What is the dosage and usage of Tigecycline (generic name) for treating complicated infections, including considerations for impaired renal function?

Tigecycline Dosing and Usage for Complicated Infections

For complicated infections, tigecycline should be administered as a 100 mg IV loading dose followed by 50 mg IV every 12 hours, with no dose adjustment required for patients with renal impairment, though a 50% dose reduction is necessary for patients with severe hepatic impairment (Child-Pugh C). 1, 2

Standard Dosing Regimen

• The FDA-approved standard dosage for tigecycline is 100 mg IV loading dose followed by 50 mg IV every 12 hours for 5-14 days 1, 3
• Tigecycline is indicated for complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) 3, 4
• No dosage adjustment is necessary based on age, gender, or race 1
• Tigecycline is not extensively metabolized and is primarily eliminated through biliary/fecal excretion (59%) and renal excretion (33%) 1

Renal Impairment Considerations

• No dose adjustment is required for patients with renal impairment or those undergoing hemodialysis 1, 2
• Tigecycline is not removed by hemodialysis, making it suitable for patients with end-stage renal disease 1
• This is a significant advantage compared to other antimicrobials that require dose adjustments in renal dysfunction 2

Hepatic Impairment Considerations

• No dose adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh A or B) 1
• For patients with severe hepatic impairment (Child-Pugh C), the maintenance dose should be reduced by 50% (50 mg loading dose followed by 25 mg every 12 hours) due to reduced systemic clearance (55%) and prolonged half-life (43%) 1

Higher Dosing for Specific Infections

• For severe infections, particularly hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), a high-dose regimen may be more effective: 200 mg IV loading dose followed by 100 mg IV every 12 hours 2, 5
• This higher dosing regimen has shown improved clinical outcomes with cure rates of 85% compared to 69.6% with standard dosing 2
• For carbapenem-resistant Enterobacterales (CRE) intra-abdominal infections, tigecycline 100 mg IV loading dose followed by 50 mg IV every 12 hours is recommended 5, 2

Pharmacokinetic Considerations

• Tigecycline has a large volume of distribution (7-9 L/kg), indicating extensive tissue penetration 1, 6
• The drug achieves high concentrations in tissues, with alveolar cell concentrations approximately 78-fold higher than serum 1
• Standard dosing achieves a serum Cmax of only 0.87 mg/L, which may be insufficient for bloodstream infections 2
• Tigecycline has a long elimination half-life of approximately 42 hours 3, 6

Important Clinical Caveats

• Tigecycline should not be used as monotherapy for bacteremia due to poor outcomes with standard dosing 2
• Not recommended as monotherapy for carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia 5
• For CRAB infections, tigecycline efficacy is associated with MIC value; comparable to polymyxin when MIC ≤2 mg/L, but inferior when MIC >2 mg/L 5
• For vancomycin-resistant Enterococci (VRE) intra-abdominal infections, the recommended dose is 100 mg IV loading dose followed by 50 mg IV every 12 hours 5
• Tigecycline can be used in combination therapy with polymyxins or carbapenems for multidrug-resistant organisms 5, 2

Adverse Effects

• Most common adverse events include nausea (28.5%), vomiting (19.4%), and diarrhea (11.6%) 3, 4
• Tigecycline-based therapy is associated with significantly lower incidence of nephrotoxicity compared to colistin-based therapy 5
• Tigecycline should be used cautiously in patients with liver insufficiency 5

By following these dosing recommendations and considering the specific clinical scenarios, tigecycline can be effectively used for treating complicated infections while minimizing adverse effects and optimizing clinical outcomes.