General Information

Xenleta (lefamulin) is a pleuromutilin antibacterial. 

Xenleta is specifically indicated for the treatment of adults with community-acquired bacterial pneumonia (CABP) caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.

Xenleta is supplied as an injection for intravenous administration or a tablet for oral administration. The recommended dose is as follows:

• 150 mg every 12 hours by intravenous infusion over 60 minutes for 5 to 7 days, with the option to switch to Xenleta tablets 600 mg every 12 hours to complete the treatment course
• 600 mg orally every 12 hours for 5 days

Mechanism of Action

Xenleta is a systemic pleuromutilin antibacterial. It inhibits bacterial protein synthesis through interactions (hydrogen bonds, hydrophobic interactions, and Van der Waals forces) with the A- and P-sites of the peptidyl transferase center (PTC) in domain V of the 23s rRNA of the 50S subunit. The binding pocket of the bacterial ribosome closes around the mutilin core for an induced fit that prevents correct positioning of tRNA. Xenleta is bactericidal in vitro against S. pneumoniae, H. influenzae and M. pneumoniae (including macrolide-resistant strains), and bacteriostatic against S. aureus and S. pyogenes at clinically relevant concentrations.

Side Effects

Adverse effects associated with the use of Xenleta may include, but are not limited to, the following:

Xenleta Injection:

• administration site reactions
• hepatic enzyme elevation
• nausea
• hypokalemia
• insomnia
• headache

Xenleta Tablets:

• diarrhea
• nausea
• vomiting
• hepatic enzyme elevation

Clinical Trial Results

FDA approval was based on two pivotal Phase 3 trials (known as LEAP 1 and LEAP 2) that evaluated the safety and efficacy of IV and oral Xenleta compared to moxifloxacin in the treatment of adults with CABP. LEAP 1 was designed to evaluate 5-to-7 days of IV/oral therapy of Xenleta versus 7-days of IV/oral moxifloxacin, with or without linezolid, with both treatment groups having the option to switch from IV to oral administration after 3-days. LEAP 2 evaluated 5-days of oral Xenleta versus 7-days of oral moxifloxacin. LEAP 1 showed comparable efficacy with moxifloxacin, with or without linezolid, while LEAP 2 showed comparable efficacy with moxifloxacin, with two fewer days of therapy.