Misplaced Pages

Ciprofloxacin: Difference between revisions

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
Browse history interactively
Page 1
Page 2
← Previous editContent deleted Content addedVisualWikitext
Revision as of 16:12, 7 August 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEBI').← Previous edit Latest revision as of 19:26, 2 December 2024 edit undoSynpath (talk | contribs)Extended confirmed users1,229 editsm adding skin-invert-image for dark mode readability (via WP:JWB) 
(936 intermediate revisions by more than 100 users not shown)
Line 1: Line 1:
{{Short description|Fluoroquinolone antibiotic}}
{{dablink|Not to be confused with Cipralex, a brand name of the antidepressant ].}}
{{Redirect|Cipro|the Rome Metro station|Cipro (Rome Metro)}} {{redirect|Cipro|the Rome Metro station|Cipro (Rome Metro)}}
{{distinguish|Ciproxifan}}
{{drugbox | Watchedfields = changed
{{Use dmy dates|date=August 2023}}
| verifiedrevid = 417426037
{{cs1 config |name-list-style=vanc |display-authors=6}}
| IUPAC_name = 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 443526033
| image = Ciprofloxacin.svg | image = Ciprofloxacin.svg
| image_class = skin-invert-image
| width = 200 | width = 200
| alt = ciprofloxacin molecule
| caption = structure
| image2 = Ciprofloxacin-zwitterion-from-xtal-3D-balls.png | image2 = Ciprofloxacin-zwitterion-from-xtal-3D-balls.png
| width2 =
| alt2 = ciprofloxacin zwitterion molecule
| caption2 = 3D model of ciprofloxacin ]


<!--Clinical data--> <!-- Clinical data -->
| pronounce =
| tradename = Ciloxan, Cipro
| tradename = Ciloxan, Cipro, Neofloxin, others
| Drugs.com = {{drugs.com|CDI|ciprofloxacin}}
| Drugs.com = {{drugs.com|monograph|ciprofloxacin}}
| MedlinePlus = a688016 | MedlinePlus = a688016
| licence_US = Ciprofloxacin | DailyMedID = Ciprofloxacin
| pregnancy_AU = B3 | pregnancy_AU = B3
| pregnancy_AU_comment = <ref name="Drugs.com Pregnancy">{{cite web |title=Ciprofloxacin Use During Pregnancy |website=Drugs.com |url=https://www.drugs.com/pregnancy/ciprofloxacin.html |date=7 January 2019 |access-date=19 December 2019}}</ref>
| pregnancy_US = C
| pregnancy_category =
| routes_of_administration = ], ], ] (]s, ]s)
| class = ]
| ATCvet =
| ATC_prefix = J01
| ATC_suffix = MA02
| ATC_supplemental = {{ATC|S01|AE03}} {{ATC|S02|AA15}} {{ATC|S03|AA07}} {{ATC|J01|RA10}} {{ATC|J01|RA11}} {{ATC|J01|RA12}}

<!-- Legal status -->
| legal_AU = S4 | legal_AU = S4
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM | legal_UK = POM
| legal_UK_comment =
| legal_US = Rx-only | legal_US = Rx-only
| legal_US_comment = <ref name="Cipro FDA label">{{cite web | title=Cipro- ciprofloxacin hydrochloride tablet, film coated; Cipro- ciprofloxacin kit | website=DailyMed | date=31 January 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=888dc7f9-ad9c-4c00-8d50-8ddfd9bd27c0 | access-date=9 February 2024}}</ref>
| routes_of_administration = ], ], ] (]s, ]s)
| legal_EU =
| legal_EU_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->


<!--Pharmacokinetic data--> <!-- Pharmacokinetic data -->
| bioavailability = 70%<ref name="pmid17154673">{{cite journal |vauthors=Zhanel GG, Fontaine S, Adam H, Schurek K, Mayer M, Noreddin AM, Gin AS, Rubinstein E, Hoban DJ |title=A Review of New Fluoroquinolones: Focus on their Use in Respiratory Tract Infections |journal=Treatments in Respiratory Medicine |volume=5 |issue=6 |pages=437–465 |year=2006 |pmid=17154673 |s2cid=26955572 |doi=10.2165/00151829-200605060-00009}}</ref>
| bioavailability = 69%<ref>{{cite journal |author=Drusano GL, Standiford HC, Plaisance K, Forrest A, Leslie J, Caldwell J |title=Absolute oral bioavailability of ciprofloxacin |journal=Antimicrob Agents Chemother. |volume=30 |issue=3 |pages=444–6 |year=1986 |month=September |pmid=3777908 |pmc=180577 |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=3777908 |doi= |first1=GL |first2=HC |first3=K |first4=A |first5=J |first6=J |issn=0066-4804}}</ref>
| protein_bound = 30%<ref name="pmid17154673" />
| metabolism = Hepatic, including ]
| metabolism = ]
| elimination_half-life = 4 hours
| metabolites =
| excretion = Renal
| onset =
| elimination_half-life = 3.5 hours<ref name="pmid17154673" />
| duration_of_action =
| excretion = ]


<!--Identifiers--> <!-- Identifiers -->
| index2_label = as HCl
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 85721-33-1 | CAS_number = 85721-33-1
| CAS_supplemental =
| ATC_prefix = J01
| ATC_suffix = MA02
| ATC_supplemental = {{ATC|S01|AX13}} {{ATC|S02|AA15}} {{ATC|S03|AA07}}
| ChEBI = 100241
| PubChem = 2764 | PubChem = 2764
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00537 | DrugBank = DB00537
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
Line 41: Line 79:
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00186 | KEGG = D00186
| KEGG2_Ref = {{keggcite|changed|kegg}}
| KEGG2 = D02216
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 100241
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 8 | ChEMBL = 8
| NIAID_ChemDB = 001992
| PDB_ligand =
| synonyms =


<!--Chemical data--> <!-- Chemical and physical data -->
| IUPAC_name = 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid
| C=17 | H=18 | F=1 | N=3 | O=3
| C=17 |H=18 |F=1 |N=3 |O=3
| molecular_weight = 331.346
| smiles = c1c2c(cc(c1F)N3CCNCC3)n(cc(c2=O)C(=O)O)C4CC4 | SMILES = C1CNCCN1c(c2)c(F)cc3c2N(C4CC4)C=C(C3=O)C(=O)O
| InChI = 1/C17H18FN3O3/c18-13-7-11-14(8-15(13)20-5-3-19-4-6-20)21(10-1-2-10)9-12(16(11)22)17(23)24/h7-10,19H,1-6H2,(H,23,24)
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C17H18FN3O3/c18-13-7-11-14(8-15(13)20-5-3-19-4-6-20)21(10-1-2-10)9-12(16(11)22)17(23)24/h7-10,19H,1-6H2,(H,23,24) | StdInChI = 1S/C17H18FN3O3/c18-13-7-11-14(8-15(13)20-5-3-19-4-6-20)21(10-1-2-10)9-12(16(11)22)17(23)24/h7-10,19H,1-6H2,(H,23,24)
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MYSWGUAQZAJSOK-UHFFFAOYSA-N | StdInChIKey = MYSWGUAQZAJSOK-UHFFFAOYSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}} }}


<!-- Definition and medical uses -->
'''Ciprofloxacin''' (]) is a synthetic ] ] of the ] drug class.<ref>{{Cite journal | last1 = Nelson | first1 = JM. | last2 = Chiller | first2 = TM. | last3 = Powers | first3 = JH. | last4 = Angulo | first4 = FJ. | title = Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story. | journal = Clin Infect Dis | volume = 44 | issue = 7 | pages = 977–80 | month = Apr | year = 2007 | doi = 10.1086/512369 | pmid = 17342653 }}</ref><ref>{{Cite journal | last1 = Kawahara | first1 = S. | title = | journal = Nippon Rinsho | volume = 56 | issue = 12 | pages = 3096–9 | month = Dec | year = 1998 | pmid = 9883617 }}</ref>
'''Ciprofloxacin''' is a ] ] used to treat a number of ].<ref name=AHFS2015>{{cite web |title=Ciprofloxacin Hydrochloride |url=https://www.drugs.com/monograph/ciprofloxacin-hydrochloride.html |publisher=The American Society of Health-System Pharmacists |access-date=23 August 2015 |url-status=live |archive-url=https://web.archive.org/web/20150923232645/http://www.drugs.com/monograph/ciprofloxacin-hydrochloride.html |archive-date=23 September 2015}}</ref> This includes bone and ]s, intra-abdominal infections, certain types of ], ]s, skin infections, ], and ]s, among others.<ref name=AHFS2015/> For some infections it is used in addition to other antibiotics.<ref name=AHFS2015/> It can be taken by mouth, as eye drops, as ear drops, or intravenously.<ref name=AHFS2015/><ref name=":0">{{cite web |url=https://www.webmd.com/drugs/2/drug-91414-6093/ciprofloxacin-ophthalmic-eye/ciprofloxacin-drops-ophthalmic/details |title=Ciprofloxacin Hcl Drops |date=22 February 2018 |website=WebMD |access-date=22 February 2018}}</ref>
It is a second-generation ] antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of protein.


<!-- Side effects and mechanism-->
Ciprofloxacin is marketed worldwide with over three hundred different brand names. In the United States, Canada, and the UK, it is marketed as '''Baycip''', '''Ciloxan''', '''Ciflox''', '''Cipro''', '''Cipro XR''', '''Cipro XL''', '''Ciproxin''', '''Prociflor''', and most recently, '''Proquin'''. It is also marketed as '''Ciprex''' in India and Russia and "Cetraxal" in Spain. In addition, ciprofloxacin is available as a generic drug under a variety of different brand names and is also available for limited use in ].
Common side effects include nausea, vomiting, and diarrhea.<ref name=AHFS2015/> Severe side effects include an increased risk of ], ], and nerve damage.<ref name=AHFS2015/> In people with ], there is worsening muscle weakness.<ref name=AHFS2015/> Rates of side effects appear to be higher than some groups of antibiotics such as ]s but lower than others such as ].<ref name=He2013>{{cite journal |vauthors=Heidelbaugh JJ, Holmstrom H |title=The perils of prescribing fluoroquinolones |url=http://www.jfponline.com/Pages.asp?AID=11235 |journal=The Journal of Family Practice |volume=62 |issue=4 |pages=191–197 |date=April 2013 |pmid=23570031}}</ref> Studies in other animals raise concerns regarding use in ].<ref name=AG2015/> No problems were identified, however, in the children of a small number of women who took the medication.<ref name=AG2015>{{cite web |title=Prescribing medicines in pregnancy database |url=http://www.tga.gov.au/hp/medicines-pregnancy.htm |url-status=live |publisher=Government of Australia |date=23 August 2015 |archive-url=https://web.archive.org/web/20140408040902/http://www.tga.gov.au/hp/medicines-pregnancy.htm |archive-date=8 April 2014}}</ref> It appears to be safe during ].<ref name=AHFS2015/> It is a second-generation fluoroquinolone with a ] that usually results in the ].<ref name=AHFS2015/><ref name=":1">{{cite journal |vauthors=Ball P |title=Quinolone generations: natural history or natural selection? |journal=The Journal of Antimicrobial Chemotherapy |volume=46 Suppl T1 |pages=17–24 |date=July 2000 |pmid=10997595 |doi=10.1093/oxfordjournals.jac.a020889 |doi-access = free | title-link = doi }}</ref><ref>{{cite journal |vauthors=Oliphant CM, Green GM |title=Quinolones: a comprehensive review |url=http://www.aafp.org/link_out?pmid=11858629 |journal=American Family Physician |volume=65 |issue=3 |pages=455–464 |date=February 2002 |doi=10.1016/s0022-5347(17)67120-9 |pmid=1185862}}</ref>


<!-- History, society and culture -->
Ciprofloxacin was first patented in 1983 by ] and subsequently approved by the ] (FDA) in 1987. Ciprofloxacin has 12 FDA-approved human uses and other veterinary uses, but it is often used for unapproved uses (off-label). Ciprofloxacin interacts with other drugs, herbal and natural supplements, and thyroid medications.<ref>{{cite journal |author=Cooper JG, Harboe K, Frost SK, Skadberg Ø |title=Ciprofloxacin interacts with thyroid replacement therapy |journal=BMJ |volume=330 |issue=7498 |page=1002 |year=2005 |month=April |pmid=15860826 |pmc=557149 |doi=10.1136/bmj.330.7498.1002 |url= |first1=JG |first2=K |first3=SK |issn=0959-8138}}</ref>
Ciprofloxacin was patented in 1980 and introduced by Bayer in 1987.<ref>{{cite book |title=Oxford Handbook of Infectious Diseases and Microbiology |url=https://books.google.com/books?id=5W-WBQAAQBAJ&pg=PT56 |url-status=live |publisher=OUP Oxford |date=2009 |page=56 |archive-url=https://web.archive.org/web/20170908143257/https://books.google.com/books?id=5W-WBQAAQBAJ&pg=PT56 |archive-date=8 September 2017 |isbn=978-0-19-103962-1}}</ref><ref name=Fis2006>{{cite book |vauthors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA500 |publisher=] |date=2006 |page=500 |isbn=978-3-527-60749-5}}</ref> It is on the ].<ref name="WHO21st">{{cite book |vauthors=((World Health Organization)) |author-link=World Health Organization |title=World Health Organization model list of essential medicines: 21st list 2019 |publisher=World Health Organization |location=Geneva |year=2019 |id=WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO |hdl=10665/325771 |hdl-access=free}}</ref><ref name="WHO22nd">{{cite book |vauthors=((World Health Organization)) |title=World Health Organization model list of essential medicines: 22nd list (2021) |publisher=World Health Organization |location=Geneva |year=2021 |id=WHO/MHP/HPS/EML/2021.02 |hdl=10665/345533 |hdl-access=free}}</ref> The World Health Organization classifies ciprofloxacin as critically important for human medicine.<ref>{{cite book |vauthors=((World Health Organization)) |title=Critically important antimicrobials for human medicine |edition=6th revision |publisher=World Health Organization |location=Geneva |year=2019 |hdl=10665/312266 |hdl-access=free |isbn=978-92-4-151552-8}}</ref> It is available as a ].<ref name=AHFS2015/><ref name=Ric2014>{{cite book |vauthors=Hamilton RJ |title=Tarascon pharmacopoeia |url=https://books.google.com/books?id=F6YdAwAAQBAJ&pg=PA85 |url-status=live |publisher=Jones & Bartlett Publishers |edition=15th |date=2014 |page=85 |archive-url=https://web.archive.org/web/20170908143257/https://books.google.com/books?id=F6YdAwAAQBAJ&pg=PA85 |archive-date=8 September 2017 |isbn=978-1-284-05671-6}}</ref> In 2022, it was the 181st most commonly prescribed medication in the United States, with more than 2{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Ciprofloxacin Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Ciprofloxacin | access-date = 30 August 2024 }}</ref>

