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Generic Name: Cephalexin
Class: First Generation Cephalosporins
CAS Number: 23325-78-2

Introduction

Antibacterial; β-lactam antibiotic; first generation cephalosporin.a

Uses for Keflex

Acute Otitis Media (AOM)

Treatment of AOM caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, staphylococci, or streptococci.100 105 110 111

When anti-infectives indicated, AAP recommends high-dose amoxicillin or amoxicillin and clavulanate as drugs of choice for initial treatment of AOM; certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) recommended as alternatives for initial treatment in penicillin-allergic patients without a history of severe and/or recent penicillin-allergic reactions.37

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci).100 105 110 111 Generally effective in eradicating S. pyogenes from nasopharynx; efficacy in prevention of subsequent rheumatic fever not established to date.100 105 110 111

Slideshow: The Shocking Truth About Antibiotic Resistance

AAP, IDSA, AHA, and others recommend a penicillin regimen (10 days of oral penicillin V or oral amoxicillin or single dose of IM penicillin G benzathine) as treatment of choice for S. pyogenes pharyngitis and tonsillitis;101 102 116 117 other anti-infectives (e.g., oral cephalosporins, oral macrolides, oral clindamycin) recommended as alternatives in penicillin-allergic patients.101 102 116 117

If an oral cephalosporin used, 10-day regimen of first generation cephalosporin (cefadroxil, cephalexin) preferred instead of other cephalosporins with broader spectrums of activity (e.g., cefaclor, cefdinir, cefixime, cefpodoxime, cefuroxime).102 116 117

Bone and Joint Infections

Treatment of bone and joint infections caused by susceptible staphylococci or Proteus mirabilis.100 105 110 111

Respiratory Tract Infections

Treatment of mild to moderate respiratory tract infections caused by susceptible S. pneumoniae.100 105 110 111

Skin and Skin Structure Infections

Treatment of mild to moderate skin and skin structure infections caused by susceptible staphylococci or streptococci.100 105 110 111

Urinary Tract Infections (UTIs)

Treatment of mild to moderate UTIs, including acute prostatitis, caused by susceptible Escherichia coli, Klebsiella pneumoniae, or P. mirabilis.100 105 110 111

Prevention of Bacterial Endocarditis

Alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis in penicillin-allergic individuals undergoing certain dental or upper respiratory tract procedures who have cardiac conditions that put them at highest risk.102 104 Should not be used in those with immediate-type penicillin hypersensitivity (see Cross-hypersensitivity under Cautions).102 104

When selecting anti-infectives for prophylaxis of bacterial endocarditis, consult most recent AHA recommendations for specific information on which cardiac conditions are associated with highest risk of endocarditis and which procedures require prophylaxis.104

Keflex Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.100 105 110 111

Reconstitution

Reconstitute oral suspension at time of dispensing by adding the amount of water specified on the container in 2 equal portions; shake after each addition.111

Reconstituted suspensions contain 125 or 250 mg of cephalexin/5 mL.105 111

Shake oral suspension well prior to administration of each dose.105 111

Dosage

Available as cephalexin monohydrate; dosage expressed in terms of cephalexin.100 105 110 111

Pediatric Patients

General Pediatric Dosage
Oral

25–50 mg/kg daily in divided doses.100 102 110 111 Manufacturers state these dosages may be doubled for severe infections.100 110 111

Children beyond neonatal period: AAP recommends 25–50 mg/kg daily in 2 or 4 equally divided doses for treatment of mild or moderate infections and 75–100 mg/kg daily in 3 or 4 equally divided doses for treatment of severe infections.102

Acute Otitis Media (AOM)
Oral

75–100 mg/kg daily in 4 divided doses.100 105 110 111

Pharyngitis and Tonsillitis
Oral

25–50 mg/kg daily in 3–4 equally divided doses for ≥10 days.100 102 105 110 111 Daily dosage may be given in divided doses every 12 hours in those >1 year of age.100 105 110 111

