What is the recommended dose of tigecycline (generic name) in patients with liver dysfunction (hepatic impairment)?

Tigecycline Dosing in Liver Dysfunction

In patients with severe hepatic impairment (Child-Pugh C), tigecycline should be administered with an initial loading dose of 100 mg followed by a reduced maintenance dose of 25 mg every 12 hours. 1

Dosing Recommendations Based on Hepatic Function

• Normal to Moderate Hepatic Impairment (Child-Pugh A and B):

  • Standard dosing: 100 mg IV loading dose followed by 50 mg IV every 12 hours 1
  • No dosage adjustment is warranted in patients with mild to moderate hepatic impairment 1, 2

• Severe Hepatic Impairment (Child-Pugh C):

  • Loading dose: 100 mg IV (unchanged from standard dosing) 1
  • Maintenance dose: 25 mg IV every 12 hours (50% reduction from standard dosing) 1, 2
  • Patients should be treated with caution and monitored for treatment response 1

Pharmacokinetic Considerations in Liver Dysfunction

• Tigecycline clearance decreases significantly with increasing severity of liver dysfunction:

  • Normal hepatic function: 29.8 ± 11.3 L/h 2
  • Child-Pugh A: 31.2 ± 13.9 L/h 2
  • Child-Pugh B: 22.1 ± 9.3 L/h 2
  • Child-Pugh C: 13.5 ± 2.7 L/h 2

• The MELD score has been identified as a significant covariate that influences tigecycline clearance, with higher MELD scores associated with decreased clearance 3

Clinical Considerations

• Tigecycline is primarily eliminated by biliary/fecal (59%) and renal (33%) excretion 4
• Higher peak plasma concentrations of tigecycline are observed in patients with severe liver failure compared to those with normal liver function 5
• Patients with hypoproteinemia may have lower peak tigecycline concentrations but similar steady-state concentrations compared to patients with normal protein levels 3

Monitoring Recommendations

• Patients with severe hepatic impairment should be closely monitored for:
  • Treatment response 1
  • Adverse effects, particularly gastrointestinal symptoms such as nausea (28.5%) and vomiting (19.4%) 4
  • Drug levels if available, especially in critically ill patients with decompensated cirrhosis 3

Efficacy Considerations

• For hospital-acquired pneumonia (HAP) and complicated intra-abdominal infections (cIAI) in Child-Pugh C patients, the reduced dose of 25 mg q12h achieves adequate coverage against most Gram-positive bacteria and some Gram-negative bacteria (E. coli and K. oxytoca) 6
• Higher doses may be required for certain difficult-to-treat Gram-negative pathogens like Enterobacter cloacae, Klebsiella pneumoniae, and Acinetobacter baumannii, even in patients with hepatic impairment 6

Important Caveats

• Tigecycline should be used with caution in patients with liver insufficiency 7
• For severe infections, particularly pulmonary infections, higher dosing regimens are typically recommended in patients with normal hepatic function, but these higher doses should be adjusted in patients with severe hepatic impairment 8
• Tigecycline should not be used as monotherapy for bacteremia due to its low serum concentrations 8