Lefamulin (Xenleta) for Community Acquired Bacterial Pneumonia

January 21, 2020

Lefamulin was approved by the FDA in August 2019 for the treatment of CABP.

Community acquired bacterial pneumonia (CABP) can result in hospitalizations, morbidity, and mortality.1

Strepococcus pneumoniae is one of the most common bacterial pathogens and has shown increased resistance to typical antibacterial therapies.2 Lefamulin, a novel pleuromutilin antibiotic that inhibits the 50S ribosomal subunit at the peptidyl transferase center, with known activity against typical CABP organisms, was approved by the FDA in August 2019 for the treatment of CABP.1,2

EFFICACY

In the LEAP 1 trial, lefamulin was shown to be noninferior to moxifloxacin ± linezolid (if MRSA coverage necessary) in the treatment of CABP in hospitalized adults. In a randomized controlled trial, IV to PO lefamulin was as successful as IV to PO moxifloxacin ± linezolid at improving at least 2 CABP symptoms without worsening of CABP or the need to receive a non-study antibiotic for treatment.2

In the LEAP 2 trial, oral lefamulin demonstrated noninferiority to oral moxifloxacin for CABP. PO lefamulin was as successful as PO moxifloxacin at achieving resolution of CABP symptoms without worsening of CABP or the need to receive a non-study antibiotic for treatment.3

Although in the LEAP 1 trial lefamulin was used to treat CABP caused by MRSA, the product package insert does not endorse that use due to only treating a small number of patients in the study and the need for additional antibiotics for treatment.4

SAFETY

Commonly reported adverse events related to lefamulin in LEAP 1 and LEAP 2 include administration site reactions, elevation of hepatic enzymes, nausea/vomiting/diarrhea, headache, insomnia, and hypokalemia. Serious adverse events include QTc prolongation and the risk of Clostridium difficile-associated diarrhea. No C. difficile infections were observed in either treatment arm of LEAP 1 and 1 incidence of C. difficile was associated with lefamulin treatment in LEAP.2,3,4

DOSING AND ADMINISTRATION

Lefamulin IV is dosed at 150 mg every 12 hours over 60 minutes for 5-7 days. It can be switched to oral therapy once the patient is clinically stable. Lefamulin IV is available as a 15 mL vial that will be further diluted by addition into a supplied diluent bag that contains 250 mL of 10 mM citrate buffered 0.9% sodium chloride. Lefamulin PO is dosed at 600 mg every 12 hours for 5 days. Take the tablets at least 1 hour before or 2 hours after a meal. The tablets cannot be crushed or split.

In patients with severe hepatic impairment (Child-Pugh Class C), lefamulin IV should be hepatically dose-adjusted to 150 mg IV every 24 hours over 60 minutes. Lefamulin PO has not been studied in patients with hepatic impairment. Both lefamulin formulations do not need to be renally dose adjusted.

 

 

References:

1. FDA.gov [Internet]. 2019 Aug 19. FDA approves new antibiotic to treat community-acquired bacterial pneumonia. Available from: https://www. fda.gov/news-events/press-announcements/ fda-approves-new-antibiotic-treat-community-acquired-bacterial-pneumonia.

2. File Jr. TM, Goldberg L, Das A, et al. Efficacy and safety of intravenous-to-oral leafmulin, a pleuromutilin antibiotic, for the treatment of community-acquired bacterial pneumonia: the phase III lefamulin evaluation against pneumonia (LEAP 1) trial. Clin Infect Dis. 2019 Feb 4. [epub ahead of print].

3. Alexander E, Goldbery L, Das A, et al. Oral lefamulin is safe and effective in the treatment of adults with community-acquired bacterial pneumonia (CABP): results of lefamulin evaluation against pneumonia (LEAP 2) study. Open Forum Infectious Diseases. 2018 Nov 26; 5(S1): S761. Available at: https://idsa.confex.com/ idsa/2018/webprogram/Paper74297.html

4. Lefamulin (Xenleta®) package insert. Nabriva Therapeutics US, Inc., of Nabriva Therapeutics Ireland DAC. 2019.

 

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