What is the recommended dosing regimen for Tigecycline (generic name) in patients with normal renal function and impaired renal function?

Tigecycline Dosing Recommendations

The recommended dosing regimen for tigecycline is a 100 mg IV loading dose followed by 50 mg IV every 12 hours for standard indications, with higher doses of 200 mg IV loading followed by 100 mg IV every 12 hours recommended for severe infections, particularly pulmonary infections. 1

Standard Dosing for Approved Indications

• The FDA-approved standard dosage for tigecycline is 100 mg IV loading dose followed by 50 mg IV every 12 hours 1
• This standard dosing is appropriate for:
  • Complicated skin and skin structure infections (cSSSIs) 2
  • Complicated intra-abdominal infections (cIAIs) 2
• No dose adjustment is required for patients with renal impairment or those on continuous renal replacement therapy 1

Higher Dosing for Severe Infections

• For severe infections, particularly pulmonary infections, a high-dose regimen is recommended: 200 mg IV loading dose followed by 100 mg IV every 12 hours 1
• This higher dosing is particularly important for:
  • Hospital-acquired pneumonia (HAP) 1, 3
  • Ventilator-associated pneumonia (VAP) 1
  • Infections caused by multidrug-resistant (MDR) organisms 4
• Higher dosing has demonstrated improved clinical outcomes in severe infections with cure rates of 85% compared to 69.6% with standard dosing 1

Specific Clinical Scenarios

• For carbapenem-resistant Enterobacterales (CRE) infections: Tigecycline can be used in combination therapy with polymyxins or meropenem 1

  • Recommended as part of combination therapy: 100 mg IV loading dose, then 50 mg IV q12h 1

• For vancomycin-resistant Enterococci (VRE) complicated intra-abdominal infections:

  • Recommended dose: 50 mg IV q12h after loading dose of 100 mg IV 1

• For Acinetobacter baumannii infections:

  • For approved indications (cSSSIs and cIAIs): Standard dosing is appropriate if MIC ≤1 mg/L 1
  • For non-approved indications (especially pulmonary infections): High-dose regimen (200 mg loading followed by 100 mg q12h) is recommended 1
  • Combination with another active agent is recommended for non-approved indications 1

Pharmacokinetic Considerations

• Tigecycline has a large volume of distribution (extensive tissue penetration) and a long terminal elimination half-life (approximately 40 hours) 5
• Standard dosing achieves serum Cmax of only 0.87 mg/L, which may be insufficient for bloodstream infections 1
• Tigecycline penetrates well into tissues but has low concentrations in endothelial lining fluid (0.01-0.02 mg/L), explaining lower efficacy in VAP with standard dosing 1
• Primary route of elimination is through feces as unchanged drug, with glucuronidation and renal elimination as secondary routes 5

Important Clinical Caveats

• Tigecycline should not be used as monotherapy for bacteremia due to poor outcomes with standard dosing 1
• For MDR organisms, combination therapy is generally preferred over tigecycline monotherapy 1
• PK/PD studies suggest that higher doses may be necessary for infections caused by organisms with MICs ≥0.5 mg/L 3
• Once-daily high-dose tigecycline (200-400 mg IV x1, then 100-200 mg IV q24h) has been studied for severe systemic infections and MDR GNB pathogens 4

Monitoring and Safety

• Most common adverse events are nausea, vomiting, and diarrhea 2
• No dose adjustment is required for renal impairment or continuous renal replacement therapy 1
• Tigecycline is generally well tolerated in patients with community-acquired pneumonia 6