Cravit IV

Cravit IV

levofloxacin

Manufacturer:

Daiichi Sankyo

Distributor:

Ouiheng International Healthcare
Full Prescribing Info
Contents
Levofloxacin.
Description
Each 50 mL, 100 mL and 150 mL. bottle of Cravit i.v. solution for infusion contains 250 mg 500 mg and 750 mg of levofloxacin (5 mg/mL) as active ingredient.
Chemical name: (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4 methyl-1 piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate.
Molecular formula: C18H20FN3O4•½H2O
Molecular weight: 370.38
Melting point: 222-230°C (decomposition).
Light yellowish white to yellowish white crystals or crystalline powder, odorless and bitter taste. Freely soluble in glacial acetic acid, sparingly soluble in water and methanol, slightly soluble in ethanol, and practically insoluble in ether. Light sensitive.
Excipients/Inactive Ingredients: Sodium chloride; sodium hydroxide; hydrochloric acid (q.s. pH 4.8) and water for injection for a volume of 50 mL, 100 mL and 150 mL. The appearance of Cravit i.v. may range from a clear yellow to a greenish-yellow solution.
Action
Pharmacology: Cravit i.v. is a broad spectrum antibacterial agent for intravenous administration containing levofloxacin, optically active (-)-S-form of racemate ofloxacin synthesized by Daiichi Sankyo Co., Ltd. Cravit shows broad and potent antibacterial activities against gram-positive bacteria such as, Staphylococcus aureus, Staphylococcus saprophyticus, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes, Enterococcus faecalis and gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, Enterobacter cloacae, Moraxella catarrhalis, Legionella pneumophila and other microorganisms such as Chlamydia pneumoniae and Mycoplasma pneumoniae. Cravit, which is transferred rapidly to each tissue in high concentrations without being accumulated there, is mostly excreted in the urine as unchanged form. Cravit shows clinical efficacy on respiratory tract infections, genitourinary tract infections and skin and skin structure infections. The data demonstrate that from pH 0.6 to 5.8, the solubility of Cravit is essentially constant (approximately 100 mg/mL). Cravit is considered soluble to freely soluble in this pH range. Above pH 5.8, the solubility increase rapidly to its maximum at pH 6.7 (272 mg/mL) and is considered freely soluble in this range. Above pH 6.7, the solubility decreases and reaches a minimum value (about 50 mg/mL) at a pH of approximately 6.9. Cravit has the potential to form stable coordinated compounds with many metal ions. This in vitro chelating potential has the following formation order: Al+3>Cu+2>Zn+2>Mg+2>Ca+2.
Pharmacokinetics: Absorption and serum concentration: Following a single 60 minutes and 90 minutes intravenous infusion of 500 mg and 750 mg of levofloxacin to healthy volunteers, the mean peak plasma concentration attained were 6.2 μg/mL and 11.5 μg/mL respectively. Levofloxacin pharmacokinetics is linear and predictable after single and multiple i.v. dosing regimens. Steady-state conditions are reached within 48 hours following a 500 mg or 750 mg once daily regimen. The peak and trough plasma concentrations attained following multiple once daily i.v. 500 mg regimens were approximately 6.4 and 0.6 μg/mL and 12.1 and 1.3 μg/mL after the 750 mg doses, respectively.
The plasma concentration profile of levofloxacin after i.v. administration is similar and comparable in extent of exposure (AUC) to that observed for levofloxacin tablets when equal doses (mg/mg) are administered. Therefore, the oral and i.v. routes of administration can be considered interchangeable.
Distribution: The mean volume of distribution of levofloxacin 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 into blister fluid is rapid and extensive. The blister fluid to plasma AUC ratio is approximately 1. Levofloxacin also penetrates well into lung tissues. Lung tissue concentrations were generally 2 to 5 fold higher than the plasma concentrations and ranged from approximately 2.4 to 11.3 μg/g over a 24 hour period after the single 500 mg oral dose.
