What are the side effects of cephalexin (cephalosporin antibiotic)?

Side Effects of Cephalexin

The most common side effects of cephalexin include gastrointestinal disturbances (particularly diarrhea), hypersensitivity reactions such as rash and urticaria, and rarely more serious allergic reactions. 1

Common Side Effects

• Gastrointestinal effects are the most frequent adverse reactions:

  • Diarrhea (most common but rarely severe enough to stop treatment) 1
  • Nausea and vomiting (reported rarely) 1
  • Dyspepsia, gastritis, and abdominal pain 1

• Hypersensitivity reactions:

  • Skin rash and urticaria 1
  • Pruritus (genital and anal) 1
  • Vaginal discharge, vaginitis, and genital moniliasis 1

• Central nervous system effects:

  • Dizziness, fatigue, and headache 1
  • Agitation, confusion (rare) 1

Rare but Serious Side Effects

• Severe allergic reactions:

  • Angioedema 1
  • Erythema multiforme 1
  • Stevens-Johnson syndrome 1
  • Toxic epidermal necrolysis 1
  • Anaphylaxis 1

• Gastrointestinal complications:

  • Pseudomembranous colitis (can occur during or after treatment) 1
  • Transient hepatitis and cholestatic jaundice (rare) 1

• Hematologic abnormalities:

  • Eosinophilia, neutropenia, thrombocytopenia 1
  • Hemolytic anemia 1
  • Prolonged prothrombin time (rare) 1

• Renal effects:

  • Reversible interstitial nephritis (rare) 1

Special Considerations

• Cross-reactivity risk in patients with penicillin allergy:

  • Modern studies show the cross-reactivity between penicillins and cephalosporins is much lower than previously thought (2-4.8%) 2
  • Cephalexin shares an identical R1 side chain with amoxicillin, which may increase cross-reactivity risk in patients with specific penicillin allergies 2

• Prolonged use concerns:

  • May result in overgrowth of non-susceptible organisms (superinfection) 1
  • Can cause positive direct Coombs' tests, which may interfere with hematologic studies or transfusion cross-matching 1

• Drug interactions:

  • Can increase plasma metformin levels (Cmax by 34% and AUC by 24%) 1

Monitoring and Precautions

• Patients should be monitored for signs of allergic reactions, especially those with previous beta-lactam allergies 1
• Cephalexin should be used with caution in patients with markedly impaired renal function 1
• Patients should complete the full course of therapy to prevent bacterial resistance 1
• Patients should be informed about the possibility of developing diarrhea, including C. difficile-associated diarrhea, which can occur up to two months after completing treatment 1

Clinical Context

• In clinical practice, cephalexin is generally well-tolerated with a relatively low incidence of side effects compared to many other antibiotics 3, 4
• When used for respiratory infections, adverse effects are mostly limited to gastrointestinal upset, rash, and urticaria, and rarely require discontinuation of the drug 3
• Even in elderly patients with underlying conditions and multiple drug therapy, cephalexin shows a favorable safety profile with only minor gastrointestinal side effects reported 5