Telavancin

Telavancin (trade name Vibativ) is a bactericidal lipoglycopeptide for use in MRSA or other Gram-positive infections. Telavancin is a semi-synthetic derivative of vancomycin.[1][2]

Telavancin
Clinical data
Trade namesVibativ
AHFS/Drugs.comMonograph
MedlinePlusa610004
License data
Routes of
administration		intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityN/A
Protein binding90%, mostly to albumin
Elimination half-life9 hours
Excretion76% in urine, <1% in feces
Identifiers
  • (1S,2R,18R,19R,22S,25R,28R,40S)-22-(2-Amino-2-oxoethyl)-5,15-dichloro-48-{[2-O-(3-{[2-(decylamino)ethyl]amino}-2,3,6-trideoxy-3-methyl-α-L-lyxo-hexopyranosyl)-β-D-glucopyranosyl]oxy}-2,18,32,35,37-pentahydroxy-19-[(N-methyl-D-leucyl)amino]-20,23,26,42,44-pentaoxo-36-{[(phosphonomethyl)amino]methyl}-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34,36,38,46,49-pentadecaene-40-carboxylic acid
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.106.567
Chemical and physical data
FormulaC80H106Cl2N11O27P
Molar mass1755.65 g·mol−1
3D model (JSmol)
  • CCCCCCCCCCNCCN[C@]1(C[C@@H](O[C@H]([C@H]1O)C)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2OC3=C4C=C5C=C3OC6=C(C=C(C=C6)[C@H]([C@H](C(=O)N[C@H](C(=O)N[C@H]5C(=O)N[C@@H]7C8=CC(=C(C=C8)O)C9=C(C(=C(C=C9[C@H](NC(=O)[C@H]([C@@H](C1=CC(=C(O4)C=C1)Cl)O)NC7=O)C(=O)O)O)CNCP(=O)(O)O)O)CC(=O)N)NC(=O)[C@@H](CC(C)C)NC)O)Cl)CO)O)O)C
  • InChI=1S/C80H106Cl2N11O27P/c1-7-8-9-10-11-12-13-14-21-85-22-23-87-80(5)32-57(115-37(4)71(80)103)119-70-68(102)67(101)55(34-94)118-79(70)120-69-53-28-41-29-54(69)117-52-20-17-40(27-46(52)82)65(99)63-77(109)91-61(78(110)111)43-30-50(96)44(33-86-35-121(112,113)114)66(100)58(43)42-25-38(15-18-49(42)95)59(74(106)93-63)90-75(107)60(41)89-73(105)48(31-56(83)97)88-76(108)62(92-72(104)47(84-6)24-36(2)3)64(98)39-16-19-51(116-53)45(81)26-39/h15-20,25-30,36-37,47-48,55,57,59-65,67-68,70-71,79,84-87,94-96,98-103H,7-14,21-24,31-35H2,1-6H3,(H2,83,97)(H,88,108)(H,89,105)(H,90,107)(H,91,109)(H,92,104)(H,93,106)(H,110,111)(H2,112,113,114)/t37-,47+,48-,55+,57-,59+,60+,61-,62+,63-,64+,65+,67+,68-,70+,71+,79-,80-/m0/s1 checkY
  • Key:ONUMZHGUFYIKPM-MXNFEBESSA-N checkY
 ☒NcheckY (what is this?)  (verify)

The FDA approved the drug in September 2009 for complicated skin and skin structure infections (cSSSI),[3] and in June 2013 for hospital-acquired and ventilator-associated bacterial pneumonia caused by Staphylococcus aureus.[4]

History

On 19 October 2007, the US Food and Drug Administration (FDA) issued an approvable letter for telavancin. Its developer, Theravance, submitted a complete response to the letter, and the FDA has assigned a Prescription Drug User Fee Act (PDUFA) target date of 21 July 2008.[5]

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).[3]

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.[6] 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.[7]

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.[8]

Mechanism of action

Like vancomycin, telavancin inhibits bacterial cell wall synthesis by binding to the D-Ala-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.[2][9]

Adverse effects

Common but harmless adverse effects include nausea, vomiting, constipation, and headache.[10]

Telavancin has a higher rate of kidney failure than vancomycin in two clinical trials.[11] It showed teratogenic effects in animal studies.[10]

Interactions

Telavancin inhibits the liver enzymes CYP3A4 and CYP3A5. No data regarding the clinical relevance are available.[10]

References
  1. Astellas, Inc. VIBATIV prescribing information, 9/2009.
  2. Higgins DL, Chang R, Debabov DV, Leung J, Wu T, Krause KM, et al. (March 2005). "Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis and cell membrane integrity in methicillin-resistant Staphylococcus aureus". Antimicrobial Agents and Chemotherapy. 49 (3): 1127–1134. doi:10.1128/AAC.49.3.1127-1134.2005. PMC 549257. PMID 15728913.
  3. "Theravance and Astellas Announce FDA Approval of Vibativ (telavancin) for the Treatment of Complicated Skin and Skin Structure Infections" (Press release). Theravance, Inc. and Astellas Pharma US, Inc. 2009-09-11. Archived from the original on 22 September 2009. Retrieved 16 September 2009.
  4. "FDA approves Vibativ for hospitalized patients with bacterial pneumonia". Food and Drug Administration. Archived from the original on 2013-08-31. Retrieved 2013-08-19.
  5. "Drugs.com, FDA Accepts for Review Response to Approvable Letter for Telavancin". Archived from the original on 2008-03-09. Retrieved 2008-03-08.
  6. Leuty R (30 November 2012). "FDA advisory group gives mixed review of Theravance pneumonia treatment". American City Business Journals/San Francisco/BiotechSF blog. Archived from the original on 2012-12-04.
  7. Leuty R (21 June 2013). "Theravance gets FDA OK for antibiotic against pneumonia, with limits". San Francisco Business Times. Archived from the original on 2013-06-23.
  8. "Clinigen and Theravance Announce Exclusive Commercialization Agreement in the EU for VIBATIV® (telavancin)". www.vibativ.eu. Archived from the original on 2014-09-13. Retrieved 2014-12-09.
  9. Spreitzer H (2 February 2009). "Neue Wirkstoffe - Telavancin". Österreichische Apothekerzeitung (in German) (3/2009).
  10. Telavancin hydrochloride Monograph
  11. Saravolatz LD, Stein GE, Johnson LB (December 2009). "Telavancin: a novel lipoglycopeptide". Clinical Infectious Diseases. 49 (12): 1908–1914. doi:10.1086/648438. PMID 19911938.
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