In vitro, over the clinically relevant range (1 to 10 μg/mL) of serum/plasma levofloxacin concentrations, levofloxacin is approximately 24 to 38% bound to serum proteins across all species studied, as determined by the equilibrium dialysis method. Levofloxacin is mainly bound to serum albumin in humans. Levofloxacin binding to serum proteins is independent of the drug concentration.
Metabolism: Levofloxacin is stereochemically stable in plasma and urine and does not invert metabolically to its enantiomer, D-ofloxacin. Levofloxacin undergoes limited metabolism in humans and is primarily excreted as unchanged drug in the urine. Following oral administration, approximately 87% of an administered dose was recovered as unchanged drug in urine within 48 hours, whereas less than 4% of the dose was recovered in the feces in 72 hours. Less than 5% of an administered dose was recovered in the urine as the desmethyl and N-oxide metabolites, the only metabolites identified in humans. These metabolites have little relevant pharmacological activity.
Excretion: Levofloxacin is excreted largely as unchanged drug in the urine. The mean terminal plasma elimination half-life of levofloxacin ranges from approximately 6 to 8 hours following single or multiple doses of levofloxacin given orally or intravenously. 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. Concomitant administration of either cimetidine or probenecid results in approximately 24% and 35% reduction in the levofloxacin renal clearance, respectively, indicating that secretion of levofloxacin occurs in the renal proximal tubule. No levofloxacin crystals were found in any of the urine samples freshly collected from subjects receiving levofloxacin.
Microbiology: Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. It is two folds stronger than that of ofloxacin. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involve inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination. Levofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Levofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.
Fluoroquinolones, including levofloxacin, differ in chemical structure and mode of action from aminoglycosides, macrolides and β-lactam antibiotics, including penicillins. Fluoroquinolones may, therefore, be active against bacteria resistant to these antimicrobials.
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.
Levofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in Indications:
Aerobic gram-positive microorganisms: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus saprophyticus, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes.
Aerobic gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa.
Other microorganisms: Chlamydia pneumoniae, Mycoplasma pneumoniae.
The following in vitro data are available, but their clinical significance is unknown.
Aerobic gram-positive microorganisms: Staphylococcus epidermidis, Streptococcus (Group C/F), Streptococcus (Group G), Streptococcus agalactiae, Streptococcus milleri and Viridans group streptococci.
Aerobic gram-negative microorganisms: Acinetobacter anitratus, Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter lwoffii, Bordetella pertussis, Citrobacter diversus, Citrobacter freundii, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter sakazakii, Klebsiella oxytoca, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas fluorescens, Serratia marcescens.
Anaerobic gram-positive microorganisms: Clostridium perfringens.
Indications/Uses
Cravit i.v. is indicated for the treatment of adults (≥16 years of age) with mild, moderate and severe infections caused by susceptible strains of the designated microorganisms in the conditions listed as follows, when intravenous administration offers a route of administartion advantageous to the patient (e.g. patient cannot tolerate an oral dosage form). Please see DOSAGE & ADMINISTRATION for specific recommendations: Community-acquired pneumonia due to Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila or Mycoplasma pneumoniae.
Nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with and anti-pseudomonal-β-lactam is recommended.
Uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to Staphylococcus aureus and Streptococcus pyogenes.
Complicated skin and skin structure infections due to methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes or Proteus mirabilis.
Urinary tract infections (mild to moderate) due to Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa or Staphylococcus saprophyticus.
Pyelonephritis (mild to moderate) caused by Escherichia coli.
Dosage/Direction for Use
Cravit i.v. should only be administered by intravenous infusion. It is not for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration. The dosage depends on the type and severity of the infection and the sensitivity of the presumed causative pathogen. The duration of therapy varies according to the course of the disease. As with antibiotic therapy in general, administration of Cravit i.v. 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 intravenous treatment to the oral route after a few days.
The usual dose is 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 as described in the following dosing chart. (See Tables 1 and 2.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

 When only the serum creatinine is known, the following formula may be used to estimate creatinine clearance. (See Equation.)

Click on icon to see table/diagram/image

The serum creatinine should represent a steady state of renal function.
PRECAUTION ASSOCIATED WITH DOSAGE AND ADMINISTRATION: General: As a general rule, the duration of administration of this drug should be limited to the minimum period required for the treatment of the patient's condition, after susceptibility of the causative bacteria to this drug has been confirmed, in order to prevent emergence of drug resistant-bacteria.
