RITEMED Levofloxacin 500mg Film-Coated Tablet 100's

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; Uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections; Complicated urinary tract infections; Chronic bacterial prostatitis.
To reduce the incidence or progression of inhalational 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 inhalation anthrax.
For the treatment of plague, including pneumonic and septicemic plague, due to Yersinia pestis and prophylaxis for plague. 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 an efficacy study done in animals.

 

Levofloxacin tablet can be taken with or without food. Administer dose at least 2 hours before or 2 hours after antacids containing calcium, magnesium or aluminum, after sucralfate or metal cations such as iron, multivitamin preparations with zinc, or didanosine. Concomitant administration with these drugs may significantly decrease levofloxacin absorption.
Patients receiving levofloxacin should be well hydrated to prevent formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones.
Levofloxacin should be given or taken at the same time each day.
Usual Adult Dose: Orally, 500 mg once every 24 hours. The duration of treatment is based on the type of infection (see table as follows). (See Table 3.)

Dosage in Adults with Renal Impairment (creatinine clearance <50 mL/min): See Table 4.

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.

Or, as prescribed by a physician.

 

Overdosage

May be taken with or without food: Take at least 2 hr before or 2 hr after antacids containing Ca/Mg/Al after sucralfate or metal cations such as Fe, multivit prep w/ Zn or didanosine.

Known hypersensitivity to levofloxacin, other quinolones or to any component of the product.

 

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: Patients receiving fluoroquinolones, including levofloxacin may experience rare cases of sensory or sensorimotor axonal polyneuropathy affecting the small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness. 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, levofloxacin should be discontinued to prevent the development of an irreversible condition.
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.
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.
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.
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.
Use in Children: Quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species (see previous text).
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 Elderly: 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 previous text).

 

Use In Pregnancy & Lactation

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, ascites, asthenia, edema, fever/pyrexia, hot flashes, influenza-like symptoms, fatigue, malaise, multiple organ failure, pain (including pain in back, chest, and extremities), rigors, syncope, changed temperature sensation, withdrawal syndrome.
Dermatologic/Hypersensitivity Reactions: Alopecia, anaphylactic/anaphylactoid reactions, anaphylactic shock, angioneurotic edema, bullous eruption (including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme), dry skin, eczema, increased sweating, leukocytoclastic vasculitis, photosensitivity/phototoxicity, pruritus, genital pruritus, acute localized exanthematous pustulosis, rash (erythematous, maculopapular), serum sickness, skin disorder, skin exfoliation, skin ulceration, urticaria.
Nervous System: Abnormal dreaming/paroniria (morbid dreams), abnormal electroencephalogram (EEG), abnormal gait, agitation, amnesia, anorexia, anxiety, ataxia, confusion, convulsions (seizures), depression, dysphonia, encephalopathy, extrapyramidal symptoms and other disorders of muscular coordination; hallucination, hyperesthesia, hypoesthesia, hyperkinesia, hypertonia, intracranial hypertension, impotence, leg cramps, involuntary muscle contractions, migraine, exacerbation of myasthenia gravis; nervousness, nightmare, paranoia, paresthesia, paralysis, sensory or sensorimotor peripheral neuropathy, pseudotumor cerebri, psychosis, sleep disorders, speech disorder, somnolence, stupor, isolated reports of suicide attempts or suicidal ideation; tremor, vertigo.
Cardiovascular: Angina pectoris, arrhythmia, atrial fibrillation, bradycardia, cardiac failure/arrest, cerebrovascular disorder, disseminated intravascular coagulation, electrocardiogram QT prolonged, flushing, gangrene, heart block, hypertension, aggravated hypertension, hypotension, myocardial infarction, palpitation, phlebitis, postural hypotension, purpura, tachycardia, thrombophlebitis (deep), vasculitis, vasodilatation, ventricular/supraventricular tachycardia, torsades de pointes, ventricular arrhythmia, ventricular fibrillation.
Respiratory: Airway obstruction, allergic pneumonitis, apnea, aspiration, asthma, bronchitis, bronchospasm, chronic obstructive airway disease, coughing, dyspnea, hemoptysis, hypoxia, laryngeal edema, laryngitis, pleural effusion, pleurisy, pneumonia, interstitial pneumonia, pneumothorax, pulmonary edema, pulmonary embolism, respiratory depression, respiratory disorder, respiratory insufficiency, rhinitis, upper respiratory tract infection.
Gastrointestinal (GI): Abdominal pain, hemorrhagic diarrhea which in very rare cases may be indicative of enterocolitis including CDAD and colitis; dry mouth, dysphagia, dyspepsia, esophagitis, flatulence, gastritis, gastroenteritis, gastroesophageal reflux, GI hemorrhage, glossitis, intestinal obstruction, melena, pancreatitis, stomatitis, tongue edema.
Metabolic and Nutritional Disorders: Dehydration, electrolyte abnormality, fluid overload, gout, hyperglycemia, hypoglycemia, hyperkalemia, hypernatremia, hyponatremia, hypokalemia, hypophosphatemia, hypomagnesemia, increased nonprotein nitrogen; thirst, decreased weight.
Hepatobiliary: Abnormal hepatic function, increased blood bilirubin; cholecystitis, cholelithiasis, 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, hematoma, leukopenia, leukocytosis, lymphadenopathy, pancytopenia, decreased prothrombin; prolonged International Normalized Ratio (INR); prolonged prothrombin time; purpura, thrombocythemia, thrombocytopenia including thrombotic thrombocytopenic purpura; neutropenia, decreased lymphocytes.
Genitourinary: Abnormal renal function, acute renal failure, crystalluria, cylindruria, hematuria, interstitial nephritis, increased blood creatinine; glomerulonephritis, nephrosis, oliguria, urinary incontinence, urinary retention, urinary tract infection, acute tubular necrosis, dysmenorrhea, leukorrhea, genital moniliasis, vaginitis.
Musculoskeletal and Connective Tissue Disorders: Arthralgia, arthritis, arthrosis, increased muscle enzymes; myalgia, myositis, muscle injury (including rupture), osteomyelitis, rhabdomyolysis (including fatal cases), skeletal pain, synovitis, tendinitis/tendinopathy /tendon disorder, tendon rupture.
Special Senses: Abnormal vision/visual disturbance including diplopia, reduced visual acuity, blurred vision; conjunctivitis, eye pain, scotomata; earache, ear disorder, hearing impairment/hypoacusis, tinnitus; anosmia, parosmia; ageusia, dysgeusia.
Other Adverse Effects: Abscess, bacterial infection, condition aggravated, carcinoma, fungal infection/moniliasis, herpes simplex, attacks of porphyria in patients with porphyria; otitis media, infection/superinfection, sepsis.
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.

 

See Table 5.

Interference with Laboratory Tests: Some fluoroquinolones, including levofloxacin, may give false-positive urine screening results for opiates using commercially available immunoassay kits. Confirmation of positive opiate screen by more specific methods may be necessary.
Levofloxacin may inhibit the growth of Mycobacterium tuberculosis, and therefore, may give false-negative results in the bacteriological diagnosis of tuberculosis.

Storage

Action

Quinolones