Altacef

Each film-coated tablet contains: Cefuroxime (as Axetil) 500 mg.
Cefuroxime (as Axetil) Tablets contains cefuroxime as Cefuroxime (as Axetil). Cefuroxime (as Axetil) is a semisynthetic, broad-spectrum cephalosporin antibiotic for oral administration.
Chemically, Cefuroxime (as Axetil), the 1-(acetyloxy) ethyl ester of cefuroxime, is (RS)-1-hydroxyethyl (6R, 7R)-7-[2-(2-furyl) glyoxyl-amido]-3-(hydroxymethyl)-8-oxo-5-thia-1 azabicyclo [4.2.0]-oct-2-ene-2-carboxylate, 72-(Z)-(Omethyl oxime), 1-acetate 3-carbamate. Its molecular formula is C20H22N4O10S, and it has a molecular weight of 510.48. Cefuroxime (as Axetil) is in the amorphous form.
Cefuroxime (as Axetil) Tablets are film-coated and contain the equivalent of 500 mg of cefuroxime as Cefuroxime (as Axetil).
Excipients/Inactive Ingredients: Cefuroxime (as Axetil) Tablets contain the inactive ingredients colloidal silicon dioxide, croscarmellose sodium, hydrogenated vegetable oil, hypromellose, methylparaben, microcrystalline cellulose, propylene glycol, propylparaben, sodium benzoate, sodium lauryl sulfate, and titanium dioxide.

Pharmacology: Absorption and Metabolism: After oral administration, Cefuroxime (as Axetil) is absorbed from the gastrointestinal tract and rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa and blood to cefuroxime. Cefuroxime is subsequently distributed throughout the extracellular fluids.
The axetil moiety is metabolized to acetaldehyde and acetic acid.
Pharmacokinetics: Approximately 50% of serum cefuroxime is bound to protein. Serum pharmacokinetic parameters for Cefuroxime (as Axetil) Tablets shown in Table 1. (See Table 1.)

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Food Effect on Pharmacokinetics: Absorption of the tablet is greater when taken after food (absolute bioavailability of Cefuroxime (as Axetil) Tablets increases from 37% to 52%). Despite this difference in absorption, the clinical and bacteriologic responses of patients were independent of food intake at the time of tablet administration in 2 studies where this was assessed.
Renal Excretion: Cefuroxime is excreted unchanged in the urine; in adults, approximately 50% of the administered dose is recovered in the urine within 12 hours. The pharmacokinetics of cefuroxime in the urine of pediatric patients has not been studied at this time. Until further data are available, the renal pharmacokinetic properties of Cefuroxime (as Axetil) established in adults should not be extrapolated to pediatric patients.
In a study of 28 adults with normal and markedly impaired renal function, the elimination half-life of cefuroxime was prolonged in relation to severity of renal impairment. In a study of 16 adult hemodialysis patients with end-stage renal disease, the majority of a cefuroxime dose was removed by hemodialysis. In a study of 20 elderly patients (mean age = 83.9 years) having a mean creatinine clearance of 34.9 mL/min, the mean serum elimination half-life was 3.5 hours. Despite the lower elimination of cefuroxime in geriatric patients, dosage adjustment based on age is not necessary (see Use in the Elderly under Precautions).
Microbiology: Mechanism of Action: Cefuroxime (as Axetil) is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefuroxime (as Axetil) has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.
Mechanism of Resistance: Resistance to Cefuroxime (as Axetil) is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), decreased permeability and the presence of bacterial efflux pumps.
Susceptibility to Cefuroxime (as Axetil) will vary with geography and time; local susceptibility data should be consulted, if available. Cefuroxime (as Axetil) has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in Indications: Gram-positive bacteria; Staphylococcus aureus (methicillin-susceptible isolates only); Streptococcus pneumoniae; Streptococcus pyogenes; Gram-negative bacteria; Escherichia coli^a; Klebsiella pneumoniae^a; Haemophilus influenzae^b; Haemophilus parainfluenzae; Moraxella catarrhalis; Neisseria gonorrhoeae; Spirochetes; Borrelia burgdorferi.
^a Most extended spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing isolates are resistant to Cefuroxime (as Axetil).
^b Beta-lactamase negative, ampicillin resistant (BLNAR) isolates of H. influenzae must be considered resistant to Cefuroxime (as Axetil).
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Cefuroxime (as Axetil). However, the efficacy of Cefuroxime (as Axetil) in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials: Gram-positive bacteria; Staphylococcus epidermidis (methicillin-susceptible isolates only); Staphylococcus saprophyticus (methicillin-susceptible isolates only); Streptococcus agalactiae; Gram-negative bacteria; Morganella morganii; Proteus inconstans; Proteus mirabilis; Providencia rettgeri; Anaerobic bacteria; Peptococcus niger.
Susceptibility Test Methods: When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.
Dilution Techniques: Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth or agar). The MIC values should be interpreted according to criteria provided in Table 2.
Diffusion Techniques: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method. This procedure uses paper disks impregnated with 30 mcg Cefuroxime (as Axetil) to test the susceptibility of microorganisms to Cefuroxime (as Axetil). The disk diffusion interpretive criteria are provided in Table 2. (See Table 2.)

