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{{Short description|Antibiotic medication}}
{{drugbox
{{Use dmy dates|date=October 2022}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Verifiedfields = changed
| verifiedrevid = 461095141
| verifiedrevid = 461095141
| image = Ertapenem.svg
| IUPAC_name = (4''R'',5''S'',6''S'')-3-[(3''S'',5''S'')-5-[(3-carboxyphenyl)carbamoyl]<br />pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-<br />oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
| width =
| image = Ertapenem Formula V.1.svg
| alt =
<!--Clinical data-->
| caption =

<!-- Clinical data -->
| pronounce =
| tradename = Invanz
| tradename = Invanz
| Drugs.com = {{drugs.com|monograph|invanz}}
| Drugs.com = {{drugs.com|monograph|ertapenem-sodium}}
| MedlinePlus = a614001
| DailyMedID = Ertapenem
| pregnancy_AU = B3
| pregnancy_AU = B3
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Ertapenem (Invanz) Use During Pregnancy | website=Drugs.com | date=24 January 2020 | url=https://www.drugs.com/pregnancy/ertapenem.html | access-date=29 July 2020}}</ref>
| pregnancy_US = B
| pregnancy_category=
| licence_EU = yes
| legal_AU = S4
| legal_status = Rx-only
| routes_of_administration = [[Intramuscular injection|Intramuscular]], [[intravenous therapy|intravenous]]
| routes_of_administration = [[Intramuscular injection|Intramuscular]], [[intravenous therapy|intravenous]]
| class =
<!--Pharmacokinetic data-->
| ATC_prefix = J01
| ATC_suffix = DH03
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment =<ref>{{cite web | title=INVANZ ertapenem (as sodium) 1g powder for injection vial (81449) | website=Therapeutic Goods Administration (TGA) | date=12 August 2022 | url=https://www.tga.gov.au/resources/artg/81449 | access-date=21 April 2023}}</ref><ref>{{cite web | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-04104-3 | title=TGA eBS - Product and Consumer Medicine Information Licence }}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Invanz 1g powder for concentrate for solution for infusion - Summary of Product Characteristics (SmPC) | website=(emc) | url=https://www.medicines.org.uk/emc/product/1713/smpc | access-date=29 July 2020}}</ref>
| legal_US = Rx-only
| legal_US_comment = <ref name="Invanz FDA label" />
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Invanz EPAR" />
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = 90% ([[intramuscular injection|intramuscular]])
| bioavailability = 90% ([[intramuscular injection|intramuscular]])
| protein_bound = Inversely proportional to concentration; 85 to 95%
| protein_bound = Inversely proportional to concentration; 85 to 95%
| metabolism = Minor [[hydrolysis]] of [[beta-lactam]] ring, [[cytochrome P450|CYP]] not involved
| metabolism = [[Hydrolysis]] of [[beta-lactam]] ring, [[cytochrome P450|CYP]] not involved
| metabolites =
| onset =
| elimination_half-life = 4 hours
| elimination_half-life = 4 hours
| duration_of_action =
| excretion = [[Kidney|Renal]] (80%) and fecal (10%)
| excretion = [[Kidney]] (80%) and [[fecal]] (10%)
<!--Identifiers-->

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 153832-46-3
| CAS_number = 153832-46-3
| ATC_prefix = J01
| ATC_suffix = DH03
| PubChem = 150610
| PubChem = 150610
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00303
| DrugBank = DB00303
Line 37: Line 73:
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1359
| ChEMBL = 1359
| NIAID_ChemDB =
<!--Chemical data-->
| PDB_ligand =
| synonyms =

<!-- Chemical and physical data -->
| IUPAC_name = (4''R'',5''S'',6''S'')-3-[(3''S'',5''S'')-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
| C=22 | H=25 | N=3 | O=7 | S=1
| C=22 | H=25 | N=3 | O=7 | S=1
| smiles = O=C(O)c1cc(ccc1)NC(=O)[C@H]4NC[C@@H](S\C3=C(\N2C(=O)[C@H]([C@H](O)C)[C@H]2[C@H]3C)C(=O)O)C4
| SMILES = O=C(O)c1cc(ccc1)NC(=O)[C@H]4NC[C@@H](S\C3=C(\N2C(=O)[C@H]([C@H](O)C)[C@H]2[C@H]3C)C(=O)O)C4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C22H25N3O7S/c1-9-16-15(10(2)26)20(28)25(16)17(22(31)32)18(9)33-13-7-14(23-8-13)19(27)24-12-5-3-4-11(6-12)21(29)30/h3-6,9-10,13-16,23,26H,7-8H2,1-2H3,(H,24,27)(H,29,30)(H,31,32)/t9-,10-,13+,14+,15-,16-/m1/s1
| StdInChI = 1S/C22H25N3O7S/c1-9-16-15(10(2)26)20(28)25(16)17(22(31)32)18(9)33-13-7-14(23-8-13)19(27)24-12-5-3-4-11(6-12)21(29)30/h3-6,9-10,13-16,23,26H,7-8H2,1-2H3,(H,24,27)(H,29,30)(H,31,32)/t9-,10-,13+,14+,15-,16-/m1/s1
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JUZNIMUFDBIJCM-ANEDZVCMSA-N
| StdInChIKey = JUZNIMUFDBIJCM-ANEDZVCMSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
}}

