VA Class:AM117

AHFS Class:

• Third Generation Cephalosporins 8:12.06.12

Generic Name(s):

• Cefpodoxime Proxetil

Chemical Name:

• [6 R -[6α,7β( Z )]]-7-[[(2-amino-4-thiazolyl)(methoxyimino) acetyl]amino]-3-(methoxymethyl)-8-oxo-,1-[[(1-methylethoxy)carbonyl)oxy]ethyl ester, 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Associated Monographs

• Cephalosporins General Statement

Cefpodoxime is a semisynthetic, third generation cephalosporin antibiotic.1,2,3,14,66

Cefpodoxime proxetil is used orally for the treatment of mild to moderate respiratory tract infections (i.e., acute exacerbations of chronic bronchitis, acute maxillary sinusitis, community-acquired pneumonia) caused by susceptible bacteria;1,14,21,22,40,57,61,66 the treatment of acute otitis media caused by susceptible bacteria;1,28,29,30,31,66 and the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci).1,10,14,23,26,27,38,40,66 The drug also is used orally for the treatment of uncomplicated gonorrhea1,10,63,66 and for the treatment of mild to moderate uncomplicated skin and skin structure1,14,24,66 or uncomplicated urinary tract infections1,14,25,66 caused by susceptible bacteria.

Prior to initiation of cefpodoxime proxetil therapy, appropriate specimens should be obtained for identification of the causative organism and in vitro susceptibility tests.1,66 Cefpodoxime proxetil may be started pending results of susceptibility tests but should be discontinued if the organism is found to be resistant to the drug.1,66

Acute Otitis Media

Oral cefpodoxime proxetil is used for the treatment of acute otitis media (AOM) caused by Streptococcus pneumoniae (penicillin-susceptible strains only), Haemophilus influenzae (including β-lactamase-producing strains), or Moraxella catarrhalis (including β-lactamase-producing strains).1,28,29,30,31,66

When anti-infective therapy is indicated for the treatment of AOM, the American Academy of Pediatrics (AAP) recommends high-dose amoxicillin or amoxicillin and clavulanate potassium as the drugs of first choice for initial treatment.37 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.37

Results of controlled clinical studies in children 2 months to 18 years of age with AOM indicate that an 8 to 10-day regimen of oral cefpodoxime proxetil is as effective as a 10-day regimen of oral amoxicillin and clavulanate potassium or a 10-day regimen of oral cefixime.28,29,31 In published studies, the overall clinical response rate to a 10-day regimen of oral cefpodoxime proxetil in pediatric patients with AOM has been 83-92% and the bacteriologic eradication rate has been 88-92%.29,31

Cefpodoxime proxetil also has been effective for the treatment of AOM in pediatric patients when administered in a 5-day regimen.1,28,30,31,66 In one study in pediatric patients 1 month to 11 years of age with AOM randomized to receive a 5-day regimen of oral cefpodoxime proxetil (5 mg/kg of cefpodoxime every 12 hours) or a 5-day regimen of oral cefaclor (40 mg/kg daily given in 3 divided doses), the clinical response rate (cure or improvement) at the end of treatment was 93.6% in those who received cefpodoxime and 91.6% in those who received cefaclor; the rate of recurrence 30 days after completion of therapy was 6.4 or 7.2%, respectively.30 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.37

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, see Acute Otitis Media under Uses: Otitis Media, in the Cephalosporins General Statement 8:12.06.

Pharyngitis and Tonsillitis

Oral cefpodoxime proxetil is used for the treatment of pharyngitis and tonsillitis caused by susceptible S. pyogenes (group A β-hemolytic streptococci).1,10,14,23,26,27,38,40,66 Although cefpodoxime usually is effective in eradicating S. pyogenes from the nasopharynx, substantial data to establish efficacy of the drug for prophylaxis of subsequent rheumatic fever are not available to date.1,66

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.16,17,41,45 No regimen has been found to date that effectively eradicates group A β-hemolytic streptococci in 100% of patients.17

Because the drugs have a narrow spectrum of activity, are inexpensive, and generally are effective with a low incidence of adverse effects, the AAP,10 Infectious Diseases Society of America (IDSA),16 American Heart Association (AHA),17 and others11 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.10,11,16,17

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).10,16,17

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,17,41,45,46,47,48,49 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.16,17