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Susceptibility of staphylococci to Cefuroxime (as Axetil) may be deduced from testing only penicillin and either cefoxitin or oxacillin.
Susceptibility of Streptococcus pyogenes may be deduced from testing penicillin.
A report of Susceptible indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentration at the infection site necessary to inhibit growth of the pathogen.
A report of Intermediate indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation.
A report of Resistant indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.
Quality Control: Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individual performing the test. The QC ranges for MIC and disk diffusion testing using the 30 mcg disk are provided in Table 3. (See Table 3.)

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Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: Although lifetime studies in animals have not been performed to evaluate carcinogenic potential, no mutagenic activity was found for Cefuroxime (as Axetil) in a battery of bacterial mutation tests. Positive results were obtained in an in vitro chromosome aberration assay; however, negative results were found in an in vivo micronucleus test at doses up to 1.5 g/kg. Reproduction studies in rats at doses up to 1,000 mg/kg/day (9 times the recommended maximum human dose based on mg/m²) have revealed no impairment of fertility.

Cefuroxime (as Axetil) Tablets are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed as follows: Pharyngitis/Tonsillitis: caused by Streptococcus pyogenes.
NOTE: The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin given by the intramuscular route. Cefuroxime (as Axetil) Tablets are generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cefuroxime in the subsequent prevention of rheumatic fever are not available. Also note that in all clinical trials, all isolates had to be sensitive to both penicillin and cefuroxime. There are no data from adequate and well controlled trials to demonstrate the effectiveness of cefuroxime in the treatment of penicillin-resistant strains of Streptococcus pyogenes.
Acute Bacterial Otitis Media: caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), Moraxella catarrhalis (including beta-lactamase-producing strains), or Streptococcus pyogenes.
Acute Bacterial Maxillary Sinusitis: caused by Streptococcus pneumoniae or Haemophilus influenzae (non-beta-lactamase-producing strains only).
NOTE: In view of the insufficient numbers of isolates of beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis that were obtained from clinical trials with Cefuroxime (as Axetil) Tablets for patients with acute bacterial maxillary sinusitis, it was not possible to adequately evaluate the effectiveness of Cefuroxime (as Axetil) Tablets for sinus infections known, suspected, or considered potentially to be caused by beta-lactamase-producing Haemophilus influenzae or Moraxella catarrhalis.
Acute Bacterial Exacerbations of Chronic Bronchitis and Secondary Bacterial Infections of Acute Bronchitis: caused by Streptococcus pneumoniae, Haemophilus influenza (beta-lactamase negative strains), or Haemophilus parainfluenzae (beta-lactamase negative strains).
Uncomplicated Skin and Skin-Structure Infections: caused by Staphylococcus aureus (including beta-lactamase-producing strains) or Streptococcus pyogenes.
Uncomplicated Urinary Tract Infections: caused by Escherichia coli or Klebsiella pneumoniae.
Uncomplicated Gonorrhea: urethral and endocervical, caused by penicillinase-producing and non-penicillinase-producing strains of Neisseria gonorrhoeae and uncomplicated gonorrhea, rectal, in females, caused by non-penicillinase-producing strains of Neisseria gonorrhoeae.
Early Lyme Disease (erythema migrans): caused by Borrelia burgdorferi.

See Table 4.

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Patients with Renal Impairment: Because cefuroxime is eliminated primarily by the kidney, a dosage interval adjustment is required for patients whose creatinine clearance is 30 mL/min, as listed in Table 5. (See Table 5.)

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Overdosage of cephalosporins can cause cerebral irritation leading to convulsions or encephalopathy. Serum levels of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.

Cefuroxime (as Axetil) products are contraindicated in patients with known allergy to the cephalosporin group of antibiotics.

