What is the appropriate tigecycline dosing and safety considerations for a patient with severe hepatic impairment (Child‑Pugh class C)?

Tigecycline Dosing in Severe Hepatic Impairment (Child-Pugh C)

For patients with severe hepatic impairment (Child-Pugh C), reduce the tigecycline maintenance dose by 50%: administer a 100 mg loading dose followed by 25 mg every 12 hours, with careful monitoring for treatment response. 1

Standard Dosing Adjustment Algorithm

Loading Dose:

• Administer 100 mg IV loading dose over 30-60 minutes regardless of hepatic function 1

Maintenance Dosing Based on Child-Pugh Classification:

• Child-Pugh A (mild impairment): 50 mg IV every 12 hours (standard dose) - no adjustment needed 1, 2
• Child-Pugh B (moderate impairment): 50 mg IV every 12 hours (standard dose) - no adjustment needed 1, 2
• Child-Pugh C (severe impairment): 25 mg IV every 12 hours (50% dose reduction) 1, 2

Pharmacokinetic Rationale

Why dose reduction is necessary in Child-Pugh C:

• Tigecycline clearance is reduced by approximately 55% in severe hepatic impairment (13.5 ± 2.7 L/h) compared to healthy subjects (29.8 ± 11.3 L/h) 2
• Peak plasma concentrations (Cmax) are significantly elevated in patients with severe liver failure 3
• The 24-hour steady-state AUC with 25 mg q12h dosing in Child-Pugh C patients is predicted to be equivalent to high-dose tigecycline exposure (100 mg q12h) in non-ICU patients 4

Hepatic metabolism considerations:

• Less than 20% of tigecycline undergoes hepatic metabolism, with biliary/fecal excretion accounting for 59% of elimination 5
• Despite limited hepatic metabolism, severe liver dysfunction significantly impacts tigecycline clearance through reduced biliary excretion 2

Critical Monitoring Requirements

In patients with severe hepatic impairment, monitor closely for:

• Treatment response and clinical efficacy 1
• Gastrointestinal adverse effects (nausea occurs in 28.5%, vomiting in 19.4%) 5
• Hepatorenal syndrome development, as these patients are at increased risk for nephrotoxicity 6
• Total bilirubin levels, which correlate with tigecycline Cmax 3

Infection-Specific Efficacy Considerations

For hospital-acquired pneumonia (HAP) and complicated intra-abdominal infections (cIAI) in Child-Pugh C patients:

• The 25 mg q12h regimen achieves CFR >90% against Gram-positive bacteria and select Gram-negative bacteria (E. coli, K. oxytoca) 7
• Dose increases may be required for Enterobacter cloacae, Klebsiella pneumoniae, and Acinetobacter baumannii infections 7
• Consider high-dose regimens (100 mg loading, then 50 mg q12h) only if treating resistant organisms with elevated MICs, but balance against increased toxicity risk in severe hepatic impairment 8, 7

Important Clinical Caveats

Avoid tigecycline in these scenarios:

• Bloodstream infections as monotherapy - associated with poor outcomes 8, 9
• Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia as monotherapy 8
• When newer agents (ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol) are available and active 9

FDA boxed warning:

• Tigecycline carries a 0.6% absolute increase in all-cause mortality compared to comparators (95% CI 0.1-1.2) 8
• Infectious disease consultation is strongly recommended when considering tigecycline use 8

Overlapping organ dysfunction:

• If concurrent renal impairment exists, no additional dose adjustment beyond the hepatic adjustment is required, as tigecycline is not significantly removed by hemodialysis 1
• Patients with severe hepatic disease require close renal function monitoring due to predisposition to hepatorenal syndrome 6

Alternative Dosing Markers

If Child-Pugh score is unavailable, consider:

• Total bilirubin levels correlate with tigecycline Cmax and can guide dosing 3
• MELD score can also predict tigecycline exposure 4
• LiMAx test (maximum liver function capacity) shows significant correlation with tigecycline plasma concentrations in critically ill patients 3