Meropenem

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Meropenem
Meropenem.svg
Meropenem-from-xtal-1992-3D-balls.png
Clinical data
Trade names Merrem, others
AHFS/Drugs.com Monograph
Pregnancy
category
  • AU: B2
  • US: B (No risk in non-human studies)
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability 100%
Protein binding Approximately 2%
Biological half-life 1 hour
Excretion Renal
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.170.691
Chemical and physical data
Formula C17H25N3O5S
Molar mass 383.464 g/mol
3D model (JSmol)
  (verify)

Meropenem, sold under the brandname Merrem among others, is an broad-spectrum antibiotic used to treat a wide variety of infections. It is a β-lactam and belongs to the subgroup of carbapenems, similar to imipenem and ertapenem.

Meropenem was developed by Dainippon Sumitomo Pharma and patented in 1983.[1][2][3] It gained US FDA approval in July 1996. It penetrates well into many tissues and body fluids, including cerebrospinal fluid, bile, heart valve, lung, and peritoneal fluid.[4] It was initially marketed by AstraZeneca. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[5]

Medical uses[edit]

The spectrum of action includes many Gram-positive and Gram-negative bacteria (including Pseudomonas) and anaerobic bacteria. The overall spectrum is similar to that of imipenem, although meropenem is more active against Enterobacteriaceae and less active against Gram-positive bacteria. It works against extended-spectrum β-lactamases, but may be more susceptible to metallo-β-lactamases.[4] Meropenem is frequently given in the treatment of febrile neutropenia. This condition frequently occurs in patients with hematological malignancies and cancer patients receiving anticancer drugs that suppress bone marrow formation. It is approved for complicated skin and skin structure infections, complicated intra-abdominal infections and bacterial meningitis.

In 2017 the FDA granted approval for the combination of meropenem and vaborbactam to treat adults with complicated urinary tract infections.[6]

Administration[edit]

Meropenem is administered intravenously as a white crystalline powder to be dissolved in 5% monobasic potassium phosphate solution. Dosing must be adjusted for altered kidney function and for haemofiltration.[7]

Side effects[edit]

The most common adverse effects are diarrhea (4.8%), nausea and vomiting (3.6%), injection-site inflammation (2.4%), headache (2.3%), rash (1.9%) and thrombophlebitis (0.9%).[8] Many of these adverse effects were observed in severely ill individuals already taking many medications including vancomycin.[9][10] One study showed Clostridium difficile-associated diarrhea happened in 3.6% of meropenem patients.[11] Meropenem has a reduced potential for seizures in comparison with imipenem. Several cases of severe hypokalemia have been reported.[12][13] Meropenem, like other carbopenems, is a potent inducer of multidrug resistance in bacteria.

Pharmacology[edit]

Mechanism of action[edit]

Meropenem is bactericidal except against Listeria monocytogenes, where it is bacteriostatic. It inhibits bacterial wall synthesis like other β-lactam antibiotics. In contrast to other beta-lactams, it is highly resistant to degradation by β-lactamases or cephalosporinases. In general, resistance arises due to mutations in penicillin-binding proteins, production of metallo-β-lactamases, or resistance to diffusion across the bacterial outer membrane.[8] Unlike imipenem, it is stable to dehydropeptidase-1, so can be given without cilastatin.

In 2016 a synthetic peptide-conjugated PMO (PPMO) was found to inhibit the expression of New Delhi Metallo-beta-lactamase, an enzyme that many drug-resistant bacteria use to destroy carbapenems.[14][15]

Society and culture[edit]

Trade names[edit]

