Lefamulin Acetate is indicated for the treatment of adults with community-acquired bacterial pneumonia (CABP) caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.

Lefamulin Acetate is a semi-synthetic antibacterial agent for oral and intravenous administration. Lefamulin features a novel mechanism of action that shows benefits against resistant bacteria that cause pneumonia. Lefamulin is a systemic pleuromutilin antibacterial. It inhibits bacterial protein synthesis through interactions (hydrogen bonds, hydrophobic interactions, and Van der Waals forces) with the A- and P-sites of the peptidyl transferase center (PTC) in domain V of the 23S rRNA of the 50S subunit.

Dosage of Lefamulin in Adult CABP Patients: Lefamulin 150 mg injection every 12 hours by intravenous infusion over 60 minutes for 5 to 7 days (with the option to switch to Lefamulin Tablets 600 mg every 12 hours to complete the treatment course). Lefamulin tablet 600 mg orally every 12 hours for 5 days. For patients with severe hepatic impairment, dosage adjustment is required.

Dosage Adjustment for Patients with Hepatic Impairment

• Lefamulin Injection: Reduce the dosage of Lefamulin Injection to 150 mg infused intravenously over 60 minutes every 24 hours for patients with severe hepatic impairment. No dosage adjustment of Lefamulin Injection is needed for patients with mild or moderate hepatic impairment.
• Lefamulin Tablets: Lefamulin Tablets have not been studied in and are not recommended for patients with moderate or severe hepatic impairment. No dosage adjustment of Lefamulin Tablets is needed for patients with mild hepatic impairment.

Important Administration Instruction

• Lefamulin Injection: Administer Lefamulin Injection by intravenous infusion over 60 minutes. Must dilute in a 250 ml solution of citrate buffered 0.9% sodium chloride for injection supplied with Lefamulin Injection before use.
• Lefamulin Tablets: Take Lefamulin Tablets at least 1 hour before a meal or 2 hours after a meal. Do not crush or divide Lefamulin Tablet.
• Missed Dose: If a dose is missed, the patient should take the dose as soon as possible and anytime up to 8 hours prior to the next scheduled dose. If less than 8 hours remain before the next scheduled dose, do not take the missed dose, and resume dosing at the next scheduled dose.

Preparation of Lefamulin Injection for Intravenous Infusion

• Dilute the entire 15 ml vial of Lefamulin Injection into the diluent bottle supplied with Lefamulin Injection that contains 250 ml citrate buffered 0.9% sodium chloride solution.
• Use aseptic technique when adding Lefamulin Injection into the diluent bottle. Mix thoroughly.
• Use the diluent bottle only if the solution is clear and the container is undamaged.
• Do not use the diluent bottle in series connections.
• Do not add other additives to the diluent bottle because their compatibilities with Lefamulin Injection have not been established.

With Medicine: Concomitant use of oral or intravenous Lefamulin with strong CYP3A4 inducers or P-glycoprotein inducers decreases Lefamulin AUC and Cmax, which may reduce the efficacy of Lefamulin. Avoid concomitant use of Lefamulin Injection with strong and moderate CYP3A4 inducers or P-glycoprotein inducers unless the benefit outweighs the risks.

With Food and Others: Exercise caution with grapefruit products. Grapefruit inhibits CYP3A, which may increase the serum concentration of Lefamulin.

Lefamulin Acetate is contraindicated in patients with known hypersensitivity to Lefamulin, pleuromutilin class drugs, or any of the components of Lefamulin, and is also contraindicated for use with CYP3A4 substrates that prolong the QT interval. Lefamulin is not recommended for pregnant women and pediatric patients below 18 years of age.

Lefamulin Acetate has the potential to prolong the QT interval. Avoid Lefamulin in patients with known QT prolongation, ventricular arrhythmias, and patients receiving drugs that may prolong the QT interval. Clostridioides difficile-associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including Lefamulin, with severity ranging from mild diarrhea to fatal colitis.

Pregnancy: No clinical studies have been performed in pregnant women. Animal studies indicate that administration of Lefamulin Acetate resulted in an increased incidence of stillbirth. Malformations were also observed in rats at systemic exposures lower than the systemic exposure in CABP patients. Lefamulin should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Lactation: There are no data on the presence of Lefamulin Acetate in human milk, its effects on the breastfed infant, or its effects on milk production. Animal studies indicate that Lefamulin was concentrated in the milk of lactating rats. Because of the potential for serious adverse reactions, including QT interval prolongation, a woman should pump and discard human milk for the duration of treatment with Lefamulin and for 2 days after the final dose.

Clostridium difficile-Associated Disease (CDAD) has been reported with the use of many antibacterial agents, including Lefamulin. CDAD may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea or symptoms of colitis, pseudomembranous colitis, toxic megacolon, or perforation of the colon subsequent to the administration of any antibacterial agent. Lefamulin has the potential to prolong the QT interval of the electrocardiogram (ECG) in some patients. Avoid Lefamulin use in the following patients:

• Patients with known prolongation of the QT interval
• Patients with ventricular arrhythmias including torsades de pointes
• Patients receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents
• Patients receiving other drugs that prolong the QT interval, such as antipsychotics, erythromycin, pimozide, moxifloxacin, and tricyclic antidepressants

Treatment of overdose with Lefamulin should consist of observation and general support measures. The stomach should be emptied. Adequate hydration should be maintained and electrolytes monitored. Electrocardiogram (ECG) monitoring is recommended. Hemodialysis will not significantly remove Lefamulin from systemic circulation.

Other antibacterial preparation

IV Infusion: Store in a refrigerator at 2°C to 8°C. Do not freeze and protect from light. Keep out of the reach of children.

Tablet: Do not store above 30°C. Do not refrigerate or freeze. Keep in a dry place. Protect from light and keep out of the reach of children.