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{{Short description|Chemical compound}}
{{Drugbox
{{More medical citations needed|date=September 2019}}
| verifiedrevid = 413512442
{{Use dmy dates|date=September 2019}}
| IUPAC_name = (6R,7R)-7-acetyl]amino]-3-sulfanyl]-8-oxo-5-thia-1-azabicyclooct-2-ene-2-carboxylate
{{Infobox drug
| image = Ceftarolinfosamil.svg
| Verifiedfields = changed
| width = 250px
| Watchedfields = changed
| alt =
| verifiedrevid = 415374479
| CAS_number = 400827-46-5
| drug_name =
| INN =
| type = <!-- empty -->
| image = Ceftaroline_fosamil2DCSD.svg
| width = 300px
| alt =
| image2 = Ceftaroline-fosamil-zwitterion-3D-spacefill.png
| width2 =
| alt2 = Space-filling model of the ceftaroline fosamil molecule as a zwitterion
| caption =

<!-- Clinical data -->
| pronounce =
| tradename = Teflaro, Zinforo
| Drugs.com = {{drugs.com|monograph|ceftaroline-fosamil}}
| MedlinePlus = a611014
| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->
| licence_EU = yes
| DailyMedID = Ceftaroline_fosamil
| licence_US = Ceftaroline
| pregnancy_AU = B1
| pregnancy_AU_comment =
| pregnancy_category=
| dependency_liability =
| addiction_liability =
| routes_of_administration = Intravenous
| class =
| ATCvet = | ATCvet =
| ATC_prefix = J01 | ATC_prefix = J01
| ATC_suffix = DI02 | ATC_suffix = DI02
| ATC_supplemental = | ATC_supplemental =

| PubChem = 16007393
<!-- Legal status -->
| DrugBank =
| legal_AU = S4
| C = 24| H = 25 | N = 8 | O = 10 |P=1 | S = 4
| legal_AU_comment =
| smiles = CCO/N=C(/C1=NSC(=N1)NP(=O)(O)O)\C(=O)N23N(C2=O)C(=C(CS3)SC4=NC(=CS4)C5=CC=(C=C5)C)C(=O).CC(=O)O
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| molecular_weight = 744.736661 g/mol
| legal_BR_comment =
| synonyms = PPI 0903, TAK-599
| 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 = <!-- 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 -->
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment = <ref name="Teflaro FDA label" />
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Zinforo 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 = | bioavailability =
| protein_bound = | protein_bound = 20%
| metabolism = | metabolism =
| metabolites =
| elimination_half-life = 2.13-2.89 hours
| excretion = 46.4% Kidney, renal | onset =
| elimination_half-life = 2.5 hours
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| duration_of_action =
| pregnancy_US = B
| excretion = Urine (88%), faeces (6%)
| pregnancy_category=

| legal_US = Rx-only
<!-- Identifiers -->
| legal_status
| CAS_number_Ref = {{cascite|correct|CAS}}
| routes_of_administration = Intravenous, Intramuscular
| CAS_number = 229016-73-3
| licence_US = Ceftaroline
| CAS_supplemental =
| PubChem = 16007393
| PubChem2= 9852981
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB06590
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 8028692
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 7P6FQA5D21
| KEGG_Ref =
| KEGG = D08884
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 70718
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 501122
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = PPI 0903, TAK-599

| index2_label = anhydrous
| CAS_number2_Ref = {{cascite|correct|CAS}}
| CAS_number2 = 400827-46-5
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = EZ9W6O5S09

<!-- Chemical and physical data -->
| IUPAC_name = (6''R'',7''R'')-7-acetyl]amino]-3-sulfanyl]-8-oxo-5-thia-1-azabicyclooct-2-ene-2-carboxylate
| chemical_formula =
| C =22 | H =21 | P =1 | S=4 | N=8 | O=8
| molecular_weight =
| SMILES = O=C4N3/C(=C(/Sc2nc(c1cc(cc1)C)cs2)CS34NC(=O)C(=N\OCC)/c5nc(sn5)NP(=O)(O)O)C()=O
| Jmol =
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C22H21N8O8PS4/c1-3-38-26-13(16-25-21(43-28-16)27-39(35,36)37)17(31)24-14-18(32)30-15(20(33)34)12(9-40-19(14)30)42-22-23-11(8-41-22)10-4-6-29(2)7-5-10/h4-8,14,19H,3,9H2,1-2H3,(H4-,24,25,27,28,31,33,34,35,36,37)/b26-13-/t14-,19-/m1/s1
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = ZCCUWMICIWSJIX-NQJJCJBVSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}} }}


