Lefabac^®

Lefabac^® is a systemic pleuromutilin antibacterial. It inhibits bacterial protein synthesis through interactions with the A- and P-sites of the peptidyl transferase center (PTC) in domain V of the 23s rRNA of the 50S subunit. The binding pocket of the bacterial ribosome closes around the mutilin core for an induced fit that prevents correct positioning of tRNA.

No Data

Lefabac^® 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.

Route of administration: Lefabac^® tablet should be taken in oral route preferably with meal. Lefabac^® injection for IV infusion should be administered as an intravenous infusion.

Lefabac^® tablet: 600 mg orally every 12 hours for 5 days.

Take Lefabac^® tablet at least 1 hour before a meal or 2 hours after a meal. Swallow Lefabac^® tablet whole with a glass of water (6 to 8 ounces). Do not crush or divide Lefabac^® tablet. 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.

Lefabac^® injection for IV infusion: 150 mg every 12 hours by intravenous infusion over 60 minutes for 5 to 7 days, with the option to switch to Lefabac" tablets 600 mg every 12 hours to complete the treatment course.

Hepatic impairment

Lefabac^® tablets are not recommended for patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment. No dosage adjustment of Lefabac^® tablets is needed for patients with mild hepatic impairment (Child-Pugh Class A). Reduce the dosage of Lefabac^® injection to 150 mg infused intravenously over 60 minutes every 24 hours for patients with severe hepatic impairment (Child-Pugh Class C). No dosage adjustment of Lefabac^® injection is needed for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.

Pregnancy: May cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with lefamulin and 2 days after the final dose.

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. Because of the potential for serious adverse reactions, including QT prolongation, a woman should pump and discard human milk for the duration of treatment and for 2 days after the final dose.

Use in children and adolescents

The safety and effectiveness of lefamulin acetate in patients less than 18 years of age have not yet been established.

Avoid use 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, antipsychotics, erythromycin, pimozide, moxifloxacin and tricyclic antidepressants. Evaluate patients who develop Clostridioides d/flfc/fe-associated diarrhea (CDAD) for which may need to be discontinued this drug.

The most common side effects are diarrhea, nausea, vomiting, administration site reactions, hepatic enzyme elevation, headache, hypokalemia and insomnia.

Lefamulin acetate is contraindicated in patients with hypersensitivity to lefamulin acetate or any of the components of this product. It is also contraindicated with sensitive CYP3A4 substrates that prolong the QT interval.

Drug interaction with medication: Concomitant use of oral or intravenous lefamulin acetate with strong CYP3A4 inducers or P-gp inducers decreases lefamulin AUG and Cmax, which may reduce the efficacy of lefamulin acetate. Concomitant use of lefamulin acetate tablet with strong CYP3A inhibitors or P-gp inhibitors increases lefamulin AUG, which may increase the risk of adverse reactions with lefamulin acetate. Concomitant use of lefamulin acetate tablet with sensitive CYP3A4 substrates increases the AUG and Cmax of CYP3A4 substrates, which may increase the risk of toxicities associated with cardiac conduction. Concomitant use with CYP3A substrates known to prolong the QT interval is contraindicated.

Drug interaction with food and others: Not applicable.

Treatment of overdose with lefamulin acetate should consist of observation and general supportive measures. Lefamulin acetate and its primary metabolite are not dialyzable.

Preparation of injection for IV infusion

• Dilute the entire 15 ml vial of Lefabac^® injection into diluent vial (Dilute-Lefa) supplied with Lefabac injection that contains 250 ml of 10 mM citrate buffered (pH 5) 0.9% w/v sodium chloride.
• Use aseptic technique when adding Lefabac^® injection into Dilute-Lefa Mix thoroughly.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Use Dilute-Lefa vial only if the solution is clear and the container is undamaged.
• Do not use Dilute-Lefa vial in series connections.
• Do not add other additives to the Dilute-Lefa vial because their compatibilities with Lefabac^® injection have not been established.

No Data

Storage

Lefabac® 600 tablet: Store in a cool (below 30°C) & dry place protected from light. Keep away from the reach of children.

Lefabac® injection for IV infusion: Store in a refrigerator at 2°C to 8°C, protected from light. Do not freeze. Diluted solution in the intravenous vial can be stored up to 24 hours at room temperature and up to 48 hours in a refrigerator at 2°C to 8°C. Keep away from the reach of children.

Packing

Lefabac® 600 tablet: Carton of 10 tablets in blister pack.

Lefabac® injection for IV infusion: Each box contains one vial of 15 ml Lefamulin Acetate solution, one vial of 250 ml Dilute-Lefa" (10 mM citrate buffered (pH 5) 0.9% w/v Sodium Chloride BP) as diluent, one infusion set, one disposable syringe (20 ml), one alcohol pad and one first aid bandage.