Results of a randomized, multicenter study in pediatric patients 18 months to 18 years of age with S. pyogenes pharyngitis and tonsillitis indicate that a 10-day regimen of oral cefpodoxime proxetil (5 mg/kg of cefpodoxime twice daily) is more effective than a 10-day regimen of oral penicillin V (13.4 mg/kg 3 times daily).26 The clinical response rate (cure plus improvement) was 83.8% in those who received cefpodoxime and 77.5% in those who received penicillin V; the bacteriologic eradication rates were 93.1 or 81.2%, respectively.26

Results of controlled comparative studies in adults and children with S. pyogenes pharyngitis and tonsillitis indicate that a 5-day regimen of oral cefpodoxime proxetil is at least as effective as a 5-day regimen of oral cefuroxime axetil or a 10-day regimen of oral penicillin V in eradicating the organism.27 In one study in adults and adolescents 11 years of age or older who were randomized to receive a 5-day regimen of oral cefpodoxime proxetil (100 mg of cefpodoxime twice daily) or a 10-day regimen of oral penicillin V (600 mg 3 times daily), the bacteriologic eradication rates were 96.7 or 94.2%, respectively.38

Respiratory Tract Infections

Acute Sinusitis

Oral cefpodoxime proxetil is used for the treatment of acute maxillary sinusitis caused by susceptible S. pneumoniae , H. influenzae (including β-lactamase-producing strains), or M. catarrhalis .1,14,23,39,40,66

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.43,44 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.43 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).43,44

In one study in adults with acute sinusitis who were randomized to receive oral cefpodoxime proxetil (200 mg of cefpodoxime twice daily) or oral cefaclor (500 mg 3 times daily), the overall clinical response rate (cure or improvement) was 95% in those who received cefpodoxime and 93% in those who received cefaclor; the bacteriologic eradication rates were 95 and 91%, respectively.39 Since sinus aspirate cultures are not routinely indicated in patients with acute sinusitis, the infection is treated empirically with an anti-infective regimen active against bacteria commonly involved in sinus infections (e.g., S. pneumoniae , H. influenzae , M. catarrhalis , S. pyogenes ).54,55,56

Acute Exacerbations of Chronic Bronchitis

Oral cefpodoxime proxetil is used for the treatment of acute exacerbations of chronic bronchitis caused by susceptible S. pneumoniae , H. influenzae (non-β-lactamase-producing strains only), or M. catarrhalis .1,14,21,61,66 The manufacturer states that there is insufficient data available to establish efficacy of the drug in the treatment of acute bacterial exacerbations of chronic bronchitis caused by β-lactamase-producing strains of H. influenzae .1,66

In one study in adults with acute exacerbations of chronic obstructive pulmonary disease who were randomized to receive a 10-day regimen of oral cefpodoxime proxetil (200 mg of cefpodoxime twice daily) or oral cefaclor (250 mg 3 times daily), the clinical response rate (cure or improvement) was 99% in those who received cefpodoxime and 92% in those who received cefaclor; the bacteriologic eradication rates were 91 and 92%, respectively.21 When results of patients who received cefpodoxime were stratified according to causative organism, the bacteriologic eradication rate was 91-100% in those with infections caused by H. influenzae (including β-lactamase-producing strains), H. parainfluenzae (including β-lactamase-producing strains), or non-β-lactamase-producing M. catarrhalis and 86% in those with infections caused by β-lactamase-producing M. catarrhalis or S. pneumoniae .21

Community-acquired Pneumonia

Oral cefpodoxime proxetil is used for the treatment of mild to moderate community-acquired pneumonia (CAP) caused by susceptible S. pneumoniae or H. influenzae (including β-lactamase-producing strains).1,14,22,66 The American Thoracic Society (ATS) and IDSA recommended cefpodoxime 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.58

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.58 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 ).58 Most experts recommend that an empiric regimen for 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.58,60

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.58 Cefuroxime and cefpodoxime may be less active against S. pneumoniae than amoxicillin or ceftriaxone.58

If an oral 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 cefdinir, cefditoren, cefpodoxime, cefprozil, or cefuroxime.51

For additional information on treatment of CAP, see Community-acquired Pneumonia under Uses: Respiratory Tract Infections, in the Cephalosporins General Statement 8:12.06.

