Ceftazidime/avibactam: Difference between revisions
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{{Drugbox |
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| Verifiedfields = changed |
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| verifiedrevid = |
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| image = Ceftazidime and avibactam.svg |
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<!--Combo data--> |
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| type = combo |
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| component1 = Ceftazidime |
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| class1 = [[Cephalosporin]] [[antibiotic]] |
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| component2 = Avibactam |
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| class2 = [[Beta-lactamase inhibitor|β-lactamase inhibitor]] |
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<!--Clinical data--> |
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| tradename = Avycaz, Zavicefta, others<ref name=FDA2015>{{cite web|title=Briefing package: ceftazidime-avibactam. Anti-infective drugs advisory committee meeting|url=http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM425458.pdf|publisher=U.S. [[Food and Drug Administration]] (FDA)|accessdate=27 June 2015|archive-url=https://web.archive.org/web/20150630120131/http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM425458.pdf|archive-date=30 June 2015|url-status=dead}}</ref> |
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| Drugs.com = {{drugs.com|monograph|ceftazidime-and-avibactam-sodium}} |
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| MedlinePlus = a615018 |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_US = B |
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| pregnancy_category = |
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| licence_EU = yes |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> |
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| legal_US = Rx-only |
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| legal_status = |
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| routes_of_administration = [[Intravenous therapy|Intravenous infusion]] |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = |
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| ATC_prefix = J01 |
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| ATC_suffix = DD52 |
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| PubChem = 90643431 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = |
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| KEGG = D10779 |
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<!--Chemical data--> |
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}} |
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<!-- Definition and medical uses --> |
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'''Ceftazidime/avibactam''', sold under the brand name '''Avycaz''' among others, is a [[combination medication]] composed of [[ceftazidime]], a [[cephalosporin antibiotic]], and [[avibactam]], a [[Beta-lactamase inhibitor|β-lactamase inhibitor]].<ref name=AHFS2019>{{cite web |title=Ceftazidime and Avibactam Sodium Monograph for Professionals |url=https://www.drugs.com/monograph/ceftazidime-and-avibactam-sodium.html |website=Drugs.com |accessdate=25 October 2019 |language=en}}</ref> It is used to treat complicated [[intra abdominal infections]], [[urinary tract infections]], and [[pneumonia]].<ref name=AHFS2019/><ref name=WHO2019>{{cite web |title=Application for inclusion of ceftazidime-avibactam |url=https://www.who.int/selection_medicines/committees/expert/22/applications/s6.2_new-antibiotics-AWaRe.pdf?ua=1 |website=WHO |accessdate=25 October 2019}}</ref> It is only recommended when other options are not appropriate.<ref name=AHFS2019/> It is given by injection into a vein.<ref name=AHFS2019/> |
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<!-- Side effects and mechanism --> |
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Common side effect include nausea, fever, liver problems, headache, trouble sleeping, and pain at the site of injection.<ref name=AHFS2019/> Severe side effects may include [[anaphylaxis]], [[seizures]], and [[Clostridium difficile-associated diarrhea|''Clostridium difficile''-associated diarrhea]].<ref name=AHFS2019/> While use appears to be safe in [[pregnancy]] the medication has not been well studied in this group.<ref name=Preg2019>{{cite web |title=Avibactam / ceftazidime (Avycaz) Use During Pregnancy |url=https://www.drugs.com/pregnancy/avibactam-ceftazidime.html |website=Drugs.com |accessdate=25 October 2019 |language=en}}</ref> Doses should be adjusted in those with [[kidney problems]].<ref name=PT2016/> Ceftazidime works by interfering with the building of the [[bacterial cell wall]] well avibactam works by preventing ceftazidime's breakdown.<ref name=AHFS2019/> |
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<!-- History and culture --> |
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The combination was approved for medical use in the United States and Europe in 2015.<ref name=AHFS2019/><ref name=WHO2019/> The combination is on the [[World Health Organization's List of Essential Medicines]], the safest and most effective medicines needed in a [[health system]].<ref name="WHO21st">{{cite document |title=World Health Organization model list of essential medicines: 21st list 2019 |date=2019|hdl=10665/325771 |last1=Organization|first1=World Health}}</ref> In the United States a course of treatment generally costs between US$7,500 to US$15,000 as of 2016.<ref name=PT2016>{{cite journal |last1=Mosley JF |first1=2nd |last2=Smith |first2=LL |last3=Parke |first3=CK |last4=Brown |first4=JA |last5=Wilson |first5=AL |last6=Gibbs |first6=LV |title=Ceftazidime-Avibactam (Avycaz): For the Treatment of Complicated Intra-Abdominal and Urinary Tract Infections. |journal=P & T : A Peer-reviewed Journal for Formulary Management |date=August 2016 |volume=41 |issue=8 |pages=479–83 |pmid=27504064|pmc=4959616 }}</ref> In the United Kingdom this amount costs the NHS about £1,800 to £3,600 as of 2019.<ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=X|edition=76}}</ref> |
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==Medical use== |
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Ceftazidime/avibactam is used to treat certain [[Multiple drug resistance|multidrug-resistant]] [[Gram-negative bacteria|gram-negative]] infections.<ref>{{cite journal |vauthors=Lagacé-Wiens P, Walkty A, Karlowsky JA |title=Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections |journal=Core Evid |volume=9 |issue= |pages=13–25 |year=2014 |pmid=24493994 |pmc=3908787 |doi=10.2147/CE.S40698 |url=}}</ref> |
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Ceftazidime/avibactam is used for the treatment of: |
