Telavancin

Antibiotic Class:

Lipoglycopeptide

Antimicrobial Spectrum:

Staphylococcus aureus (including Methicillin-resistant isolates), Coagulase-negative Staphylococci, Streptococcus pneumoniae, Streptococcus viridans group, Enterococcus spp. (including some vancomycin-resistant isolates), Corynebacterium spp.

Mechanism of Action:

Telavancin inhibits bacterial cell wall biosynthesis by interfering with peptidoglycan production, and also causes depolarization of bacterial membrane

Pharmacodynamics:

Combination of both concentration-dependent effects (Cpeak:MIC) and AUC:MIC ratio

Pharmacokinetics:

Healthy volunteers given 7.5mg/kg/day at steady state – Cmax: mean of 96.7mg/L; Half-life: mean of 8.83h; Volume of distribution: mean of 105ml/kg

Adverse Effects:

Skin: Red man’s syndrome

CNS: Headache, dizziness

GI: nausea, vomiting

Cardiac: QT prolongation

Metabolic: Hypokalemia

Kidney: Increased serum creatinine

Otic: Tinnitus, transient hearing loss

Other: Taste disturbance (metallic or soap)

Dosage:

Not commercially available. Phase II/III studies for cSSI have evaluated daily doses of 7.5mg/kg and 10mg/kg. One phase III study for hospital acquired pneumonia studied daily doses of 10mg/kg.

Disease state based dosing:

Not determined, however phase II and phase III studies have recommended dosage adjustments in patients with renal insufficiency, yet without recommendations for adjustments in hepatic insufficiency.

Contraindications/Warnings/Precautions:

Not yet formally established. It is known however that telavancin prolongs the QT interval

Current speculation exists regarding black box warning for pregnancy

Drug Interactions:

Limited data. No clinical significant interaction with aztreonam or piperacillin/tazobactam

Pregnancy:

Unknown – potential for black boxed warning when released due to lack of data.

Monitoring Requirements:

Data are limited, however at present:

Efficacy/Toxicity:  Serum creatinine

Brand names/Manufacturer:

Brand name to be determined/Theravance, Inc.