Special population: Careful administration should be considered in the following patients group: Patients with impaired liver function: No adjustment of dosage is required since levofloxacin is not metabolized to any relevant extent by liver and is mainly excreted by kidney.
Patients with impaired renal function: Blood concentrations of leveofloxacin are sustained in patients with renal dysfunction. It is advisable, therefore, that the dose be reduced and the dosing interval lengthened is required (see Patients with impaired renal function in previous text).
Pediatric patients: As the safety and effectiveness of levofloxacin in low birth weight infants, new born infants, infants or children and adolescents below the age of 16 years has not been established, levofloxacin should not be administrated in pediatric patients. In animal studies, arthropathy was noted [in juvenile dogs, young adult dogs (13-month-old), and juvenile rats].
Geriatric patients: The pharmacokinetic properties of levofloxacin 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, care should be taken in dose selection, and it may be useful to monitor renal function.
For compatibility and incompatibility with other infusion solution see Cautions for Usage.
Overdosage
According to toxicity studies in animals, the most important signs to be expected following acute overdosage of Cravit i.v. solution for infusion are central nervous system symptoms such as confusion, dizziness, impairment of consciousness, and convulsive seizures, as well as gastrointestinal reactions such as nausea and mucosal erosions.
In the event of an acute overdosage, the stomach should be emptied. Antacid may be used for protection of gastric mucosa. No specific antidote exists. The patient should be observed and appropriate hydration maintained. Levofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis.
Contraindications
Levofloxacin is contraindicated in the following patients: Patients with a history of hypersensitivity to levofloxacin, ofloxacin or any excipients of this product; Patients with epilepsy; Patients with history of tendon disorder related to fluoroquinolones administration; Children or adolescents below the age of 16 years; Pregnant women or women suspected of being pregnant; Breast-feeding women.
Special Precautions
Cravit i.v. should be administered with caution in the following patients: Patients with severe renal impairment: Levofloxacin is excreted mainly by the kidneys and persistence of high serum level in patients with renal impairment has been reported.
Patients with known or suspected CNS disorder such as epilepsy or with a history of convulsive diseases that may predispose to seizures or lower the seizure threshold, convulsion may occur.
Diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (especially, sulfonylureas) or with insulin preparations.
Patients with history of hypersensitivity to quinolone antibiotics.
Patients with serious heart diseases (e.g. arrhythmia and ischemic heart disease), patients with uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesemia) and patients receiving Class IA and III antiarrythmic agents. QT prolongation may occur. (See SERIOUS ADVERSE REACTIONS under ADVERSE REACTIONS and INTERACTIONS).
Patient with myasthenia gravis: Levofloxacin may cause exacerbation of myasthenia gravis symptom.
Rapid or bolus intravenous injection may result in hypotension. Cravit i.v. should only be administered by slow intravenous infusion over a period of 60 minutes or 90 minutes.
Levofloxacin is more soluble than other quinolones; adequate hydration of patients receiving levofloxacin should be maintained to prevent the formation of highly concentrated urine.
Levofloxacin may inhibit the growth of Mycobacterium tuberculosis, and therefore, may give false-negative results in the bacteriological diagnosis of tuberculosis.
Some undesirable effects (see ADVERSE REACTIONS) may impair the patient's ability to concentration and react, and therefore may constitute a risk in situation where these abilities are of special importance (e.g. driving a car or operating machinery).
Excessive exposure to sunlight should be avoided. However, phototoxicity has been observed very rare: incidence < 0.01%. Therapy should be discontinued if phototoxicity (e.g. a skin eruption) occurs.
Patients complicated with aortic aneurysm or aortic dissection, or patients who have a previous history, positive family history, or risk factors (Marfan syndrome, etc.) of aortic aneurysm or aortic dissection [The increased risk of aortic aneurysm and dissection after intake of fluoroquinolones have been reported in overseas epidemiologic studies (see SERIOUS ADVERSE REACTIONS under ADVERSE REACTIONS)].
