1. Aschenbrenner, Diane S. MS, RN


* Lefamulin (Xenleta) is a new antibiotic approved to treat adults with community-acquired bacterial pneumonia.


* Lefamulin's labeling warns of the risk of QT interval prolongation, the potential for fetal harm, and the risk of Clostridium difficile-associated diarrhea.



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The Food and Drug Administration has approved lefamulin (Xenleta) to treat adults with community-acquired bacterial pneumonia caused by the following microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legion-ella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. Lefamulin is a semisynthetic pleuromutilin antibiotic that selectively inhibits a certain ribosomal protein synthesis; this action may lower the probability of cross-resistance to other antimicrobial classes.


Lefamulin's labeling contains three warnings and precautions. First, lefamulin can prolong the QT interval, increasing the risk of cardiac arrythmias. Second, lefamulin may cause fetal harm. The adverse effects of lefamulin in animal studies included fetal loss and stillbirths, deaths during lactation, low fetal body weight, and malformations. Third, common to antibiotics, there is the possibility of Clostridium difficile-associated diarrhea. The most common adverse effects of injectable lefamulin include nausea, injection site reactions, elevated liver enzymes, hypokalemia, insomnia, and headache. The most common adverse effects of oral lefamulin include diarrhea, nausea, vomiting, and elevations in hepatic enzymes.


The concomitant use of lefamulin with moderate-to-strong cytochrome P-450 (CYP) 3A4 isoenzyme inducers or P-glycoprotein (P-gp) inducers can significantly decrease the circulating levels of lefamulin, causing the drug to be less effective. The concomitant use of lefamulin with moderate-to-strong CYP3A4 inhibitors or P-gp inhibitors will do the opposite, increasing the circulating levels of lefamulin and the risk of adverse effects.


Two multicenter, international, randomized, double-blind, double-dummy, noninferiority phase 3 trials evaluated lefamulin as monotherapy. A total of 1,289 patients with community-acquired bacterial pneumonia were treated with oral or intravenous lefamulin, moxifloxacin, or moxifloxacin with linezolid. Lefamulin monotherapy was found to be as effective as the other treatment options.


Nurses can administer lefamulin orally or intravenously, and patients can change from the intravenous route to the oral route during treatment. Nurses should instruct patients to take oral lefamulin at least one hour before a meal or two hours after a meal; the tablet should be swallowed whole with water. Infusions of lefamulin should be slowly administered over one hour. Patients should be assessed for QT prolongation, ventricular arrythmias (including torsades de pointes), and coadministration of other drugs that lengthen the QT interval (class Ia or class III antiarrhythmics, antipsychotics, erythromycin, pimozide, moxifloxacin, and tricyclic antidepressants); the coadministration of lefamulin and these drugs is contraindicated. A drug database can be used to determine if a drug is a strong inhibitor or inducer of CYP3A4 or P-gp.


Nurses should teach women of childbearing age about the potential risks of fetal harm from lefamulin and to use effective contraception during treatment and for two days after the final dose. The manufacturer, Nabriva Therapeutics, has a surveillance program for any woman who has inadvertently taken lefamulin during pregnancy. Patients can participate in this registry by calling 1-855-5NABRIVA. Patients who develop diarrhea should be evaluated for C. difficile.


For complete prescribing information for lefamulin, go to,211673s000lb.