Prosweal Healthcare


Prosweal Healthcare
Full Prescribing Info
Levofloxacin hemihydrate.
Film-coated tablet: Each film coated tablet contains: Levofloxacin Hemihydrate equivalent to Levofloxacin 500 mg.
Solution for infusion: Each mL contains: Levofloxacin (as hemihydrate) 5 mg.
Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone class and is the S (-) enantiomer of the racemic drug substance ofloxacin.
Pharmacology: Levofloxacin, a fluoroquinolone, is the optical S-(-) isomer of ofloxacin. It has a wide-spectrum of antibacterial effect. Levofloxacin is active against gram-positive and gram-negative bacterial including anaerobes.
Moreover, levofloxacin has shown antibacterial activity against Chlamydia pneumonia and Mycoplasma pneumonia. Levofloxacin is often bactericidal concentrations equal to or slightly greater than the inhibitory concentration. The main mechanism of action of levofloxacin is through the inhibition of DNA replication and transcription. Levofloxacin is rapidly and essentially completely absorbed after administration. Peak plasma concentrations are usually attained one to two hours after dosing. The absolute bioavailability of a 500 mg dose of levofloxacin is approximately 99%. The peak and trough plasma concentrations attained following multiple once daily 500 mg regimens were approximately 5.7 and 0.5 mg/mL respectively. Levofloxacin is widely distributed throughout the body in high concentrations, generally 2 to 5 fold higher than plasma concentrations and ranged from approximately 2.4 to 11.3 mg/g over a 24 hours period after a single 500 mg dose. Clearance of levofloxacin is reduced and plasma elimination half-life is prolonged in patients with impaired renal function (creatinine clearance <80 mL/min), requiring dosage adjustment in such patients to avoid accumulation. The majority of the drug is not metabolized in the body. About 85% of the administered dose is excreted in urine as an unchanged form.
Pharmacokinetics: Solution for infusion: Levofloxacin is rapidly and completely absorbed following administration with peak plasma concentrations achieved within an hour of dose. It is distributed into body tissues including the bronchial mucosa and lungs. But penetration into CSF is relatively poor. Levofloxacin is approximately 30-40% bound to plasma proteins. It is only metabolized to a small degree to inactive metabolites. The elimination half-life of Levofloxacin is 6-8 hours, although this may be prolonged in patients with renal impairment. Levofloxacin is excreted largely unchanged, primarily in the urine.
Film-coated tablet: Levofloxacin is indicated in infections with susceptible microorganism, such as acute maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis, community acquired pneumonia, uncomplicated skin and skin structure infections, complicated urinary tract infections.
Solution for infusion: Levofloxacin is indicated in infections with susceptible microorganism, such as community acquired pneumonia, complicated urinary tract infections and skin and soft tissue infections.
Dosage/Direction for Use
Patients with impaired renal function: Creatinine clearance of 50 to 80 mL/min: no dosage adjustment required.
Creatinine clearance of 20 to 49 mL/min: Initial dose 500 mg, subsequent dose 250 mg every 24 hours.
Creatinine clearance of 10 to 19 mL/min, hemodialysis and chronic ambulatory peritoneal dialysis: initial dose 500 mg, subsequent dose 250 mg every 48 hours.
Film-coated tablet: Usual dose in patients with normal renal function: 250 mg-500 mg orally once daily for 7-14 days depending on the severity of the disease.
Solution for infusion: IV infusions of Levofloxacin should be infused slowly, Levofloxacin doses of 250 or 500 mg should be administrated over a period of 60 minutes. Levofloxacin doses of 750 mg should be administrated over a period of 90 minutes. Because of the risk of hypotension, more rapid or bolus IV infusion should be avoided. Levofloxacin solutions should be inspected visually for particulate matter prior to administration or as prescribed by a physician.
Because only limited information is available on the physical and/or chemical compatibility of Levofloxacin and other drugs, Levofloxacin should not be admixed with other drugs or infused simultaneously through the same tubing with other drugs. Fluoroquinolones, including Levofloxacin should not infused through the same tubing with any solution containing multivalent cations (e.g. Magnesium). If the same administration set is used for sequential infusion of several different drugs, the tubing should be flushed before and after administration of Levofloxacin with an IV solution that is compatible with both Levofloxacin and the other drug(s).
When Levofloxacin therapy is initiated using IV Levofloxacin, therapy may be changed when appropriate to oral Levofloxacin given in the same dosage to complete the course of therapy. The timing of the change form IV to oral therapy should be individualized, taking into account the clinical status of the patient.
Dosage of Levofloxacin does not need to be modified in geriatric patients based on age alone. However, the dosage of Levofloxacin for geriatric patients should be selected carefully because renal function is more likely to be decreased in these patients, such that monitoring renal function may be useful.