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* complicated intra-abdominal infections. In these cases it is often used in combination with [[metronidazole]], which provides coverage for anaerobic pathogens.<ref name=PT2016/> |
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* complicated [[urinary tract infections]], including acute [[pyelonephritis]], in adults. |
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* hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.<ref>https://www.allergan.com/assets/pdf/avycaz_pi</ref> |
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===Bacterial activity=== |
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For many bacterial infections, it offers little or no advantage over ceftazidime monotherapy, due to the widespread expression of resistance mechanisms other than β-lactamase production. These include ''Haemophilus'', ''Moraxella'' and ''Neisseria'' pathogens, and infections caused by ''Acinectobacter baumannii''.<ref>{{cite journal |vauthors=Lagacé-Wiens P, Walkty A, Karlowsky JA |title=Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections |journal=Core Evid |volume=9 |issue= |pages=13–25 |year=2014 |pmid=24493994 |pmc=3908787 |doi=10.2147/CE.S40698 |url=}}</ref> |
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The antibacterial spectrum of ceftazidime/avibactam includes nearly all [[Enterobacteriaceae]], including ceftazidime-resistant strains. The activity of ceftazidime/avibactam against the important hospital pathogen ''Pseudomonas aeruginosa'' is variable, due to the potential presence of other resistance mechanisms in addition to β-lactamase production. Synergy was observed for avibactam with ceftazidime in the ''Burkholderia cepacia'' complex.<ref>{{cite journal |vauthors=Mushtaq S, Warner M, Livermore DM |title=In vitro activity of ceftazidime+NXL104 against Pseudomonas aeruginosa and other non-fermenters |journal=J Antimicrob Chemother |volume=65 |issue=11 |pages=2376–2381 |year=2010 |doi=10.1093/jac/dkq306 |pmid=20801783}}</ref> |
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==Adverse events== |
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When used to treat life-threatening infections, ceftazidime/avibactam is more likely than carbapenem antibiotics to cause serious adverse events, including worsening kidney function and gastrointestinal adverse effects.<ref>{{cite journal |vauthors=Sternbach N, Leibovici Weissman Y, Avni T, Yahav D |title=Efficacy and safety of ceftazidime/avibactam: a systematic review and meta-analysis |journal=J. Antimicrob. Chemother. |volume=73 |issue=8 |pages=2021–2029 |date=August 2018 |pmid=29659836 |doi=10.1093/jac/dky124 |url=}}</ref> |
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==Mechanism of action== |
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Bacterial resistance to cephalosporins is often due to bacterial production of [[Beta-lactamase|β-lactamase enzymes]] that deactivate these antibiotics. Avibactam inhibits some (but not all) bacterial ß-lactamases. Also, some bacteria are resistant to cephalosporins by other mechanisms, and therefore avibactam doesn't work. Avibactam is not active against [[New Delhi metallo-beta-lactamase 1|New Delhi metallo-β-lactamase 1]] (NDM-1).<ref>{{cite journal |vauthors=Lohans CT, Brem J, Schofield CJ |title=New Delhi Metallo-β-Lactamase 1 Catalyzes Avibactam and Aztreonam Hydrolysis |journal=Antimicrob. Agents Chemother. |volume=61 |issue=12 |pages= |date=December 2017 |pmid=28971873 |pmc=5700305 |doi=10.1128/AAC.01224-17 |url=}}</ref> Avibactam inhibits ''[[Klebsiella pneumoniae]]'' [[Beta-lactamase#Carbapenemases|carbapenemases]] (KPCs), and [[Beta-lactamase#AmpC-type .CE.B2-lactamases .28Class C.29|AmpC-type β-lactamases]], which are resistant to the other clinically-available β-lactamases, [[tazobactam]] and [[clavulanic acid]].<ref>{{cite web |url=http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000MedR.pdf |title=Clinical Review, NDA 206494, Ceftazidime-avibactam |publisher=Food and Drug Administration (FDA) |date=2015-02-18 }}</ref> |
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== Regulatory == |
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It was granted approval for marketing in the United States by the Food and Drug Administration (FDA) in February 2015.<ref>{{cite web | url=https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/206494Orig1s000ltr.pdf | title=AVYCAZ (ceftazidime-avibactam) approval letter | date=2015-02-25 | access-date=September 10, 2019 | publisher=Food and Drug Administration (FDA) }}</ref> It was granted approval for marketing in [[Europe]] by the [[European Medicines Agency]] in 2016. During its clinical development, ceftazidime/avibactam was designated as a Qualified Infectious Disease Product under the [[Generating Antibiotic Incentives Now]] provision of the [[Food and Drug Administration Safety and Innovation Act]].<ref>{{Cite press release|title = FDA approves new antibacterial drug Avycaz|url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm435629.htm|publisher = Food and Drug Administration (FDA)|accessdate = 2015-11-16|archive-url = https://web.archive.org/web/20151117082448/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm435629.htm|archive-date = 2015-11-17|url-status = dead}}</ref><ref>{{Cite web|title = FDA clears Actavis' combination antibacterial Avycaz|url = http://www.firstwordpharma.com/node/1265732 |website = FirstWord Pharma|accessdate = 2015-11-16}}</ref> Development of ceftazidime/avibactam was [[Fast track (FDA)|fast-tracked]] by the FDA due to the shortage of drugs for treatment of infections due to antibiotic-resistant bacteria.{{cn|date=September 2019}} |
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==References== |
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{{reflist}} |
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==External links== |
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{{commons category|Avibactam}} |
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* [https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d9c2803f-dc9c-4b19-b4a3-8303bc8c15fd DailyMed by the NIH] |
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{{Beta-lactam antibiotics}} |
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{{Portal bar|Pharmacy and pharmacology|Medicine}} |
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{{DEFAULTSORT:Avibactam ceftazidime}} |
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[[Category:Combination antibiotics]] |
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[[Category:World Health Organization essential medicines]] |
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[[Category:RTT]] |
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Revision as of 12:12, 14 November 2019
