Ceftriaxone: Difference between revisions
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{{Short description|Antibiotic medication}} |
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{{Use dmy dates|date=March 2024}} |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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{{Drugbox |
{{Drugbox |
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| Watchedfields = changed |
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| verifiedrevid = 443510921 |
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| verifiedrevid = 460025108 |
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| IUPAC_name = (6''R'',7''R'')-7-{[(2''Z'')-2-(2-amino-1,3-thiazol-4-yl)->2-(methoxyimino)acetyl]amino}-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid |
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| drug_name = |
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| image = Ceftriaxone structure.png |
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| image = Ceftriaxone-skeletal.svg |
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| width = 200 |
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| alt = |
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| image2 = Ceftriaxone-from-PDB-6XQV-3D-bs-17.png |
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| alt2 = |
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<!--Clinical data--> |
<!-- Clinical data --> |
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| pronounce = {{IPAc-en|ˌ|s|ɛ|f|t|r|aɪ|ˈ|æ|k|s|oʊ|n}} |
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| tradename = Rocephin |
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| tradename = Rocephin, Epicephin, Wintriaxone, others |
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| Drugs.com = {{drugs.com|monograph|rocephin}} |
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| Drugs.com = {{drugs.com|monograph|Ceftriaxone_Sodium}} |
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| MedlinePlus = a685032 |
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| DailyMedID = Ceftriaxone |
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| pregnancy_AU = B1 |
| pregnancy_AU = B1 |
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| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Ceftriaxone (Rocephin) Use During Pregnancy | website=Drugs.com | date=12 December 2019 | url=https://www.drugs.com/pregnancy/ceftriaxone.html | access-date=24 December 2019 | archive-date=23 August 2016 | archive-url=https://web.archive.org/web/20160823194224/https://www.drugs.com/pregnancy/ceftriaxone.html | url-status=live }}</ref> |
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| pregnancy_US = B |
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| legal_AU = S4 |
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| routes_of_administration = [[Intravenous therapy|Intravenous]], [[Intramuscular injection|intramuscular]] |
| routes_of_administration = [[Intravenous therapy|Intravenous]], [[Intramuscular injection|intramuscular]] |
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| class = [[Third-generation cephalosporin]] |
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| ATC_prefix = J01 |
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| ATC_suffix = DD04 |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024 | archive-date=6 July 2023 | archive-url=https://web.archive.org/web/20230706023149/https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | url-status=live }}</ref> |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F--> |
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| legal_BR_comment = |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled--> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US_comment = |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV--> |
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| legal_UN_comment = |
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| legal_status = <!--For countries not listed above--> |
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<!--Pharmacokinetic data--> |
<!--Pharmacokinetic data--> |
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| bioavailability = n/a |
| bioavailability = n/a |
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| metabolism = Negligible |
| metabolism = Negligible |
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| elimination_half-life = 5.8–8.7 hours<ref name="pmid3906584">{{cite journal | vauthors = Beam TR | title = Ceftriaxone: a beta-lactamase-stable, broad-spectrum cephalosporin with an extended half-life | journal = Pharmacotherapy | volume = 5 | issue = 5 | pages = 237–253 | date = 1985 | pmid = 3906584 | doi = 10.1002/j.1875-9114.1985.tb03423.x | s2cid = 25559476 }}</ref> |
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| elimination_half-life = 5.8–8.7 hours |
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| excretion = 33–67% [[ |
| excretion = 33–67% [[kidney]], 35–45% [[biliary]] |
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<!--Identifiers--> |
<!--Identifiers--> |
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| IUPHAR_ligand = 5326 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 73384-59-5 |
| CAS_number = 73384-59-5 |
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| ATC_prefix = J01 |
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| ATC_suffix = DD04 |
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| PubChem = 5479530 |
| PubChem = 5479530 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 161 |
| ChEMBL = 161 |
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<!--Chemical data--> |
<!--Chemical data--> |
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| IUPAC_name = (6''R'',7''R'')-7-{[(2''Z'')-2-(2-amino-1,3-thiazol-4-yl)->2-(methoxyimino)acetyl]amino}-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid |
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| C=18 | H=18 | N=8 | O=7 | S=3 |
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| C=18 | H=18 | N=8 | O=7 | S=3 |