Children >15 years of age: 500 mg every 12 hours for ≥10 days.100 105 110 111

Bone and Joint Infections
Oral

25–50 mg/kg daily in 3–4 equally divided doses for mild to moderate infections.100 102 105 Manufacturers state dosage may be doubled for severe infections.100 105 110 111

Respiratory Tract Infections
Oral

25–50 mg/kg daily in 3–4 equally divided doses for mild to moderate infections.100 102 105 Manufacturers state dosage may be doubled for severe infections.100 105

Skin and Skin Structure Infections
Oral

25–50 mg/kg daily in divided doses every 12 hours for mild to moderate infections.100 105 110 111

Children >15 years of age: 500 mg every 12 hours for mild to moderate infections.100 105 110 111

Manufacturers state dosage may be doubled for severe infections.100 105 110 111

Urinary Tract Infections (UTIs)
Oral

25–50 mg/kg daily in 3–4 equally divided doses for mild to moderate infections.100 102 105

Children >15 years of age with uncomplicated cystitis: 500 mg every 12 hours for 7–14 days.100 105

Manufacturers state dosage may be doubled for severe infections.100 105 110 111

Prevention of Bacterial Endocarditis
Patients Undergoing Certain Dental or Upper Respiratory Tract Procedures
Oral

50 mg/kg (up to 2 g) as a single dose given 0.5–1 hour prior to the procedure.104

Adults

General Adult Dosage
Oral

Usual dosage ranges from 1–4 g daily given in divided doses.100 105 If dosage >4 g daily is required, consider initial therapy with a parenteral cephalosporin.100 105

Acute Otitis Media (AOM)
Oral

250 mg every 6 hours.100 105 Higher dosage may be needed for severe infections or those caused by less susceptible bacteria.100 105

Pharyngitis and Tonsillitis
Oral

500 mg every 12 hours for ≥10 days.100 105 110 111

Bone and Joint Infections
Oral

250 mg every 6 hours.100 105 Higher dosage may be needed for severe infections or those caused by less susceptible bacteria.100 105

Respiratory Tract Infections
Oral

250 mg every 6 hours for mild to moderate infections.100 105 Higher dosage may be needed for more severe infections or those caused by less susceptible bacteria.100 105

Skin and Skin Structure Infections
Oral

500 mg every 12 hours for mild to moderate infections.100 105 110 111 Higher dosage may be needed for severe infections or those caused by less susceptible bacteria.100 105

Urinary Tract Infections (UTIs)
Oral

500 mg every 12 hours for 7–14 days for mild to moderate infections.100 105 110 111 Higher dosage may be needed for severe infections or those caused by less susceptible bacteria.100 105 110 111

Prevention of Bacterial Endocarditis
Patients Undergoing Certain Dental or Upper Respiratory Tract Procedures
Oral

2 g as a single dose given 0.5–1 hour prior to the procedure.104

Special Populations

Renal Impairment

Use with caution in patients with markedly impaired renal function; close clinical observation and appropriate laboratory tests recommended because safe dosage may be lower than usual dosages.100 105

Some clinicians suggest that the usual adult dosage be used for the initial dose.b Then, for subsequent doses, use 500 mg every 8–12 hours if Clcr 11–40 mL/minute, 250 mg every 12 hours if Clcr 5–10 mL/minute, or 250 mg every 12–24 hours if Clcr <5 mL/minute.b

Geriatric Patients

Cautious dosage selection because of age-related decreases in renal function.100 (See Renal Impairment under Dosage and Administration.)

