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Cravit IV Solution for Infusion 5mg/ml
Antibacterial spectrumThe prevalence of resistance may vary geographically and with time for selected species andlocal information on resistance is desirable, particularly when treating severe infections. As 1 NAME OF THE MEDICINAL PRODUCT
Increased coagulation tests (PT/INR) and/or bleeding, which may be severe, have been reported in necessary, expert advice should be sought when the local prevalence of resistance is such that the patients treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin). utility of the agent in at least some types of infections is questionable 2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Coagulation tests, therefore, should be monitored in patients treated with vitamin K antagonists Commonly susceptible species
250 mg of levofloxacin in a 50 ml glass bottle Aerobic Gram-positive bacteria
500 mg of levofloxacin in a 100 ml glass bottle Drugs known to prolong QT interval
Staphylococcus aureus* methicillin-susceptible One ml of solution for infusion contains 5 mg of levofloxacin Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs Staphylococcus saprophyticus Streptococci, group C and G For a full list of excipients, see section 6.1 known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, Streptococcus agalactiae Streptococcus pneumoniae * 3 PHARMACEUTICAL FORM
macrolides). (See section 4.4 QT interval prolongation).
4.6 Pregnancy and lactation
Aerobic Gram- negative bacteria
Burkholderia cepacia$ Eikenella corrodens 4 CLINICAL PARTICULARS
Reproductive studies in animals did not raise specific concern. However in the absence of human Haemophilus influenzae * Haemophilus para-influenzae * 4.1 Therapeutic indications
data and due to the experimental risk of damage by fluoroquinolones to the weightbearing cartilage Klebsiella oxytoca Klebsiella pneumoniae * In adults for whom intravenous therapy is considered to be appropriate, Cravit solution for infusion of the growing organism, Cravit must not be used in pregnant women (see sections 4.3 and 5.3).
Moraxella catarrhalis * Pasteurella multocida is indicated for the treatment of the following infections when due to levofloxacinsusceptible Lactation
In the absence of human data and due to the experimental risk of damage by fluoroquinolones to Anaerobic bacteria
the weight-bearing cartilage of the growing organism, Cravit solution for infusion must not be used ‧Complicated urinary tract infections including pyelonephritis.
in breast-feeding women (see sections 4.3 and 5.3).
4.7 Effects on ability to drive and use machines
Chlamydophila pneumoniae* Chlamydophila psittaci Some undesirable effects (e.g. dizziness/vertigo, drowsiness, visual disturbances) may impair the Before prescribing Cravit, consideration should be given to national and/or local guidance on the patient's ability to concentrate and react, and therefore may constitute a risk in situations where appropriate use of fluoroquinolones.
these abilities are of special importance (e.g. driving a car or operating machinery).
Mycoplasma pneumoniae* Mycoplasma hominis 4.2 Posology and method of administration
4.8 Undesirable effects
Cravit solution for infusion is administered by slow intravenous infusion once or twice daily. The The information given below is based on data from clinical studies in more than 5000 patients and Species for which acquired resistance may be a problem
dosage depends on the type and severity of the infection and the sensitivity of the presumed on extensive post marketing experience.
causative pathogen. It is usually possible to switch from initial intravenous treatment to the oral The adverse reactions are described according to the MedDRA system organ class in the table Enterococcus faecalis* Staphylococcus aureus methicillin-resistant route after a few days (Cravit 250 or 500 mg tablets), according to the condition of the patient. Given the bioequivalence of the parenteral and oral forms, the same dosage can be used.
Frequencies in this table are defined using the following convention: very common (.1/10), common (.1/100, <1/10), uncommon (.1/1000, .1/100), rare (.1/10000, .1/1000), very rare Acinetobacter baumannii * Citrobacter freundii * The duration of treatment varies according to the course of the disease. As with antibiotic therapy (.1/10000), not known (cannot be estimated from the available data).
