Levox

Levofloxacin.

Antibacterial.
Pharmacology: Mechanism of Action: Levofloxacin is a synthetic broad spectrum fluoroquinolone for oral and intravenous administration. It is the S (-) enantiomer of the racemic drug, Ofloxacin. Levofloxacin acts on the DNA-DNA gyrase complex and topoisomerase IV.
750 mg Infusion: Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antibacterial agent. The mechanism of action of levofloxacin and other quinolones involves inhibition of bacterial topoisomerase II (DNA gyrase) and topoisomerase IV enzymes which are essential for DNA replication, transcription, repair, and recombination.
Pharmacokinetics: Bioavailability: Levofloxacin pharmacokinetics are linear and predictable after single and multiple oral/or i.v. dosing regimens. Steady-state conditions are reached within 48 hours following a 500 mg or 750 mg once daily dosage regimen. The mean + SD peak and trough plasma concentrations attained following multiple once-daily oral dosage regimens were approximately 5.7 + 1.4 and 0.5 + 0.2 ug/mL after the 500 mg doses, and 8.6 + 1.9 and 1.1 + 0.4 ug/mL after the 750 mg doses, respectively. The mean + SD peak and trough plasma concentrations attained following multiple once-daily i.v. regimens were approximately 6.4 + 0.8 and 0.6 + 0.2 ug/mL after the 500 mg doses, and 12.1 + 4.1 and 1.3 + 0.71 ug/mL after the 750 mg doses, respectively. Plasma concentration profiles for Levofloxacin I.V. and Levofloxacin oral are nearly superimposable in the post-peak, distribution-elimination phase. Absolute bioavailability after oral administration is almost 100% and approximates that of intravenous administration.
Levofloxacin distributes rapidly throughout the body, achieving concentrations in lung, sputum, otorhinolaryngeal, prostatic and gynecologic tissues and in bronchoalveolar, lacrimal, intraocular, inflammatory and spinal fluids, delivering drug concentrations that greatly exceed MICs of major pathogens.
Levofloxacin is metabolized to a very small extent (< 5%); the metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. Levofloxacin, following oral and intravenous administration, is eliminated relatively slowly from the plasma (t½ of 6 to 8 h), thereby allowing once-daily dosing. Excretion is primarily by the renal route (> 85% of the administered dose).
750 mg Infusion: Levofloxacin pharmacokinetics are linear and predictable after single and multiple oral/intravenous (IV) dosing regimens. Steady-state conditions are reached within 48 hours after a 500 mg or 750 mg once daily dosage regimen. The oral and IV route of administration may also be considered interchangeable since levofloxacin's plasma concentration profiles are nearly superimposable in the post-peak, distribution-elimination phase.
The mean volume of distribution generally ranges from 74 to 112 L after single and multiple 500 mg or 750 mg doses, indicating widespread distribution into body tissues. Penetration of levofloxacin in skin tissues and in blister fluid is rapid and extensive. It also penetrates well into lung tissues. Protein binding is approximately 24% to 38% and is independent of drug concentration.
Levofloxacin is stereochemically stable in plasma and urine and undergoes limited metabolism in humans with less than 5% of an administered dose recovered in the urine.
Plasma half-life (t_1/2) ranges from approximately 6 to 8 hours. The mean apparent total body clearance and renal clearance range from approximately 144 to 226 mL/min and 96 to 142 mL/min, respectively. Renal clearance in excess of the glomerular filtration rate suggests that tubular secretion of levofloxacin occurs in addition to its glomerular filtration.
Microbiology: Spectrum of Activity: Levofloxacin is active against a wide spectrum of Gram-positive and Gram-negative microorganisms. Levofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.
Resistance to Levofloxacin due to spontaneous mutation in vitro is a rare occurrence (range: 10-9 to 10-10). Although cross-resistance has been observed between Levofloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to Levofloxacin.
750 mg Infusion: Levofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections: See Table 1.

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Levofloxacin has been shown to be active in vitro against most strains of the following organisms; however, the clinical significance of these data is unknown: See Table 2.

