Kefsyn/Kefsyn 750

Kefsyn FC tab: White, elongated, biconvex, on one side scored and plain on the other side film-coated tablets.
Each film-coated tablet contains: Cefuroxime Axetil, BP eq. to Cefuroxime 500 mg.
Kefsyn 750: Faintly yellow powder.
Each vial contains: Cefuroxime (as sodium), USP 750 mg.
Each ampoule contains: Sterile Water for Injection, BP 10 mL.

Pharmacotherapeutic group: Antibacterials for systemic use, second-generation cephalosporins.
Pharmacology: Kefsyn FC tab: In vivo bactericidal activity of Cefuroxime is due to Cefuroxime's binding to essential target proteins and the resultant inhibition of cell wall synthesis.
Cefuroxime has bactericidal activity against a wide range of common pathogens, including many beta-lactamase-producing strains. Cefuroxime is stable to many bacterial beta-lactamases, especially plasmid-mediated enzymes that are commonly found in enterobacteriaceae.
Pharmacodynamics: Mechanism of action: Kefsyn FC tab: Cefuroxime axetil owes its in vivo bactericidal activity to the parent compound Cefuroxime. Cefuroxime is a well characterised and effective antibacterial agent which has bactericidal activity against a wide range of common pathogens, including β-lactamase producing strains.
Cefuroxime has good stability to bacterial β-lactamase, and consequently is active against many ampicillin-resistant or amoxicillin-resistant strains.
The bactericidal action of Cefuroxime results from inhibition of cell wall synthesis by binding to essential target proteins.
Kefsyn 750: Like other beta-lactam drugs, cefuroxime exerts antibacterial activity by binding to and inhibiting the action of certain bacterial cell wall synthetic enzymes namely the penicillin-binding proteins. This results in the interruption of cell wall (peptidoglycan) biosynthesis which leads to bacterial cell lysis and death.
Pharmacokinetics: Cefuroxime is widely distributed in the body including pleural fluid, sputum, bone, synovial fluid, and aqueous humour, but only achieves therapeutic concentrations in the CSF when the meninges are inflamed. It crosses the placenta and has been detected in breast milk. It is excreted unchanged by glomerular filtration and renal tubular secretion, and high concentrations are achieved in the urine. Following injection, most of a dose of cefuroxime is excreted within 24 hours, the majority within 6 hours. Probenecid competes for renal tubular secretion with cefuroxime resulting in higher and more prolonged plasma concentrations of cefuroxime. Small amounts of cefuroxime are excreted in bile. Plasma concentrations are reduced by dialysis.
Kefsyn FC tab: Cefuroxime is absorbed from the gastrointestinal tract and is rapidly hydrolysed in the intestinal mucosa and blood to release Cefuroxime; absorption is enhanced in the presence of food. Peak plasma concentrations are reported about 2 to 3 hours after an oral dose.
Kefsyn FC tab/Kefsyn 750: The sodium salt is given by intramuscular or intravenous injection. Peak plasma concentrations of about 27 micrograms/mL have been achieved 45 minutes after an intramuscular dose of 750 mg with measurable amounts present 8 hours after a dose. Up to 50% of Cefuroxime in the circulation is bound to plasma proteins. The plasma half-life is about 70 minutes and is prolonged in patients with renal impairment and in neonates.

Used in the treatment of susceptible infections such as bone and joint infections, bronchitis (and other lower respiratory tract infections), gonorrhea, meningitis (although treatment failures have been reported in H. influenzae meningitis), otitis media, peritonitis, pharyngitis, sinusitis, skin infections (including soft-tissue infections), and urinary tract infections. It is also used for surgical infection prophylaxis.