Enterobacter aerogenes Enterobacter agglomerans in general, administration of Cravit (solution for infusion or tablets) should be continued for a Within each frequency grouping, undesirable effects are presented in order of decreasing Enterobacter cloacae * Escherichia coli * minimum of 48 to 72 hours after the patient has become afebrile or evidence of bacterial Infections and infestations
Providencia stuartii Pseudomonas aeruginosa* Uncommon : Fungal infection (and proliferation of other resistant microorganisms) Cravit solution for infusion is only intended for slow intravenous infusion; it is administered once or Anaerobic bacteria
twice daily. The infusion time must be at least 30 minutes for 250 mg or 60 minutes for 500 mg Cravit solution for infusion (see section 4.4). It is possible to switch from an initial intravenous Bacteroides thetaiotamicron$ Bacteroides vulgatus$ application to the oral route at the same dosage after a few days, according to the condition of the Not Known : Pancytopenia, haemolytic anaemia * Clinical efficacy has been demonstrated for susceptible isolates in the approved clinical For incompatibilities see section 6.2 and compatibility with other infusion solutions see section 6.6.
Immune system disorders
Very rare : Anaphylactic shock (see section 4.4) The following dose recommendations can be given for Cravit: Anaphylactic and anaphylactoid reactions may sometimes occur even after the first dose
Other information
Dosage in patients with normal renal function (creatinine clearance > 50 ml/min) Not known : Hypersensitivity (see section 4.4) Nosocomial infections due to P. aeruginosa may require combination therapy.
Daily dose regimen (according to severity)
Metabolism and nutrition disorders
5.2 Pharmacokinetic properties
Very rare : Hypoglycemia, particularly in diabetic patients (see section 4.4) Orally administered levofloxacin is rapidly and almost completely absorbed with peak plasma Psychiatric disorders
concentrations being obtained within 1 h. The absolute bioavailability is approximately 100%.
Food has little effect on the absorption of levofloxacin.
Rare : Psychotic disorder, depression, confusional state, agitation, anxiety Distribution
Very rare : Psychotic reactions with self-endangering behaviour including suicidal ideation or acts Approximately 30 - 40 % of levofloxacin is bound to serum protein. 500 mg once daily multiple   Consideration should be given to increasing the dose in cases of severe infection.
dosing with levofloxacin showed negligible accumulation. There is modest but predictable Special populations
Nervous system disorders
accumulation of levofloxacin after doses of 500 mg twice daily. Steady-state is achieved within 3 Impaired renal function (creatinine clearance≦50ml/min) Uncommon : Dizziness, headache, somnolence Dose regimen
Penetration into tissues and body fluids: Very rare : sensory or sensorimotor peripheral neuropathy, dysgeusia including ageusia, parosmia Penetration into Bronchial Mucosa, Epithelial Lining Fluid (ELF) 250mg/24h
Maximum levofloxacin concentrations in bronchial mucosa and epithelial lining fluid after 500 mg po Creatinine
Eye disorders
were 8.3μ g/g and 10.8μg/ml respectively. These were reached approximately one hour after Ear and Labyrinth disorders
Maximum levofloxacin concentrations in lung tissue after 500 mg po were approximately 11.3μg/g and were reached between 4 and 6 hours after administration. The concentrations in the lungs consistently exceeded those in plasma.
Cardiac disorders
Maximum levofloxacin concentrations of about 4.0 and 6.7μg/ml in the blister fluid were reached 2 Not Known : Electrocardiogram QT prolonged (see section 4.4 QT interval prolongation and No additional doses are required after haemodialysis or continuous ambulatory peritoneal - 4 hours after administration following 3 days dosing at 500 mg once or twice daily respectively.
Penetration into Cerebro-Spinal Fluid Vascular disorders
Levofloxacin has poor penetration into cerebro-spinal fluid.
No adjustment of dosage is required since levofloxacin is not metabolised to any relevant extent by the liver and is mainly excreted by the kidneys.
After administration of oral 500mg levofloxacin once a day for three days, the mean concentrations Respiratory, thoracic and mediastinal disorders
In the elderly
in prostatic tissue were 8.7μg/g, 8.2μg/g and 2.0 μg/g respectively after 2 hours, 6 hours and 24 No adjustment of dosage is required in the elderly, other than that imposed by consideration of hours; the mean prostate/plasma concentration ratio was 1.84.
renal function (See section 4.4 QT interval prolongation).