Cautions for Keflex

Contraindications

  • Known hypersensitivity to cephalexin or other cephalosporins.100 105 110 111

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi with prolonged use.100 105 Careful observation of the patient is essential.100 105 Institute appropriate therapy if superinfection occurs.100 105

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.100 105 142 C. difficile infections (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including cephalexin, and may range in severity from mild diarrhea to fatal colitis.100 110 142 C. difficile produces toxins A and B which contribute to development of CDAD;100 110 142 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.100 110

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.100 105 110 142 Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.100 110 142

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.100 105 110 142 Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.100 105 110 142

Sensitivity Reactions

Hypersensitivity Reactions

Possible hypersensitivity reactions (e.g., urticaria, pruritus, rash, fever and chills, eosinophilia, joint pain or inflammation, edema, erythema, genital and anal pruritus, angioedema, shock, hypotension, vasodilatation, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, exfoliative dermatitis, anaphylaxis).100 105 110 111 a

If a hypersensitivity reaction occurs, discontinue cephalexin immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).100 105 110 111 a

Cross-hypersensitivity

Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.100 105 110 111 a

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.100 105 110 111 a Cautious use recommended in patients with a history of hypersensitivity to penicillins:100 105 110 111 avoid use in those who have had an immediate-type (anaphylactic) hypersensitivity reaction104 a and administer with caution in those who have had a delayed-type (e.g., rash, fever, eosinophilia) reaction.a

General Precautions

History of GI Disease

Cephalosporins should be used with caution in patients with a history of GI disease, particularly colitis.100 105 110 111 a (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions.)

Coombs’ Test Results

Positive direct Coombs’ test results reported with cephalosporins.100 105 110 111 a This may interfere with certain hematologic studies or transfusion cross-matching procedures.100 105 110 111 a May also cause positive Coombs’ tests in neonates whose mothers received a cephalosporin prior to delivery.100 105 110 111 a

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of cephalexin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.100 110 111

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.100 110 111 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.100 110 111

Specific Populations

Pregnancy

Category B.100 105 110 111

Lactation

Distributed into milk.100 105 110 111 Use with caution.100 105 110 111

Pediatric Use

Safety and efficacy in pediatric patients is based on clinical trials that used recommended dosages administered as capsules or oral suspension.100 110

Use cephalexin capsules in children and adolescents only in those able to ingest capsules.100 110

Geriatric Use

No overall differences in safety and efficacy in adults ≥65 years of age compared with younger adults, but the possibility of increased sensitivity in some geriatric individuals cannot be ruled out.100 110 111

Substantially eliminated by kidneys; risk of toxicity may be greater in those with impaired renal function.100 110 111 Select dosage with caution and consider monitoring renal function because of age-related decreases in renal function.100 110 111 (See Renal Impairment under Dosage and Administration.)

Renal Impairment

Decreased clearance and increased plasma half-life.b

Use with caution in those with markedly impaired renal function;100 105 close clinical observation and appropriate laboratory tests recommended.100 105

Reduced dosage has been recommended in those with Clcr ≤ 40 mL/minute.a (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Adverse GI effects, including diarrhea, nausea, vomiting, dyspepsia, gastritis, abdominal pain.100 105

Interactions for Keflex

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Metformin

Increased plasma concentrations and AUC and decreased renal clearance of metformin;100 111 potential for increased adverse effects associated with metformin100 111

Monitor closely; adjust metformin dosage if necessary100 111

Probenecid

Decreased renal excretion and increased plasma concentrations of cephalexin100 105

Tests for glucose

Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution100 105 a

Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)a

Keflex Pharmacokinetics

Absorption

Bioavailability

Rapidly and completely absorbed from the GI tract.100 105 Peak serum concentrations within 1 hour.100 105

Food

Although peak serum concentrations are slightly lower and attained later when administered with food, total amount of drug absorbed is unchanged.b

Distribution

Extent

Cephalosporins widely distributed into tissues and fluids.a

Distributed into milk.100 105

Plasma Protein Binding

6–15%.a

Elimination

Metabolism

Not appreciably metabolized.a

Elimination Route

Excreted in urine as unchanged drug by renal tubular secretion and glomerular filtration.100 105

At least 70–90% of a dose eliminated in urine within 8–12 hours in adults with normal renal function.100 105 b

Half-life

Adults with normal renal function: 0.5–1.2 hours.b

Children: about 5 hours in neonates and 2.5 hours in children 3–12 months of age.b

