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ORCHIDPHARMA, I
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cefuroxime axetil 250 mg tab

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Uses

Cefuroxime axetil is used orally for the treatment of mild to moderate respiratory tract infections (i.e., acute maxillary sinusitis, acute exacerbations of chronic bronchitis, secondary infections of acute bronchitis, community-acquired pneumonia) caused by susceptible bacteria; acute bacterial otitis media; pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci); mild to moderate uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including β-lactamase-producing strains) or S. pyogenes; and uncomplicated urinary tract infections caused by Escherichia coli or Klebsiella pneumoniae. Cefuroxime axetil also is used orally for the treatment of Lyme disease and has been used for the treatment of uncomplicated gonorrhea. The manufacturers of cefuroxime axetil oral suspension state that safety and efficacy of the suspension have been established only for the treatment of pharyngitis and tonsillitis, acute otitis media, and impetigo caused by susceptible bacteria. and for the treatment of Lyme disease.

Cefuroxime sodium is used parenterally in the treatment of lower respiratory tract infections (including pneumonia), serious skin and skin structure infections, genitourinary tract infections, bone and joint infections, septicemia, and meningitis caused by susceptible organisms. Cefuroxime sodium also has been used parenterally for perioperative prophylaxis.

Because cefuroxime, like other second generation cephalosporins, generally is less active against susceptible gram-positive cocci than are first generation cephalosporins, most clinicians state that cefuroxime probably should not be used in the treatment of infections caused by gram-positive bacteria when a penicillin or a first generation cephalosporin could be used. In addition, because cefuroxime generally is less active in vitro against Enterobacteriaceae than third generation cephalosporins, some clinicians state that a third generation drug such as cefotaxime or ceftriaxone generally is preferred if a parenteral cephalosporin is indicated in the treatment of infections known or suspected to be caused by these gram-negative bacteria.

Prior to initiation of cefuroxime therapy, appropriate specimens should be obtained for identification of the causative organism and in vitro susceptibility tests. If cefuroxime is started pending results of susceptibility tests, it should be discontinued if the causative organism is found to be resistant to the drug. In the treatment of known or suspected sepsis or the treatment of other serious infections when the causative organism is unknown, concomitant therapy with an aminoglycoside may be indicated pending results of in vitro susceptibility tests.

Acute Otitis Media

Cefuroxime axetil is used orally for the treatment of acute otitis media (AOM) caused by S. pneumoniae, H. influenzae (including β-lactamase-producing strains), M. catarrhalis (including β-lactamase-producing strains), or S. pyogenes.

When anti-infective therapy is indicated for the treatment of AOM, the American Academy of Pediatrics (AAP) recommends high-dose amoxicillin and amoxicillin and clavulanate potassium as the drugs of first choice for initial treatment. These experts recommend certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) as alternatives for initial treatment in penicillin-allergic patients who do not have a history of severe and/or recent penicillin-allergic reactions.

Results of controlled clinical studies in children 3 months to 12 years of age with AOM indicate that a 10-day regimen of oral cefuroxime axetil is as effective or more effective than a 10-day regimen of oral cefaclor, oral amoxicillin, or oral amoxicillin and clavulanate potassium. In published studies, the overall clinical response rate to a 10-day regimen of oral cefuroxime axetil in pediatric patients with AOM has ranged from 62-94%.

Cefuroxime axetil also has been effective for the treatment of AOM in pediatric patients when administered in a 5-day regimen. In a randomized study in children 3 months to 12 years of age with AOM, a satisfactory bacteriologic response (cure or presumed cure) was obtained in 92% of those who received a 5-day regimen of cefuroxime axetil (30 mg/kg daily given in 2 divided doses), 84% of those who received a 10-day regimen or cefuroxime axetil (30 mg/kg daily given in 2 divided doses), or 95% of those who received a 10-day regimen of amoxicillin and clavulanate potassium (40 mg/kg daily given in 3 divided doses). There is evidence from a randomized study in children 6-36 months of age with AOM that a 5-day regimen of oral cefuroxime axetil is as effective as and may be better tolerated than an 8- or 10-day regimen of oral amoxicillin and clavulanate potassium. The AAP states that oral anti-infective regimens of less than 10 days' duration are not recommended for the treatment of AOM in children younger than 2 years of age or in patients with severe symptoms.

For additional information regarding treatment of AOM, including information on diagnosis and management strategies, anti-infectives for initial treatment, duration of initial treatment, and anti-infectives after initial treatment failure, .

Pharyngitis and Tonsillitis

Cefuroxime axetil is used orally for the treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci). Although cefuroxime usually is effective in eradicating S. pyogenes from the nasopharynx, efficacy of the drug in the subsequent prevention of rheumatic fever remains to be established.

Selection of an anti-infective for the treatment of S. pyogenes pharyngitis and tonsillitis should be based on the drug's spectrum of activity, bacteriologic and clinical efficacy, potential adverse effects, ease of administration, patient compliance, and cost. No regimen has been found to date that effectively eradicates group A β-hemolytic streptococci in 100% of patients.

Because the drugs have a narrow spectrum of activity, are inexpensive, and generally are effective with a low frequency of adverse effects, the AAP, Infectious Diseases Society of America (IDSA), American Heart Association (AHA), and others recommend a penicillin regimen (i.e., 10 days of oral penicillin V or oral amoxicillin or a single dose of IM penicillin G benzathine) as the treatment of choice for S. pyogenes pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever. Other anti-infectives (e.g., oral cephalosporins, oral macrolides, oral clindamycin) are recommended as alternatives in penicillin-allergic individuals.

If an oral cephalosporin is used for the treatment of S. pyogenes pharyngitis and tonsillitis, a 10-day regimen of a first generation cephalosporin (cefadroxil, cephalexin) is preferred instead of other cephalosporins with broader spectrums of activity (e.g., cefaclor, cefdinir, cefixime, cefpodoxime, cefuroxime).

Although there is some evidence that a shorter duration of therapy with certain oral cephalosporins (e.g., a 5-day regimen of cefadroxil, cefdinir, cefixime, or cefpodoxime proxetil or a 4- or 5-day regimen of cefuroxime axetil) achieves bacteriologic and clinical cure rates equal to or greater than those achieved with the traditional 10-day oral penicillin V regimen, the IDSA and AHA state that use of cephalosporin regimens administered for 5 days or less for the treatment of S. pyogenes pharyngitis and tonsillitis cannot be recommended at this time.

A 10-day regimen of oral cefuroxime axetil is at least as effective as a 10-day regimen of oral penicillin V for the treatment of S. pyogenes pharyngitis and tonsillitis. In addition, results of a prospective, randomized study in children 2-15 years of age indicate that a 4-day regimen of oral cefuroxime axetil (20 mg/kg of cefuroxime in 2 divided doses daily) is as effective as a 10-day regimen of oral penicillin V (45 mg/kg daily in 3 divided doses). The clinical response rate was 94.8% in those who received the 4-day cefuroxime regimen and 96.1% in those who received the 10-day penicillin regimen; 30 days after treatment, the bacteriologic relapse rate was 2.8 and 2.3%, respectively.

Respiratory Tract Infections

Cefuroxime axetil is used orally for the treatment of mild to moderate respiratory tract infections, including acute maxillary sinusitis caused by susceptible Streptococcus pneumoniae or Haemophilus influenzae (non-β-lactamase-producing strains only) and acute exacerbations of chronic bronchitis and secondary infections of acute bronchitis caused by susceptible S. pneumoniae, H. influenzae (non-β-lactamase-producing strains only), or H. parainfluenzae (non-β-lactamase-producing strains only).

Cefuroxime sodium is used parenterally for the treatment of lower respiratory tract infections, including pneumonia, caused by susceptible S. pneumoniae, Staphylococcus aureus (penicillinase- and nonpenicillinase-producing strains), S. pyogenes (group A β-hemolytic streptococci), H. influenzae (including ampicillin-resistant strains), Escherichia coli, and Klebsiella.

Acute Sinusitis

Cefuroxime axetil is used orally for the treatment of acute maxillary sinusitis caused by susceptible S. pneumoniae or H. influenzae (non-β-lactamase-producing strains only). The manufacturers state that insufficient data exist to establish efficacy of cefuroxime axetil in the treatment of acute bacterial maxillary sinusitis that is known or suspected to be caused by β-lactamase-producing strains of H. influenzae or M. catarrhalis.

