Telavancin

Telavancin
Names
Trade namesVibativ
IUPAC name
  • (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
Clinical data
Drug classLipoglycopeptide[1]
Main usesSkin and skin structure infections (SSSI), hospital acquired pneumonia[1]
Side effectsNausea, diarrhea, headache, trouble sleeping, foamy urine, kidney problems, red man syndrome, QT prolongation, Clostridioides difficile infection[1]
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Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    use    		Intravenous
    Typical dose10 mg/kg[1]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa610004
    Legal
    License data
    Legal status
    Pharmacokinetics
    BioavailabilityN/A
    Protein binding90%, mostly to albumin
    Elimination half-life9 hours
    Excretion76% in urine, <1% in feces
    Chemical and physical data
    FormulaC80H106Cl2N11O27P
    Molar mass1755.65 g·mol−1
    3D model (JSmol)
    SMILES
    • 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
    • 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

    Telavancin, sold under the brand name Vibativ among others, is an antibiotics used to treat skin and skin structure infections (SSSI) and hospital acquired pneumonia.[1] This includes that due to MRSA.[1] It is given by injection into a vein.[1]

    Common side effects include nausea, diarrhea, headache, trouble sleeping, and foamy urine.[1] Other side effects include kidney problems, red man syndrome, QT prolongation, and Clostridioides difficile infection.[1] Use during pregnancy may harm the baby.[1] It is a semi-synthetic lipoglycopeptide derived from vancomycin.[1] It works by stopping bacteria from forming a cell wall.[2]

    Telavancin was approved for medical use in the United States in 2009.[1] While it was approved in Europe in 2011, this approval was subsequently withdrawn.[3] In the United States the medication costs about 570 USD per day as of 2021.[4]

    Medical uses

    For skin infections there does not appear to be any benefit over vancomycin.[5]

    Dosage

    The typical dose is 10 mg/kg once per day for one to three weeks.[1]

    Side effects

    Common side effects include nausea, vomiting, constipation, and headache.[6]

    Telavancin has a higher rate of kidney failure than vancomycin in two trials.[7] It showed teratogenic effects in animal studies.[6]

    Interactions

    Telavancin inhibits the liver enzymes CYP3A4 and CYP3A5. No data regarding the clinical relevance are available.[6]

    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.[8][9]

    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.[10]

    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).[11]

    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.[12] 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.[13]

    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 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.[14]

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 13 "Telavancin Monograph for Professionals". Drugs.com. Archived from the original on 19 January 2021. Retrieved 25 September 2021.
    2. ↑ "Vibativ" (PDF). Archived (PDF) from the original on 25 September 2021. Retrieved 25 September 2021.
    3. ↑ "Vibativ". Archived from the original on 2 March 2021. Retrieved 25 September 2021.
    4. ↑ "Vibativ Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 19 January 2021. Retrieved 25 September 2021.
    5. ↑ "Vibativ: Withdrawal of the marketing authorisation application". Archived from the original on 5 July 2019. Retrieved 25 September 2021.
    6. 1 2 3 Telavancin hydrochloride Monograph
    7. ↑ Saravolatz LD, Stein GE, Johnson LB (2009). "Telavancin: a novel lipoglycopeptide". Clinical Infectious Diseases. 49 (12): 1908–1914. doi:10.1086/648438. PMID 19911938.
    8. ↑ Higgins, DL; Chang, R; Debabov, DV; Leung, J; Wu, T; Krause, KM; Sandvik, E; Hubbard, JM; et al. (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.
    9. ↑ H. Spreitzer (2 February 2009). "Neue Wirkstoffe - Telavancin". Österreichische Apothekerzeitung (in Deutsch) (3/2009).
    10. ↑ "Drugs.com, FDA Accepts for Review Response to Approvable Letter for Telavancin". Archived from the original on 2008-03-09. Retrieved 2008-03-08.
    11. ↑ "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.
    12. ↑ FDA advisory group gives mixed review of Theravance pneumonia treatment. 30 Nov 2012 Archived 2012-12-04 at the Wayback Machine American City Business Journals/San Francisco/BiotechSF blog
    13. ↑ Leuty, Ron. Theravance gets FDA OK for antibiotic against pneumonia, with limits. Archived 2013-06-23 at the Wayback Machine San Francisco Business Times. Jun 21, 2013.
    14. ↑ "www.vibativ.eu, Clinigen and Theravance Announce Exclusive Commercialization Agreement in the EU for VIBATIV® (telavancin)". Archived from the original on 2014-09-13. Retrieved 2014-12-09.
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