lefamulin

Pleuromutilin · Antibiotic (Protein Synthesis Inhibitor) / Anti-infective agent indicated for the treatment of community-acquired bacterial pneumonia. It is a pleuromutilin, available for both oral and intravenous administration, with potent activity against gram-positive pathogens (except enterococci), including MRSA and penicillin-resistant S. pneumoniae. It typically exhibits bactericidal activity. The mechanism of action involves inhibiting bacterial protein synthesis by targeting the 50S ribosomal subunit near the A and P sites, resulting in inhibition of peptide bond formation. There is little cross-resistance with other protein synthesis inhibitors. It also has some activity against Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Chlamydia trachomatis. After intravenous administration, it achieves peak plasma concentrations of approximately 1.5-2 mg/L. The oral formulation has a relatively low bioavailability of about 25%, which is modestly reduced by food, but higher oral doses can achieve comparable plasma concentrations to IV. It is highly protein-bound (~95%) and has a half-life of about 12 hours, allowing for twice-daily dosing. Elimination is largely unchanged in the feces, and no dose adjustment is needed in renal or hepatic dysfunction. The typical adult dosage is 150 mg IV or 600 mg orally every 12 hours. Common adverse effects include gastrointestinal effects such as nausea and diarrhea. Serious adverse effects include prolongation of the QT interval, which may warrant monitoring in patients with risk factors for arrhythmia. It is a substrate of CYP3A4. Concomitant use with strong inducers or inhibitors of CYP3A4 should be avoided or undertaken with caution. This monograph provides a comprehensive overview of lefamulin's clinical indications, mechanism, pharmacokinetic properties, dosing, and significant safety considerations, particularly for cardiac effects and drug interactions, positioning it as an important agent for respiratory infections. This monograph summarizes all relevant clinical data from the chapter.