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It is suggested to carry out susceptibility tests.

For the treatment of adults (≥ 18 years old) with mild, moderate, or severe infections caused by susceptible strains of the designated microorganisms for the following conditions: Acute bacterial sinusitis; Acute bacterial exacerbation of chronic bronchitis; Community-acquired pneumonia; Healthcare-associated pneumonia; Complicated skin and skin structure infections (SSSI); Uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections; Complicated and uncomplicated urinary tract infections (UTIs); Acute pyelonephritis; Chronic bacterial prostatitis.
To reduce the incidence or progression of inhalational anthrax in adults and children ≥ 6 months old, following exposure to aerosolized Bacillus anthracis. The effectiveness of levofloxacin is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. Levofloxacin has not been tested in humans for the post-exposure prevention of inhalational anthrax.
For the treatment of plague, including pneumonic and septicemic plague due to Yersinia pestis and prophylaxis for plague in adults and children ≥ 6 months old. Efficacy studies of levofloxacin could not be conducted in humans with plague for ethical and feasibility reasons. The approval of this indication was based on efficacy study done in animals.
750 mg Infusion: Uncomplicated urinary tract infections.

Tablet: Adult Dose: Orally, 250 to 500 mg once daily.
Administer the dose at least two hours before or two hours after antacids containing magnesium, or aluminum; after sucralfate or metal cations such as iron, and multivitamin preparations with zinc. Concomitant administration with these drugs may significantly decrease Levofloxacin absorption.
Vial: Levofloxacin solution should only be administered by intravenous infusion. It is not for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.
Caution: Rapid or bolus intravenous infusion must be avoided.
Usual dose: 500 mg administered by slow infusion over 60 minutes every 24 hours or 750 mg administered by slow infusion over 90 minutes every 24 hours.
It is usually possible to switch from initial intravenous treatment to the oral route after a few days, depending on patient's condition.
As with antibiotic therapy in general, administration of Levofloxacin solution for infusion should be continued for a minimum of 48 to 72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained.
750 mg Infusion: Patients receiving oral or intravenous (IV) levofloxacin should be well hydrated to prevent formation of highly concentrated urine. Crystalluria and cylinduria have been reported with quinolones.
Levofloxacin should be given or taken at the same time each day.
Levofloxacin solution for infusion should only be administered by IV infusion. It is NOT for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.
Caution: Rapid or bolus IV infusion must be avoided because it may result to hypotension.
Usual Recommended Dose: 750 mg administered by slow IV infusion over 90 minutes once every 24 hours. The dose and duration of treatment are based on the type and severity of infection being treated (see Dosing Table).
As with other parenteral antibiotic therapy in general, administration of levofloxacin solution for infusion should be continued for a minimum of 48 to 72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained. It is usually possible to switch from initial IV treatment to the oral route after a few days, depending on the patient's condition and the physician's discretion.
Levofloxacin IV Dosing in Adult Patients with Normal Renal Function (creatinine clearance ≥ 50 mL/min): See Tables 3 and 4.

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When only the serum creatinine value is available, the following formula may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function: See Equation.

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Levofloxacin Oral or IV Dosing in Children: See Table 5.

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Or, as prescribed by a physician.

Clinical features of acute overdosage of levofloxacin may include CNS symptoms such as confusion, dizziness, impairment of consciousness, and convulsive seizures, as well as GI reactions such as nausea and mucosal erosions.
In the event of overdose, symptomatic treatment should be implemented. The patient should be observed and proper hydration maintained. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
The administration of activated charcoal as soon as possible after oral overdose may prevent excessive increase of systemic levofloxacin exposure. Antacids may be used for protection of the gastric mucosa.
Hemodialysis, including peritoneal dialysis and CAPD, are not effective in removing levofloxacin from the body. No specific antidote exists.

750 mg Infusion: Fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.

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.

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.
750 mg Infusion: (Pregnancy Category C). There are no adequate and well-controlled studies using levofloxacin in pregnant women. Since levofloxacin, as with most other fluoroquinolones, causes arthropathy in immature animals, the drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (see Precautions).
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.
750 mg Infusion: Levofloxacin has not been measured in human milk. However, based on the ofloxacin data, it can be presumed that levofloxacin will be excreted in human milk. Therefore, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother as well as the possible serious adverse effects to the infant.