When anti-infective therapy is indicated for the treatment of acute bacterial sinusitis, the IDSA recommends amoxicillin and clavulanate potassium and the AAP recommends either amoxicillin or amoxicillin and clavulanate potassium as the drug of choice for initial empiric treatment. Because of variable activity against S. pneumoniae and H. influenzae, the IDSA no longer recommends second or third generation oral cephalosporins for empiric monotherapy of sinusitis in adults or children. If an oral cephalosporin is used as an alternative for empiric treatment of acute bacterial sinusitis in children (e.g., in penicillin-allergic individuals), the IDSA and AAP recommend a combination regimen that includes a third generation cephalosporin (cefixime or cefpodoxime) and clindamycin (or linezolid).

Community-Acquired Pneumonia

Oral cefuroxime axetil is used for the treatment of mild to moderate community-acquired pneumonia (CAP). The American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) recommended cefuroxime as an alternative for treatment of CAP caused by penicillin-susceptible S. pneumoniae and as an alternative in certain combination regimens used for empiric treatment of CAP.

Initial treatment of CAP generally involves use of an empiric anti-infective regimen based on the most likely pathogens and local susceptibility patterns; therapy may then be changed (if possible) to provide a more specific regimen (pathogen-directed therapy) based on results of in vitro culture and susceptibility testing. The most appropriate empiric regimen varies depending on the severity of illness at the time of presentation and whether outpatient treatment or hospitalization in or out of an intensive care unit (ICU) is indicated and the presence or absence of cardiopulmonary disease and other modifying factors that increase the risk of certain pathogens (e.g., penicillin- or multidrug-resistant Streptococcus pneumoniae, enteric gram-negative bacilli, Pseudomonas aeruginosa). Most experts recommend that an empiric regimen for the treatment of CAP include an anti-infective active against S. pneumoniae since this organism is the most commonly identified cause of bacterial pneumonia and causes more severe disease than many other common CAP pathogens.

For empiric outpatient treatment of CAP when risk factors for drug-resistant S. pneumoniae are present (e.g., comorbidities such as chronic heart, lung, liver, or renal disease, diabetes, alcoholism, malignancies, asplenia, immunosuppression; use of anti-infectives within the last 3 months), ATS and IDSA recommend monotherapy with a fluoroquinolone active against S. pneumoniae (moxifloxacin, gemifloxacin, levofloxacin) or, alternatively, a combination regimen that includes a β-lactam active against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline. Cefuroxime and cefpodoxime may be less active against S. pneumoniae than amoxicillin or ceftriaxone.

A sequential regimen of parenteral cefuroxime sodium (given for 48-72 hours) followed by oral cefuroxime axetil (given for 7 days) has been used effectively for the treatment of CAP in adults. If a parenteral cephalosporin is used as an alternative to penicillin G or amoxicillin for treatment of CAP caused by penicillin-susceptible S. pneumoniae, ATS and IDSA recommend ceftriaxone, cefotaxime or cefuroxime; if an oral cephalosporin is used for treatment of these infections, ATS and IDSA recommend cefpodoxime, cefprozil, cefuroxime, cefdinir, or cefditoren.

For additional information on treatment of CAP,

Gonorrhea and Associated Infections

IM cefuroxime sodium has been used in conjunction with oral probenecid for the treatment of uncomplicated gonorrhea and disseminated gonococcal infections caused by Neisseria gonorrhoeae, including penicillinase-producing strains (PPNG). Cefuroxime axetil has been used orally for the treatment of uncomplicated urethral and endocervical gonorrhea caused by N. gonorrhoeae and for the treatment of uncomplicated rectal gonorrhea in females caused by nonpenicillinase-producing strains of the organism. However, parenteral cefuroxime sodium and oral cefuroxime axetil are not included in current US Centers for Disease Control and Prevention (CDC) recommendations for the treatment of gonococcal infections.

Because of concerns related to recent reports of N. gonorrhoeae with reduced susceptibility to cephalosporins, the CDC states that oral cephalosporins are no longer recommended as first-line treatment for uncomplicated gonorrhea. For the treatment of uncomplicated urogenital, anorectal, or pharyngeal gonorrhea, the CDC recommends a combination regimen that includes a single dose of IM ceftriaxone and either a single dose of oral azithromycin or a 7-day regimen of oral doxycycline.

The CDC states that cefuroxime axetil at the dosage recommended by the manufacturers (single 1-g oral dose of cefuroxime) meets the minimum efficacy criteria for treatment of urogenital and rectal gonococcal infections, but the pharmacodynamics of this oral drug are less favorable than those of IM ceftriaxone, oral cefixime, or oral cefpodoxime. In addition, cefuroxime axetil has unsatisfactory efficacy in pharyngeal infections.

For additional information on current recommendations for the treatment of gonorrhea and associated infections, .

Lyme Disease

Oral cefuroxime axetil is used in adults and children for the treatment of early Lyme disease manifested as erythema migrans. When an oral regimen is indicated, oral cefuroxime axetil also is used in the treatment of early neurologic Lyme disease in patients with cranial nerve palsy alone without evidence of meningitis, Lyme carditis, borrelial lymphocytoma, and uncomplicated Lyme arthritis without clinical evidence of neurologic disease.

Lyme disease is a tick-borne spirochetal disease. In the US, Lyme disease is caused by the spirochete Borrelia burgdorferi, which is transmitted by the bite of Ixodes scapularis or I. pacificus ticks. For additional information on Lyme disease,

Early Lyme Disease

Erythema Migrans

Oral cefuroxime axetil is used for the treatment of early Lyme disease manifested as erythema migrans.

The IDSA, AAP, and other clinicians recommend oral doxycycline, oral amoxicillin, or oral cefuroxime axetil as first-line therapy for the treatment of early localized or early disseminated Lyme disease associated with erythema migrans, in the absence of specific neurologic involvement or advanced atrioventricular (AV) heart block. The IDSA states that a 14-day regimen (range 14-21 days) of any of these oral anti-infectives (doxycycline, amoxicillin, cefuroxime axetil) may be used for initial treatment of early Lyme disease since all 3 drugs have been shown to be effective for the treatment of erythema migrans and associated symptoms in prospective clinical studies. Doxycycline offers the advantage of also being effective for the treatment of human granulocytic anaplasmosis (HGA, formerly known as human granulocytic ehrlichiosis), which may occur simultaneously with early Lyme disease.

Efficacy of cefuroxime axetil for the treatment of early Lyme disease has been evaluated in studies that included adults and pediatric patients 12 years of age or older with physician-documented erythema migrans (with or without systemic manifestations of infection), and results of these studies indicate that the drug is as effective as oral doxycycline in producing resolution of erythema migrans and preventing the development of manifestations of late Lyme disease. The clinical diagnosis of early Lyme disease in study patients was validated objectively by a blinded expert who examined available photographs of skin lesions taken before therapy and/or by serologic evidence of antibodies specific to B. burgdorferi identified using enzyme-linked immunosorbent assay (ELISA) and Western immunoblot. Patients were randomized to receive oral cefuroxime axetil (500 mg of cefuroxime twice daily) or oral doxycycline (100 mg 3 times daily) for 20 days and evaluated during treatment (days 8-12) and posttreatment (days 1-5, 1 month, and then at 3-month intervals for up to 1 year). In patients who were evaluated at 1 month posttreatment, a satisfactory clinical response consisting of either clinical success (defined as resolution of erythema migrans and other manifestations of infection within 5 days posttreatment and maintained through follow-up at 1 month posttreatment) or clinical improvement (defined as resolution of erythema migrans within 5 days posttreatment with incomplete resolution of other manifestations of infection at that time but further improvement or complete resolution of manifestations by follow-up at 1 month posttreatment) was attained in 91 or 93% of patients who received cefuroxime axetil or doxycycline, respectively. Clinical success was attained in 72 or 73% of patients receiving cefuroxime axetil or doxycycline, respectively; clinical improvement was attained in 19% of patients receiving either drug. In patients evaluated at 1 year, a satisfactory clinical outcome consisting of success (defined as the absence of signs or symptoms of late Lyme disease throughout the 1-year follow-up) or clinical improvement (defined as the presence of some signs or symptoms consistent with late Lyme disease but no objective evidence of active disease throughout the 1-year follow-up) was attained in 84 or 87% of patients who received cefuroxime axetil or doxycycline, respectively. Success at 1 year was attained in 73% of patients receiving either drug; clinical improvement was attained in 10% of patients receiving cefuroxime axetil and 13% of patients receiving doxycycline.