Gastrointestinal disorders
In children
The mean urine concentrations 8 -12 hours after a single oral dose of 150 mg, 300 mg or 500mg Cravit is contraindicated in children and growing adolescents (see section 4.3).
levofloxacin were 44 mg/L, 91 mg/L and 200 mg/L, respectively.
Uncommon : Vomiting, abdominal pain, dyspepsia, flatulence, constipation Biotransformation
4.3 Contraindications
Rare : Diarrhoea aemorrhagic which in very rare cases may be indicative of enterocolitis, including Levofloxacin is metabolised to a very small extent, the metabolites being desmethyllevofloxacin and Cravit solution for infusion must not be used: levofloxacin N-oxide. These metabolites account for < 5 % of the dose excreted in urine. ‧in patients hypersensitive to levofloxacin or any other quinolone and any of the excipients, Hepatobiliary disorders
Levofloxacin is stereochemically stable and does not undergo chiral inversion.
Common : Hepatic enzyme increased (ALT/AST, alkaline phosphatase, GGT) Elimination
‧in patients with history of tendon disorders related to fluoroquinolone administration, Following oral and intravenous administration of levofloxacin, it is eliminated relatively slowly from the plasma (t : 6 - 8 h). Excretion is primarily by the renal route (> 85 % of the administered dose).
Not known: Jaundice and severe liver injury, including cases with acute liver failure, have been There are no major differences in the pharmacokinetics of levofloxacin following intravenous and reported with levofloxacin, primarily in patients with severe underlying diseases (see section 4.4).
oral administration, suggesting that the oral and intravenous routes are interchangeable.
4.4 Special warnings and precautions for use
Skin and subcutaneous tissue disorders
In the most severe cases of pneumococcal pneumonia Cravit may not be the optimal therapy.
Levofloxacin obeys linear pharmacokinetics over a range of 50 to 600 mg.
Nosocomial infections due to P. aeruginosa may require combination therapy.
Subjects with renal insufficiency
Very rare : Angioneurotic oedema, photosensitivity reaction The pharmacokinetics of levofloxacin are affected by renal impairment. With decreasing renal The recommended infusion time of at least 30 minutes for 250 mg or 60 minutes for 500mg Cravit Not Known : Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, function renal elimination and clearance are decreased, and elimination half-lives increased as solution for infusion should be observed. It is known for ofloxacin, that during infusion tachycardia and a temporary decrease in blood pressure may develop. In rare cases, as a consequence of a Mucocutaneous reactions may sometimes occur even after the first dose profound drop in blood pressure, circulatory collapse may occur.
Musculoskeletal and Connective tissue disorders
Should a conspicuous drop in blood pressure occur during infusion of levofloxacin, (l-isomer of Rare : Tendon disorder (see section 4.4) including tendinitis (e.g. Achilles tendon), arthralgia, ofloxacin) the infusion must be halted immediately.
Very rare : Tendon rupture (see section 4.4). This undesirable effect may occur within 48 hours of Tendinitis may rarely occur. It most frequently involves the Achilles tendon and may lead to tendon starting treatment and may be bilateral, muscular weakness which may be of special importance in rupture. The risk of tendinitis and tendon rupture is increased in the elderly and in patients using Elderly subjects
corticosteroids. Close monitoring of these patients is therefore necessary if they are prescribed There are no significant differences in levofloxacin pharmacokinetics between young and elderly Cravit. All patients should consult their physician if they experience symptoms of tendinitis. If Renal and urinary disorders
subjects, except those associated with differences in creatinine clearance.
tendinitis is suspected, treatment with Cravit must be halted immediately, and appropriate Gender differences
treatment (e.g. immobilisation) must be initiated for the affected tendon.