'''Ceftaroline fosamil''' (]) ({{pron-en|sɛfˈtærɵliːn}}, brand name '''Teflaro''') is an advanced generation<ref name="pmid20001879">{{cite journal |author=Kollef MH |title=New antimicrobial agents for methicillin-resistant Staphylococcus aureus |journal=Crit Care Resusc |volume=11 |issue=4 |pages=282–6 |year=2009 |month=December |pmid=20001879 |doi= |url=}}</ref> ] ]. It is active against ] (MRSA) and ] bacteria. It retains the activity of later generation cephalosporins having broad spectrum activity against ] bacteria. It is currently being investigated for ]<ref name="eckberg2009"/> and ].<ref name="corey2008"/><ref name="pmid19207097"/><ref name="pmid18246523"/> '''Ceftaroline fosamil''' (]) {{IPAc-en|s|ɛ|f|ˈ|t|ær|oʊ-|l|iː|n}}, brand name '''Teflaro''' in the US and '''Zinforo''' in Europe,<ref name="Teflaro FDA label">{{cite web | title=Teflaro- ceftaroline fosamil powder, for solution | website=DailyMed | date=24 September 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ecde48b-75a2-4beb-9999-369f3f61bb8a | access-date=1 March 2020}}</ref><ref name="Zinforo EPAR">{{cite web | title=Zinforo EPAR | website=] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zinforo | access-date=1 March 2020}}</ref> is a ] ] with anti-MRSA activity.<ref name="pmid20001879">{{cite journal | vauthors = Duplessis C, Crum-Cianflone NF | title = Ceftaroline: A New Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA) | journal = Clinical Medicine Reviews in Therapeutics | volume = 3 | pages = a2466 | date = February 2011 | pmid = 21785568 | pmc = 3140339 | doi = 10.4137/CMRT.S1637 }}</ref> Ceftaroline fosamil is a prodrug of ceftaroline. It is active against ] (MRSA) and other ] bacteria. It retains some activity of later-generation cephalosporins having broad-spectrum activity against ] bacteria, but its effectiveness is relatively much weaker.<ref>{{cite journal | vauthors = Karlowsky JA, Adam HJ, Decorby MR, Lagacé-Wiens PR, Hoban DJ, Zhanel GG | title = In vitro activity of ceftaroline against gram-positive and gram-negative pathogens isolated from patients in Canadian hospitals in 2009 | journal = Antimicrobial Agents and Chemotherapy | volume = 55 | issue = 6 | pages = 2837–2846 | date = June 2011 | pmid = 21402844 | pmc = 3101400 | doi = 10.1128/aac.01787-10 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Flamm RK, Sader HS, Jones RN | title = Spectrum and potency of ceftaroline against leading pathogens causing community-acquired respiratory tract and skin and soft tissue infections in Latin America, 2010 | journal = The Brazilian Journal of Infectious Diseases | volume = 17 | issue = 5 | pages = 564–572 | date = October 2010 | pmid = 23916453 | pmc = 9425132 | doi = 10.1016/j.bjid.2013.02.008 | doi-access = free }}</ref> It is currently being investigated for ]<ref name="eckberg2009"/> and ].<ref name="corey2008"/><ref name="pmid19207097"/><ref name="pmid18246523"/>


