Cefpodoxime Proxetil
Cefpodoxime proxetil (Pfizer’s Vantin, Sanofi-Aven-tis’ Orelox, Sankyo’s Banan) is an extended-spectrum, third-generation, oral cephalosporin. Sankyo originally developed cefpodoxime proxetil and first launched the cephalosporin in Japan in 1989. It was marketed in the United States by Upjohn (later Pharmacia) in 1992; Aventis marketed the agent in Europe. A generic version of cefpodoxime developed by Ranbaxy has been approved in the United States. Cefpodoxime is indicated for the treatment of community-acquired pneumonia caused by S. pneumoniae and H. influenzae (including β-lactamase-producing strains).
Cefpodoxime proxetil is an esterified pro-drug of cefpodoxime created for oral formulation. It is stable in the presence of most β-lactamase enzymes, effectively extending its spectrum of activity against several gram-positive and gram-negative bacteria that are resistant to penicillins and other cephalosporins. However, some extended-spectrum β-lactamase enzymes can inactivate cephalosporins. Clinical studies have shown cefpodoxime to be active against S. pneumoniae, S. aureus, H. influenzae, E. coli, K. pneumoniae, and M. catarrhalis and inactive against enterococci and Pseudomonas species.
In a comparative trial in more than 200 patients with community-acquired pneumonia, 200 mg of cefpodoxime proxetil, administered twice daily for 5 to 10 days, was compared with 500 mg of amoxicillin administered three times daily. The study established that the clinical and bacteriologic efficacy of the two antibiotics were comparable.
In clinical trials of cefpodoxime, 7.0% of treated patients experienced diarrhea, 3.3% reported nausea, 1.0% reported vaginal fungal infections, and 1.2% experienced abdominal pain. The frequency of side effects is similar to frequency associated with other oral cephalosporins.
Cefotaxime
Cefotaxime (Abbott/Sanofi-Aventis’s Claforan, generics) is a third-generation, parenteral cephalosporin available for intravenous (IV) or intramuscular (IM) administration. Cefotaxime was first marketed in 1981 in the United States, where generic versions of the injection are now available. The cephalosporin is also marketed by Roche in Japan.
Cefotaxime is stable in the presence of many β-lactamase enzymes, effectively extending its spectrum of activity against a number of gram-positive and gram-negative bacteria resistant to penicillins and other cephalosporins. Clinical and laboratory studies have demonstrated the activity of cefotaxime against S. aureus, S. pneumoniae, and other streptococci. Gram-negative species susceptible to cefotaxime include E. coli, H. influenzae, H. parainfluenzae, K. pneumoniae, and others. It is also active against P. aeruginosa.
Cefotaxime is indicated for treatment of lower respiratory tract infections caused by S. pneumoniae, S. pyogenes, and other streptococci (but not enterococci), S. aureus, E. coli, K. pneumoniae and other Klebsiella species, H. influenzae (including ampicillin-resistant strains), H. parainfluenzae, and Pseudomonas species (including P. aeruginosa). A clinical trial examined the efficacy of cefotaxime in treating patients with severe respiratory infections, including pneumonia. One hundred and ninety patients were treated with 2.25-3.0 g of cefotaxime daily for an average of 9 days and displayed a favorable clinical response in 91% of 184 evaluable cases.
Cefotaxime is generally well tolerated, but some adverse reactions have been documented, including local inflammation at point of IV administration (4.3%) and gastrointestinal disturbances (1.4%). Systemic adverse reactions to cefotaxime have been rare. The frequency of side effects is similar to frequency associated with other parenteral cephalosporins.
| Dosage forms of Cefpodoxime: | |||
|---|---|---|---|
| Cefpodoxime 100 mg tablet | Vantin 100 mg tablet | Cefpodoxime 200 mg tablet | Cefpodoxime Proxetil 200 mg tablet |
| Vantin 200 mg tablet | Vantin 50 mg/5ml Suspension 50ml Bottle | Vantin 50 mg/5ml Suspension 100ml Bottle | Vantin 100 mg/5ml Suspension 100ml Bottle |
| Vantin 20 100 mg tablet Bottle | Vantin 20 200 mg tablet Bottle | ||
Uses
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; the treatment of acute otitis media caused by susceptible bacteria; and the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A b-hemolytic streptococci).
The drug also is used orally for the treatment of uncomplicated gonorrhea and for the treatment of mild to moderate uncomplicated skin and skin structure or uncomplicated urinary tract infections 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. 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.