'''Ertapenem''' is a [[carbapenem]] [[antibiotic]] marketed by [[Merck & Co.|Merck]] as '''Invanz'''.<ref>{{cite journal |vauthors=Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA |title=Carbapenems: past, present, and future |journal=Antimicrob. Agents Chemother. |volume=55 |issue=11 |pages=4943–60 | date=November 2011 |pmid=21859938 |pmc=3195018 |doi=10.1128/AAC.00296-11 |url=}}</ref>
'''Ertapenem''', sold under the brand name '''Invanz''', is a [[carbapenem]] [[antibiotic]] medication used for the treatment of infections of the [[abdomen]], the lungs, the upper part of the [[female reproductive system]], and the [[diabetic foot]].<ref name="AHFS2020" /><ref name="Papp-Wallace">{{cite journal | vauthors = Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA | title = Carbapenems: past, present, and future | journal = Antimicrobial Agents and Chemotherapy | volume = 55 | issue = 11 | pages = 4943–4960 | date = November 2011 | pmid = 21859938 | pmc = 3195018 | doi = 10.1128/AAC.00296-11 | doi-access = free }}</ref>

The most common side effects include diarrhoea, nausea (feeling sick), headache, and problems around the area where the medicine is infused. It can significantly reduce the concentrations of [[valproic acid]], an anti-seizure medication, in the blood to the point where it loses its effectiveness.<ref name="Invanz EPAR" />

Ertapenem was approved for medical use in the United States in November 2001,<ref name="Invanz FDA label" /><ref name="USApproval" /> and in the European Union in April 2002.<ref name="Invanz EPAR" /> It is marketed by [[Merck & Co.|Merck]].<ref name="Invanz FDA label" /><ref name="Invanz EPAR" />


==Medical uses==
==Medical uses==
Ertapenem is used for the treatment of [[Abdominal cavity|intra-abdominal]] infections, [[community-acquired pneumonia]], [[pelvic infection]]s, and [[diabetic foot]] infections, with bacteria that are susceptible to this drug, or expected to be so. It can also be used to prevent infections after [[colorectal surgery]]. It is given as an [[intravenous infusion]] or [[intramuscular injection]]. The drug is not approved for children under three months of age.<ref name="EPAR">{{cite web|url=https://www.ema.europa.eu/en/documents/product-information/invanz-epar-product-information_en.pdf|title=Invanz: EPAR – Product Information|publisher=[[European Medicines Agency]]|date=2019-11-19}}</ref><ref name="Drugs.com">Invanz {{drugs.com|monograph|invanz}}. Retrieved 2020-07-29.</ref>
Ertapenem is indicated for the treatment of [[Abdominal cavity|intra-abdominal]] infections, [[community-acquired pneumonia]], [[pelvic infection]]s, and [[diabetic foot]] infections, with bacteria that are susceptible to this drug, or expected to be so. It can also be used to prevent infections after [[colorectal surgery]]. In the United States it is also indicated for the treatment of complicated [[urinary tract infection]]s including [[pyelonephritis]].<ref name="Invanz FDA label" /><ref name="AHFS2020" /><ref name="EPAR" /> It is a potential effective alternative treatment for [[ceftriaxone]]-resistant [[gonorrhoea]].<ref>{{cite journal | vauthors = de Vries HJ, de Laat M, Jongen VW, Heijman T, Wind CM, Boyd A, de Korne-Elenbaas J, van Dam AP, Schim van der Loeff MF | title = Efficacy of ertapenem, gentamicin, fosfomycin, and ceftriaxone for the treatment of anogenital gonorrhoea (NABOGO): a randomised, non-inferiority trial | journal = The Lancet. Infectious Diseases | volume = 22 | issue = 5 | pages = 706–717 | date = May 2022 | pmid = 35065063 | doi = 10.1016/S1473-3099(21)00625-3 | s2cid = 246129045 }}</ref><ref>{{cite web |title=Antibiotic Ertapenem is alternative drug in treatment of gonorrhea |url=https://www.amsterdamumc.org/en/research/institutes/amsterdam-institute-for-infection-and-immunity/news/antibiotic-ertapenem-is-alternative-drug-in-treatment-of-gonorrhea.htm |website=Amsterdam UMC |access-date=8 July 2022 |date=20 January 2022}}</ref>

