Lefamulin

Lefamulin (tradename Xenleta) is an antibiotic used it to treat adults with community-acquired bacterial pneumonia.[1][2] It is taken by mouth or by injection into a vein.[1][2][3]

Lefamulin

Clinical data
Trade names	Xenleta
Other names	BC-3781
AHFS/Drugs.com	Monograph
License data	US DailyMed: Lefamulin
Routes of administration	Intravenous, by mouth
ATC code	J01XX12 (WHO)
Legal status
Legal status	US: ℞-only
Identifiers
IUPAC name (1S,2R,3S,4S,6R,7R,8R,14R)-3-Hydroxy-2,4,7,14-tetramethyl-9-oxo-4-vinyltricyclo[5.4.3.0^1,8]tetradec-6-yl {[(1R,2R,4R)-4-amino-2-hydroxycyclohexyl]sulfanyl}acetate
CAS Number	1061337-51-6
PubChem CID	25185057
DrugBank	DB12825
ChemSpider	32701544
UNII	21904A5386
KEGG	D11631
ChEMBL	ChEMBL3291398
Chemical and physical data
Formula	C28H45NO5S
Molar mass	507.73 g·mol^−1
3D model (JSmol)	Interactive image
SMILES C[C@@H]1CC[C@@]23CCC(=O)[C@H]2[C@@]1([C@@H](C[C@@]([C@H]([C@@H]3C)O)(C)C=C)OC(=O)CS[C@@H]4CC[C@H](C[C@H]4O)N)C
InChI InChI=1S/C28H45NO5S/c1-6-26(4)14-22(34-23(32)15-35-21-8-7-18(29)13-20(21)31)27(5)16(2)9-11-28(17(3)25(26)33)12-10-19(30)24(27)28/h6,16-18,20-22,24-25,31,33H,1,7-15,29H2,2-5H3/t16-,17+,18-,20-,21-,22-,24+,25+,26-,27+,28+/m1/s1 Key:KPVIXBKIJXZQJX-FCEONZPQSA-N

Relatively common side effects include diarrhea, nausea, pain at the site of injection, and liver inflammation.[1][4] It is a pleuromutilin antibiotic that inhibits the large subunit of bacterial ribosomes.[5]

Lefamulin was approved for medical use in the United States in 2019.[1] On 28 May 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Xenleta, intended for the treatment of community-acquired pneumonia (CAP) in adults.[6]

Medical uses

Lefamulin is used to treat adults with community-acquired bacterial pneumonia.[1][2] It was also investigated for treatment of acute bacterial skin and skin-structure infections (ABSSSI).[7]

Spectrum of activity

Lefamulin has in vitro activity against Streptococcus viridans, Moraxella catarrhalis, Enterococcus faecium, methicillin-resistant Staphylococcus aureus (MRSA), among other bacteria.[8][9]

History

It was developed by Nabriva Therapeutics and approved in the United States in 2019.[1] It was granted fast track status by the US Food and Drug Administration (FDA) in 2014. Although pleuromutilin antibiotics were first developed in the 1950s, lefamulin is the first to be used for systemic treatment of bacterial infections in humans.[10]

On 28 May 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Xenleta, intended for the treatment of community-acquired pneumonia (CAP) in adults.[6]

References

1. "FDA approves new antibiotic to treat community-acquired bacterial pneumonia". U.S. Food and Drug Administration (FDA) (Press release). 19 August 2019. Archived from the original on 20 November 2019. Retrieved 19 November 2019. This article incorporates text from this source, which is in the public domain.
2. "Drug Trials Snapshots: Xenleta". U.S.Food and Drug Administration (FDA). 4 September 2019. Archived from the original on 20 November 2019. Retrieved 19 November 2019.
3. File TM, Goldberg L, Das A, Sweeney C, Saviski J, Gelone SP, Seltzer E, Paukner S, Wicha WW, Talbot GH, Gasink LB (February 2019). "Efficacy and Safety of IV-to-Oral Lefamulin, a Pleuromutilin Antibiotic, for Treatment of Community-Acquired Bacterial Pneumonia: The Phase 3 LEAP 1 Trial". Clin. Infect. Dis. doi:10.1093/cid/ciz090. PMID 30722059.
4. Alexander E, Goldberg L, Das AF, Moran GJ, Sandrock C, Gasink LB, Spera P, Sweeney C, Paukner S, Wicha WW, Gelone SP, Schranz J (September 2019). "Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial". JAMA. doi:10.1001/jama.2019.15468. PMC 6865224. PMID 31560372.
5. Andrei S, Droc G, Stefan G (December 2019). "FDA approved antibacterial drugs: 2018-2019" (PDF). Discoveries (Craiova). 7 (4): Article e102. doi:10.15190/d.2019.15. PMID 32309620.
6. "Xenleta: Pending EC decision". European Medicines Agency (EMA). 29 May 2020. Retrieved 16 July 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
7. Zeitlinger, M; Schwameis, R; Burian, A; Burian, B; Matzneller, P; Müller, M; Wicha, W. W.; Strickmann, D. B.; Prince, W (2016). "Simultaneous assessment of the pharmacokinetics of a pleuromutilin, lefamulin, in plasma, soft tissues and pulmonary epithelial lining fluid". Journal of Antimicrobial Chemotherapy. 71 (4): 1022–6. doi:10.1093/jac/dkv442. PMID 26747098.
8. H. Spreitzer (23 May 2016). "Neue Wirkstoffe - Lefamulin". Österreichische Apothekerzeitung (in German) (11/2016).
9. Mendes, R. E.; Farrell, D. J.; Flamm, R. K.; Talbot, G. H.; Ivezic-Schoenfeld, Z; Paukner, S; Sader, H. S. (2016). "In vitro activity of lefamulin tested against Streptococcus pneumoniae with defined serotypes, including multidrug-resistant isolates causing lower respiratory tract infections in the United States". Antimicrobial Agents and Chemotherapy. 60: AAC.00627–16. doi:10.1128/AAC.00627-16. PMC 4914675. PMID 27161634.
10. Veve, MP; Wagner, JL (September 2018). "Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic". Pharmacotherapy. 38 (9): 935–946. doi:10.1002/phar.2166. PMID 30019769.

External links

• "Lefamulin". Drug Information Portal. U.S. National Library of Medicine.