As of 2011 the FDA has added two ] for this drug in reference to spontaneous tendon ruptures and the fact that ciprofloxacin may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Such an adverse reaction is a potentially life-threatening event and may require ventilatory support.<ref>http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019537s075,020780s033lbl.pdf</ref>


==Medical uses== ==Medical uses==
Ciprofloxacin is used to treat a number of infections including: infections of bones and joints, ], ], ], ], ], ], ], ], ], among others.<ref name=AHFS>{{cite web|title=Ciprofloxacin-Hydrochloride|url=http://www.drugs.com/monograph/ciprofloxacin-hydrochloride.html|work=The American Society of Health-System Pharmacists|accessdate=3 April 2011}}</ref> Ciprofloxacin is used to treat a wide variety of infections, including ], ], bacterial ], ], ], ], ], ], ], ], and ].<ref name=AHFS2015/>


Ciprofloxacin only treats bacterial infections; it does not treat viral infections such as the ]. For certain uses including acute sinusitis, lower respiratory tract infections and uncomplicated ], ciprofloxacin is not considered a first-line agent.
*]s (not recommended as a first-line antibiotic)<ref>{{cite web |title=Fluroquinolone Drug Class Review |url=http://pharmacy.oregonstate.edu/drug_policy/pages/dur_board/reviews/articles/fluroquinolone-lit.html |publisher=Oregon State University College of Pharmacy |year=2002 |accessdate=4 September 2009}}</ref>
*Acute uncomplicated ] in females
*] (not recommended as a first-line antibiotic choice)<ref>{{cite journal |pmid=15492337 |url=http://www.annals.org/content/141/8/581.full.pdf |journal=Annals of Internal Medicine |title=Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial |volume=141 |issue=8 |pages=581–9 |date= October 19, 2004 | last1 = Alexander | first1 = RB | last2 = Propert | first2 = KJ | last3 = Schaeffer | first3 = AJ | last4 = Landis | first4 = JR | last5 = Nickel | first5 = JC | last6 = O'Leary | first6 = MP | last7 = Pontari | first7 = MA | last8 = McNaughton-Collins | first8 = M | last9 = Shoskes | first9 = DA |quote=Conclusion: Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms. }}</ref><ref>{{cite web |author=J. Dimitrakov |coauthors=J. Tchitalov, T. Zlatanov, D. Dikov |title=A Prospective, Randomized, Double-Blind, Placebo-Controlled Study Of Antibiotics For The Treatment Of Category Iiib Chronic Pelvic Pain Syndrome In Men |url=http://www.prostatitis.org/a92000.html |publisher=Third International Chronic Prostatitis Network |accessdate=4 September 2009}}</ref>
*]s (not recommended as a first-line antibiotic choice)<ref name=cfaeocb>{{cite journal |author=Zuger A |date=3 November 1998 |title=Ciprofloxacin for Acute Exacerbations of Chronic Bronchitis |journal=Journal Watch (General) |url=http://general-medicine.jwatch.org/cgi/content/citation/1998/1103/4 |quote=Because of its unpredictable activity against the pneumococcus, ciprofloxacin is not usually considered a first-line treatment for respiratory infections... |volume=1998 |issue=1103 |page=4 }}</ref><ref>{{Cite journal | last1 = Vardakas | first1 = KZ | last2 = Siempos | first2 = II | last3 = Grammatikos | first3 = A | last4 = Athanassa | first4 = Z | last5 = Korbila | first5 = IP | last6 = Falagas | first6 = ME |title = Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials | journal = CMAJ | volume = 179 | issue = 12 | pages = 1269–77 | year = 2008 | month = December | doi = 10.1503/cmaj.080358 | pmid = 19047608 | pmc = 2585120 }}</ref><ref name="pmid8019264">{{cite journal | last1 = Donaldson | first1 = PM | last2 = Pallett | first2 = AP | last3 = Carroll | first3 = MP | title = Ciprofloxacin in general practice | journal = BMJ (Clinical Research Ed.) | volume = 308 | issue = 6941 | page = 1437 | year = 1994 | month = May | pmid = 8019264 | pmc = 2540361 | issn = 0959-8138 }}</ref>
*] (not recommended as a first-line antibiotic choice)<ref name="Karageorgopoulos-2008">{{Cite journal | last1 = Karageorgopoulos | first1 = DE. | last2 = Giannopoulou | first2 = KP. | last3 = Grammatikos | first3 = AP. | last4 = Dimopoulos | first4 = G. | last5 = Falagas | first5 = ME. | title = Fluoroquinolones compared with beta-lactam antibiotics for the treatment of acute bacterial sinusitis: a meta-analysis of randomized controlled trials | journal = CMAJ | volume = 178 | issue = 7 | pages = 845–54 | month = March | year = 2008 | doi = 10.1503/cmaj.071157 | pmid = 18362380 | pmc = 2267830}}</ref>
*Skin and skin structure infections
*Bone and joint infections
*Infectious diarrhea
*] (enteric fever) caused by ''Salmonella typhi''
*Uncomplicated cervical and urethra gonorrhea (due to ''N. gonorrhoeae'') – however, this indication is no longer effective in some areas (for example, Asian countries,<ref>(World Health Organization (WHO) Western Pacific Region Gonococcal Antimicrobial Susceptibility Programme (GASP) Report- 2000. Commun Dis Intell 2001; 25:274-277).
</ref> United States (including Hawaii), Canada,<ref>{{cite web |author=DEPARTMENT OF HEALTH AND HUMAN SERVICES |authorlink=DEPARTMENT OF HEALTH AND HUMAN SERVICES |coauthors=] |title=Gonococcal Isolate Surveillance Project (GISP) Annual Report - 2003 |url=http://www.cdc.gov/STD/gisp2003/GISP2003.pdf |publisher=Center for Disease Controlo |location=USA |format=PDF |month=November |year=2004 |accessdate=31 August 2009}}</ref> and Scotland)<ref>{{cite journal |author=Hugh Young |date=22 July 2003 |title=Ciprofloxacin resistant gonorrhoea: the situation in Scotland and implications for therapy |journal=SCIEH Weekly Report - SCOTTISH CENTRE FOR INFECTION AND ENVIRONMENTAL HEALTH |volume=37 |publisher=National Health Service |location=Scotland |issn=1357-4493 |doi= |url=http://www.documents.hps.scot.nhs.uk/ewr/pdf2003/0329.pdf |format=PDF }}</ref> due to bacterial resistance. Fluoroquinolones are no longer recommended in the USA for this indication.<ref>{{cite journal |date=13 April 2007 |title=Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections.|journal=Morbidity and Mortality Weekly Report |volume=56 |issue=14 |pages=332–336 |publisher=Center for Disease Control |location=USA |url=Center for Disease Control |format=PDF |accessdate=31 August 2009 |pmid=17431378 |author1=Centers for Disease Control and Prevention (CDC) }}</ref>


Ciprofloxacin occupies an important role in treatment guidelines issued by major medical societies for the treatment of serious infections, especially those likely to be caused by Gram-negative bacteria, including '']''. For example, ciprofloxacin in combination with ] is one of several first-line antibiotic regimens recommended by the ] for the treatment of community-acquired abdominal infections in adults.<ref>{{cite journal |vauthors = Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP, Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB, Sawyer RG, Bartlett JG |title = Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America |journal = Clinical Infectious Diseases |volume = 50 |issue = 2 |pages = 133–64 |date = January 2010 |pmid = 20034345 |doi = 10.1086/649554 |author-link11 = Sherwood Gorbach |doi-access = free | title-link = doi }}</ref> It also features prominently in treatment guidelines for acute pyelonephritis, complicated or hospital-acquired urinary tract infection, acute or chronic prostatitis,<ref name=uroweb2013>{{cite web |vauthors = Grabe M, Bjerklund-Johansen TE, Botto H, Çek M, Naber KG, Pickard RS, Tenke P, Wagenlehner F, Wullt B |title = Guidelines on Urological Infections |publisher = European Association of Urology |archive-url = https://web.archive.org/web/20131231000606/http://www.uroweb.org/gls/pdf/18_Urological%20infections_LR.pdf |archive-date=31 December 2013 |date=2013 |url=http://www.uroweb.org/gls/pdf/18_Urological%20infections_LR.pdf |url-status=dead}}</ref> certain types of endocarditis,<ref>{{cite journal |vauthors = Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF, Levison ME, Ferrieri P, Gerber MA, Tani LY, Gewitz MH, Tong DC, Steckelberg JM, Baltimore RS, Shulman ST, Burns JC, Falace DA, Newburger JW, Pallasch TJ, Takahashi M, Taubert KA |title = Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America |journal = Circulation |volume = 111 |issue = 23 |pages = e394–434 |date = June 2005 |pmid = 15956145 |doi = 10.1161/CIRCULATIONAHA.105.165564 |author23 = Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia |author22 = Council on Cardiovascular Disease in the Young |author21 = Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease |author25 = Infectious Diseases Society of America |author24 = American Heart Association |doi-access = free | title-link = doi }}</ref> certain skin infections,<ref>{{cite journal |vauthors = Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan EL, Montoya JG, Wade JC |title = Practice guidelines for the diagnosis and management of skin and soft-tissue infections |journal = Clinical Infectious Diseases |volume = 41 |issue = 10 |pages = 1373–406 |date = November 2005 |pmid = 16231249 |doi = 10.1086/497143 |doi-access = free | title-link = doi }}</ref> and prosthetic joint infections.<ref>{{cite journal |vauthors = Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, Rao N, Hanssen A, Wilson WR |title = Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America |journal = Clinical Infectious Diseases |volume = 56 |issue = 1 |pages = e1–e25 |date = January 2013 |pmid = 23223583 |doi = 10.1093/cid/cis803 |author10 = Infectious Diseases Society of America. |doi-access = free | title-link = doi }}</ref>
Ciprofloxacin is not recommended for the treatment of ].<ref>{{cite journal |pmid=16034951 |year=2005 |month=July |title=Fluoroquinolones for treating tuberculosis |volume= |issue=3 |pages=CD004795 |issn= |doi=10.1002/14651858.CD004795.pub2 |journal=Cochrane database of systematic reviews (Online) | last1 = Ziganshina | first1 = LE | last2 = Vizel | first2 = AA | last3 = Squire | first3 = SB | editor1-last = Ziganshina | editor1-first = Lilia }}</ref>


In other cases, treatment guidelines are more restrictive, recommending in most cases that older, narrower-spectrum drugs be used as first-line therapy for less severe infections to minimize fluoroquinolone-resistance development. For example, the Infectious Diseases Society of America recommends the use of ciprofloxacin and other fluoroquinolones in urinary tract infections be reserved to cases of proven or expected resistance to narrower-spectrum drugs such as ] or ].<ref>{{cite journal |vauthors = Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE |title = International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases |journal = Clinical Infectious Diseases |volume = 52 |issue = 5 |pages = e103–20 |date = March 2011 |pmid = 21292654 |doi = 10.1093/cid/ciq257 |doi-access = free | title-link = doi }}</ref> The ] recommends ciprofloxacin as an alternative regimen for the treatment of uncomplicated urinary tract infections, but cautions that the potential for "adverse events have to be considered".<ref name=uroweb2013/>
As well as in combination with other specific drugs:


Although approved by regulatory authorities for the treatment of respiratory infections, ciprofloxacin is not recommended for respiratory infections by most treatment guidelines due in part to its modest activity against the common respiratory pathogen '']''.<ref name=cfaeocb>{{cite journal |vauthors=Hoogkamp-Korstanje JA, Klein SJ |title=Ciprofloxacin in acute exacerbations of chronic bronchitis |journal=The Journal of Antimicrobial Chemotherapy |volume=18 |issue=3 |pages=407–413 |date=September 1986 |pmid=3490468 |doi=10.1093/jac/18.3.407}}</ref><ref>{{cite journal |vauthors=Vardakas KZ, Siempos II, Grammatikos A, Athanassa Z, Korbila IP, Falagas ME |title=Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials |journal=] |volume=179 |issue=12 |pages=1269–1277 |date=December 2008 |pmid= 19047608 |pmc=2585120 |doi=10.1503/cmaj.080358}}</ref><ref name="pmid8019264">{{cite journal |vauthors=Donaldson PM, Pallett AP, Carroll MP |title=Ciprofloxacin in general practice |journal=BMJ |volume=308 |issue=6941 |page=1437 |date=May 1994 |pmid=8019264 |pmc=2540361 |doi=10.1136/bmj.308.6941.1437}}</ref> "Respiratory quinolones" such as ], having greater activity against this pathogen, are recommended as first line agents for the treatment of community-acquired pneumonia in patients with important co-morbidities and in patients requiring hospitalization (Infectious Diseases Society of America 2007). Similarly, ciprofloxacin is not recommended as a first-line treatment for ].<ref name="Karageorgopoulos-2008">{{cite journal |vauthors=Karageorgopoulos DE, Giannopoulou KP, Grammatikos AP, Dimopoulos G, Falagas ME |title=Fluoroquinolones compared with beta-lactam antibiotics for the treatment of acute bacterial sinusitis: a meta-analysis of randomized controlled trials |journal=Canadian Medical Association Journal |volume=178 |issue=7 |pages=845–854 |date=March 2008 |pmid=18362380 |pmc=2267830 |doi=10.1503/cmaj.071157}}</ref><ref>{{cite journal |vauthors=Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJ, Hicks LA, Pankey GA, Seleznick M, Volturo G, Wald ER, File TM |title=IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults |journal=Clinical Infectious Diseases |volume=54 |issue=8 |pages=e72–e112 |date=April 2012 |s2cid=1946193 |pmid=22438350 |doi=10.1093/cid/cir1043|doi-access = free | title-link = doi }}</ref>
*Complicated intra-abdominal infections (in combination with metronidazole);
*Empirical therapy for febrile neutropenic patients (in combination with piperacillin)


