Pleuromutilin Antibiotic (Community-Acquired Pneumonia) Pregnancy: US label §8.1: based on findings from animal studies, lefamulin may cause fetal harm when administered to pregnant women. There are no available data on use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal studies of intravenous lefamulin during organogenesis showed increased prenatal mortality, decreased fetal body weights, apparent delay in sexual maturation and malformations in rats at exposures at or below the mean clinical exposure. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception (§5.2, §8.3).

Lefamulin

Brand names: Xenleta

Lefamulin is a pleuromutilin antibacterial, available in oral and intravenous forms, used for community-acquired pneumonia in adults.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Community-acquired bacterial pneumonia (CABP) in adults: 150 mg every 12 hours by intravenous infusion over 60 minutes for 5 to 7 days, with the option to switch to 600 mg orally every 12 hours to complete the treatment course; or 600 mg orally every 12 hours for 5 days for an oral-only course

Route: Intravenous infusion over 60 minutes (must be diluted before use), or oral tablets

Frequency: Every 12 hours

US FDA prescribing information §2 (XENLETA, Meitheal Pharmaceuticals, label date 2026-07-22) - NO UK SPC posology was available in this bundle, so this is US labelling and must be verified against the UK SPC before use. Indication in the fetched label is treatment of adults with CABP. HEPATIC IMPAIRMENT (§2.2): reduce XENLETA Injection to 150 mg infused over 60 minutes every 24 hours in severe hepatic impairment (Child-Pugh Class C); no adjustment of the injection is needed in mild (Child-Pugh A) or moderate (Child-Pugh B) impairment. XENLETA Tablets have not been studied in and are not recommended for patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment; no adjustment of tablets is needed in mild hepatic impairment (Child-Pugh A). Monitor patients with hepatic impairment for adverse reactions throughout treatment. ADMINISTRATION (§2.3-2.4): tablets must be taken at least 1 hour before a meal or 2 hours after a meal and swallowed whole with water (6 to 8 ounces) - do not crush or divide. The injection must be diluted - dilute the entire 15 mL vial into the supplied diluent bag containing 250 mL of 10 mM citrate-buffered 0.9% sodium chloride, mix thoroughly, and infuse over 60 minutes; do not add other additives and do not use in series connections. After dilution the injection may be stored for up to 24 hours at room temperature and up to 48 hours refrigerated at 2 to 8 degrees C. MISSED DOSE: take as soon as possible any time up to 8 hours before the next scheduled dose; if less than 8 hours remain, skip it and resume at the next scheduled dose. QT (§5.1): avoid in patients with known QT prolongation, ventricular arrhythmias including torsades de pointes, or receiving Class IA or Class III antiarrhythmics or other QT-prolonging drugs; in patients with renal failure requiring dialysis, and in patients with mild, moderate or severe hepatic impairment, metabolic disturbances may lead to QT prolongation. PAEDIATRIC: safety and effectiveness in patients less than 18 years of age have not yet been established - verify any paediatric use against a children's formulary.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Known hypersensitivity to lefamulin, to pleuromutilin class drugs, or to any of the components of XENLETA (US label §4.1)
Concomitant use of XENLETA Tablets with sensitive CYP3A4 substrates that prolong the QT interval, for example pimozide - increased plasma concentrations may lead to QT prolongation and torsades de pointes (US label §4.2)

Side effects

XENLETA Injection, most common (incidence 2% or greater): administration site reactions, hepatic enzyme elevation, nausea, hypokalaemia, insomnia, headache
XENLETA Tablets, most common (incidence 2% or greater): diarrhoea, nausea, vomiting, hepatic enzyme elevation
QT prolongation (US label §5.1)
Clostridioides difficile-associated diarrhoea - evaluate patients who develop diarrhoea (US label §5.3)
Embryo-fetal toxicity - may cause fetal harm (US label §5.2)

Interactions

Strong or moderate CYP3A inducers or P-gp inducers (both injection and tablets) - avoid unless the benefit outweighs the risk; monitor for reduced efficacy (US label §7.1)
Strong CYP3A inhibitors or P-gp inhibitors with XENLETA Tablets - avoid (US label §7.1)
Moderate CYP3A inhibitors or P-gp inhibitors with XENLETA Tablets - monitor for adverse reactions (US label §7.1)
CYP3A substrates that prolong the QT interval - concomitant use is contraindicated (US label §4.2, §7.2)
Midazolam and other sensitive CYP3A substrates - monitor for adverse reactions (US label §7.2)
Other QT-prolonging drugs including Class IA antiarrhythmics (e.g. quinidine, procainamide), Class III antiarrhythmics (e.g. amiodarone, sotalol), antipsychotics, erythromycin, pimozide, moxifloxacin and tricyclic antidepressants - avoid (US label §5.1)

Clinical monograph

How it works

It inhibits bacterial protein synthesis by binding the peptidyl transferase centre of the 50S ribosomal subunit.

Prescribing in practice

It can prolong the QT interval, so avoid use with other QT-prolonging drugs and in patients with significant pre-existing QT prolongation.
It is contraindicated in pregnancy unless effective contraception is used, based on reproductive toxicity findings.
It is a CYP3A4 substrate, so review interacting medicines that may alter its levels.

Monitoring

Consider ECG monitoring in patients at risk of QT prolongation and review concomitant medicines and liver function as clinically indicated.

Counselling the patient

Diarrhoea, nausea and injection-site reactions can occur.
Tell your clinician about heart-rhythm problems and all other medicines you take.
Complete the full course even if you feel better.

Evidence & guidelines

Non-inferiority to moxifloxacin in community-acquired pneumonia was shown in the LEAP 1 and LEAP 2 trials.

Reference: File et al. NEJM 2019 (LEAP-1); Paukner et al. NEJM 2019 (LEAP-2); MHRA SPC Xenleta; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways