Lefamulin
Pleuromutilins
PleuromutilinsPregnancy: avoid
Avoided in pregnancy: it caused malformations in animals and has not been studied in pregnant women. A negative pregnancy test is required before starting.
First systemic pleuromutilin, oral or IV, for community-acquired pneumonia: covers pneumococcus and atypicals. Prolongs the QT interval.
Quick facts
- Group
- Pleuromutilins
- Target
- Bacterial ribosome, 50S subunit (peptidyl transferase centre)
- Key effects
- Diarrhoea · Infusion-site reactions
- Monitor
- ECG in people with long QT
- ATC
- J01XX12
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows lefamulin bound to the 50S ribosomal subunit of Staphylococcus aureus.
Lefamulin binds the peptidyl transferase centre of the 50S subunit, near the A and P sites. The binding pocket closes over it and keeps transfer RNA from sitting properly, so no peptide bond forms. It is bactericidal against respiratory gram-positives and active against Mycoplasma, Legionella and Chlamydophila.
- Enters the 50S peptidyl transferase centre
- The pocket closes around the drug
- tRNA cannot settle in the A and P sites
- No peptide bond forms
Indications
- Community-acquired bacterial pneumonia in adults Community-acquired pneumonia →
Adverse effects
Common
- Diarrhoea, nausea and vomiting (oral form)
- Infusion-site reactions (IV form)
Contraindications
- Allergy to lefamulin or other pleuromutilins (retapamulin)
- Use together with pimozide
Key interactions
- Strong CYP3A4 inducers and inhibitors
- Lower or raise lefamulin levels; avoided or used with caution.
- Pimozide and other QT-prolonging drugs
- Additive QT prolongation; never combined with pimozide.
- St John's wort
- A CYP3A4 inducer that can lower its levels.
What is monitored
- ECG in people with long QT, arrhythmias or QT-prolonging drugs
- Pregnancy test before starting in women who can become pregnant
- Diarrhoea during and after treatment
Administration and safety
- Oral on an empty stomach: at least 1 hour before or 2 hours after a meal, with a glass of water
- Tablets are swallowed whole, not split or chewed
- The IV route can cause pain or phlebitis at the infusion site
Pregnancy and breastfeeding
Avoided in pregnancy: it caused malformations in animals and has not been studied in pregnant women. A negative pregnancy test is required before starting.
Nursing care
- Review the medicines for CYP3A4 inhibitors or inducers and QT-prolonging drugs
- Confirm a negative pregnancy test and explain contraception during treatment and for two days after
- Watch for palpitations, dizziness or fainting
- Teach to finish the course
Pharmacokinetics
- Absorption
- Oral with low bioavailability (about 25%), lower with food; also IV.
- Distribution
- Highly bound to plasma proteins.
- Metabolism
- Hepatic, by CYP3A4.
- Elimination
- Mainly in the faeces; no adjustment in kidney failure.
Test yourself
Think of the answer, then tap the question to see it.
Where does lefamulin's class come from, and where does it act?
It is a pleuromutilin, derived from a product of Pleurotus fungi; it acts at the peptidyl transferase centre of the 50S ribosome.
Which test is required before starting lefamulin in a woman who can become pregnant?
A negative pregnancy test, because it caused malformations in animals.
Which enzyme metabolises lefamulin, and what does that imply?
CYP3A4: strong inhibitors and inducers change its levels and are avoided or used with caution.
Which cardiac effect means the other drugs of someone on lefamulin are reviewed?
QT prolongation; it is not combined with pimozide and is watched with other QT-prolonging drugs.
Connections
← Back to the class: Pleuromutilins
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Lefamulin: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); The crystal structure of the large ribosomal subunit of Staphylococcus aureus in complex with lefamulin (RCSB Protein Data Bank, 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.