It is given as an [[intravenous infusion]] or [[intramuscular injection]]. The drug is not approved for children under three months of age.<ref name="Invanz FDA label">{{cite web | title=Invanz- ertapenem sodium injection, powder, lyophilized, for solution | website=DailyMed | date=13 February 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=33f3b99b-fa82-42e0-26bf-f49891ae3d22 | access-date=29 July 2020}}</ref><ref name="AHFS2020">{{cite web | title=Ertapenem Sodium Monograph for Professionals | publisher=The American Society of Health-System Pharmacists | website=Drugs.com | date=29 June 2020 | url=https://www.drugs.com/monograph/ertapenem-sodium.html | access-date=29 July 2020}}</ref><ref name="EPAR">{{cite web|url=https://www.ema.europa.eu/en/documents/product-information/invanz-epar-product-information_en.pdf|title=Invanz: EPAR – Product Information|publisher=[[European Medicines Agency]]|date=19 November 2019}}</ref>


==Contraindications==
==Contraindications==
The drug is contraindicated in people with known [[hypersensitivity]] to ertapenem or other carbapenem type antibiotics, or severe hypersensitivity reactions (such as [[anaphylaxis]] or severe skin reactions) to other [[beta-lactam antibiotic]]s.<ref name="EPAR" /><ref name="Drugs.com" />
The drug is contraindicated in people with known [[hypersensitivity]] to ertapenem or other carbapenem type antibiotics, or with severe hypersensitivity reactions (such as [[anaphylaxis]] or severe skin reactions) to other [[beta-lactam antibiotic]]s in the past.<ref name="Invanz FDA label" /><ref name="AHFS2020" /><ref name="EPAR" />

==Side effects==
Common side effects are [[diarrhoea]] (in 5% of people receiving ertapenem), [[nausea]] (in 3%) and vomiting, reactions at the injection site (5%, including pain and inflammation of the vein), and headache. Uncommon but possibly serious side effects include [[candida infection]]s, [[seizure]]s, skin reactions such as rashes (including [[nappy rash]] in children), and anaphylaxis.<ref name="EPAR" /><ref name="mediQ" /> Hypersensitivity [[Cross-reactivity#In immunology|cross-reactions]] with [[penicillin]]s are rare.<ref name="Mutschler" />

Ertapenem also can have an effect on some blood tests such as [[liver enzyme]]s and [[platelet count]].<ref name="AHFS2020" /><ref name="EPAR" />


==Overdose==
==Overdose==
Overdosing is unlikely. In adults receiving the threefold therapeutic dose over eight days, no significant toxicity was observed.<ref name="EPAR" />
Overdosing is unlikely. In adults receiving the threefold therapeutic dose over eight days, no significant [[toxicity]] was observed.<ref name="EPAR" />


==Interactions==
== Interactions ==
Drug interactions via the [[cytochrome P450]] enzyme system or the [[P-glycoprotein]] transporter are considered unlikely. However, ertapenem can reduce the concentrations of [[valproic acid]], an [[epilepsy]] medication, by 60% to 100% within 24 hours; this can result in seizures.<ref name="EPAR" /><ref name="mediQ">{{cite web|url=https://www.mediq.ch/|publisher=mediQ|title=Ertapenem|accessdate=2020-07-29}}</ref>


Ertapenem can reduce the concentrations of [[valproic acid]], an [[epilepsy]] medication, by 70% and perhaps up to 95% within 24 hours; this can result in inadequate control of seizures.<ref name="mediQ">{{cite web|url=https://www.mediq.ch/|publisher=mediQ|title=Ertapenem|access-date=29 July 2020}}</ref><ref name="Wu">{{cite journal | vauthors = Wu CC, Pai TY, Hsiao FY, Shen LJ, Wu FL | title = The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/Cilastatin, and Meropenem) on Serum Valproic Acid Concentrations | journal = Therapeutic Drug Monitoring | volume = 38 | issue = 5 | pages = 587–592 | date = October 2016 | pmid = 27322166 | doi = 10.1097/FTD.0000000000000316 | s2cid = 25445129 }}</ref> The effect is described for other carbapenem antibiotics as well, but seems to be most pronounced for ertapenem and [[meropenem]].<ref name="Wu" /> This is likely caused by several mechanisms: carbapenems inhibit transport of valproic acid from the gut into the body; they may increase metabolization of valproic acid to its [[glucuronide]]; they may reduce [[enterohepatic circulation]] and recycling of valproic acid glucuronide by acting against [[gut bacteria]]; and they may block [[transporter protein]]s that pump valproic acid out of [[red blood cell]]s into the [[blood plasma]].<ref>{{cite journal | vauthors = Mancl EE, Gidal BE | title = The effect of carbapenem antibiotics on plasma concentrations of valproic acid | journal = The Annals of Pharmacotherapy | volume = 43 | issue = 12 | pages = 2082–2087 | date = December 2009 | pmid = 19934386 | doi = 10.1345/aph.1M296 | s2cid = 207263641 }}</ref><ref>{{cite book|title=Arzneimittel-Interaktionen|publisher=Österreichischer Apothekerverlag|lang=de|year=2019|isbn=978-3-85200-254-5|page=760}}</ref> The effect is also seen in reverse: in cases where ertapenem has been withdrawn blood concentrations of valproate have been reported to rise.<ref>{{cite book | vauthors = Zaccara G | veditors = Aronson JK |title=Side Effects of Drugs Annual 34: A worldwide yearly survey of new data in adverse drug reactions|chapter-url=https://books.google.com/books?id=7kSIUZtYO0kC&pg=PA121|date=31 December 2012|publisher=Newnes|isbn=978-0-444-59503-4|page=121|chapter=Antiepileptic drugs}}</ref><ref name="Liao Huang Chen 2010">{{cite journal | vauthors = Liao FF, Huang YB, Chen CY | title = Decrease in serum valproic acid levels during treatment with ertapenem | journal = American Journal of Health-System Pharmacy | volume = 67 | issue = 15 | pages = 1260–1264 | date = August 2010 | pmid = 20651316 | doi = 10.2146/ajhp090069 }}</ref>
==References==
{{reflist}}