Kefsyn FC tab: For Uncomplicated Urinary Tract Infections: 125 mg twice daily.
For Respiratory Tract Infections: 250 to 500 mg twice daily.
A dose for children more than 3 months of age: 125 mg twice daily or 10 mg/kg twice daily to a maximum of 250 mg daily.
Children over 2 years of age with otitis media: 250 mg twice daily or 15 mg/kg twice daily to a maximum of 500 mg daily.
Adults with Pneumonia or with Acute Exacerbations of Chronic Bronchitis: 1.5 g twice daily or 750 mg twice daily, respectively, in parenteral route followed by oral Cefuroxime 500 mg twice daily in each case.
For Lyme disease in adults: 500 mg is given twice daily for 20 days.
For Uncomplicated Gonorrhea: A single 1g oral dose of Cefuroxime can be given. In each case an oral dose of Probenecid 1g may be given with Cefuroxime. Or as prescribed by the physician.
Kefsyn 750: Cefuroxime may be administered intravenously or intramuscularly.
Adults: The usual dose of Cefuroxime is 750 mg three times daily by I.M. or I.V. Injection, which may be increased to 1.5 g three times daily I.V. in severe infections. The frequency of administration can be increased to six-hourly, if necessary, giving total doses of 3 g to 6 g daily.
Infants and children: 30 to 60 mg/kg/day increased to 100 mg/kg daily, if necessary, given as three or four divided doses. A dose of 60 mg/kg/day will be appropriate for most infections.
Elderly: As prescribed by the physician.
Dosage in impaired renal function: As Cefuroxime is excreted by the kidneys, the dosage of Cefuroxime should be reduced in patients with creatinine clearance below 20 mL/min, 750 mg twice daily is recommended and with 10 mL/min, 750 mg once daily is adequate. For patients on hemodialysis, a further 750 mg dose should be given at the end of each dialysis. In case of continuous peritoneal dialysis, 750 mg twice daily is recommended.

Kefsyn FC tab: Overdose can lead to neurological sequelae including encephalopathy, convulsions and coma. Symptoms of overdose can occur if the dose is not reduced appropriately in patients with renal impairment.
Serum levels of Cefuroxime can be reduced by haemodialysis and peritoneal dialysis.
Kefsyn 750: Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of Cefuroxime can be reduced by hemodialysis or peritoneal dialysis.

Cefuroxime is contraindicated in patients with known hypersensitivity to cephalosporin antibiotics.

Kefsyn 750: Before instituting therapy with Cefuroxime, careful history of hypersensitivity reactions to Cefuroxime, cephalosporins, penicillins or other drugs should be obtained. Therefore, caution should be exercised while treating such patients, as cross sensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy.
If an allergic reaction to Cefuroxime occurs, discontinue the drug. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines and airway management, as clinically indicated. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including Cefuroxime, and may range from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia, such as, Clostridium difficile which is a primary cause of "antibiotic-associated colitis". In case of the occurrence of pseudomembranous colitis, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug effective against Clostridium difficile.