Ciprofloxacin is approved for the treatment of gonorrhea in many countries, but this recommendation is widely regarded as obsolete due to resistance development.<ref>{{cite web |title=Gonococcal Isolate Surveillance Project (GISP) Annual Report – 2003 |url=https://www.cdc.gov/STD/gisp2003/GISP2003.pdf |publisher=U.S. ] (CDC) |date=November 2004 |access-date=31 August 2009 |url-status=live |archive-url=https://web.archive.org/web/20090424062831/http://www.cdc.gov/std/GISP2003/GISP2003.pdf |archive-date=24 April 2009}}</ref><ref>{{cite journal |vauthors = Young H, Palmer J, Winter A |date=22 July 2003 |title=Ciprofloxacin resistant gonorrhoea: the situation in Scotland and implications for therapy |journal=SCIEH Weekly Report |volume=37 |issn=1357-4493 |url=http://www.documents.hps.scot.nhs.uk/ewr/pdf2003/0329.pdf |url-status=dead |archive-url= https://web.archive.org/web/20110722204213/http://www.documents.hps.scot.nhs.uk/ewr/pdf2003/0329.pdf |archive-date=22 July 2011|access-date=30 August 2009}}</ref><ref>{{cite journal |title = Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections |journal = MMWR. Morbidity and Mortality Weekly Report |volume = 56 |issue = 14 |pages = 332–336 |date = April 2007 |pmid = 17431378 |url = https://www.cdc.gov/mmwr/PDF/wk/mm5614.pdf |author1 = Centers for Disease Control and Prevention (CDC) }}</ref>
Oral and intravenous fluoroquinolones are not licensed by the U.S. FDA for use in children due to the risk of permanent injury to the musculoskeletal system, with two exceptions as outlined below. Within the studies submitted in response to a Pediatric Written Request (ciprofloxacin, circa 2004) the rate of arthropathy was reported to be 9.3% at one month and 13.6% at one year.<ref name=dospidp>{{cite web |first=Joette |last=Meyer |first2 = Renata |last2 = Albrecht |title = Summary of Clinical Review of Studies Submitted in Response to a Pediatric Written Request |url=http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4152b1_03_03_Cipro%20medical.pdf |publisher=] (FDA) |date=16 March 2004 |accessdate=31 August 2009}}</ref> As such the pediatric use of ciprofloxacin is restricted to proven complicated urinary tract infections and ] due to ''E. coli '' and inhalation ].<ref name=ctcos>{{cite web |title=Cipro Labeling Revision 10/03/2008 Supplement 068 |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019537s68,19847s42,19857s49,20780s26,21473s24lbl.pdf |publisher=] (FDA) |date = 2008-10-03 |accessdate=31 August 2009}}</ref> Although claimed to be effective, ciprofloxacin is not to be considered a first line agent for inhalation anthrax in the pediatric population.<ref name=dospidp/><ref>{{cite journal |issn= 0031-4005|pmid=12777590 |url=http://pediatrics.aappublications.org/cgi/reprint/111/6/e714 |format=PDF |doi= 10.1542/peds.111.6.e714 |title= Fluoroquinolone Safety in Pediatric Patients: A Prospective, Multicenter, Comparative Cohort Study in France |year= 2003 |author= Chalumeau, M. |journal= Pediatrics |volume= 111 |pages= e714 |month= June |first1= M |first2= S |first3= P |first4= JM |first5= D |first6= G |first7= G |first8= Investigators |issue= 6 Pt 1 |last2= Tonnelier |last3= D'athis |last4= Tréluyer |last5= Gendrel |last6= Bréart |last7= Pons |author8= Pediatric Fluoroquinolone Safety Study Investigators }}</ref><ref>62 Meeting of the Anti-Infective Drugs Advisory Committee</ref><ref>{{cite web |first=Evelyn R |last=Farinas |author=Public Health Service Food And Drug Administration Center For Drug Evaluation And Research |coauthors=Department Of Health And Human |title=Consult: One-Year Post Pediatric Exclusivity Postmarketing Adverse Events Review |url=http://www.fda.gov/OHRMS/DOCKETS/AC/05/briefing/2005-4152b1_03_01_Cipro%20AE.pdf |publisher=] (FDA) |date=1 March 2005 |accessdate=31 August 2009}}</ref> The CDC revoked its recommendation regarding the use of ciprofloxacin as a first line agent in treating anthrax due to the unacceptable risk documented within the Antimicrobial Postexposure Prophylaxis for Anthrax study (aka Cipro 60 day study).<ref>{{cite journal |publisher=] |location=USA |issn= 1080-6040|pmid=12396927 |url=http://www.cdc.gov/ncidod/EID/vol8no10/02-0349.htm |year=2002 |month=October |title=Antimicrobial postexposure prophylaxis for anthrax: adverse events and adherence. |volume=8 |issue=10 |pages=1124–32 |journal=Emerging infectious diseases |first1=CW |first2=M |first3=ER |first4=J |first5=S |first6=S |first7=S |first8=J |first9=R |author1=Shepard, Cw |author2=Soriano-gabarro, M |author3=Zell, Er |author4=Hayslett, J |author5=Lukacs, S |author6=Goldstein, S |author7=Factor, S |author8=Jones, J |author9=Ridzon, R |first=Group |last2=Cdc Adverse Events Working |author=Cdc, Adverse |pmc=2730317}}</ref> However, the fluoroquinolones are licensed to treat lower respiratory infections in children with cystic fibrosis in the UK.


===Pregnancy===
Current recommendations by the American Academy of Pediatrics note the systemic use of ciprofloxacin in children should be restricted to infections caused by multidrug resistant pathogens or when no safe or effective alternatives are available.<ref name=c2009>{{cite web |author=Lexi-Comp |title=Ciprofloxacin |url=http://www.merck.com/mmpe/lexicomp/ciprofloxacin.html |publisher=Merk |month=February |year=2009 |accessdate=4 September 2009}}</ref>
An expert review of published data on experiences with ciprofloxacin use during pregnancy concluded therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (quantity and quality of data=fair), but the data are insufficient to state no risk exists.<ref>{{cite journal |vauthors = Barolin GS |title = |journal = Wiener Medizinische Wochenschrift |volume = 141 |issue = 22 |pages = 512–25 |date = May 1995 |pmid = 1801454 |pmc = 1801454 }}</ref> Exposure to quinolones, including levofloxacin, during the first-trimester is not associated with an increased risk of stillbirths, premature births, birth defects, or low birth weight.<ref>{{cite journal |vauthors=Ziv A, Masarwa R, Perlman A, Ziv D, Matok I |title=Pregnancy Outcomes Following Exposure to Quinolone Antibiotics – a Systematic-Review and Meta-Analysis |journal=Pharm. Res. |volume=35 |issue=5 |pages=109 |date=March 2018 |pmid=29582196 |doi=10.1007/s11095-018-2383-8 |s2cid=4724821 }}</ref>


Two small post-marketing epidemiology studies of mostly short-term, first-trimester exposure found that fluoroquinolones did not increase risk of major malformations, spontaneous abortions, premature birth, or low birth weight.<ref name="pmid9624471">{{cite journal |vauthors = Loebstein R, Addis A, Ho E, Andreou R, Sage S, Donnenfeld AE, Schick B, Bonati M, Moretti M, Lalkin A, Pastuszak A, Koren G |title = Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study |journal = Antimicrobial Agents and Chemotherapy |volume = 42 |issue = 6 |pages = 1336–9 |date = June 1998 |pmid = 9624471 |pmc = 105599 |doi = 10.1128/AAC.42.6.1336 }}</ref><ref name="pmid8902438">{{cite journal |vauthors = Schaefer C, Amoura-Elefant E, Vial T, Ornoy A, Garbis H, Robert E, Rodriguez-Pinilla E, Pexieder T, Prapas N, Merlob P |title = Pregnancy outcome after prenatal quinolone exposure. Evaluation of a case registry of the European Network of Teratology Information Services (ENTIS) |journal = European Journal of Obstetrics, Gynecology, and Reproductive Biology |volume = 69 |issue = 2 |pages = 83–9 |date = November 1996 |pmid = 8902438 |doi = 10.1016/0301-2115(95)02524-3}}</ref>
Indications include:


===Breastfeeding===
*Complicated urinary tract infections and ] due to ''Escherichia coli''<ref name=cipro2004>{{cite web |author=Renata Albrecht |title=Cipro Labeling Revision Letter 03/25/2004 Supplement 049 Patient Population Altered |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/19537s049,19857s031,19847s027,20780s013ltr.pdf |publisher=] (FDA) |date=25 March 2004 |accessdate=7 September 2009}}</ref>
Fluoroquinolones have been reported as present in a mother's milk and thus passed on to the nursing child.<ref>{{cite journal |vauthors = Shin HC, Kim JC, Chung MK, Jung YH, Kim JS, Lee MK, Amidon GL |title = Fetal and maternal tissue distribution of the new fluoroquinolone DW-116 in pregnant rats |journal = Comparative Biochemistry and Physiology. Toxicology & Pharmacology |volume = 136 |issue = 1 |pages = 95–102 |date = September 2003 |pmid = 14522602 |doi = 10.1016/j.cca.2003.08.004 }}</ref><ref>{{cite journal |vauthors = Dan M, Weidekamm E, Sagiv R, Portmann R, Zakut H |title = Penetration of fleroxacin into breast milk and pharmacokinetics in lactating women |journal = Antimicrobial Agents and Chemotherapy |volume = 37 |issue = 2 |pages = 293–6 |date = February 1993 |pmid = 8452360 |pmc = 187655 |doi = 10.1128/AAC.37.2.293 |doi-access=free }}</ref>


===Children===
*Inhalational ] (postexposure)<ref>{{cite web |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2000/20780S08ltr.pdf |title=Cipro Labeling Revision Letter 08/30/2000 Supplement 008 New or Modified Indication |author=Dianne Murphy |publisher=] (FDA) | date = 2000-08-30 }}</ref>
Oral and intravenous ciprofloxacin are approved by the FDA for use in children for only two indications due to the risk of permanent injury to the musculoskeletal system:
# Inhalational ] (postexposure)<ref>{{cite web |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2000/20780S08ltr.pdf |title=Cipro Labeling Revision Letter 08/30/2000 Supplement 008 New or Modified Indication |vauthors = Murphy D |publisher=U.S. ] |date=30 August 2000 |url-status=live |archive-url=https://web.archive.org/web/20121018202604/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2000/20780S08ltr.pdf |archive-date=18 October 2012}}</ref>
# Complicated urinary tract infections and ] due to ''Escherichia coli'',<ref name=cipro2004>{{cite web |vauthors = Albrecht R |title=Cipro Labeling Revision Letter 03/25/2004 Supplement 049 Patient Population Altered |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/19537s049,19857s031,19847s027,20780s013ltr.pdf |publisher=U.S. ] |date=25 March 2004 |access-date=7 September 2009 |url-status=live |archive-url=https://web.archive.org/web/20121018202556/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/19537s049,19857s031,19847s027,20780s013ltr.pdf |archive-date=18 October 2012}}</ref> but never as first-line agents.


===Spectrum of activity===
Ciprofloxacin is not recommended to treat community acquired pneumonia (CAP) as a stand-alone first-line agent. The current guidelines (Infectious Diseases Society of America 2007) state, in very limited circumstances, ciprofloxacin or levofloxacin should be combined with other drugs such as a beta-lactam drug to treat specific CAP infections, but neither drug is recommended to be used separately as a stand-alone first-line agent. In addition, the current guidelines state: "Data exist suggesting that resistance to macrolides and older fluoroquinolones (ciprofloxacin and levofloxacin) results in clinical failure. Other studies have shown that repeated use of fluoroquinolones predicts an increased risk of infection with fluoroquinolone-resistant pneumococci...."<ref>{{Cite journal | last1 = Mandell | first1 = LA. | last2 = Wunderink | first2 = RG. | last3 = Anzueto | first3 = A. | last4 = Bartlett | first4 = JG. | last5 = Campbell | first5 = GD. | last6 = Dean | first6 = NC. | last7 = Dowell | first7 = SF. | last8 = File | first8 = TM. | last9 = Musher | first9 = DM. | title = Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. | journal = Clin Infect Dis | volume = 44 Suppl 2 | url = http://www.thoracic.org/sections/publications/statements/resources/idsaats-cap.pdf | format = PDF | pages = S27–72 | month = Mar | year = 2007 | doi = 10.1086/511159 | pmid = 17278083 }}{{dead link|date=April 2011}}</ref>
Its spectrum of activity includes most strains of bacterial pathogens responsible for ]s, ], ]s, and gastroenteritis.<ref>{{cite book |title=Pharmcards review cards for medical students |vauthors = Johannsen EC, Sabatine MS |date=2010 |publisher=Wolters Kluwer{{!}}Lippincott Williams & Wilkins |isbn=978-0-7817-8741-3 |edition=4th |location= Philadelphia |oclc=893525059 }}{{page needed|date=July 2018}}</ref> Ciprofloxacin is particularly effective against ] (such as '']'', '']'', '']'', '']'', '']'', '']'', and '']''), but is less effective against ] (such as methicillin-sensitive '']'', '']'', and '']'') than newer fluoroquinolones.<ref>{{cite web |url=https://www.uptodate.com/contents/fluoroquinolones |title=Fluoroquinolones |vauthors = Hooper D |date=12 February 2018 |website=UpToDate |access-date=26 February 2018}}</ref>


===Bacterial resistance===
As such, the general opinion stated in 1994 that ciprofloxacin "is not to be considered a suitable agent for use in general practice for the blind initial treatment of chest infections...."<ref name="pmid8019264" /><ref>{{Cite journal | last1 = Körner | first1 = RJ. | last2 = Reeves | first2 = DS. | last3 = MacGowan | first3 = AP. | title = Dangers of oral fluoroquinolone treatment in community acquired upper respiratory tract infections. | journal = BMJ | volume = 308 | issue = 6922 | pages = 191–2 | month = January | year = 1994 | url = http://www.bmj.com/cgi/content/extract/308/6922/191 | pmid = 8312775 | pmc = 2542530 }}</ref> does not appear to have changed within these current guidelines.
{{see also|Antibiotic abuse|Antibiotic resistance}}


