Lefamulin Disease Interactions

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

The use of lefamulin should be avoided in patients with known QT prolongation, ventricular arrhythmias including torsades de pointes, and patients receiving drugs that prolong the QT interval such as antiarrhythmic agents. In patients predisposed to QT prolongation, or those receiving another drug that prolongs the QT interval, ECG monitoring is recommended during treatment.

The half-life of lefamulin is prolonged in subjects with severe hepatic impairment. Lefamulin tablets have not been studied in patients with hepatic impairment. It is not recommended to use them in patients with moderate or severe hepatic impairment. The dosage of lefamulin injection should be reduced by extending the dosing interval for patients with severe hepatic impairment. In patients with mild, moderate, or severe hepatic impairment, metabolic disturbances associated with hepatic impairment may lead to QT prolongation. Caution is advised.

No dosage adjustment of lefamulin is warranted in patients with renal impairment, including those on hemodialysis. However, in patients with renal failure who require dialysis, metabolic disturbances associated with renal failure may lead to QT prolongation. Monitoring is advised.