Ceftaroline is being developed by ], under a license from ].<ref name="pmid18246523">{{cite journal| author = Parish D, Scheinfeld N| title = Ceftaroline fosamil, a cephalosporin derivative for the potential treatment of MRSA infection| journal = Current Opinion in Investigational Drugs (London, England : 2000)| volume = 9| issue = 2| pages = 201–9| year = 2008| month = February| pmid = 18246523}}</ref> '' Ceftaroline is being developed{{when|date=September 2019}} by ], under a license from ].<ref name="pmid18246523">{{cite journal | vauthors = Parish D, Scheinfeld N | title = Ceftaroline fosamil, a cephalosporin derivative for the potential treatment of MRSA infection | journal = Current Opinion in Investigational Drugs | volume = 9 | issue = 2 | pages = 201–209 | date = February 2008 | pmid = 18246523 }}</ref>
Ceftaroline has received approval from the U.S. Food and Drug Administration for the treatment of community-acquired bacterial ] and acute bacterial skin infections on October 29, 2010.<ref>{{cite press release Ceftaroline received approval from the U.S. ] (FDA) for the treatment of community-acquired bacterial ] and acute bacterial skin infections on 29 October 2010.<ref>{{cite press release
| title = Forest Announces FDA Approval of Teflaro(TM) (ceftaroline fosamil) for the Treatment of Community-Acquired Bacterial Pneumonia and Acute Bacterial Skin and Skin Structure Infection | title = Forest Announces FDA Approval of Teflaro (ceftaroline fosamil) for the Treatment of Community-Acquired Bacterial Pneumonia and Acute Bacterial Skin and Skin Structure Infection
| publisher = Forest Laboratories | publisher = Forest Laboratories
| date = 2010-10-29 | date = 2010-10-29
| url = http://www.frx.com/news/PressRelease.aspx?ID=1489398 | url = http://www.frx.com/news/PressRelease.aspx?ID=1489398
| accessdate = October 30, 2010 | access-date = 30 October 2010
}}</ref> ''In vitro'' studies show that it has a similar spectrum to ], the only other fifth-generation cephalosporin to date, although no head to head clinical trials have been conducted. Currently, ceftaroline and ceftobiprole are on an unnamed subclass of cephalosporins by the Clinical and Laboratory Standards Institute (CLSI). }}</ref> ''In vitro'' studies show it has a similar spectrum to ],{{Citation needed lead|date=September 2019}} the only other fifth-generation cephalosporin to date,{{when|date=September 2019}} although no head-to-head clinical trials have been conducted. Ceftaroline and ceftobiprole are on an unnamed subclass of cephalosporins by the ] (CLSI).{{Citation needed lead|date=September 2019}}


It was removed from the ] in 2019.<ref>{{cite book | vauthors = ((World Health Organization)) | year = 2019 | title = Executive summary: the selection and use of essential medicines 2019: report of the 22nd WHO Expert Committee on the selection and use of essential medicines | publisher = World Health Organization | location = Geneva | author-link = World Health Organization | hdl = 10665/325773 | id = WHO/MVP/EMP/IAU/2019.05. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>
== Mechanism of action ==
]s inhibit bacterial ] synthesis by binding the ] (PBPs) in the bacterial cell wall. Inhibition of PBPs leads to irregularities in cell wall structures, such as elongation, lesions, loss of selective permeability, and eventual cell death and lysis. In particular, ceftaroline can effectively bind to and inhibit PBP-2a, the type of PBP produced by ] and ] currently in clinical use.<ref name="pmid18582062">{{cite journal| author = Villegas-Estrada A, Lee M, Hesek D, Vakulenko SB, Mobashery S| title = Co-opting the cell wall in fighting methicillin-resistant ''Staphylococcus aureus'': potent inhibition of PBP 2a by two anti-MRSA beta-lactam antibiotics| journal = ]| volume = 130| issue = 29| pages = 9212–3| year = 2008| month = July| pmid = 18582062| pmc = 2747592| doi = 10.1021/ja8029448}}</ref><ref name="pmid19441869">{{cite journal| author = Zhanel GG, Sniezek G, Schweizer F, Zelenitsky S, Lagacé-Wiens PR, Rubinstein E, Gin AS, Hoban DJ, Karlowsky JA| title = Ceftaroline: a novel broad-spectrum cephalosporin with activity against meticillin-resistant ''Staphylococcus aureus''| journal = Drugs| volume = 69| issue = 7| pages = 809–31| year = 2009| pmid = 19441869| doi = 10.2165/00003495-200969070-00003}}</ref>


== Clinical use == == Clinical use ==
{{main|Cephalosporin}} {{main|Cephalosporin}}


