Cephalexin

 Cephalexin is a cephalosporin antibacterial drug indicated for the treatment of the following infections caused by susceptible isolates of designated bacteria:

•  Respiratory tract infection (
  1.1 Respiratory Tract Infections

  Cephalexin is indicated for the treatment of respiratory tract infections caused by susceptible isolates of

  Streptococcus pneumoniae

  and

  Streptococcus pyogenes.
  )
  
  
•  Otitis media  (
  1.2 Otitis Media

  Cephalexin is indicated for the treatment of otitis media caused by susceptible isolates of

  Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, and Moraxella catarrhalis.
  )
  
  
•  Skin and skin structure infections  (
  1.3 Skin and Skin Structure Infections

  Cephalexin is indicated for the treatment of skin and skin structure infections caused by susceptible isolates of the following Gram-positive bacteria:

  Staphylococcus aureus

  and

  Streptococcus pyogenes.
  )
  
  
•  Bone infections (1.4)
  
  
•  Genitourinary tract infections (
  1.5 Genitourinary Tract Infections

  Cephalexin is indicated for the treatment of genitourinary tract infections, including acute prostatitis, caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae.
  )
  
  

 To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin and other antibacterial drugs, Cephalexin should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. (1.6)

• Duration of therapy ranges from 7 to14 days depending on the infection type and severity. (
  2 DOSAGE & ADMINISTRATION

  
  
  

  Adults and patients at least 15 years of age	The usual dose is 250 mg every 6 hours, but a dose of 500 mg every 12 hours may be administered
  Pediatric patients (over 1 year of age)	Otitis media: 75 to 100 mg/kg in equally divided doses every 6 hours  All other indications: 25 to 50 mg/kg given in equally divided doses In severe infections: 50 to 100 mg/kg may be administered in equally divided doses

  • Duration of therapy ranges from 7 to14 days depending on the infection type and severity. 
  • Dosage adjustment is required in patients with severe and end stage renal disease (ESRD) defined as creatinine clearance below 30 mL/min.
    
    

  2.1 Adults and Pediatric Patients at Least 15 Years of Age

  The usual dose of oral Cephalexin capsule, USP is 250 mg every 6 hours, but a dose of 500 mg every 12 hours may be administered. Treatment is administered for 7 to 14 days.

  For more severe infections larger doses of oral Cephalexin capsules, USP may be needed, up to 4 grams daily in two to four equally divided doses.

  2.2 Pediatric Patients (over 1 year of age)

  The recommended total daily dose of oral Cephalexin capsules, USP for pediatric patients is 25 to 50 mg/kg given in equally divided doses for 7 to 14 days. In the treatment of β-hemolytic streptococcal infections, duration of at least 10 days is recommended. In severe infections, a total daily dose of 50 to 100 mg/kg may be administered in equally divided doses.

  For the treatment of otitis media, the recommended daily dose is 75 to 100 mg/kg given in equally divided doses.

  2.3 Dosage Adjustments in Adult and Pediatric Patients at Least 15 Years of Age with Renal Impairment

  Administer the following dosing regimens for Cephalexin capsules, USP to patients with  renal impairment [see

  Warnings and Precautions (5.4)

  and

  Use in Specific Populations (8.6)

  ]

  .

  
  
  
  
  

  Table 1. Recommended Dose Regimen for Patients with Renal Impairment

  
  
  

  Renal function	Dose regimen recommendation
  Creatinine clearance >60mL/min.	No dose adjustment
  Creatinine clearance 30 to 59 mL/min	No dose adjustment; maximum daily dose should not exceed 1 g
  Creatinine clearance 15 to 29 mL/min	250 mg, every 8 hours or every 12 hours
  Creatinine clearance 5 to 14 mL/min not yet on dialysis*	250 mg, every 24 hours
  Creatinine clearance 1 to 4 mL/min not yet on dialysis*	250 mg, every 48 hours or every 60 hours

  *There is insufficient information to make dose adjustment recommendations in patients on hemodialysis.
  )
• Dosage adjustment is required in patients with severe and end stage renal disease (ESRD) defined as creatinine clearance below 30 mL/min. ( 
  2.3 Dosage Adjustments in Adult and Pediatric Patients at Least 15 Years of Age with Renal Impairment

  Administer the following dosing regimens for Cephalexin capsules, USP to patients with  renal impairment [see

  Warnings and Precautions (5.4)

  and

  Use in Specific Populations (8.6)

  ]

  .

  
  
  
  
  

  Table 1. Recommended Dose Regimen for Patients with Renal Impairment

  
  
  

  Renal function	Dose regimen recommendation
  Creatinine clearance >60mL/min.	No dose adjustment
  Creatinine clearance 30 to 59 mL/min	No dose adjustment; maximum daily dose should not exceed 1 g
  Creatinine clearance 15 to 29 mL/min	250 mg, every 8 hours or every 12 hours
  Creatinine clearance 5 to 14 mL/min not yet on dialysis*	250 mg, every 24 hours
  Creatinine clearance 1 to 4 mL/min not yet on dialysis*	250 mg, every 48 hours or every 60 hours

  *There is insufficient information to make dose adjustment recommendations in patients on hemodialysis.
   )
  
  

Renal Impairment: Monitor patients longer for toxicity and drug interactions due to delayed clearance. (

• Serious hypersensitivity (anaphylactic) reactions
  : Prior to use, inquire regarding history of hypersensitivity to beta-lactam antibacterial drugs. Discontinue the drug if signs or symptoms of an allergic reaction occur and institute supportive measures. (
  5.1 Hypersensitivity Reactions

  
  
  

  Allergic reactions in the form of rash, urticaria, angioedema, anaphylaxis, erythema multiforme, Stevens- Johnson syndrome, or toxic epidermal necrolysis have been reported with the use of cephalexin. Before therapy with cephalexin is instituted, inquire whether the patient has a history of hypersensitivity reactions to cephalexin, cephalosporins, penicillins, or other drugs. Cross-hypersensitivity among beta-lactam antibacterial drugs may occur in up to 10% of patients with a history of penicillin allergy.
  
  If an allergic reaction to cephalexin occurs, discontinue the drug and institute appropriate treatment.
  )
• Clostridium difficile-associated diarrhea (CDAD
  ): Evaluate if diarrhea occurs. (
  5.2 Clostridium difficile-Associated Diarrhea

  Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cephalexin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

  C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

  If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
  )
  
  
• Direct Coomb’s Test Seroconversion
  : If anemia develops during or after cephalexin therapy, evaluate for drug-induced hemolytic anemia. (
  5.3 Direct Coombs’ Test Seroconversion

  Positive direct Coombs’ tests have been reported during treatment with the cephalosporin antibacterial drugs including cephalexin. Acute intravascular hemolysis induced by cephalexin therapy has been reported. If anemia develops during or after cephalexin therapy, perform a diagnostic work-up for drug-induced hemolytic anemia, discontinue cephalexin and institute appropriate therapy.
  )
  
  
• Seizure Potential
  : Use lower dose in patients with renal impairment. (
  5.4 Seizure Potential

  Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures occur, discontinue cephalexin. Anticonvulsant therapy can be given if clinically indicated.
  )