XENLETA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XENLETA (XENLETA).
Lefamulin inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit, preventing peptide bond formation and inhibiting protein translation.
| Metabolism | Primarily metabolized by CYP3A4; also a substrate of P-glycoprotein. |
| Excretion | Primarily eliminated unchanged via the kidneys; approximately 75% of administered dose is recovered in urine as unchanged drug, with about 20% in feces. |
| Half-life | Terminal elimination half-life is approximately 4.5 hours in healthy subjects, allowing twice-daily dosing for treatment of acute bacterial skin and skin structure infections. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is about 0.36 L/kg, indicating distribution primarily in extracellular fluid and moderate tissue penetration. |
| Bioavailability | Oral bioavailability is approximately 100% under fasted conditions; administration with high-fat meals may reduce absorption. |
| Onset of Action | Intravenous: onset of clinical effect occurs within minutes to hours; oral: plasma concentrations reach therapeutic levels within 1-2 hours after a loading dose. |
| Duration of Action | Duration of action is approximately 12 hours, supporting twice-daily administration; clinical effect persists throughout the dosing interval. |
600 mg intravenously every 12 hours for 7-14 days.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | No dose adjustment required for mild or moderate hepatic impairment (Child-Pugh class A or B). Not studied in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. |
| Geriatric use | No overall differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XENLETA (XENLETA).
| Breastfeeding | Unknown whether lefamulin is excreted in human breast milk. M/P ratio not determined. Due to potential for adverse effects in nursing infants from systemic exposure, breastfeeding should be discontinued during therapy or therapy should be discontinued, taking into account importance of drug to mother. |
| Teratogenic Risk | FDA Pregnancy Category C. In animal studies, lefamulin (XENLETA) was associated with increased postimplantation loss, reduced fetal body weights, and skeletal variations at maternal toxic doses. No adequate and well-controlled studies in pregnant women. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to lefamulin or any component of the formulation.","Concomitant administration with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort).","Use in patients with known QT prolongation or receiving class IA or III antiarrhythmic agents."]
| Precautions | ["May cause QT prolongation; avoid use in patients with known QT prolongation or with concurrent use of QT-prolonging drugs.","Increased risk of diarrhea including Clostridioides difficile-associated diarrhea.","Avoid use in patients with moderate to severe hepatic impairment (Child-Pugh B or C).","Not recommended for use in pregnancy or during breastfeeding due to potential fetal harm based on animal studies."] |
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| Fetal Monitoring | For pregnant women, monitor fetal development with serial ultrasound and fetal growth assessments if used. Hepatic function should be monitored due to potential for hepatotoxicity. ECG monitoring recommended due to risk of QT prolongation. |
| Fertility Effects | In animal studies, no adverse effects on male or female fertility were observed at exposures up to 2 times the human exposure. No human data available on fertility effects. |