrhythmic agents, and cisapride. Elderly patients generally may be more susceptible to drug-associated effects on the QT interval.
Clostridium difficile-associated diarrhea (CDAD): This has been observed with the use of nearly all antibacterial agents, including levofloxacin, and may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea following administration of antibacterial agents.
Musculoskeletal Disorders in Children: Levofloxacin is indicated in children ≥ 6 months old only for the prevention of inhalational anthrax (post-exposure) and for plague. An increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, and gait abnormality) compared to controls has been observed in pediatric patients receiving levofloxacin.
Oral and IV administration of levofloxacin in immature rats and dogs increased the incidence and severity of 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.
Blood Glucose Disturbances: As with other fluoroquinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glibenclamide) or with insulin. Careful monitoring of blood glucose is recommended in these patients. Levofloxacin should be discontinued and appropriate therapy initiated immediately if a hypoglycemic reaction occurs. Serious hypoglycemia and hyperglycemia have also occurred in patients without a history of diabetes.
Patients with G-6-phosphate dehydrogenase deficiency: Use with caution in patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity who may be prone to hemolytic reactions when treated with fluoroquinolones.
Photosensitivity/Phototoxicity: Moderate to severe photosensitivity/ phototoxicity reactions manifesting as exaggerated sunburn reaction have been observed in patients exposed to direct sunlight or ultraviolet (UV) light while receiving fluoroquinolones; hence, direct exposure to excessive sunlight or UV radiation should be avoided during treatment. Therapy should be discontinued if photosensitization occurs.
IV Administration: Since rapid or bolus IV injection may result in hypotension, Levofloxacin 750 mg/150 mL injection should only be administered by slow IV infusion over a period of 90 minutes.
Other Precautions: As with any potent antimicrobial drug, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, is advisable during treatment.
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.
As with other antibacterial drugs, long term or repeated use may result in overgrowth of non-susceptible organisms, including fungi.
Renal Impairment: Since clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in patients with renal impairment (creatinine clearance <50 mL/min), adjustment of the dosage regimen in such patients is necessary to avoid drug accumulation (see Dosage & Administration).
Hepatic Impairment: Pharmacokinetic studies in patients with liver impairment have not been conducted. Due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment.
Effects on Ability to Drive and Use Machines: Since there is a potential for levofloxacin to cause dizziness and lightheadedness, patients should be advised to avoid performing tasks which require complete mental alertness such as driving and operating machinery until effects of drug to the individual are known.
Use in Children: Safety and efficacy in pediatric patients and adolescents below the age of 18 years have not been established. Quinolones, including Levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species.
750 mg Infusion: Quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species (see Precautions).
Levofloxacin is indicated in pediatric patients ≥ 6 months old, for inhalational anthrax (post-exposure) and for the treatment of plague, including pneumonic and septicemic plague due to Yersinia pestis and prophylaxis for plague. The risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate.
Safety and effectiveness in pediatric patients <6 months old have not been established.
Use in the Elderly: In Phase III clinical trials, 1,190 Levofloxacin-treated patients (25%) were 65 years of age or older. Of these, 675 patients (14%) were between the ages of 65 and 74 and 515 patients (11%) were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Levofloxacin's pharmacokinetic properties in younger adults and elderly adults do not differ significantly when creatinine clearance is taken into consideration. However, since the drug is known to be substantially excreted by the kidney, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, exercise care in dose selection. It may be useful to monitor renal function.
750 mg Infusion: No dosage adjustment is necessary for elderly patients with normal renal function. However, since levofloxacin is substantially excreted by the kidneys and some elderly patients experience age-related reduction in renal function, care should be taken in dose selection and renal function monitoring is recommended.
Elderly patients are at increased risk of developing severe tendon disorders including tendon rupture, fatal hepatotoxicity, or prolonged QT interval leading to ventricular arrhythmias when being treated with a fluoroquinolone such as levofloxacin (see Precautions).
Use in Pregnancy: Category C. In the absence of human data and due to the experimental risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism, Levofloxacin solution for infusion must not be used in pregnant and lactating women.
Use in Lactation: Levofloxacin has not been measured in human milk. Based upon Ofloxacin data, it can be presumed that Levofloxacin will be excreted in human milk. Because of the potential for serious adverse reactions from Levofloxacin in nursing infants, decide whether to discontinue drug or discontinue nursing, taking into account the importance of the drug to the mother.