What is the recommended dose of tigecycline (generic name) for patients with severe hepatic impairment?

Tigecycline Dosing in Severe Hepatic Impairment

For patients with severe hepatic impairment (Child-Pugh C), the recommended tigecycline dosing regimen is 100 mg IV loading dose followed by a reduced maintenance dose of 25 mg every 12 hours. 1

Dosing Recommendations Based on Hepatic Function

• Standard dosing for patients with normal hepatic function or mild to moderate hepatic impairment (Child-Pugh A and B): 100 mg IV loading dose followed by 50 mg IV every 12 hours 1
• For patients with severe hepatic impairment (Child-Pugh C): 100 mg IV loading dose followed by 25 mg IV every 12 hours (50% reduction in maintenance dose) 1, 2
• Patients with severe hepatic impairment should be treated with caution and monitored closely for treatment response 1

Pharmacokinetic Rationale

• Tigecycline clearance is significantly reduced in patients with severe hepatic impairment (Child-Pugh C): 13.5 ± 2.7 L/h compared to 29.8 ± 11.3 L/h in healthy subjects 2
• The MELD score significantly influences tigecycline clearance, with higher MELD scores associated with decreased drug elimination, necessitating lower maintenance doses 3
• Despite <20% of tigecycline being metabolized by the liver, severe hepatic dysfunction significantly impacts drug clearance, requiring dose adjustment 2, 4

Clinical Considerations for Severe Infections

• For severe infections like hospital-acquired pneumonia (HAP) in patients with normal hepatic function, higher doses (200 mg loading followed by 100 mg every 12 hours) are typically recommended 5
• However, in patients with severe hepatic impairment, the standard reduced dose (100 mg loading followed by 25 mg every 12 hours) should be maintained even for severe infections 1, 2
• For complicated intra-abdominal infections in Child-Pugh C patients, the 25 mg q12h regimen achieves adequate coverage against Gram-positive bacteria and some Gram-negative bacteria (E. coli and K. oxytoca) 6

Important Monitoring Considerations

• Patients with severe hepatic impairment receiving tigecycline should be closely monitored for:
  • Clinical response to therapy 1
  • Signs of drug toxicity, particularly nausea and vomiting which are common adverse effects 4
  • Potential need for combination therapy when treating resistant organisms like Acinetobacter baumannii 7

Special Considerations for Specific Pathogens

• For multidrug-resistant Acinetobacter baumannii infections in patients with severe hepatic impairment:
  • The reduced dose may be less effective against certain Gram-negative pathogens including A. baumannii 6
  • Consider combination therapy with another active agent if possible 7
• For infections caused by organisms with higher MICs, therapeutic drug monitoring may be beneficial to ensure adequate drug exposure 3

Administration Guidelines

• Tigecycline should be administered intravenously over approximately 30 to 60 minutes 1
• The reconstituted solution should be yellow to orange in color; discard if not within this color range 1
• Duration of therapy should be guided by the severity and site of infection, typically 5-14 days for complicated skin and skin structure infections or complicated intra-abdominal infections 1