Solution for infusion: According to toxicity studies in animals or clinical pharmacology studies performed with supra-therapeutic doses, the most important signs to be expected following acute overdose of Levofloxacin solution for infusion are central nervous system symptoms such as confusion, dizziness, impairment of consciousness, and convulsive seizures, increases in QT interval.
CNS effects including confusional state, convulsion, hallucination, and tremor have been observed in post marketing experience.
In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Haemodialysis, including peritoneal dialysis and CAPD, are not effective in removing levofloxacin from the body. No specific antidote exists.
Hypersensitivity to antimicrobial agents or to any other components of this product.
The safety and efficacy of levofloxacin in children, adolescents (under the age of the 18 years), pregnant women and nursing women have not been established.
In immature rats and dogs, the oral and intravenous administrations of levofloxacin increased the incidence and severity of osteochondrosis. Other fluoroquinolones also produce similar erosions in the weight hearing joints and other signs of arthropathy in immature animals of various species.
Convulsions and toxic psychoses have been reported in patients receiving quinolones, including levofloxacin. Quinolones may also cause increased intracranial pressure and central nervous system stimulation which may lead to tremors, restlessness, anxiety, lightheadness, 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 patient receiving levofloxacin, the drug should be used with caution in patients with a known or suspected CNS disorder that may predispose to seizure threshold (e.g. severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold (e.g. certain drug therapy, renal dysfunction).
Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with quinolones. These reactions often occur following the first dose. Some reactions have accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioderm (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. Levofloxacin should 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.
Serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones. 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-Johnsons Syndrome); vasculitis, myalgia, serum sickness, allergic pneumonitis, interstitial nephritis, acute renal insufficiency or failure, hepatitis, jaundice, acute hepatic necrosis or failure, anemia including purpura, leukopenia, agranulocytosis, pancytopenia, and/or other hematologic abnormalities. The dug should be discontinued immediately at first appearance of a risk rash or any other sign of hypersensitivity and supportive measure instituted.
Pseudomembranous colitis has been reported with nearly all bacterial agents, including levofloxacin and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administrations of any bacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicated that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis".
After the diagnosis of pseudomembranous colitis has been established, therapeutic measure should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, considerations should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.
Ruptures of the shoulder, hand and achilles tendons that require surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones. Levofloxacin should be discontinued if patients experience pain, inflammation or rupture of a tendon. Patients should rest and refrain from exercise until diagnosis of tendinitis or tendon rupture has been confidently excluded. Tendon rupture can occur during or after therapy with quinolones, including levofloxacin.
Special Precautions
General: Although levofloxacin is more soluble than other quinolones, adequate hydration of patient receiving levofloxacin should be maintained to prevent the formation of a highly concentrated urine.
Administer levofloxacin with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced. In patients with impaired renal function (creatinine clearance <80 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance.
Moderate to severe phototoxicity reaction have been observed in patients exposed to direct sunlight while receiving drugs in this class. Excessive exposure of sunlight should be avoided. However, in clinical trials with levofloxacin, phototoxicity has been observed in less than 0.1% of patients. Therapy should be discontinued if phototoxicity (e.g. skin eruption) occurs.
As with other quinolones, levofloxacin should be used with caution in any patients with a known of or suspected CNS disorder that may predispose to seizures or lower the seizure threshold (e.g. severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold (e.g. certain drug therapy, renal dysfunction).
As with other quinolones, disturbance of blood glucose, including symptomatic hyperglycemia and hypoglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g. glyburide/glybenclamide) 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 immediately and appropriate therapy should be initiated immediately.
As with any potent antimicrobial drug, periodic assessment of organ system functions including renal, hepatic and hematopoietic is advisable therapy.
Use In Pregnancy & Lactation
Solution for infusion: Do not have this medicine if: The patient is pregnant, might become pregnant or thinks the patient may be pregnant.
The patient is breast-feeding or planning to breast-feed.
Adverse Reactions
The incidence of drug-related adverse reactions in patients phase 2 and 3 clinical trials conducted in North America was 6.2%. Among patients receiving multiple-dose therapy 3.7% discontinued therapy with levofloxacin due to adverse experience. In clinical trials, the following events were considered likely to be drug-related in patients receiving multiple doses of levofloxacin; diarrhea 1.2%, nausea 1.2%, vaginitis 0.8%, flatulence 0.5%, pruritis 0.5%, rash 0.3%, abdominal pain 0.3%, insomnia 0.3%, taste perversion 0.2%, vomiting 0.2% , anorexia 0.1%, anxiety 0.1%, constipation 0.1%, edema 0.1%, fatigue 0.1%, headache 0.1%, increased sweating 0.1%, leukorrhea 0.1%, malaise 0.1%, nervousness 0.1%, sleep disorders 0.1%, tremor 0.1%, urticaria 0.1%. In clinical trials, the most frequently reported adverse events occurring in >3% of the study population regardless of drug relationship were: nausea 6.6%, diarrhea 5.4%, headache 5.4%, constipation 3.1%. In clinical trials, the following events occurred in 1 to 3 patients regardless of drug relationship: insomnia 2.9%, dizziness 2.5%, vomiting 2.1%, abdominal pain 2.0%, dyspepsia 2.0%, rash 1.7%, vaginitis 1.8%, flatulence 1.6%, pruritis 1.6%, pain 1.4%, chest pain 1.1%, back pain 1.0%. The following adverse events occurred in clinical trials at rate of 0.5 to less than 1% regardless of drug relationship: agitation, anorexia, anxiety, arthralgia, dry mouth, dyspnea, edema, fatigue, fever, genital pruritis, increased sweating, nervousness, pharyngitis, rhinitis, skin disorder, somnolence, taste perversion.
