5 Things You Must Know Before Taking Lefamulin-APICDMO
1. What Is Lefamulin?
Lefamulin(CAS:1061337-51-6) is a pleuromutilin antibacterial used to treat community-acquired bacterial pneumonia (CABP).Lefamulin is a pleuromutilin antibiotic used for the treatment of bacterial community-acquired pneumonia. A pleuromotilin is a more recently developed type of antibiotic that is derived from the fungus, Pleurotus mutilus.
Lefamulin is available in intravenous and oral preparations and was granted FDA approval in August 2019.This drug is the first semi-synthetic pleuromutilin that has been designed for systemic administration. Lefamulin features a novel mechanism of action that shows benefit against resistant bacteria that cause pneumonia.The chemical structure of lefamulin contains a tricyclic mutilin core that is necessary for some of its antimicrobial activity.
2. How Does Lefamulin Work?
Lefamulin inhibits prokaryotic ribosomal protein synthesis via its binding to the peptidyl transferase center (PTC) of the ribosomal bacterial 50S subunit. It
inhibits protein translation through binding to both the A and P sites of the PTC via four hydrogen bonds, resulting in the interruption of peptide bond formation.Lefamulin's tricyclic mutilin core is the common moiety for binding of all members of its drug class, the pleuromutilins. Although the tricyclic motilin core doesn’t form any hydrogen bonds with the PTC nucleotides, it is stabilized or anchored by hydrophobic and Van der Waals interactions.Lefamulin exerts a selective inhibition of protein translation in eukaryotes, however, does not affect ribosomal translation of eukaryotes. Lefamulin demonstrates a unique induced-fit type of action that closes the binding pocket within a ribosome, conferring close contact of the drug to its target, therefore improving therapeutic efficacy.Because of its mechanism of action that differs from that of other antimicrobials, cross-resistance to other antibiotic classes is less likely.
3. What Are the Possible Side Effects of Lefamulin?
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have:
♦ severe stomach pain, diarrhea that is watery or bloody (even if it occurs months after your last dose);
♦ low potassium level --leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.
Common side effects may include:
▪ nausea, vomiting, diarrhea;
▪ sleep problems (insomnia);
▪ low potassium;
▪ headache;
▪ abnormal liver function tests; or
▪ pain, bruising, swelling, or irritation where the medicine was injected.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
4. What Other Drugs will Affect Lefamulin?
Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.
Lefamulin can cause a serious heart problem. Your risk may be higher if you also use certain other medicines for infections, asthma, heart problems, high blood pressure, depression, mental illness, cancer, malaria, or HIV.
Many drugs can affect lefamulin. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any medicine you start or stop using.
5. How To Storage Lefamulin?
Consult the product instructions and your pharmacist for storage details. Keep all medications away from children and pets.
Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
【Reference】
[1] Sader HS, Biedenbach DJ, Paukner S, et al. Antimicrobial activity of the investigational pleuromutilin compound BC-3781 tested against Gram-positive organisms commonly associated with acute bacterial skin and skin structure infections. Antimicrob Agents Chemother 2012;56:1619-1623.
[2] File TM, Goldberg L, Das A, et al. Efficacy and safety of IV-to-oral lefamulin, a pleuromutilin antibiotic, for treatment of community-acquired bacterial pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial. Clin Infect Dis 2019;69:1856-1867.
[3] Wicha WW, Prince WT, Lell C, Heilmayer W, Gelone SP: Pharmacokinetics and tolerability of lefamulin following intravenous and oral dosing. J Antimicrob Chemother. 2019 Apr 1;74(Supplement_3):iii19-iii26. doi: 10.1093/jac/dkz087.
[4] Eyal Z, Matzov D, Krupkin M, Paukner S, Riedl R, Rozenberg H, Zimmerman E, Bashan A, Yonath A: A novel pleuromutilin antibacterial compound, its binding mode and selectivity mechanism. Sci Rep. 2016 Dec 13;6:39004. doi: 10.1038/srep39004.