Respiratory Tract Infections
Acute Exacerbations of Chronic Bronchitis
Oral cefpodoxime proxetil is used for the treatment of acute exacerbations of chronic bronchitis caused by susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae (non-b-lactamase-producing strains only), or Moraxella (formerly Branhamella) catarrhalis.
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 b-lactamase-producing strains of H. influenzae. 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. 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 b-lactamase-producing strains), H. parainfluenzae (including b-lactamase-producing strains), or non-b-lactamase-producing M. catarrhalis and 86% in those with infections caused by b-lactamase-producing M. catarrhalis or S. pneumoniae.
Acute Sinusitis
Oral cefpodoxime proxetil is used for the treatment of acute maxillary sinusitis caused by susceptible strains of S. pneumoniae, H. influenzae (including b-lactamase-producing strains), or M. catarrhalis. 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.
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). Various anti-infectives have been shown to be effective for the treatment acute community-acquired sinusitis (e.g., amoxicillin and clavulanate potassium, cefaclor, cefixime, cefpodoxime, cefprozil, cefuroxime axetil, co-trimoxazole, levofloxacin, loracarbef), and the most appropriate drug for the individual patient usually is selected based on considerations relating to cost, convenience, and tolerability.
Community-acquired Pneumonia
Oral cefpodoxime proxetil is used for the treatment of mild to moderate community-acquired pneumonia (CAP) caused by susceptible strains of S. pneumoniae or H. influenzae (including b-lactamase-producing strains).
The American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) suggest that certain oral cephalosporins can be used for the outpatient treatment of CAP. Initial treatment of CAP generally involves use of an empiric anti-infective regimen based on the most likely pathogens; therapy may then be changed (if possible) to a pathogen-specific regimen based on results of in vitro culture and susceptibility testing, especially in hospitalized patients.
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 outpatient 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; some other pathogens often involved in outpatient CAP are Mycoplasma pneumoniae, Chlamydia pneumoniae, respiratory viruses, and Haemophilus influenzae (especially in cigarette smokers).
For empiric outpatient treatment of acute CAP in immunocompetent adults, the IDSA recommends monotherapy with an oral macrolide (azithromycin, clarithromycin, erythromycin), oral doxycycline, or an oral fluoroquinolone active against S. pneumoniae (e.g., gatifloxacin, levofloxacin, moxifloxacin) and states that alternative empiric regimens include oral amoxicillin and clavulanate or certain oral cephalosporins (cefpodoxime, cefprozil, cefuroxime axetil).
For outpatient treatment of CAP in immunocompetent adults without cardiopulmonary disease or other modifying factors that would increase the risk of multidrug-resistant S. pneumoniae or gram-negative bacteria, the ATS recommends an empiric regimen of monotherapy with azithromycin or clarithromycin or, alternatively, doxycycline. However, for the outpatient treatment of immunocompetent adults with cardiopulmonary disease (congestive heart failure or chronic obstructive pulmonary disease [COPD]) and/or other modifying factors that increase the risk for multidrug-resistant S. pneumoniae or gram-negative bacteria, the ATS recommends a 2-drug empiric regimen consisting of a b-lactam anti-infective (e.g. oral cefpodoxime, oral cefuroxime axetil, high-dose amoxicillin, amoxicillin and clavulanate, parenteral ceftriaxone followed by oral cefpodoxime) and a macrolide or doxycycline or, alternatively, monotherapy with a fluoroquinolone active against S. pneumoniae (e.g., ciprofloxacin, ofloxacin, gatifloxacin, levofloxacin, moxifloxacin, sparfloxacin, trovafloxacin [risk of hepatic toxicity should be considered]).
The US Centers for Disease Control and Prevention (CDC) suggest that use of these oral fluoroquinolones in the outpatient treatment of CAP be reserved for when other anti-infectives are ineffective or cannot be used or when highly penicillin-resistant S. pneumoniae (i.e., penicillin MICs 4 mcg/mL or greater) are identified as the cause of infection. For inpatient treatment of CAP patients who require hospitalization in an ICU or non-ICU patient-care setting, various parenteral regimens are recommended. (See Community-acquired Pneumonia under Uses: Respiratory Tract Infections, in the Cephalosporins General Statement 8:12.06.)
Acute Otitis Media
Oral cefpodoxime proxetil is used for the treatment of acute otitis media caused by S. pneumoniae (penicillin-susceptible strains only), H. influenzae (including b-lactamase-producing strains), or M. catarrhalis (including b-lactamase-producing strains).