Before therapy with Cefuroxime (as Axetil) products is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to Cefuroxime (as Axetil) products, other cephalosporins, penicillins, or other drugs. If this product is to be given to penicillin-sensitive patients, caution should be exercised because cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If a clinically significant allergic reaction to Cefuroxime (as Axetil) products occurs, discontinue the drug and institute appropriate therapy. 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.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefuroxime (as Axetil), and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

General: As with other broad-spectrum antibiotics, prolonged administration of Cefuroxime (as Axetil) may result in overgrowth of non-susceptible microorganisms (Candida, Enterococci, Clostridium difficile). If superinfection occurs during therapy, appropriate measures should be taken.
Cephalosporins, including Cefuroxime (as Axetil), should be given with caution to patients receiving concurrent treatment with potent diuretics because these diuretics are suspected of adversely affecting renal function.
Cefuroxime (as Axetil), as with other broad-spectrum antibiotics, should be prescribed with caution in individuals with a history of colitis. The safety and effectiveness of Cefuroxime (as Axetil) have not been established in patients with gastrointestinal malabsorption. Patients with gastrointestinal malabsorption were excluded from participating in clinical trials of Cefuroxime (as Axetil).
Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic 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.
Prescribing Cefuroxime (as Axetil) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
Use in Children: The safety and effectiveness of Cefuroxime (as Axetil) have been established for pediatric patients aged 3 months to 12 years for acute bacterial maxillary sinusitis based upon its approval in adults. Use of Cefuroxime (as Axetil) in pediatric patients is supported by pharmacokinetic and safety data in adults and pediatric patients, and by clinical and microbiological data from adequate and well-controlled studies of the treatment of acute bacterial maxillary sinusitis in adults and of acute otitis media with effusion in pediatric patients. It is also supported by postmarketing adverse events surveillance (see Pharmacology under Actions, Indications, Adverse Reactions, and Dosage & Administration).
Use in the Elderly: Of the total number of subjects who received Cefuroxime (as Axetil) in 20 clinical studies of Cefuroxime (as Axetil), 375 were 65 and older while 151 were 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger adult subjects. The geriatric patients reported somewhat fewer gastrointestinal events and less frequent vaginal candidiasis compared with patients aged 12 to 64 years old; however, no clinically significant differences were reported between the elderly and younger adult patients. Other reported clinical experience has not identified differences in responses between the elderly and younger adult patients.

Pregnancy: Teratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in mice at doses up to 3,200 mg/kg/day (14 times the recommended maximum human dose based on mg/m²) and in rats at doses up to 1,000 mg/kg/day (9 times the recommended maximum human dose based on mg/m²) and have revealed no evidence of impaired fertility or harm to the fetus due to Cefuroxime (as Axetil). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Labor and Delivery: Cefuroxime (as Axetil) has not been studied for use during labor and delivery.
Nursing Mothers: Because cefuroxime is excreted in human milk, consideration should be given to discontinuing nursing temporarily during treatment with Cefuroxime (as Axetil).

General: The following hypersensitivity reactions have been reported: Anaphylaxis, angioedema, pruritus, rash, serum sickness-like reaction, urticaria, drug fever.
Gastrointestinal: Pseudomembranous colitis (see Warnings).
Hematologic: Hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia, and increased prothrombin time.
Hepatic: Hepatic impairment including hepatitis and cholestasis, jaundice.
Neurologic: Seizure, encephalopathy.
Skin: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Urologic: Renal dysfunction.
Cephalosporin Class Adverse Reactions: In addition to the adverse reactions listed above that have been observed in patients treated with Cefuroxime (as Axetil), the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: Toxic nephropathy, aplastic anemia, hemorrhage, increased BUN, increased creatinine, false-positive test for urinary glucose, increased alkaline phosphatase, neutropenia, elevated bilirubin, and agranulocytosis.
Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see Dosage & Administration and Overdosage). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Drug/Laboratory Test Interactions: A false-positive reaction for glucose in the urine may occur with copper reduction tests (Benedict's or Fehling's solution), but not with enzyme-based tests for glycosuria. As a false-negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase method be used to determine blood/plasma glucose levels in patients receiving Cefuroxime (as Axetil). The presence of cefuroxime does not interfere with the assay of serum and urine creatinine by the alkaline picrate method.
Drug/Drug Interactions: Concomitant administration of probenecid with Cefuroxime (as Axetil) tablets increases the area under the serum concentration versus time curve by 50%. The peak serum cefuroxime concentration after a 1.5-g single dose is greater when taken with 1 g of probenecid (mean = 14.8 mcg/mL) than without probenecid (mean = 12.2 mcg/mL).
Drugs that reduce gastric acidity may result in a lower bioavailability of Cefuroxime (as Axetil) compared with that of fasting state and tend to cancel the effect of postprandial absorption.
In common with other antibiotics, Cefuroxime (as Axetil) may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

Store at temperatures not exceeding 25°C.
Protect from moisture & light.

Cephalosporins

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

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