Telavancin (trade name Vibativ) is a bactericidal lipoglycopeptide for use in

MRSA Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...

or other

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

infections. Telavancin is a semi-synthetic derivative of

vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, ...

. The FDA approved the drug in September 2009 for complicated skin and skin structure infections (cSSSI), and in June 2013 for hospital-acquired and ventilator-associated bacterial pneumonia caused by Staphylococcus aureus.

History

On 19 October 2007, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) issued an

approvable letter Approvable letters, and the related non-approvable letters (alternately not-approvable letters), were notifications sent out by the Food and Drug Administration (FDA) to drug manufacturers alerting them to the approval prospects of their drugs unde ...

for telavancin. Its developer, Theravance, submitted a complete response to the letter, and the FDA has assigned a

Prescription Drug User Fee Act The ''Prescription Drug User Fee Act'' (PDUFA) was a law passed by the United States Congress in 1992 which allowed the Food and Drug Administration (FDA) to collect fees from drug manufacturers to fund the new drug approval process. The Act prov ...

(PDUFA) target date of 21 July 2008. On 19 November 2008, an FDA antiinfective drug advisory committee concluded that they would recommend telavancin be approved by the FDA. The FDA approved the drug on 11 September 2009 for complicated skin and skin structure infections ( cSSSI). Theravance has also submitted telavancin to the FDA in a second indication, nosocomial pneumonia, sometimes referred to as hospital-acquired pneumonia, or HAP. On 30 November 2012, an FDA advisory panel endorsed approval of a once-daily formulation of telavancin for nosocomial pneumonia when other alternatives are not suitable. However, telavancin did not win the advisory committee's recommendation as first-line therapy for this indication. The committee indicated that the trial data did not prove "substantial evidence" of telavancin's safety and efficacy in hospital-acquired pneumonia, including ventilator-associated pneumonia caused by Gram-positive organisms ''Staphylococcus aureus'' and ''Streptococcus pneumoniae''. On 21 June 2013 FDA gave approval for telavancin to treat patients with hospital-acquired pneumonia, but indicated it should be used only when alternative treatments are not suitable. FDA staff had indicated telavancin has a "substantially higher risk for death" for patients with kidney problems or diabetes compared to vancomycin. On March 11 2013, Clinigen Group plc and Theravance, Inc. announced that they have entered into an exclusive commercialization agreement in the European Union (EU) and certain other countries located in Europe for VIBATIV® (telavancin) for the treatment of nosocomial pneumonia (hospital-acquired), including ventilator-associated pneumonia, known or suspected to be caused by methicillin resistant Staphylococcus aureus (MRSA) when other alternatives are not suitable.

Mechanism of action

Like vancomycin, telavancin inhibits bacterial cell wall synthesis by binding to the D-

Ala Ala, ALA, Alaa or Alae may refer to: Places * Ala, Hiiu County, Estonia, a village * Ala, Valga County, Estonia, a village * Ala, Alappuzha, Kerala, India, a village * Ala, Iran, a village in Semnan Province * Ala, Gotland, Sweden * Alad, S ...

-D-Ala terminus of the peptidoglycan in the growing cell wall (see Pharmacology and chemistry of vancomycin). In addition, it disrupts bacterial membranes by

depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is ess ...

Adverse effects

Common but harmless adverse effects include nausea, vomiting, constipation, and headache.Telavancin hydrochloride Telavancin has a higher rate of kidney failure than

in two clinical trials. It showed

teratogenic Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related t ...

effects in animal studies.

Interactions

Telavancin inhibits the liver enzymes CYP3A4 and

CYP3A5 Cytochrome P450 3A5 is a protein that in humans is encoded by the ''CYP3A5'' gene. Tissue distribution ''CYP3A5'' encodes a member of the cytochrome P450 superfamily of enzymes. Like most of the cytochrome P450, the CYP3A5 is expressed in the ...

. No data regarding the clinical relevance are available.

References

External links

Theravance, Inc.

Vibativ information

Vibativ Europe
{{Cell wall disruptive antibiotics Antibiotics Halogen-containing natural products Astellas Pharma