Very rare : Renal failure acute (e.g. due to nephritis interstitial) Separate analysis for male and female subjects showed small to marginal gender differences in General disorders and administration site conditions
levofloxacin pharmacokinetics. There is no evidence that these gender differences are of clinical Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with Cravit solution for infusion, may be symptomatic of Clostridium difficile-associated disease, the most 5.3 Preclinical safety data
severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, Acute toxicity
Cravit solution for infusion must be stopped immediately and patients should be treated with The median lethal dose (LD ) values obtained in mice and rats after intravenous administration of Not known : Pain (including pain in back, chest, and extremities) supportive measures ± specific therapy without delay (e.g. oral vancomycin).
levofloxacin were in the range 250-400 mg/kg; in dogs the LD value was approximately 200 mg/kg Other undesirable effects which have been associated with fluoroquinolone administration Products inhibiting the peristalsis are contraindicated in this clinical situation.
with one of two animals which received this dose dying.
Repeated dose toxicity
‧extrapyramidal symptoms and other disorders of muscular coordination, Studies of one month duration with intravenous administration have been carried out in the rat (20, Cravit solution for infusion is contraindicated in patients with a history of epilepsy and, as with other 60, 180 mg/kg/day) and monkey (10, 25, 63 mg/kg/day) and a three-month study has also been quinolones, should be used with extreme caution in patients predisposed to seizures, such as ‧attacks of porphyria in patients with porphyria.
carried in the rat (10, 30, 90 mg/kg/day).
patients with pre-existing central nervous system lesions, concomitant treatment with fenbufen and 4.9 Overdose
The "No Observed Adverse Effect Levels" (NOEL) in the rat studies were concluded to be 20 and similar non-steroidal anti-inflammatory drugs or with drugs which lower the cerebral seizure According to toxicity studies in animals or clinical pharmacology studies performed with supra- 30 mg/kg/day in the one-month and three-month studies respectively. Crystal deposits in urine were threshold, such as theophylline (see section 4.5). In case of convulsive seizures, treatment with therapeutic doses, the most important signs to be expected following acute overdosage of Cravit seen in both studies at doses of 20 mg/kg/day and above. High doses (180 mg/kg/day for 1 month levofloxacin should be discontinued.
solution for infusion are central nervous system symptoms such as confusion, dizziness, or 30 mg/kg/day and above for 3 months) slightly decreased food consumption and body weight Patients with G-6- phosphate dehydrogenase deficiency
impairment of consciousness, and convulsive seizures, increases in QT interval.
gain. Haematological examination showed reduced erythrocytes and increased leucocytes and Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should reticulocytes at the end of the 1 month, but not the 3 months study.
to haemolytic reactions when treated with quinolone antibacterial agents, and so levofloxacin be undertaken, because of the possibility of QT interval prolongation. Haemodialysis, including The NOEL in the monkey study was concluded to be 63 mg/kg/day with only minor reduction in peritoneal dialysis and CAPD, are not effective in removing levofloxacin from the body. No specific food and water consumption at this dose.
Reproductive toxicity
Since levofloxacin is excreted mainly by the kidneys, the dose of Cravit should be adjusted in Levofloxacin caused no impairment of fertility or reproductive performance in rats at oral doses as 5 PHARMACOLOGICAL PROPERTIES
patients with renal impairment (see section 4.2).
high as 360 mg/kg/day or intravenous doses up to 100 mg/kg/day.
5.1 Pharmacodynamic properties
Levofloxacin was not teratogenic in rats at oral doses as high as 810 mg/kg/day, or at intravenous Pharmacotherapeutic group: quinolone antibacterials, fluoroquinolones Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g. angioedema up to doses as high as 160 mg/kg/day. No teratogenicity was observed when rabbits were dosed orally with up to 50 mg/kg/day or intravenously with up to 25 mg/kg/day.
anaphylactic shock), occasionally following the initial dose (see section 4.8). Patients should Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone class and is the S (-) Levofloxacin had no effect on fertility and its only effect on fetuses was delayed maturation as a discontinue treatment immediately and contact their physician or an emergency physician, who will enantiomer of the racemic drug substance ofloxacin.
initiate appropriate emergency measures.