Skin and Skin Structure Infections

Oral cefpodoxime proxetil is used for the treatment of mild to moderate uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including penicillinase- and non-penicillinase-producing strains) or S. pyogenes .1,14,24,66 The manufacturer cautions that results of clinical trials indicate that effective treatment of skin and skin structure infections generally requires cefpodoxime dosages higher than those used for the treatment of other infections.1,66 (See Dosage and Administration: Dosage.) When cefpodoxime is used in the treatment of skin and skin structure infections, the fact that abscesses usually require surgical drainage should be considered.1,66

Urinary Tract Infections

Oral cefpodoxime proxetil is used for the treatment of uncomplicated urinary tract infections (cystitis) caused by susceptible Escherichia coli , Klebsiella pneumoniae , Proteus mirabilis , or S. saprophyticus .1,14,25,66

In clinical studies in adults with uncomplicated urinary tract infections who received oral cefpodoxime proxetil (100 mg of cefpodoxime twice daily), the bacteriologic eradication rate has been 75-80% for infections caused by E. coli , P. mirabilis , or S. saprophyticus 1,25 or 100% for infections caused by Klebsiella .25 However, the manufacturer cautions that cefpodoxime therapy has been associated with a lower clinical cure rate and a lower bacteriologic eradication rate than some other anti-infectives used for the treatment of cystitis, and this fact should be considered when selecting an anti-infective agent for the treatment of these infections.1

Some clinicians suggest that certain oral third generation cephalosporins (cefdinir, cefpodoxime, ceftibuten) are one of several alternatives that can be used for the outpatient treatment of recurrent urinary tract infections or urinary tract infections that occur in patients who have indwelling urinary catheters or are acquired in hospitals or nursing homes since these infections are likely to be caused by multidrug-resistant gram-negative bacilli.11

Gonorrhea and Associated Infections

Uncomplicated Gonorrhea

Oral cefpodoxime proxetil has been used for the treatment of acute uncomplicated urethral gonorrhea in men and uncomplicated urethral or endocervical gonorrhea in women caused by penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) or nonpenicillinase-producing strains of the organism.1,10,13,63,66 The drug also has been used for the treatment of anorectal gonococcal infections in women, but efficacy for the treatment of anorectal gonococcal infections in men or pharyngeal gonococcal infections in men or women have not been established.1,66

Because of concerns related to recent reports of N. gonorrhoeae with reduced susceptibility to cephalosporins, the US Centers for Disease Control and Prevention (CDC) states that oral cephalosporins are no longer recommended as first-line treatment for uncomplicated gonorrhea.68 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.68

For information on current recommendations for the treatment of gonorrhea and associated infections, see Uses: Gonorrhea and Associated Infections in Ceftriaxone 8:12.06.12.

Reconstitution and Administration

Cefpodoxime proxetil is administered orally.1,66

Cefpodoxime proxetil tablets should be administered with food to enhance GI absorption of the drug.1 (See Pharmacokinetics: Absorption.)

Cefpodoxime proxetil for oral suspension may be administered without regard to meals.66

Reconstitution

Cefpodoxime proxetil powder for oral suspension should be reconstituted at the time of dispensing by adding the amount of distilled water specified on the container to provide a suspension containing 50 or 100 mg of cefpodoxime per 5 mL.66 The water should be added in 2 approximately equal portions and the bottle shaken vigorously after each addition.66

The oral suspension should be shaken prior to administration of each dose.66

Dosage

Cefpodoxime is commercially available as cefpodoxime proxetil; dosage is expressed in terms of cefpodoxime.1,66

Adult Dosage

Pharyngitis and Tonsillitis

The usual dosage of cefpodoxime for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci) in adults and adolescents 12 years of age or older is 100 mg every 12 hours for 5-10 days.1,66

Cephalosporin regimens administered for 5 days or less are not recommended for the treatment of group A β-hemolytic streptococcal pharyngitis and tonsillitis.16,17 (See Uses: Pharyngitis and Tonsillitis.)