Results of controlled clinical studies in children 2 months to 18 years of age with acute otitis media 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. In published studies, the overall clinical response rate to a 10-day regimen of oral cefpodoxime proxetil in pediatric patients with acute otitis media has been 83-92% and the bacteriologic eradication rate has been 88-92%.
Cefpodoxime proxetil also has been effective for the treatment of acute otitis media in pediatric patients when administered in a 5-day regimen. In one study in pediatric patients 1 month to 11 years of age with acute otitis media 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.% in those who received cefpodoxime and 91.% in those who received cefaclor; the rate of recurrence 30 days after completion of therapy was 6.4 or 7.2%, respectively. Some clinicians caution that short-term anti-infective regimens (i.e., 5 days or less) may not be appropriate for the treatment of acute otitis media in children younger than 2 years of age or for patients with underlying disease, recurrent or chronic acute otitis media, or perforated tympanic membranes with spontaneous purulent drainage. For additional information regarding treatment of acute otitis media, 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 b-hemolytic streptococci). 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. 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).
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. 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. 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.
Selection of an anti-infective agent regimen for the treatment of S. pyogenes pharyngitis and tonsillitis should be based on the drug’s spectrum of activity as well as the regimen’s bacteriologic and clinical efficacy, potential adverse effects, ease of administration and patient compliance, and cost. No regimen has been found to date that effectively eradicates group A b-hemolytic streptococci in 100% of patients.
Because penicillin has a narrow spectrum of activity, is inexpensive, and generally is effective, the CDC, American Academy of Pediatrics (AAP),American Academy of Family Physicians (AAFP), IDSA, American Heart Association (AHA), American College of Physicians-American Society of Internal Medicine (ACP-ASIM), and others consider natural penicillins (i.e., 10 days of oral penicillin V or a single IM dose of penicillin G benzathine) the treatment of choice for streptococcal pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever, although oral amoxicillin often is used instead of penicillin V in small children because of a more acceptable taste.
Other anti-infectives (e.g., oral cephalosporins, oral macrolides) generally are considered alternatives. There is some evidence that bacteriologic and clinical cure rates reported with 10-day regimens of certain oral cephalosporins (e.g., cefaclor, cefadroxil, cefdinir, cefixime, cefpodoxime proxetil, cefprozil, cefuroxime axetil, ceftibuten, cephalexin) are slightly higher than those reported with the 10-day oral penicillin V regimen. In addition, 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.
Based on these results, some clinicians suggest that oral cephalosporins be included as agents of choice for the treatment of S. pyogenes pharyngitis and tonsillitis. However, the IDSA states that first generation cephalosporins can be used for the treatment of pharyngitis in patients hypersensitive to penicillins (except those with immediate-type hypersensitivity to b-lactam anti-infectives) but that cephalosporins appear to offer no advantage over penicillins since they have a broader spectrum of activity and generally are more expensive. In addition, because of limited data to date, the IDSA states that use of cephalosporin regimens administered for 5 days or less for the treatment of S. pyogenes pharyngitis cannot be recommended at this time.
Uncomplicated Gonorrhea
Oral cefpodoxime proxetil is effective when given in a single-dose regimen 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 gonorrhea (PPNG) or nonpenicillinase-producing strains of the organism. The drug also has been effective when given in a single-dose regimen for the treatment of anorectal gonococcal infections in women, but efficacy of the drug for the treatment of anorectal infections in men has not been established. In addition, data do not support the use of cefpodoxime proxetil for the treatment of pharyngeal gonococcal infections in men or women. Cefpodoxime is not included in current Centers for Disease Control and Prevention (CDC) recommendations for the treatment of gonococcal infections in adults or children. (See Uses: Gonorrhea and Associated 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. 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. (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.
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. 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 or 100% for infections caused by Klebsiella. 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.
The most appropriate agent for the treatment of urinary tract infections should be selected based on the severity of the infection and results of culture and in vitro susceptibility testing.
Some clinicians suggest that certain oral third generation cephalosporins (cefdinir, cefixime, cefpodoxime proxetil, ceftibuten) are one of several alternatives that can be used for the outpatient treatment of recurrent urinary tract infections or urinary tract infections acquired in hospitals or nursing homes since these infections are likely to be caused by multidrug-resistant gram-negative bacilli; however, these oral cephalosporins are not appropriate for the treatment of more severely ill patients hospitalized with urinary tract infections.