Gastrointestinal/Metabolism: Occasional: Nausea, diarrhea; Rare: Anorexia, vomiting, abdominal pain, dyspepsia; Very rare: Bloody diarrhea, which in extremely rare cases may be indicative of enterocolitis, including pseudomembranous colitis; Extremely rare: Hypoglycemia, particularly in diabetic patients.
Neurological: Rare: Headache, dizziness/vertigo, drowsiness, and insomnia; Very rare: Paresthesia, tremor, anxiety, agitation, confusions, and convulsion; Extremely rare: Hypoesthesia, visual and auditory disturbances, disturbances of taste and smell and hallucinations.
Musculo-skeletal: Very rare: Arthralgia, myalgia, tendon disorders, including Tendinitis; Extremely rare: Tendon rupture, muscular weakness; Isolated case: Rhabdomyolysis.
Mucocutaneous/Anaphylactic Reactions which may sometimes occur even after the first dose: Occasional: Pain, reddening of the infusion site, phlebitis; Rare: Pruritus, rash; Very rare: Urticaria, bronchospasm/dyspnea; Extremely rare: Angioedema, hypotension, anaphylactic-like shock, photosensitisation; Isolated cases: Severe bullous eruptions such as Stevens Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and erythema exsudativum multiforme.
Liver/Kidney: Occasional: Increase in liver enzymes (ALT, AST); Rare: Increase in bilirubin, increase in serum creatinine; Extremely rare: Liver reactions such as hepatitis, acute kidney failure.
Blood: Rare: Eosinophilia, leukopenia; Very rare: Neutropenia, thrombocytopenia; Extremely rare: Agranulocytosis.
Others: Rare: Asthenia, fungal overgrowth and proliferation of other resistant microorganisms; Extremely rare: Allergic pneumonitis, fever; Some other fluoroquinolones are known to possibly trigger attacks of porphyria in patients with porphyria.
Other possible undesirable effects related to the class of fluoroquinolones: Extremely rare: Psychotic reactions such as acute confusional states and depressive mood changes occur.
Extrapyramidal symptoms and other disorders of muscular coordination.
Hypersensitivity vasculitis.
750 mg Infusion: The most common adverse reactions reported with the use of levofloxacin include nausea, vomiting, diarrhea, constipation, headache, insomnia, and dizziness.
The following undesirable effects of potential medical importance have occurred in patients receiving levofloxacin, regardless of relationship to the drug: Body as a Whole: Allergic reaction, asthenia, edema, fever/pyrexia, injection/infusion site reaction (pain, reddening, inflammation), multiple organ failure, pain (including pain in back, chest, and extremities), syncope.
Dermatologic/Hypersensitivity Reactions: anaphylactic/anaphylactoid reactions, anaphylactic shock, angioneurotic edema, bullous eruption (including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme), leukocytoclastic vasculitis, photosensitivity/phototoxicity, pruritus, genital pruritus, rash serum sickness, urticaria.
Nervous System: Abnormal dreaming/dreams, abnormal electroencephalogram (EEG), abnormal gait, agitation, amnesia, anorexia, anxiety, confusion, convulsions (seizures), depression, dysphonia, encephalopathy, extrapyramidal symptoms and other disorders of muscular coordination; hallucination, , hyperkinesia, hypertonia, exacerbation of myasthenia gravis; nervousness, nightmare, paranoia, paresthesia, sensory or sensorimotor peripheral neuropathy, pseudotumor cerebri, psychosis, sleep disorders, somnolence, isolated reports of suicide attempts or suicidal ideation; tremor, vertigo.
Cardiovascular: cardiac failure/arrest, electrocardiogram QT prolonged, palpitation, phlebitis, tachycardia, vasculitis, vasodilatation, ventricular tachycardia, torsades de pointes, ventricular arrhythmia.
Respiratory: allergic pneumonitis, apnea, dyspnea, laryngeal edema, interstitial pneumonia.
Gastrointestinal (GI): Abdominal pain, hemorrhagic diarrhea which in very rare cases may be indicative of enterocolitis including CDAD and colitis; dyspepsia, esophagitis, gastritis, gastroenteritis, GI hemorrhage, glossitis, pancreatitis, stomatitis.
Metabolic and Nutritional Disorders: hyperglycemia, hypoglycemia, hyperkalemia.
Hepatobiliary: Abnormal hepatic function, increased hepatic enzymes [alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT)]; jaundice/severe liver injury, hepatic failure (including fatal cases), hepatic necrosis, hepatitis.
Hematologic: Agranulocytosis, anemia (including aplastic and hemolytic anemia), epistaxis, eosinophilia, granulocytopenia, leukopenia, pancytopenia, prolonged International Normalized Ratio (INR); prolonged prothrombin time; thrombocythemia, thrombocytopenia including thrombotic thrombocytopenic purpura; neutropenia.
Genitourinary: Abnormal renal function, acute renal failure, interstitial nephritis, increased blood creatinine; glomerulonephritis, nephrosis, genital moniliasis, vaginitis.
Musculoskeletal and Connective Tissue Disorders: Arthralgia, arthritis, increased muscle enzymes; ligament rupture, myalgia, myositis, muscle injury (including rupture), rhabdomyolysis (including fatal cases), skeletal pain, tendinitis/tendinopathy/tendon disorder, tendon rupture.
Special Senses: Abnormal vision/visual disturbance including diplopia, reduced visual acuity, blurred vision; scotoma; hearing impairment/hypoacusis, tinnitus; anosmia, parosmia; ageusia, dysgeusia, uveitis.
Other Adverse Effects: fungal infection/moniliasis.
In clinical trials using multiple dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been observed in patients undergoing treatment with other quinolones. However, the relationship of the drugs to these events has not been definitely established.