Drug interactions via the [[cytochrome P450]] enzyme system or the [[P-glycoprotein]] transporter are considered unlikely, as these proteins are not involved in the metabolism of ertapenem.<ref name="EPAR" />
== External links ==

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/ertapenem | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Ertapenem }}
==Pharmacology==
===Mechanism of action===
{{main|β-lactam antibiotic#Mechanism of action}}
Like all beta-lactam antibiotics, ertapenem is [[bactericidal]].<ref name="Mutschler" /> It inhibits cross-linking of the [[peptidoglycan]] layer of bacterial cell walls by blocking a type of [[enzyme]]s called [[penicillin-binding protein]]s (PBPs). When a bacterial cell tries to synthesize new cell wall in order to grow and divide, the attempt fails, rendering the cell vulnerable to [[osmotic]] disruption. Additionally, the surplus of peptidoglycan precursors triggers [[autolytic]] enzymes of the bacterium, which disintegrate the existing wall.<ref>{{cite book | vauthors = Pandey N, Cascella M | chapter = Beta-Lactam Antibiotics | date = June 2023 | title = StatPearls [Internet]. | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 31424895 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK545311/ }}</ref>

[[File:Penicillin spheroplast generation horizontal.svg|thumb|upright=2|Bacteria attempting to grow and divide in the presence of ertapenem shed their cell walls, forming fragile [[spheroplast]]s.<ref>{{cite journal | vauthors = Cushnie TP, O'Driscoll NH, Lamb AJ | title = Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action | journal = Cellular and Molecular Life Sciences | volume = 73 | issue = 23 | pages = 4471–4492 | date = December 2016 | pmid = 27392605 | doi = 10.1007/s00018-016-2302-2 | pmc = 11108400 | hdl-access = free | s2cid = 2065821 | hdl = 10059/2129 }}</ref>]]
{{clear left}}

===Susceptible bacteria===
Bacteria that are normally susceptible to ertapenem treatment (at least in Europe) include:<ref name="EPAR" />
* [[Gram-positive]] [[aerobe]]s
** [[Methicillin]]-susceptible ''[[Staphylococcus]]'' species (including ''[[Staphylococcus aureus]]'')
** ''[[Streptococcus agalactiae]]''
** ''[[Streptococcus pneumoniae]]'' (not established for penicillin-resistant strains)
* [[Gram-negative]] aerobes
** ''[[Escherichia coli]]''
** ''[[Haemophilus influenzae]]''
** ''[[Klebsiella pneumoniae]]''
** ''[[Moraxella catarrhalis]]''
** ''[[Proteus mirabilis]]''
* [[Anaerobe]]s:
** ''[[Clostridium]]'' species (excluding ''[[Clostridioides difficile]]'')
** ''[[Eubacterium]]'' species
** ''[[Fusobacterium]]'' species
** ''[[Peptostreptococcus]]'' species
** ''[[Porphyromonas]] asaccharolytica''
** ''[[Prevotella]]'' species

* The US [[Food and Drug Administration]] (FDA) label specifies activity against additional anaerobes:<ref name="Invanz FDA label" />
** ''[[Bacteroides distasonis]]''
** ''[[Bacteroides fragilis]]''
** ''[[Bacteroides ovatus]]''
** ''[[Bacteroides thetaiotaomicron]]''
** ''[[Bacteroides uniformis]]''