Dosage and Administration
Reconstitution and Administration
Cefpodoxime proxetil is administered orally. To enhance GI absorption of the drug, cefpodoxime proxetil tablets should be administered with food; however, cefpodoxime proxetil for oral suspension may be administered without regard to meals.
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. The water should be added in 2 approximately equal portions and the bottle shaken vigorously after each addition.
Dosage
Dosage of cefpodoxime proxetil is expressed in terms of cefpodoxime.
Adult Dosage
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.
Pharyngitis and Tonsillitis
The usual dosage of cefpodoxime for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A b-hemolytic streptococci) in adults and adolescents 12 years of age or older is 100 mg every 12 hours for 5-10 days. (See Uses: Pharyngitis and Tonsillitis.)
Uncomplicated Gonorrhea
Although not considered a drug of choice, if cefpodoxime is used for the treatment of uncomplicated urethral gonorrhea in men or uncomplicated urethral, endocervical, or anorectal gonorrhea in women, adults and adolescents 12 years of age and older should receive a single 200-mg dose of the drug given in conjunction with an anti-infective regimen effective for the presumptive treatment of chlamydial infections.
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.
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.
Pediatric Dosage
Children 12 years of age or older may receive the usual adult dosage of cefpodoxime.
Acute Otitis Media
For the treatment of acute otitis media 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 5 days.
Pharyngitis and Tonsillitis
For the treatment of mild to moderate pharyngitis and tonsillitis caused by S. pyogenes (group A b-hemolytic streptococci) in children 2 months to 12 years of age, the usual dosage of cefpodoxime is 5 mg/kg (up to 100 mg) every 12 hours for 5-10 days. (See Uses: Pharyngitis and Tonsillitis.)
Acute Sinusitis
For the treatment of mild to moderate acute maxillary sinusitis in children 2 months to 12 years of age, the usual dosage of cefpodoxime is 5 mg/kg (up to 200 mg) every 12 hours for 10 days.
Dosage in Renal and Hepatic Impairment
Patients with creatinine clearances of 30 mL/minute or greater may receive the usual dosage of cefpodoxime. Patients with creatinine clearances less than 30 mL/minute should receive the usual dose of cefpodoxime given every 24 hours. However, patients maintained on hemodialysis should receive the usual dose 3 times weekly following dialysis. The manufacturer states that modification of the usual dosage of cefpodoxime is not necessary in patients with hepatic impairment.
Cautions
Adverse Effects
Adverse effects reported with cefpodoxime proxetil are similar to those reported with other oral cephalosporins. (See Cautions in the Cephalosporins General Statement 8:12.06.) Cefpodoxime proxetil generally is well tolerated. Most adverse effects are transient and mild to moderate in severity, but have been severe enough to require discontinuance of the drug in up to 2% of patients.
GI effects, including diarrhea, loose stools, nausea, and vomiting, are the most frequent adverse reactions reported with cefpodoxime. Adverse GI effects may be dose related.
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.
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. Prior to initiation of cefpodoxime proxetil therapy, careful inquiry should be made concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.
There is clinical and laboratory evidence of partial cross-allergenicity among cephalosporins and other b-lactam antibiotics, including penicillins and cephamycins.
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. Use of cephalosporins should be avoided in patients who have had an immediate-type (anaphylactic) hypersensitivity reaction to penicillins. 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.
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 children younger than 2 months of age have not been established. 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).
Geriatric Precautions
Efficacy and safety of cefpodoxime proxetil in geriatric adults are similar to those observed in younger adults. 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. (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. Long-term animal studies have not been performed to date to evaluate the carcinogenic potential of the drug.
Pregnancy, Fertitlity and Lactation
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. T
here 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.
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.
Cefpodoxime is distributed into milk in low concentrations following oral administration. 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. Spectrum Based on its spectrum of activity, cefpodoxime is classified as a third generation cephalosporin.
For information on the classification of cephalosporins and closely related b-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 b-lactamases produced by gram-positive and gram-negative bacteria. 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. Cefpodoxime generally is inactive against enterococci (e.g., Enterococcus faecalis [formerly Streptococcus faecalis], methicillin-resistant staphylococci, Pseudomonas, Enterobacter, and anaerobic bacteria.
In Vitro Susceptibility Testing
The National Committee for Clinical Laboratory Standards (NCCLS) states that, if results of in vitro susceptibility testing indicate that a clinical isolate is susceptible to cefpodoxime, then an infection caused by this strain may be appropriately treated with the dosage of the drug recommended for that type of infection and infecting species, unless otherwise contraindicated.
