What is the latest recommended dosing schedule for Tigecycline (generic name)?

Tigecycline Latest Dosing Schedule

The latest recommended dosing schedule for tigecycline is a 100 mg IV loading dose followed by 50 mg IV every 12 hours for standard indications, with higher dosing of 200 mg IV loading dose followed by 100 mg IV every 12 hours recommended for severe infections, particularly pulmonary infections. 1, 2

Standard FDA-Approved Dosing

• The FDA-approved standard dosage regimen for tigecycline is an initial dose of 100 mg IV, followed by 50 mg IV every 12 hours 2
• IV infusions should be administered over approximately 30-60 minutes 2
• Recommended duration of treatment varies by indication:
  • Complicated skin and skin structure infections: 5-14 days 2
  • Complicated intra-abdominal infections: 5-14 days 2
  • Community-acquired bacterial pneumonia: 7-14 days 2

Higher Dosing for Severe Infections

• For severe infections, particularly hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), a high-dose regimen shows better outcomes: 200 mg IV loading dose followed by 100 mg IV every 12 hours 1, 3
• Higher dosing has demonstrated improved clinical cure rates of 85% compared to 69.6% with standard dosing in respiratory infections 1
• PK/PD analysis supports higher dosing for difficult-to-treat infections to achieve adequate tissue concentrations 4, 5

Special Population Dosing Adjustments

• Hepatic Impairment:
  • No dosage adjustment needed for mild to moderate hepatic impairment (Child-Pugh A and B) 2
  • For severe hepatic impairment (Child-Pugh C): 100 mg loading dose followed by reduced maintenance dose of 25 mg every 12 hours 2
• Renal Impairment:
  • No dose adjustment required for patients with renal impairment or those on continuous renal replacement therapy 1, 2

Specific Clinical Scenarios

• Carbapenem-resistant Enterobacterales (CRE):

  • For bloodstream infections: 100 mg IV loading dose, then 50 mg IV q12h in combination with polymyxin or meropenem 6, 1
  • For complicated intra-abdominal infections: 100 mg IV loading dose, then 50 mg IV q12h 6, 3

• Carbapenem-resistant Acinetobacter baumannii (CRAB):

  • For pneumonia or bloodstream infections: Consider combination therapy with colistin plus tigecycline 100 mg IV loading dose, then 50 mg IV q12h 6, 1
  • Tigecycline monotherapy is not recommended for CRAB pneumonia 3

• Vancomycin-resistant Enterococci (VRE):

  • For complicated intra-abdominal infections: 100 mg IV loading dose, then 50 mg IV q12h 6, 3

Pharmacokinetic Considerations

• Standard dosing achieves serum Cmax of only 0.87 mg/L, which may be insufficient for bloodstream infections 1
• Tigecycline has a large volume of distribution (7-10 L/kg), indicating extensive tissue penetration 7
• Long terminal elimination half-life (approximately 40 hours) allows for twice-daily dosing 7
• Low concentrations in endothelial lining fluid (0.01-0.02 mg/L) explain reduced efficacy in VAP with standard dosing 1

Important Clinical Caveats

• Tigecycline should not be used as monotherapy for bacteremia due to poor outcomes with standard dosing 1, 3
• Not indicated for diabetic foot infections or hospital-acquired/ventilator-associated pneumonia per FDA label 2
• For multidrug-resistant organisms, combination therapy is generally preferred over tigecycline monotherapy 1, 3
• An increase in all-cause mortality has been observed in meta-analysis of clinical trials in tigecycline-treated patients versus comparator, with a mortality risk difference of 0.6% 2

Monitoring

• Patients with severe hepatic impairment should be treated with caution and monitored for treatment response 2
• Monitor for common adverse effects including nausea (26%), vomiting (18%), and diarrhea (12%) 8
• Lower incidence of nephrotoxicity compared to colistin-based therapy makes it a good option for patients with renal concerns 3