lefamulin

Acts as a pleuromutilin that ultimately interferes with bacterial protein synthesis at the level of the 50S ribosome.

Therapeutic effects:

Resolution of pneumonia.

Spectrum:

Active against gram-positive pathogens, including
- Staphylococcus aureus(methicillin-sensitive strains only),
- Streptococcus pneumoniae.
Also active against the following gram-negative pathogen:
- Haemophilus influenzae.
Also active against several other pathogens, including
- Legionella pneumophilia,
- Chlamydia pneumoniae,
- Mycoplasma pneumoniae.

Pharmacokinetics ⬆ ⬇

Absorption: 25% absorbed following oral administration; IV administration results in complete bioavailability.

Distribution: Extensively distributed to tissues.

Protein Binding: 94–97%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme. Primarily excreted in feces (77%; 4–9% as unchanged drug), with 15% excreted in urine (9–14% as unchanged drug).

Half-Life: 8 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	0.88–2 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to lefamulin or retapamulin;
Concurrent use of CYP3A4 substrates that prolong the QT interval;
QT interval prolongation or a history of ventricular arrhythmias (including torsades de pointes);
Moderate or severe hepatic impairment (oral tablets only);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe hepatic impairment (↑ dosing interval for IV injection);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: QT interval prolongation

F and E: hypokalemia

GI: diarrhea, ↑liver enzymes, CLOSTRIDIOIDES DIFFICILE ASSOCIATED DIARRHEA (CDAD), nausea, vomiting

Local: injection site reactions

Neuro: headache, insomnia

Interactions ⬆ ⬇

Drug-drug:

CYP3A4 substrates that prolong the QT interval, including pimozide, may ↑ the risk of QT interval prolongation and torsades de pointes; concurrent use contraindicated.
Class Ia antiarrhythmics or Class III antiarrhythmics may ↑ the risk of QT interval prolongation and torsades de pointes; avoid concurrent use.
QT interval prolonging medications, including antipsychotics, erythromycin, moxifloxacin, or tricyclic antidepressants, may ↑ the risk of QT interval prolongation and torsades de pointes; avoid concurrent use.
Strong CYP3A4 inhibitors or P-glycoprotein (P-gp) inhibitors may ↑ levels and risk of toxicity of oral lefamulin; avoid concurrent use.
Moderate or strong CYP3A4 inducers or P-gp inducers may ↓ levels and effectiveness of either oral or IV lefamulin; avoid concurrent use.
Lefamulin tablets may ↑ levels of CYP3A4 substrates, including benzodiazepines, diltiazem, lovastatin, PDE5 inhibitors, simvastatin, and verapamil; monitor closely for adverse reactions.

Route/Dosage ⬆ ⬇

IV (Adults ): 150 mg every 12 hr for 5–7 days; may switch at any time to oral regimen to complete the treatment course.
PO (Adults ): 600 mg every 12 hr for 5 days.

Hepatic Impairment

IV (Adults ): Severe hepatic impairment: 150 mg every 24 hr for 5–7 days.

Availability ⬆ ⬇

Film-coated tablets: 600 mg
Solution for injection: 10 mg/mL

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy, especially in geriatric patients.
Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.
Monitor ECG for QT interval prolongation in patients with ventricular arrhythmias or those on other drugs that prolong QT interval.
Monitor for signs and symptoms of hypersensitivity reactions (rash, hives, swelling of face or throat) during therapy.

Lab Test Considerations:

Obtain a negative pregnancy test before starting therapy.

Implementation ⬆ ⬇

PO: Administer at least 1 hr before or 2 hr after a meal. Swallow tablets whole with 6–8 oz of water; DNC: Do not crush, break, or chew film-coated tablets.
Intermittent Infusion: Dilute entire 15 mL vial into diluent bag supplied containing 250 mL of 10 mM citrate buffered 0.9% NaCl. Mix thoroughly. Solution is clear and colorless; do not administer solutions that are discolored or contain particulate matter. Solution is stable for 24 hr at room temperature or 48 hr if refrigerated.
Rate: Infuse over 60 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take lefamulin as directed. Take missed doses as soon as remembered up to 8 hr before next dose. If less than 8 hr before next dose, omit dose and resume dosing at next scheduled dose.
Instruct patient to notify health care professional immediately if rash, diarrhea, abdominal cramping, fever, or bloody stools occur and not to treat with antidiarrheals without consulting health care professionals.
Advise patient to report the signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools) to health care professional.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for 2 days after final dose. If patient becomes pregnant while taking lefamulin, encourage patient to enrol in registry to monitor pregnancy outcomes by calling 1-855-5NABRIVA to enroll.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