Early Neurologic Lyme Disease

Oral cefuroxime axetil is used in the treatment of early neurologic Lyme disease in patients with cranial nerve palsy alone without evidence of meningitis. Parenteral anti-infectives (IV ceftriaxone, IV penicillin G sodium, IV cefotaxime) are recommended for the treatment of early Lyme disease when there are acute neurologic manifestations such as meningitis or radiculopathy. However, some clinicians suggest that a 14-day regimen (range: 14-21 days) of oral anti-infectives (amoxicillin, doxycycline, cefuroxime axetil) may be used in patients with cranial nerve palsy without clinical evidence of meningitis (i.e., those with normal CSF examinations or those for whom CSF examination is deemed unnecessary because there are no clinical signs of meningitis). Although there is some experience using oral anti-infectives in patients with seventh cranial nerve palsy, it is unclear whether an oral regimen would be as effective for patients with other cranial neuropathies. Although anti-infectives may not hasten resolution of seventh cranial nerve palsy associated with B. burgdorferi infection, anti-infectives should be given to prevent further sequelae.

Lyme Carditis

Oral cefuroxime axetil is used in the treatment of Lyme carditis. The IDSA states that patients with AV heart block and/or myopericarditis associated with early Lyme disease may be treated with a 14-day regimen (range: 14-21 days) of oral or parenteral anti-infectives. Although there is no evidence to date to suggest that a parenteral regimen is more effective than an oral regimen for the treatment of Lyme carditis, a parenteral regimen usually is recommended for initial treatment of hospitalized patients; an oral regimen can be used to complete therapy and for the treatment of outpatients. When a parenteral regimen is used, IV ceftriaxone or, alternatively, IV cefotaxime or IV penicillin G sodium is recommended. When an oral regimen is used, oral doxycycline, oral amoxicillin, or oral cefuroxime axetil is recommended.

Borrelial Lymphocytoma

Although experience is limited, the IDSA states that available data indicate that borrelial lymphocytoma may be treated with a 14-day regimen (range 14-21 days) of oral doxycycline, oral amoxicillin, or oral cefuroxime axetil in the dosages used for the treatment of erythema migrans.

Late Lyme Disease

Lyme Arthritis

Patients with uncomplicated Lyme arthritis without clinical evidence of neurologic disease generally can be treated with a 28-day regimen of oral doxycycline, oral amoxicillin, or oral cefuroxime axetil. Patients with Lyme arthritis and concomitant neurologic disease should receive a parenteral regimen of IV ceftriaxone or, alternatively, IV cefotaxime or IV penicillin G sodium. While oral regimens are easier to administer, associated with fewer serious adverse effects, and less expensive than IV regimens, some patients with Lyme arthritis treated with oral anti-infectives have subsequently developed overt neuroborreliosis, which may require IV therapy for successful resolution. Therefore, additional study is needed to fully evaluate the comparative safety and efficacy of oral versus IV anti-infectives for the treatment of Lyme arthritis.

In patients who have persistent or recurrent joint swelling after a recommended oral regimen, the IDSA and other clinicians recommend retreatment with the oral regimen or a switch to a parenteral regimen. Some clinicians prefer retreatment with an oral regimen for patients whose arthritis substantively improved but did not completely resolve; these clinicians reserve parenteral regimens for those patients whose arthritis failed to improve or worsened. It has been suggested that clinicians should consider allowing several months for joint inflammation to resolve after initial treatment before an additional course of anti-infectives is given.

Meningitis

Parenteral cefuroxime has been used in neonates, children, and adults for the treatment of meningitis caused by susceptible S. pneumoniae, H. influenzae (including ampicillin-resistant strains), N. meningitidis, or S. aureus (penicillinase- and nonpenicillinase-producing strains); however, cefuroxime is not considered a drug of choice for these infections. Treatment failures have been reported when cefuroxime was used in the treatment of meningitis, especially in meningitis caused by H. influenzae. In addition, while results of some studies in pediatric patients with meningitis indicate that the clinical cure rate with IV cefuroxime is similar to that reported for IV ceftriaxone, the bacteriologic response to cefuroxime appears to be slower, which may increase the risk for hearing loss and neurologic sequelae. In a study in children 44 days to 16 years of age with acute bacterial meningitis who were randomized to receive empiric therapy with IV ceftriaxone (100 mg/kg once daily) or IV cefuroxime (240 mg/kg daily in 4 doses), all patients in both groups were considered clinically cured; however, the rate of sterilization of CSF after the first 18-36 hours of therapy was higher in those who received ceftriaxone (98%) than in those who received cefuroxime (88%). When a cephalosporin is indicated for the treatment of bacterial meningitis, a parenteral third generation cephalosporin (usually ceftriaxone or cefotaxime) generally is recommended.

Perioperative Prophylaxis

IV cefuroxime sodium is used for perioperative prophylaxis in patients undergoing cardiac surgery and is considered a drug of choice for cardiac procedures (e.g., coronary artery bypass, pacemaker or other cardiac device insertion, ventricular assist devices). IV cefuroxime also is considered a drug of choice when used alone for perioperative prophylaxis in patients undergoing clean head and neck surgery involving placement of prosthesis (excluding tympanostomy) and when used in conjunction with metronidazole for perioperative prophylaxis in patients undergoing clean-contaminated cancer surgery of the head and neck or other clean-contaminated head and neck procedures (excluding tonsillectomy and functional endoscopic sinus procedures).

IV cefuroxime also has been used for perioperative prophylaxis in patients undergoing noncardiac thoracic surgery, GI or biliary tract surgery, gynecologic or obstetric surgery (e.g., vaginal hysterectomy), orthopedic procedures, or heart transplantation. However, other anti-infectives (e.g., cefazolin) usually are recommended for perioperative prophylaxis in patients undergoing these procedures.

Dosage and Administration

Reconstitution and Administration

Cefuroxime axetil is administered orally. Cefuroxime sodium is administered by IV injection or infusion or by deep IM injection. The drug should be given IV rather than IM in patients with septicemia or other severe or life-threatening infections or in patients with lowered resistance, particularly if shock is present.

Oral Administration

Cefuroxime axetil oral suspension must be administered with food. Although cefuroxime axetil film-coated tablets may be given orally without regard to meals, administration with food maximizes bioavailability of the drug.(See Pharmacokinetics: Absorption.)

In children aged 3 months to 12 years who are unable to swallow tablets, cefuroxime may be administered as the commercially available oral suspension. Although commercially available cefuroxime axetil tablets have been crushed and mixed with food (e.g., applesauce, ice cream), the crushed tablets have a strong, persistent taste and the manufacturers state that the drug should not be administered in this manner.(See Cautions: Pediatric Precautions.) Cefuroxime axetil tablets also have been allowed to disintegrate in a small amount (60-90 mL) of beverage (e.g., apple juice or milk) and the beverage stirred and ingested immediately followed by additional amounts of beverage; disintegration of the tablets is optimal when the beverage is at room temperature.

Limited data from a study conducted by the manufacturer suggest that cefuroxime axetil is stable for 2 hours at room temperature when added as single 125- or 250-mg tablets to 40 mL of Tropicana orange juice, Welch's grape juice, or Nestle's chocolate milk. However, extemporaneous preparation of an oral suspension of the drug intended for multiple dosing currently is not recommended since stability information for more prolonged periods currently is not available and because the drug is commercially available as an oral suspension.

The child's tolerance of the taste of cefuroxime axetil should be ascertained by the clinician and parent, preferably when prescription of the drug is being considered (e.g., while the child is still in the physician's office).

Reconstitution

Cefuroxime axetil powder for oral suspension should be reconstituted at the time of dispensing by adding the amount of water specified on the bottle to provide a suspension containing 125 or 250 mg of cefuroxime (as cefuroxime axetil) per 5 mL of suspension. After tapping the bottle to thoroughly loosen the powder for oral suspension, the water should be added in one portion and the suspension agitated well.

The suspension should be agitated well just prior to each use and the cap replaced securely after each opening.

Intermittent IV Injection

For direct intermittent IV injection, vials labeled as containing 750 mg or 1.5 g of cefuroxime should be reconstituted with 8 or 16 mL, respectively, of sterile water for injection to provide solutions containing approximately 90 mg/mL; the entire contents of the vial should be withdrawn for each dose.

The appropriate dose should then be injected directly into a vein over a 3- to 5-minute period or injected slowly into the tubing of a freely flowing compatible IV solution.

Intermittent or Continuous IV Infusion

ADD-Vantage (TwistVial) vials labeled as containing 750 mg or 1.5 g of cefuroxime should be reconstituted with 50 or 100 mL of 5% dextrose injection, 0.9% sodium chloride injection, or 0.45% sodium chloride injection in a compatible flexible container according to the manufacturer's directions.

Alternatively, the commercially available Duplex drug delivery system containing 750 mg or 1.5 g of cefuroxime and 50 mL of dextrose 4.1 or 2.9% injection, respectively, in separate chambers should be reconstituted (activated) according to the manufacturer's directions and administered by IV infusion.