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| molecular_weight = 554.58 [[Gram|g]]/[[Mole (unit)|mol]] |
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| |
| SMILES = O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(=O)C(=N\OC)/c3nc(sc3)N)CS\C4=N\C(=O)C(=O)NN4C)C(=O)O |
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| InChI = 1/C18H18N8O7S3/c1-25-18(22-12(28)13(29)23-25)36-4-6-3-34-15-9(14(30)26(15)10(6)16(31)32)21-11(27)8(24-33-2)7-5-35-17(19)20-7/h5,9,15H,3-4H2,1-2H3,(H2,19,20)(H,21,27)(H,23,29)(H,31,32)/b24-8-/t9-,15-/m1/s1 |
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| InChIKey = VAAUVRVFOQPIGI-SPQHTLEEBA |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C18H18N8O7S3/c1-25-18(22-12(28)13(29)23-25)36-4-6-3-34-15-9(14(30)26(15)10(6)16(31)32)21-11(27)8(24-33-2)7-5-35-17(19)20-7/h5,9,15H,3-4H2,1-2H3,(H2,19,20)(H,21,27)(H,23,29)(H,31,32)/b24-8-/t9-,15-/m1/s1 |
| StdInChI = 1S/C18H18N8O7S3/c1-25-18(22-12(28)13(29)23-25)36-4-6-3-34-15-9(14(30)26(15)10(6)16(31)32)21-11(27)8(24-33-2)7-5-35-17(19)20-7/h5,9,15H,3-4H2,1-2H3,(H2,19,20)(H,21,27)(H,23,29)(H,31,32)/b24-8-/t9-,15-/m1/s1 |
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| StdInChIKey = VAAUVRVFOQPIGI-SPQHTLEESA-N |
| StdInChIKey = VAAUVRVFOQPIGI-SPQHTLEESA-N |
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}} |
}} |
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<!-- Definition and medical uses --> |
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'''Ceftriaxone''' ([[International Nonproprietary Name|INN]]) ({{IPAc-en|icon|ˌ|s|ɛ|f|t|r|aɪ|ˈ|æ|k|s|oʊ|n}}) is a third-generation [[cephalosporin]] [[antibiotic]]. Like other third-generation cephalosporins, it has broad spectrum activity against [[Gram-positive bacteria|Gram-positive]] and [[Gram-negative bacteria|Gram-negative]] [[bacteria]]. In most cases, it is considered to be equivalent to [[cefotaxime]] in terms of safety and efficacy. Ceftriaxone sodium is marketed by [[Hoffman-La Roche]] under the [[trade name]] '''Rocephin'''. |
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'''Ceftriaxone''', sold under the brand name '''Rocephin''', is a third-generation [[Cephalosporin|cephalosporin antibiotic]] used for the treatment of a number of [[bacterial infection]]s.<ref name=AHFS2016/> These include [[acute otitis media|middle ear infections]], [[endocarditis]], [[meningitis]], [[pneumonia]], bone and joint infections, intra-abdominal infections, skin infections, [[urinary tract infections]], [[gonorrhea]], and [[pelvic inflammatory disease]].<ref name=AHFS2016/> It is also sometimes used before surgery and following a [[bite wound]] to try to prevent infection.<ref name=AHFS2016/> Ceftriaxone can be given by [[intravenous|injection into a vein]] or [[intramuscular injection|into a muscle]].<ref name=AHFS2016>{{Cite web|title = Ceftriaxone Sodium Monograph for Professionals |publisher=Drugs.com |url = https://www.drugs.com/monograph/ceftriaxone-sodium.html| access-date = 27 August 2016|url-status = live|archive-url = https://web.archive.org/web/20160531224338/http://www.drugs.com/monograph/ceftriaxone-sodium.html|archive-date = 31 May 2016}}</ref> |
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<!-- Side effects and mechanism --> |
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== Clinical use == |
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Common side effects include pain at the site of injection and [[allergic reaction]]s.<ref name=AHFS2016/> Other possible side effects include [[C. difficile associated diarrhea|''C. difficile''-associated diarrhea]], [[hemolytic anemia]], [[gall bladder disease]], and [[seizures]].<ref name=AHFS2016/> It is not recommended in those who have had [[anaphylaxis]] to [[penicillin]] but may be used in those who have had milder reactions.<ref name=AHFS2016/> The intravenous form should not be given with intravenous [[calcium]].<ref name=AHFS2016/> There is tentative evidence that ceftriaxone is relatively safe during pregnancy and breastfeeding.<ref name="Drugs.com pregnancy" /> It is a [[Cephalosporin#Classification|third-generation cephalosporin]] that works by preventing bacteria from making a [[cell wall]].<ref name=AHFS2016/> |
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{{Main|Cephalosporin}} |
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<!-- History, society, and culture --> |
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Ceftriaxone is often used (in combination, but not direct, with [[macrolide]] and/or [[aminoglycoside]] antibiotics) for the treatment of community-acquired or mild to moderate health care-associated [[pneumonia]]. It is also a choice drug for treatment of [[bacterial meningitis]]. In pediatrics, it is commonly used in [[febrile]] infants between 4 and 8 weeks of age who are admitted to the hospital to exclude [[sepsis]]. |
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Ceftriaxone was patented in 1978 and approved for medical use in 1982.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=495 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA495 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=AHFS2016/> |
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The dosage for acute ear infection in the very young is 50 mg/kg IM, one dose only. It has also been used in the treatment of [[Lyme disease]], [[typhoid fever]] and [[gonorrhea]].{{Citation needed|date=November 2009}} |
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== Medical use == |
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Intravenous dosages may be adjusted for body mass in younger patients and is administered every 12–24 hours, at a dose that depends on the type and severity of the infection. |
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[[Image:Цефтриаксон.JPG|thumb|A vial of ceftriaxone, manufactured and sold in Russia]] |