Ceftaroline is a novel cephalosporin that has activity against MRSA with ] for complicated skin and skin structure infections with reported non-inferior efficacy against MRSA compared to ] and ]<ref name="corey2008">{{cite conference| first = Corey| last = R| coauthors = Wilcox M, Talbot GH, et al.| title = CANVAS-1: Randomized, Double-blinded, Phase 3 Study (P903-06) of the Efficacy and Safety of Ceftaroline vs. Vancomycin plus Aztreonam in Complicated Skin and Skin Structure Infections (cSSSI).| conference = 2008 Interscience Conference on Antimicrobial Agents and Chemotherapy / Infectious Disease Society of America Conference}}</ref><ref name="pmid19207097">{{cite journal| author = Kanafani ZA, Corey GR| title = Ceftaroline: a cephalosporin with expanded Gram-positive activity| journal = Future Microbiology| volume = 4| pages = 25–33| year = 2009| month = February| pmid = 19207097| doi = 10.2217/17460913.4.1.25| url = http://www.futuremedicine.com/doi/abs/10.2217/17460913.4.1.25?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov}}</ref> Recently,{{When|date=February 2011}} ceftaroline has completed phase III clinical trials for community-acquired pneumonia comparing it against ] with non-inferior results and similar adverse reaction profile.<ref name="eckberg2009">{{cite conference| first = Eckberg| last = P| coauthors = Friedland HD, et al.| title = FOCUS 1 and 2: Randomized, Double-blinded, Multicenter Phase 3 Trials of the Efficacy and Safety of Ceftaroline (CPT) vs. Ceftriaxone (CRO) in Community-acquired pneumonia (CAP).| conference = 2009 Interscience Conference on Antimicrobial Agents and Chemotherapy / Infectious Disease Society of America Conference}}</ref> However there are only published results for Phase II clinical trials in treatment of complicated skin and skin structure infections.<ref name="pmid17682094">{{cite journal| author = Talbot GH, Thye D, Das A, Ge Y| title = Phase 2 study of ceftaroline versus standard therapy in treatment of complicated skin and skin structure infections| journal = ]| volume = 51| issue = 10| pages = 3612–6| year = 2007| month = October| pmid = 17682094| pmc = 2043268| doi = 10.1128/AAC.00590-07| url = http://aac.asm.org/cgi/pmidlookup?view=long&pmid=17682094}}</ref> The manufacturer plans to file a New Drug Application (NDA) to the Food and Drug Administration by the end of this year for both community-acquired pneumonia and complicated skin and skin structure infections.<ref name="forest2009">{{cite press release |title=Forest Laboratories Presents Analysis of Two Positive Pivotal Phase III Studies of Ceftaroline for the Treatment of Community-Acquired Pneumonia (CAP) at ICAAC |url=http://www.businesswire.com/news/home/20090912005009/en |publisher=BUSINESS WIRE |date=2009-09-12 |accessdate=2009-10-19}}</ref> Ceftaroline is a novel cephalosporin with activity against methicillin-resistant ''S. aureus'' (MRSA) with ] for complicated skin and skin structure infections with reported non-inferior efficacy against MRSA compared to ] and ].<ref name="corey2008">{{cite conference| vauthors = Corey R, Wilcox M, Talbot GH| title = CANVAS-1: Randomized, Double-blinded, Phase 3 Study (P903-06) of the Efficacy and Safety of Ceftaroline vs. Vancomycin plus Aztreonam in Complicated Skin and Skin Structure Infections (cSSSI).| conference = 2008 Interscience Conference on Antimicrobial Agents and Chemotherapy / Infectious Disease Society of America Conference|display-authors=etal}}</ref><ref name="pmid19207097">{{cite journal | vauthors = Kanafani ZA, Corey GR | title = Ceftaroline: a cephalosporin with expanded Gram-positive activity | journal = Future Microbiology | volume = 4 | issue = 1 | pages = 25–33 | date = February 2009 | pmid = 19207097 | doi = 10.2217/17460913.4.1.25 }}</ref> In 2009, ceftaroline had completed phase-III clinical trials for ] comparing it against ] with non-inferior results and similar adverse reaction profile.<ref name="eckberg2009">{{cite conference | vauthors = Eckberg P, Friedland HD | title = FOCUS 1 and 2: Randomized, Double-blinded, Multicenter Phase 3 Trials of the Efficacy and Safety of Ceftaroline (CPT) vs. Ceftriaxone (CRO) in Community-acquired pneumonia (CAP).| conference = 2009 Interscience Conference on Antimicrobial Agents and Chemotherapy / Infectious Disease Society of America Conference|display-authors=etal}}</ref> However, only results for phase-II clinical trials in treatment of complicated skin and skin structure infections have been published.<ref name="pmid17682094">{{cite journal | vauthors = Talbot GH, Thye D, Das A, Ge Y | title = Phase 2 study of ceftaroline versus standard therapy in treatment of complicated skin and skin structure infections | journal = Antimicrobial Agents and Chemotherapy | volume = 51 | issue = 10 | pages = 3612–3616 | date = October 2007 | pmid = 17682094 | pmc = 2043268 | doi = 10.1128/AAC.00590-07 }}</ref> Sept 2009 : Phase III trials results reported.<ref name="forest2009">{{cite press release |title=Forest Laboratories Presents Analysis of Two Positive Pivotal Phase III Studies of Ceftaroline for the Treatment of Community-Acquired Pneumonia (CAP) at ICAAC |url=http://www.businesswire.com/news/home/20090912005009/en |publisher=BUSINESS WIRE |date=2009-09-12 |access-date=2009-10-19}}</ref>
In Oct 2010 the FDA approval was gained for ] (CABP) and acute bacterial ]s (ABSSSI), including methicillin-resistant Staphylococcus aureus (MRSA).<ref>{{cite news |url=http://www.ibtimes.com/articles/77358/20101030/fda-teflaro-forests-laboratories-inc-bacterial-infections.htm |title=FDA approves Teflaro for treatment of bacterial infections |date=30 Oct 2010 }}</ref> On 8 September 2010, the FDA Advisory Committee recommended approval for the treatment of community acquired bacterial pneumonia and complicated skin and skin structure infections.<ref>{{Cite web |url=https://www.drugs.com/newdrugs.html |title=New Drug Approvals |date=2010-10-29 |access-date=2010-11-08}}</ref>
In October 2010, FDA approval was gained for treatment of ] and acute bacterial ]s, including MRSA.<ref>{{cite news |url=http://www.ibtimes.com/articles/77358/20101030/fda-teflaro-forests-laboratories-inc-bacterial-infections.htm |title=FDA approves Teflaro for treatment of bacterial infections |date=30 October 2010 |access-date=1 November 2010 |archive-date=4 November 2010 |archive-url=https://web.archive.org/web/20101104085917/http://www.ibtimes.com/articles/77358/20101030/fda-teflaro-forests-laboratories-inc-bacterial-infections.htm |url-status=dead }}</ref>


