What is the recommended dosage of tigecycline (Tygacil) for treating infections?

Tigecycline Dosing Recommendations

The standard FDA-approved dosage for tigecycline is 100 mg IV loading dose followed by 50 mg IV every 12 hours for 5-14 days, with no dose adjustment required for patients with renal impairment. 1

Standard Dosing for Approved Indications

• The FDA-approved standard dosage regimen for tigecycline is an initial dose of 100 mg IV, followed by 50 mg IV every 12 hours 1
• Intravenous infusions should be administered over approximately 30 to 60 minutes 1
• The recommended duration of treatment is:
  • 5 to 14 days for complicated skin and skin structure infections 1
  • 5 to 14 days for complicated intra-abdominal infections 1
  • 7 to 14 days for community-acquired bacterial pneumonia 1

Dosage Adjustments for Special Populations

• No dosage adjustment is required for patients with renal impairment or those on continuous renal replacement therapy 2, 1
• For patients with hepatic impairment:
  • No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh A and B) 1
  • In patients with severe hepatic impairment (Child Pugh C), the initial dose should remain 100 mg followed by a reduced maintenance dose of 25 mg every 12 hours 1

Higher Dosing for Severe Infections

• For severe infections, particularly pulmonary infections, a high-dose regimen may be more effective: 200 mg IV loading dose followed by 100 mg IV every 12 hours 2
• Higher dosing has shown improved outcomes in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), with cure rates of 85% compared to 69.6% with standard dosing 2

Specific Clinical Scenarios

• For carbapenem-resistant Acinetobacter baumannii infections:
  • When used in combination therapy, tigecycline dosing is 100 mg IV loading dose followed by 50 mg IV every 12 hours 3
  • Tigecycline should be used only if MIC ≤2 mg/L 3
• Standard dosing achieves serum Cmax of only 0.87 mg/L, which may be insufficient for bloodstream infections 2, 3
• Tigecycline should not be used as monotherapy for bacteremia due to poor outcomes with standard dosing 2

Preparation and Administration

• Each vial should be reconstituted with 5.3 mL of 0.9% Sodium Chloride Injection, USP, 5% Dextrose Injection, USP, or Lactated Ringer's Injection, USP to achieve a concentration of 10 mg/mL 1
• The reconstituted solution must be transferred and further diluted for intravenous infusion:
  • For a 100 mg dose, reconstitute two vials and add to a 100 mL intravenous bag 1
  • For a 50 mg dose, reconstitute one vial and add to a 100 mL intravenous bag 1

Pharmacokinetic Considerations

• Tigecycline has a large volume of distribution (7-9 L/kg), indicating extensive tissue penetration 4
• The elimination half-life is approximately 42.4 hours 4
• Elimination occurs primarily through biliary/fecal (59%) and renal (33%) excretion 4, 5
• Unchanged tigecycline is the predominant drug-related compound in serum, urine, and feces 5

Important Clinical Caveats

• For multidrug-resistant organisms, combination therapy is generally preferred over tigecycline monotherapy 2
• The most common adverse events include nausea (28.5%), vomiting (19.4%), and diarrhea (11.6%) 4
• Monte Carlo simulations suggest that standard dosing is effective for:
  • Complicated skin infections with MICs ≤0.25 mg/L
  • Complicated intra-abdominal infections with MICs ≤1 mg/L
  • Hospital-acquired pneumonia with MICs ≤0.5 mg/L 6