Lefabac150 mg vial

Lefabac is a systemic pleuromutilin antibacterial agent indicated for the treatment of specific bacterial infections in adults.

Established / FDA-Approved Use

• Community-Acquired Bacterial Pneumonia (CABP): Lefabac is approved for the treatment of CABP in adults caused by susceptible isolates of Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.

Not Established / Off-Label

Lefabac has not been established as safe and effective for infections other than CABP. It should not be used for other types of infections (e.g., skin and soft tissue infections, urinary tract infections) outside of clinical trial settings, as robust evidence for these uses is lacking.

Each film-coated tablet for oral use contains Lefamulin Acetate equivalent to 600 mg of lefamulin base.

Each single-dose vial for intravenous infusion contains Lefamulin Acetate equivalent to 150 mg of lefamulin base per 15 mL (10 mg/mL) solution.

Lefabac is the first systemic pleuromutilin antibacterial approved for use in humans. It is a semi-synthetic antibiotic derived from the pleuromutilin class, available in both oral tablet and intravenous infusion formulations, which allows for flexible step-down therapy from IV to oral administration.

Lefabac works by a mechanism distinct from other commonly used antibiotic classes (such as beta-lactams, macrolides, and fluoroquinolones), making it a therapeutic option for community-acquired bacterial pneumonia, including cases involving atypical pathogens.

Pleuromutilin-class antibacterial (Lefabac is the first systemic pleuromutilin approved for human use).

Pharmacodynamics

Lefamulin Acetate exhibits activity against a range of Gram-positive, atypical, and select Gram-negative respiratory pathogens by inhibiting bacterial protein synthesis (see Mode of Action). Its binding site is distinct from other antibiotic classes, which limits cross-resistance with beta-lactams, macrolides, fluoroquinolones, and tetracyclines.

Pharmacokinetics

• Absorption: Oral Lefamulin Acetate is absorbed with an absolute bioavailability of approximately 25%; administration with a high-fat meal reduces exposure, so it should be taken on an empty stomach.
• Distribution: Approximately 94-96% protein bound; distributes well into epithelial lining fluid and alveolar macrophages of the lung.
• Metabolism: Metabolized primarily via CYP3A4-mediated oxidation.
• Elimination: Eliminated mainly via the biliary/fecal route, with a minor renal component; terminal half-life is approximately 8 hours (IV) and 9-10 hours (oral).

Oral Lefabac tablets should be taken whole with water on an empty stomach, at least 1 hour before or 2 hours after eating. The intravenous formulation must be diluted and given as a slow infusion over 60 minutes via a dedicated intravenous line, never as a bolus. See Dosage and Administration for full details.

Contraindicated Combination

Concurrent use of Lefabac with CYP3A substrate drugs that are known to prolong the QT interval is contraindicated, as this combination may increase plasma concentrations of the interacting drug and compound the risk of serious ventricular arrhythmias (e.g., torsades de pointes). See Contraindications.

Strong CYP3A4 Inducers

Co-administration of Lefabac with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort) can substantially decrease Lefabac plasma concentrations, potentially leading to therapeutic failure; concurrent use should be avoided.

Strong CYP3A4/P-glycoprotein Inhibitors

Co-administration of intravenous Lefabac with strong CYP3A4/P-glycoprotein inhibitors (e.g., itraconazole, clarithromycin, ritonavir) may increase Lefabac exposure; caution and clinical monitoring are advised.

Other QT-Prolonging Drugs

Use of Lefabac with other drugs known to prolong the QT interval (that are not CYP3A substrates) should be approached with caution, as the risk of additive QT prolongation cannot be excluded (see Precautions and Warnings).

The most commonly reported adverse reactions with Lefabac include:

• Diarrhea
• Nausea and vomiting
• Headache
• Insomnia
• Injection site reactions (with the intravenous formulation)
• Elevated liver enzymes (transaminases)
• Hypokalemia

Less common but clinically important effects include QT interval prolongation and hypersensitivity reactions; see Precautions and Warnings for details. Clostridioides difficile-associated diarrhea has been reported with nearly all antibacterial agents, including Lefabac, and should be considered in patients presenting with diarrhea during or after treatment.

