Cefudyne

Film-coated tablet: White to off-white colored, oval shaped biconvex, compressed, film-coated tablets, plain on one side and having a break line on the other side.
Each film-coated tablet contains: Cefuroxime (as axetil), USP 500 mg.
Powder for Suspension: Cefuroxime Axetil (Cefudyne) 250 mg/5 mL powder for suspension when reconstituted gives an orange flavored suspension containing 250 mg Cefuroxime (as Axetil) per teaspoon (5 mL) of suspension.
Each 5 mL (1 teaspoonful) of reconstituted suspension contains: Cefuroxime (as Axetil), USP 250 mg.

Antibacterial (Cephalosporin).
Pharmacology: Pharmacodynamics: Film-coated tablet: Mechanism of action: Cefuroxime axetil undergoes hydrolysis by esterase enzymes to the active antibiotic, cefuroxime.
Cefuroxime inhibits bacterial cell wall synthesis following attachment to penicillin-binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.
Mechanism of resistance: Bacterial resistance to cefuroxime may be due to one or more of the following mechanisms: hydrolysis by beta-lactamases; including (but not limited to) by extended-spectrum beta-lactamases (ESBLs), and AmpC enzymes that may be induced or stably derepressed in certain aerobic gram-negative bacteria species; reduced affinity of penicillin-binding proteins for cefuroxime; outer membrane impermeability, which restricts access of cefuroxime to penicillin-binding proteins in gram-negative bacteria; bacterial efflux pumps.
Organisms that have acquired resistance to other injectable cephalosporins are expected to be resistant to cefuroxime.
Depending on the mechanism of resistance, organisms with acquired resistance to penicillins may demonstrate reduced susceptibility or resistance to cefuroxime.
Cefuroxime axetil breakpoints: Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows: See Table 1.

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Microbiological susceptibility: The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of cefuroxime axetil in at least some types of infections is questionable.
Cefuroxime is usually active against the following microorganisms in vitro. (See Table 2.)

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Powder for Suspension: Cefuroxime is bactericidal and has similar spectrum of antimicrobial action and pattern of resistance to those of cefamandole. It is more resistant to hydrolysis by beta-lactamases than cefamandole, and therefore may be more active against beta-lactamase-producing strains of Haemophilus influenzae and Neisseria gonorrhoeae.
Pharmacokinetics: Film-coated tablet: Absorption: After oral administration, cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly hydrolyzed in the intestinal mucosa and blood to release cefuroxime into the circulation. Optimum absorption occurs when it is administered shortly after a meal.
Following administration of cefuroxime axetil tablets, peak serum levels (2.1 mcg/mL for a 125 mg dose, 4.1 mcg/mL for a 250 mg dose, 7.0 mcg/mL for a 500 mg dose and 13.6 mcg/mL for a 1,000 mg dose) occur approximately 2 to 3 hours after dosing when taken with food. The rate of absorption of cefuroxime from the suspension is reduced compared with the tablets, leading to later, lower peak serum levels and reduced systemic bioavailability (4 to 17% less). Cefuroxime axetil oral suspension was not bioequivalent to cefuroxime axetil tablets when tested in healthy adults and therefore is not substitutable on a milligram-per-milligram basis. The pharmacokinetics of cefuroxime is linear over the oral dosage range of 125 to 1,000 mg. No accumulation of cefuroxime occurred following repeat oral doses of 250 to 500 mg.
Distribution: Protein binding has been stated as 33 to 50% depending on the methodology used. Following a single dose of cefuroxime axetil 500 mg tablet, the apparent volume of distribution was 50 L (CV%=28%). Concentrations of cefuroxime in excess of the minimum inhibitory levels for common pathogens can be achieved in the tonsilla, sinus tissues, bronchial mucosa, bone, pleural fluid, joint fluid, synovial fluid, interstitial fluid, bile, sputum and aqueous humor. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.
Biotransformation: Cefuroxime is not metabolized.
Elimination: The serum half-life is between 1 and 1.5 hours. Cefuroxime is excreted by glomerular filtration and tubular secretion. The renal clearance is in the region of 125 to 148 mL/min/1.73 m².
Special patient populations: Gender: No differences in the pharmacokinetics of cefuroxime were observed between males and females.
Elderly: No special precaution is necessary in the elderly patients with normal renal function at dosages up to the normal maximum of 1 g per day. Elderly patients are more likely to have decreased renal function; therefore, the dose should be adjusted in accordance with the renal function in the elderly.
Pediatrics: In older infants (aged >3 months) and in children, the pharmacokinetics of cefuroxime are similar to that observed in adults.
There is no clinical trial data available on the use of cefuroxime axetil in children under the age of 3 months.
Renal impairment: Cefuroxime is primarily excreted by the kidneys. Therefore, as with all such antibiotics, in patients with markedly impaired renal function (i.e., Clcr <30 mL/minute) it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion. Cefuroxime is effectively removed by dialysis.
Hepatic impairment: There are no data available for patients with hepatic impairment. Since cefuroxime is primarily eliminated by the kidney, the presence of hepatic dysfunction is expected to have no effect on the pharmacokinetics of cefuroxime.
Pharmacokinetic/pharmacodynamic relationship: For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy has been shown to be the percentage of the dosing interval (%T) that the unbound concentration remains above the minimum inhibitory concentration (MIC) of cefuroxime for individual target species (i.e., %T>MIC).
Powder for Suspension: Cefuroxime axetil is absorbed from the gastrointestinal tract and is rapidly hydrolyzed in the intestinal mucosa and blood to cefuroxime; absorption is enhanced in the presence of food. Peak plasma concentrations are reported about 2 to 3 hours after an oral 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.
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.
Cefuroxime is excreted unchanged, by glomerular filtration and renal tubular secretion, and high concentrations are achieved in the urine. 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.