MRSA can develop resistance to ] through the alteration of penicillin-binding proteins. Amino acid-altering mutations in the ceftaroline-binding pocket of the transpeptidase region of penicillin-binding protein 2a (PBP2a) confer resistance to ceftaroline.<ref>Long SW, Olsen RJ, Mehta SC, et al. PBP2a mutations causing high-level Ceftaroline resistance in clinical methicillin-resistant ''Staphylococcus aureus'' isolates. Antimicrob Agents Chemother. 2014;58(11):6668-6674. doi:10.1128/AAC.03622-14</ref> Ceftaroline- and methicillin-resistant strains of ''S. aureus'' have been identified in Europe and Asia, but have not been identified in the United States.<ref>Long SW, Olsen RJ, Mehta SC, et al. PBP2a mutations causing high-level Ceftaroline resistance in clinical methicillin-resistant ''Staphylococcus aureus'' isolates. Antimicrob Agents Chemother. 2014;58(11):6668-6674. doi:10.1128/AAC.03622-14</ref> While cephalosporinases (a type of beta-lactamase that inactivates cephalosporins) confers resistance to other cephalosporins, cephalosporinases have not yet been identified as a mechanism of resistance to ceftaroline.{{cn|date=March 2023}}
On November 1, 2010 the FDA approved ceftaroline for bacterial infections. Also, on September 8, 2010 the FDA Advisory Committee recommended approval for the treatment of community acquired bacterial pneumonia and complicated skin and skin structure infections.<ref>{{Cite web |url=http://www.drugs.com/newdrugs.html |title=New Drug Approvals |date=2010-10-29 |accessdate=2010-11-08}}</ref>