Aortic aneurysm or aortic dissection may occur; there-fore, patients should be carefully observed and instructed to seek medical attention immediately if they experience symptoms, e.g. in case of pain in the abdomen, chest, or back. Imaging assessment should be considered if necessary, for patients complicated with aortic aneurysm or aortic dissection, or patients who have a previous history, positive family history, or risk factors of aortic aneurysm or aortic dissection (see Serious Adverse Reactions under Adverse Reactions).
Use in Elderly: Since renal function is generally depressed in geriatric patients and levofloxacin is excreted mainly by the kidneys, levofloxacin should be used with caution in this population. (See Geriatric patients under Dosage & Administration).
Effect on ability to drive and use machine: Neurologic adverse effects such as dizziness/vertigo and somnolence may occur. Therefore, patients should be instructed that such neurologic adverse effects may impair the patient's ability to concentrate and react, and therefore may constitute a risk in situation where these abilities are of special importance (e.g. activities at high place, driving a car or operating machinery).
Use In Pregnancy & Lactation
Use during pregnancy: Levofloxacin must not be used in pregnant women or women suspected of being pregnant since the safety of the product in pregnant women has not been established (see CONTRAINDICATIONS).
Use during lactation: Since ofloxacin is known to be excreted in breast milk, nursing mothers should be guided to avoid the breast-feeding during treatment with levofloxacin (see CONTRAINDICATIONS).
Adverse Reactions
The following adverse reactions have been reported in clinical studies and post marketing experience. The incidence identified below reflects exposure to 500 mg tablet of levofloxacin in total of 1,930 patients in pooled Phase 3 and Phase 4 clinical trials (e.g., 1,582 patients from Phase 3 clinical trials conducted in Japan (337 patients) and China (1,245 patients) and 348 patients from Phase 4 clinical trials) or 29,880 patients in a post marketing studies conducted in Japan. If the incidence category of an adverse reaction is different between each source (i.e., the incidence from the pooled clinical trials and the incidence from the post marketing study), the higher frequency is represented.
The following CIOMS frequency rating is used: Very common: 10% ≤ incidence; Common: 1% ≤ incidence < 10%; Uncommon: 0.1% ≤ incidence < 1%; Rare: 0.01% ≤ incidence < 0.1%; Very rare: incidence <0.01%.
*: see SERIOUS ADVERSE REACTIONS in the following text, each incidence is based on serious reactions.
Blood and lymphatic system disorders: Common: anemia.
Very rare: thrombocytopenia*.
Incidence unknown: pancytopenia*, agranulocytosis*, hemolytic anemia with hemoglobinuria*.
Immune system disorder: Incidence unknown: anaphylactoid reaction*.
Metabolism and nutrition disorder: Uncommon: anorexia.
Incidence unknown: hypoglycemia (hypoglycemic coma may occur)*, hyperglycemia*.
Psychiatric disorders: Common: sleep loss.
Rare: hallucination.
Incidence unknown: psychiatric symptoms such as confusion*, delirium*, depression*.
Nervous system disorders: Common: dizziness /vertigo, headache.
Uncommon: somnolence, numbness, tremor, mental dullness, dysgeusia.
Rare: consciousness disturbed.
Very rare: convulsion*, ageusia.
Incidence unknown: peripheral nerve disorder, extrapyramidal disorder, anosmia, parosmia.
Eye disorders: Rare: abnormal vision.
Ear and labyrinth disorders: Uncommon: tinnitus.
Incidence unknown: hearing losses.
Cardiac disorders: Uncommon: palpitations.
Incidence unknown: ventricular tachycardia (including Torsades de pointes)*, QT prolonged*, tachycardia.
Vascular disorders: Very rare: shock*.
Incidence unknown: hypotension.
Respiratory, thoracic and mediastinal disorders: Uncommon: dry throat.
Incidence unknown: interstitial pneumonia*, eosinophilic pneumonia*.
Gastrointestinal disorders: Common: nausea, vomiting, diarrhea, abdominal discomfort, constipation.
Uncommon: abdominal pain, dyspepsia, abdominal distension, constipation.
Rare: stomatitis.
Very rare: glossitis.