The 7.5-g pharmacy bulk vial should be reconstituted according to the manufacturer's directions. The pharmacy bulk vial is not intended for direct IV infusion.

Thawed solutions of the commercially available frozen premixed cefuroxime sodium injection should be administered only by intermittent or continuous IV infusion. The frozen injection should be thawed at room temperature (25°C) or under refrigeration (5°C); the injection should not be thawed by warming in a water bath or by exposure to microwave radiation. Precipitates that may have formed in the frozen injection usually will dissolve with little or no agitation when the injection reaches room temperature; potency is not affected. After thawing to room temperature, the injection should be agitated and the container checked for minute leaks by firmly squeezing the bag; the container may be fragile and should be handled with care. The injection should be discarded if container seals or outlet ports are not intact or leaks are found or if the solution is cloudy or contains an insoluble precipitate. Additives should not be introduced into the injection container. The injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.

Other IV solutions flowing through a common administration tubing or site should be discontinued while cefuroxime is being infused unless the solutions are known to be compatible and the flow rate is adequately controlled. If an aminoglycoside is administered concomitantly with cefuroxime, the drugs should be administered at separate sites.

Rate of Administration

Intermittent IV infusions of cefuroxime generally are infused over 15-60 minutes.

IM Injection

IM injections of Zinacef are prepared by adding 3 mL of sterile water for injection to a vial labeled as containing 750 mg of cefuroxime to provide a suspension containing approximately 220 mg/mL. The suspension should be shaken gently prior to administration, and the entire contents of the vial should be withdrawn for each dose.

IM injections should be made deeply into a large muscle mass such as the gluteus or lateral aspect of the thigh. The plunger of the syringe should be drawn back before IM injection to ensure that the needle is not in a blood vessel.

Dosage

Dosage of cefuroxime axetil is expressed in terms of cefuroxime. Cefuroxime axetil tablets and oral suspension are not bioequivalent and are not substitutable on a mg/mg basis.(See Pharmacokinetics: Absorption.)

Dosage of cefuroxime sodium also is expressed in terms of cefuroxime and is identical for IM or IV administration.

Adult Dosage

General Oral Adult Dosage

For the treatment of uncomplicated skin and skin-structure infections in adults and adolescents 13 years of age or older, the usual oral dosage of cefuroxime given as cefuroxime axetil tablets is 250 or 500 mg twice daily for 10 days. For the treatment of uncomplicated urinary tract infections (UTIs), the usual oral dosage of cefuroxime given as cefuroxime axetil tablets is 125 or 250 mg twice daily for 7-10 days.

The usual parenteral adult dosage of cefuroxime given as cefuroxime sodium is 750 mg to 1.5 g every 8 hours. Uncomplicated UTIs, skin and skin structure infections, and uncomplicated pneumonia in adults generally respond to a parenteral dosage of 750 mg every 8 hours. Severe or complicated infections or bone and joint infections in adults generally require 1.5 g every 8 hours and life-threatening infections or infections caused by less susceptible organisms may require 1.5 g every 6 hours. Dosage of parenteral cefuroxime for the treatment of bacterial meningitis in adults should not exceed 3 g every 8 hours.

Pharyngitis and Tonsillitis

For the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci) in adults and adolescents 13 years of age or older, the usual oral dosage of cefuroxime given as cefuroxime axetil tablets is 250 mg twice daily for 10 days.

Respiratory Tract Infections

For the treatment of acute bacterial maxillary sinusitis in adults and adolescents 13 years of age or older, the usual oral dosage of cefuroxime given as cefuroxime axetil tablets is 250 mg twice daily for 10 days. For the treatment of acute bacterial exacerbations of chronic bronchitis and secondary bacterial infections of acute bronchitis in adults and adolescents 13 years of age or older, the usual oral dosage of cefuroxime given as cefuroxime axetil tablets is 250 or 500 mg twice daily. The manufacturers recommend that therapy be continued for 10 days for the treatment of acute bacterial exacerbations of chronic bronchitis or for 5-10 days for the treatment of secondary bacterial infections of acute bronchitis. While there is evidence that a 5-day regimen of cefuroxime axetil is as effective as a 10-day regimen of the drug for the treatment of secondary bacterial infections of acute bronchitis, efficacy of the shorter regimen for the treatment of acute exacerbations of chronic bronchitis has not been established.

If cefuroxime axetil is used for the outpatient treatment of community-acquired pneumonia (CAP) in adults, the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) recommend an oral dosage of 500 mg of cefuroxime twice daily. For empiric treatment of CAP, cefuroxime must be used in conjunction with other anti-infectives.(See Community-acquired Pneumonia under Uses: Respiratory Tract Infections.)

For the treatment of uncomplicated pneumonia in adults, the manufacturers recommend a parenteral cefuroxime dosage of 750 mg every 8 hours. In severe or complicated infections, a dosage of 1.5 g every 8 hours is recommended.

Gonorrhea and Associated Infections

For the parenteral treatment of uncomplicated gonorrhea caused by Neisseria gonorrhoeae, including penicillinase-producing strains (PPNG), the manufacturer of Zinacef recommends that adults receive a single 1.5-g IM dose of cefuroxime and 1 g of oral probenecid; the cefuroxime dose should be divided and given at 2 different sites. For the parenteral treatment of disseminated gonococcal infections, the manufacturers recommend that adults receive 750 mg of cefuroxime IM or IV every 8 hours.

For the oral treatment of uncomplicated urethral or endocervical gonorrhea caused by N. gonorrhoeae or for the oral treatment of uncomplicated rectal gonorrhea in females caused by nonpenicillinase-producing strains of the organism, adults and adolescents 13 years of age or older have received a single 1-g dose of cefuroxime.

The US Centers for Disease Control and Prevention (CDC) does not recommend oral or parenteral cefuroxime for the treatment of gonococcal infections.(See Uses: Gonorrhea and Associated Infections.)

Lyme Disease

For the treatment of early Lyme disease manifested as erythema migrans, the manufacturers recommend that adults and adolescents 13 years of age or older receive 500 mg of oral cefuroxime twice daily for 20 days.

IDSA and other clinicians recommend that adults receive 500 mg of oral cefuroxime twice daily for 14 days (range: 14-21 days) for the treatment of early localized or early disseminated Lyme disease manifested as erythema migrans, in the absence of specific neurologic involvement or advanced atrioventricular (AV) heart block.

If an oral regimen is used for the treatment of early neurologic Lyme disease in patients with cranial nerve palsy alone without clinical evidence of meningitis (see Early Neurologic Lyme Disease under Uses: Lyme Disease), Lyme carditis, or borrelial lymphocytoma, the IDSA recommends that adults receive 500 mg of oral cefuroxime twice daily for 14 days (range: 14-21 days).

If an oral regimen is used for the treatment of uncomplicated Lyme arthritis in patients without clinical evidence of neurologic disease (see Late Lyme Disease under Uses: Lyme Disease), the IDSA recommends that adults receive 500 mg of oral cefuroxime twice daily for 28 days.

Perioperative Prophylaxis

For perioperative prophylaxis in adults undergoing open-heart surgery, the manufacturers recommend that a single 1.5-g dose of cefuroxime be given IV at the time of induction of anesthesia and every 12 hours thereafter for a total dosage of 6 g (i.e., up to 48 hours). Some experts recommend that 1.5 g of cefuroxime be given within 1 hour prior to surgical incision and that additional 1.5-g doses be given every 4 hours during prolonged procedures (longer than 4 hours) or if major blood loss occurs. Various data support a duration of perioperative prophylaxis ranging from a single preoperative dose to continuation of prophylaxis for 24 hours postoperatively; there is no evidence of benefit beyond 48 hours and no evidence to support continuing prophylaxis until all drains and indwelling catheters are removed.

If cefuroxime is used for perioperative prophylaxis in other clean-contaminated or potentially contaminated surgery (e.g., vaginal hysterectomy), the manufacturers recommend that adults receive 1.5 g of cefuroxime IV just prior to surgery (approximately 30-60 minutes before the initial incision) and, in lengthy operations, 750 mg of the drug IV or IM every 8 hours. For most procedures, postoperative doses are usually unnecessary and may increase the risk of bacterial resistance. If the procedure is prolonged (longer than 4 hours) or if major blood loss occurs, 1.5-g doses of cefuroxime may be given IV every 4 hours.

Pediatric Dosage

Cefuroxime axetil film-coated tablets and oral suspension are not bioequivalent and are not substitutable on a mg/mg basis.(See Pharmacokinetics: Absorption.)

