The Lefamulin Dose Calculator is a clinical support tool designed to determine the appropriate dosage of lefamulin (Xenleta®) for adult patients with community-acquired bacterial pneumonia (CABP). It provides tailored recommendations by considering the route of administration (intravenous or oral) and the patient's degree of hepatic impairment, as defined by the Child-Pugh classification. This ensures dosing aligns with FDA-approved guidelines, optimizing efficacy while minimizing potential risks.

After you input the patient's details, the calculator will provide the following key information:

• Recommended Dose: The precise amount of lefamulin in milligrams (mg) for a single administration.
• Route: The method of administration, either Intravenous (IV) or Oral (PO).
• Frequency: How often the dose should be administered (e.g., every 12 hours or every 24 hours).
• Administration Notes: Important instructions, such as infusion time for IV administration or dietary considerations for oral tablets.
• Dose Adjustment Alerts: Specific warnings or notes when a dose modification is required (e.g., for severe hepatic impairment) or when a formulation is not recommended.

To use the calculator, follow these simple steps:

1. Select Route of Administration: Choose whether the patient will receive lefamulin intravenously (IV) or orally (PO).
2. Select Patient's Hepatic Function: Choose the patient's level of liver function based on the Child-Pugh score: Normal/Mild (Class A), Moderate (Class B), or Severe (Class C).
3. Review the Results: The calculator will automatically display the recommended dosing schedule based on your selections. The "Reset" button will return all inputs to their default state for a new calculation.

The recommended dosage for lefamulin in adults depends on hepatic function and the chosen route of administration. No dose adjustment is required for renal impairment.

Patients who begin treatment with intravenous lefamulin may be switched to the oral formulation to complete their course of therapy. The decision to switch should be based on the treating physician's clinical judgment. The recommended oral dose after IV therapy is 600 mg every 12 hours. This switch can be made when the patient is clinically stable and able to tolerate oral medications.

If a dose of lefamulin is missed, the patient should take the dose as soon as they remember. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. Patients should not take two doses at the same time to make up for a missed one. The regular dosing schedule should be resumed thereafter.

• QT Prolongation: Lefamulin can prolong the QT interval. It should be avoided in patients with a known history of QT prolongation, certain cardiac conditions, and those on specific antiarrhythmic medications (Class IA or Class III).
• Embryo-Fetal Toxicity: This medication may cause harm to a developing fetus. Pregnancy status should be confirmed in females of reproductive potential before starting treatment, and effective contraception is advised during treatment.
• Drug Interactions: Co-administration with strong or moderate CYP3A4 inhibitors can increase lefamulin exposure. Avoid concurrent use with strong CYP3A4 inducers (e.g., rifampin), as this may reduce lefamulin's effectiveness.

• Does renal impairment require a lefamulin dose adjustment?
  No, dosage adjustment is not necessary for patients with any degree of renal impairment, including those on hemodialysis.
• Is the dose different for elderly patients or based on body weight?
  No, dose adjustments are not required based on age, weight, or BMI.
• Why is oral lefamulin not recommended for moderate or severe hepatic impairment?
  In patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment, the body's ability to process oral lefamulin is significantly reduced, leading to a substantial increase in drug exposure and a higher risk of adverse effects. The IV formulation allows for a more controlled dose.
• What is the typical duration of lefamulin therapy for CABP?
  The recommended duration is typically 5 to 7 days, depending on the route and clinical response. The final duration should always be guided by clinical assessment.
• How should oral lefamulin be taken in relation to meals?
  Oral lefamulin should be taken on an empty stomach, at least 1 hour before or 2 hours after a meal, as food can affect its absorption.
• What does the calculator show for a patient with severe hepatic impairment receiving oral lefamulin?
  The calculator will display a warning message indicating that the oral route is not recommended for patients with Child-Pugh Class B or C hepatic impairment and will suggest considering the IV route or an alternative antibiotic.
• Can a patient switch from IV to oral therapy?
  Yes, a switch from IV to oral lefamulin is possible at the discretion of the healthcare provider once the patient is clinically stable.
• What is the Child-Pugh classification?
  It is a scoring system used to assess the prognosis of chronic liver disease, primarily cirrhosis. It uses five clinical measures to grade the severity of liver disease into Class A (mild), B (moderate), or C (severe).

• XENLETA® (lefamulin) Prescribing Information. U.S. Food and Drug Administration. Revised: August 2019.
• XENLETA® (lefamulin) for Healthcare Professionals. Nabriva Therapeutics US, Inc.
• Lefamulin Evaluation Against Pneumonia (LEAP 1). ClinicalTrials.gov. U.S. National Library of Medicine.
• Lefamulin Evaluation Against Pneumonia (LEAP 2). ClinicalTrials.gov. U.S. National Library of Medicine.