Film-coated tablet: Cefuroxime is indicated for the treatment of the infections listed as follows in adults and children from the age of 3 months: Acute streptococcal tonsillitis and pharyngitis; Acute bacterial sinusitis; Acute otitis media; Acute exacerbations of chronic bronchitis; Cystitis; Pyelonephritis; Uncomplicated skin and soft tissue infections; Treatment of early Lyme disease.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Powder for Suspension: For treatment of susceptible infections including those of bone and joint infections, bronchitis (and other lower respiratory tract infections), gonorrhea, meningitis, otitis media, peritonitis, pharyngitis, sinusitis, skin infections (including soft tissue infections) and urinary tract infections. Also can be used for surgical infection prophylaxis.

Film-coated 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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Powder for Suspension: The usual duration of treatment is seven days (range: 5-10 days).
Administer oral suspension with food.
Dosage adjustment is required for patients with impaired renal function. (See Tables 4 and 5.)

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Film-coated tablet: 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 hemodialysis and peritoneal dialysis.
Powder for Suspension: Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.

Film-coated tablet: Hypersensitivity to cefuroxime or to any of the excipients; Patients with known hypersensitivity to cephalosporin antibiotics; History of severe hypersensitivity (e.g., anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).
Powder for Suspension: Cefuroxime should not be given to patients who are hypersensitive to it or to other cephalosporins. Care is also necessary in patients with history of allergy.

Film-coated tablet: 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 axetil 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 has 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.
Powder for Suspension: Cefuroxime should be given with caution to patients with renal impairment; a dosage reduction may be necessary. Renal hematological status should be monitored especially during prolonged and high-dose therapy.

Film-coated tablet: Pregnancy: There are limited data from the use of cefuroxime in pregnant women.
Cefuroxime should be prescribed to pregnant women only if the benefit outweighs the risk.
Breastfeeding: Cefuroxime is excreted in human milk in small quantities. Adverse effects at therapeutic doses are not expected, although a risk of diarrhea and fungal infection of the mucous membranes cannot be excluded. Breastfeeding might have to be discontinued due to these effects. The possibility of sensitization should be taken into account. Cefuroxime should only be used during breastfeeding after benefit/risk assessment by the physician-in-charge.
Fertility: There are no data on the effects of cefuroxime axetil on fertility in humans.
Powder for Suspension: There is no experimental evidence of embryonic or teratogenic effects attributable to cefuroxime axetil but, as with all drugs, it should be administered with caution during the early months of pregnancy. Cefuroxime is excreted in human milk, and consequently caution should be exercised when cefuroxime axetil is administered to a nursing mother.

Film-coated tablet: The most common adverse reactions are Candida overgrowth, eosinophilia, headache, dizziness, gastrointestinal disturbances and transient rise in liver enzymes.
The frequency categories assigned to the adverse reactions as follows are estimates, as for most reactions suitable data for calculating incidence were not available. In addition, the incidence of adverse reactions associated with cefuroxime axetil may vary according to the indication.
Treatment-related adverse reactions, all grades, are listed as follows by MedDRA body system organ class, frequency and grade of severity. The following convention has been utilized for the classification of frequency: very common ≥1/10; common ≥1/100 to <1/10; uncommon ≥1/1,000 to <1/100; rare ≥1/10,000 to <1/1,000; very rare <1/10,000 and not known (cannot be estimated from the available data). (See Table 6.)

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Pediatric population: The safety profile for cefuroxime axetil in children is consistent with the profile in adults.
Powder for Suspension: Gastrointestinal disturbances, including diarrhea, nausea, and vomiting, have occurred in some patients receiving cefuroxime. There have been rare reports of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Film-coated tablet: Drugs which reduce gastric acidity may result in a lower bioavailability of cefuroxime axetil compared with that of the fasting state and tend to cancel the effect of enhanced absorption after food.
Cefuroxime axetil may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral contraceptives.
Cefuroxime is excreted by glomerular filtration and tubular secretion. Concomitant use of probenecid is not recommended. Concurrent administration of probenecid significantly increases the peak concentration, area under the serum concentration time curve and elimination half-life of cefuroxime. Concomitant use with oral anticoagulants may give rise to increased INR.
Powder for Suspension: Probenecid reduces the renal clearance of cefuroxime. Drugs which reduce gastric acidity may result in a lower bioavailability of Cefuroxime (as Axetil) compared with that of the fasting state and tend to cancel the effect of enhanced post-prandial absorption.

Powder for Suspension: Directions for Reconstitution: Always shake the bottle vigorously in a diagonal direction for 1-2 minutes before use.
1. Shake the bottle to loosen powder completely. Remove the cap and the seal liner.
2. Add gradually the total amount of purified water stated in Table 7 and replace the cap. (See Table 7.)

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3. Invert the bottle and vigorously rock the bottle from side to side for at least 20 seconds.
4. Turn the bottle into an upright position and vigorously shake it in a diagonal direction for 1-2 minutes until powder is evenly suspended.
5. Store the reconstituted suspension either at room temperature (not exceeding 30°C) or in a refrigerator (2-8°C).
If the reconstituted suspension has been stored in refrigerator (2-8°C), let it stand at room temperature for 5 minutes then shake the bottle vigorously in a diagonal direction for 1-2 minutes before use.
After reconstitution, shake well before using.
To be taken after meals.

Store at temperatures not exceeding 30°C.
Powder for suspension: Protect from light.
The reconstituted suspension is stable for 7 days at temperatures not exceeding 30°C and 14 days under refrigeration (2-8°C).

Cephalosporins

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

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