General Pediatric Dosage

For the treatment of most susceptible infections (except bone and joint infections or meningitis) in children 3 months of age or older, the manufacturers recommend a cefuroxime dosage of 50-100 mg/kg daily given IM or IV in equally divided doses every 6-8 hours; the manufacturer states that 100 mg/kg should be given IM or IV for more severe infections. The IM or IV dosage of cefuroxime recommended by the manufacturers for the treatment of bone and joint infections in children 3 months of age or older is 150 mg/kg daily in 3 divided doses every 8 hours.

The American Academy of Pediatrics (AAP) recommends that neonates 7 days of age or younger receive IM or IV cefuroxime in a dosage of 50 mg/kg every 12 hours, regardless of weight. Neonates 8-28 days of age should receive a dosage of 50 mg/kg every 8-12 hours if they weigh 2 kg or less or 50 mg/kg every 8 hours if they weigh more than 2 kg.

For pediatric patients beyond the neonatal period, the AAP recommends an IM or IV cefuroxime dosage of 75-100 mg/kg daily given in 3 equally divided doses for the treatment of mild to moderate infections or 100-200 mg/kg daily in 3 or 4 equally divided doses for the treatment of severe infections. These clinicians recommend that children beyond the neonatal period receive oral cefuroxime in a dosage of 20-30 mg/kg daily in 2 equally divided doses for the treatment of mild to moderate infections. The AAP states that oral cefuroxime is inappropriate for the treatment of severe infections.

Acute Otitis Media

For the treatment of acute otitis media in children 3 months to 12 years of age who can swallow tablets whole, the usual oral dosage of cefuroxime as cefuroxime axetil film-coated tablets is 250 mg twice daily for 10 days. Alternatively, children 3 months to 12 years of age with acute otitis media can receive cefuroxime as cefuroxime axetil oral suspension in a dosage of 30 mg/kg daily (maximum 1 g daily) given in 2 divided doses for 10 days.

Cefuroxime axetil has been administered in a 5-day regimen for the treatment of acute otitis media in children 3 months to 12 years of age. The AAP states that oral anti-infective regimens of less than 10 days' duration are not recommended for the treatment of AOM in children younger than 2 years of age or in patients with severe symptoms.

Pharyngitis and Tonsillitis

For the treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci) in children 3 months to 12 years of age who can swallow tablets whole, the usual oral dosage of cefuroxime as cefuroxime axetil film-coated tablets is 125 mg every 12 hours for 10 days. Alternatively, children 3 months to 12 years of age may receive cefuroxime as cefuroxime axetil oral suspension in a dosage of 20 mg/kg daily (maximum 500 mg daily) in 2 divided doses for 10 days.

Acute Sinusitis

For the treatment of acute bacterial maxillary sinusitis in children 3 months to 12 years of age who can swallow tablets whole, the usual oral dosage of cefuroxime as cefuroxime axetil film-coated tablets is 250 mg twice daily for 10 days. Alternatively, children 3 months to 12 years of age may receive cefuroxime as cefuroxime axetil oral suspension in a dosage of 30 mg/kg daily (maximum 1 g daily) given in 2 divided doses for 10 days.

Lyme Disease

For the treatment of early localized or early disseminated Lyme disease manifested as erythema migrans, in the absence of specific neurologic involvement or advanced AV heart block, the manufacturer, IDSA, AAP, and other clinicians recommend that children receive oral cefuroxime in a dosage of 30 mg/kg daily (up to 1 g daily) administered in 2 divided doses for 14 days (range 14-21 days).

If an oral regimen is used for the treatment of early neurologic Lyme disease in patients with cranial nerve palsy alone without clinical evidence of meningitis (see Early Neurologic Lyme Disease under Uses: Lyme Disease), Lyme carditis, or borrelial lymphocytoma, the IDSA recommends that children receive oral cefuroxime in a dosage of 30 mg/kg daily in 2 equally divided doses (up to 500 mg per dose) for 14 days (range 14-21 days).

If an oral regimen is used for the treatment of uncomplicated Lyme arthritis in patients without clinical evidence of neurologic disease (see Late Lyme Disease under Uses: Lyme Disease), the IDSA and AAP recommend that children receive oral cefuroxime in a dosage of 30 mg/kg daily in 2 equally divided doses (up to 500 mg per dose) for 28 days.

Meningitis

For the treatment of bacterial meningitis in children 3 months of age or older, the usual dosage of IV cefuroxime is 200-240 mg/kg daily given in divided doses every 6-8 hours.

Skin and Skin Structure Infections

For the treatment of impetigo in children 3 months to 12 years of age, the usual oral dosage of cefuroxime as cefuroxime axetil oral suspension is 30 mg/kg daily (maximum 1 g daily) in 2 divided doses for 10 days.

Perioperative Prophylaxis

If cefuroxime is used for perioperative prophylaxis in children, some clinicians recommend that 50 mg/kg of cefuroxime be given within 1 hour prior to surgical incision. If the procedure is prolonged (longer than 4 hours) or if major blood loss occurs, additional 50-mg/kg doses may be given IV. Various data support a duration of perioperative prophylaxis ranging from a single preoperative dose to continuation of prophylaxis for 24 hours postoperatively; there is no evidence of benefit beyond 48 hours and no evidence to support continuing prophylaxis until all drains and indwelling catheters are removed.

Duration of Therapy

The duration of cefuroxime therapy depends on the type of infection but should generally be continued for at least 48-72 hours after the patient becomes afebrile or evidence of eradication of the infection is obtained.

For the treatment of uncomplicated UTIs, the manufacturers recommend that therapy with cefuroxime axetil tablets be continued for 7-10 days. For the treatment of uncomplicated skin and skin-structure infections, or acute otitis media caused by susceptible organisms, the manufacturers recommend that therapy with cefuroxime axetil tablets be continued for 10 days.

Chronic urinary tract infections may require several weeks of cefuroxime therapy, and bacteriologic and clinical assessments should be made frequently during therapy and for several months after the drug is discontinued. When cefuroxime is used in the treatment of staphylococcal and other infections involving a collection of pus, surgical drainage should be performed when indicated.

Dosage in Renal Impairment

Modification of usual dosage of parenteral cefuroxime is unnecessary in patients with creatinine clearances greater than 20 mL/minute. However, in patients with creatinine clearances of 20 mL/minute or less, doses and/or frequency of administration of parenteral cefuroxime must be modified in response to the degree of renal impairment, severity of the infection, and susceptibility of the causative organism. The manufacturers and some clinicians recommend that adults with creatinine clearances of 10-20 mL/minute receive 750 mg IM or IV every 12 hours and that adults with creatinine clearances less than 10 mL/minute receive 750 mg IM or IV every 24 hours. In children with impaired renal function, the manufacturers recommend that the frequency of administration of parenteral cefuroxime be modified based on the recommendations for adults with impaired renal function.

In patients undergoing hemodialysis, a supplemental dose of parenteral cefuroxime should be given after each dialysis period.

Safety and efficacy of oral cefuroxime axetil in patients with renal impairment have not been established.

Cautions

Adverse effects reported with cefuroxime axetil and cefuroxime sodium are similar to those reported with other cephalosporins.

Dermatologic and Sensitivity Reactions

Hypersensitivity reactions have been reported in less than 1% of patients receiving cefuroxime axetil or cefuroxime sodium. These reactions include rash (e.g., morbilliform), fever, pruritus, erythema, urticaria, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, serum sickness-like reactions, angioedema, and anaphylaxis. At least one case of severe bronchospasm has been reported in a patient who received cefuroxime axetil. Positive direct antiglobulin (Coombs') test results have also been reported in a few patients receiving oral or parenteral cefuroxime; however, it is not clear whether the mechanism of this reaction is immunologic in nature. If a severe hypersensitivity reaction occurs during cefuroxime therapy, the drug should be discontinued and the patient given appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated.

There is clinical and laboratory evidence of partial cross-allergenicity among cephalosporins and other β-lactam antibiotics including penicillins and cephamycins; however, the true incidence of cross-allergenicity among these anti-infectives has not been established. When cefuroxime axetil was used in patients with a history of delayed hypersensitivity reactions to penicillins and no history of hypersensitivity to cephalosporins, a delayed hypersensitivity reaction occurred in about 3% of these patients. The manufacturer states that when cefuroxime sodium was used in patients with a history of hypersensitivity to penicillin, rash reportedly occurred in 4.4-6.7% of these patients.

Local Effects

The most frequent adverse reactions to IM or IV cefuroxime sodium are local reactions at the injection site. Mild to moderate pain, which persists for less than 5 minutes, has been reported in up to 95% of patients following IM administration of cefuroxime. Severe pain has been reported occasionally. IM injections of cefuroxime reportedly are less painful when the drug is administered as a suspension rather than a solution and are also less painful when the injection is given into the buttock rather than the thigh.

