VA Class:AM115

AHFS Class:

• First Generation Cephalosporins 8:12.06.04

Generic Name(s):

• Cephalexin

Associated Monographs

• Cephalosporins General Statement

Cephalexin is a semisynthetic, first generation cephalosporin antibiotic.

Acute Otitis Media

Oral cephalexin is used for the treatment of acute otitis media (AOM) caused by susceptible Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis , staphylococci, or streptococci.100,105,110,111

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

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 cephalexin is used for the treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci).100,105,110,111 Although cephalexin 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.100,105,110,111

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 AAP,102 Infectious Diseases Society of America (IDSA),116 American Heart Association (AHA),117 and others101 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.101,102,111,116,117

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).102,116,117

Bone and Joint Infections

Oral cephalexin is used for the treatment of bone and joint infections caused by susceptible staphylococci or Proteus mirabilis .100,105,110,111

Respiratory Tract Infections

Oral cephalexin is used for the treatment of mild to moderate respiratory tract infections caused by susceptible S. pneumoniae .100,105,110,111

Skin and Skin Structure Infections

Oral cephalexin is used for the treatment of mild to moderate skin and skin structure infections caused by susceptible staphylococci or streptococci.100,105,110,111

Urinary Tract Infections

Oral cephalexin is used for the treatment of mild to moderate urinary tract infections, including acute prostatitis, caused by susceptible Escherichia coli , Klebsiella pneumoniae , or P. mirabilis .100,105,110,111

Prevention of Bacterial Endocarditis

Oral cephalexin 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.102,104 Cephalexin should not be used for such prophylaxis in those with a history of immediate-type hypersensitivity to penicillins (e.g., urticaria, angioedema, anaphylaxis).102,104

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 AHA should be consulted.104

Reconstitution and Administration

Cephalexin is administered orally.100,105,110,111

Although food may decrease the rate of absorption of cephalexin (see Pharmacokinetics: Absorption),103 the manufacturers state that the drug may be administered without regard to meals.100,105,110,111

Reconstitution

Cephalexin 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 or 250 mg of cephalexin per 5 mL.105,111 The water should be added in 2 equal portions and the bottle shaken after each addition.111

The oral suspension should be shaken well prior to administration of each dose.105,111

Dosage

Cephalexin is commercially available as the monohydrate; dosage is expressed in terms of cephalexin.100,105,110,111

Adult Dosage

General Adult Dosage

The usual adult dosage of cephalexin ranges from 1-4 g daily given in divided doses.100,105,110,111 Dosage usually is 250 mg every 6 hours or 500 mg every 12 hours.100,105,110,111 For severe infections or those caused by less susceptible organisms, higher dosage may be needed (up to 4 g daily in adults).100,105

If dosage greater than 4 g daily is required, initial therapy with a parenteral cephalosporin should be considered.100,105,110,111

Pharyngitis and Tonsillitis

For the treatment of group A β-hemolytic streptococcal pharyngitis and tonsillitis in patients older than 15 years of age, the usual dosage is 500 mg of cephalexin every 12 hours given for at least 10 days.100,105,110,111

Bone and Joint Infections

For the treatment of bone and joint infections in patients older than 15 years of age, the manufacturer recommends 250 mg every 6 hours.100,105 Higher dosages may be needed for severe infections or those caused by less susceptible bacteria.100,105

Respiratory Tract Infections

For the treatment of respiratory tract infections in patients older than 15 years of age, the manufacturer recommends 250 mg every 6 hours for mild to moderate infections.100,105 Higher dosages may be needed for more severe infections or those caused by less susceptible bacteria.100,105

Skin and Skin Structure Infections

For the treatment of skin and skin structure infections in patients older than 15 years of age, the usual dosage is 500 mg of cephalexin every 12 hours.100,105,110,111

Urinary Tract Infections

For the treatment of uncomplicated cystitis in patients older than 15 years of age, the usual dosage is 500 mg of cephalexin every 12 hours given for 7-14 days.100,105,110,111

Prevention of Bacterial Endocarditis

If cephalexin is used as an alternative to amoxicillin or ampicillin for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in penicillin-allergic individuals considered to be at highest risk for bacterial endocarditis following certain dental or upper respiratory tract procedures, adults should receive a single 2-g dose administered 0.5-1 hour prior to the procedure.104

Pediatric Dosage

General Pediatric Dosage

The manufacturers state that the usual dosage of cephalexin for children is 25-50 mg/kg daily in divided doses;100,102,110,111 however, these dosages may be doubled for severe infections.100,110,111

The American Academy of Pediatrics (AAP) recommends that pediatric patients beyond the neonatal period receive cephalexin in a dosage of 25-50 mg/kg daily in 2 or 4 equally divided doses for the treatment of mild or moderate infections and 75-100 mg/kg daily in 3 or 4 equally divided doses for the treatment of severe infections.102

Acute Otitis Media

For the treatment of otitis media, the manufacturers recommend a pediatric dosage of 75-100 mg/kg daily in 4 equally divided doses.100,105,110,111

Pharyngitis and Tonsillitis

The usual dosage of cephalexin for the treatment of group A β-hemolytic streptococcal pharyngitis in children older than 1 year of age is 25-50 mg/kg daily in equally divided doses every 12 hours given for at least 10 days.100,102,105,110,111