As a result of its widespread use to treat minor infections readily treatable with older, narrower-spectrum antibiotics, many bacteria have developed resistance to this drug, leaving it significantly less effective than it would have been otherwise.<ref name="pmid10341191">{{cite journal |vauthors = Vatopoulos AC, Kalapothaki V, Legakis NJ |title = Bacterial resistance to ciprofloxacin in Greece: results from the National Electronic Surveillance System. Greek Network for the Surveillance of Antimicrobial Resistance |journal = Emerging Infectious Diseases |volume = 5 |issue = 3 |pages = 471–6 |date = 1999 |pmid = 10341191 |pmc = 2640758 |doi = 10.3201/eid0503.990325 }}</ref><ref>{{cite web |url = http://www.health.state.mn.us/news/pressrel/2009/bacterial022609.html |title=Bacterial resistance prompts concern among health officials |publisher= Minnesota Department of Health |date=26 February 2009 |url-status=dead |archive-url=https://web.archive.org/web/20090305232555/http://www.health.state.mn.us/news/pressrel/2009/bacterial022609.html |archive-date=5 March 2009 }}</ref>
Antibiotics may not improve the long-term clinical outcome for sinusitis.<ref>{{cite journal | author=van Buchem, F. L. | journal=The Lancet | volume=349 | issue=9053 | pages=683–687 | date= March 8, 1997 | doi=10.1016/S0140-6736(96)07585-X | title=Primary-care-based randomised placebo-controlled trial of antibiotic treatment in acute maxillary sinusitis | pmid=9078199}}</ref>
When prescribed for chronic bronchitis and acute bacterial sinusitis, the use of the fluoroquinolone class offers no compelling advantages over established treatment.<ref>{{cite journal |pmid=15310155 |url=http://dtb.bmj.com/cgi/content/abstract/42/8/61 |doi=10.1136/dtb.2004.42861 |title= Moxifloxacin - a new fluoroquinolone antibacterial |year=2004 |journal=Drug and Therapeutics Bulletin |volume=42 |page=61 |month=August |issue=8 |issn=0012-6543 }}</ref> Nor does antibiotic treatment help sore throats.<ref>{{cite journal |pmid=9270442 |url= http://www.bmj.com/archive/7104/7104e1.htm |year=1997 |month=August |title=Acute otitis media in children. |volume=315 |issue=7104 |pages=321–2 |issn=0959-8138 |pmc=2127258 |journal=BMJ (Clinical research ed.) |first1=A |first2=T |author1=Majeed, A |author2=Harris, T}}{{dead link|date=April 2011}}</ref> The use of antibiotics such as ciprofloxacin to treat bronchitis is to be considered unnecessary and as such exposes the patient to an unacceptable risk of suffering a severe adverse reaction.<ref>{{cite journal |pmid=9071245 |year=1997 |month=March |author=Hueston, Wj |title=Antibiotics: neither cost effective nor 'cough' effective. |volume=44 |issue=3 |pages=261–5 |journal=The Journal of family practice |url= http://www.nlm.nih.gov/medlineplus/antibiotics.html|format=Free full text |first1=WJ |issn=0094-3509}}</ref> Additionally, antibiotics have no effect upon viral infections, such as the common head cold or viral respiratory infections.


] to ciprofloxacin and other ]s may evolve rapidly, even during a course of treatment. Numerous ]s, including ], '']'' , and '']'' (quinolone-resistant) now exhibit resistance.<ref>M Jacobs, Worldwide Overview of Antimicrobial Resistance. International Symposium on Antimicrobial Agents and Resistance 2005.</ref> Widespread veterinary usage of fluoroquinolones, particularly in Europe, has been implicated.<ref>{{cite press release |title=Update on Extra-Label Use of Fluoroquinolones |url=https://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm127657.htm |publisher=] (CVM) |date=16 July 1996 |access-date=12 August 2009 |url-status=live |archive-url=https://web.archive.org/web/20100309003153/https://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm127657.htm |archive-date=9 March 2010}}</ref> Meanwhile, some '']'', '']'', and '']'' strains have developed resistance to ciprofloxacin to varying degrees.<ref>{{cite web |title=Ciprofloxacin Data Sheet |url=http://www.toku-e.com/Upload/Products/PDS/20120618005735.pdf |date=1 December 2010 |publisher=Toku-E |url-status=dead |archive-url=https://web.archive.org/web/20131009014110/http://www.toku-e.com/Upload/Products/PDS/20120618005735.pdf |archive-date=9 October 2013 |access-date=20 June 2012}}</ref>
Note: Ciprofloxacin may be licensed for other uses, or restricted, by the various regulatory agencies worldwide.


Fluoroquinolones had become the class of antibiotics most commonly prescribed to adults in 2002.<ref name="pmid15745724">{{cite journal |vauthors = Linder JA, Huang ES, Steinman MA, Gonzales R, Stafford RS |title = Fluoroquinolone prescribing in the United States: 1995 to 2002 |journal = The American Journal of Medicine |volume = 118 |issue = 3 |pages = 259–68 |date = March 2005 |pmid = 15745724 |doi = 10.1016/j.amjmed.2004.09.015 }}</ref> Nearly half (42%) of those prescriptions in the US were for conditions not approved by the FDA, such as acute bronchitis, otitis media, and acute upper respiratory tract infection.<ref name="pmid15745724"/>
===Availability===
Ciprofloxacin is available as tablets, intravenous solutions, eye and ear drops


==Contraindications== ==Contraindications==
Contraindications include:<ref name="Cipro FDA label" />
As noted above, under licensed use, ciprofloxacin is also now considered to be contraindicated for the treatment of certain sexually transmitted diseases by some experts due to bacterial resistance.<ref name="nycms.org">{{cite web |author=Susan Blank |coauthors=Julia Schillinger |title=DOHMH ALERT #8:Fluoroquinolone-resistant gonorrhea, NYC |url=http://www.nycms.org/article_view.php3?view=947&part=1 |publisher=New York County Medical Society |location=USA |date=14 May 2004 |accessdate=22 July 2009}}</ref>
* Taking ] at the same time
* Use by those who are hypersensitive to any member of the ] class of antimicrobial agents
* Use by those who are diagnosed with myasthenia gravis, as muscle weakness may be exacerbated<ref>{{cite book |vauthors=Thai T, Salisbury BH, Zito PM |chapter=Ciprofloxacin |chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK535454/ |title=StatPearls |publisher=StatPearls Publishing |location=Treasure Island, FL |date=2022 |pmid=30571075 |access-date=31 January 2022}}</ref>


Ciprofloxacin is also considered to be contraindicated in children (except for the indications outlined above), in ], to nursing mothers, and in people with ] or other ] disorders.
There are only four contraindications found within the 2009 package insert:<ref name="accessdata.fda.gov">{{cite web |title=Cipro Labeling Revision 02/25/2011 Supplement 075 |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019537s075,020780s033lbl.pdf |publisher=] (FDA) |date=2011-02-25 |accessdate=1 April 2011 }}</ref>


Caution may be required in people with ] or ].<ref>{{cite journal |vauthors=LeMaire SA, Zhang L, Zhang NS, Luo W, Barrish JP, Zhang Q, Coselli JS, Shen YH |title=Ciprofloxacin accelerates aortic enlargement and promotes dissection and rupture in Marfan mice |journal=] |volume=163 |issue=3 |pages=e215–e226 |date=March 2022 |s2cid=224937717 |pmid=34586071 |doi=10.1016/j.jtcvs.2020.09.069|doi-access=free }}</ref>
*"Coadministration of ciprofloxacin with other drugs primarily metabolized by ] results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the coadministered drug."


==Adverse effects==
*"Concomitant administration with ] is contraindicated."
Adverse effects can involve the tendons, muscles, joints, nerves, and the central nervous system.<ref name=FDA2018>{{cite web |title=Drug Safety and Availability – FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects |url=https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm |publisher=U.S. ] (FDA) |access-date=10 January 2018}}</ref><ref name="Fluoroquinolones increase the risk">{{cite journal |vauthors=Liu X, Ma J, Huang L, Zhu W |title=Fluoroquinolones increase the risk of serious arrhythmias: A systematic review and meta-analysis |journal=Medicine (Baltimore) |volume=96 |issue=44 |pages=e8273 |date=November 2017 |pmid=29095256 |pmc=5682775 |doi=10.1097/MD.0000000000008273}}</ref>


Rates of adverse effects appear to be higher than with some groups of antibiotics such as ]s but lower than with others such as ].<ref name=He2013/> Compared to other antibiotics some studies find a higher rate of adverse effects<ref name=Br2013>{{cite journal |vauthors = Brown KA, Khanafer N, Daneman N, Fisman DN |title = Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection |journal = Antimicrobial Agents and Chemotherapy |volume = 57 |issue = 5 |pages = 2326–32 |date = May 2013 |pmid = 23478961 |pmc = 3632900 |doi = 10.1128/AAC.02176-12 }}</ref><ref name=Fal2006>{{cite journal |vauthors = Falagas ME, Matthaiou DK, Vardakas KZ |title = Fluoroquinolones vs beta-lactams for empirical treatment of immunocompetent patients with skin and soft tissue infections: a meta-analysis of randomized controlled trials |journal = Mayo Clinic Proceedings |volume = 81 |issue = 12 |pages = 1553–66 |date = December 2006 |pmid = 17165634 |doi = 10.4065/81.12.1553 }}</ref> while others find no difference.<ref name=Kn2012>{{cite journal |vauthors = Knottnerus BJ, Grigoryan L, Geerlings SE, Moll van Charante EP, Verheij TJ, Kessels AG, ter Riet G |title = Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: network meta-analysis of randomized trials |journal = Family Practice |volume = 29 |issue = 6 |pages = 659–70 |date = December 2012 |pmid = 22516128 |doi = 10.1093/fampra/cms029 |doi-access = free | title-link = doi }}</ref>
*"Ciprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components."


In clinical trials most of the adverse events were described as mild or moderate in severity, abated soon after the drug was discontinued, and required no treatment.<ref name="Cipro FDA label" /> Some adverse effects may be permanent.<ref name=FDA2018/> Ciprofloxacin was stopped because of an adverse event in 1% of people treated with the medication by mouth. The most frequently reported drug-related events, from trials of all formulations, all dosages, all drug-therapy durations, and for all indications, were nausea (2.5%), diarrhea (1.6%), abnormal liver function tests (1.3%), vomiting (1%), and rash (1%). Other adverse events occurred at rates of <1%.<ref name=CiproIV>{{cite web |title=Cipro IV Meta-analysis |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019847s046,019857s053lbl.pdf |archive-url=https://web.archive.org/web/20170218081012/http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019847s046,019857s053lbl.pdf |archive-date=18 February 2017 |url-status=live |publisher=U.S. ] (FDA) |date=November 2011}}</ref>
*"Local I.V. site reactions are more frequent if the infusion time is 30 minutes or less. These may appear as local skin reactions that resolve rapidly upon completion of the infusion. Subsequent intravenous administration is not contraindicated unless the reactions recur or worsen."


===Tendon problems===
Due to growing prevalence of antibiotic resistance to the fluoroquinolones in southeast Asia, the use of ciprofloxacin in patients having been to southeast Asia is increasingly being discouraged.<ref>{{cite journal |title=Fluoroquinolone resistance in Neisseria gonorrhoeae—Colorado and Washington, 1995 |journal=MMWR Morb Mortal Wkly Rep. |volume=44 |issue=41 |pages=761–4 |year=1995 |month=October |pmid=7565558 |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/00039305.htm |issn=0149-2195 |author1=Centers for Disease Control and Prevention (CDC)}}</ref>
Ciprofloxacin includes a ] in the United States due to an increased risk of ] and tendon rupture, especially in people who are older than 60 years, people who also use corticosteroids, and people with kidney, lung, or heart transplants.<ref>{{cite journal |vauthors=Stephenson AL, Wu W, Cortes D, Rochon PA |title=Tendon Injury and Fluoroquinolone Use: A Systematic Review |journal=Drug Saf |volume=36 |issue=9 |pages=709–21 |date=September 2013 |pmid=23888427 |doi=10.1007/s40264-013-0089-8 |s2cid=24948660}}</ref> Tendon rupture can occur during therapy or even months after discontinuation of the medication.<ref>{{cite journal |vauthors = Saint F, Gueguen G, Biserte J, Fontaine C, Mazeman E |title = |language = fr |journal = Revue de Chirurgie Orthopedique et Reparatrice de l'Appareil Moteur |volume = 86 |issue = 5 |pages = 495–7 |date = September 2000 |pmid = 10970974 |url = http://www.masson.fr/masson/MDOI-RCO-09-2000-86-5-0035-1040-101019-ART7 |trans-title = Rupture of the patellar ligament one month after treatment with fluoroquinolone }}</ref> One study found that fluoroquinolone use was associated with a 1.9-fold increase in tendon problems. The risk increased to 3.2 in those over 60 years of age and to 6.2 in those over the age of 60 who were also taking corticosteroids. Among the 46,766 quinolone users in the study, 38 (0.08%) cases of Achilles tendon rupture were identified.<ref>{{cite journal |vauthors = Corrao G, Zambon A, Bertù L, Mauri A, Paleari V, Rossi C, Venegoni M |title = Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control study |journal = Drug Safety |volume = 29 |issue = 10 |pages = 889–96 |year = 2006 |pmid = 16970512 |doi = 10.2165/00002018-200629100-00006 |s2cid = 21513856 }}</ref>


===Cardiac arrhythmia===
Ciprofloxacin is also considered to be contraindicated within the pediatric population (except for the indications outlined under licensed use above), ], nursing mothers, and in patients with ] or other seizure disorders.
The fluoroquinolones, including ciprofloxacin, are associated with an increased risk of cardiac toxicity, including ] prolongation, '']'', ventricular arrhythmia, and ].<ref>{{cite journal |vauthors=Gorelik E, Masarwa R, Perlman A, Rotshild V, Abbasi M, Muszkat M, Matok I |title=Fluoroquinolones and Cardiovascular Risk: A Systematic Review, Meta-analysis and Network Meta-analysis |journal=Drug Saf |volume= 42|issue= 4|pages= 529–538|date=October 2018 |pmid=30368737 |doi=10.1007/s40264-018-0751-2 |s2cid=53105534 }}</ref><ref name="Fluoroquinolones increase the risk"/>