Respiratory Tract Infections

For the treatment of mild to moderate acute maxillary sinusitis, mild to moderate acute exacerbations of chronic bronchitis, or mild to moderate community-acquired pneumonia in adults and adolescents 12 years of age or older, the usual dosage of cefpodoxime is 200 mg every 12 hours for 10, 10, or 14 days, respectively.1,66

Skin and Skin Structure Infections

For mild to moderate uncomplicated skin and skin structure infections in adults and adolescents 12 years of age or older, the usual dosage of cefpodoxime is 400 mg every 12 hours for 7-14 days.1,66

Urinary Tract Infections

For the treatment of mild to moderate uncomplicated urinary tract infections in adults and adolescents 12 years of age or older, the usual dosage of cefpodoxime is 100 mg every 12 hours for 7 days.1,66

Gonorrhea and Associated Infections

In adults and adolescents 12 years of age or older, the manufacturer states that a single 200-mg dose of cefpodoxime can be used for the treatment of uncomplicated urethral gonorrhea in men or uncomplicated urethral, endocervical, or anorectal gonorrhea in women.1,66 However, the US Centers for Disease Control and Prevention (CDC) does not recommend oral cephalosporins for first-line treatment of uncomplicated gonorrhea.68 (See Uses: Gonorrhea and Associated Infections.)

Pediatric Dosage

Children 12 years of age or older may receive the usual adult dosage of cefpodoxime.1,66

General Pediatric Dosage

For pediatric patients beyond the neonatal period, the American Academy of Pediatrics (AAP) recommends a cefpodoxime dosage of 10 mg/kg daily given in 2 divided doses for the treatment of mild to moderate infections.10 The AAP states that cefpodoxime is inappropriate for the treatment of severe infections.10

Acute Otitis Media

For the treatment of acute otitis media (AOM) in children 2 months through 12 years of age, the dosage of cefpodoxime recommended by the manufacturer is 5 mg/kg (up to 200 mg) every 12 hours for 5 days.66

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.37

Pharyngitis and Tonsillitis

For the treatment of mild to moderate pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci) in children 2 months through 12 years of age, the usual dosage of cefpodoxime is 5 mg/kg (up to 100 mg) every 12 hours for 5-10 days.66

Cephalosporin regimens administered for 5 days or less are not recommended for the treatment of group A β-hemolytic streptococcal pharyngitis and tonsillitis.16,17 (See Uses: Pharyngitis and Tonsillitis.)

Acute Sinusitis

For the treatment of mild to moderate acute maxillary sinusitis in children 2 months through 12 years of age, the usual dosage of cefpodoxime is 5 mg/kg (up to 200 mg) every 12 hours for 10 days.66

Dosage in Renal and Hepatic Impairment

Patients with creatinine clearances of 30 mL/minute or greater may receive the usual dosage of cefpodoxime.1,66

Patients with creatinine clearances less than 30 mL/minute should receive the usual dose of cefpodoxime given once every 24 hours.1,66 Patients maintained on hemodialysis should receive the usual dose 3 times weekly following dialysis.1,66

The manufacturer states that modification of the usual dosage of cefpodoxime is not necessary in patients with hepatic impairment.1,66

Adverse Effects

Adverse effects reported with cefpodoxime proxetil are similar to those reported with other oral cephalosporins.1,2,14,66 (See Cautions in the Cephalosporins General Statement 8:12.06.) Cefpodoxime proxetil generally is well tolerated.2,25 Most adverse effects are transient and mild to moderate in severity,2,14,25,26 but have been severe enough to require discontinuance of the drug in up to 2% of patients.1,14,25,40,66 GI effects, including diarrhea, loose stools, nausea, and vomiting, are the most frequent adverse reactions reported with cefpodoxime.1,2,14,40 Adverse GI effects may be dose related.1,40 Diarrhea or loose stools have been reported in about 6% of adults receiving a dosage of 200 mg of cefpodoxime daily, but have been reported in up to 11% of those receiving a dosage of 800 mg daily.1

Precautions and Contraindications

Cefpodoxime proxetil shares the toxic potentials of other cephalosporins, and the usual cautions, precautions, and contraindications associated with cephalosporin therapy should be observed.1,66 Prior to initiation of cefpodoxime proxetil therapy, careful inquiry should be made concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.1,66 There is clinical and laboratory evidence of partial cross-allergenicity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.1,50,66 Cefpodoxime proxetil is contraindicated in patients who are hypersensitive to the drug or other cephalosporins and should be used with caution in patients with a history of hypersensitivity to penicillins.1,66 Use of cephalosporins should be avoided in patients who have had an immediate-type (anaphylactic) hypersensitivity reaction to penicillins.50,51,53 If a hypersensitivity reaction occurs during cefpodoxime proxetil therapy, the drug should be discontinued and the patient treated with appropriate therapy (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen) as indicated.1,66