Tablet: Antacids, sucralfate, metal cations, and zinc-containing multivitamin preparations may interfere with the gastrointestinal absorption of Levofloxacin resulting in systemic levels considerably lower than desired.
Vial: There are no data concerning an interaction of Levofloxacin I.V. with oral antacids, sucralfate, multivitamins, didanosine, or metal cations. However, do not co-administer quinolone with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line.
Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs: No pharmacokinetic interactions of Levofloxacin are found with Theophylline. However, there are indications of a pronounced lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs that lower the seizure threshold or with Fenbufen or similar non-steroidal anti-inflammatory drugs.
Interference with Laboratory Tests: Levofloxacin may inhibit the growth of Mycobacterium tuberculosis, and therefore, may give false-negative results in the bacteriological diagnosis of tuberculosis.
750 mg Infusion: See Table 6.

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750 mg Infusion: Directions for Use, Compatibility and Stability: No further dilution of levofloxacin solution for infusion is necessary.
Prior to administration, parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and container permit.
Observe strict aseptic technique when inserting the cannula of the infusion set into the spout of levofloxacin solution for infusion. If contaminated, it has the potential to become a source of infection to patients. The cannula of the infusion set should be inserted fully and not halfway into the spout of the levofloxacin solution for infusion container to avoid leakage.
Since only limited data are available on the compatibility of levofloxacin solution for infusion with other IV substances, additives or other medications should not be added to levofloxacin IV or infused simultaneously through the same IV line. If the same IV line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of levofloxacin IV with an infusion solution compatible with levofloxacin IV and with any other drugs administered via this common line.
Levofloxacin solution should not be mixed with heparin or alkaline solution (e,g., sodium bicarbonate, etc.).
Levofloxacin solution for infusion should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same IV line.
Levofloxacin solution for infusion is for single-use only; any unused portion should be discarded properly.
Levofloxacin solution should be used within 3 hours after rubber stopper opening in order to prevent bacterial contamination.

750 mg Infusion: Store in hermetic container at a dry place at temperatures not exceeding 30°C. Protect from light.

Quinolones

J01MA12 - levofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.

Rx