What are the considerations for using tigecycline (generic name) in patients with acute kidney injury (Impaired renal function)?

Tigecycline Use in Acute Kidney Injury

Tigecycline does not require dose adjustment in patients with acute kidney injury as it is primarily eliminated through biliary/fecal excretion with minimal renal clearance. 1, 2

Pharmacokinetics in Renal Impairment

• Tigecycline's primary route of elimination is biliary excretion of unchanged drug and its metabolites, with renal excretion being only a secondary route 1
• A pharmacokinetic study demonstrated that tigecycline clearance was not significantly altered in patients with severe renal impairment (creatinine clearance <30 mL/min) compared to those with normal renal function 2
• Approximately 22% of the total dose is excreted as unchanged tigecycline in urine, making renal function a minor factor in its elimination 1
• Tigecycline is not efficiently removed by hemodialysis, allowing administration without regard to dialysis timing 2

Clinical Considerations in AKI

• In patients receiving continuous renal replacement therapy (CRRT), tigecycline has high dialysability but the contribution of CRRT to total clearance remains modest compared to non-renal clearance 3
• Despite high saturation coefficients in CRRT (0.79-0.90), the dialysis clearance (1.69-2.71 L/h) is small compared to physiological clearance (18.3 L/h), indicating no need for dose adjustment 3
• Unlike polymyxins which require cautious use in renal insufficiency, tigecycline can be safely administered to patients with AKI 4

Dosing Recommendations

• Standard dosing of tigecycline (100 mg loading dose followed by 50 mg every 12 hours) can be maintained in patients with any degree of renal impairment 1, 2
• No modification in dosing schedule is needed for patients undergoing hemodialysis or continuous renal replacement therapies 2, 3
• For patients with both hepatic and renal impairment, the hepatic function should guide dosing decisions, as liver dysfunction has a greater impact on tigecycline clearance than renal dysfunction 1, 5

Advantages in AKI Setting

• Tigecycline represents a valuable treatment option for multidrug-resistant infections in patients with AKI, particularly when polymyxin-based therapies might be contraindicated due to nephrotoxicity concerns 4
• In treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) pulmonary infections, tigecycline-based therapy is associated with significantly lower nephrotoxicity compared to colistin-based regimens (RR = 0.23,95% CI 0.11-0.46) 4
• Implementation guidelines specifically note that "polymyxin should be used judiciously in patients with renal insufficiency and tigecycline should be used cautiously in patients with liver insufficiency" 4

Monitoring Considerations

• While renal function monitoring is not necessary for tigecycline dose adjustment, baseline and periodic assessment of hepatic function is important, as tigecycline clearance is reduced by 55% in patients with severe hepatic impairment 1
• Monitor for common adverse effects including nausea, vomiting (6.3%), and abdominal pain (18.8%), which may occur regardless of renal function 4
• Regular assessment of treatment efficacy is essential, as tigecycline efficacy correlates with MIC values rather than renal function 4

Important Limitations and Precautions

• Tigecycline may not be suitable for urinary tract infections in AKI patients due to its limited urinary excretion 4
• For complicated urinary tract infections (cUTI), aminoglycosides have demonstrated superior efficacy compared to tigecycline, despite the need for dose adjustment in renal impairment 4
• Tigecycline should be used cautiously in patients with both AKI and severe hepatic impairment (Child-Pugh C), as dose reduction to 25 mg every 12 hours may be necessary due to the hepatic rather than renal dysfunction 1, 5
• For bloodstream infections and hospital-acquired/ventilator-associated pneumonia, evidence suggests potential limitations of tigecycline, and alternative agents should be considered when possible 4

Therapeutic Alternatives in AKI

• For patients with AKI requiring treatment of carbapenem-resistant Enterobacterales (CRE), newer agents such as ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-cilastatin-relebactam may be preferred over tigecycline when available 4
• When treating intra-abdominal infections in patients with AKI, tigecycline remains a viable option without need for dose adjustment 4, 1
• For respiratory infections in AKI patients, high-dose tigecycline regimens may be considered to achieve adequate pulmonary concentrations, as tigecycline concentration in lung tissue is approximately 2-fold higher than serum levels 4, 1