===Resistance===
Bacteria that show no clinically relevant response to ertapenem include methicillin-resistant ''Staphylococcus'' species (including [[Methicillin-resistant Staphylococcus aureus|MRSA]]) as well as ''[[Acinetobacter]]'', ''[[Aeromonas]]'', ''[[Enterococcus]]'', and ''[[Pseudomonas]]''.<ref name="EPAR" /><ref name="Mutschler">{{Cite book| vauthors = Mutschler E |title=Arzneimittelwirkungen |language=German |location= Stuttgart |publisher= Wissenschaftliche Verlagsgesellschaft|year=2013|edition=10th |pages=740, 753|isbn=978-3-8047-2898-1}}</ref>

Microorganisms can become resistant to ertapenem by producing [[carbapenemase]]s, enzymes that inactivate the drug by opening the beta-lactam ring. Other mechanisms of resistance against carbapenems are development of [[efflux pump]]s that transport the antibiotics out of the bacterial cells, mutations of PBPs, and mutations of Gram-negative bacteria's [[porin (protein)|porin]]s which are necessary for carbapenems to enter the bacteria.<ref name="Papp-Wallace" />

===Pharmacokinetics===
[[File:Ertapenem open-ring metabolite.svg|thumb|The main [[metabolite]] in humans, which is pharmacologically inactive<ref name="AHFS2020" /><ref>{{cite web | title = Ertapenem Ring Open Impurity | work = PubChem | publisher = U.S. National Library of Medicine | url = https://pubchem.ncbi.nlm.nih.gov/compound/45105276 | access-date = 30 July 2020 | id = CID 45105276 }}</ref>]]

The route of administration has only a slight effect on the drug's concentrations in the bloodstream: when given as an [[intramuscular injection]], its [[bioavailability]] is 90% (as compared to the 100% availability when given directly into a vein), and its highest concentrations in the [[blood plasma]] are reached after about 2.3 hours. In the blood, 85–95% of ertapenem are bound to [[plasma protein]]s, mostly [[albumin]]. Plasma protein binding is higher for lower concentrations, and vice versa. The drug is only partially [[drug metabolism|metabolized]], with 94% circulating in form of the parent substance and 6% as metabolites. The main metabolite is the inactive [[hydrolysis]] product with the ring opened.<ref name="AHFS2020" />

Ertapenem is mainly eliminated via the kidneys and urine (80%) and to a minor extent via the faeces (10%). Of the 80% found in the urine, 38% is excreted as the parent drug and 37% as the ring-opened metabolite. The [[biological half-life]] is about 3.5 hours in women, 4.2 hours in men and 2.5 hours in children up to 12 years of age.<ref name="AHFS2020" /><ref name="mediQ" />

===Comparison with other antibiotics===
Like all carbapenem antibiotics, ertapenem has a broader spectrum of activity than other beta-lactams like penicillins and [[cephalosporin]]s. Similar to [[doripenem]], [[meropenem]] and [[biapenem]], ertapenem has slightly better activity against many Gram-negative bacteria than other carbapenems such as [[imipenem]]. In contrast to imipenem, doripenem and meropenem, it is not active against ''Enterococcus'', ''Pseudomonas'' and ''Acinetobacter'' species.<ref name="Papp-Wallace" /><ref name="Mutschler" />

For diabetic foot infections, ertapenem as a single treatment or in combination with [[vancomycin]] has been found to be more effective and have fewer side effects than [[tigecycline]], but in severe cases it is less effective than [[piperacillin/tazobactam]].<ref>{{cite journal | vauthors = Selva Olid A, Solà I, Barajas-Nava LA, Gianneo OD, Bonfill Cosp X, Lipsky BA | title = Systemic antibiotics for treating diabetic foot infections | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 9 | pages = CD009061 | date = September 2015 | pmid = 26337865 | pmc = 8504988 | doi = 10.1002/14651858.CD009061.pub2 }}</ref><ref>{{cite journal | vauthors = Tchero H, Kangambega P, Noubou L, Becsangele B, Fluieraru S, Teot L | title = Antibiotic therapy of diabetic foot infections: A systematic review of randomized controlled trials | journal = Wound Repair and Regeneration | volume = 26 | issue = 5 | pages = 381–391 | date = September 2018 | pmid = 30099812 | doi = 10.1111/wrr.12649 | s2cid = 51966152 }}</ref>

Regarding pharmacokinetics, imipenem, doripenem and meropenem have lower plasma protein bindings (up to 25%) and shorter half-lives (about one hour) than ertapenem.<ref name="Mutschler" />