To reduce development of drug-resistant bacteria and maintain effectiveness of cefpodoxime 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.1,66 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.1,66 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.1,66

Patients should be advised that antibacterials (including cefpodoxime) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1,66 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 cefpodoxime or other antibacterials in the future.1,66

Because Clostridium 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 cephalosporins, it should be considered in the differential diagnosis of patients who develop diarrhea during or after cefpodoxime therapy.1,42,66 Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually ends 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.1,66

Individuals with phenylketonuria should be cautioned that, depending on the manufacturer, cefpodoxime oral suspension may contain aspartame (NutraSweet^®) that is metabolized in the GI tract to provide 17 mg of phenylalanine per 5 mL.66,101,102,103,104,105

For a more complete discussion of these and other precautions associated with the use of cefpodoxime proxetil, see Cautions: Precautions and Contraindications in the Cephalosporins General Statement 8:12.06.

Pediatric Precautions

Safety and efficacy of cefpodoxime proxetil in neonates and infants younger than 2 months of age have not been established.1,66

Adverse effects reported in pediatric patients receiving oral cefpodoxime proxetil are similar to those reported in adults receiving the drug and include mild to moderate GI effects (diarrhea, vomiting) and dermatologic effects (rash, urticaria, pruritus).1,14,22,26,29,30,31,66

Geriatric Precautions

Efficacy and safety of cefpodoxime proxetil in geriatric adults are similar to those observed in younger adults.1,66 Although the plasma half-life of cefpodoxime may be slightly longer in geriatric adults than in younger adults, other pharmacokinetic parameters are unaffected and no adjustments in cefpodoxime dosage appear to be necessary in geriatric patients other than those related to renal impairment.1,32,33,66 (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.)

Mutagenicity and Carcinogenicity

In vivo and in vitro studies evaluating cefpodoxime have not shown evidence of mutagenicity.1,66 Long-term animal studies have not been performed to date to evaluate the carcinogenic potential of the drug.1,66

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in rats or rabbits using cefpodoxime dosages up to 100 mg/kg daily (approximately 2 times the usual human dosage on a mg/m² basis) or 30 mg/kg daily (approximately 1-2 times the usual human dosage on a mg/m² basis), respectively, have not revealed evidence of teratogenicity or harm to the fetus.1,66 There are no adequate and controlled studies using cefpodoxime proxetil in pregnant women or during labor and delivery, and the drug should be used during pregnancy only when clearly needed.1,66

Fertility

Studies in rats using oral cefpodoxime in dosages up to 100 mg/kg daily (approximately 2 times the usual human dosage based on a mg/m² basis) have not revealed evidence of impaired fertility.1,66

Lactation

Cefpodoxime is distributed into milk in low concentrations following oral administration.1,66 Because of the potential for serious adverse effects in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.1,66

Spectrum

Based on its spectrum of activity, cefpodoxime is classified as a third generation cephalosporin.2,7,8,9 For information on the classification of cephalosporins and closely related β-lactam antibiotics based on spectra of activity, see Spectrum in the Cephalosporins General Statement 8:12.06.

Cefpodoxime is stable in the presence of a variety of β-lactamases produced by gram-positive and gram-negative bacteria.1,2,14,66 Like other currently available oral third generation cephalosporins (e.g., cefdinir, cefixime, ceftibuten), cefpodoxime has an expanded spectrum of activity against aerobic gram-negative bacteria compared with first and second generation cephalosporins.2,7,8,9,14

Cefpodoxime generally is inactive against enterococci (e.g., Enterococcus faecalis ), methicillin-resistant (oxacillin-resistant) staphylococci, Pseudomonas , Enterobacter , and anaerobic bacteria.1,14,66

In Vitro Susceptibility Testing

Strains of staphylococci resistant to penicillinase-resistant penicillins (methicillin-resistant [oxacillin-resistant] staphylococci) should be considered resistant to cefpodoxime, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.65

For information on interpreting results of in vitro susceptibility testing (disk susceptibility tests, dilution susceptibility tests) when cefpodoxime susceptibility testing is performed according to the standards of the Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards [NCCLS]), see Spectrum: In Vitro Susceptibility Testing, in the Cephalosporins General Statement 8:12.06.