Kefsyn FC tab: Hypersensitivity reactions: Special care is indicated in patients who have experienced an allergic reaction to penicillins or other beta-lactam antibiotics because there is a risk of cross-sensitivity. As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. In case of severe hypersensitivity reactions, treatment with Cefuroxime must be discontinued immediately and adequate emergency measures must be initiated. Before beginning treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to Cefuroxime, to other cephalosporins or to any other type of beta-lactam agent. Caution should be used if Cefuroxime is given to patients with a history of non-severe hypersensitivity to other beta-lactam agents.
Jarisch-Herxheimer reaction: The Jarisch-Herxheimer reaction has been seen following Cefuroxime axetil treatment of Lyme disease. It results directly from the bactericidal activity of Cefuroxime axetil on the causative bacteria of Lyme disease, the spirochaete Borrelia burgdorferi. Patients should be reassured that this is a common and usually self-limiting consequence of antibiotic treatment of Lyme disease.
Overgrowth of non-susceptible microorganisms: As with other antibiotics, use of Cefuroxime may result in the overgrowth of Candida. Prolonged use may also result in the overgrowth of other non-susceptible microorganisms (e.g. Enterococci and Clostridium difficile), which may require interruption of treatment. Antibacterial agent-associated pseudomembranous colitis have been reported with nearly all antibacterial agents, including Cefuroxime and may range in severity from mild to life threatening. This diagnosis should be considered in patients with diarrhea during or subsequent to the administration of Cefuroxime. Discontinuation of therapy with Cefuroxime and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
Interference with diagnostic tests: The development of a positive Coombs Test associated with the use of Cefuroxime may interfere with cross matching of blood. As a false negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving Cefuroxime axetil.
Cefuroxime axetil should be given with caution to patients with renal impairment, dosage reduction may be necessary.
Renal and haematological status should be monitored especially during prolonged and high dose therapy.
Pseudomembranous colitis has been reported with the use of broad-spectrum antibiotics, therefore, it is important to consider its diagnosis in patients who develop serious diarrhea during or after antibiotic use.
Effects on ability to drive and use machines: Cefuroxime axetil has no reported influence on the ability to drive and use machines. No studies on the effects on the ability to drive and use machines have been performed.
Kefsyn 750: Although Cefuroxime rarely produces alterations in kidney function, evaluation of renal status during treatment is recommended, especially in patients receiving the maximum doses.
Cephalosporins should be given with caution to patients receiving concurrent diuretics. Caution is advised in patients with marked to severe renal impairment; reduced dosages should be administered. As with other antibiotics, prolonged use of Cefuroxime results in overgrowth of nonsusceptible organisms. Careful observation of the patient is essential.
In case superinfection occurs, appropriate measures should be taken.
Use in Children: Safety and effectiveness of Cefuroxime in children below 3 months of age have not been established.

Cefuroxime is excreted in human milk, and consequently caution should be exercised when Cefuroxime axetil is administered to a nursing mother.
Kefsyn FC tab: Pregnancy: Cefuroxime axetil should be administered with caution during the early months of pregnancy. This drug should be used during pregnancy only, if clearly needed.
Kefsyn 750: As there are no well-controlled clinical trials of Cefuroxime in pregnant women, it should be administered only, if necessary and with caution.

Kefsyn FC tab: Gastrointestinal disturbances, including diarrhea, nausea, and vomiting, have occurred in some patients receiving Cefuroxime axetil.
There have been rare reports of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Mild to moderate hearing loss has been reported in some children given Cefuroxime for the treatment of meningitis.
Kefsyn 750: Cefuroxime is generally well tolerated. Adverse reactions have been generally mild and transient in nature.
Local reactions: Transient pain at the site of intramuscular injection, which is more likely to occur with higher doses.
Hypersensitivity reactions: Skin rashes (maculopapular and urticaria), drug fever and very rarely anaphylaxis have been reported.
Gastrointestinal: Diarrhea and nausea. Pseudomembranous colitis may occur during or after treatment.
Blood: Decreased hemoglobin concentration and/or eosinophilia, leukopenia and neutropenia may occur. As with other cephalosporins, there have been very rare reports of thrombocytopenia.
Hepatic: Transient rise in serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT), and bilirubin may occur.

Kefsyn FC tab: Probenecid reduces the renal clearance of Cefuroxime.
Kefsyn 750: Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics, like furosemide and aminoglycosides, as these combinations are suspected of adversely affecting renal function, though this is not likely to be a problem at the recommended dose levels.

Direction for Reconstitution: Kefsyn 750: Intramuscular Injection: Add 3 mL of sterile water for injection and shake gently for dispersion.
Intravenous Injection: Add 6 mL of sterile water for injection and shake gently for dispersion. Reconstituted solution stored at temperature not exceeding 30°C should be used within 24 hours. Reconstituted solution stored at refrigerated condition (2°C to 8°C) should be used within 7 days.

Store at temperatures not exceeding 30°C.

Cephalosporins

J01DC02 - cefuroxime ; Belongs to the class of second-generation cephalosporins. Used in the systemic treatment of infections.

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