What are the approved adult indications, dosing regimen (including loading dose and maintenance dose), recommended treatment duration, dose adjustments for hepatic impairment (Child‑Pugh class C), and major adverse effects of tigecycline?

Tigecycline: Approved Indications, Dosing, and Safety Profile

FDA-Approved Adult Indications

Tigecycline is FDA-approved for three specific indications in adults ≥18 years: 1

• Complicated skin and skin structure infections (cSSSI) caused by susceptible organisms including MRSA, MSSA, E. faecalis (vancomycin-susceptible), E. coli, and anaerobes 1
• Complicated intra-abdominal infections (cIAI) caused by susceptible Enterobacteriaceae, enterococci, S. aureus, B. fragilis, Clostridium perfringens, and other anaerobes 1
• Community-acquired bacterial pneumonia (CABP) caused by S. pneumoniae (penicillin-susceptible, including concurrent bacteremia), H. influenzae, and Legionella pneumophila 1

Critical limitations: Tigecycline is NOT approved for diabetic foot infections (failed non-inferiority trial) or hospital-acquired/ventilator-associated pneumonia (increased mortality observed in comparative trials). 1

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Standard Dosing Regimen

The FDA-approved dosing for all three indications is: 1

• Loading dose: 100 mg IV infused over 30–60 minutes
• Maintenance dose: 50 mg IV every 12 hours, infused over 30–60 minutes

Treatment duration: 1

• cSSSI and cIAI: 5–14 days
• CABP: 7–14 days
• Duration should be guided by infection severity, site, and clinical/bacteriological response 1

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Dose Adjustment for Severe Hepatic Impairment (Child-Pugh Class C)

For patients with Child-Pugh class C hepatic impairment, reduce the maintenance dose by 50%: 1

• Loading dose: 100 mg IV (unchanged)
• Maintenance dose: 25 mg IV every 12 hours (reduced from 50 mg)

No dose adjustment is required for: 1

• Mild to moderate hepatic impairment (Child-Pugh A or B)
• Any degree of renal impairment, including patients on hemodialysis (tigecycline is not significantly removed by dialysis) 2, 1

Important monitoring: Patients with severe hepatic impairment should be treated with caution and monitored closely for treatment response and hepatic enzyme elevations. 1

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Major Adverse Effects and Safety Concerns

Boxed Warning: Increased Mortality

The FDA issued a boxed warning regarding increased all-cause mortality with tigecycline. 3

• Meta-analysis of Phase 3 and 4 trials showed 0.6% absolute increase in mortality (95% CI 0.1–1.2%) compared to comparators 3
• Consultation with an infectious disease specialist is strongly recommended when considering tigecycline 3

Common Adverse Effects (≥5%)

Gastrointestinal effects are most frequent: 4

• Nausea: 28.5% 4
• Vomiting: 19.4% 4
• Diarrhea: 11.6% 4
• Abdominal pain: 6.0% 4
• Local IV-site reactions: 8.2% 4
• Infection: 6.7% 4
• Fever: 6.3% 4
• Headache: 5.6% 4

Serious Adverse Effects Requiring Monitoring

Coagulation abnormalities: 2, 5

• Tigecycline can prolong prothrombin time (PT) and activated partial thromboplastin time (aPTT) 2, 5
• Monitor coagulation parameters during therapy 2

Hepatotoxicity: 2

• Elevated hepatic enzymes reported during therapy 2
• Periodic liver function test monitoring recommended 2

Metabolic disturbances: 2

• Hypoglycemia and hypoproteinemia have been observed 2
• Metabolic monitoring advised 2

Contraindications and Precautions

Absolute contraindications: 2, 1

• Known hypersensitivity to tigecycline or any tetracycline-class antibiotic 2
• Pregnancy (animal studies demonstrated fetal harm; crosses placenta and deposits in fetal bone) 1
• Breastfeeding (excreted in animal milk; caution advised in humans) 1
• Children <8 years of age (risk of permanent tooth discoloration) 2, 1

Pediatric use (8–17 years): 1

• Generally avoided due to increased mortality risk in adults 1
• Only use when no alternative antibiotics exist 1
• Ages 8–11 years: 1.2 mg/kg IV every 12 hours (maximum 50 mg per dose) 2
• Ages 12–17 years: adult dosing (100 mg loading, then 50 mg every 12 hours) 2, 5

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Critical Clinical Caveats

Tigecycline should NOT be used as monotherapy for bacteremia due to poor serum concentrations (Cmax only 0.87 mg/L with standard dosing) and documented poor outcomes. 2, 3

Pseudomonas aeruginosa and Proteus species are intrinsically resistant to tigecycline and are not covered. 6

Nephrotoxicity is significantly lower compared to polymyxin-based regimens (RR 0.23,95% CI 0.11–0.46), making tigecycline preferable in patients at risk for renal injury. 3