Pharmacokinetics

Cefpodoxime proxetil is a prodrug and is inactive until hydrolyzed in vivo to cefpodoxime.1,6,14,66 Following oral administration of cefpodoxime proxetil, the drug is almost completely hydrolyzed to cefpodoxime by nonspecific esterases within the intestinal lumen.2,6

In all studies described in the pharmacokinetics section, cefpodoxime was administered orally as cefpodoxime proxetil and dosages and concentrations of the drug are expressed in terms of cefpodoxime.1,6,14,19,32,33,34,35,36,57,66 Results of a study in healthy adults who received single 100-mg doses of cefpodoxime as cefpodoxime proxetil film-coated tablets or cefpodoxime proxetil oral suspension indicate that these formulations are bioequivalent.1,66

Cefpodoxime exhibits linear pharmacokinetics over the oral dosage range of 100-400 mg;1,6,14,32 however, the drug exhibits nonlinear, dose-dependent pharmacokinetics at doses exceeding 400 mg.6,32 There is no evidence that cefpodoxime accumulates in plasma following multiple oral doses (up to 400 mg every 12 hours) in adults with normal renal function.1,6,14

Studies in healthy geriatric adults indicate that the plasma half-life of cefpodoxime is increased slightly compared with the plasma half-life reported in younger adults, but other pharmacokinetic parameters are similar to those reported in younger adults.1,6,32,33,66 Studies in adults with impaired renal function indicate that the pharmacokinetics of cefpodoxime are affected by the degree of renal impairment and plasma half-life of the drug increases with decreasing renal impairment.1,6,66 The pharmacokinetics of cefpodoxime generally are unaffected by hepatic impairment, and the presence of ascites does not appear to affect pharmacokinetic parameters of the drug in individuals with cirrhosis.1,66

Absorption

Following oral administration of a single 100-mg oral dose of cefpodoxime in fasting adults, approximately 50% of the dose is absorbed from the GI tract.1,6,14,66

Presence of food in the GI tract affects the bioavailability of cefpodoxime proxetil film-coated tablets,1,6 but does not appear to affect the bioavailability of cefpodoxime proxetil oral suspension.1,6,57,66 Compared with administration in the fasting state, administration of a 200-mg dose of cefpodoxime as cefpodoxime proxetil tablets with a meal results in a 21-33% increase in the area under the concentration-time curve (AUC) and a 15-24% increase in average peak plasma concentrations of the drug; the time to peak plasma concentrations is not affected.1,6 While administration of the commercially available oral suspension of cefpodoxime proxetil with food decreases the rate of absorption, the extent of absorption and peak plasma concentrations are not affected.1,57,66

In healthy fasting adults who receive a single 100-, 200-, or 400-mg oral dose of cefpodoxime as cefpodoxime proxetil film-coated tablets, peak plasma concentrations of cefpodoxime are attained within 2-3 hours and average 1.4, 2.3, or 3.9 mcg/mL, respectively; plasma concentrations 8 hours after the dose average 0.29, 0.62, or 1.3 mcg/mL, respectively.1

In pediatric patients 1-17 years of age who receive a single 5-mg/kg dose of cefpodoxime as cefpodoxime proxetil oral suspension, plasma concentrations of cefpodoxime average 1.4, 2.1, 1.7, 0.9, and 0.4 mcg/mL at 1, 2, 4, 6, and 8 hours, respectively, after the dose.66

Distribution

The apparent volume of distribution of cefpodoxime ranges from 0.7-1.15 L/kg in healthy adults with normal renal function.14

Following oral administration, cefpodoxime is distributed into blister fluid,1,6,66 interstitial fluid,14 middle ear fluid,19 tonsils,1,6,14,36,66 maxillary sinus mucosa,6 bronchial mucosa,14 pleural fluid,6,14,35 lung tissue,1,6,20,34,66 epithelial lining fluid,20 myometrium,6,14 seminal fluid,6,14 prostatic adenoma tissue,6,14 and bile.6 In patients receiving cefpodoxime in an oral dosage of 200- or 400-mg every 12 hours for 5 days, peak concentrations of the drug in blister fluid averaged 1.6 or 2.8 mcg/mL, respectively; blister fluid concentrations 12 hours after dosing averaged 0.2 or 0.4 mcg/mL, respectively.1,66

