RiteMED Cefuroxime

RiteMED Cefuroxime

cefuroxime

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Full Prescribing Info
Contents
Cefuroxime (tab: axetil; inj: sodium).
Description
Tablet: Each tablet contains: Cefuroxime (as axetil) 250 mg or 500 mg.
Injection: Each vial contains: Cefuroxime (as sodium), USP 750 mg.
Each diluent ampoule contains: Sterile Water for Injection, USP 10 mL.
Action
Pharmacology: Pharmacodynamics: Tablet: Cefuroxime, a semi-synthetic second generation cephalosporin, has antibacterial activity similar to penicillins, carbacephems and cephamycins. Cefuroxime exerts its bactericidal activity by interfering with the synthesis of the bacterial cell wall. It binds to specific penicillin-binding proteins responsible for the synthesis of peptidoglycan, a heteropolymeric structure that gives the cell wall its mechanical stability. The final stage of the peptidoglycan synthesis involves the completion of the cross-linking of the terminal glycine residue of the pentaglycine bridge to the fourth residue of the pentapeptide. The transpeptidase that catalyzes this step is inhibited by cephalosporins. Thus, inhibition of the transpeptidase interrupts peptidoglycan synthesis, causing formation of defective cell walls and osmotically unstable spheroplasts and lysis of the bacteria.
Injection: Mechanism of Action: The bactericidal action of cefuroxime results from inhibition of cell wall synthesis by binding to essential target protein. Cefuroxime has bactericidal activity against a wide range of common pathogens, including beta-lactamase-producing strains and consequently is active against many ampicillin-resistant or amoxicillin-resistant strains.
Pharmacokinetics: Tablet: The bioavailability of cefuroxime axetil after oral administration is variable and depends on the formulation used. The tablet/capsule formulations should not, therefore be substituted with powder for oral suspension formulations on a mg/mg basis.
The bioavailability of cefuroxime axetil is significantly increased from 37% to 52% by coadministration with food.
Average peak serum of cefuroxime concentrations of 4.1, 7, or 13.6 mcg/mL are attained approximately 2 to 3 hours after oral administration in adults of a single 250 mg, 500 mg or 1 g dose, respectively. Average serum concentrations after 6 hours are 0.7, 2.2, or 3.4 mcg/mL, respectively. The area under the curve (AUC) of the drug averaged 12.9, 27.4, or 50 mcg-hr/mL, respectively.
Cefuroxime's apparent volume of distribution in healthy adult ranges from 9.3 to 15.8 L per 1.73 m2. The drug is 33-50% protein-bound. Cefuroxime readily crosses the placenta and can also be detected in human milk.
After oral administration of cefuroxime axetil, the drug undergoes rapid hydrolysis by nonspecific esterases in the intestinal mucosa and blood to yield the active parent drug cefuroxime, which is released into the systemic circulation. The axetil moiety of the drug is metabolized to acetaldehyde and acetic acid. Cefuroxime itself is not metabolized and its serum level is much closer to the minimum inhibitory concentration (MIC) of important pathogens than cefuroxime axetil.
Cefuroxime is excreted unchanged primarily in the urine by both glomerular filtration and tubular secretion.
In adults, the serum plasma half-life (t1/2) after oral administration of cefuroxime axetil ranges from 1.2 to 1.6 hours and about 50% of an administered dose is recovered in the urine within 12 hours.
In patients with renal impairment, the serum t1/2 of the drug is prolonged and generally ranges from 1.9-16.1 hours depending on the degree of renal impairment.
Injection: 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 neonates.
Cefuroxime is widely distributed in the body including pleural fluid, sputum, bone, synovial fluid, & 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.
Cefuroxime 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.
Microbiology: Tablet: Antimicrobial Spectrum of Activity: Cefuroxime has demonstrated against most strains of the following microorganisms both in vitro and in clinical infections: See Table 1.

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Cefuroxime has also demonstrated in vitro activity against most strains of the following microorganism; however, clinical significance is unknown: See Table 2.

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Listeria monocytogenes and certain strains of enterococci, e.g., Enterococcus faecalis (formerly Streptococcus faecalis), are resistant to cefuroxime. Methicillin-resistant staphylococci are resistant to cefuroxime.
Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Legionella spp., and most strains of Serratia spp. and Proteus vulgaris are resistant to most first- and second-generation cephalosporins. Some strains of Morganella morganii, Enterobacter cloacae, and Citrobacter spp. have been shown by in vitro tests to be resistant to cefuroxime and other cephalosporins.
Most strains of Clostridium difficile and Bacteroides fragilis are resistant to cefuroxime.
