VA Class:AM115

AHFS Class:

• First Generation Cephalosporins 8:12.06.04

Generic Name(s):

• Cefadroxil

Associated Monographs

• Cephalosporins General Statement

Cefadroxil is a semisynthetic, first generation cephalosporin antibiotic.

Pharyngitis and Tonsillitis

Oral cefadroxil is used for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci).100,120,121 Although cefadroxil generally is effective in eradicating S. pyogenes from the nasopharynx, efficacy of the drug in prevention of subsequent rheumatic fever has not been established to date.100,120,121

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.116,117 No regimen has been found to date that effectively eradicates group A β-hemolytic streptococci in 100% of patients.117

Because the drugs have a narrow spectrum of activity, are inexpensive, and generally are effective with a low frequency of adverse effects, the American Academy of Pediatrics (AAP),119 Infectious Diseases Society of America (IDSA),116 American Heart Association (AHA),117 and others111 recommend a penicillin regimen (i.e., 10 days of oral penicillin V or oral amoxicillin or 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.111,116,117,119

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).116,117,119

Skin and Skin Structure Infections

Oral cefadroxil is used for the treatment of mild to moderate skin and skin structure infections caused by susceptible staphylococci or streptococci.100,120,121

Urinary Tract Infections

Oral cefadroxil is used for the treatment of mild to moderate urinary tract infections, including acute prostatitis, caused by susceptible Escherichia coli , Klebsiella , or Proteus mirabilis .100,120,121

Prevention of Bacterial Endocarditis

Oral cefadroxil is used as an alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in penicillin-allergic individuals undergoing certain dental or upper respiratory tract procedures who have underlying cardiac conditions that put them at highest risk of adverse outcomes from endocarditis.115,119 Cefadroxil should not be used for such prophylaxis in those with a history of immediate-type hypersensitivity to penicillins (e.g., urticaria, angioedema, anaphylaxis).115,119

For information on which cardiac conditions are associated with highest risk of endocarditis and which procedures require prophylaxis, see Prevention under Uses: Endocarditis, in the Cephalosporins General Statement 8:12.06. When selecting anti-infectives for prophylaxis of bacterial endocarditis, the current recommendations published by the AHA should be consulted.115

Reconstitution and Administration

Cefadroxil is administered orally.100,120,121

Cefadroxil may be administered without regard to meals.100,120,121 Administration with food may minimize adverse GI effects.100,120,121

Reconstitution

Cefadroxil powder for oral suspension should be reconstituted at the time of dispensing by adding the amount of water specified on the container to provide a suspension containing 125, 250, or 500 mg of cefadroxil per 5 mL.121 The water should be added in 2 equal portions and the bottle shaken after each addition.121

The oral suspension should be shaken well prior to administration of each dose.121

Dosage

Adult Dosage

Pharyngitis and Tonsillitis

For the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci), the usual adult dosage of cefadroxil is 1 g daily given as a single dose or in 2 equally divided doses for 10 days.100,120,121

Skin and Skin Structure Infections

For the treatment of skin and skin structure infections, the usual adult dosage of cefadroxil is 1 g daily given as a single dose or in 2 equally divided doses.100,120,121

Urinary Tract Infections

For the treatment of uncomplicated urinary tract infections (i.e., cystitis), the usual adult dosage of cefadroxil is 1 or 2 g daily given as a single dose or in 2 equally divided doses.100,120,121 The usual adult dosage for the treatment of other urinary tract infections is 2 g daily given in 2 equally divided doses.100,120,121

Pediatric Dosage

General Pediatric Dosage

The American Academy of Pediatrics (AAP) recommends that pediatric patients beyond the neonatal period receive cefadroxil in a dosage of 30 mg/kg daily in 2 equally divided doses for the treatment of mild or moderate infections.119 The AAP states that the drug is inappropriate for the treatment of severe infections.119

Pharyngitis and Tonsillitis

For the treatment of group A β-hemolytic streptococcal pharyngitis and tonsillitis, the usual pediatric dosage of cefadroxil is 30 mg/kg daily given as a single dose or in 2 equally divided doses for 10 days.100,120,121

Skin and Skin Structure Infections

For the treatment of impetigo, pediatric patients should receive cefadroxil in a dosage of 30 mg/kg daily given as a single dose or in 2 equally divided doses.100,120,121 For the treatment of other skin and skin structure infections, children should receive 30 mg/kg daily given in divided doses every 12 hours.100,120,121

