Trigenna

Cefuroxime axetil.

Cefuroxime axetil is a 2nd generation semisynthetic, broad-spectrum cephalosporin antibiotic for oral administration.
Chemically, cefuroxime 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)-(O-methyl-oxime), 1-acetate 3-carbamate. Its molecular formula is C₂₀H₂₂N₄O₁₀S, and it has a molecular weight of 510.48.

Pharmacokinetics: After oral administration, cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa and blood to cefuroxime; absorption is enhanced in the presence of food. Cefuroxime is subsequently distributed throughout the body including pleural fluid, sputum bone, synovial fluid and aqueous humour, but only achieves therapeutic concentrations in the cerebrospinal fluid when the meninges are inflamed. Cefuroxime crosses the placenta and has been detected in breast milk. Approximately 50% of serum cefuroxime is bound to protein. Serum pharmacokinetic parameters are shown in the table.

Click on icon to see table/diagram/image

Cefuroxime is excreted unchanged by glomerular filtration and renal tubular secretion and high concentrations are achieved in the urine. Small amounts are excreted in bile. Dialysis reduces plasma concentrations.
The axetil moiety is metabolized to acetaldehyde and acetic acid.

Treatment of mild to moderate infections caused by susceptible strains of designated microorganisms: Pharyngitis/tonsilitis caused by Streptococcus pyogenes; acute bacterial otitis media caused by Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), Moraxella catarrhalis (including β-lactamase-producing strains) or Streptococcus pyogenes; acute bacterial maxillary sinusitis caused by Streptococcus pneumoniae or Haemophilus influenzae (non-β-lactamase-producing strains only); acute bacterial exacerbations of chronic bronchitis and secondary bacterial infections of acute bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae (β-lactamase negative strains) or Haemophilus parainfluenzae (β-lactamase negative strains); uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including β-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- and nonpenicillinase-producing strains of Neisseria gonorrhoeae and uncomplicated gonorrhea, rectal in females, caused by nonpenicillinase-producing strains of Neisseria gonorrhoeae; and early Lyme disease (erythema migrans) caused by Borrelia burgdorferi.

Cefuroxime axetil may be administered with or after meals at the following regimen:
Adults and Children ≥13 years: Pharyngitis/Tonsillitis: 250 mg twice daily for 10 days.
Acute Bacterial Maxillary Sinusitis: 250 mg twice daily for 10 days.
Acute Bacterial Exacerbations of Chronic Bronchitis: 250 or 500 mg twice daily for 10* days.
Secondary Bacterial Infection of Acute Bronchitis: 250 or 500 mg twice daily for 5-10* days.
Uncomplicated Skin and Skin Structure Infections and Urinary Tract Infections: 250 mg twice daily for 7-10 days.
Uncomplicated Gonorrhea: 1000 mg once with single dose of probenecid 1000 mg.
Early Lyme Disease: 500 mg twice daily for 20 days.
Children (who can swallow tablets whole): Acute Otitis Media and Acute Bacterial Maxillary Sinusitis: 250 mg twice daily for 10 days.
*The safety and effectiveness when administered for <10 days in patients with acute exacerbations of chronic bronchitis have not been established.

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

Known allergy to cephalosporin group of antibiotics.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents including cefuroxime 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.
Clostridium difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile caused 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 >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.

As with other broad-spectrum antibiotics, cefuroxime axetil should be prescribed with caution in individuals with history of colitis. Prolonged administration of cefuroxime axetil may also result in overgrowth of nonsusceptible microorganisms. If superinfection occurs during therapy, appropriate measures should be taken.
Cephalosporins, including cefuroxime axetil, should be given with caution to patients receiving concurrent treatment with potent diuretics because these diuretics are suspected of adversely affecting renal function.
Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment of 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.
Use in pregnancy: US FDA Pregnancy Category B: Reproduction studies have been performed in mice at doses up to 3200 mg/kg/day (14 times the recommended maximum human dose based in mg/m²) and in rats at doses up to 1000 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 axetil. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Trigenna should be used during pregnancy only if clearly needed.
Use in lactation: Because cefuroxime is excreted in human milk, consideration should be given to discontinuing nursing temporarily during treatment with cefuroxime axetil.

Use in pregnancy: US FDA Pregnancy Category B: Reproduction studies have been performed in mice at doses up to 3200 mg/kg/day (14 times the recommended maximum human dose based in mg/m²) and in rats at doses up to 1000 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 axetil. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Trigenna should be used during pregnancy only if clearly needed.
Use in lactation: Because cefuroxime is excreted in human milk, consideration should be given to discontinuing nursing temporarily during treatment with cefuroxime axetil.

The following hypersensitivity reactions with cefuroxime axetil have been reported: Anaphylaxis, angiodema, pruritus, rash, serum sickness-like reaction, urticaria, pseudomembranous colitis (see Warnings), hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia, increased prothrombin time, hepatic impairment including hepatitis and cholestasis, jaundice, seizure, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, renal dysfunction.
The following are also reported: Diarrhea/loose stools, nausea/vomiting, transient elevation in AST, ALT and LDH, eosinophilia, abdominal pain and cramps, flatulence, indigestion, headache, vaginitis, vulvar itch, rash, hives, itch, dysuria, chills, chest pain, shortness of breath, mouth ulcers, swollen tongue, sleepiness, thirst, anorexia, positive Coombs' test and mild to moderate hearing loss.

Concomitant administration of probenecid with cefuroxime 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 probenecid 1 g (mean = 14.8 mcg/mL) than without probenecid (mean = 12.2 mcg/mL).
Drugs that reduce the gastric acidity may result in a lower bioavailability of cefuroxime axetil compared with that of fasting state and tend to cancel the effect of postprandial absorption.
In common with other antibiotics, cefuroxime axetil may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

Store at a temperature not exceeding 30°C. Protect from direct light.

Cephalosporins

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

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