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Ceftriaxone and other third-generation cephalosporin antibiotics are used to treat organisms that tend to be resistant to many other antibiotics.<ref name="Katzung-2012">{{Cite book | vauthors = Katzung B, Masters S, Trevor A |title = Basic and Clinical Pharmacology |publisher = McGraw-Hill|year = 2012|isbn = 978-0-07-176402-5|pages = 797–801 }}</ref> Due to emergent resistance, ceftriaxone should not be used for the treatment of ''[[Enterobacter]]'' infections.<ref name="Katzung-2012" /> Before using ceftriaxone, it is important to determine the susceptibility of the bacteria.<ref name="DailyMed-2019">{{cite web | title=Ceftriaxone- ceftriaxone sodium injection, powder, for solution | website=DailyMed | date=31 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5cd2d96f-83e5-4326-ae87-d0ede4ba493a | access-date=1 February 2020|url-status = live|archive-url = https://web.archive.org/web/20151117032102/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61c6334c-d6fe-4663-ad29-eaee8dc169a6 |archive-date = 17 November 2015}}</ref> If sepsis is being considered, empiric therapy may be initiated prior to susceptibility testing.<ref name="Katzung-2012" /> |
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For the treatment of [[gonorrhea]], a single intramuscular injection is usually given. Treatment for [[chlamydia infection]] is also recommended (usually with [[azithromycin]]) unless it is specifically ruled out.<ref>{{cite web |url=http://cme.medscape.com/viewarticle/555228 |last=Barclay |first=Laurie |title=CDC issues new treatment recommendations for gonorrhea |publisher=[[Medscape]] |date=April 16, 2007 |accessdate=2009-07-01}}</ref><!-- need verify dual treatment - surely patients also swabbed specifically for chlamydia as well as a general swab ? --> |
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Medical uses include:<ref name="DailyMed-2019"/> |
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It must not be mixed or administered simultaneously (within 48 hours) with calcium-containing solutions or products for patients younger than 28 days old,<ref>{{cite web|url=http://healthcare.utah.edu/pharmacy/alerts/243.htm|title=FDA Updates warning on Ceftriaxone-Calcium injection}}</ref> even via different infusion lines (rare fatal cases of calcium-ceftriaxone precipitates in lung and kidneys in [[neonates]] have been described).<ref>{{cite journal |title=Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events |journal=Pediatrics |volume=123 |issue=4 |year=2009 |month= April |pages=e609–13 |pmid=19289450 |author1=Bradley JS |author2=Wassel RT |author3=Lee L |author4=Nambiar S |author-separator=, |author-name-separator= |doi=10.1542/peds.2008-3080}}</ref> |
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* [[lower respiratory tract infection]]s |
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* acute bacterial [[otitis media]] |
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* skin and skin structure infections |
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* [[urinary tract infection]]s |
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* uncomplicated [[gonorrhea]] |
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* [[pelvic inflammatory disease]] |
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* bacterial [[sepsis]] |
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* intra-abdominal infections |
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* [[meningitis]] |
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* surgical prophylaxis |
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* [[Lyme disease]]<ref name=AHFS2016/> |
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Ceftriaxone is also a choice drug for treatment of [[bacterial meningitis]] caused by [[pneumococci]], [[meningococci]], ''[[Haemophilus influenzae]]'', and "susceptible enteric Gram-negative rods, but not ''[[Listeria monocytogenes]]''."<ref name="Katzung 2009 783–7842">{{cite book| vauthors = Katzung B |title = Basic and Clinical Pharmacology, Eleventh Edition|date = 2009|publisher = McGraw-Hill|location = New York|isbn = 978-0-07-160405-5|pages = 783–784}}</ref> |
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To reduce the pain of intramuscular injection, ceftriaxone may be reconstituted with 1% [[lidocaine]].<ref>{{cite journal |title=Lidocaine as a diluent for ceftriaxone in the treatment of gonorrhea. Does it reduce the pain of the injection? |journal=Arch Pediatr Adolesc Med |volume=148 |issue=1 |pages=72–5 |year=1994 |month=January |pmid=8143016 |author1=Schichor A |author2=Bernstein B |author3=Weinerman H |author4=Fitzgerald J |author5=Yordan E |author6=Schechter N |author-separator=, |author-name-separator=}}</ref> |
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In combination with [[doxycycline]] or [[azithromycin]], ceftriaxone used to be recommended by the United States [[Centers for Disease Control and Prevention]] (CDC) for the treatment of uncomplicated [[gonorrhea]]. Due to increased risk of developing azithromycin resistant strains and the high efficacy of higher doses of ceftriaxone the guidance has been updated to mono-antibiotic therapy with a higher dose of ceftriaxone.<ref>{{cite journal | vauthors = St Cyr S, Barbee L, Workowski KA, Bachmann LH, Pham C, Schlanger K, Torrone E, Weinstock H, Kersh EN, Thorpe P | title = Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 69 | issue = 50 | pages = 1911–1916 | date = December 2020 | pmid = 33332296 | pmc = 7745960 | doi = 10.15585/mmwr.mm6950a6 }}</ref> |
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Ceftriaxone has also been investigated for efficacy in preventing relapse to cocaine addiction.<ref>{{cite journal |title=Ceftriaxone restores glutamate homeostasis and prevents relapse to cocaine-seeking |journal=Biol Psychiatry |year=2009 |month=August |pmid=19717140 |author1=Knackstedt LA |author2=Melendez RI |author3=Kalivas PW |author-separator=, |author-name-separator= |doi=10.1016/j.biopsych.2009.07.018 |volume=67 |issue=1 |pages=81–4 |pmc=2795043}}</ref> |
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=== Spectrum of activity === |