Injection: Cefuroxime is usually active against the following organisms in vitro: Aerobes Gram-negative: Escherichia coli, Klebsiella spp., (including ampicillin-resistant strains), (including ampicillin-resistant strains), Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae (including penicillinase and non-penicillinase producing strains), Neisseria meningitides, Salmonella spp.
Aerobes Gram-positive: Staphylococcus aureus and Staphylococcus epidermidis (including penicillinase-producing strains but excluding methicillin-resistant strains), Streptococcus mitis (viridans groups), Bordetella pertussis.
Anaerobes: Gram-positive and Gram-negative cocci (including Peptococcus and Peptostreptococcus species). Gram-positive bacilli (including most Clostridium species) and Gram-negative bacilli (including Bacteroides and Fusobacterium species), Propionibacterium spp.
Other organisms: Borrelia burgdorferi.
The following organisms are not susceptible to cefuroxime: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Listeria monocytogenes, methicillin-resistant strains of Staphylococcus epidermidis, Legionella spp.
Some strains of the following genera are not susceptible to cefuroxime: Enterococcus (Streptococcus) faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp., Bacteroides fragilis.
Indications/Uses
Tablet: For the treatment of the following infections caused by susceptible organisms: Upper respiratory tract infections including: Acute sinusitis, acute otitis media, acute tonsillopharyngitis.
Lower respiratory tract infections including: Acute bacterial exacerbations of chronic bronchitis, secondary bacterial infections of acute bronchitis.
Uncomplicated skin and skin structure infections including furunculosis, pyoderma and impetigo.
Uncomplicated urinary tract infections including pyelonephritis.
Uncomplicated gonorrhea.
Early Lyme disease (erythema migrans).
Step down treatment for infections due to susceptible organisms, initially given antimicrobial therapy, particularly parenteral cefuroxime.
Injection: For the treatment of infections caused by susceptible organisms including lower respiratory tract infections, urinary tract infections, skin and soft tissue infections, septicemia, meningitis, gonorrhea, and bone and joint infections.
Dosage/Direction for Use
Tablet: In general, most infections in adults and adolescents (13 years and older) will respond to 250 mg every 12 hours. However, for more severe infections, 500 mg every 12 hours may be recommended. (See Table 3.)

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Injection: Cefuroxime is given by deep intramuscular injection, by slow IV injection over 3 to 5 minutes or by intravenous infusion.
ADULT: Usual dose: 750 mg by IM or IV injection every 8 hours.
Severe infection: 1.5 g IV every 6 to 8 hours. Pneumonia: 1.5 g IM or IV injection twice daily for 48 to 72 hours followed by oral cefuroxime therapy for 7 to 10 days.
Acute exacerbations of chronic bronchitis: 750 mg IM or IV injection twice daily followed by oral cefuroxime therapy for 5 to 10 days.
Duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical status of the patient.
Meningitis: 3 g IV every 8 hours.
Gonorrhea: 1.5 g IM single dose, divided between 2 different injection sites.
Surgical infection prophylaxis: Usual dose: 1.5 g IV before the procedure; this may be supplemented by 750 mg IM every 8 hours for up to 24 to 48 hours depending upon the procedure.
INFANTS AND CHILDREN: 30 to 60 mg/kg daily, increase to 100 mg/kg daily if necessary, given in 3 or 4 divided doses.
NEONATES: May be given similar total daily doses but in 2 or 3 divided doses.
Meningitis: Infants and Children: 200 to 400 mg/kg daily IV in 3 to 4 divided doses, decreased to 100 mg/kg daily after 3 days or when there is clinical improvement.
Neonates: 100 mg/kg IV daily, decreased to 50 mg/kg daily when indicated.
Impaired Renal Function: Reduce dosage of cefuroxime in patients with markedly impaired renal function.
Adults with marked renal impairment: (creatinine clearance 10-20 mL/min) 750 mg twice daily is recommended and with severe impairment (creatinine clearance <10 mL/min) 750 mg once daily is adequate.
For patients on hemodialysis: 750 mg dose should be given IV or IM at the end of each dialysis. In addition to the parenteral use, cefuroxime can be incorporated into the peritoneal dialysis fluid (usually 250 mg for every 2 liters of dialysis fluid).
Or, as prescribed by the physician.
Directions for Reconstitution: Intramuscular injection: For IM injection, add 3 mL Sterile Water for Injection to 750 mg cefuroxime. Shake gently to produce an opaque solution. Administer by deep IM injection into a large muscle mass (such as the gluteus or lateral part of the thigh). Before injecting intramuscularly, aspiration is necessary to avoid inadvertent injection into a blood vessel.