As a fluoroquinolone antibacterial agent, levofloxacin acts on the DNA-DNA-gyrase complex and Levofloxacin did not induce gene mutations in bacterial or mammalian cells but did induce As with all quinolones, hypoglycemia has been reported, usually in diabetic patients receiving chromosome aberrations in Chinese hamster lung (CHL) cells in vitro at or above 100μg/ml, in the concomitant treatment with an oral hypoglycemic agent (e.g., glibenclamide) or with insulin.
absence of metabolic activation. In vivo tests (micronucleus, sister chromatid exchange, In these diabetic patients, careful monitoring of blood glucose is recommended. (See section 4.8).
unscheduled DNA synthesis, dominant lethal tests) did not show any genotoxic potential.
The degree of the bactericidal activity of levofloxacin depends on the ratio of the maximum Phototoxic potential
concentration in serum (Cmax) or the area under the curve (AUC) and the minimal inhibitory Although photosensitisation is very rare with levofloxacin, it is recommended that patients should Studies in the mouse after both intravenous and oral dosing showed levofloxacin to have not expose themselves unnecessarily to strong sunlight or to artificial UV rays (e.g. sunray lamp, phototoxic activity only at very high doses. Levofloxacin did not show any genotoxic potential in a solarium), in order to prevent photosensitisation.
photomutagenicity assay, and it reduced tumour development in a photocarcinogenicity assay.
The main mechanism of resistance is due to a gyr-A mutation. In vitro there is a crossresistance Patients treated with Vitamin K antagonists
Carcinogenic potential
between levofloxacin and other fluoroquinolones.
Due to possible increase in coagulation tests (PT/INR) and/or bleeding in patients treated with No indication of carcinogenic potential was seen in a two-year study in the rat with dietary Due to the mechanism of action, there is generally no cross-resistance between levofloxacin and Cravit in combination with a vitamin K antagonist (e.g. warfarin), coagulation tests should be administration (0, 10, 30 and 100 mg/kg/day).
other classes of antibacterial agents.
monitored when these drugs are given concomittantly (see section 4.5).
Toxicity to joints
Psychotic reactions
In common with other fluoroquinolones, levofloxacin showed effects on cartilage (blistering and The EUCAST recommended MIC breakpoints for levofloxacin, separating susceptible from cavities) in rats and dogs. These findings were more marked in young animals.
Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. In intermediately susceptible organisms and intermediately susceptible from resistant organisms are 6 PHARMACEUTICAL PARTICULARS
very rare cases these have progressed to suicidal thoughts and selfendangering behaviour- presented in the below table for MIC testing (mg/L).
6.1 List of excipients
sometimes after only a single dose of levofloxacin (see section 4.8). In the event that the patient EUCAST clinical MIC breakpoints for levofloxacin (2006-06-20): develops these reactions, levofloxacin should be discontinued and appropriate measures instituted. Caution is recommended if levofloxacin is to be used in psychotic patients or in patients with Water for injection (Na concentration: 154 mmol / L).
QT interval prolongationCaution should be taken when using fluoroquinolones, including levofloxacin, in patients with 6.2 Incompatibilities
Cravit 5 mg/ml solution for infusion should not be mixed with heparin or alkaline solutions (e.g.
factors for prolongation of the QT interval such as, for example: This medicinal product must not be mixed with other medicinal products except those mentioned in - concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides).
6.3 Shelf life
- uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesemia) Shelf life after removal of the outer packaging: 3 days (under indoor light conditions).
- cardiac disease (e.g. heart failure, myocardial infarction, bradycardia) Shelf life after perforation of the rubber stopper: immediate use (see section 6.6).
From a microbiological point of view, the solution for infusion should be used immediately. If not (See section 4.2 Elderly, section 4.5, section 4.8, section 4.9).
used immediately, in-use storage times and conditions are the responsibility of the user.
Peripheral neuropathy
1 the S/I-breakpoint was increased from 1.0 to 2.0 to avoid dividing the wild type MIC distribution. 6.4 Special precautions for storage
Sensory or sensorimotor peripheral neuropathy has been reported in patients receiving The breakpoints relate to high dose therapy.
Keep the bottle in the outer carton in order to protect from light (see section 6.3).
fluoroquinolones, including levofloxacin, which can be rapid in its onset. Levofloxacin should be 2 Strains with MIC values above the S/I breakpoint are very rare or not yet reported. The Inspect visually prior to use. Only clear solutions without particles should be used.
discontinued if the patient experiences symptoms of neuropathy in order to prevent the identification and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed the isolate sent to a reference laboratory.