Thrombophlebitis reportedly occurs in approximately 2% of patients receiving cefuroxime IV.

GI Effects

Nausea and vomiting have been reported in 2.6-6.7% and diarrhea or loose stools have been reported in 3.7-10.6% of patients receiving oral cefuroxime axetil. A strong, persistent, bitter taste has been reported when cefuroxime axetil was administered as crushed tablets(see Pediatric Precautions). In addition, up to 5% of children receiving the commercially available oral suspension of cefuroxime axetil disliked the taste of the suspension; during clinical trials, discontinuance of therapy because of the taste of the suspension or other problems with administration occurred in 1.4% of patients.

Gagging, epigastric burning, GI bleeding, abdominal pain, flatulence, GI infection, ptyalism, indigestion, mouth ulcers, swollen tongue, anorexia, thirst, dyspepsia, and stomach cramps also have been reported in patients receiving the drug orally.

The frequency of adverse GI effects (particularly diarrhea) may be greater with oral cefuroxime axetil than with oral cefaclor, and nausea appears to be more common when oral cefuroxime axetil is used concomitantly with oral probenecid than when the antibiotic is used alone. In addition, adverse GI effects were reported more frequently with previously available oral formulations of cefuroxime axetil, and, in part, prompted several reformulations of the product. Adverse GI effects including nausea and diarrhea have been reported in less than 1% of patients receiving IM or IV cefuroxime sodium.

Clostridium difficile-associated Diarrhea and Colitis

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.

C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives, including cefuroxime, and may range in severity from mild diarrhea to fatal colitis.C. difficile produces toxins A and B which contribute to the development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

CDAD should be considered in the differential diagnosis in patients who develop diarrhea during or after anti-infective therapy and managed accordingly. Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.

If CDAD is suspected or confirmed, anti-infectives not directed against C. difficile should be discontinued whenever possible. Patients should be managed with appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.

Hematologic Effects

Decreased hemoglobin concentration and decreased hematocrit have been reported in about 10% of patients receiving cefuroxime. Transient eosinophilia occurs less frequently, and transient neutropenia, pancytopenia, thrombocytopenia, and leukopenia occur rarely. Thrombocytosis, lymphocytosis, hemolytic anemia, and increased prothrombin time also have been reported.

CNS Effects

Headache, dizziness, somnolence or sleepiness, hyperactivity, irritable behavior, seizures, myoclonic jerks, and generalized hyperexcitability have been reported rarely in patients receiving cefuroxime.

A psychotic reaction, consisting of disorientation, fluctuating consciousness, and episodes of restlessness, agitation, and anxiety, occurred in a geriatric patient who received IV cefuroxime sodium; symptoms resolved within 24 hours after the drug was discontinued. Some patients who experienced adverse CNS effects while receiving cefuroxime had preexisting renal impairment.

Hepatic Effects

Transient increases in serum AST (SGOT), ALT (SGPT), alkaline phosphatase, LDH, and bilirubin concentrations have been reported in less than 5% of patients receiving oral or parenteral cefuroxime. Jaundice has been reported rarely.

Renal and Genitourinary Effects

Acute renal failure and interstitial nephritis have been reported rarely in patients receiving cefuroxime. Although a causal relationship has not been established, transient increases in BUN and/or serum creatinine concentrations and decreased creatinine clearance have been reported in a few patients receiving cefuroxime. Bilateral renal cortical necrosis that appeared to be a hypersensitivity reaction has been reported in at least one patient who received cefuroxime axetil.

Urinary tract infection, kidney pain, urethral pain or bleeding, dysuria, vaginitis, vaginal candidiasis, vulvovaginal pruritus, and vaginal discharge or irritation have been reported in less than 1% of patients receiving oral cefuroxime axetil therapy.

Other Adverse Effects

Jarisch-Herxheimer reaction has occurred in 5.6% of patients receiving cefuroxime axetil for the treatment of Lyme disease. In a clinical study in patients with early Lyme disease, the Jarisch-Herxheimer reaction occurred in 11.8% of patients receiving cefuroxime axetil and 11.5% of patients receiving doxycycline. These transient reactions generally last only 1-2 days.

Overgrowth with nonsusceptible organisms (e.g., perianal, oral, or vaginal candidiasis; pseudomembranous colitis; superinfection) has occurred in patients receiving cefuroxime sodium or cefuroxime axetil.(See Cautions: GI Effects and also see Precautions and Contraindications.)

Mild to severe hearing loss has been reported in a few pediatric patients receiving cefuroxime sodium for the treatment of meningitis. Persistence of positive CSF cultures at 18-36 hours has been observed with cefuroxime sodium injection; however, the clinical relevance of this finding is unknown.

Muscle spasm of the neck, muscle cramps or stiffness, chest pain or tightness, shortness of breath, tachycardia, chills, lockjaw-type reaction, viral illness, upper respiratory infection, sinusitis, fever, cough, joint swelling, and arthralgia have been reported in less than 1% of patients receiving oral cefuroxime axetil therapy. Diaper rash has been reported in 3.4% of pediatric patients receiving cefuroxime axetil as the commercially available oral suspension.

Precautions and Contraindications

Prior to initiation of cefuroxime therapy, careful inquiry should be made concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs. Cefuroxime axetil and cefuroxime sodium are contraindicated in patients who are hypersensitive to cefuroxime or other cephalosporins and should be used with caution in patients with a history of hypersensitivity to penicillins. Use of cephalosporins should be avoided in patients who have had an immediate-type (anaphylactic) hypersensitivity reaction to penicillins. Although it has not been definitely proven that allergic reactions to antibiotics are more frequent in atopic individuals, the manufacturer states that parenteral cefuroxime should be used with caution in patients with a history of allergy, particularly to drugs.

To reduce development of drug-resistant bacteria and maintain effectiveness of cefuroxime and other antibacterials, the drug should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria. When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used. In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.

Patients should be advised that antibacterials (including cefuroxime) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold). Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cefuroxime or other antibacterials in the future.

As with other anti-infectives, prolonged use of cefuroxime axetil or cefuroxime sodium may result in overgrowth of nonsusceptible organisms. Careful observation of the patient during cefuroxime therapy is essential. If suprainfection or superinfection occurs, appropriate therapy should be instituted.

Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that Ceftin oral suspensions containing 125 or 250 mg of cefuroxime per 5 mL contains aspartame (NutraSweet), which is metabolized in the GI tract to provide 11.8 or 25.2 mg of phenylalanine/5 mL, respectively.

Like other dextrose-containing solutions, the commercially available Duplex drug delivery system containing 750 mg or 1.5 g of cefuroxime and 50 mL of dextrose injection should be used with caution in patients with overt or known subclinical diabetes mellitus or in patients with carbohydrate intolerance for any reason.

Because CDAD has been reported with the use of cefuroxime and other cephalosporins, it should be considered in the differential diagnosis of patients who develop diarrhea during or after cefuroxime therapy.(See Clostridium difficile-associated Diarrhea and Colitis under Cautions: GI Effects.) Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually resolves when the drug is discontinued; however, they should contact a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose. Cefuroxime should be used with caution in patients with a history of GI disease, particularly colitis. The safety and efficacy of cefuroxime axetil therapy in patients with GI malabsorption have not been established.

Although cefuroxime sodium only rarely causes adverse renal effects, the manufacturers state that renal function should be monitored during therapy with the drug, especially when maximum dosage is used in seriously ill patients.

Safety and efficacy of oral cefuroxime axetil in patients with renal impairment have not been established. Because serum concentrations of cefuroxime are higher and more prolonged in patients with renal impairment than in patients with normal renal function, dose and/or frequency of administration of parenteral cefuroxime sodium should be decreased in patients with transient or persistent renal impairment.(See Dosage in Renal Impairment in Dosage and Administration: Dosage.)

Several 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 associated with cefuroxime develop, the drug should be discontinued and anticonvulsant therapy initiated as clinically indicated.

Because some cephalosporins have been associated with a decrease in prothrombin activity, the manufacturers state that prothrombin time (PT) should be monitored when cefuroxime is used in patients with renal or hepatic impairment, in patients with poor nutritional status, in patients receiving a protracted course of anti-infective therapy, or in those previously stabilized on anticoagulant therapy. Vitamin K should be administered if indicated.

Pediatric Precautions

Safety and efficacy of oral cefuroxime axetil or parenteral cefuroxime sodium in children younger than 3 months of age have not been established.

In vitro studies indicate that cefuroxime does not appear to displace bilirubin appreciably from albumin binding sites in neonates.