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Ceftriaxone seems to increase [[EAAT2]] pump expression in central nervous system and has therefore a potential to reduce glutamatergic toxicity<ref>{{cite journal |title=Mechanism of Ceftriaxone Induction of Excitatory Amino Acid Transporter-2 Expression and Glutamate Uptake in Primary Human Astrocytes |journal=The Journal of Biological Chemistry |year=2008 |doi=10.1074/jbc.M707697200 |volume=283 |pages=13116–13123 |pmid=18326497 |pmc=2442320 |author=Lee SG, Su ZZ, Emdad L, Gupta P, Sarkar D, Borjabad A, Volsky DJ, Fisher PB |issue=19}}</ref>. Despite earlier negative results in 1990s, new, large clinical trials are underway to test its effacy in [[Amyotrophic lateral sclerosis]] (ALS) patients. |
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Like other third-generation cephalosporins, ceftriaxone is active against ''[[Citrobacter]]'' spp., ''[[Serratia marcescens]]'', and beta-lactamase-producing strains of ''[[Haemophilus]]'' and ''[[Neisseria]]''.<ref name="Katzung-2012" /> However, unlike [[ceftazidime]] and [[cefoperazone]], ceftriaxone does not have useful activity against ''[[Pseudomonas aeruginosa]]''.<ref name="Katzung-2012" /> It is generally not active against ''[[Enterobacter]]'' species, and its use should be avoided in the treatment of ''Enterobacter'' infections, even if the isolate appears susceptible, because of the emergence of resistance.<ref name="Katzung-2012" /> Some organisms, such as ''Citrobacter'', ''[[Providencia (bacterium)|Providencia]]'', and ''[[Serratia]]'', have the ability to become resistant through the development of [[cephalosporinase]]s (enzymes that [[hydrolysis|hydrolyze]] cephalosporins and render them inactive).<ref name="Katzung-2012" /> |
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Although not being used as first line therapy against ''Staphylococcus aureus'', ceftriaxone retains activity against isolates of methicillin-susceptible ''S. aureus'' and is used in clinic for infections sustained by this bacterium. In this case the dose should be doubled (e.g. 2 g intravenously every 12 hours).<ref>{{Cite journal | vauthors = Di Bella S, Gatti M, Principe L |date=29 April 2023 |title=Ceftriaxone for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia: a matter of dosages? |journal=European Journal of Clinical Microbiology & Infectious Diseases |volume=42 |issue=7 |pages=917–918 |language=en |doi=10.1007/s10096-023-04612-x |pmid=37119346 |s2cid=258423746 |issn=1435-4373}}</ref> |
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=== Available forms === |
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Ceftriaxone is available for administration via the [[intramuscular]] or the [[intravenous]] routes.<ref name="DailyMed-2019"/> Ceftriaxone is stored as a dry powder in a vial, and is reconstituted (dissolved) immediately before use. The solution is used promptly after preparation, still, reconstituted solutions retain their physical and chemical stability for 24 hours at 25°C (or for 3 days when stored between 2 and 8°C).<ref name="tevanz">https://web.archive.org/web/20231206072711/https://www.medsafe.govt.nz/profs/datasheet/c/ceftriaxoneinjDEVA.pdf {{Bare URL PDF|date=August 2024}}</ref> The solutions are pale yellowish in color,<ref name="tevanz"/> but the change of color to amber or reddish suggests hydrolysis of the [[amide bond]] of the β-lactam ring, thereby affecting the antimicrobial activity of the antibiotic.<ref name="pmid23163348">{{cite journal |vauthors=Palzkill T |title=Metallo-β-lactamase structure and function |journal=Ann N Y Acad Sci |volume=1277 |issue= 1|pages=91–104 |date=January 2013 |pmid=23163348 |pmc=3970115 |doi=10.1111/j.1749-6632.2012.06796.x|bibcode=2013NYASA1277...91P }}</ref> Diluents containing calcium are not used to reconstitute ceftriaxone, and it must not be administered in intravenous lines containing other calcium-containing solutions, as a ceftriaxone-calcium precipitate could form.<ref name="DailyMed-2019"/><ref>https://web.archive.org/web/20230813180009/https://www.pbm.va.gov/PBM/vacenterformedicationsafety/nationalpbmbulletin/CeftriaxoneNationalPBMBulletin.pdf {{Bare URL PDF|date=August 2024}}</ref> This precipitation risk is particularly high in newborns (up to age 28 days), especially if they are premature or have impaired bilirubin binding.<ref>{{cite web | url=https://www.gov.uk/drug-safety-update/ceftriaxone-rocephin-incompatible-with-solutions-containing-calcium | archive-url=https://web.archive.org/web/20231208090719/https://www.gov.uk/drug-safety-update/ceftriaxone-rocephin-incompatible-with-solutions-containing-calcium | archive-date=8 December 2023 | title=Ceftriaxone (Rocephin): Incompatible with solutions containing calcium }}</ref><ref>https://web.archive.org/web/20240222194630/https://www.hpra.ie/docs/default-source/Safety-Notices/ceftriaxone---march-2010---final.pdf {{Bare URL PDF|date=August 2024}}</ref> |
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=== Specific populations === |
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====Pregnancy==== |
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Ceftriaxone is pregnancy category B {{clarify|date=February 2024}}.<ref name="DailyMed-2019"/><ref name="Drugs.com pregnancy" /> It has not been observed to cause birth defects in animal studies, but a lack of well-controlled studies done in pregnant women exists.<ref name="DailyMed-2019"/> |
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====Breastfeeding==== |
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Low concentrations of ceftriaxone are excreted in [[breast milk]] that are "not expected to cause adverse effects in breastfed infants."<ref>{{Cite web|title = TOXNET|url = http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed:@term+@DOCNO+57|website = toxnet.nlm.nih.gov|access-date = 4 November 2015|url-status = dead|archive-url = https://web.archive.org/web/20170908213423/https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed%253A%2540term+%2540DOCNO+57|archive-date = 8 September 2017}}</ref>{{Failed verification|date=May 2020}} The manufacturer recommends that caution be exercised when administering ceftriaxone to women who breastfeed.<ref name="DailyMed-2019"/> |
