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 S. pneumoniae, Haemophilus influenzae, M. catarrhalis, or staphylococci or streptococci.^{100 105 110 111}

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci).^{100 105 110 111} Generally effective in eradicating S. pyogenes from the nasopharynx, but efficacy in prevention of subsequent rheumatic fever has not been established to date.^{100 105 110 111}

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CDC, AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;^{102 107 108 109} oral cephalosporins and oral macrolides considered alternatives.^{102 107 108 109} Amoxicillin sometimes used instead of penicillin V, especially for young children.^{102 107}

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 Streptococcus 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.¹⁰⁴ Should not be used in those with immediate-type penicillin hypersensitivity (see Cross-hypersensitivity under Cautions).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.^{105 111}

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

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

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 that these dosages may be doubled for severe infections;^{100 110 111} AAP states that cephalexin is inappropriate for 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} AAP states the drug is inappropriate for severe infections.¹⁰²

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} AAP states the drug is inappropriate for severe infections.¹⁰²

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} AAP states the drug is inappropriate for severe infections.¹⁰²

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} AAP states the drug is inappropriate for severe infections.¹⁰²

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 Cl_cr 11–40 mL/minute, 250 mg every 12 hours if Cl_cr 5–10 mL/minute, or 250 mg every 12–24 hours if Cl_cr <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 may permit overgrowth of Clostridium difficile.^{100 105} C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including cephalexin, and may range in severity from mild diarrhea to fatal colitis.¹⁰⁰

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.^{100 105} Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.¹⁰⁰

If CDAD is suspected or confirmed, the anti-infective may need to be discontinued.^{100 105} Some mild cases may respond to discontinuance alone.^{100 105 a} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.^{100 105 a}

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 reaction^{104 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

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

Specific Populations

Pregnancy

Category B.^{100 105}

Lactation

Distributed into milk.^{100 105} Use with caution.^{100 105}

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

Substantially eliminated by kidneys; risk of toxicity may be greater in those with impaired renal function.¹⁰⁰ Select dosage with caution and consider monitoring renal function because of age-related decreases in renal function.¹⁰⁰ (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 Cl_cr ≤ 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 potential for increased adverse effects associated with metformin	Monitor closely; adjust metformin dosage if necessary100
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 Cl_cr <13.5 mL/minute.^b

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).^{100 105}

For Suspension

15–30°C in tight, light-resistant container.¹⁰⁵ After reconstitution, refrigerate in a tight container for up to 14 days.¹⁰⁵

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

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

• 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

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

• 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.

• Importance of informing patients of other important precautionary information. (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	Lupin, Ranbaxy, Teva, West-Ward
			Keflex	Middlebrook
		333 mg	Keflex	Middlebrook
		500 mg*	Cephalexin Capsules	Lupin, Ranbaxy, Teva, West-Ward
			Keflex	Middlebrook
		750 mg	Keflex	Middlebrook
	For suspension	125 mg/5 mL*	Cephalexin for Suspension	Lupin, Ranbaxy, Teva
			Keflex	Middlebrook
		250 mg/5 mL*	Cephalexin for Suspension	Lupin, Ranbaxy, Teva
			Keflex	Middlebrook
	Tablets, film-coated	250 mg*	Cephalexin Film-coated Tablets	Teva
		500 mg*	Cephalexin Film-coated Tablets	Teva

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. 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