===Nervous system===
*'''Pregnancy'''
Because Ciprofloxacin is lipophilic, it has the ability to cross the ].<ref name="babar2013">{{cite journal |vauthors = Babar SM |title = SIADH associated with ciprofloxacin |journal = The Annals of Pharmacotherapy |volume = 47 |issue = 10 |pages = 1359–63 |date = October 2013 |pmid = 24259701 |doi = 10.1177/1060028013502457 |s2cid = 36759747 }}</ref> The 2013 FDA label warns of nervous system effects. Ciprofloxacin, like other fluoroquinolones, is known to trigger seizures or lower the seizure threshold, and may cause other central nervous system adverse effects. Headache, dizziness, and insomnia have been reported as occurring fairly commonly in postapproval review articles, along with a much lower incidence of serious CNS adverse effects such as tremors, psychosis, anxiety, hallucinations, paranoia, and suicide attempts, especially at higher doses.<ref name=He2013/> Like other fluoroquinolones, it is also known to cause peripheral neuropathy that may be irreversible, such as weakness, burning pain, tingling or numbness.<ref>{{cite web |url=https://www.fda.gov/Drugs/DrugSafety/ucm365050.htm |title=FDA Drug Safety Communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection |publisher=U.S. ] (FDA) |url-status=dead |archive-url=https://web.archive.org/web/20160528231716/https://www.fda.gov/Drugs/DrugSafety/ucm365050.htm |archive-date=28 May 2016}}</ref>
The fluoroquinolones rapidly cross the blood-placenta and blood-milk barriers, and are extensively distributed into the fetal tissues. For this reason, the fluoroquinolones are contraindicated during pregnancy due to the risk of spontaneous abortions and birth defects. The fluoroquinolones have also been reported as being present in the mother's milk and are passed on to the nursing child, which may increases the risk of the child suffering from this syndrome as well, even though the child had never been prescribed or taken any of the drugs found within this class.<ref>{{cite journal |author=Shin HC, Kim JC, Chung MK |title=Fetal and maternal tissue distribution of the new fluoroquinolone DW-116 in pregnant rats |journal=Comp. Biochem. Physiol. C Toxicol. Pharmacol. |volume=136 |issue=1 |pages=95–102 |year=2003 |month=September |pmid=14522602 |doi= 10.1016/j.cca.2003.08.004|url= |first1=HC |first2=JC |first3=MK |first4=YH |first5=JS |first6=MK |first7=GL |issn=1532-0456}}</ref><ref>{{cite journal |author=Dan M, Weidekamm E, Sagiv R, Portmann R, Zakut H |title=Penetration of fleroxacin into breast milk and pharmacokinetics in lactating women |journal=Antimicrob. Agents Chemother. |volume=37 |issue=2 |pages=293–6 |year=1993 |month=February |pmid=8452360 |pmc=187655 |doi= |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=8452360 |first1=M |first2=E |first3=R |first4=R |first5=H |issn=0066-4804}}</ref>


Fluoroquinolones have already been reported for movement disorders.<ref name=":0" /> In this context, ciprofloxacin is especially associated with ], which derives the term "ciproclonus."<ref name=":1" />
*'''Pediatric population'''
Fluoroquinolones are not licensed by the U.S. FDA for use in children due to the risk of fatalities<ref name="pmid1592498">{{cite journal |author=Karande SC, Kshirsagar NA |title=Adverse drug reaction monitoring of ciprofloxacin in pediatric practice |journal=Indian Pediatr |volume=29 |issue=2 |pages=181–8 |year=1992 |month=February |pmid=1592498 |first1=SC |first2=NA |issn=0019-6061 }}</ref> as well as permanent injury to the musculoskeletal system, with two exceptions. Ciprofloxacin is being licensed for the treatment of complicated urinary tract infections and pyelonephritis due to ''Escherichia coli'', and inhalational anthrax (postexposure), and levofloxacin was recently licensed for the treatment of inhalational anthrax (postexposure). However, the fluoroquinolones are licensed to treat lower respiratory infections in children with cystic fibrosis in the UK.


===Cancer===
Within the studies submitted in response to a Pediatric Written Request (ciprofloxacin, circa 2004), the rate of atrophy was reported to be 9.3%.<ref name=dospaidos>{{cite web |author=Joette Meyer |coauthors=Renata Albrecht |title=Division of Special Pathogen and Immunologic Drug Products Summary of Clinical Review of Studies Submitted in Response to a Pediatric Written Request |url=http://www.fda.gov/ohrms/dockets/AC/05/briefing/2005-4152b1_03_03_Cipro%20medical.pdf |publisher=] (FDA) |date=16 March 2004 |accessdate=22 July 2009}}</ref>
Ciprofloxacin is active in six of eight ''in vitro'' assays used as rapid screens for the detection of genotoxic effects, but is not active in ''in vivo'' assays of genotoxicity.<ref name="Cipro FDA label" /> Long-term carcinogenicity studies in rats and mice resulted in no carcinogenic or tumorigenic effects due to ciprofloxacin at daily oral dose levels up to 250 and 750&nbsp;mg/kg to rats and mice, respectively (about 1.7 and 2.5 times the highest recommended therapeutic dose based upon mg/m<sup>2</sup>). Results from photo co-carcinogenicity testing indicate ciprofloxacin does not reduce the time to appearance of UV-induced skin tumors as compared to vehicle control.<ref name="Cipro FDA label" />
Within the BPCA Pediatric Studies Summary for ciprofloxacin,<ref name=dospaidos/> it was stated that the overall incidence of adverse events at six weeks was 41%. This would be consistent with the safety profile found with the other fluoroquinolones studied in the pediatric population. As such, the current ban on the use of the fluoroquinolones in the pediatric population is both reasonable and supported by various clinical studies. The most recent long term study, ''BAY 0 9867 Cipro Pediatric Use Study (QUIP)'', which followed pediatric patients from 1999–2008,<ref></ref> supports the current expert opinion that the risk of permanent injury continues to outweigh the potential benefits of ciprofloxacin therapy in the pediatric population.


===Other===
Within the United States, the FDA has stated it is their intention to pursue the licensing of the fluoroquinolones for pediatric use in spite of the evidence presented at that 62 Meeting of the Anti-Infective Drugs Advisory Committee that the fluoroquinolones cause irreversible joint damage in the pediatric population.<ref>62 Meeting of the Anti-Infective Drugs Advisory Committee </ref>
The other black box warning is that ciprofloxacin should not be used in people with ] due to possible exacerbation of muscle weakness which may lead to breathing problems resulting in death or ventilator support. Fluoroquinolones are known to block neuromuscular transmission.<ref name="Cipro FDA label" /> There are concerns that fluoroquinolones including ciprofloxacin can affect cartilage in young children.<ref name="Cipro FDA label" />


'']''-associated diarrhea is a serious adverse effect of ciprofloxacin and other fluoroquinolones; it is unclear whether the risk is higher than with other broad-spectrum antibiotics.<ref name="pmid18067688">{{cite journal |vauthors = Deshpande A, Pant C, Jain A, Fraser TG, Rolston DD |title = Do fluoroquinolones predispose patients to Clostridium difficile associated disease? A review of the evidence |journal = Current Medical Research and Opinion |volume = 24 |issue = 2 |pages = 329–33 |date = February 2008 |pmid = 18067688 |doi = 10.1185/030079908X253735 |s2cid = 280563}}</ref>
==Special precautions==
The status of the patient's renal function and hepatic function must also be taken into consideration to avoid an accumulation that may lead to an overdose and the development of toxicity. Ciprofloxacin is eliminated primarily by renal excretion. However, the drug is also metabolized and partially cleared through the liver and the intestines. Modification of the dosage is ''recommended'' using the table found within the package insert for those with impaired liver or kidney function. However, since the drug is known to be substantially excreted by the kidneys, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. The duration of treatment depends upon the severity of infection and is usually 7 to 14 days.<ref name=ctcos/>


A wide range of rare but potentially fatal adverse effects reported to the US FDA or the subject of case reports includes ],<ref>{{cite web |url=https://www.fda.gov/Drugs/DrugSafety/ucm628753.htm |title=Drug Safety and Availability – FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients |publisher=U.S. ] (FDA) |access-date=4 January 2019}}</ref> ], ], low blood pressure, allergic pneumonitis, bone marrow suppression, hepatitis or liver failure, and sensitivity to light.<ref name="Cipro FDA label" /><ref name="pmid24352180">{{cite journal |vauthors=Alshammari TM, Larrat EP, Morrill HJ, Caffrey AR, Quilliam BJ, LaPlante KL |title=Risk of hepatotoxicity associated with fluoroquinolones: a national case-control safety study |journal=American Journal of Health-System Pharmacy |volume=71 |issue=1 |pages=37–43 |date=January 2014 |pmid=24352180 |doi=10.2146/ajhp130165}}</ref> The medication should be discontinued if a rash, jaundice, or other sign of hypersensitivity occurs.<ref name="Cipro FDA label" />
==Adverse effects==
{{See also|Adverse effects of fluoroquinolones}}
Serious adverse events occur more commonly with fluoroquinolones than with any other antibiotic drug classes. In most, adverse reactions are mild to moderate; however, occasionally serious adverse effects occur.<ref>{{cite journal |pmid=15942881 |year=2005 |month=July |last1=Owens Rc |first1=Jr |last2=Ambrose |first2=PG |title=Antimicrobial safety: focus on fluoroquinolones. |volume=41 Suppl 2 |pages=S144–57 |issn=1058-4838 |doi=10.1086/428055 |journal=Clinical Infectious Diseases |author2=Ambrose }}</ref><ref name="pmid11172695">{{cite journal |author=De Sarro A, De Sarro G |title=Adverse reactions to fluoroquinolones. an overview on mechanistic aspects |journal=Curr. Med. Chem. |volume=8 |issue=4 |pages=371–84 |year=2001 |month=March |pmid=11172695 |doi= |url=http://www.fqresearch.org/pdf_files/cmc.pdf |format=PDF}}</ref> There have been a number of regulatory actions taken as a result of such adverse reactions, which included published warnings,<ref>{{cite press release |title=FDA Requests Boxed Warnings on Fluoroquinolone Antimicrobial Drugs |url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116919.htm |publisher=] (FDA) |date=8 July 2008 |accessdate=5 September 2009}}</ref><ref>{{cite web |title=Information for Healthcare Professionals: Fluoroquinolone Antimicrobial Drugs |url=http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126085.htm |publisher= ] (FDA) |date=2008-07-08 |accessdate=5 September 2009}}</ref> additional warnings and safety information added to the package inserts<ref>{{cite web |title=Drugs at FDA: FDA Approved Drug Products |url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist |publisher=] (FDA) |accessdate=5 September 2009}}{{Verify source|date=April 2011}}</ref> together with the issuance of "Dear Doctor Letters"<ref>{{cite web |author=Paul MacCarthy |title=Important Change in the Avelox (moxifloxacin hydrochloride) and Cipro (ciprofloxacin) Complete Prescribing Information – Addition of Boxed Warning and Medication Guide Regarding Tendinitis and Tendon Rupture |url=http://www.avelox.com/html/pdf/dhpl.pdf |publisher=Bayer healthcare pharmaceuticals |format=PDF |date=22 October 2008 |accessdate=5 September 2009}}</ref> concerning the recent addition of Black Box Warnings. In 2004, the U.S. FDA requested new warning labels to be added to all of the fluoroquinolones, including ciprofloxacin, regarding ] (irreversible nerve damage), tendon damage, heart problems (prolonged QT Interval / ]), ], ] (muscle breakdown), ], as well as concurrent usage of ] contributing to the severity of these reactions.{{Citation needed|date=April 2011}}


Children and the elderly are at a much greater risk of experiencing adverse reactions.<ref name="autogenerated1403">{{cite journal |vauthors = Iannini PB |title = The safety profile of moxifloxacin and other fluoroquinolones in special patient populations |journal = Current Medical Research and Opinion |volume = 23 |issue = 6 |pages = 1403–13 |date = June 2007 |pmid = 17559736 |doi = 10.1185/030079907X188099 |s2cid = 34091286 }}</ref><ref>{{cite journal |vauthors = Owens RC, Ambrose PG |title = Antimicrobial safety: focus on fluoroquinolones |journal = Clinical Infectious Diseases |volume = 41 |pages = S144–57 |date = July 2005 |issue = Suppl 2 |pmid = 15942881 |doi = 10.1086/428055 |doi-access = free | title-link = doi }}</ref>
Subsequent to this, on 25 June 2007, the U.S. FDA required manufacturers to add an additional warning to the package inserts that stated "Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported in patients receiving therapy with quinolones, including ciprofloxacin."<ref>{{cite web |author=Renata Albrecht |title=Cipro Labeling Revision Letter 06/19/2006 Supplement 062 |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2006/019537s62,020780s23,019847s37,019857s42,021473s16LTR.pdf |publisher=] (FDA) |date=19 June 2006 |accessdate=5 September 2009}}</ref> It was not until 2008, (four years later) that the label revisions for ciprofloxacin included any warnings concerning heart problems (prolonged QT interval / ]). Warnings concerning rhabdomyolysis and Stevens-Johnson syndrome were still absent from the package inserts {{as of|2009|09|lc=on}}.