Trade names
Country Name Maker
India Inzapenum Dream India
Aurobindo Pharma
Penmer Biocon
Meronir Nirlife
Merowin Strides Acrolab
Aktimer Aktimas Biopharmaceuticals
Neopenem Neomed
Mexopen Samarth life sciences
Meropenia SYZA Health Sciences LLP
Ivpenem Medicorp Pharmaceuticals
Merofit
Lykapiper Lyka Labs
Winmero Parabolic drugs
Pharmaceuticals
Bangladesh I-Penam Incepta
Merocil Pharmacil
Indonesia Merofen Kalbe
Brazil Zylpen Aspen Pharma
Japan, Korea Meropen
Australia Merem
Taiwan Mepem
Germany Meronem
US Meronem AstraZeneca
... Merosan Sanbe Farma
Merobat Interbat
Zwipen
Carbonem
Ronem Opsonin Pharma, BD
Neopenem
Merocon Continental
Carnem Laderly Biotech
Penro Bosch
Meroza German Remedies
Merotrol Lupin)
Meromer Orchid Chemicals
Mepenox BioChimico
Meromax Eurofarma

References[edit]

  1. ^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 490. ISBN 9783527607495. 
  2. ^ Edwards, JR; Turner, PJ; Wannop, C; Withnell, ES; Grindey, AJ; Nairn, K (February 1989). "In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I". Antimicrobial Agents and Chemotherapy. 33 (2): 215–22. PMC 171460Freely accessible. PMID 2655530. doi:10.1128/AAC.33.2.215. 
  3. ^ "Creation of Meropen® - Story of the Creation of Pharmaceuticals - Research and Development". Sumitomo Dainippon Pharma. 
  4. ^ a b AHFS Drug Information (2006 ed.). American Society of Health-System Pharmacists. 2006. 
  5. ^ "WHO Model List of Essential Medicines (20th List)" (PDF). World Health Organization. March 2017. Retrieved 29 June 2017. 
  6. ^ Commissioner, Office of the. "Press Announcements - FDA approves new antibacterial drug". www.fda.gov. 
  7. ^ Bilgrami, I; Roberts, JA; Wallis, SC; Thomas, J; Davis, J; Fowler, S; Goldrick, PB; Lipman, J (July 2010). "Meropenem dosing in critically ill patients with sepsis receiving high-volume continuous venovenous hemofiltration". Antimicrobial Agents and Chemotherapy. 54 (7): 2974–8. PMC 2897321Freely accessible. PMID 20479205. doi:10.1128/AAC.01582-09. 
  8. ^ a b Mosby's Drug Consult 2006 (16 ed.). Mosby, Inc. 2006. 
  9. ^ Erden, M; Gulcan, E; Bilen, A; Bilen, Y; Uyanik, A; Keles, M (7 March 2013). "Pancytopenýa and Sepsýs due to Meropenem: A Case Report" (PDF). Tropical Journal of Pharmaceutical Research. 12 (1). doi:10.4314/tjpr.v12i1.21. 
  10. ^ "Meropenem side effects - from FDA reports". eHealthMe. 
  11. ^ Yeung, EYH; Gore JG; Auersperg EV (2012). "A Retrospective Analysis of the Incidence of Clostridium Difficile Associated Diarrhea with Meropenem and Piperacillin-tazobactam" (PDF). International Journal of Collaborative Research on Internal Medicine & Public Health. 4 (8): 1567–1576. 
  12. ^ Margolin, L (2004). "Impaired rehabilitation secondary to muscle weakness induced by meropenem". Clinical drug investigation. 24 (1): 61–2. PMID 17516692. doi:10.2165/00044011-200424010-00008. 
  13. ^ Bharti, R; Gombar, S; Khanna, AK (2010). "Meropenem in critical care - uncovering the truths behind weaning failure". Journal of Anaesthesiology Clinical Pharmacology. 26 (1): 99–101. 
  14. ^ "New molecule knocks out superbugs' immunity to antibiotics". newatlas.com. Retrieved 2017-01-25. 
  15. ^ K., Sully, Erin; L., Geller, Bruce; Lixin, Li,; M., Moody, Christina; M., Bailey, Stacey; L., Moore, Amy; Michael, Wong,; Patrice, Nordmann,; M., Daly, Seth. "Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo". Journal of Antimicrobial Chemotherapy. doi:10.1093/jac/dkw476/2691388/peptide-conjugated-phosphorodiamidate-morpholino. 

External links[edit]