Meropenem
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| Clinical data |
| Trade names |
Merrem, others |
| AHFS/Drugs.com |
Monograph |
Pregnancy
category |
- AU: B2
- US: B (No risk in non-human studies)
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Routes of
administration |
Intravenous |
| ATC code |
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| Legal status |
| Legal status |
- AU: S4 (Prescription only)
- UK: POM (Prescription only)
- US: ℞-only
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| Pharmacokinetic data |
| Bioavailability |
100% |
| Protein binding |
Approximately 2% |
| Biological half-life |
1 hour |
| Excretion |
Renal |
| Identifiers |
IUPAC name
- (4R,5S,6S)-3-(((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-yl)thio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
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| CAS Number |
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| PubChem CID |
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| DrugBank |
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| ChemSpider |
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| UNII |
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| KEGG |
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| ChEBI |
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| ChEMBL |
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| PDB ligand |
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| ECHA InfoCard |
100.170.691 |
| Chemical and physical data |
| Formula |
C17H25N3O5S |
| Molar mass |
383.464 g/mol |
| 3D model (JSmol) |
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SMILES
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O=C3N2\C(=C(\S[C@H]1C[C@@H](C(=O)N(C)C)NC1)[C@H](C)[C@@H]2[C@H]3[C@H](O)C)C(=O)O
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InChI
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InChI=1S/C17H25N3O5S/c1-7-12-11(8(2)21)16(23)20(12)13(17(24)25)14(7)26-9-5-10(18-6-9)15(22)19(3)4/h7-12,18,21H,5-6H2,1-4H3,(H,24,25)/t7-,8-,9+,10+,11-,12-/m1/s1 Y
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Key:DMJNNHOOLUXYBV-PQTSNVLCSA-N Y
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| (verify) |
Meropenem, sold under the brandname Merrem among others, is a broad-spectrum antibiotic used to treat a variety of bacterial infections.[1] Some of these include meningitis, intraabdominal infection, pneumonia, sepsis, and anthrax.[1] It is given by injection into a vein.[1]
Common side effects include nausea, diarrhea, constipation, headache, rash, and pain at the site of infection.[1] Serious side effects include Clostridium difficile infection, seizures, and allergic reactions including anaphylaxis.[1] Those who are allergic to other β-lactam antibiotics are more likely to be allergic to meropenem.[1] Use in pregnancy appears to be safe.[1] It is in the carbapenem family of medications.[1] Meropenem usually results in bacterial death through blocking their ability to make a cell wall.[1]
Meropenem was patented in 1983.[2] It was approved for medical use in the United States in 1996.[1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] The wholesale cost is the developing world is between 3.44 and 20.58 USD per one gram vial as of 2015.[4] In the United Kingdom this amount costs the NHS about 16 pound in 2015.[5]
Contents
- 1 Medical uses
- 2 Side effects
- 3 Pharmacology
- 4 Society and culture
- 5 References
- 6 External links
Medical uses
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.[6] 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.[7]
Administration
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.[8]
Side effects
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%).[9] Many of these adverse effects were observed in severely ill individuals already taking many medications including vancomycin.[10][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 carbapenems, is a potent inducer of multidrug resistance in bacteria.
Pharmacology
Mechanism of action
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.[9] 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
Trade names
Trade names
| Country |
Name |
Maker |
| India |
Inzapenum |
Dream India |
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Aurobindo Pharma |
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Penmer |
Biocon |
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Meronir |
Nirlife |
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Merowin |
Strides Acrolab |
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Aktimer |
Aktimas Biopharmaceuticals |
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Neopenem |
Neomed |
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Mexopen |
Samarth life sciences |
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Meropenia |
SYZA Health Sciences LLP |
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Ivpenem |
Medicorp Pharmaceuticals |
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Merofit |
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Lykapiper |
Lyka Labs |
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Winmero |
Parabolic drugs |
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Pharmaceuticals |
| Bangladesh |
I-Penam |
Incepta |
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Merocil |
Pharmacil |
| Indonesia |
Merofen |
Kalbe |
| Brazil |
Zylpen |
Aspen Pharma |
| Japan, Korea |
Meropen |
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| Australia |
Merem |
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| Taiwan |
Mepem |
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| Germany |
Meronem |
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| US |
Meronem |
AstraZeneca |
| ... |
Merosan |
Sanbe Farma |
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Merobat |
Interbat |
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Zwipen |
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Carbonem |
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Ronem |
Opsonin Pharma, BD |
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Neopenem |
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Merocon |
Continental |
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Carnem |
Laderly Biotech |
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Penro |
Bosch |
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Meroza |
German Remedies |
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Merotrol |
Lupin) |
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Meromer |
Orchid Chemicals |
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Mepenox |
BioChimico |
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Meromax |
Eurofarma |
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Meropex |
Apex Pharma Ltd. |
References
- ^ a b c d e f g h i j "Meropenem". The American Society of Health-System Pharmacists. Retrieved 8 December 2017.
- ^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 497. ISBN 9783527607495.
- ^ "WHO Model List of Essential Medicines (20th List)" (PDF). World Health Organization. March 2017. Retrieved 29 June 2017.
- ^ "Single Drug Information". International Medical Products Price Guide. Retrieved 9 December 2017.
- ^ British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 379. ISBN 9780857111562.
- ^ AHFS Drug Information (2006 ed.). American Society of Health-System Pharmacists. 2006.
- ^ Commissioner, Office of the. "Press Announcements - FDA approves new antibacterial drug". www.fda.gov.
- ^ 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. doi:10.1128/AAC.01582-09. PMC 2897321 . PMID 20479205.
- ^ a b Mosby's Drug Consult 2006 (16 ed.). Mosby, Inc. 2006.
- ^ 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.
- ^ "Meropenem side effects - from FDA reports". eHealthMe.
- ^ Margolin, L (2004). "Impaired rehabilitation secondary to muscle weakness induced by meropenem". Clinical drug investigation. 24 (1): 61–2. doi:10.2165/00044011-200424010-00008. PMID 17516692.
- ^ 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.
- ^ "New molecule knocks out superbugs' immunity to antibiotics". newatlas.com. Retrieved 2017-01-25.
- ^ 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
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Antibiotics active on the cell wall and envelope (J01C-J01D)
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| Intracellular |
- Inhibit peptidoglycan subunit synthesis and transport: NAM synthesis inhibition (Fosfomycin)
- DADAL/AR inhibitors (Cycloserine)
- bactoprenol inhibitors (Bacitracin)
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| Glycopeptide |
- Inhibit PG chain elongation: Vancomycin# (Oritavancin
- Telavancin)
- Teicoplanin (Dalbavancin)
- Ramoplanin
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β-lactams/
(inhibit PBP
cross-links) |
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| Other |
- polymyxins/detergent
- depolarizing
- Hydrolyze NAM-NAG
- Tyrothricin
- Isoniazid#
- Teixobactin
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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