If results indicate that a clinical isolate has intermediate susceptibility to cefpodoxime, then the strain has a minimum inhibitory concentration (MIC) that approaches usually attainable blood and tissue drug concentrations and response rates may be lower than for strains identified as susceptible.
Therefore, the intermediate category implies clinical applicability in body sites where the drug is physiologically concentrated (e.g., urine) or when a high dosage of the drug can be used. This intermediate category also includes a buffer zone which should prevent small, uncontrolled technical factors from causing major discrepancies in interpretation, especially for drugs with narrow pharmacotoxicity margins.
If results of in vitro susceptibility testing indicate that a clinical isolate is resistant to cefpodoxime, the strain is not inhibited by systemic concentrations of the drug achievable with usual dosage schedules and/or MICs fall in the range where specific microbial resistance mechanisms are likely and efficacy has not been reliably demonstrated in clinical trials. Strains of staphylococci resistant to penicillinase-resistant penicillins should be considered resistant to cefpodoxime, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.
Disk Susceptibility Tests
When the disk-diffusion procedure is used to test susceptibility to cefpodoxime, a disk containing 10 mcg of cefpodoxime should be used. When disk-diffusion susceptibility testing is performed according to NCCLS standardized procedures using NCCLS interpretive criteria, Staphylococcus or Enterobacteriaceae (except Morganella) with growth inhibition zones of 21 mm or greater are susceptible to cefpodoxime, those with zones of 18-20 mm have intermediate susceptibility, and those with zones of 17 mm or less are resistant to the drug.
When disk-diffusion susceptibility testing for Haemophilus is performed according to NCCLS standardized procedures using Haemophilus test medium (HTM), Haemophilus with growth inhibition zones of 21 mm or greater are considered susceptible to cefpodoxime.
Because of limited data on resistant strains of these organisms, NCCLS recommends that any Haemophilus isolate that appears to be nonsusceptible to cefpodoxime be submitted to a reference laboratory for further testing.
When disk-diffusion susceptibility testing is performed according to NCCLS standardized procedures using GC agar base (with 1% defined growth supplement), N. gonorrhoeae with growth inhibition zones of 29 mm or greater are considered susceptible to cefpodoxime. Because of limited data on resistant strains of these organisms, NCCLS recommends that any N. gonorrhoeae isolate that appears to be nonsusceptible to cefpodoxime be submitted to a reference laboratory for further testing. Interpretive criteria are not available to determine susceptibility of Streptococcus pneumoniae to cefpodoxime using the cefpodoxime disk; however, NCCLS states that S. pneumoniae found to be susceptible to penicillin using the NCCLS standardized disk-diffusion procedure and a 1-mcg oxacillin disk can be considered susceptible to cefpodoxime. In addition, other Streptococcus (b-hemolytic streptococci, viridans streptococci) found to be susceptible to penicillin using NCCLS standardized procedures can be considered susceptible to cefpodoxime.
Dilution Susceptibility Tests
When dilution susceptibility testing (agar or broth dilution) is performed according to NCCLS standardized procedures using NCCLS interpretive criteria, Staphylococcus or Enterobacteriaceae with MICs of 2 mcg/mL or less are susceptible to cefpodoxime, those with MICs of 4 mcg/mL have intermediate susceptibility, and those with MICs of 8 mcg/mL or greater are resistant to the drug. When dilution susceptibility testing of Haemophilus is performed according to NCCLS standardized procedures using HTM, Haemophilus with MICs of 2 mcg/mL or less are considered susceptible to cefpodoxime.
Because of limited data on resistant strains of these organisms, NCCLS recommends that any Haemophilus isolate that appears to be nonsusceptible to cefpodoxime be submitted to a reference laboratory for further testing. When dilution susceptibility testing is performed according to NCCLS standardized procedures using GC agar base (with 1% defined growth supplement), N. gonorrhoeae with MICs of 0.5 mcg/mL or less are considered susceptible to cefpodoxime.
