What is the half-life of Dalbavancin?

Dalbavancin Half-Life

Dalbavancin has a terminal half-life of approximately 346 hours (14.4 days), with an effective half-life of approximately 8.5 days (204 hours) based on population pharmacokinetic analyses, making it one of the longest-acting antibiotics available. 1

Pharmacokinetic Properties

The extended half-life of dalbavancin is its defining pharmacokinetic characteristic:

• Terminal elimination half-life ranges from 147 to 258 hours in various studies, with FDA labeling documenting 346 hours following a single 1,000 mg dose 1, 2, 3
• The effective half-life is approximately 8.5 days (204 hours) based on population pharmacokinetic modeling in patients 1
• This exceptionally long half-life is significantly longer than other lipoglycopeptides: oritavancin has a half-life of 393 hours, while telavancin requires daily dosing 2
• The prolonged half-life results from the lipophilic side chain that anchors to cell membranes and high protein binding (93%) 1, 2

Clinical Implications of Extended Half-Life

The pharmacokinetic profile enables unique dosing strategies:

• Once-weekly dosing is feasible: the standard regimen is 1,000 mg on Day 1 followed by 500 mg on Day 8 1, 3
• No drug accumulation occurs with weekly dosing for up to 8 weeks in patients with normal renal function 1
• Single-dose regimens have been studied: a single 1,100 mg dose showed lower efficacy (61.5% success) compared to the two-dose regimen (94.1% success) 4
• The long half-life allows therapeutic drug concentrations to persist for more than 14 days, enabling treatment completion with just two doses 5

Tissue Distribution and Half-Life

Dalbavancin's half-life is even longer in tissues than in plasma:

• Skin blister fluid concentrations remain above 30 mg/L for up to 7 days post-dose 1
• Tissue half-life (skin, bone) exceeds plasma half-life, contributing to sustained antimicrobial activity at infection sites 6
• The AUC ratio of skin blister fluid to plasma is 0.60, indicating excellent tissue penetration 1

Impact of Renal Function on Half-Life

Renal impairment modestly affects dalbavancin elimination:

• Plasma clearance is reduced by 47% in patients with creatinine clearance <30 mL/min, which would further prolong the already extended half-life 1
• Hemodialysis removes less than 6% of the dose over 3 hours, so the half-life remains prolonged in dialysis patients 1
• Despite reduced clearance, no dose adjustment is needed for regularly scheduled hemodialysis patients 1

Pharmacodynamic Considerations

The extended half-life supports concentration-dependent killing:

• The pharmacodynamic parameter is fAUC/MIC (free area under the curve to minimum inhibitory concentration ratio), with a target 24-hour fAUC/MIC of at least 27.1 for S. aureus 1, 6
• The long half-life maintains therapeutic concentrations throughout the dosing interval, optimizing AUC/MIC ratios 2, 6
• This allows infrequent dosing while maintaining efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive pathogens 5, 7

Practical Clinical Applications

The prolonged half-life offers specific advantages:

• Eliminates need for prolonged indwelling catheters in patients requiring extended antibiotic therapy 3
• Facilitates outpatient parenteral antibiotic therapy (OPAT) for people who inject drugs (PWID) and other challenging populations 5
• Redosing strategies for complicated infections can be implemented with weekly or biweekly administration 6

A critical caveat: emerging evidence suggests potential for treatment-emergent dalbavancin resistance and cross-resistance to daptomycin and vancomycin, warranting caution with widespread use 5