Tigecycline Dosing in Severe Hepatic Dysfunction
For a patient with severe hepatic impairment (indicated by AST levels of 2918 and 5457 IU/L), tigecycline should be dosed at 100 mg IV loading dose followed by 25 mg IV every 12 hours—a 50% reduction in the maintenance dose. 1
Dosing Algorithm for Hepatic Impairment
The FDA-approved dosing adjustment is based on Child-Pugh classification 1:
- Child-Pugh A (mild): No dose adjustment needed—standard 100 mg loading, then 50 mg every 12 hours 1
- Child-Pugh B (moderate): No dose adjustment needed—standard 100 mg loading, then 50 mg every 12 hours 1
- Child-Pugh C (severe): Reduced maintenance dose required—100 mg loading, then 25 mg every 12 hours 1
Your patient's markedly elevated transaminases (AST 2918 and 5457 IU/L) indicate severe hepatic dysfunction, placing them in the Child-Pugh C category requiring dose reduction 1.
Pharmacokinetic Rationale
The dose reduction is necessary because 2, 3:
- Tigecycline clearance decreases significantly with worsening liver function: 31.2 L/h in Child-Pugh A, 22.1 L/h in Child-Pugh B, and 13.5 L/h in Child-Pugh C 2
- Peak plasma concentrations are significantly higher in severe liver failure compared to normal liver function 4
- Tigecycline is eliminated primarily by biliary/fecal excretion (59%), making hepatic function critical for drug clearance 3
- The elimination half-life is prolonged to 42.4 hours, which is further extended in severe hepatic impairment 3
Critical Monitoring Requirements
Patients with severe hepatic impairment (Child-Pugh C) must be treated with caution and monitored closely for treatment response 1. Specific monitoring should include:
- Hepatotoxicity surveillance: Tigecycline itself can cause drug-induced liver injury (DILI) with an incidence of 5.7%, predominantly cholestatic pattern 5
- High-dose tigecycline (100 mg maintenance) and prolonged duration (>14 days) significantly increase DILI risk 5
- The reduced 25 mg dose in severe hepatic impairment helps mitigate additional hepatotoxic risk 6
Important Clinical Caveats
Do not use tigecycline as monotherapy for bacteremia in this patient, as low serum concentrations (Cmax only 0.87 mg/L with standard dosing) result in poor outcomes 7, 6. The reduced dose of 25 mg every 12 hours will achieve even lower serum levels 6.
For severe infections requiring tigecycline in this hepatically impaired patient 8, 9:
- Combination therapy is essential—pair tigecycline with another active agent (e.g., polymyxins, carbapenems) 9, 7
- The 25 mg every 12 hours dose achieves adequate coverage against most Gram-positive bacteria and some Gram-negative bacteria, but may be insufficient for severe infections 6
- Consider alternative agents when possible, as newer beta-lactam/beta-lactamase inhibitor combinations have better efficacy profiles in hepatically impaired patients 6
Avoid prolonged treatment duration (>14 days) as this is an independent risk factor for tigecycline-associated DILI (OR = 1.208, p < 0.001), particularly dangerous in a patient with pre-existing severe liver dysfunction 5.
The concomitant use of multiple hepatotoxic drugs should be minimized, as the number of hepatotoxic drugs is an independent risk factor for tigecycline-associated DILI (OR = 2.232, p < 0.001) 5.