What are the side effects of intravenous cefazolin (Ancef)?

Intravenous Cefazolin (Ancef) Side Effects

Cefazolin is generally well-tolerated with a low incidence of adverse reactions, but clinicians must be vigilant for allergic reactions (including rare anaphylaxis), gastrointestinal disturbances, and local injection site reactions as the most clinically relevant side effects. 1

Common Side Effects

Gastrointestinal Effects

• Diarrhea is among the most frequently reported adverse effects 1
• Nausea and vomiting occur rarely 1
• Oral candidiasis (thrush), stomach cramps, and anorexia have been documented 1
• Pseudomembranous colitis (C. difficile infection) may occur during or after treatment and requires immediate discontinuation if suspected 1

Local Injection Site Reactions

• Phlebitis at the injection site occurs rarely 1
• Pain after intramuscular administration (though IV is the recommended route) 1
• Some induration at injection sites has been reported 1

Serious Allergic Reactions

Immediate Hypersensitivity

• Anaphylaxis is the most serious allergic reaction, though sufficiently rare that benefits outweigh risks in appropriate patients 2
• The estimated rate of anaphylaxis ranges from 4 per 10,000 to 4 per 100,000 recipients 2
• Urticaria, angioedema, and drug fever may occur 1
• Eosinophilia has been documented 1

Severe Cutaneous Reactions

• Stevens-Johnson syndrome is a rare but life-threatening delayed hypersensitivity reaction 1
• Toxic epidermal necrolysis and erythema multiforme are class effects of cephalosporins 1
• Maculopapular rash is the most common allergic manifestation, occurring in 0.7-4.0% of beta-lactam courses 2

Critical Safety Context for Penicillin-Allergic Patients

• Cefazolin has negligible cross-reactivity with penicillins due to its unique R1 side chain structure, with reaction rates of only 0.7-0.8% even in confirmed penicillin allergy 3, 4
• An estimated 10% of penicillin-allergic patients may have immediate hypersensitivity to cephalosporins, though this is primarily with cephalosporins sharing similar side chains 2
• Cefazolin should only be avoided in patients with severe delayed hypersensitivity reactions to penicillins (Stevens-Johnson syndrome, hepatitis, nephritis, serum sickness, hemolytic anemia) 4

Hematologic Effects

• Neutropenia and leukopenia have been reported 1
• Thrombocytopenia and thrombocythemia may occur 1
• Hemolytic anemia and aplastic anemia are rare class effects 1
• Positive direct Coombs' test (without clinical hemolysis) 1
• Prolonged prothrombin time has been documented 1

Hepatic Effects

• Transient elevation of liver enzymes (SGOT, SGPT, alkaline phosphatase) is common and usually clinically insignificant 1
• Hepatitis has been reported as a class effect of cephalosporins 1
• Elevated bilirubin and LDH may occur 1
• Cholestasis is a rare complication 1

Renal Effects

• Increased BUN and creatinine levels have been observed 1
• Renal failure has been reported, particularly in patients with pre-existing renal impairment 1
• Toxic nephropathy is a rare class effect 1

Genitourinary Effects

• Genital and anal pruritus including vulvar pruritus 1
• Genital moniliasis (yeast infections) 1
• Vaginitis 1

Neurologic Effects

• Seizures may be triggered, particularly in patients with renal impairment when dosage is not appropriately reduced 1
• If seizures occur, the drug must be discontinued immediately and anticonvulsant therapy given if indicated 1
• Reversible hyperactivity and hypertonia have been reported as class effects 1

Laboratory Test Interference

• False-positive urinary glucose tests may occur 1
• Positive direct Coombs' test without hemolysis 1

Risk Mitigation Strategies

Anaphylaxis Prevention

• The first dose should be administered in a setting where rapid intervention for anaphylaxis is available, especially in patients with any beta-lactam allergy history 2, 3
• Maternal anaphylaxis during intrapartum prophylaxis is rare, with only single cases reported in large surveillance samples of thousands of deliveries 2

Dosing Adjustments

• Renal dose adjustment is critical to prevent seizures and nephrotoxicity in patients with impaired kidney function 1
• Standard prophylactic dosing is 2g IV initially, then 1g IV every 8 hours 5

Monitoring Recommendations

• Monitor for signs of pseudomembranous colitis (severe diarrhea, abdominal pain) during and after treatment 1
• Observe injection sites for phlebitis 1
• In patients with renal impairment, monitor renal function and adjust dosing accordingly 1

Common Pitfalls to Avoid

• Do not avoid cefazolin in penicillin-allergic patients based solely on outdated cross-reactivity concerns; cefazolin's unique side chain makes it safe for most penicillin-allergic individuals 3, 4
• Do not use cefazolin in patients with severe delayed hypersensitivity reactions to any beta-lactam (Stevens-Johnson syndrome, DRESS, hepatitis, nephritis) 4
• Do not fail to reduce dosing in renal impairment, as this significantly increases seizure risk 1
• Recognize that >90% of reported penicillin allergies are not true IgE-mediated allergies on testing 4