==Overdose==
The serious adverse effects that may occur as a result of ciprofloxacin therapy include irreversible ],<ref>{{cite web |author=Renata Albrecht |title=Cipro Labeling Revision Letter 07/14/2004 Supplement 053 |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/19537s053,054,20780s017,018ltr.pdf |publisher=] (FDA) |date=14 July 2004 |accessdate=5 September 2009}}</ref><ref>{{cite journal |pmid=7488901 |quote=One case of peripheral neuropathy has been reported. We report two cases of generalised painful dysaesthesia due to ciprofloxacin, a reaction not previously associated with this particular fluoroquinolone |year=1995 |month=November |last1=Zehnder |first1=D |last2=Hoigné |first2=R |last3=Neftel |first3=KA |last4=Sieber |first4=R |title=Painful dysaesthesia with ciprofloxacin. |volume=311 |issue=7014 |page=1204 |issn=0959-8138 |journal=BMJ (Clinical research ed.) |author2=Hoigné |author3=Neftel |author4=Sieber |pmc=2551120 }}</ref> spontaneous ] and ],<ref name=FDA1996/><ref>{{cite web |author=Renata Albrecht |title=Cipro Labeling Revision Letter 03/15/2004 Supplement 048 |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/19537slr048,050,051,20780slr012,014,015ltr.pdf |publisher=] (FDA) |date=15 March 2004 |accessdate=5 September 2009}}</ref><ref></ref><ref>{{cite web |author=Renata Albrecht |title=Cipro Labeling Revision letter 10/03/2008 Supplement 068 |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/019537s068,019847s042ltr.pdf |publisher=] (FDA) |date=3 October 2008 |accessdate=5 September 2009}}</ref> acute ] or serious liver injury (]),<ref>{{cite journal |pmid=7841570 |year=1994 |month=October |last1=Sherman |first1=O |last2=Beizer |first2=JL |title=Possible ciprofloxacin-induced acute cholestatic jaundice. |volume=28 |issue=10 |pages=1162–4 |issn=1060-0280 |journal=The Annals of pharmacotherapy |url=http://www.nlm.nih.gov/medlineplus/bileductdiseases.html |format=Free full text |author2=Beizer }}</ref><ref>{{cite journal |pmid=14994731 |year=2004 |month=January |last1=Zimpfer |first1=A |last2=Propst |first2=A |last3=Mikuz |first3=G |last4=Vogel |first4=W |last5=Terracciano |first5=L |last6=Stadlmann |first6=S |title=Ciprofloxacin-induced acute liver injury: case report and review of literature. |volume=444 |issue=1 |pages=87–9 |issn=0945-6317 |journal=Virchows Archiv : an international journal of pathology |doi=10.1007/s00428-003-0917-9 |author2=Propst |author3=Mikuz |author4=Vogel |author5=Terracciano |author6=Stadlmann }}</ref> QTc prolongation/torsades de pointes,<ref name=ctcos/> ] (TEN),<ref>{{cite journal |pmid=14735388 |year=2003 |month=December |last1=Jongen-Lavrencic |first1=M |last2=Schneeberger |last3=Van Der Hoeven |title=Ciprofloxacin-induced toxic epidermal necrolysis in a patient with systemic lupus erythematosus. |volume=31 |issue=6 |pages=428–9 |issn=0300-8126 |doi=10.1007/s15010-003-2128-3 |journal=Infection |author2=Schneeberger |author3=Van Der Hoeven }}</ref><ref name="ReferenceA">{{cite journal |pmid=8305780 |year=1993 |month=December |last1=Moshfeghi |first1=M |last2=Mandler |title=Ciprofloxacin-induced toxic epidermal necrolysis. |volume=27 |issue=12 |pages=1467–9 |issn=1060-0280 |journal=The Annals of pharmacotherapy |url= |author2=Mandler}}</ref><ref name="ReferenceA"/> and Stevens-Johnson syndrome, severe central nervous system disorders (CNS)<ref name=cipro2004/> and ] associated disease (CDAD: ]),<ref>{{cite journal |pmid=18067688 |year=2008 |month=February |last1=Deshpande |first1=A |last2=Pant |last3=Jain |last4=Fraser |last5=Rolston |title=Do fluoroquinolones predispose patients to Clostridium difficile associated disease? A review of the evidence. |volume=24 |issue=2 |pages=329–33 |issn=0300-7995 |doi=10.1185/030079908X253735 |journal=Current medical research and opinion |author2=Pant |author3=Jain |author4=Fraser |author5=Rolston }}</ref><ref>{{cite web |author=Renata Albrecht |title=Cipro Labeling Revision letter 06/25/2007 Supplement 065 |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2007/019537s65,19847s39,19857s46,20780s24,21473s22ltr.pdf |publisher=] (FDA) |date=25 June 2007 |accessdate=4 September 2009}}</ref> as well as photosensitivity/] reactions.
Overdose of ciprofloxacin may result in reversible renal toxicity. Treatment of overdose includes emptying of the stomach by induced vomiting or ], as well as administration of antacids containing magnesium, aluminium, or calcium to reduce drug absorption. Renal function and urinary pH should be monitored. Important support includes adequate hydration and urine acidification if necessary to prevent crystalluria. ] or ] can only remove less than 10% of ciprofloxacin.<ref name="FDA 81532304, R.1">{{cite web |title=Cipro Labeling Revision 04/06/2009 Supplement 073 |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019537s073,020780s030lbl.pdf |publisher=U.S. ] (FDA) |date=6 April 2009 |access-date=8 September 2009 |url-status=live |archive-url=https://web.archive.org/web/20100705053513/http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019537s073,020780s030lbl.pdf |archive-date=5 July 2010}}</ref> Ciprofloxacin may be quantified in plasma or serum to monitor for drug accumulation in patients with hepatic dysfunction or to confirm a diagnosis of poisoning in acute overdose victims.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 313–315. {{ISBN|978-0-9626523-7-0}}.</ref>


== Interactions ==
Psychotic reactions and confusional states, ],<ref>{{cite journal |pmid=11129278 |year=2000 |month=December |last1=Mann |first1=S |last2=Thillainayagam |title=Is ciprofloxacin a new cause of acute pancreatitis? |volume=31 |issue=4 |page=336 |issn=0192-0790 |journal=Journal of Clinical Gastroenterology |doi=10.1097/00004836-200012000-00014 |author2=Thillainayagam }}</ref> ], ] and ] may also occur during ciprofloxacin therapy.<ref>{{cite journal |pmid=10616701 |year=1999 |month=September |last1=Dutta |first1=TK |last2=Badhe |title=Ciprofloxacin-induced bone marrow depression. |volume=75 |issue=887 |pages=571–3 |issn=0032-5473 |journal=Postgraduate medical journal |author2=Badhe |pmc=1741342 }}</ref><ref>{{cite journal |pmid=12911170 |year=2003 |month=July |last1=Lim |first1=S |last2=Alam |title=Ciprofloxacin-induced acute interstitial nephritis and autoimmune hemolytic anemia. |volume=25 |issue=4 |pages=647–51 |issn=0886-022X |journal=Renal failure |doi=10.1081/JDI-120022557 |author2=Alam }}</ref> Additional serious adverse reactions include temporary, as well as permanent, ],<ref>{{cite journal |pmid=2374675 |year=1990 |month=June |last1=Vrabec |first1=TR |last2=Sergott |last3=Jaeger |last4=Savino |last5=Bosley |title=Reversible visual loss in a patient receiving high-dose ciprofloxacin hydrochloride (Cipro) |volume=97 |issue=6 |pages=707–10 |issn=0161-6420 |journal=Ophthalmology |url= |author2=Sergott |author3=Jaeger |author4=Savino |author5=Bosley }}</ref><ref>{{cite journal |pmid=17300586 |year=2007 |month=January |last1=Samarakoon |first1=N |last2=Harrisberg |last3=Ell |title=Ciprofloxacin-induced toxic optic neuropathy. |volume=35 |issue=1 |pages=102–4 |issn=1442-6404 |doi=10.1111/j.1442-9071.2007.01427.x |journal=Clinical & experimental ophthalmology |author2=Harrisberg |author3=Ell }}</ref> irreversible ],<ref name=pmid19643481>{{cite journal |pmid=19643481 |year=2009 |month=September |last1=Fraunfelder |first1=FW |last2=Fraunfelder |title=Diplopia and fluoroquinolones |volume=116 |issue=9 |pages=1814–7 |issn=0161-6420 |doi=10.1016/j.ophtha.2009.06.027 |journal=Ophthalmology |author2=Fraunfelder }}</ref> drug induced psychosis<ref>{{cite journal |pmid=7604468 |year=1995 |month=July |last1=Mulhall |first1=JP |last2=Bergmann |title=Ciprofloxacin-induced acute psychosis. |volume=46 |issue=1 |pages=102–3 |issn=0090-4295 |doi=10.1016/S0090-4295(99)80171-X |journal=Urology |author2=Bergmann }}</ref><ref>{{cite journal |pmid=1504404 |year=1992 |month=July |last1=Reeves |first1=RR |title=Ciprofloxacin-induced psychosis. |volume=26 |issue=7-8 |pages=930–1 |issn=1060-0280 |journal=The Annals of pharmacotherapy |url= }}</ref> and ] (involuntary muscle movements),<ref>{{cite journal |pmid=15739219 |year=2005 |month=April |last1=Azar |first1=S |last2=Ramjiani |last3=Van Gerpen |title=Ciprofloxacin-induced chorea. |volume=20 |issue=4 |pages=513–4; author reply 514 |issn=0885-3185 |doi=10.1002/mds.20425 |journal=Movement disorders : official journal of the Movement Disorder Society |author2=Ramjiani |author3=Van Gerpen }}</ref> impaired ], ], abdominal pain, ], ], ] and ].<ref>{{cite journal |pmid=3053554 |year=1988 |month=August |title=Therapy of acute and chronic gram-negative osteomyelitis with ciprofloxacin. Report from a Swedish Study Group. |volume=22 |issue=2 |pages=221–8 |issn=0305-7453 |journal=The Journal of antimicrobial chemotherapy |doi=10.1093/jac/22.2.221 }}</ref><ref>{{cite journal |pmid=7488901 |quote=One case of peripheral neuropathy has been reported. We report two cases of generalised painful dysaesthesia due to ciprofloxacin, a reaction not previously associated with this particular fluoroquinolone. |year=1995 |month=November |last1=Zehnder |first1=D |last2=Hoigné |last3=Neftel |last4=Sieber |title=Painful dysaesthesia with ciprofloxacin. |volume=311 |issue=7014 |page=1204 |issn=0959-8138 |journal=BMJ (Clinical research ed.) |author2=Hoigné |author3=Neftel |author4=Sieber |pmc=2551120 }}</ref> ], commonly known as idiopathic intracranial hypertension (IIH), (also referred to as increased intracranial pressure), has been reported to occur as a serious adverse reaction to ciprofloxacin.<ref>{{cite journal |pmid=2248512 |year=1990 |month=October |last1=Winrow |first1=AP |last2=Supramaniam |title=Benign intracranial hypertension after ciprofloxacin administration. |volume=65 |issue=10 |pages=1165–6 |issn=0003-9888 |journal=Archives of disease in childhood |doi=10.1136/adc.65.10.1165 |author2=Supramaniam |pmc=1792342 }}</ref>
Ciprofloxacin interacts with certain foods and several other drugs leading to undesirable increases or decreases in the serum levels or distribution of one or both drugs.


Ciprofloxacin should not be taken with antacids containing magnesium or aluminum, highly buffered drugs (], ], ], ]), or with supplements containing calcium, iron, or zinc. It should be taken two hours before or six hours after these products. Magnesium or aluminum antacids turn ciprofloxacin into insoluble salts that are not readily absorbed by the intestinal tract, reducing peak serum concentrations by 90% or more, leading to therapeutic failure. Additionally, it should not be taken with dairy products or calcium-fortified juices alone, as peak serum concentration and the area under the serum concentration-time curve can be reduced up to 40%. However, ciprofloxacin may be taken with dairy products or calcium-fortified juices as part of a meal.<ref name="FDA 81532304, R.1"/><ref>{{cite journal |vauthors = Rodvold KA, Piscitelli SC |title = New oral macrolide and fluoroquinolone antibiotics: an overview of pharmacokinetics, interactions, and safety |journal = Clinical Infectious Diseases |volume = 17 |pages = S192–9 |date = August 1993 |issue = Suppl 1 |pmid = 8399914 |doi = 10.1093/clinids/17.supplement_1.s192 }}</ref><ref name="Bolhuis MS, Panday PN, Pranger AD, Kosterink JG, Alffenaar JW 2011 865–913">{{cite journal |vauthors = Bolhuis MS, Panday PN, Pranger AD, Kosterink JG, Alffenaar JW |title = Pharmacokinetic drug interactions of antimicrobial drugs: a systematic review on oxazolidinones, rifamycines, macrolides, fluoroquinolones, and Beta-lactams |journal = Pharmaceutics |volume = 3 |issue = 4 |pages = 865–913 |date = November 2011 |pmid = 24309312 |pmc = 3857062 |doi = 10.3390/pharmaceutics3040865 |doi-access = free | title-link = doi }}</ref>
Children and the elderly are at a much greater risk of experiencing such adverse reactions.<ref name="autogenerated1403">{{cite journal |pmid=17559736 |year=2007 |month=June |last1=Iannini |first1=PB |title=The safety profile of moxifloxacin and other fluoroquinolones in special patient populations. |volume=23 |issue=6 |pages=1403–13 |issn=0300-7995 |doi=10.1185/030079907X188099 |journal=Current medical research and opinion }}</ref><ref>{{cite journal |pmid=15942881 |year=2005 |month=July |last1=Owens Rc |first1=Jr |last2=Ambrose |title=Antimicrobial safety: focus on fluoroquinolones. |volume=41 Suppl 2 |pages=S144–57 |issn=1058-4838 |doi=10.1086/428055 |journal=Clinical Infectious Diseases |author2=Ambrose }}</ref> Such reactions may manifest during fluoroquinolone therapy, and long after it had been discontinued.<ref>{{cite journal |pmid=10970974 |year=2000 |month=September |last1=Saint |first1=F |last2=Gueguen |last3=Biserte |last4=Fontaine |last5=Mazeman |title=Rupture of the patellar ligament one month after treatment with fluoroquinolone |volume=86 |issue=5 |pages=495–7 |issn=0035-1040 |journal=Revue de chirurgie orthopedique et reparatrice de l'appareil moteur |author2=Gueguen |author3=Biserte |author4=Fontaine |author5=Mazeman }}</ref>