Incidence unknown: colitis with bloody stool, such as pseudomembranous colitis*.
Hepatobiliary disorders: Uncommon: hepatic function abnormal (severe hepatic function disorder* may rarely occur).
Incidence unknown: hepatitis fulminant*, jaundice*.
Skin and subcutaneous tissue disorders: Uncommon: pruritus, rash.
Rare: hyperhidrosis, urticaria.
Very rare: photosensitivity.
Incidence unknown: toxic epidermal necrolysis (TEN)*, oculomucocutaneous syndrome (Stevens-Johnson syndrome) *, hypersensitivity vasculitis*.
Musculoskeletal and connective tissue disorders: Uncommon: arthralgia, pain in extremity, back pain, weakness.
Rare: arthropathy, myalgia.
Incidence unknown: rhabdomyolysis*, tendon disorders such as Achilles tendonitis or tendon rupture*, exacerbation of myasthenia gravis *, muscle rupture.
Renal and urinary disorders: Uncommon: hematuria, urinary retention.
Rare: pollakiuria, oliguria, acute renal failure*.
Incidence unknown: interstitial nephritis*, anuria, dysuria.
General disorders and administration site conditions: Very common#: infusion site reaction (erythema, pruritus, swelling, pain, induration, warmth, discomfort, phlebitis, vasculitis, angiopathy, puncture site pain).
#: The incidence of the relevant event is based on data from Japan clinical studies in 586 patients intravenously treated with levofloxacin.
Uncommon: thirst, chest discomfort, malaise, feeling hot, edema.
Very rare: #pyrexia.
Incidence unknown: chest pain.
Investigations: Common: AST increased, ALT increased, LDH increased, white blood cell count decreased, eosinophil count increased.
Uncommon: creatinine increased, urinary protein positive, alkaline phosphatase increased, γ-GTP increased, blood bilirubin increased, lymphocyte count decreased, neutrophil count decreased, CPK increased, glucose urine present, blood glucose decreased, platelet count decreased.
Rare: BUN increased, urine output decreased.
Very rare: blood glucose increased.
The events of which frequency category observed in Japanese clinical studies in 586 patients and post-marketing study in 1138 patients intravenously treated with levofloxacin is higher than the rating shown in this section is listed as follows.
Psychiatric disorders:
Uncommon: hallucination.
Respiratory, thoracic and mediastinal disorders: Uncommon: interstitial pneumonia*.
Gastrointestinal disorders: Common: constipation; Uncommon: glossitis.
Hepatobiliary disorders: Common: hepatic function abnormal (severe hepatic function disorder* may uncommon occur).
Musculoskeletal and connective tissue disorders: Uncommon: myalgia.
General disorders and administration site conditions: Uncommon: pyrexia.
Investigations: Common: γ-GTP increased, alkaline phosphatase increased.
Serious Adverse Reaction: The following serious adverse reactions have been reported in patients receiving therapy with levofloxacin. If the following reactions are suspected, treatment with levofloxacin should be discontinued immediately and appropriate therapeutic measure should be taken: Shock or anaphylactoid reaction (initial symptoms: erythema, rigor, dyspnea, etc.).
Toxic epidermal necrolysis (TEN) or oculomucocutaneous syndrome (Stevens-Johnson syndrome).
Convulsion.
QT prolonged and ventricular tarchycardia (including Torsades de pointes): During post-marketing surveillance, prolonged QT which may sometimes lead to the occurrence of ventricular tachycardia including torsades de pointes have been reported spontaneously in patients taking levofloxacin. The risk of the events may be increased in patients with serious heart diseases (e.g. arrhythmia and ischemic heart disease), patients with uncorrected hypokalemia, patients receiving Class IA (quinidine sulfate, procainamide hydrochloride) and Class III (amiodarone hydrochloride, sotalol hydrochloride) antiarrhythmic agents and in geriatric patients.
Acute renal failure or interstitial nephritis.
Hepatitis fulminant, hepatic function disorder or jaundice (initial symptoms: nausea, vomiting, anorexia, malaise, pruritus, etc.)