Intravenous Injection: For IV injection, add 6 mL Sterile Water for Injection to 750 mg cefuroxime. For direct intermittent IV administration, slowly inject the solution into a vein over a period of 3 to 5 minutes or give through the tubing system by which the patient is also receiving other IV solutions.
Intravenous infusion: For short intravenous infusion (e.g., up to 30 minutes) 1.5 g cefuroxime may be dissolved in 50-100 mL Sterile Water for Injection. This solution may be given directly into a vein or introduced into the tubing of the infusion set if the patient is receiving parenteral fluids.
For continuous IV infusion, a solution of cefuroxime may be added to an IV infusion pack containing one of the following fluids: 0.9% sodium chloride, 5% dextrose injection, 10% dextrose injection, 5% dextrose and 0.45% sodium chloride injection and 1/6 molar sodium lactate injection.
Solutions of cefuroxime should not be added to solutions of aminoglycosides. Each of the antibiotics can be administered separately to the same patient.
The reconstituted solution is stable for 6 hours at temperatures not exceeding 25°C (or 24 hours at 2°-8°C).
Overdosage
Tablet: Limited information is available on the acute toxicity of cefuroxime in humans. Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. If acute overdosage occurs, cefuroxime may be removed by hemodialysis or peritoneal dialysis.
Contraindications
Known hypersensitivity to cefuroxime or any component of the product.
Special Precautions
Tablet: A thorough inquiry about the patient's previous hypersensitivity history should be made. Cefuroxime, like other cephalosporins, penicillins and other drugs, may cause serious hypersensitivity reactions and should be used with caution in any patient who has demonstrated some allergy to any drug. Although it has not been established, allergic reactions to antibiotics may occur more frequently in atopic individuals.
Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures including oxygen, intravenous (IV) fluids and IV antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated.
Clostridium difficile-associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including cefuroxime, and may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea following administration of antibacterial agents.
As with other broad-spectrum antibacterial agents, cefuroxime should be used with caution in patients with a history of gastrointestinal disease, particularly colitis.
Cephalosporins, including cefuroxime, have been associated with the development of seizures, particularly in patients with renal impairment, in whom dosage of the drug was not reduced. If seizures due to cefuroxime develop, the drug should be discontinued and treatment with an anticonvulsant be given as clinically indicated.
Cephalosporins may be associated with a fall in prothrombin activity. Patients who are at risk are those with kidney or liver impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous Vitamin K administered as indicated.
The patient's renal function should be carefully monitored when cefuroxime is given concurrently with aminoglycosides and/or diuretics because adverse renal effects may occur (see Interactions).
The Jarisch-Herxheimer reaction, transient immunological reaction lasting 1 to 2 days, has been observed following cefuroxime treatment of Lyme disease.
Cefuroxime is considered to be unsafe in patients with porphyria although there is conflicting experimental evidence of porphyrinogenicity.
Since cefuroxime may cause dizziness, patients should be advised to avoid performing tasks which require complete mental alertness such as driving and operating machinery.
Prescribing cefuroxime in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication in unlikely to provide benefit to the patient and increases the risk of antibiotic resistance.
As with other antibacterial agents, long term or repeated use may result in overgrowth of non-susceptible organisms, including fungi.
Patients with Renal Impairment: The safety and efficacy of oral cefuroxime axetil in patients with renal impairment have not been established. Since cefuroxime is renally eliminated, its half-life will be prolonged in patients with reduced renal function.
Injection: Careful use in patients who have experienced an allergic reaction to penicillins or other beta-lactams. Renal function should be monitored in patients receiving high dose cephalosporins, the elderly, and those with pre-existing renal impairment.
Use in Children: Cefuroxime's serum t1/2 is inversely proportional to age when given in children and neonates.
Use in Elderly: There are no apparent differences in efficacy and safety of cefuroxime between the elderly and younger adults. However, since elderly patients have increased risk of renal impairment, dose adjustment and renal function monitoring may be necessary.
Use In Pregnancy & Lactation
Pregnancy: (Pregnancy Category B) Since there are no adequate and well controlled studies to date using cefuroxime in pregnant women, use in pregnancy only if the potential benefit justifies the potential risk to fetus.
Lactation: Cefuroxime is distributed to human milk and should be used with caution in breastfeeding women.