Because of limited data on resistant strains of these organisms, NCCLS recommends that any N. gonorrhoeae isolate that appears to be nonsusceptible to cefpodoxime be submitted to a reference laboratory for further testing. When broth dilution is performed according to NCCLS standardized procedures using cation-adjusted Mueller-Hinton broth (with 2-5% lysed horse blood), S. pneumoniae with MICs of 0.5 mcg/mL or less are susceptible to cefpodoxime, those with MICs of 1 mcg/mL have intermediate susceptibility, and those with MICs of 2 mcg/mL or greater are resistant to the drug. NCCLS states that S. pneumoniae and other streptococci (b-hemolytic streptococci, viridans streptococci) found to be susceptible to penicillin using the NCCLS standardized dilution procedure can be considered susceptible to cefpodoxime.
Pharmacokinetics
Cefpodoxime proxetil is a prodrug and is inactive until hydrolyzed in vivo to cefpodoxime. Following oral administration of cefpodoxime proxetil, the drug is almost completely hydrolyzed to cefpodoxime by nonspecific esterases within the intestinal lumen. 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. 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.
Cefpodoxime exhibits linear pharmacokinetics over the oral dosage range of 100-400 mg; however, the drug exhibits nonlinear, dose-dependent pharmacokinetics at doses exceeding 400 mg. 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. 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.
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. 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.
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. Presence of food in the GI tract affects the bioavailability of cefpodoxime proxetil film-coated tablets, but does not appear to affect the bioavailability of cefpodoxime proxetil oral suspension.
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.
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. 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. 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.
Distribution
The apparent volume of distribution of cefpodoxime ranges from 0.7-1. L/kg in healthy adults with normal renal function.
Following oral administration, cefpodoxime is distributed into blister fluid, interstitial fluid, middle ear fluid, tonsils, maxillary sinus mucosa, bronchial mucosa, pleural fluid, lung tissue, epithelial lining fluid, myometrium, seminal fluid, prostatic adenoma tissue, and bile. 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.
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. 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.
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. Information on distribution of cefpodoxime into CSF is not available.
Cefpodoxime is distributed into milk in low concentrations following oral administration. 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. Cefpodoxime is 22-33% bound to serum proteins or 21-29% bound to plasma proteins; binding is independent of drug concentration over the range of 0.1-7. mcg/mL.
Elimination
In adults with normal renal function, the plasma half-life of cefpodoxime ranges from 2.1-2.9 hours. 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. 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.
The plasma half-life of cefpodoxime is prolonged in patients with renal impairment. 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.
Cefpodoxime is removed by hemodialysis; approximately 23% of a single oral dose of the drug is removed by a 3-hour period of dialysis.
Chemistry and Stability
Chemistry
Cefpodoxime is a semisynthetic cephalosporin antibiotic.
The drug is an oral aminothiazolyl cephalosporin. Cefpodoxime is structurally similar to other oral (cefdinir, cefixime, ceftibuten) and parenteral (cefepime, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone) cephalosporins that contain an aminothiazolyl side chain at position 7 of the cephalosporin nucleus. The aminothiazolyl group enhances antibacterial activity, particularly against Enterobacteriaceae, and generally results in enhanced stability against b-lactamases. Cefpodoxime is commercially available for oral administration as cefpodoxime proxetil, the isopropyloxycarbonylethyl ester of cefpodoxime.
Cefpodoxime proxetil is a prodrug of cefpodoxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefpodoxime. 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. Potency of cefpodoxime proxetil is expressed in terms of cefpodoxime. Following reconstitution, cefpodoxime proxetil oral suspension containing 50 or 100 mg of cefpodoxime per 5 mL occurs as a lemon-flavored suspension.
Stability
Cefpodoxime proxetil tablets and powder for oral suspension should be stored at 20-25°C. Following reconstitution, cefpodoxime proxetil oral suspension should be stored in a tight container and is stable for 14 days when refrigerated at 2-8°C; any unused suspension should be discarded after this period. 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.
Preparations
Cefpodoxime Proxetil Oral For suspension 50 mg (of cefpodoxime) per 5 Vantin®, mL Pfizer 100 mg (of cefpodoxime) per Vantin®, 5 mL Pfizer Tablets, film- 100 mg (of cefpodoxime) Vantin®, (with propylene coated glycol) Pfizer 200 mg (of cefpodoxime) Vantin®, (with propylene glycol) Pfizer
Synonyms of Cefpodoxime:
Cefpodoxime Proxetil, CPDX-PR, RU 51807
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Therapeutic classes of Cefpodoxime:
Anti-Bacterial Agents, Antibacterial Agents, Cephalosporins
Delivery
Australia, Canada, Mexico, New Zealand, USA, Europe [Belgium, France, Norway, Holland, Ireland, Spain, Switzerland, Great Britain (UK), Italy] and etc.