Tigecycline Dosing in Hepatic Impairment
For patients with severe hepatic impairment (Child-Pugh C), reduce the tigecycline maintenance dose to 25 mg IV every 12 hours after the standard 100 mg loading dose. 1
Dosing Algorithm by Hepatic Function
Mild to Moderate Hepatic Impairment (Child-Pugh A and B)
- No dose adjustment required 1
- Use standard dosing: 100 mg IV loading dose, then 50 mg IV every 12 hours 1
- This applies to both compensated and moderately decompensated cirrhosis 2
Severe Hepatic Impairment (Child-Pugh C)
- 100 mg IV loading dose, then 25 mg IV every 12 hours 1, 2
- This 50% dose reduction is necessary because tigecycline clearance decreases by approximately 55% in Child-Pugh C patients (13.5 L/h vs 29.8 L/h in healthy subjects) 2
- Monitor closely for treatment response and adverse events 1
Clinical Context and Evidence Quality
The FDA label provides the definitive dosing guidance, which is supported by pharmacokinetic studies demonstrating progressive reductions in tigecycline clearance with worsening hepatic function 1, 2. In Child-Pugh A patients, clearance remains near normal (31.2 L/h), drops to 22.1 L/h in Child-Pugh B, and falls to 13.5 L/h in Child-Pugh C 2.
Monte Carlo simulations confirm that 25 mg every 12 hours achieves adequate coverage (>90% CFR) against most Gram-positive bacteria and select Gram-negative organisms (E. coli, K. oxytoca) in Child-Pugh C patients with hospital-acquired pneumonia and complicated intra-abdominal infections 3. However, higher doses may be needed for more resistant organisms like Enterobacter cloacae, Klebsiella pneumoniae, and Acinetobacter baumannii 3.
Important Clinical Caveats
- Tigecycline should not be used as monotherapy for bacteremia due to low serum concentrations, regardless of hepatic function 4, 5
- The reduced dose in Child-Pugh C patients produces exposures equivalent to high-dose tigecycline (100 mg every 12 hours) in non-ICU patients, which may explain why adequate efficacy is maintained despite dose reduction 6
- Combination therapy is preferred over monotherapy when treating multidrug-resistant organisms, particularly in patients with hepatic impairment 4, 5
- Less than 20% of tigecycline undergoes hepatic metabolism, which is why mild-moderate impairment requires no adjustment 7
- No renal dose adjustment is needed, as tigecycline clearance is minimally affected by renal impairment 1, 8
Monitoring Recommendations
- Assess hepatic function using Child-Pugh classification before initiating therapy 1
- Monitor for treatment response more frequently in Child-Pugh C patients 1
- Watch for common adverse events including nausea (28.5%), vomiting (19.4%), and diarrhea (11.6%), which may be more problematic in cirrhotic patients 7
- Consider tigecycline's potential to prolong PT and aPTT, particularly relevant in patients with baseline coagulopathy from liver disease 9