Is a renal adjusted dose of tigecycline (generic name) necessary in pediatric patients with impaired renal function?

Tigecycline Dosing in Pediatric Patients with Renal Impairment

No renal dose adjustment of tigecycline is necessary in pediatric patients with impaired renal function, as tigecycline is primarily eliminated through biliary/fecal excretion rather than renal clearance. 1, 2

Pharmacokinetic Rationale

The elimination profile of tigecycline makes it unique among antibiotics in terms of renal dosing requirements:

• Tigecycline undergoes predominantly biliary/fecal elimination (59% of dose), with only 33% excreted renally 1
• Approximately 22% of the total dose is excreted as unchanged tigecycline in urine, making renal clearance a minor pathway 1
• In adults with severe renal impairment (creatinine clearance <30 mL/min), tigecycline clearance was reduced by only approximately 20%, with AUC increased by approximately 30%—changes not considered clinically significant 2
• Tigecycline is not efficiently removed by hemodialysis and can be administered without regard to timing of dialysis 1, 2

Pediatric-Specific Dosing

The standard pediatric dosing regimens apply regardless of renal function:

• For children aged 12-16 years: 50 mg IV every 12 hours (after 100 mg loading dose) 1
• For children aged 8-11 years: 1.2 mg/kg IV every 12 hours (after appropriate loading dose) 1
• These doses achieve exposures comparable to adults and require no modification for renal impairment 1

Important Clinical Caveats

Hepatic Impairment Requires Adjustment

While renal function does not affect tigecycline dosing, hepatic impairment does require dose reduction:

• No adjustment needed for Child-Pugh A (mild hepatic impairment) 1, 3
• Reduce maintenance dose by 50% in Child-Pugh C (severe hepatic impairment) to 25 mg every 12 hours in adults 1, 3
• For pediatric patients with severe hepatic impairment, proportional dose reductions would apply 4

Contrast with Other Antibiotics

This lack of renal adjustment distinguishes tigecycline from many other antibiotics used in similar clinical scenarios:

• Aminoglycosides (streptomycin, amikacin, kanamycin) require substantial dosage adjustments with frequency reduced to 2-3 times weekly in renal impairment 5, 6
• Ganciclovir and foscarnet both require dose adjustment in renal impairment 5
• Lamivudine requires dose adjustment in patients with renal impairment 5

Evidence Limitations in Pediatrics

A critical gap exists in pediatric renal dosing evidence across most medications:

• Only 14% of pediatric renal dosing recommendations in standard handbooks reference actual pediatric clinical studies 7
• Most pediatric renal dosing recommendations extrapolate from adult data on manufacturer labels 7
• For tigecycline specifically, the FDA label explicitly states no dosage adjustment is necessary in patients with renal impairment based on adult pharmacokinetic studies 1

Monitoring Recommendations

Despite not requiring dose adjustment, appropriate monitoring remains important:

• Monitor for gastrointestinal adverse events (nausea 28.5%, vomiting 19.4%, diarrhea 11.6%), which are the most common side effects 3
• Assess hepatic function if prolonged therapy is anticipated, as tigecycline relies on biliary elimination 1
• Standard therapeutic drug monitoring is not routinely performed for tigecycline, unlike aminoglycosides 2

Common Pitfalls to Avoid

• Do not reduce tigecycline doses in pediatric patients with renal impairment—this may lead to subtherapeutic concentrations and treatment failure 1, 2
• Do not assume all broad-spectrum antibiotics require renal adjustment; tigecycline's unique elimination pathway makes it an exception 1
• Avoid confusing renal dosing requirements (none needed) with hepatic dosing requirements (adjustment needed for severe impairment) 1, 3