Skin and Skin Structure Infections

For the treatment of skin and skin structure infections in pediatric patients, the usual dosage of cephalexin is 25-50 mg/kg daily in equally divided doses every 12 hours.100,105,110,111

Prevention of Bacterial Endocarditis

If cephalexin is used as an alternative to amoxicillin or ampicillin for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in penicillin-allergic individuals considered to be at highest risk for bacterial endocarditis following certain dental or upper respiratory tract procedures, pediatric patients should receive a single 50-mg/kg dose (no more than 2 g) administered 0.5-1 hour prior to the procedure.104

Dosage in Renal Impairment

The manufacturers state that cephalexin should be used with caution in patients with markedly impaired renal function, and close clinical observation and laboratory studies are recommended in such patients because safe dosage may be lower than usual dosages.100,105

Some clinicians state that modification of the usual dosage does not appear to be necessary in patients with creatinine clearances greater than 40 mL/minute. These clinicians suggest that the usual adult dosage be used for the initial dose. Then, for subsequent doses, adults with creatinine clearances of 11-40 mL/minute should receive 500 mg every 8-12 hours, those with creatinine clearances of 5-10 mL/minute should receive 250 mg every 12 hours, and those with creatinine clearances less than 5 mL/minute should receive 250 mg every 12-24 hours.

Cephalexin 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.)

Pediatric Precautions

Cephalexin is labeled for use in pediatric patients;100,105,110,111 safety and efficacy were established based on clinical trials using recommended dosages of the drug administered as capsules or oral suspension.100,110

Cephalexin capsules should only be used in children and adolescents who are able to ingest capsules.100,110

Spectrum

Based on its spectrum of activity, cephalexin 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., cefadroxil, cefazolin), cephalexin 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.112

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

Cephalexin (as the monohydrate) is acid-stable and is rapidly and completely absorbed from the GI tract.100,105,110,111 Following oral administration in healthy, fasting adults with normal renal function of a single 250-mg, 500-mg, or 1-g dose of cephalexin, peak serum cephalexin concentrations are attained within 1 hour and average 9, 18, or 32 mcg/mL, respectively.100,105,110,111 Serum concentrations of cephalexin were still detectable 6 hours after the dose.100,105,110,111

Peak serum concentrations are slightly lower and are attained later when cephalexin is administered with food, although the total amount of drug absorbed is unchanged. Following oral administration of cephalexin in healthy, fasting adults, serum concentrations 15 and 30 minutes after a single 500-mg dose averaged about 0.2 and 12 mcg/mL, respectively.103

Absorption of cephalexin is delayed in young children and may be decreased up to 50% in neonates. Peak serum concentrations of the drug have been reported to occur within 3 hours in infants younger than 6 months of age, within 2 hours in children 9-12 months of age, and within 1 hour in older children.

Elimination

The serum half-life of cephalexin is 0.5-1.2 hours in adults with normal renal function. The serum half-life of the drug is reported to be about 5 hours in neonates and 2.5 hours in children 3-12 months of age. In one study, the serum half-life was 7.7 hours in adults with creatinine clearances of 13.5 mL/minute, 10.8 hours in adults with creatinine clearances of 9.2 mL/minute, and 13.9 hours in adults with creatinine clearances of 4 mL/minute.

Cephalexin is excreted in urine as unchanged drug via both glomerular filtration and tubular secretion.100,105,110,111 Approximately 70-90% of a single 250- or 500-mg oral dose is excreted within 8-12 hours in adults with normal renal function. Cephalexin concentrations of 0.2 (range: 0.054-0.67) or 0.11-4 mg/mL have been reported in urine collected over a 6-hour period following a single 250- or 500-mg dose, respectively, in adults with normal renal function. Peak urine concentrations of the drug averaging about 2 mg/mL occur 2 hours after a single 500-mg oral dose of cephalexin.103

Chemistry and Stability

Chemistry

Cephalexin is a semisynthetic cephalosporin antibiotic.100,105 Cephalexin is commercially available as the monohydrate.100,105,110,111 Cephalexin (as the monohydrate) occurs as a white to off-white, crystalline powder and is slightly soluble in water and practically insoluble in alcohol.

Stability

Cephalexin capsules should be stored in tight, light-resistant containers at 20-25°C,100,105,110 but may be exposed to temperatures ranging from 15-30°C.100

Cephalexin powder for oral suspension should be stored at 20-25°C.111 After reconstitution, cephalexin oral suspension should be refrigerated in a tight container; any unused suspension should be discarded if not used within 14 days.105,111

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 cephalexin, see the Cephalosporins General Statement 8:12.06.

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

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100. Shionogi Inc. Keflex^® (cephalexin) capsules prescribing information. Florham Park, NJ; 2011 Aug.

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

102. 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.

103. Kamar A, Murray DL, Hanna CB et al. Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections. Antimicrob Agents Chemother . 1988; 32:882-5. [PubMedCentral][PubMed 3046484]

104. 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]

105. Ranbaxy Pharmaceuticals Inc. Cephalexin capsules and cephalexin oral suspension prescribing information. Jacksonville, FL; 2007 Jan.

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110. Lupin Pharmaceuticals, Inc. Cephalexin capsules prescribing information. Baltimore, MD; 2012 Jun.

111. Lupin Pharmaceuticals, Inc. Cephalexin for oral suspension prescribing information. Baltimore, MD; 2005 May.

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

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]

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