Cefuroxime Axetil

The manufacturers state that safety and efficacy of cefuroxime axetil for the treatment of acute bacterial maxillary sinusitis in pediatric patients 3 months to 12 years of age have been established based on safety and efficacy of the drug in adults. In addition, use of cefuroxime axetil in pediatric patients is supported by pharmacokinetic and safety data in adult and pediatric patients, clinical and microbiologic data from adequate and well-controlled studies of the treatment of acute bacterial maxillary sinusitis in adults and acute otitis media with effusion in pediatric patients, and postmarketing surveillance of adverse effects.

Cefuroxime axetil tablets and oral suspension generally are well tolerated in children aged 3 months to 12 years. Cefuroxime axetil has a strong, persistent, bitter taste and complaints caused by the taste were reported in up to 66% of children who received the drug as crushed tablets and vomiting was induced aversively in some of these children. This bitter taste and/or problems with administering the drug required discontinuance of such cefuroxime axetil therapy in 2-28% of children in clinical trials. Although discontinuance of therapy with the suspension because of its taste or other problems with administration occurred in 1.4% of children receiving the oral suspension, the commercially available oral suspension should be used in children who cannot swallow the tablets whole.

Cefuroxime Sodium

To avoid overdosage, the commercially available Duplex drug delivery system containing 750 mg or 1.5 g of cefuroxime should not be used in pediatric patients only if the entire 750-mg or 1.5-g dose in the container is required.

Geriatric Precautions

In clinical studies of cefuroxime axetil, 375 patients were 65 years of age or older and 151 were 75 years of age or older. There were no apparent differences in safety or effectiveness between these individuals and younger adults. Although the group of patients aged 65 years or older experienced a lower incidence of some adverse effects (e.g., vaginal candidiasis, GI effects) compared with patients 12-64 years of age, no clinically important differences were observed between geriatric and younger patients and there have been no reports of differences in response in either group.

In clinical studies of cefuroxime sodium involving over 1900 patients, approximately 47% of the patients were 65 years of age or older and 22% were 75 years of age or older. Although no overall differences in efficacy or safety were observed between geriatric and younger patients, and other clinical experience revealed no evidence of age-related differences, the possibility that some geriatric patients may exhibit increased sensitivity to the drug cannot be ruled out.

Cefuroxime is substantially excreted by the kidney, and renal elimination of the drug may be decreased and the risk of severe adverse reactions may be increased in patients with impaired renal function. Limited data indicate that mean serum elimination half-life of cefuroxime is prolonged in geriatric patients (mean age: 83.9 years) who have a mean creatinine clearance of approximately 35 mL/minute. Despite this prolonged elimination, the manufacturers state that age-based dosage adjustment does not appear to be necessary. However, because geriatric patients are more likely to have decreased renal function, dosage should be selected with caution in these patients and monitoring of renal function may be useful.

Mutagenicity and Carcinogenicity

No evidence of mutagenicity was observed with cefuroxime in various in vitro and in vivo test systems, including the mouse lymphoma assay, micronucleus test, and bacterial mutation tests. Cefuroxime produced positive results in the in vitro chromosome aberration assay. Studies have not been performed to date to evaluate the carcinogenic potential of cefuroxime.

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in mice and rabbits using cefuroxime sodium in dosages up to 6 and 2 times the usual human dosage based on mg/m, respectively, and reproduction studies in mice and rats using cefuroxime axetil in dosages up to 14 and 9 times, respectively, the usual human dosage based on mg/m have not revealed evidence of impaired fertility or harm to the fetus. There are no adequate and controlled studies to date using cefuroxime in pregnant women, and cefuroxime axetil and cefuroxime sodium should be used during pregnancy only when clearly needed. Cefuroxime axetil has not been studied for use during labor and delivery.

Lactation

Because cefuroxime is distributed into milk, cefuroxime axetil and cefuroxime sodium should be used with caution in nursing women.

Drug Interactions

Aminoglycosides

In vitro studies indicate that the antibacterial activity of cefuroxime and aminoglycosides may be additive or synergistic against some organisms including Enterobacter,Escherichia coli,Klebsiella,Proteus mirabilis, and Serratia marcescens.

Concurrent use of aminoglycosides and certain cephalosporins reportedly may increase the risk of nephrotoxicity during therapy. Although this effect has not been reported to date with cefuroxime, the possibility that nephrotoxicity may be potentiated should be considered if the drug is used concomitantly with an aminoglycoside.

Diuretics

The manufacturers state that cefuroxime should be used with caution in patients receiving diuretics because concurrent use of these drugs may increase the risk of adverse renal effects.

Estrogens or Progestins

Cefuroxime axetil may affect gut flora, leading to decreased estrogen reabsorption and reduced efficacy of oral contraceptives containing estrogen and progestin.

Probenecid

Oral probenecid administered shortly before or concomitantly with cefuroxime usually slows the rate of tubular secretion of cefuroxime and produces higher and more prolonged serum concentrations of cefuroxime. This effect has been used to therapeutic advantage in the treatment of gonorrhea. Peak serum concentrations of cefuroxime and the half-life of the drug are reportedly increased by up to 30% when probenecid is administered concomitantly; the area under the concentration-time curve (AUC) of cefuroxime is increased by about 50%. Concomitant administration of probenecid also reportedly decreases the apparent volume of distribution of cefuroxime by about 20%.

Pharmacokinetics

In all studies described in the Pharmacokinetics section, cefuroxime was administered orally as the 1-(acetyloxy)ethyl ester (i.e., cefuroxime axetil) and parenterally as the sodium salt; dosages and concentrations of the drug are expressed in terms of cefuroxime. Because cefuroxime axetil is hydrolyzed rapidly (t½: 3.5 minutes) in vitro in blood or serum, some clinicians recommend that acetonitrile be added immediately to blood or serum samples intended for pharmacokinetic determinations of the drug in order to prevent further hydrolysis and resultant falsely high concentrations of active drug.

Absorption

Cefuroxime Axetil

Following oral administration of cefuroxime axetil, the drug is absorbed as the 1-(acetyloxy)ethyl ester from the GI tract and rapidly hydrolyzed to cefuroxime by nonspecific esterases in the intestinal mucosa and blood. Cefuroxime remaining within the intestinal lumen following hydrolysis of the ester is not absorbed appreciably. The drug has little, if any, microbiologic activity until hydrolyzed in vivo to cefuroxime.

Bioavailability following oral administration of cefuroxime axetil is variable and depends on the formulation used and presence of food in the GI tract. Many published studies on the pharmacokinetics of the drug used various formulations that provided poorer bioavailability than the currently available tablets and cannot be used to provide information on the currently available preparation.

When tested in healthy adults, the bioavailability of cefuroxime axetil oral suspension was found not to be equivalent to that of cefuroxime axetil tablets. Mean area under the concentration-time curve (AUC) for the oral suspension was 91% of the AUC for the tablets, and the mean peak plasma concentration of cefuroxime following administration of the cefuroxime axetil oral suspension was 71% of that achieved following administration of cefuroxime axetil tablets. Therefore, cefuroxime axetil oral suspension and tablet formulations are not substitutable on a mg/mg basis.(See Dosage: Pediatric Dosage in Dosage and Administration.)

In adults, bioavailability of cefuroxime following oral administration of commercially available cefuroxime axetil tablets averages about 37% when given in the fasting state and 52% when given with or shortly after food. Absorption of the drug is increased when given with milk or infant formula. In one study, the extent but not the rate of absorption was substantially greater when the drug was administered concomitantly with milk compared with applesauce or fasting.

Following oral administration in adults of a single 125-mg, 250-mg, 500-mg, or 1-g dose of commercially available cefuroxime axetil tablets immediately following a meal, peak serum cefuroxime concentrations are attained approximately 2-3 hours after the dose and average 2.1, 4.1, 7, or 13.6 mcg/mL, respectively; serum concentrations 6 hours after the dose average 0.3, 0.7, 2.2, or 3.4 mcg/mL, respectively. AUC of the drug in these individuals averaged 6.7, 12.9, 27.4, or 50 mcg-h/mL, respectively.

Results of a study in healthy adults indicate that cefuroxime axetil oral suspensions containing 125 mg/5 mL or 250 mg/5 mL are bioequivalent. In healthy adults who received a 250-mg dose of cefuroxime axetil given as a suspension containing 125 mg/5 mL or 250 mg/5 mL with food, peak plasma concentrations of cefuroxime were 2.4 or 2.2 mcg/mL, respectively, and were attained 3 hours after the dose.

In pharmacokinetic studies of cefuroxime axetil oral suspension in children, the drug was administered postprandially or with food; no data are available regarding absorption of the suspension in fasting children. Following oral administration to children 3 months to 12 years of age (mean age: 23 months) of a single 10-, 15-, or 20-mg/kg dose of commercially available cefuroxime axetil oral suspension concomitantly with milk or milk products, peak serum cefuroxime concentrations are attained approximately 3.6, 2.7, or 3.1 hours after the dose, respectively, and average 3.3, 5.1, or 7 mcg/mL, respectively.