== Safety == == Safety ==
The clinical studies indicated that ceftaroline was well-tolerated. The overall rate of adverse events was comparable between the two treatment groups (The CANVAS I and CANVAS II trials evaluated ceftaroline monotherapy versus vancomycin plus aztreonam in adult patients with complicated skin and skin structure infections caused by gram-positive and gram-negative bacteria.). The clinical studies indicated ceftaroline was well tolerated. The overall rate of adverse events was comparable between the two treatment groups (The CANVAS I and CANVAS II trials evaluated ceftaroline monotherapy versus vancomycin plus aztreonam in adult subjects with complicated skin and skin structure infections caused by Gram-positive and Gram-negative bacteria.). The overall discontinuation rate for ceftaroline-treated subjects was 2.7% compared to a rate of 3.7% for the comparator group-treated subjects. The most common adverse reactions occurring in > 2% of subjects receiving ceftaroline in the pooled phase-III clinical trials were diarrhea, nausea, and rash.:<ref name="drug information online">{{Cite web |url=https://www.drugs.com/teflaro.html |title=Teflaro |date=2010-10-29 |access-date=2010-11-08}}</ref>
The overall discontinuation rate for ceftaroline-treated patients was 2.7% compared to a rate of 3.7% for the comparator group-treated patients. The most common adverse reactions occurring in > 2% of patients receiving ceftaroline in the pooled Phase 3 clinical trials were diarrhea, nausea, and rash.:<ref name="drug information online">{{Cite web |url=http://www.drugs.com/teflaro.html |title=Teflaro |date=2010-10-29 |accessdate=2010-11-08}}</ref>


== Contraindications == == Contraindications ==
* Known serious ] to ceftaroline or other members of the cephalosporin class. * Known serious ] to ceftaroline or other members of the cephalosporin class
* ] and anaphylactoid reactions have been reported with ceftaroline.<ref name="drug information online" /> * ] and anaphylactoid reactions<ref name="drug information online" />


== Warnings and precautions == == Warnings and precautions ==
{{unreferenced section|date=September 2019}}

The warnings and precautions associated with ceftaroline include:<ref name="drug information online" /> The warnings and precautions associated with ceftaroline include:<ref name="drug information online" />


===Hypersensitivity reactions=== ===Hypersensitivity reactions===
Serious hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported with beta-lactam antibiotics, including ceftaroline. Exercise caution in patients with known hypersensitivity to beta-lactam antibiotics including ceftaroline. Before therapy with ceftaroline is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. If this product is to be given to penicillin or other beta-lactam-allergic patient, caution should be exercised because cross sensitivity among beta-lactam antibacterial agents has been clearly established. If an allergic reaction to ceftaroline occurs, the drug should be discontinued. Serious acute hypersensitivity (anaphylactic) reactions require emergency treatment with epinephrine and other emergency measures, that may include airway management, oxygen, intravenous fluids, antihistamines, corticosteroids, and vasopressors as clinically indicated. Serious hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported with beta-lactam antibiotics, including ceftaroline. Exercise caution in people with known hypersensitivity to beta-lactam antibiotics including ceftaroline. Before therapy with ceftaroline is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. If this product is to be given to penicillin- or other beta-lactam-allergic people, caution should be exercised because cross sensitivity among beta-lactam antibacterial agents has been clearly established. If an allergic reaction to ceftaroline occurs, the drug should be discontinued. Serious acute hypersensitivity reactions require emergency treatment with epinephrine and other emergency measures, that may include airway management, oxygen, intravenous fluids, antihistamines, corticosteroids, and vasopressors as clinically indicated.


===Clostridium difficile associated diarrhea=== ===''Clostridioides difficile''-associated diarrhea===
] (CDAD) has been reported for nearly all antibacterial agents including ceftaroline, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible. ] (CDAD) has been reported for nearly all antibacterial agents including ceftaroline, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterials not directed against'' C. difficile'' should be discontinued, if possible.


