Lefamulin

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Lefamulin
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omid Afkhami-Ardakani

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Overview

Lefamulin is a Pleuromutilin Antibiotic that is FDA approved for the treatment of adults with community-acquired bacterial pneumonia (CABP) caused by susceptible microorganisms.. Common adverse reactions include injection: administration site reactions, hepatic enzyme elevation, nausea, hypokalemia, insomnia, headache.​

Oral: diarrhea, nausea, vomiting, hepatic enzyme elevation..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Lefamulin FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Lefamulin in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Lefamulin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Lefamulin FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Lefamulin in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Lefamulin in pediatric patients.

Contraindications

There is limited information regarding Lefamulin Contraindications in the drug label.

Warnings

QT Prolongation: Lefamulin may cause QT interval prolongation, which can lead to an increased risk of ventricular arrhythmias, including torsades de pointes. Avoid use in patients with known QT prolongation, ventricular arrhythmias, and patients receiving drugs that prolong the QT interval. ​

Embryo-Fetal Toxicity: Lefamulin may cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for two days after the final dose. ​

Clostridium difficile-associated Diarrhea (CDAD): Evaluate patients who develop diarrhea for CDAD, as it has been reported with nearly all systemic antibacterial agents.

Adverse Reactions

Clinical Trials Experience

njection: administration site reactions, hepatic enzyme elevation, nausea, hypokalemia, insomnia, headache.

Oral: diarrhea, nausea, vomiting, hepatic enzyme elevation.

Postmarketing Experience

There is limited information regarding Lefamulin Postmarketing Experience in the drug label.

Drug Interactions

CYP3A4 Substrates That Prolong the QT Interval: Concomitant use of Lefamulin tablets with CYP3A substrates that prolong the QT interval is contraindicated.

Strong or Moderate CYP3A Inducers or P-gp Inducers: Avoid Lefamulin unless the benefit outweighs the risk. Monitor for reduced efficacy.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): May cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for two days after the final dose.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Lefamulin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Lefamulin during labor and delivery.

Nursing Mothers

A lactating woman should pump and discard human milk for the duration of treatment with Lefamulin and for two days after the final dose.

Pediatric Use

There is no FDA guidance on the use of Lefamulin in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Lefamulin in geriatric settings.

Gender

There is no FDA guidance on the use of Lefamulin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Lefamulin with respect to specific racial populations.

Renal Impairment

No dosage adjustment is necessary in patients with renal impairment, including those on hemodialysis.

Hepatic Impairment

Reduce the dosage of Lefamulin Injection to 150 mg infused over 60 minutes every 24 hours in patients with severe hepatic impairment (Child-Pugh Class C). Lefamulin Tablets have not been studied in and are not recommended for patients with moderate (Child-Pugh Class B) or severe hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Lefamulin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Lefamulin in patients who are immunocompromised.

Administration and Monitoring

Administration

Injection: Administer by intravenous infusion over 60 minutes. Must dilute in a 250 mL solution of 10 mM citrate buffered 0.9% sodium chloride for injection before use.

Tablets: Take at least 1 hour before a meal or 2 hours after a meal. Swallow tablets whole with water (6 to 8 ounces). ​

Monitoring

QT Interval: Monitor ECG in patients with known risk factors for QT prolongation. ​ Liver Function Tests: Monitor hepatic enzymes during treatment.

IV Compatibility

Dilution: Dilute the entire 15 mL vial of Lefamulin Injection into the diluent bag supplied that contains 250 mL of 10 mM citrate buffered 0.9% sodium chloride.

Overdosage

There is limited information regarding Lefamulin overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Lefamulin Pharmacology in the drug label.

Mechanism of Action

Lefamulin is a pleuromutilin antibiotic that inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit. This unique mechanism interferes with the positioning of transfer RNA, thereby preventing peptide bond formation and inhibiting bacterial growth.

Structure

There is limited information regarding Lefamulin Structure in the drug label.

Pharmacodynamics

Lefamulin exhibits bactericidal activity against certain pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae, and bacteriostatic activity against Staphylococcus aureus and Streptococcus pyogenes.

Pharmacokinetics

Absorption: After oral administration, lefamulin reaches peak plasma concentrations within approximately 1 hour.​ Distribution: Lefamulin is extensively distributed throughout the body, with a volume of distribution of about 100 L.​ Metabolism: It is metabolized primarily by the liver, involving cytochrome P450 enzymes, particularly CYP3A4.​ Elimination: The elimination half-life is approximately 8 hours. Excretion occurs via feces (approximately 77%) and urine (approximately 16%). ​

Nonclinical Toxicology

There is limited information regarding Lefamulin Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Lefamulin Clinical Studies in the drug label.

How Supplied

Tablets: 600 mg, oval, white to off-white, debossed with "LEF" on one side.​ Injection: 150 mg/15 mL solution in a single-dose vial.

Storage

Tablets: Store at room temperature, 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C and 30°C (59°F to 86°F).​

Injection: Store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

QT Prolongation: Advise patients of the potential risk of QT interval prolongation and to inform their healthcare provider of any history of cardiac conditions or use of medications that may prolong the QT interval.​ Diarrhea: Inform patients that diarrhea is a common side effect. Instruct them to contact their healthcare provider if they experience severe or persistent diarrhea, as this may indicate Clostridium difficile-associated diarrhea (CDAD).​ Pregnancy and Lactation: Advise females of reproductive potential to inform their healthcare provider if they are pregnant or plan to become pregnant. Discuss the potential risks to the fetus and the need for effective contraception during treatment and for two days after the final dose.​ Drug Interactions: Counsel patients to inform their healthcare provider of all medications they are taking, including over-the-counter drugs and herbal supplements, due to potential interactions.

Precautions with Alcohol

There are no specific contraindications regarding alcohol consumption with lefamulin. However, patients should consult their healthcare provider regarding alcohol use during treatment, especially if they have liver disease or are taking other medications that may interact with alcohol.

Brand Names

Lefamulin is marketed under the brand name XENLETA.

Look-Alike Drug Names

There is limited information regarding Lefamulin Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.