6.5 Nature and contents of container
development of an irreversible condition.
3 Non-species related breakpoints have been determined mainly on the basis of pharmacokinetic 50 ml type I glass bottle with flanged aluminium cap, chlorobutyl rubber stopper and tear-off /pharmacodynamic data and are independent of MIC distributions of specific species. They are polypropylene lid. Each bottle contains 50 ml solution for infusion. Pack sizes of 1 and 5 bottles.
In patients treated with levofloxacin, determination of opiates in urine may give false-positive for use only for species that have not been given a species-specific breakpoint and are not for 100ml type I glass bottle with flanged aluminium cap, chlorobutyl rubber stopper and tear-off use with species where susceptibility testing is not recommended or for which there is insufficient results. It may be necessary to confirm positive opiate screens by more specific method. evidence that the species in question is a good target (Enterococcus, Neisseria, Gram negative polypropylene lid. Each bottle contains 100 ml solution for infusion. Pack sizes of 1, 5 and 20 Cases of hepatic necrosis up to life threatening hepatic failure have been reported with levofloxacin, primarily in patients with severe underlying diseases, e.g. sepsis (see section 4.8). The CLSI (Clinical And Laboratory Standards Institute, formerly NCCLS)recommended MIC 6.6 Special precautions for disposal
Patients should be advised to stop treatment and contact their doctor if signs and symptoms of breakpoints for levofloxacin, separating susceptible from intermediately susceptible organisms and Cravit solution for infusion should be used immediately (within 3 hours) after perforation of the hepatic disease develop such as anorexia, jaundice, dark urine, pruritus or tender abdomen.
intermediately susceptible from resistant organisms are presented in the below table for MIC rubber stopper in order to prevent any bacterial contamination. No protection from light is 4.5 Interaction with other medicinal products and other forms of interaction
testing (μg/mL) or disc diffusion testing (zone diameter [mm] using a 5 μg levofloxacin disc).
Effect of other medicinal products on Cravit
CLSI recommended MIC and disc diffusion breakpoints for levofloxacin (M100-S17, 2007): As for all medicines, any unused medicinal product should be disposed of accordingly and incompliance with local environmental regulations.
Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs
Mixture with other solutions for infusion: No pharmacokinetic interactions of levofloxacin were found with theophylline in a clinical study. Cravit solution for infusion is compatible with the following solutions for infusion: However a pronounced lowering of the cerebral seizure threshold may occur when quinolones are 0.9 % sodium chloride solution USP.
given concurrently with theophylline, non-steroidal anti-inflammatory drugs, or other agents which Levofloxacin concentrations were about 13% higher in the presence of fenbufen than when Combination solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).
See section 6.2 for incompatibilities.
Probenecid and cimetidine had a statistically significant effect on the elimination of levofloxacin. The renal clearance of levofloxacin was reduced by cimetidine (24%) and probenecid (34%). This is because both drugs are capable of blocking the renal tubular secretion of levofloxacin. However, Manufactured by Sanofi-Aventis Deutschland GmbH
at the tested doses in the study, the statistically significant kinetic differences are unlikely to be of Bruningstrasse 50, D-65926 Frankfurt am Main, Germany
Caution should be exercised when levofloxacin is coadministered with drugs that affect the tubular renal secretion such as probenecid and cimetidine, especially in renally impaired patients.
Other relevant information
Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin were not affected to any clinically relevant extent when levofloxacin was administered together with the following drugs: calcium carbonate, digoxin, glibenclamide, ranitidine.
Effect of Cravit on other medicinal products
The absence or rare occurrence of resistant strains precludes defining any results categories other than < susceptible> for strains yielding results suggestive of a <nonsuceptible> category, organism identification and antimicrobial susceptibility test The half-life of ciclosporin was increased by 33% when coadministered with levofloxacin.
results should be confirmed by a reference laboratory using CLSI reference dilution method.
Vitamin K antagonists


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