===Development of drug-resistant bacteria=== ===Development of drug-resistant bacteria===
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===Direct Coombs test seroconversion=== ===Direct Coombs test seroconversion===
In the pooled Phase 3 CABP trials, 51/520 (9.8%) of patients treated with ceftaroline compared to 24/534 (4.5%) of patients treated with ceftriaxone seroconverted from a negative to a positive direct Coombs' test result. No clinical adverse reactions representing hemolytic anemia were reported in any treatment group. If anemia develops during or after treatment with ceftaroline, drug-induced hemolytic anemia should be considered. If drug-induced hemolytic anemia is suspected, discontinuation of ceftaroline should be considered and supportive care should be administered to the patient if clinically indicated. In the pooled phase-III CABP trials, 51/520 (9.8%) of subjects treated with ceftaroline compared to 24/534 (4.5%) of subjects treated with ceftriaxone seroconverted from a negative to a positive direct Coombs' test result. No clinical adverse reactions representing hemolytic anemia were reported in any treatment group. If anemia develops during or after treatment with ceftaroline, drug-induced hemolytic anemia should be considered. If drug-induced hemolytic anemia is suspected, discontinuation of ceftaroline should be considered and supportive care should be administered to the patient if clinically indicated.


===Interactions=== === Interactions ===
No clinical drug-drug interaction studies have been conducted with ceftaroline fosamil. In vitro studies in human liver microsomes indicated that neither ceftaroline fosamil nor ceftaroline inhibits the major cytochrome P450 isoenzymes. Therefore neither ceftaroline fosamil nor ceftaroline are expected to inhibit or induce the clearance of drugs that are metabolized by these metabolic pathways in a clinically relevant manner. No clinical drug-drug interaction studies have been conducted with ceftaroline fosamil. In vitro studies in human liver microsomes indicated that neither ceftaroline fosamil nor ceftaroline inhibits the major cytochrome P450 isoenzymes. Therefore, neither ceftaroline fosamil nor ceftaroline is expected to inhibit or induce the clearance of drugs that are metabolized by these metabolic pathways in a clinically relevant manner.


===Use in specific populations=== ===Use in specific populations===
For pregnant or nursing mothers, ceftaroline fosamil should only be used if the potential benefit outweighs the potential risk to the fetus or child. For pregnant or nursing mothers, ceftaroline fosamil should be used only if the potential benefit outweighs the potential risk to the fetus or child. Safety and effectiveness in pediatric children has not been studied.


Because elderly people 65 years of age or older are more likely to have decreased renal function and ceftaroline is excreted primarily by the kidney, care should be taken in dose selection in this age group as in younger people with impaired renal function. Dosage adjustment is required in people with moderately (30 to ‰¤ 50 mL/min) or severely (< 30 mL/min) impaired renal function.
Safety and effectiveness in pediatric patients has not been studied.


The pharmacokinetics of ceftaroline in people with hepatic impairment have not been established.
Because elderly patients greater-than or equal to 65 years of age are more likely to have decreased renal function and ceftaroline is excreted primarily by the kidney, care should be taken in dose selection in this age group as in younger patients with impaired renal function

Dosage adjustment is required in patients with moderately (30 to ‰¤ 50 mL/min) or severely (< 30 mL/min) impaired renal function

The pharmacokinetics of ceftaroline in patients with hepatic impairment have not been established


== Side effects == == Side effects ==
No adverse reactions occurred in greater than 5% of patients receiving ceftaroline. No adverse reactions occurred in greater than 5% of people receiving ceftaroline. The most common adverse reactions occurring in > 2% of people receiving ceftaroline in the pooled phase-III clinical trials were:<ref name="drug information online" />
The most common adverse reactions occurring in > 2% of patients receiving ceftaroline in the pooled Phase 3 clinical trials were:<ref name="drug information online" />