Ciprofloxacin inhibits the drug-metabolizing enzyme ] and thereby can reduce the clearance of drugs metabolized by that enzyme. CYP1A2 substrates that exhibit increased serum levels in ciprofloxacin-treated patients include ], ], ], ], ], ], and ]. Co-administration of ciprofloxacin with the CYP1A2 substrate tizanidine (Zanaflex) is contraindicated due to a 583% increase in the peak serum concentrations of tizanidine when administered with ciprofloxacin as compared to administration of tizanidine alone. Use of ciprofloxacin is cautioned in patients on theophylline due to its narrow therapeutic index. The authors of one review recommended that patients being treated with ciprofloxacin reduce their caffeine intake. Evidence for significant interactions with several other CYP1A2 substrates such as ] is equivocal or conflicting.<ref name="Bolhuis MS, Panday PN, Pranger AD, Kosterink JG, Alffenaar JW 2011 865–913"/><ref name="Cipro FDA label" /><ref>{{cite journal |vauthors = Janknegt R |title = Drug interactions with quinolones |journal = The Journal of Antimicrobial Chemotherapy |volume = 26 Suppl D |pages = 7–29 |date = November 1990 |pmid = 2286594 |doi = 10.1093/jac/26.suppl_D.7 }}</ref>
Serious visual complications have also been reported to occur with ] fluoroquinolone therapy, which may also occur with ciprofloxacin eye drops, especially ], but also ] and ]. This increased incidents of corneal perforation may be due to fluoroquinolones causing alterations in ] ], leading to a reduction in ] strength.<ref>{{cite journal |pmid=10729294 |year=2000 |month=April |last1=Gangopadhyay |first1=N |last2=Daniell |last3=Weih |last4=Taylor |title=Fluoroquinolone and fortified antibiotics for treating bacterial corneal ulcers. |volume=84 |issue=4 |pages=378–84 |issn=0007-1161 |journal=The British journal of ophthalmology |author2=Daniell |author3=Weih |author4=Taylor |pmc=1723447 |doi=10.1136/bjo.84.4.378 }}</ref><ref>{{cite journal |pmid=17068466 |year=2006 |month=August |last1=Walter |first1=K |last2=Tyler |title=Severe corneal toxicity after topical fluoroquinolone therapy: report of two cases. |volume=25 |issue=7 |pages=855–7 |issn=0277-3740 |journal=Cornea |author2=Tyler |doi=10.1097/01.ico.0000224642.43601.14 }}</ref> As noted previously permanent double vision (diplopia) has also been reported.<ref name=pmid19643481/>
An unusual case of seizures has also been reported with ciprofloxacin ear drops in an elderly patient.<ref>{{cite journal |issn= 0025-729X|pmid=12670280 |url=http://www.mja.com.au/public/issues/178_07_070403/orr10717_fm.html |year= 2003 |month= April |title= Eardrop attacks: seizures triggered by ciprofloxacin eardrops. |volume= 178 |issue= 7 |page= 343 |journal= The Medical journal of Australia |author1= Orr, Cf |author2= Rowe, Db }}</ref>


The ] and the FDA warn that ] adverse effects, including seizure risk, may be increased when ]s are combined with quinolones.<ref name="Cipro FDA label" /><ref>{{cite book |title=British National Formulary (BNF 57) |author=Royal Pharmaceutical Society of Great Britain |author-link=Royal Pharmaceutical Society of Great Britain |publisher=BMJ Group and RPS Publishing |chapter=5 Infections |year=2009 |isbn=978-0-85369-845-6 |title-link=British National Formulary }}</ref> The mechanism for this interaction may involve a ] increased antagonism of GABA neurotransmission.<ref name="pmid11172695">{{cite journal |vauthors = De Sarro A, De Sarro G |title = Adverse reactions to fluoroquinolones. an overview on mechanistic aspects |journal = Current Medicinal Chemistry |volume = 8 |issue = 4 |pages = 371–84 |date = March 2001 |pmid = 11172695 |doi = 10.2174/0929867013373435 }}</ref><ref>{{cite journal |vauthors = Brouwers JR |title = Drug interactions with quinolone antibacterials |journal = Drug Safety |volume = 7 |issue = 4 |pages = 268–81 |year = 1992 |pmid = 1524699 |doi = 10.2165/00002018-199207040-00003 |s2cid = 6701544 }}</ref>
Some groups refer to these adverse events as "]". These groups of people claim to have suffered serious long term harm to their health from using fluoroquinolones. This has led to a class action lawsuit by people harmed by the use of fluoroquinolones, as well as legal action by the consumer advocate group ].<ref>{{cite web |title=Public Citizen Warns of Cipro Dangers |url=http://www.consumeraffairs.com/news04/2006/08/pubcit_cipro.html |publisher=Consumer affairs |location=USA |date=30 August 2006 |accessdate=7 September 2009}}</ref> Partly as a result of the efforts of the State of Illinois and Public Citizen, the FDA ordered black box warnings on all fluoroquinolones advising consumers of the possible toxic effects of fluoroquinolones on tendons.<ref>{{cite news |url=http://www.cnn.com/2008/HEALTH/07/08/antibiotics.risk/index.html|title=FDA orders 'black box' label on some antibiotics |accessdate=2008-07-08 | work=CNN | date=8 July 2008}}</ref>


Altered serum levels of the antiepileptic drugs ] and ] (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.<ref name="Cipro FDA label" /><ref>{{cite journal |vauthors = Shahzadi A, Javed I, Aslam B, Muhammad F, Asi MR, Ashraf MY |title = Therapeutic effects of ciprofloxacin on the pharmacokinetics of carbamazepine in healthy adult male volunteers |journal = ] |volume = 24 |issue = 1 |pages = 63–8 |date = January 2011 |pmid = 21190921 }}</ref><ref>{{cite journal |vauthors = Springuel P |title = Risk of seizures from concomitant use of ciprofloxacin and phenytoin in patients with epilepsy |journal = Canadian Medical Association Journal |volume = 158 |issue = 1 |pages = 104–5, 108–9 |date = January 1998 |pmid = 9475922 }}</ref>
==Interactions==
The toxicity of drugs that are metabolised by the ] system is enhanced by concomitant use of some quinolones. Coadministration may dangerously increase coumarin (]) activity; INR should be monitored closely. They may also interact with the ] and cause neurological symptoms; this effect is augmented by certain ]s.<ref>{{cite journal |author=Brouwers JR |title=Drug interactions with quinolone antibacterials |journal=Drug Saf |volume=7 |issue=4 |pages=268–81 |year=1992 |pmid=1524699 |doi=10.2165/00002018-199207040-00003 |month=July |first1=JR |issn=0114-5916 }}</ref> ], a flavonol, occasionally used as a ], may interact with fluoroquinolones, as quercetin competitively binds to bacterial DNA gyrase. Some foods, such as ] and ]s, contain high levels of quercetin; whether this inhibits or enhances the effect of fluoroquinolones is not entirely clear.<ref>{{cite journal |author=Hilliard JJ, Krause HM, Bernstein JI |title=A comparison of active site binding of 4-quinolones and novel flavone gyrase inhibitors to DNA gyrase |journal=Adv Exp Med Biol. |volume=390 |pages=59–69 |year=1995 |pmid=8718602 |first1=JJ |first2=HM |first3=JI |first4=JA |first5=V |first6=KA |first7=JF |issn=0065-2598 }}</ref> Ciprofloxacin can reduce ] plasma levels, which may, in some cases, result in seizures.<ref>{{cite web |url=http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/medeff/carn-bcei_v8n1-eng.pdf |title=Risk of seizures from concomitant use of ciprofloxacin and phenytoin in patients with epilepsy |accessdate= 2009-01-30 |author=Carol Langlois |coauthors=Pascale Springuel |year=1998 |month=January |format=PDF |publisher=Canadian Adverse Drug Reaction Newsletter |location=Canada}}</ref> Ciprofloxacin may interfere with the levels of thyroid medications resulting in ].<ref>{{cite journal |author=Cooper JG, Harboe K, Frost SK, Skadberg Ø |title=Ciprofloxacin interacts with thyroid replacement therapy |journal=BMJ |volume=330 |issue=7498 |page=1002 |year=2005 |month=April |pmid=15860826 |pmc=557149 |doi=10.1136/bmj.330.7498.1002 |first1=JG |first2=K |first3=SK |issn=0959-8138}}</ref>


Ciprofloxacin is a potent inhibitor of ], ], and ].<ref name="HaddadDavis2006">{{cite journal |vauthors = Haddad A, Davis M, Lagman R |title = The pharmacological importance of cytochrome CYP3A4 in the palliation of symptoms: review and recommendations for avoiding adverse drug interactions |journal = Supportive Care in Cancer |volume = 15 |issue = 3 |pages = 251–7 |date = March 2007 |pmid = 17139496 |doi = 10.1007/s00520-006-0127-5 |s2cid = 9186457 }}</ref>
On 9 November 2005, the U.S. FDA required manufacturers to provide additional warnings within the package inserts concerning ciprofloxacin being an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. The new warning stated: <blockquote>"Coadministration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the coadministered drug."<ref>{{cite web |author=Renata Albrecht |title=Cipro Labeling Revision letter 11/09/2005 Supplement 060 |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2005/019537s60,019847s36,019857s41,020780s20,021473s13ltr.pdf |publisher=] (FDA) |date=2005-11-09 |accessdate=2009-09-08}}</ref></blockquote>


==Mechanism of action==
Concurrent administration of ciprofloxacin with magnesium or aluminum antacids, sucralfate or products containing calcium, iron, or zinc (including multivitamins or other dietary supplements) may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired.<ref name="FDA 81532304, R.1"/>
Ciprofloxacin is a ] of the ] class. It is active against some ] and many ] bacteria.<ref>{{cite book |title=First aid for the USMLE step 2 CK |url=https://archive.org/details/firstaidcasesfor00taol |url-access=registration |publisher=McGraw-Hill Medical |isbn=978-0-07-148795-5 |edition=6th |date=June 2007 }}</ref> It functions by inhibiting a type II ] (]) and topoisomerase IV,<ref>{{cite journal |vauthors = Drlica K, Zhao X |title = DNA gyrase, topoisomerase IV, and the 4-quinolones |journal = Microbiology and Molecular Biology Reviews |volume = 61 |issue = 3 |pages = 377–92 |date = September 1997 |doi = 10.1128/mmbr.61.3.377-392.1997 |pmid = 9293187 |pmc = 232616 }}</ref><ref>{{cite journal |vauthors = Pommier Y, Leo E, Zhang H, Marchand C |title = DNA topoisomerases and their poisoning by anticancer and antibacterial drugs |journal = Chemistry & Biology |volume = 17 |issue = 5 |pages = 421–33 |date = May 2010 |pmid = 20534341 |doi = 10.1016/j.chembiol.2010.04.012 |pmc = 7316379 |doi-access = free | title-link = doi }}</ref> necessary to separate bacterial DNA, thereby inhibiting cell division. Bacterial DNA fragmentation will occur as a result of inhibition of the enzymes.


==Pharmacokinetics==
===Significant drug interactions===
Ciprofloxacin for systemic administration is available as immediate-release tablets, extended-release tablets, an oral suspension, and as a solution for intravenous administration. When administered over one hour as an intravenous infusion,<ref name="Cipro FDA label" /> ciprofloxacin rapidly distributes into the tissues, with levels in some tissues exceeding those in the serum. Penetration into the central nervous system is relatively modest, with cerebrospinal fluid levels normally less than 10% of peak serum concentrations. The serum half-life of ciprofloxacin is about 4–6 hours, with 50–70% of an administered dose being excreted in the urine as unmetabolized drug. An additional 10% is excreted in urine as metabolites. Urinary excretion is virtually complete 24 hours after administration. Dose adjustment is required in the elderly and in those with renal impairment.<ref name="Cipro FDA label" />
Ciprofloxacin can alter and be altered by the metabolism and effects of other drugs, resulting in some significant drug-drug interactions that may affect the ], ], ], and other systems.


Ciprofloxacin is weakly bound to serum proteins (20–40%). It is an inhibitor of the drug-metabolizing enzyme ], which leads to the potential for clinically important drug interactions with drugs metabolized by that enzyme.<ref name=AHFS2015 /> Ciprofloxacin is about 70% available when administered orally.<ref name="Cipro FDA label" />
Current or past treatment with oral ] is associated with an increased risk of ] rupture, especially in elderly patients who are also taking the ].<ref>{{cite journal |author=van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HM, Rowlands S, Stricker BH |title=Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids |journal=Arch. Intern. Med. |volume=163 |issue=15 |pages=1801–7 |year=2003 |pmid=12912715 |doi=10.1001/archinte.163.15.1801 |url=http://archinte.ama-assn.org/cgi/content/full/163/15/1801 |month=August |first1=PD |first2=MC |first3=RM |first4=HM |first5=S |first6=BH |issn=0003-9926}}</ref> This is the subject of ]s in FDA and ] labeling for quinolones.


The extended release tablets<ref>{{cite web |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21554_ciproXR_lbl.pdf |title=Cipro XR Prescribing Information |publisher=U.S. ] (FDA) |url-status=live |archive-url=https://web.archive.org/web/20131230232923/http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21554_ciproXR_lbl.pdf |archive-date=30 December 2013}}</ref> allow once-daily administration by releasing the drug more slowly in the gastrointestinal tract. These tablets contain 35% of the administered dose in an immediate-release form and 65% in a slow-release matrix. Maximum serum concentrations are achieved between 1 and 4 hours after administration. Compared to the 250- and 500-mg immediate-release tablets, the 500-mg and 1000-mg XR tablets provide higher C<sub>max</sub>, but the 24‑hour AUCs are equivalent.
The ] and the FDA warn that ] adverse effects, including seizure risk, may be increased when NSAIDs are combined with quinolones.<ref name=ctcos/><ref>{{cite book |title=] (BNF 57) |author=Royal Pharmaceutical Society of Great Britain |authorlink=Royal Pharmaceutical Society of Great Britain |publisher=BMJ Group and RPS Publishing |chapter=5 Infections |year=2009 |isbn=9780853698456 }}</ref> The interaction between quinolones and NSAIDs is important, because it has the potential for considerable CNS toxicity. The mechanism for this interaction is believed to be due to a ] increased antagonism of GABA neurotransmission.<ref name="pmid11172695"/>


Ciprofloxacin immediate-release tablets contain ciprofloxacin as the hydrochloride salt, and the XR tablets contain a mixture of the hydrochloride salt and the free base.<ref name="Cipro FDA label" />
Ciprofloxacin's renal clearance may affect other drugs subject to renal clearance or otherwise affecting the kidney. The use of ciprofloxacin concomitantly with ] has also been associated with transient elevations in serum ]. Renal tubular transport of ] may be inhibited by concomitant administration of ciprofloxacin, potentially leading to increased plasma levels of methotrexate and risk of methotrexate toxicity. ] interferes with renal tubular secretion of ciprofloxacin and produces an increase in the level of ciprofloxacin in serum.<ref name=ctcos/>


