What are the potential drug interactions with cefoperazone?

Cefoperazone Drug Interactions

Cefoperazone has several important drug interactions that require careful monitoring, with the most significant being its potential to cause disulfiram-like reactions with alcohol and its interaction with anticoagulants due to its effects on vitamin K-dependent clotting factors. 1

Major Drug Interactions

Alcohol

• Cefoperazone can cause disulfiram-like reactions when combined with alcohol due to its methylthiotetrazole side chain, which inhibits aldehyde dehydrogenase 1
• Patients should avoid alcohol consumption during treatment and for 72 hours after the last dose 1

Anticoagulants

• Cefoperazone may increase the risk of bleeding when used with anticoagulants like warfarin 1
• The drug interferes with vitamin K-dependent clotting factors, potentially enhancing anticoagulant effects 1
• Careful monitoring of coagulation parameters is recommended when these agents are used concurrently 1

Bile Acid Sequestrants

• Cholestyramine and colestipol can bind to cefoperazone in the gastrointestinal tract, reducing its absorption 1
• Administration should be separated by at least 1 hour before or 4-6 hours after bile acid sequestrants 1

Nephrotoxic Medications

• Concurrent use with aminoglycosides may increase the risk of nephrotoxicity 2
• This combination should be used with caution, especially in patients with pre-existing renal impairment 2
• Monitoring of renal function is essential when these combinations are necessary 2

Pharmacokinetic Considerations Affecting Drug Interactions

Hepatic Metabolism and Excretion

• Cefoperazone is primarily eliminated through biliary excretion (70-85%) 3, 4
• Only 15-36% is excreted via the kidneys, making it unique among cephalosporins 3
• Severe hepatic dysfunction can increase cefoperazone's half-life 2-4 fold, potentially intensifying drug interactions 3, 5

Protein Binding

• Cefoperazone is approximately 90% protein-bound 3
• May compete with other highly protein-bound drugs, potentially increasing free concentrations of either agent 3

Special Populations and Considerations

Patients with Hepatic Impairment

• Dosage adjustment is recommended in severe hepatic dysfunction due to prolonged half-life 5
• Drug interactions may be more pronounced in these patients due to altered pharmacokinetics 5

Patients with Renal Impairment

• Unlike most cephalosporins, cefoperazone does not require significant dosage adjustment in renal impairment 6, 5
• However, when combined with nephrotoxic drugs, closer monitoring is warranted 2

Antimicrobial Combinations

• Cefoperazone-sulbactam combinations are commonly used for resistant infections, particularly carbapenem-resistant Acinetobacter baumannii (CRAB) 1
• When combined with imipenem-cilastatin, this combination has shown significantly lower mortality than cefoperazone-sulbactam alone for CRAB bloodstream infections 1

Clinical Implications and Monitoring

• Monitor coagulation parameters when used with anticoagulants 1
• Assess renal function when combined with potentially nephrotoxic agents 2
• Advise patients to avoid alcohol during treatment and for 72 hours afterward 1
• Consider therapeutic drug monitoring in patients with severe hepatic dysfunction 5

Common Pitfalls to Avoid

• Failing to warn patients about alcohol interactions 1
• Not accounting for the primarily biliary (rather than renal) excretion pattern when considering drug interactions 3, 4
• Overlooking potential bleeding risks when combined with anticoagulants 1
• Not separating administration times with bile acid sequestrants 1