Following a single 100-mg oral dose of cefpodoxime as cefpodoxime proxetil film-coated tablets, peak concentrations of cefpodoxime in tonsillar tissue are attained 4 hours after the dose and average 0.24 mcg/mL; tonsillar tissue concentrations average 0.09 mcg/mL 7 hours after the dose and are undetectable 12 hours after the dose.1,66

Following a single 4-mg/kg dose of cefpodoxime as cefpodoxime proxetil oral suspension in children 5 months to 9 years of age with acute otitis media, peak concentrations of the drug in middle ear fluid average 0.87 mcg/mL 2 hours after the dose.19

Following a single 200-mg oral dose of cefpodoxime as cefpodoxime proxetil film-coated tablets, peak concentrations of the drug in lung tissue are attained 3 hours after the dose and average 0.63 mcg/mL; concentrations in lung tissue average 0.52 or 0.19 mcg/mL at 6 or 12 hours, respectively, after the dose.1,66

Information on distribution of cefpodoxime into CSF is not available.1,66

Cefpodoxime is distributed into milk in low concentrations following oral administration.1,14,66 In 3 nursing women who received a single 200-mg oral dose of cefpodoxime, concentrations of the drug in milk 4 hours after the dose were 0, 2, or 6% of concurrent plasma concentrations; milk concentrations 6 hours after the dose were 0, 9, or 16% of concurrent plasma concentrations.1,66

Cefpodoxime is 22-33% bound to serum proteins or 21-29% bound to plasma proteins;1,66 binding is independent of drug concentration over the range of 0.1-7.1 mcg/mL.14

Elimination

In adults with normal renal function, the plasma half-life of cefpodoxime ranges from 2.1-2.9 hours.1,6,14

Studies in healthy adults using radiolabeled cefpodoxime proxetil oral solution indicate that approximately 53% of the radioactivity is eliminated in urine and 43% is eliminated in feces as cefpodoxime.6 Studies in healthy adults indicate that approximately 29-33% of a single 100- to 400-mg oral dose of cefpodoxime is eliminated in urine within 12 hours.1,6,66

The plasma half-life of cefpodoxime is prolonged in patients with renal impairment.1,66 In patients with mild renal impairment (creatinine clearance of 50-80 mL/minute), plasma half-life of the drug averages 3.5 hours; however, in those with moderate impairment (creatinine clearance of 30-49 mL/minute) or severe impairment (creatinine clearance 5-29 mL/minute), half-life of the drug averages 5.9 or 9.8 hours, respectively.1,66

Cefpodoxime is removed by hemodialysis;1,6,66 approximately 23% of a single oral dose of the drug is removed by a 3-hour period of dialysis.1,66

Chemistry and Stability

Chemistry

Cefpodoxime is a semisynthetic cephalosporin antibiotic.1,2,3,14,66 The drug is an oral aminothiazolyl cephalosporin.2 Cefpodoxime is structurally similar to other oral (cefdinir, cefixime, ceftibuten) and parenteral (cefepime, cefotaxime, ceftazidime, ceftriaxone) cephalosporins that contain an aminothiazolyl side chain at position 7 of the cephalosporin nucleus.2 The aminothiazolyl group enhances antibacterial activity, particularly against Enterobacteriaceae, and generally results in enhanced stability against β-lactamases.2

Cefpodoxime is commercially available for oral administration as cefpodoxime proxetil, the isopropyloxycarbonylethyl ester of cefpodoxime.1,2,3,4,5,6,32,66 Cefpodoxime proxetil is a prodrug of cefpodoxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefpodoxime.1,5,6,14,66 Esterification of the carboxy C-4 group of cefpodoxime results in a more lipophilic form of the drug that is more readily absorbed from the GI tract.4,5,6,32 Potency of cefpodoxime proxetil is expressed in terms of cefpodoxime.1,66

Following reconstitution, cefpodoxime proxetil oral suspension contains 50 or 100 mg of cefpodoxime per 5 mL.66

Stability

Cefpodoxime proxetil tablets and powder for oral suspension should be stored at 20-25°C.1,66

Following reconstitution, cefpodoxime proxetil oral suspension should be stored in a tight container at 2-8°C; any unused suspension should be discarded after 14 days.66

Additional Information

For further information on chemistry, mechanism of action, spectrum, resistance, uses, cautions, acute toxicity, drug interactions, or laboratory test interferences of cefpodoxime proxetil, see the Cephalosporins General Statement 8:12.06.

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