Additional adverse events occurring in clinical trials at a rate of 0.3 to less than 0.5% regardless of drug relationship include: cardiac failure, hypertension, leukorrhea, myocardial infarctions, myalgia, purpura, tinnitus, tremor, urticaria.
Events occurring at a frequency lower than 0.3% regardless of drug relationship but considered medically important include: abnormal coordination, abnormal dreaming, abnormal hepatic function, abnormal platelets, abnormal renal function, abnormal vision, acute renal failure, aggravated diabetes mellitus, aggressive reactions, anemia angina pectoris, ARDS, arrhythmia, arthritis, asthma, bradycardia, cardiac arrest, cerebrovascular disorder, circulatory failure, coma, confusion, convulsions (seizures), coronary thrombosis, delirium, depression, diplopia, embolism blood clot, emotional lability, erythema nodosum, G.I. hemorrhage, granulocytopenia, hallucination, heart block, hepatic coma, hypoglycemia, hypotension, impaired concentration, increase LDH, jaundice, leukocytosis, leukopenia, lymphadenopathy, manic reactions, mental deficiency, muscle weakness, pancreatitis, paralysis, paranoia, postural hypertension, pseudomembranous colitis, rhabdomyolysis, sleep disorder, stupor, syncope, tachycardia, tendinitis, thrombocytopenia, vertigo, weight decrease, WBC abnormal not otherwise specified. In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctuate lenticular opacities, have been noted in patients undergoing treatment with other quinolones. The relationship of the drugs to these events is not presently established. Crystalluria and cylindruria have been reported with other quinolones. The following laboratory abnormalities appeared in 1.9% of patients receiving multiple doses of levofloxacin. It is not known whether these abnormalities were caused by the drug or the underlying condition being treated. Blood chemistry: decreased glucose, lymphocytes.
Post-Marketing Adverse Reactions: Additional serious adverse reactions reported from the marketing experience of levofloxacin outside of the United States regardless of drug relationship include: allergic pneumonitis, anaphylactic shock, anaphylactoid reaction, dysphonia, abnormal EEG, encephalopathy, eosinophilia, erythema multiforme, hemolytic anemia, multi-system organ failure, palpitation, paresthesia, Stevens-Johnsons Syndrome, tendon rupture, vasodilation.
Drug Interactions
Levofloxacin has potential to form stable coordination compounds with metal ions. This in vitro chelation potential has following formation with Al+3 > Cu+2 > Zn+2 > Ca+2. Antacid containing aluminum or magnesium and drugs containing iron decrease absorption of levofloxacin. The administration of these drugs is recommended at least 2 hours before or after levofloxacin administration.
The concomitant administration of non-steroidal anti-inflammatory drug with quinolone, including levofloxacin, may increase the risk of CNS stimulation and convulsive seizures.
Anti-diabetic agents, disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered.
Store at temperatures not exceeding 30°C.
Film-coated tablet: Protect from direct sunlight.
Patient Counseling Information
Information for patients: Patients should be advised: To drink fluid liberally.
That levofloxacin may cause neurologic adverse effects (e.g. dizziness, lightheadedness) and that patients should be advised before they operate automobile or machinery or engage in other activities requiring mental alertness and coordination.
To discontinue treatment and inform their physician if they experience pain, inflammation or rupture of a tendon, and to rest and refrain from exercise until the diagnosis of tendinitis or tendon rupture has been confidently excluded.
That levofloxacin may be associated with hypersensitivity reactions, even following the first dose, and to discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (e.g. swelling of the lips, tongue, face tightness of the throat, hoarseness), or other symptoms of an allergic reaction.
To avoid excessive sunlight or artificial ultraviolet light while receiving levofloxacin and to discontinue therapy if phototoxicity (i.e. skin eruption) occurs.
That if they are diabetic and are being treated with insulin or a hypoglycemic reaction occurs, they should discontinue levofloxacin and consult a physician.
Film-coated tablet: That antacids containing magnesium or aluminum as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc should be taken at least two hours before or two hours after levofloxacin administration.
MIMS Class
ATC Classification
J01MA12 - levofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.
FC tab 500 mg x 10's, 60's. Soln for infusion (vial) 5 mg/mL x 100 mL.
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