Urinary Tract Infections

For the treatment of urinary tract infections, the usual pediatric dosage of cefadroxil is 30 mg/kg daily given in divided doses every 12 hours.100,120,121

Dosage in Renal Impairment

In patients with creatinine clearances of 50 mL/minute per 1.73 m² or lower, doses and/or frequency of administration of cefadroxil must be modified in response to the degree of renal impairment.100,120,121 The manufacturers recommend that adults receive an initial dose of 1 g followed by 500-mg maintenance doses at the following dosage intervals based on the patient's creatinine clearance:100,120,121 (See Table 1.)

Cefadroxil shares the toxic potentials of other cephalosporins, and the usual cautions, precautions, and contraindications associated with cephalosporin therapy should be observed. (See Cautions in the Cephalosporins General Statement 8:12.06.)

Spectrum

Based on its spectrum of activity, cefadroxil is classified as a first generation cephalosporin. 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. Like other first generation cephalosporins (e.g., cefazolin, cephalexin), cefadroxil is active in vitro against many gram-positive aerobic cocci but has limited activity against gram-negative bacteria.

In Vitro Susceptibility Testing

Strains of staphylococci resistant to penicillinase-resistant penicillins (methicillin-resistant [oxacillin-resistant] staphylococci) should be considered resistant to cephalexin, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.118

For information on interpreting results of in vitro susceptibility testing (disk susceptibility tests, dilution susceptibility tests) when cefadroxil 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

Absorption

Cefadroxil is acid-stable100,121 and is rapidly and almost completely absorbed from the GI tract.100,101,102,103,104,105,106,120,121 The rate of absorption and peak serum concentrations of cefadroxil are not affected when the drug is administered with food.102,107,108,109,121

Following oral administration in healthy adults with normal renal function, peak serum cefadroxil concentrations are attained within 1-2 hours101,102,103,104,105,106,107,108,109,110,112,113 and average about 10-18 mcg/mL following a single 500-mg dose100,101,103,104,107,110,120,121 and 24-35 mcg/mL following a single 1-g dose.100,102,103,105,106,108,110,113,120,121

In a group of children 13 months to 12 years of age with normal renal function, peak serum concentrations of cefadroxil averaged 13.7 mcg/mL and were attained within 1 hour after a single oral dose of 15 mg/kg; serum concentrations of the drug were 0.6-1.8 mcg/mL at 6 hours.109

Elimination

The serum half-life of cefadroxil is 1.1-2 hours in adults with normal renal function.103,105,107,108,110,112

Cefadroxil is excreted unchanged in urine.100,101,102,103,104,105,106,107,110,112,113,120,121 In adults with normal renal function, from 70 to more than 90% of a single 500-mg or 1-g oral dose of the drug is excreted unchanged in urine within 24 hours,100,101,102,103,104,105,108,113,120,121 principally within the first 6-9 hours after administration.101,103,106,107,110,112,113 In adults with normal renal function, peak urine concentrations of cefadroxil of 1.8 mg/mL may be attained following a single 500-mg oral dose.100,120,121

The serum half-life of cefadroxil is prolonged in patients with impaired renal function.105,114 The half-life of cefadroxil is 2.5-8.5 hours in patients with creatinine clearances of 20-50 mL/minute per 1.73 m² and 13.3-25.5 hours in patients with creatinine clearances less than 20 mL/minute per 1.73 m².105,114 Renal elimination of cefadroxil is substantially reduced in patients with creatinine clearances less than 20 mL/minute per 1.73 m², with about 10-30% of a single oral dose excreted unchanged in urine within 24 hours.105,114

Cefadroxil is removed by hemodialysis.100,105,120,121

Chemistry and Stability

Chemistry

Cefadroxil is a semisynthetic cephalosporin antibiotic.100,121 Cefadroxil is commercially available as the monohydrate100,121 which occurs as a white to yellowish-white, crystalline powder and is soluble in water and slightly soluble in alcohol.

Stability

Cefadroxil capsules and tablets should be stored in tight containers at 20-25°C.100

Cefadroxil powder for oral suspension should be stored at 20-25°C.121 After reconstitution, cefadroxil oral suspension should be refrigerated in a tight container; any unused suspension should be discarded if not used within 14 days.121

Additional Information

For further information on chemistry, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of cefadroxil, see the Cephalosporins General Statement 8:12.06.