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==== Newborns ==== |
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[[Hyperbilirubinemia|Hyperbilirubinemic]] [[neonates]] are contraindicated for the use of ceftriaxone.<ref name="DailyMed-2019"/> It can compete with [[bilirubin]] and displace it from binding to [[Human serum albumin|albumin]], increasing the risk of bilirubin [[encephalopathy]].<ref name="DailyMed-2019"/> |
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==== Elderly ==== |
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According to the package insert, clinical studies did not |
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show differences in efficacy and safety of ceftriaxone in geriatrics compared to younger patients but "greater sensitivity of some older individuals cannot be ruled out."<ref name="DailyMed-2019"/> |
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== Adverse effects == |
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Although generally well tolerated, the most common adverse reactions associated with ceftriaxone are changes in white blood cell counts, local reactions at site of administration, rash, and diarrhea.<ref name="Roche" /> |
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Incidence of adverse effects greater than 1%: |
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* [[Eosinophilia]] (6%) |
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* [[Thrombocytosis]] (5.1%) |
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* Elevations in [[liver enzyme]]s (3.1–3.3%) |
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* Diarrhea (2.7%) |
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* [[Leukopenia]] (2.1%) |
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* Elevation in [[Blood urea nitrogen|BUN]] (1.2%) |
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* Local reactions: pain, tenderness, irritation (1%) |
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* Rash (1.7%)<ref name="Roche" /> |
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Some less frequently reported adverse events (incidence < 1%) include [[phlebitis]], itchiness, fever, chills, nausea, vomiting, elevations of [[bilirubin]], elevations in [[creatinine]], headache and dizziness.<ref name="Roche" /> |
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Ceftriaxone may precipitate in bile, causing [[biliary sludge]], [[biliary pseudolithiasis]], and [[gallstone]]s, especially in children. [[Hypoprothrombinemia|Hypoprothrombinaemia]] and bleeding are specific side effects. Haemolysis is reported.<ref name="pmid2227290">{{cite journal | vauthors = Shiffman ML, Keith FB, Moore EW | title = Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility | journal = Gastroenterology | volume = 99 | issue = 6 | pages = 1772–1778 | date = December 1990 | pmid = 2227290 | doi = 10.1016/0016-5085(90)90486-K }}</ref><ref>{{cite journal | vauthors = Shrimali JD, Patel HV, Gumber MR, Kute VB, Shah PR, Vanikar AV, Trivedi HL | title = Ceftriaxone induced immune hemolytic anemia with disseminated intravascular coagulation | journal = Indian Journal of Critical Care Medicine | volume = 17 | issue = 6 | pages = 394–395 | date = November 2013 | pmid = 24501497 | pmc = 3902580 | doi = 10.4103/0972-5229.123465 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Guleria VS, Sharma N, Amitabh S, Nair V | title = Ceftriaxone-induced hemolysis | journal = Indian Journal of Pharmacology | volume = 45 | issue = 5 | pages = 530–531 | date = Sep–Oct 2013 | pmid = 24130395 | pmc = 3793531 | doi = 10.4103/0253-7613.117758 | doi-access = free }}</ref> It has also been reported to cause post kidney failure in children.<ref>{{cite journal | vauthors = Li N, Zhou X, Yuan J, Chen G, Jiang H, Zhang W | title = Ceftriaxone and acute renal failure in children | journal = Pediatrics | volume = 133 | issue = 4 | pages = e917–e922 | date = April 2014 | pmid = 24664092 | doi = 10.1542/peds.2013-2103 | s2cid = 2854637 | url = https://publications.aap.org/pediatrics/article-pdf/133/4/e917/1099407/peds_2013-2103.pdf | access-date = 22 February 2024 | archive-date = 22 February 2024 | archive-url = https://web.archive.org/web/20240222203721/https://publications.aap.org/pediatrics/article-pdf/133/4/e917/1099407/peds_2013-2103.pdf | url-status = live }}</ref> Like other antibiotics, ceftriaxone use can result in [[Clostridium difficile colitis|''Clostridioides difficile'']]-associated diarrhea ranging from mild diarrhea to fatal colitis.<ref name="Roche" /> In this regard it has been reported that shifting from ceftriaxone to [[cefotaxime]] would have a lower impact on ''C. difficile'' infection rates, since cefotaxime is almost entirely excreted by the kidneys <ref>{{cite journal | vauthors = Patel KB, Nicolau DP, Nightingale CH, Quintiliani R | title = Pharmacokinetics of cefotaxime in healthy volunteers and patients | journal = Diagnostic Microbiology and Infectious Disease | volume = 22 | issue = 1–2 | pages = 49–55 | date = May 1995 | pmid = 7587050 | doi = 10.1016/0732-8893(95)00072-I }}</ref> while ceftriaxone has a 45% biliary excretion <ref>{{cite journal | vauthors = Guggenbichler JP, Allerberger FJ, Dierich M | title = Influence of cephalosporines III generation with varying biliary excretion on fecal flora and emergence of resistant bacteria during and after cessation of therapy | journal = Padiatrie und Padologie | volume = 21 | issue = 4 | pages = 335–342 | date = 1986 | pmid = 3562044 | url = https://pubmed.ncbi.nlm.nih.gov/3562044/ | access-date = 29 April 2023 | archive-date = 29 April 2023 | archive-url = https://web.archive.org/web/20230429154021/https://pubmed.ncbi.nlm.nih.gov/3562044/ | url-status = live }}</ref> |
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===Contraindications=== |