==History==
Ertapenem is marketed by [[Merck & Co.|Merck]]. It was approved for use by the US Food and Drug Administration in November 2001,<ref name="USApproval">{{cite web | title=Drug Approval Package: Invanz I.V. or I.M. (Ertapenem Sodium) NDA #21-337 | website=U.S. [[Food and Drug Administration]] (FDA) | date=20 November 2001 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21337_Invanz.cfm | access-date=29 July 2020}}</ref> and by the [[European Medicines Agency]] in April 2002.<ref name="Invanz EPAR">{{cite web | title=Invanz EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/invanz | access-date=29 July 2020}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite web|url=https://www.ema.europa.eu/en/documents/overview/invanz-epar-summary-public_en.pdf|title=Invanz: EPAR – Summary for the public|publisher=[[European Medicines Agency]]|date=2 December 2016}}</ref>

== References ==
{{reflist}}


{{CephalosporinAntiBiotics}}
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[[Category:Carbapenem antibiotics]]
[[Category:Carbapenem antibiotics]]
[[Category:Benzoic acids]]
[[Category:Benzoic acids]]
[[Category:Anilides]]
[[Category:Anilides]]
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[[Category:Pyrrolidines]]
[[Category:Pyrrolidines]]


{{antiinfective-drug-stub}}

Latest revision as of 21:52, 20 October 2024

Ertapenem
Clinical data
Trade namesInvanz
AHFS/Drugs.comMonograph
MedlinePlusa614001
License data
Pregnancy
category
Routes of
administration		Intramuscular, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability90% (intramuscular)
Protein bindingInversely proportional to concentration; 85 to 95%
MetabolismHydrolysis of beta-lactam ring, CYP not involved
Elimination half-life4 hours
ExcretionKidney (80%) and fecal (10%)
Identifiers
  • (4R,5S,6S)-3-[(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC22H25N3O7S
Molar mass475.52 g·mol−1
3D model (JSmol)
  • O=C(O)c1cc(ccc1)NC(=O)[C@H]4NC[C@@H](S\C3=C(\N2C(=O)[C@H]([C@H](O)C)[C@H]2[C@H]3C)C(=O)O)C4
  • InChI=1S/C22H25N3O7S/c1-9-16-15(10(2)26)20(28)25(16)17(22(31)32)18(9)33-13-7-14(23-8-13)19(27)24-12-5-3-4-11(6-12)21(29)30/h3-6,9-10,13-16,23,26H,7-8H2,1-2H3,(H,24,27)(H,29,30)(H,31,32)/t9-,10-,13+,14+,15-,16-/m1/s1 checkY
  • Key:JUZNIMUFDBIJCM-ANEDZVCMSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Ertapenem, sold under the brand name Invanz, is a carbapenem antibiotic medication used for the treatment of infections of the abdomen, the lungs, the upper part of the female reproductive system, and the diabetic foot.[7][8]

The most common side effects include diarrhoea, nausea (feeling sick), headache, and problems around the area where the medicine is infused. It can significantly reduce the concentrations of valproic acid, an anti-seizure medication, in the blood to the point where it loses its effectiveness.[6]

Ertapenem was approved for medical use in the United States in November 2001,[5][9] and in the European Union in April 2002.[6] It is marketed by Merck.[5][6]

Medical uses

[edit]

Ertapenem is indicated for the treatment of intra-abdominal infections, community-acquired pneumonia, pelvic infections, and diabetic foot infections, with bacteria that are susceptible to this drug, or expected to be so. It can also be used to prevent infections after colorectal surgery. In the United States it is also indicated for the treatment of complicated urinary tract infections including pyelonephritis.[5][7][10] It is a potential effective alternative treatment for ceftriaxone-resistant gonorrhoea.[11][12]

It is given as an intravenous infusion or intramuscular injection. The drug is not approved for children under three months of age.[5][7][10]

Contraindications

[edit]

The drug is contraindicated in people with known hypersensitivity to ertapenem or other carbapenem type antibiotics, or with severe hypersensitivity reactions (such as anaphylaxis or severe skin reactions) to other beta-lactam antibiotics in the past.[5][7][10]

Side effects

[edit]

Common side effects are diarrhoea (in 5% of people receiving ertapenem), nausea (in 3%) and vomiting, reactions at the injection site (5%, including pain and inflammation of the vein), and headache. Uncommon but possibly serious side effects include candida infections, seizures, skin reactions such as rashes (including nappy rash in children), and anaphylaxis.[10][13] Hypersensitivity cross-reactions with penicillins are rare.[14]

Ertapenem also can have an effect on some blood tests such as liver enzymes and platelet count.[7][10]

Overdose

[edit]

Overdosing is unlikely. In adults receiving the threefold therapeutic dose over eight days, no significant toxicity was observed.[10]

Interactions

[edit]