Adverse Reactions
Tablet: The following adverse events have been reported with the use of cefuroxime, although in many instances the casual relationship to the drug has not been established: Dermatologic/Hypersensitivity Reactions: Rash (e.g., morbilliform), pruritus/itch, erythema, urticaria/hives, drug fever, chills, edema, facial edema, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (exanthemic necrolysis), serum sickness-like reactions, shock, hypotension, vasodilatation, shortness of breath, bronchospasm, angioedema, anaphylaxis, candida overgrowth.
Gastrointestinal (GI): Nausea, vomiting, diarrhea, or loose stools, gagging, abdominal/epigastric pain, abdominal cramps, dyspepsia, flatulence, heartburn, indigestion, GI bleeding, tenesmus, GI infection, decreased salivation, ptyalism, glossitis/swollen tongue, taste alteration, mouth ulcers/candidiasis, decreased appetite/anorexia, thirst, Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis).
Hematologic: Decreased hematocrit and hemoglobin concentrations, transient eosinophilia and neutropenia, pancytopenia, thrombocytopenia, leukopenia, lymphocytopenia, agranulocytosis, leukocytosis, lymphocytosis, monocytosis, thrombocytosis, basophilia, anemia, aplastic anemia, hemolytic anemia, epistaxis or hemorrhage, increased erythrocyte sedimentation rate, prolonged prothrombin time (PT), prolonged activated partial thromboplastin time (APTT), and/or hypoprothrombinemia (with or without bleeding).
Nervous System: Headache, dizziness, vertigo, malaise, fatigue, drowsiness, somnolence or sleepiness, weakness, insomnia, nightmares, irritable behavior, seizures, myoclonic jerks, generalized hyperexcitability, hyperactivity, nervousness or anxiety, agitation, confusion, hallucinations, alteration in color perception, hot flushes, hypertonia.
Musculoskeletal: Muscle spasm of the neck, muscle cramps of stiffness, arthralgia/joint pain or swelling.
Genitounitary: Acute renal failure and interstitial nephritis, transient increases in blood urea nitrogen (BUN) and serum creatinine concentrations; decreased creatinine clearance; renal dysfunction, toxic nephropathy, bilateral renal cortical necrosis, kidney pain, urinary tract infection, urethral pain or bleeding, dysuria, vaginitis, vaginal candidiasis, vulvovaginal pruritus, vaginal discharge or irritation, menstrual irregularities.
Hepatic: Hepatic impairment including hepatitis and cholestasis, jaundice; transient increases in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase, alkaline phosphatase, lactate dehydrogense (LDH), and bilirubin concentrations; decreased serum albumin and/or total protein.
Respiratory: Pleural effusion, pulmonary infiltrate, dyspnea or respiratory distress, upper respiratory infection, rhinitis, sinusitis, cough.
Cardiovascular: Chest pain or tightness, tachycardia.
Other Adverse Effects: Jarisch-Herxheimer reaction, mild to severe hearing loss, increased or decreased serum glucose concentration, lockjaw-type reaction, viral illness.
Injection: The most common adverse effects have been local reactions following IV administration. Gastrointestinal disturbances, including diarrhea, nausea, and vomiting have occurred in some patients. There have been rare reports of erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis. Mild to moderate hearing loss have been reported in some children given cefuroxime for the treatment of meningitis.
Drug Interactions
Tablet: Probenecid: Probenecid, given together with or right before administration of cefuroxime, slows down tubular secretion of cefuroxime and produces higher and more prolonged serum cefuroxime concentrations. This drug interaction is usually used beneficially in treating gonorrhea.
Aminoglycosides: The risk of nephrotoxicity may increase when aminoglycosides and cephalosporins are given concomitantly. This has not been reported with cefuroxime use to date. Monitoring of the patient's renal function is advisable when these drugs are given together.
Diuretics: Studies suggest that the concomitant use of potent diuretics, including furosemide and ethacrynic acid, may increase the risk of renal toxicity with cephalosporins.
Oral Antacids: These drugs may result in lower bioavailability of cefuroxime compared with that of the fasting state and tend to cancel the effect of enhanced postprandial absorption.
Oral Contraceptives: As with other antibacterial agents, cefuroxime may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral contraceptives.
Injection: Probenecid reduces the renal clearance of cefuroxime.
Storage
Store in a cool, dry and dark place at temperatures not exceeding 30°C.
Injection: Protect from light.
MIMS Class
Cephalosporins
ATC Classification
J01DC02 - cefuroxime ; Belongs to the class of second-generation cephalosporins. Used in the systemic treatment of infections.
Presentation/Packing
Tab (white to off-white colored, biconvex capsule-shaped, film-coated with break line on one side) 250 mg x 100's. 500 mg x 60's. Powd for inj (vial + 10 mL diluent) 750 mg x 1's.
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