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Ceftriaxone should not be used in those with an allergy to ceftriaxone or any component of the formulation. Although there is negligible cross-reactivity between penicillins and third-generation cephalosporins,<ref name="Katzung 2009 783–7842" /><ref>{{Cite web|title = The Use of Cephalosporins in Penicillin-allergic Patients|url = http://www.medscape.com/viewarticle/764042|website = www.medscape.com|access-date = 10 November 2015|url-status = live|archive-url = https://web.archive.org/web/20151114135258/http://www.medscape.com/viewarticle/764042|archive-date = 14 November 2015}}</ref> caution should still be used when using ceftriaxone in penicillin-sensitive patients.<ref name="Roche">{{Cite web|url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050585s061lbl.pdf|title = Rocephin Prescribing Information|access-date = 1 November 2015|publisher = Roche|url-status = live|archive-url = https://web.archive.org/web/20160304055415/http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050585s061lbl.pdf|archive-date = 4 March 2016}}</ref> Caution should be used in people who have had previous severe penicillin allergies.<ref name="Roche" /> It should not be used in hyperbilirubinemic neonates, particularly those who are premature because ceftriaxone is reported to displace bilirubin from albumin binding sites, potentially causing bilirubin encephalopathy. Concomitant use with intravenous calcium-containing solutions/products in neonates (≤28 days) is contraindicated <ref>{{cite web|url = http://healthcare.utah.edu/pharmacy/alerts/243.htm|title = FDA Updates warning on Ceftriaxone-Calcium injection|url-status = live|archive-url = https://web.archive.org/web/20091128093447/http://healthcare.utah.edu/pharmacy/alerts/243.htm|archive-date = 28 November 2009}}</ref> even if administered through different infusion lines due to rare fatal cases of calcium-ceftriaxone precipitations in neonatal lungs and kidneys.<ref name="Roche" /><ref>{{cite journal | vauthors = Bradley JS, Wassel RT, Lee L, Nambiar S | title = Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events | journal = Pediatrics | volume = 123 | issue = 4 | pages = e609–e613 | date = April 2009 | pmid = 19289450 | doi = 10.1542/peds.2008-3080 | s2cid = 22718923 | url = https://publications.aap.org/pediatrics/article-pdf/123/4/e609/1022852/zpe0040900e609.pdf | access-date = 22 February 2024 | archive-date = 22 February 2024 | archive-url = https://web.archive.org/web/20240222203720/https://publications.aap.org/pediatrics/article-pdf/123/4/e609/1022852/zpe0040900e609.pdf | url-status = live }}</ref> |
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==Mechanism of action== |
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Ceftriaxone is a third-generation antibiotic from the [[cephalosporin]] family of antibiotics.<ref name="Katzung-2012"/> It is within the [[β-lactam antibiotic|β-lactam family of antibiotics]]. Ceftriaxone selectively and irreversibly inhibits bacterial cell wall synthesis by binding to transpeptidases, also called transamidases, which are [[Penicillin binding proteins|penicillin-binding proteins]] (PBPs) that catalyze the cross-linking of the [[peptidoglycan]] polymers forming the bacterial cell wall.<ref name="Lippincott Williams & Wilkins-2013">{{Cite book|title = Foye's Principles of Medicinal Chemistry|publisher = Lippincott Williams & Wilkins|year = 2013|isbn = 978-1-60913-345-0|location = Philadelphia, PA|pages = 1093–1094, 1099–1100| veditors = Lemke TL, Williams DA |edition = Seventh}}</ref> The peptidoglycan cell wall is made up of pentapeptide units attached to a polysaccharide backbone with alternating units of N-acetylglucosamine and N-acetylmuramic acid.<ref>{{cite journal | vauthors = van Heijenoort J | title = Formation of the glycan chains in the synthesis of bacterial peptidoglycan | journal = Glycobiology | volume = 11 | issue = 3 | pages = 25R–36R | date = March 2001 | pmid = 11320055 | doi = 10.1093/glycob/11.3.25r | s2cid = 46066256 | doi-access = free }}</ref><ref name="Scheffers-2005">{{cite journal | vauthors = Scheffers DJ, Pinho MG | title = Bacterial cell wall synthesis: new insights from localization studies | journal = Microbiology and Molecular Biology Reviews | volume = 69 | issue = 4 | pages = 585–607 | date = December 2005 | pmid = 16339737 | pmc = 1306805 | doi = 10.1128/MMBR.69.4.585-607.2005 }}</ref> PBPs act on a terminal D-alanyl-D-alanine moiety on a pentapeptide unit and catalyze the formation of a peptide bond between the penultimate D-alanine and a glycine unit on an adjacent peptidoglycan strand, releasing the terminal D-alanine unit in the process.<ref name="Lippincott Williams & Wilkins-2013"/><ref name="Scheffers-2005" /> The structure of ceftriaxone mimics the D-alanyl-D-alanine moiety, and the PBP attacks the beta-lactam ring in ceftriaxone as if it were its normal D-alanyl-D-alanine substrate.<ref name="Lippincott Williams & Wilkins-2013"/> The [[peptidoglycan]] cross-linking activity of PBPs is a construction and repair mechanism that normally helps to maintain bacterial cell wall integrity, so the inhibition of PBPs leads to damage and destruction of the cell wall and eventually to cell lysis.<ref name="Lippincott Williams & Wilkins-2013"/> |
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==Pharmacokinetics== |
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'''Absorption:''' Ceftriaxone can be administered intravenously and intramuscularly, and the drug is completely absorbed.<ref name="DailyMed-2019"/><ref>{{cite journal | vauthors = Patel IH, Kaplan SA | title = Pharmacokinetic profile of ceftriaxone in man | journal = The American Journal of Medicine | volume = 77 | issue = 4C | pages = 17–25 | date = October 1984 | pmid = 6093513 }}</ref> It is not available orally.<ref>{{Cite book|title = Red Book: Pharmacy's Fundamental Reference|publisher = PDR Network, LLC.|year = 2010|isbn = 978-1-56363-751-3|edition = 114th}}</ref><ref>{{Cite web|title = DailyMed – Search Results for ceftriaxone|url = http://dailymed.nlm.nih.gov/dailymed/search.cfm?query=ceftriaxone&searchdb=all&labeltype=all&sortby=rel&audience=professional&page=1&pagesize=100|website = dailymed.nlm.nih.gov|access-date = 4 November 2015|url-status = live|archive-url = https://web.archive.org/web/20160306075340/http://dailymed.nlm.nih.gov/dailymed/search.cfm?query=ceftriaxone&searchdb=all&labeltype=all&sortby=rel&audience=professional&page=1&pagesize=100|archive-date = 6 March 2016}}</ref> |