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== Chemistry == == Chemistry ==
Ceftaroline fosamil is a ] that is converted to active metabolite ceftaroline and inactive metabolite ceftaroline-M1. Initial ''in vitro'' and ''in vivo'' animal studies referred to ceftaroline fosamil acetate as PPI-0903.<ref name="ge2006">{{cite conference| first = Ge| last = Y| coauthors = Floren L, Redman R, et. al.| title = The pharmacokinetics and safety of ceftaroline (PPI-0903) in healthy subjects receiving multiple-dose intravenous infusions.| conference = 2006 Interscience Conference on Antimicrobial Agents and Chemotherapy / Infectious Disease Society of America Conference}}</ref><ref name="yukihiro2008">{{cite journal |author=Yukihiro I, Junko B |year=2008 |title=Stability and Stabilization Studies of TAK-599 (Ceftaroline Fosamil) a Novel N-Phosphono Type Prodrug of Anti-methicillin Resistant Staphylococcus aureus Cephalosporin T-91825 |journal= Chem Pharm Bull |volume=56 |issue=10 |pages=1406–11 |url=http://www.jstage.jst.go.jp/article/cpb/56/10/1406/_pdf |doi=10.1248/cpb.56.1406 |pmid=18827379}}</ref> Ceftaroline fosamil is used in form of the ]. It is a ] that is converted to active metabolite ceftaroline and inactive metabolite ceftaroline-M1. Initial ''in vitro'' and ''in vivo'' animal studies referred to ceftaroline fosamil acetate as PPI-0903.<ref name="ge2006">{{cite conference| vauthors = Ge Y, Floren L, Redman R | title = The pharmacokinetics and safety of ceftaroline (PPI-0903) in healthy subjects receiving multiple-dose intravenous infusions.| conference = 2006 Interscience Conference on Antimicrobial Agents and Chemotherapy / Infectious Disease Society of America Conference|display-authors=etal}}</ref><ref name="yukihiro2008">{{cite journal | vauthors = Ikeda Y, Ban J, Ishikawa T, Hashiguchi S, Urayama S, Horibe H | title = Stability and stabilization studies of TAK-599 (Ceftaroline Fosamil), a novel N-phosphono type prodrug of anti-methicillin resistant Staphylococcus aureus cephalosporin T-91825 | journal = Chemical & Pharmaceutical Bulletin | volume = 56 | issue = 10 | pages = 1406–1411 | date = October 2008 | pmid = 18827379 | doi = 10.1248/cpb.56.1406 | doi-access = free }}</ref>


Characteristic of cephalosporins, ceftaroline has a bicyclic ring with four member ] ring fused to a six member ] ring. Ceftaroline is thought to have activity against MRSA with its 1,3 thiazole ring.<ref name="ishikawa2003">{{cite journal |author=Ishikawa t, Nobuyuki M, et al. |year=2003 |title=TAK-599, a novel N-phosphono type prodrug of anti-MRSA cephalosporin T-91825: Synthesis, physicochemical and pharmacological properties |journal= Bioorg Med Chem |volume=11 |issue=11 |pages=2427–2437 |pmid=12735989 }}</ref> Characteristic of cephalosporins, ceftaroline has a bicyclic ring with four-member ] ring fused to a six-member ] ring. Ceftaroline is thought to have activity against MRSA with its 1,3-thiazole ring.<ref name="ishikawa2003">{{cite journal | vauthors = Ishikawa T, Matsunaga N, Tawada H, Kuroda N, Nakayama Y, Ishibashi Y, Tomimoto M, Ikeda Y, Tagawa Y, Iizawa Y, Okonogi K, Hashiguchi S, Miyake A | display-authors = 6 | title = TAK-599, a novel N-phosphono type prodrug of anti-MRSA cephalosporin T-91825: synthesis, physicochemical and pharmacological properties | journal = Bioorganic & Medicinal Chemistry | volume = 11 | issue = 11 | pages = 2427–2437 | date = May 2003 | pmid = 12735989 | doi = 10.1016/s0968-0896(03)00126-3 }}</ref>


== References == == References ==
{{reflist|2}} {{reflist}}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/rn/229016-73-3 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Ceftaroline fosamil }}


{{CephalosporinAntiBiotics}} {{CephalosporinAntiBiotics}}
{{Portal bar|Medicine}}


{{DEFAULTSORT:Ceftaroline Fosamil}} {{DEFAULTSORT:Ceftaroline Fosamil}}
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