Cefuroxime Sodium

Cefuroxime sodium is not appreciably absorbed from the GI tract and must be given parenterally. Following IM administration of a single 500-mg, 750-mg, or 1-g dose of cefuroxime in healthy adults with normal renal function, peak serum concentrations of the drug are attained within 15-60 minutes and range from 20.8-25.7, 26-34.9, and 32-40 mcg/mL, respectively. In one study following IM administration of a single 750-mg dose of cefuroxime in healthy adults, serum concentrations of the drug averaged 32.8 mcg/mL 40 minutes after the dose, 19.1 mcg/mL 2 hours after the dose, 6.1 mcg/mL 4 hours after the dose, 1.5 mcg/mL 6 hours after the dose, and 0.7 mcg/mL 8 hours after the dose. IM injection of a single 1.5-g dose of the drug reportedly results in peak serum concentrations averaging 46 mcg/mL. Mean peak serum concentrations of cefuroxime and the areas under the concentration-time curve (AUC) are not substantially different after IM injection of cefuroxime as a suspension or as a solution. The AUC of cefuroxime is proportional to the dose administered and is similar following IM or IV administration of the drug. In one preliminary study in women, serum concentrations of cefuroxime were lower when IM injections of the drug were given into the gluteus maximus than when the same dose was given into the thigh.

In one study in healthy adults with normal renal function, a single 500-mg or 1-g dose of cefuroxime given by IV injection over 3 minutes resulted in serum concentrations of cefuroxime that averaged 66.3 and 99.2 mcg/mL, respectively, immediately after the injection; serum concentrations of the drug averaged 2.1 and 3.6 mcg/mL, respectively, 4 hours after the injection. In another study in healthy adults with normal renal function, IV injection over 2-3 minutes of a single 750-mg dose of cefuroxime resulted in serum concentrations of cefuroxime that averaged 52.6 mcg/mL 15 minutes after the injection, 24 mcg/mL 1 hour after the injection, 9.7 mcg/mL 2 hours after the injection, 3.5 mcg/mL 4 hours after the injection, and 0.5 mcg/mL 8 hours after the injection.

IV infusion over 30 minutes of a single 500- or 750-mg dose of cefuroxime reportedly results in peak serum concentrations of the drug averaging 37.8 and 51.1 mcg/mL, respectively. IV infusion over 1 hour of a single 750-mg or 1-g dose of cefuroxime reportedly results in peak serum concentrations of the drug averaging 38 and 64.4 mcg/mL, respectively.

In one study in neonates, IM administration of a single cefuroxime dose of 25 mg/kg resulted in serum concentrations of the drug that averaged 45 mcg/mL 30 minutes after the injection, 35 mcg/mL 3 hours after the injection, and 10.5 mcg/mL 12 hours after the injection. IM administration of a single cefuroxime dose of 10 mg/kg in neonates younger than 3 weeks of age reportedly resulted in serum concentrations of the drug that ranged from 15-25 mcg/mL 30-60 minutes after injection.

Distribution

The apparent volume of distribution of cefuroxime in healthy adults ranges from 9.3-15.8 L/1.73 m.

Following IM or IV administration of usual dosages of cefuroxime, the drug is widely distributed into body tissues and fluids including the kidneys, heart, gallbladder, liver, prostatic adenoma tissue, uterine and ovarian tissue, aqueous humor, saliva, sputum, bronchial secretions, bone, bile, adipose tissue, wound exudates, peritoneal fluid, ascitic fluid, synovial fluid, pericardial fluid, and pleural fluid.

Following oral administration of cefuroxime axetil in pediatric patients with acute otitis media with effusion or with chronic or recurrent otitis media with effusion, cefuroxime is distributed into middle ear effusions. In a study in pediatric patients 1-4 years of age with acute otitis media with effusion who received a single 15 mg/kg dose of cefuroxime as cefuroxime axetil oral suspension, cefuroxime concentrations in middle ear effusions 2-5 hours after a dose ranged from 0.2-3.6 mcg/mL; concurrent serum concentrations were 2.8-7.3 mcg/mL.

Cefuroxime is 33-50% bound to serum proteins.

Cefuroxime concentrations in CSF are low following IV administration of usual dosages of the drug in patients with uninflamed meninges; however, therapeutic concentrations of cefuroxime may be attained following IV administration of the drug in patients with inflamed meninges. In one study in adults receiving 1-2 g of cefuroxime IV every 8 hours, the maximum CSF concentration of cefuroxime in patients with uninflamed or inflamed meninges was 0.1 or 8.28 mcg/mL, respectively. In adults with meningitis receiving 1.5 g of cefuroxime every 6 or 8 hours, mean CSF concentrations of the drug attained within 8 hours after dosing are 6 mcg/mL (range: 1.5-13.5) or 5.2 mcg/mL (range: 2.7-8.9), respectively. In one study in children 1-4 years of age with meningitis receiving rapid IV injection of cefuroxime 50 mg/kg every 6 hours, CSF concentrations of the drug after at least 2 days of therapy ranged from 1.1-9.8 mcg/mL in CSF specimens obtained 2 hours after a dose. In pediatric patients 4 weeks to 6.5 years of age with meningitis receiving 50 mg/kg every 6 hours, mean CSF concentrations of cefuroxime were 6.6 mcg/mL (range: 0.9-17.3). In another study in pediatric patients 7 months to 9 years of age with meningitis receiving 67-77 mg/kg every 8 hours, mean CSF concentrations of cefuroxime were 8.3 mcg/mL (range: less than 2 up to 22.5).

Cefuroxime readily crosses the placenta. Amniotic fluid concentrations of cefuroxime reportedly average 17-18.6 mcg/mL 3-5.5 hours after a single 750-mg IM dose of the drug. Cefuroxime is distributed into milk.

Elimination

In adults, the serum or plasma half-life of cefuroxime following oral administration of commercially available cefuroxime axetil tablets or oral suspension ranges from 1.2-1.6 hours. In adults with normal renal function, the serum half-life of cefuroxime following IM or IV administration reportedly ranges from 1-2 hours. In adults, approximately 50% of an administered dose of cefuroxime axetil is recovered in the urine within 12 hours.

In patients with renal impairment, the serum half-life of the drug is prolonged and generally ranges from 1.9-16.1 hours depending on the degree of impairment. In one study, the serum half-life of cefuroxime was 1 hour in patients with creatinine clearances of 50-79 mL/minute, 2.55 hours in patients with creatinine clearances of 25-46 mL/minute, 5.1 hours in patients with creatinine clearances of 10-24 mL/minute, and 14.8 hours in patients with creatinine clearances less than 10 mL/minute. A serum half-life of 15-22 hours has been reported in anuric patients.

In neonates and children, the serum half-life of cefuroxime is inversely proportional to age. Following oral administration of cefuroxime axetil oral suspension in children 3 months to 12 years of age, the serum half-life of cefuroxime averages 1.4-1.9 hours. The serum half-life of cefuroxime following IM or IV administration is reportedly 5.1-5.8 hours in neonates 3 days of age or younger, 2-4.2 hours in neonates 6-14 days of age, and 1-1.5 hours in neonates 3-4 weeks of age. The manufacturers of cefuroxime axetil state that the urinary pharmacokinetics of cefuroxime axetil have not been determined in children and that the renal pharmacokinetics of oral cefuroxime axetil as established in the adult population should not be extrapolated to children.

Following oral administration, cefuroxime axetil is rapidly hydrolyzed to cefuroxime by nonspecific esterases in the intestinal mucosa and blood; the axetil moiety is metabolized to acetaldehyde and acetic acid. Cefuroxime is not metabolized and is excreted unchanged principally in urine by both glomerular filtration and tubular secretion. In adults with normal renal function, 90-100% of a single IM or IV dose of cefuroxime is excreted unchanged in urine within 24 hours; most of the dose is excreted within the first 6 hours following administration. Following IM administration of a single 750-mg dose of cefuroxime, urinary concentrations of the drug average 1.3 mg/mL in urine collected during the first 8 hours after administration. Urinary concentrations of cefuroxime average 1.15 or 2.5 mg/mL in urine collected over the first 8 hours following IV administration of a single 750-mg or 1.5-g dose of the drug, respectively.

Concomitant administration of probenecid competitively inhibits renal tubular secretion of cefuroxime and produces higher and more prolonged serum concentrations of the drug.(See Drug Interactions: Probenecid.)

Cefuroxime is removed by hemodialysis and by peritoneal dialysis.

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