Pregnancy

Lefabac should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus. Animal reproduction studies have shown evidence of embryo-fetal toxicity at clinically relevant exposures. Because of this risk, effective contraception is recommended for patients of reproductive potential during treatment and for a short period after the last dose; consult a physician before use in pregnancy.

Lactation

There is limited information on the presence of Lefabac in human milk or its effects on the breastfed infant. Based on animal data suggesting potential adverse effects, breastfeeding is generally not recommended during treatment with Lefabac and for approximately 2 days after the final dose. A physician should be consulted to weigh the benefits of breastfeeding against the potential risk to the infant.

QT Interval Prolongation

Lefabac can prolong the QT interval. Avoid use in patients with congenital long QT syndrome, in those taking other QT-prolonging drugs, in patients with uncorrected hypokalemia or hypomagnesemia, and in patients with clinically significant bradycardia, cardiac arrhythmia, or uncompensated heart failure. Correct electrolyte abnormalities before starting therapy.

Embryo-Fetal Toxicity

See Pregnancy and Lactation for details; effective contraception is advised during treatment.

Hepatic Effects

Elevations in liver enzymes have been observed with Lefabac; monitor liver function in patients with pre-existing hepatic impairment or who develop signs of hepatic dysfunction during treatment.

Clostridioides difficile-Associated Diarrhea

As with other antibacterial agents, Lefabac may be associated with C. difficile-associated diarrhea, ranging from mild to life-threatening colitis; evaluate patients who develop diarrhea during or after treatment.

Hypersensitivity Reactions

Serious hypersensitivity reactions have been reported; discontinue Lefabac immediately if signs of an allergic reaction occur.

Effects on Bone and Cartilage

Juvenile animal studies with Lefabac showed effects on cartilage; see Use in Special Populations for pediatric considerations.

Antibiotic Stewardship

Take Lefabac exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice, in order to ensure effectiveness and reduce the development of drug-resistant bacteria.

There is limited clinical experience with overdose of Lefabac. In the event of a suspected overdose, seek immediate medical attention or contact a poison control center/emergency services without delay. Management should be supportive, with particular attention to cardiac monitoring given the potential for QT interval prolongation; no specific antidote is available. Hemodialysis is not expected to significantly remove Lefabac from the circulation due to its high protein binding.

Store at room temperature (below 30°C), away from light and moisture. The intravenous solution should be protected from light and used according to the diluted-solution stability instructions provided by the manufacturer. Keep out of reach of children.

Renal Impairment

No dose adjustment of oral Lefabac is needed. Use the intravenous formulation with caution in severe renal impairment or dialysis-dependent patients only if the benefit outweighs the risk (see Dosage and Administration).

Hepatic Impairment

No adjustment is needed for mild-to-moderate impairment; intravenous Lefabac is not recommended in severe hepatic impairment.

Elderly Patients

No overall differences in safety or effectiveness have been observed between elderly and younger adult patients, though elderly patients may be more susceptible to drug-associated QT prolongation and should be monitored accordingly.

Pediatric Patients

See Pediatric Uses. Safety and efficacy of Lefabac have not been established in patients under 18 years of age.

The recommended duration of treatment with Lefabac for community-acquired bacterial pneumonia is 5 days for the oral regimen and 5 to 7 days for the intravenous (or IV-to-oral switch) regimen, depending on clinical response and severity. Treatment duration should be individualized by the prescribing physician and should not be extended or shortened without medical advice.

Pleuromutilin antibacterials (systemic); Lefamulin Acetate is the sole approved member of this class for human use.

Lefamulin Acetate inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit at the peptidyl transferase center, interfering with peptide bond formation, tRNA positioning, and the translocation of the ribosome along messenger RNA. This binding site is structurally distinct from the sites targeted by other major antibiotic classes (e.g., macrolides, lincosamides, beta-lactams, fluoroquinolones), which results in a low likelihood of cross-resistance with these agents.

The safety and effectiveness of Lefabac have not been established in pediatric patients younger than 18 years of age. In juvenile animal studies, exposure to Lefabac was associated with effects on cartilage. Because of this potential risk to developing bone and joint tissue, Lefabac is not recommended for use in children or adolescents unless a physician determines that no suitable alternative therapy is available and the potential benefit outweighs the risk.