Special Populations

Decreased clearance and increased half-life in patients with renal impairment.b Half-life is 7.7–13.9 in adults with Clcr <13.5 mL/minute.b

Stability

Storage

Oral

Capsules

20–25°C (may be exposed to 15–30°C); tight, light-resistant container.100 105 110

For Suspension

20–25°C.111 After reconstitution, refrigerate in a tight container; discard after 14 days.105 111

Actions and Spectrum

  • First generation cephalosporin with a limited spectrum of activity compared with second and third generation cephalosporins.a

  • Usually bactericidal.100 105

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.a

  • In vitro spectrum of activity includes some gram-positive aerobic bacteria and some gram-negative aerobic bacteria.100 105 a Inactive against anaerobic bacteria, fungi, and viruses.a

  • Gram-positive aerobes: active in vitro and in clinical infections against gram-positive aerobic bacteria including Staphylococcus aureus and S. epidermidis (including penicillinase-producing strains), Streptococcus pyogenes (group A β-hemolytic streptococci), and S. pneumoniae.100 105 a Oxacillin-resistant (methicillin-resistant) staphylococci and most enterococci are resistant.100 a

  • Gram-negative aerobes: active in vitro and in clinical infections against some gram-negative aerobic bacteria including Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis.100 105 a Inactive against Acinetobacter, Citrobacter, Enterobacter, Listeria monocytogenes, Morganella morganii, Providencia, Pseudomonas, and Serratia.100 105 a b

Advice to Patients

  • Advise patients that antibacterials (including cephalexin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).100 110 111

  • Importance of completing full course of therapy, even if feeling better after a few days.100 110 111

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cephalexin or other antibacterials in the future.100 110 111

  • Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.100 110 Importance of contacting 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.100 110

  • Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.100

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.100

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.100

  • Importance of informing patients of other important precautionary information.100 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Cephalexin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

250 mg*

Cephalexin Capsules

Keflex

Shionogi

333 mg*

Cephalexin Capsules

500 mg*

Cephalexin Capsules

Keflex

Shionogi

750 mg*

Cephalexin Capsules

Keflex

Shionogi

For suspension

125 mg/5 mL*

Cephalexin for Suspension

250 mg/5 mL*

Cephalexin for Suspension

Tablets, film-coated

250 mg*

Cephalexin Film-coated Tablets

500 mg*

Cephalexin Film-coated Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Cephalexin 125MG/5ML Suspension (TEVA PHARMACEUTICALS USA): 100/$15.99 or 200/$21.98

Cephalexin 250MG Capsules (LUPIN PHARMACEUTICALS): 30/$14.99 or 60/$19.97

Cephalexin 250MG/5ML Suspension (LUPIN PHARMACEUTICALS): 200/$22.99 or 600/$68.97

Cephalexin 250MG/5ML Suspension (TEVA PHARMACEUTICALS USA): 100/$26.99 or 200/$45.97

Cephalexin 500MG Capsules (WEST-WARD): 30/$16.99 or 60/$25.98

Keflex 500MG Capsules (SHIONOGI PHARMA): 30/$175.99 or 90/$514.95

Keflex 750MG Capsules (SHIONOGI PHARMA): 50/$215.98 or 150/$630.00

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 11, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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

37. Lieberthal AS, Carroll AE, Chonmaitree T et al. The diagnosis and management of acute otitis media. Pediatrics. 2013; 131:e964-99. [PubMed 23439909]

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. [IDIS 244249] [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 Apr 19. (Epub ahead of print).

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

109. Cooper RJ, Hoffman JR, Bartlett JG et al. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med. 2001; 134:509-17. [IDIS 460578] [PubMed 11255530]

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]

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]

a. AHFS Drug Information 2003. McEvoy GK, ed. Cephalosporins General Statement. American Society of Health-System Pharmacists; 2003:125-39.

b. AHFS Drug Information 2003, McEvoy GK, ed. Cephalexin/ Cephalexin Hydrochloride. American Society of Health-System Pharmacists; 2003:231-2.

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