Ertapenem can reduce the concentrations of valproic acid, an epilepsy medication, by 70% and perhaps up to 95% within 24 hours; this can result in inadequate control of seizures.[13][15] The effect is described for other carbapenem antibiotics as well, but seems to be most pronounced for ertapenem and meropenem.[15] This is likely caused by several mechanisms: carbapenems inhibit transport of valproic acid from the gut into the body; they may increase metabolization of valproic acid to its glucuronide; they may reduce enterohepatic circulation and recycling of valproic acid glucuronide by acting against gut bacteria; and they may block transporter proteins that pump valproic acid out of red blood cells into the blood plasma.[16][17] The effect is also seen in reverse: in cases where ertapenem has been withdrawn blood concentrations of valproate have been reported to rise.[18][19]

Drug interactions via the cytochrome P450 enzyme system or the P-glycoprotein transporter are considered unlikely, as these proteins are not involved in the metabolism of ertapenem.[10]

Pharmacology

[edit]

Mechanism of action

[edit]
Main article: β-lactam antibiotic § Mechanism of action

Like all beta-lactam antibiotics, ertapenem is bactericidal.[14] It inhibits cross-linking of the peptidoglycan layer of bacterial cell walls by blocking a type of enzymes called penicillin-binding proteins (PBPs). When a bacterial cell tries to synthesize new cell wall in order to grow and divide, the attempt fails, rendering the cell vulnerable to osmotic disruption. Additionally, the surplus of peptidoglycan precursors triggers autolytic enzymes of the bacterium, which disintegrate the existing wall.[20]

Bacteria attempting to grow and divide in the presence of ertapenem shed their cell walls, forming fragile spheroplasts.[21]

Susceptible bacteria

[edit]

Bacteria that are normally susceptible to ertapenem treatment (at least in Europe) include:[10]

Resistance

[edit]

Bacteria that show no clinically relevant response to ertapenem include methicillin-resistant Staphylococcus species (including MRSA) as well as Acinetobacter, Aeromonas, Enterococcus, and Pseudomonas.[10][14]

Microorganisms can become resistant to ertapenem by producing carbapenemases, enzymes that inactivate the drug by opening the beta-lactam ring. Other mechanisms of resistance against carbapenems are development of efflux pumps that transport the antibiotics out of the bacterial cells, mutations of PBPs, and mutations of Gram-negative bacteria's porins which are necessary for carbapenems to enter the bacteria.[8]

Pharmacokinetics

[edit]
The main metabolite in humans, which is pharmacologically inactive[7][22]

The route of administration has only a slight effect on the drug's concentrations in the bloodstream: when given as an intramuscular injection, its bioavailability is 90% (as compared to the 100% availability when given directly into a vein), and its highest concentrations in the blood plasma are reached after about 2.3 hours. In the blood, 85–95% of ertapenem are bound to plasma proteins, mostly albumin. Plasma protein binding is higher for lower concentrations, and vice versa. The drug is only partially metabolized, with 94% circulating in form of the parent substance and 6% as metabolites. The main metabolite is the inactive hydrolysis product with the ring opened.[7]

Ertapenem is mainly eliminated via the kidneys and urine (80%) and to a minor extent via the faeces (10%). Of the 80% found in the urine, 38% is excreted as the parent drug and 37% as the ring-opened metabolite. The biological half-life is about 3.5 hours in women, 4.2 hours in men and 2.5 hours in children up to 12 years of age.[7][13]

Comparison with other antibiotics

[edit]

Like all carbapenem antibiotics, ertapenem has a broader spectrum of activity than other beta-lactams like penicillins and cephalosporins. Similar to doripenem, meropenem and biapenem, ertapenem has slightly better activity against many Gram-negative bacteria than other carbapenems such as imipenem. In contrast to imipenem, doripenem and meropenem, it is not active against Enterococcus, Pseudomonas and Acinetobacter species.[8][14]

For diabetic foot infections, ertapenem as a single treatment or in combination with vancomycin has been found to be more effective and have fewer side effects than tigecycline, but in severe cases it is less effective than piperacillin/tazobactam.[23][24]

Regarding pharmacokinetics, imipenem, doripenem and meropenem have lower plasma protein bindings (up to 25%) and shorter half-lives (about one hour) than ertapenem.[14]

History

[edit]

Ertapenem is marketed by Merck. It was approved for use by the US Food and Drug Administration in November 2001,[9] and by the European Medicines Agency in April 2002.[6][25]

