What are the side effects of Keflex (cephalexin)?

Side Effects of Keflex (Cephalexin)

The most common side effects of cephalexin are gastrointestinal disturbances, particularly diarrhea, which is rarely severe enough to require discontinuation, along with allergic reactions including rash and urticaria. 1

Common Adverse Effects

Gastrointestinal Effects

• Diarrhea is the most frequent side effect, though very rarely severe enough to warrant cessation of therapy 1
• Nausea and vomiting have been reported rarely 1
• Dyspepsia, gastritis, and abdominal pain can occur 1
• Genital and anal pruritus, genital moniliasis, vaginitis, and vaginal discharge have been reported 1

Allergic and Hypersensitivity Reactions

• Allergic reactions manifest as rash, urticaria, and angioedema 1
• Rarely, severe cutaneous reactions including erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis can occur 1
• Anaphylaxis has been reported and requires immediate discontinuation with emergency treatment including epinephrine, oxygen, IV fluids, antihistamines, corticosteroids, and airway management 1
• Cross-hypersensitivity with penicillins may occur in up to 10% of patients with penicillin allergy history 1

Neurological Effects

• Dizziness, fatigue, and headache have been observed 1
• Agitation, confusion, and hallucinations can occur 1
• Seizures may be triggered, particularly in patients with renal impairment when dosage is not reduced 1

Serious but Rare Adverse Effects

Clostridium difficile-Associated Diarrhea (CDAD)

• CDAD can range from mild diarrhea to fatal colitis and must be considered in all patients presenting with diarrhea following cephalexin use 1
• Can occur over two months after antibiotic administration 1
• Requires discontinuation of cephalexin and appropriate management including fluid/electrolyte management and C. difficile-directed therapy 1

Hepatic Effects

• Transient hepatitis and cholestatic jaundice have been reported rarely 1
• Elevated AST, ALT, alkaline phosphatase, bilirubin, and LDH can occur 1

Renal Effects

• Reversible interstitial nephritis has been reported rarely 1
• Increased BUN and creatinine may occur 1

Hematologic Effects

• Eosinophilia, neutropenia, thrombocytopenia, and hemolytic anemia have been reported 1
• Aplastic anemia, pancytopenia, leukopenia, and agranulocytosis are rare but possible 1
• Positive direct Coombs' tests have been reported during cephalosporin treatment 1

Musculoskeletal Effects

• Arthralgia, arthritis, and joint disorders have been observed 1

Coagulation Effects

• Cephalosporins may be associated with decreased prothrombin activity, particularly in patients with renal/hepatic impairment, poor nutritional state, protracted antimicrobial therapy, or those on anticoagulants 1
• Prolonged prothrombin time can occur 1

Clinical Context from Guidelines

Tolerability Profile

• In comparative studies, cephalexin demonstrated good tolerability with overall side effect incidence of approximately 13.7%, with about 60% being gastrointestinal disturbances 2
• Adverse effects are mostly mild or moderate in severity, with discontinuation rates being low 3
• The drug is "essentially nontoxic at recommended doses" according to clinical experience 4

Special Populations

• In pediatric populations, adverse effects including gastrointestinal upsets, rash, and urticaria have been relatively infrequent and have not required drug discontinuance 3
• The drug possesses "near absence of side effects" in infants and children 5

Prophylactic Use Considerations

• When used for UTI prophylaxis, potential adverse effects of gastrointestinal disturbances and skin rash are commonly associated with cephalexin 6
• Intermittent dosing is associated with decreased risk of adverse events including gastrointestinal symptoms and vaginitis 6

Important Clinical Pitfalls

• Do not ignore diarrhea developing during or after treatment—always consider CDAD, which can be life-threatening 1
• Monitor patients with penicillin allergy carefully, as cross-reactivity can occur despite being relatively uncommon 1
• Cephalexin is not associated with photosensitivity reactions, unlike tetracyclines, making it a preferred alternative for photosensitivity-concerned patients 7
• If facial flushing occurs with urticaria, angioedema, respiratory symptoms, or hypotension, treat as potential anaphylaxis immediately 7