Pancytopenia, agranulocytosis (initial symptoms: pyrexia, pharynx pain, malaise, etc.), hemolytic anemia with hemoglobinuria or thrombocytopenia;
Interstitial pneumonia or eosinophilic pneumonia accompanied with pyrexia, cough, dyspnea, abnormal chest X-ray, or eosinophilia, etc.
Serious colitis with bloody stool, such as pseudomembranous colitis: If such symptoms as abdominal pain and frequent diarrhea are noted, treatment with levofloxacin should be discontinued immediately and appropriate therapeutic measures taken.
Rhabdomyolysis characterized by myalgia, weakness, elevated CK (CPK) and increased myoglobin in plasma and urine, etc., and accompanied with acute exacerbation of renal function.
Dysglycemia: During post-marketing surveillance, hypoglycemia and hyperglycemia have been reported in patients taking levofloxacin. Serious symptoms such as hypoglycemic coma have been reported in patients receiving levofloxacin. Hypoglycemia may be prone to develop in patients with diabetes mellitus (especially, those receiving sulfonylureas or insulin preparations), patients with impaired renal function and geriatric patients.
Tendon disorders such as Achilles tendonitis or tendon rupture: If symptoms such as pain and edema in the peritendinous region are observed, treatment with levofloxacin should be discontinued immediately and appropriate therapeutic measures taken. The risk of tendonitis and tendon rupture is increased in those over age 60, in those on concomitant corticosteroid therapy, and transplant recipients.
Psychiatric symptoms such as confusion, delirium and depression.
Hypersensitivity vasculitis: If symptoms such as pyrexia, abdominal pain, arthralgia, purpura or maculopapules, and skin biopsy evidence of leukocytoclastic vasculitis are observed, treatment with levofloxacin should be discontinued immediately and appropriate therapeutic measures taken.
Exacerbation of myasthenia gravis.
Aortic aneurysm, aortic dissection (incidence unknown): Aortic aneurysm or aortic dissection may occur. If any abnormalities are observed, appropriate medical treatment should be taken. (see Precautions).
Drug Interactions
Antacids, Sucralfate, Metal Cations and Multivitamins: There are no data concerning an interaction of intravenous quinolones with oral antacid, sucralfate, multivitamins, or metal cation. However, no quinolones should be co-administered with any solution containing multivitamin cation, e.g. magnesium, through the same intravenous line.
Theophylline, Fenbufen, or similar non-steroidal anti-inflammatory drugs (phenylacetic acid/propionic acid derivatives): No pharmacokinetic interactions of levofloxacin were found with theophylline in a clinical study. However, there are indications of a pronounced lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs that lower seizure threshold (e.g. theophylline) or with fenbufen or similar non-steroidal anti-inflammatory drugs.
Antidiabetic 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.
Anticoagulant drug (warfarin and its derivatives): Coadministration of warfarin and its derivatives has been reported that the effect of warfarin was potentiated (hepatic metabolism of warfain may be inhibited, or free warfarin may be increased by competitive displacement from the protein-binding site) and therefore prothrombin time prolonged.
Class IA antiarrythmics and Class III antiarrythmics: Levofloxacin should be used with caution in patients receiving drug known to cause QT prolonged, Class IA antiarrythmics (e.g. quinidine sulfate and procainamide hydrochloride), Class III antiarrythmics (e.g. amiodarone hydrochloride and sotalol hydrochloride) QT prolongation may occur.
Caution For Usage
Incompatibility: Cravit i.v. solution for infusion should not be mixed with heparin or alkaline solution (e.g. sodium hydrogen carbonate).
Compatibility: Cravit i.v. solution for infusion is compatible with the following solution for infusion: 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 2.5% Dextrose in Ringer Solution.
Combination solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).
Storage
Protect from light.
Store below 30°C.
Shelf-Life: Shelf-life after removal of the outer packaging: 3 days.
Shelf-life after perforation of the rubber stopper: 3 hours.
MIMS Class
ATC Classification
J01MA12 - levofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.
Presentation/Packing
Infusion (vial) (clear, ready for use solution) 250 mg/50 mL x 1's. 500 mg/100 mL x 1's. 750 mg/150 mL x 1's.
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