References

[edit]
  1. ^ "Ertapenem (Invanz) Use During Pregnancy". Drugs.com. 24 January 2020. Retrieved 29 July 2020.
  2. ^ "INVANZ ertapenem (as sodium) 1g powder for injection vial (81449)". Therapeutic Goods Administration (TGA). 12 August 2022. Retrieved 21 April 2023.
  3. ^ "TGA eBS - Product and Consumer Medicine Information Licence".
  4. ^ "Invanz 1g powder for concentrate for solution for infusion - Summary of Product Characteristics (SmPC)". (emc). Retrieved 29 July 2020.
  5. ^ a b c d e f g "Invanz- ertapenem sodium injection, powder, lyophilized, for solution". DailyMed. 13 February 2020. Retrieved 29 July 2020.
  6. ^ a b c d e "Invanz EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 29 July 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. ^ a b c d e f g h "Ertapenem Sodium Monograph for Professionals". Drugs.com. The American Society of Health-System Pharmacists. 29 June 2020. Retrieved 29 July 2020.
  8. ^ a b c Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA (November 2011). "Carbapenems: past, present, and future". Antimicrobial Agents and Chemotherapy. 55 (11): 4943–4960. doi:10.1128/AAC.00296-11. PMC 3195018. PMID 21859938.
  9. ^ a b "Drug Approval Package: Invanz I.V. or I.M. (Ertapenem Sodium) NDA #21-337". U.S. Food and Drug Administration (FDA). 20 November 2001. Retrieved 29 July 2020.
  10. ^ a b c d e f g h i "Invanz: EPAR – Product Information" (PDF). European Medicines Agency. 19 November 2019.
  11. ^ de Vries HJ, de Laat M, Jongen VW, Heijman T, Wind CM, Boyd A, et al. (May 2022). "Efficacy of ertapenem, gentamicin, fosfomycin, and ceftriaxone for the treatment of anogenital gonorrhoea (NABOGO): a randomised, non-inferiority trial". The Lancet. Infectious Diseases. 22 (5): 706–717. doi:10.1016/S1473-3099(21)00625-3. PMID 35065063. S2CID 246129045.
  12. ^ "Antibiotic Ertapenem is alternative drug in treatment of gonorrhea". Amsterdam UMC. 20 January 2022. Retrieved 8 July 2022.
  13. ^ a b c "Ertapenem". mediQ. Retrieved 29 July 2020.
  14. ^ a b c d e Mutschler E (2013). Arzneimittelwirkungen (in German) (10th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 740, 753. ISBN 978-3-8047-2898-1.
  15. ^ a b Wu CC, Pai TY, Hsiao FY, Shen LJ, Wu FL (October 2016). "The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/Cilastatin, and Meropenem) on Serum Valproic Acid Concentrations". Therapeutic Drug Monitoring. 38 (5): 587–592. doi:10.1097/FTD.0000000000000316. PMID 27322166. S2CID 25445129.
  16. ^ Mancl EE, Gidal BE (December 2009). "The effect of carbapenem antibiotics on plasma concentrations of valproic acid". The Annals of Pharmacotherapy. 43 (12): 2082–2087. doi:10.1345/aph.1M296. PMID 19934386. S2CID 207263641.
  17. ^ Arzneimittel-Interaktionen (in German). Österreichischer Apothekerverlag. 2019. p. 760. ISBN 978-3-85200-254-5.
  18. ^ Zaccara G (31 December 2012). "Antiepileptic drugs". In Aronson JK (ed.). Side Effects of Drugs Annual 34: A worldwide yearly survey of new data in adverse drug reactions. Newnes. p. 121. ISBN 978-0-444-59503-4.
  19. ^ Liao FF, Huang YB, Chen CY (August 2010). "Decrease in serum valproic acid levels during treatment with ertapenem". American Journal of Health-System Pharmacy. 67 (15): 1260–1264. doi:10.2146/ajhp090069. PMID 20651316.
  20. ^ Pandey N, Cascella M (June 2023). "Beta-Lactam Antibiotics". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID 31424895.
  21. ^ Cushnie TP, O'Driscoll NH, Lamb AJ (December 2016). "Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action". Cellular and Molecular Life Sciences. 73 (23): 4471–4492. doi:10.1007/s00018-016-2302-2. hdl:10059/2129. PMC 11108400. PMID 27392605. S2CID 2065821.
  22. ^ "Ertapenem Ring Open Impurity". PubChem. U.S. National Library of Medicine. CID 45105276. Retrieved 30 July 2020.
  23. ^ Selva Olid A, Solà I, Barajas-Nava LA, Gianneo OD, Bonfill Cosp X, Lipsky BA (September 2015). "Systemic antibiotics for treating diabetic foot infections". The Cochrane Database of Systematic Reviews. 2015 (9): CD009061. doi:10.1002/14651858.CD009061.pub2. PMC 8504988. PMID 26337865.
  24. ^ Tchero H, Kangambega P, Noubou L, Becsangele B, Fluieraru S, Teot L (September 2018). "Antibiotic therapy of diabetic foot infections: A systematic review of randomized controlled trials". Wound Repair and Regeneration. 26 (5): 381–391. doi:10.1111/wrr.12649. PMID 30099812. S2CID 51966152.
  25. ^ "Invanz: EPAR – Summary for the public" (PDF). European Medicines Agency. 2 December 2016.
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