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'''Distribution:''' Ceftriaxone penetrates tissues and body fluids well, including [[cerebrospinal fluid]] to treat central nervous system infections.<ref name="DailyMed-2019" /><ref>{{cite journal | vauthors = Nau R, Sörgel F, Eiffert H | title = Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections | journal = Clinical Microbiology Reviews | volume = 23 | issue = 4 | pages = 858–883 | date = October 2010 | pmid = 20930076 | pmc = 2952976 | doi = 10.1128/CMR.00007-10 }}</ref> Ceftriaxone is reversibly bound to human plasma proteins and the binding of ceftriaxone decreases with increasing concentration from a value of 95% at plasma concentrations less than 25 mcg/mL to 85% at plasma concentration of 300 mcg/mL. Over a 0.15 to 3 g dose range in healthy adult subjects, the apparent [[volume of distribution]] ranged from 5.8 to 13.5 L.<ref name="DailyMed-2019" /> |
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'''Metabolism:''' 33–67% of ceftriaxone is renally excreted as unchanged drug, but no dose adjustments are required in renal impairment with dosages up to 2 grams per day.<ref name="DailyMed-2019" /> The rest<ref name="pmid6292158">{{cite journal | vauthors = Arvidsson A, Alván G, Angelin B, Borgå O, Nord CE | title = Ceftriaxone: renal and biliary excretion and effect on the colon microflora | journal = The Journal of Antimicrobial Chemotherapy | volume = 10 | issue = 3 | pages = 207–215 | date = September 1982 | pmid = 6292158 | doi = 10.1093/jac/10.3.207 }}</ref> is excreted in the bile as unchanged drug<ref name="pmid1918224">{{cite journal | vauthors = Blumer J | title = Pharmacokinetics of ceftriaxone | journal = Hospital Practice | volume = 26 | issue = Suppl 5| pages = 7–13; discussion 52–4 | date = September 1991 | pmid = 1918224 | doi = 10.1080/21548331.1991.11707737 }}</ref> which is ultimately excreted in feces as inactive compounds from hepatic and gut flora metabolism.<ref name="DailyMed-2019" /><ref>{{cite journal | vauthors = Balant L, Dayer P, Auckenthaler R | title = Clinical pharmacokinetics of the third generation cephalosporins | journal = Clinical Pharmacokinetics | volume = 10 | issue = 2 | pages = 101–143 | date = 1 April 1985 | pmid = 3888488 | doi = 10.2165/00003088-198510020-00001 | s2cid = 23478077 }}</ref><ref>{{Cite book|title = Nursing Pharmacology Made Incredibly Easy!|url = https://books.google.com/books?id=NA41OnSGFWEC|publisher = Lippincott Williams & Wilkins|date = 7 March 2012|isbn = 978-1-4511-4624-0 |page = 496|url-status = live|archive-url = https://web.archive.org/web/20160603234922/https://books.google.com/books?id=NA41OnSGFWEC|archive-date = 3 June 2016}}</ref> |
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'''Elimination:''' The average elimination half-life in healthy adults is 5.8–8.7 (mean 6.5) hours,<ref name="pmid3906584"/> with some reviews estimated half-life is up to 10 hours.<ref name="pmid7791418">{{cite journal | vauthors = Klein NC, Cunha BA | title = Third-generation cephalosporins | journal = The Medical Clinics of North America | volume = 79 | issue = 4 | pages = 705–719 | date = July 1995 | pmid = 7791418 | doi = 10.1016/s0025-7125(16)30034-7 | doi-access = free }}</ref> In people with renal impairment, the average elimination half-life increases to 11.4–15.7 hours.<ref name="DailyMed-2019" /> |
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== Chemistry == |
== Chemistry == |
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Ceftriaxone is a white crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The [[pH]] of a 1% aqueous solution is approximately 6.7. |
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Ceftriaxone is commercially available as a white to yellowish-orange crystalline powder for reconstitution.<ref name="DailyMed-2019"/> Reconstituted ceftriaxone injection solutions are light yellow- to amber-colored depending on how long the solution had been reconstituted, the concentration of ceftriaxone in the solution, and the diluent used.<ref name="DailyMed-2019"/> To reduce pain with intramuscular injections, ceftriaxone may be reconstituted with [[lidocaine]].<ref>{{cite journal | vauthors = Schichor A, Bernstein B, Weinerman H, Fitzgerald J, Yordan E, Schechter N | title = Lidocaine as a diluent for ceftriaxone in the treatment of gonorrhea. Does it reduce the pain of the injection? | journal = Archives of Pediatrics & Adolescent Medicine | volume = 148 | issue = 1 | pages = 72–75 | date = January 1994 | pmid = 8143016 | doi = 10.1001/archpedi.1994.02170010074017 }}</ref> |
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The ''syn''-configuration of the [[methoxy]][[imino]] moiety confers stability to [[beta lactamase|β-lactamase]] enzymes produced by many [[Gram-negative bacteria]]. Such stability to β-lactamases increases the activity of ceftriaxone against otherwise resistant Gram-negative bacteria. In place of the easily [[hydrolysis|hydrolysed]] [[acetyl]] group of cefotaxime, ceftriaxone has a metabolically stable [[thiotriazinedione]] moiety. |
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== Adverse Effect == |
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[[Hypoprothrombinemia|Hypoprothombinaemia]] and bleeding are specific side effects. Haemolysis is reported. [[Gallstone|Biliary sludging]] is another known though rare adverse effect which occurs primarily in [[neonate]]s<ref name="pmid2227290">{{cite journal |author=Shiffman ML, Keith FB, Moore EW |title=Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility |journal=Gastroenterology |volume=99 |issue=6 |pages=1772–8 |year=1990 |month=December |pmid=2227290 |doi= |url=}}</ref>. |