Only references cited for selected revisions after 1984 are available electronically.

100. West-ward Pharmaceutical Corp. Cefadroxil tablets, film coated and cefadroxil capsules prescribing information. Eatontown, NJ; 2011 Feb.

101. Hartstein AI, Patrick KE, Jones SR et al. Comparison of pharmacological and antimicrobial properties of cefadroxil and cephalexin. Antimicrob Agents Chemother . 1977; 12:93-7. [PubMedCentral][PubMed 883822]

102. Lode VH, Stahlmann R, Dzwillo G et al. Vergleichende Pharmakokinetik oraler Cephalosporine: Cephalexin, Cefaclor und Cefadroxil. (German; with English abstract.) Arzneim-Forsch . 1980; 30:505-9.

103. Marino EL, Dominguez-Gil A. Influence of dose on the pharmacokinetics of cefadroxil. Eur J Clin Pharmacol . 1980; 18:505-9. [PubMed 7461017]

104. Marino EL, Dominguez-Gil A, Muriel C. Influence of dosage form and administration route on the pharmacokinetic parameters of cefadroxil. Int J Clin Pharmacol Ther Toxicol . 1982; 20:73-7. [PubMed 7061182]

105. Humbert G, Leroy A, Fillastre JP et al. Pharmacokinetics of cefadroxil in normal subjects and in patients with renal insufficiency. Infection . 1980; 8(Suppl 5):S598-602.

106. Hampel B, Lode H, Wagner J et al. Pharmacokinetics of cefadroxil and cefaclor during an eight-day dosage period. Antimicrob Agents Chemother . 1982; 22:1061-3. [PubMedCentral][PubMed 7159069]

107. Pfeffer M, Jackson A, Ximenes J et al. Comparative human oral clinical pharmacology of cefadroxil, cephalexin, and cephradine. Antimicrob Agents Chemother . 1977; 11:331-8. [PubMedCentral][PubMed 848940]

108. Lode H, Stahlmann R, Koeppe P. Comparative pharmacokinetics of cephalexin, cefaclor, cefadroxil, and CGP 9000. Antimicrob Agents Chemother . 1979; 16:1-6. [PubMedCentral][PubMed 475366]

109. Ginsburg CM, McCracken GH, Clahsen JC et al. Clinical pharmacology of cefadroxil in infants and children. Antimicrob Agents Chemother . 1978; 13:845-8. [PubMedCentral][PubMed 666305]

110. La Rosa F, Ripa S, Prenna M et al. Pharmacokinetics of cefadroxil after oral administration in humans. Antimicrob Agents Chemother . 1982; 21:320-2. [PubMedCentral][PubMed 7073267]

111. Anon. Drugs for bacterial infections. Med Lett Treat Guid . 2010; 8:43-52.

112. Welling PG, Selen A, Pearson JG et al. A pharmacokinetic comparison of cephalexin and cefadroxil using HPLC assay procedures. Biopharm Drug Dispos . 1985; 6:147-57. [PubMed 4005394]

113. Adam D, Gierschik P. Vergleichende Untersuchungen zur Pharmakokinetik von Cefadroxil und Amoxicillin nach oraler Nuchterngabe. (German; with English abstract.) Infection . 1980; 8(Suppl 5):S567-72.

114. Cutler RE, Blair AD, Kelly MR. Cefadroxil kinetics in patients with renal insufficiency. Clin Pharmacol Ther . 1979; 25:514-21. [PubMed 436355]

115. Wilson W, Taubert KA, Gewitz M et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation . 2007; 116:1736-54. [PubMed 17446442]

116. Shulman ST, Bisno AL, Clegg HW et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis . 2012; 55:1279-82. [PubMed 23091044]

117. Gerber MA, Baltimore RS, Eaton CB et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation . 2009; 119:1541-51. [PubMed 19246689]

118. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: Twenty-first informational supplement. CLSI document M100-S21. Wayne, PA; 2011.

119. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

120. Ranbaxy. Cefadroxil tablets and capsules USP prescribing information. Princeton, NJ. 2002 May.

121. Ranbaxy Pharmaceuticals Inc. Cefadroxil monohydrate powder for oral suspension prescribing information. Jacksonville, FL; 2007 Mar.

142. Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol . 2010; 31:431-55. [PubMed 20307191]