Merck Manual

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Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Last full review/revision May 2020| Content last modified May 2020
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Lefamulin is a pleuromutilin antibiotic that inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S bacterial ribosome, thus preventing the binding of transfer RNA.


Oral bioavailability is about 25%, and consequently the oral dose is 4 times higher (600 mg every 12 hours) than the IV dose (150 mg every 12 hours). Lefamulin has minimal renal clearance and does not require dose adjustment in patients with kidney disease.

Indications for Lefamulin

Lefamulin is indicated for the treatment of community-acquired bacterial pneumonia (CABP) caused by the following susceptible microorganisms:

  • Streptococcus pneumoniae

  • Staphylococcus aureus (methicillin-susceptible isolates

  • Haemophilus influenzae

  • Legionella pneumophila

  • Mycoplasma pneumoniae

  • Chlamydophila pneumoniae

Contraindications to Lefamulin

Use of lefamulin with CYP3A4 substrates that prolong the QT interval, such as tacrolimus, dofetilide, and quetiapine, is contraindicated.

Use in Pregnancy and Breastfeeding

Animal reproduction studies with lefamulin show some risk, and no adequate, well-controlled studies have been done in pregnant women. Alternatives to lefamulin should be considered in pregnant women until better safety data are available. Females with reproductive potential should use contraception while on therapy and for 2 days after the last dose.

Animal lactation studies suggest that lefamulin concentrates in breast milk. It is advised that lactating women taking lefamulin pump and discard while taking lefamulin and for 2 days after the last dose.

Adverse Effects of Lefamulin

Lefamulin may cause QT prolongation especially if combined with other drugs that prolong the QT interval.

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