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The ''syn''-configuration of the [[methoxy]] [[oxime]] moiety confers resistance to [[Beta lactamase|beta-lactamase]] enzymes produced by many [[Gram-negative bacteria]].<ref name="Lippincott Williams & Wilkins-2013"/> The stability of this configuration results in increased activity of ceftriaxone against otherwise resistant Gram-negative bacteria.<ref name="Lippincott Williams & Wilkins-2013" /> In place of the easily [[Hydrolysis|hydrolyzed]] [[acetyl]] group of cefotaxime, ceftriaxone has a metabolically stable {{chem name|thiotriazinedione}} moiety.<ref name="Lippincott Williams & Wilkins-2013" /> |
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== References == |
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{{reflist|2}} |
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*[http://www.rocheusa.com/products/rocephin/pi.pdf Ceftriaxone package insert] |
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==Research== |
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== External links == |
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*[http://www.nlm.nih.gov/medlineplus/druginfo/meds/a685032.html MedlinePlus Drug Information: Ceftriaxone Injection] |
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*[http://www.rocheusa.com/products/rocephin/ Rocephin U.S. Prescribing Information] |
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*[http://antibiotics.emedtv.com/rocephin/side-effects-of-rocephin.html Side Effects of Rocephin] |
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* [http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Ceftriaxone U.S. National Library of Medicine: Drug Information Portal - Ceftriaxone] |
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Ceftriaxone has also been investigated for efficacy in preventing relapse to cocaine addiction.<ref>{{cite journal | vauthors = Knackstedt LA, Melendez RI, Kalivas PW | title = Ceftriaxone restores glutamate homeostasis and prevents relapse to cocaine seeking | journal = Biological Psychiatry | volume = 67 | issue = 1 | pages = 81–84 | date = January 2010 | pmid = 19717140 | pmc = 2795043 | doi = 10.1016/j.biopsych.2009.07.018 }}</ref> |
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{{CephalosporinAntiBiotics}} |
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Ceftriaxone seems to increase [[EAAT2|excitatory amino acid transporter-2]] pump expression and activity in the central nervous system, so has a potential to reduce glutamatergic toxicity.<ref>{{cite journal | vauthors = Verma R, Mishra V, Sasmal D, Raghubir R | title = Pharmacological evaluation of glutamate transporter 1 (GLT-1) mediated neuroprotection following cerebral ischemia/reperfusion injury | journal = European Journal of Pharmacology | volume = 638 | issue = 1–3 | pages = 65–71 | date = July 2010 | pmid = 20423712 | doi = 10.1016/j.ejphar.2010.04.021 }}</ref><ref>{{cite journal | vauthors = Lee SG, Su ZZ, Emdad L, Gupta P, Sarkar D, Borjabad A, Volsky DJ, Fisher PB | title = Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes | journal = The Journal of Biological Chemistry | volume = 283 | issue = 19 | pages = 13116–13123 | date = May 2008 | pmid = 18326497 | pmc = 2442320 | doi = 10.1074/jbc.M707697200 | doi-access = free }}</ref> |
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Ceftriaxone has been shown to have neuroprotective properties in a number of neurological disorders, including [[spinal muscular atrophy]]<ref>{{cite journal | vauthors = Hedlund E | title = The protective effects of β-lactam antibiotics in motor neuron disorders | journal = Experimental Neurology | volume = 231 | issue = 1 | pages = 14–18 | date = September 2011 | pmid = 21693120 | doi = 10.1016/j.expneurol.2011.06.002 | s2cid = 26353910 }}</ref> and [[amyotrophic lateral sclerosis]] (ALS).<ref>{{cite journal | vauthors = Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ, Gupta P, Fisher PB | title = Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression | journal = Nature | volume = 433 | issue = 7021 | pages = 73–77 | date = January 2005 | pmid = 15635412 | doi = 10.1038/nature03180 | s2cid = 4301666 | bibcode = 2005Natur.433...73R }}</ref> Despite earlier negative results in the 1990s, a large clinical trial was undertaken in 2006 to test ceftriaxone in ALS patients, but was stopped early after it became clear that the results would not meet the predetermined criteria for efficacy.<ref>{{cite web|url = http://www.alsconsortium.org/news_ceftriaxone_announcement.php|title = Statement on the Clinical Trial of Ceftriaxone|date = 8 August 2012|publisher = The Northeast ALS Consortium (NEALS)|access-date = 10 May 2013|url-status = dead|archive-url = https://web.archive.org/web/20130528204018/http://www.alsconsortium.org/news_ceftriaxone_announcement.php|archive-date = 28 May 2013}}</ref> |
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== References == |
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{{reflist}} |
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{{Cell wall disruptive antibiotics}} |
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{{portal bar|Medicine}} |
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[[Category:Acetaldehyde dehydrogenase inhibitors]] |
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[[Category:Cephalosporin antibiotics]] |
[[Category:Cephalosporin antibiotics]] |
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[[Category:Drugs developed by Hoffmann-La Roche]] |
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[[Category:Thiazoles]] |
[[Category:Thiazoles]] |
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[[Category:Triazines]] |
[[Category:Triazines]] |
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[[Category:World Health Organization essential medicines]] |
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[[Category:Wikipedia medicine articles ready to translate]] |
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[[ar:سيفترياكسون]] |
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[[Category:Oxime ethers]] |
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[[de:Ceftriaxon]] |
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[[zh:頭孢曲松]] |