==Chemical properties==
Some quinolones, including ciprofloxacin, exert an inhibitory effect on the cytochrome P-450 enzyme CYP1A2, thereby reducing clearance, and thus increasing blood levels of ] and ] (for example,, ] and ]).<ref>{{cite journal |author=Harder S, Fuhr U, Staib AH, Wolff T |title=Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations |journal=Am. J. Med. |volume=87 |issue=5A |pages=89S–91S |year=1989 |month=November |pmid=2589393 |doi= 10.1016/0002-9343(89)90031-4|url= |first1=S |first2=U |first3=AH |first4=T |issn=0002-9343 |format=Free full text}}</ref><ref>{{cite journal |author=Janknegt R |title=Drug interactions with quinolones |journal=J. Antimicrob. Chemother. |volume=26 Suppl D |issue= |pages=7–29 |year=1990 |month=November |pmid=2286594 |doi= |url= |first1=R |issn=0305-7453}}</ref> The quinolones have also been reported to enhance the effects of ] or its derivatives.<ref name=ctcos/> Such interactions can augment the effects of the co-administered drug, including adverse effects. Ciprofloxacin can reduce effects of other drugs; for example, it has been shown to interact with thyroid medications (]), resulting in unexplained ].<ref>{{cite journal |author=Cooper JG, Harboe K, Frost SK, Skadberg Ø |title=Ciprofloxacin interacts with thyroid replacement therapy |journal=BMJ |volume=330 |issue=7498 |page=1002 |month=April |date=2005-04 |pmid=15860826 |pmc=557149 |doi=10.1136/bmj.330.7498.1002 |url=http://www.bmj.com/cgi/content/full/330/7498/1002 |first1=JG |first2=K |first3=SK |issn=0959-8138}}</ref> Altered serum levels of ] (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.<ref name=ctcos/>

==Overdose==
Overdose of ciprofloxacin may result in reversible renal toxicity. Treatment of overdose includes emptying of the stomach via induced vomiting or by ]. Careful monitoring and supportive treatment, monitoring of renal function and maintaining adequate hydration is recommended by the manufacturer. Administration of magnesium, aluminum, or calcium containing antacids can reduce the absorption of ciprofloxacin. ] or ] removes only less than 10 percent of ciprofloxacin.<ref name="FDA 81532304, R.1">{{cite web |title=Cipro Labeling Revision 04/06/2009 Supplement 073 |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019537s073,020780s030lbl.pdf |publisher=] (FDA) |date=2009-04-06 |accessdate=8 September 2009}}</ref> Ciprofloxacin may be quantitated in plasma or serum to monitor for drug accumulation in patients with hepatic dysfunction or to confirm a diagnosis of poisoning in acute overdose victims.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 313-315. ISBN 978-0-9626523-7-0.</ref>

==Mechanism of action==
Ciprofloxacin is a ] active against both ] and ] bacteria. It functions by inhibiting ], a type II ], and topoisomerase IV,<ref>{{cite journal |author=Drlica K, Zhao X |title=DNA gyrase, topoisomerase IV, and the 4-quinolones |journal=Microbiol Mol Biol Rev. |volume=61 |issue=3 |pages=377–92 |pmid=9293187 |pmc=232616 |url=http://mmbr.asm.org/cgi/pmidlookup?view=long&pmid=9293187 |date= September 1, 1997 |first1=K |first2=X |issn=1092-2172}}</ref> enzymes necessary to separate bacterial DNA, thereby inhibiting cell division.

This mechanism can also affect mammalian cell replication. In particular, some congeners of this drug family (for example those that contain the C-8 fluorine)<ref>{{cite journal |author=Robinson MJ, Martin BA, Gootz TD, McGuirk PR, Osheroff N |title=Effects of novel fluoroquinolones on the catalytic activities of eukaryotic topoisomerase II: Influence of the C-8 fluorine group |journal=Antimicrob. Agents Chemother. |volume=36 |issue=4 |pages=751–6 |year=1992 |month=April |pmid=1323952 |pmc=189387 |doi= |url=http://aac.asm.org/cgi/reprint/36/4/751.pdf |format=PDF |first1=MJ |first2=BA |first3=TD |first4=PR |first5=N |issn=0066-4804}}</ref> display high activity not only against bacterial topoisomerases but also against eukaryotic topoisomerases and are toxic to cultured mammalian cells and ''in vivo'' tumor models.<ref name="pmid14529452">{{cite journal |author=Sissi C, Palumbo M |title=The quinolone family: from antibacterial to anticancer agents |journal=Curr Med Chem Anticancer Agents |volume=3 |issue=6 |pages=439–50 |year=2003 |month=November |pmid=14529452 |doi= 10.2174/1568011033482279|url=http://openurl.ingenta.com/content/nlm?genre=article&issn=1568-0118&volume=3&issue=6&spage=439&aulast=Sissi |quote=The present review focuses on the structural modifications responsible for the transformation of an antibacterial into an anticancer agent. Indeed, a distinctive feature of drugs based on the quinolone structure is their remarkable ability to target different type II topoisomerase enzymes. In particular, some congeners of this drug family display high activity not only against bacterial topoisomerases but also against eukaryotic topoisomerases and are toxic to cultured mammalian cells and in vivo tumor models. |first1=C |first2=M |issn=1568-0118}}</ref>
Although quinolones are highly toxic to mammalian cells in culture, its mechanism of cytotoxic action is not known. Quinolone-induced DNA damage was first reported in 1986 (Hussy and others.).<ref>{{cite journal |author=Hussy P, Maass G, Tümmler B, Grosse F, Schomburg U |title=Effect of 4-quinolones and novobiocin on calf thymus DNA polymerase alpha primase complex, topoisomerases I and II, and growth of mammalian lymphoblasts |journal=Antimicrob. Agents Chemother. |volume=29 |issue=6 |pages=1073–8 |year=1986 |month=June |pmid=3015015 |pmc=180502 |doi= |url=http://aac.asm.org/cgi/reprint/29/6/1073.pdf |format=PDF|first1=P |first2=G |first3=B |first4=F |first5=U |issn=0066-4804}}</ref>

Recent studies have demonstrated a correlation between mammalian cell cytotoxicity of the quinolones and the induction of ].<ref>{{cite journal |last= |first= |author=Hosomi JA |year=1988 |title=Mutagenicity of norfloxacin and AM-833 in bacteria and mammalian cells |journal=Rev. Infect |volume=10 |series=1 |pages=S148–S149 |publisher=jstor.org |url=http://www.jstor.org/pss/4454399 |first2= . |first3= . |first4= . |author5= Yokota |author2= Hosomi, J |author3= Maeda, A |author4= Oomori, Y }}</ref><ref>{{cite journal |author=Forsgren A, Bredberg A, Pardee AB, Schlossman SF, Tedder TF |title=Effects of ciprofloxacin on eucaryotic pyrimidine nucleotide biosynthesis and cell growth |journal=Antimicrob. Agents Chemother. |volume=31 |issue=5 |pages=774–9 |year=1987 |month=May |pmid=3606077 |pmc=174831 |doi= |url=http://aac.asm.org/cgi/reprint/31/5/774.pdf |format=PDF |first1=A |first2=A |first3=AB |first4=SF |first5=TF |issn=0066-4804}}</ref><ref>{{cite journal |author=Gootz TD, Barrett JF, Sutcliffe JA |title=Inhibitory effects of quinolone antibacterial agents on eucaryotic topoisomerases and related test systems |journal=Antimicrob. Agents Chemother. |volume=34 |issue=1 |pages=8–12 |year=1990 |month=January |pmid=2158274 |pmc=171510 |doi= |first1=TD |first2=JF |first3=JA |issn=0066-4804}}</ref><ref>{{cite journal |author=Lawrence JW, Darkin-Rattray S, Xie F, Neims AH, Rowe TC |title=4-Quinolones cause a selective loss of mitochondrial DNA from mouse L1210 leukemia cells |journal=J. Cell. Biochem. |volume=51 |issue=2 |pages=165–74 |year=1993 |month=February |pmid=8440750 |doi=10.1002/jcb.240510208 |url= |first1=JW |first2=S |first3=F |first4=AH |first5=TC |issn=0730-2312 |format=Free full text}}</ref>
As such, some fluoroquinolones may cause injury to the chromosome of eukaryotic cells.<ref>{{cite journal |author=Elsea SH, Osheroff N, Nitiss JL |title=Cytotoxicity of quinolones toward eukaryotic cells. Identification of topoisomerase II as the primary cellular target for the quinolone CP-115,953 in yeast |journal=J. Biol. Chem. |volume=267 |issue=19 |pages=13150–3 |year=1992 |month=July |pmid=1320012 |doi= |url=http://www.jbc.org/cgi/reprint/267/19/13150 |first1=SH |first2=N |first3=JL |issn=0021-9258}}</ref><ref>{{cite journal |author=Suto MJ, Domagala JM, Roland GE, Mailloux GB, Cohen MA |title=Fluoroquinolones: relationships between structural variations, mammalian cell cytotoxicity, and antimicrobial activity |journal=J. Med. Chem. |volume=35 |issue=25 |pages=4745–50 |year=1992 |month=December |pmid=1469702 |doi= 10.1021/jm00103a013|url= |first1=MJ |first2=JM |first3=GE |first4=GB |first5=MA |issn=0022-2623}}</ref><ref>{{cite journal |author=Enzmann H, Wiemann C, Ahr HJ, Schlüter G |title=Damage to mitochondrial DNA induced by the quinolone Bay y 3118 in embryonic turkey liver |journal=Mutat. Res. |volume=425 |issue=2 |pages=213–24 |year=1999 |month=April |pmid=10216214 |doi= 10.1016/S0027-5107(99)00044-5|url= |first1=H |first2=C |first3=HJ |first4=G |issn=0027-5107}}</ref><ref>{{cite journal |author=Kashida Y, Sasaki YF, Ohsawa K |title=Mechanistic study on flumequine hepatocarcinogenicity focusing on DNA damage in mice |journal=Toxicol. Sci. |volume=69 |issue=2 |pages=317–21 |year=2002 |month=October |pmid=12377980 |doi= 10.1093/toxsci/69.2.317|url=http://toxsci.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12377980 |first1=Y |first2=YF |first3=K |first4=N |first5=A |first6=T |first7=K |issn=1096-6080}}</ref><ref>{{cite journal |author=Thomas A, Tocher J, Edwards DI |title=Electrochemical characteristics of five quinolone drugs and their effect on DNA damage and repair in ''Escherichia coli'' |journal=J. Antimicrob. Chemother. |volume=25 |issue=5 |pages=733–44 |year=1990 |month=May |pmid=2165050 |doi= 10.1093/jac/25.5.733|url=http://jac.oxfordjournals.org/cgi/reprint/25/5/733 |first1=A |first2=J |first3=DI |issn=0305-7453}}</ref><ref>{{cite web | url = http://www.academy.org.uk/pharmacy/fluoroq.htm| title = Fluoroquinolones and Quinolones| accessdate = 29 January 2009| publisher = The American Academy of Optometry (British Chapter) }}</ref>

There continues to be debate as to whether or not this DNA damage is to be considered one of the mechanisms of action concerning the severe adverse reactions experienced by some patients following fluoroquinolone therapy.<ref name="pmid14529452"/><ref>{{cite journal |title=A new class of dihaloquinolones bearing N'-aldehydoglycosylhydrazides, mercapto-1,2,4-triazole, oxadiazoline and a-amino ester precursors: synthesis and antimicrobial activity |journal=J. Braz. Chem. Soc |volume=14 |issue=5 |pages= |year=2003 |month=|doi=10.1590/S0103-50532003000500014 |url=http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532003000500014&lng=es&nrm=iso&tlng=es |quote=Nevertheless, some quinolones cause injury to the chromosome of eukaryotic cells.21,22 These findings prompted us to optimize the substituent at C-3, by... |author1=Al-soud, Yaseen A |author2=Al-masoudi, Najim A |last1=Al-Soud |first1=Yaseen A.}}</ref><ref>{{cite journal |author=Yaseen A. Al-Soud a and Najim A. Al-Masoudi |title=A New Class of Dihaloquinolones Bearing N'-Aldehydoglycosylhydrazides, Mercapto-1,2,4-triazole, Oxadiazoline and α-Amino Ester Precursors: Synthesis and Antimicrobial Activity |journal=J. Braz. Chem. Soc |volume=14 |issue=5 |pages=790–796 |year=2003 |url=http://jbcs.sbq.org.br/jbcs/2003/v14_n5/13-048-02.pdf |format=PDF|quote=Although the current quinolones are not considered to be potent inhibitors of eucaryotic topoisomerases, some effects on these and other enzymes involved with DNA replication have been observed |doi=10.1590/S0103-50532003000500014}}</ref>

==Chemistry==
Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C<sub>17</sub>H<sub>18</sub>FN<sub>3</sub>O<sub>3</sub> and its molecular weight is 331.4 g/mol. It is a faintly yellowish to light yellow crystalline substance.<ref name="FDA 81532304, R.1" /> Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C<sub>17</sub>H<sub>18</sub>FN<sub>3</sub>O<sub>3</sub> and its molecular weight is 331.4 g/mol. It is a faintly yellowish to light yellow crystalline substance.<ref name="FDA 81532304, R.1" />


Ciprofloxacin hydrochloride (]) is the monohydrochloride monohydrate salt of ciprofloxacin. It is a faintly yellowish to light yellow crystalline substance with a molecular weight of 385.8 g/mol. Its empirical formula is C<sub>17</sub>H<sub>18</sub>FN<sub>3</sub>O<sub>3</sub>HCl•H<sub>2</sub>O.<ref name="FDA 81532304, R.1" /> Ciprofloxacin hydrochloride (]) is the monohydrochloride monohydrate salt of ciprofloxacin. It is a faintly yellowish to light yellow crystalline substance with a molecular weight of 385.8 g/mol. Its empirical formula is C<sub>17</sub>H<sub>18</sub>FN<sub>3</sub>O<sub>3</sub>HCl•H<sub>2</sub>O.<ref name="FDA 81532304, R.1" />


==Usage==
==Pharmacokinetics==
Ciprofloxacin is the most widely used of the second-generation quinolones.<ref>{{cite journal |vauthors = Goossens H, Ferech M, Coenen S, Stephens P |title = Comparison of outpatient systemic antibacterial use in 2004 in the United States and 27 European countries |journal = Clinical Infectious Diseases |volume = 44 |issue = 8 |pages = 1091–5 |date = April 2007 |pmid = 17366456 |doi = 10.1086/512810 |doi-access = free | title-link = doi }}</ref><ref>{{cite web |url=http://www.bccdc.ca/NR/rdonlyres/BC629780-7E03-4153-B67B-5CFD4F521DAC/0/Full2010AntibioticConsumptionReport_aug2012.pdf |title=British Columbia Annual Summary of Antibiotics Utilization 2010 |url-status=dead |archive-url=https://web.archive.org/web/20131230232309/http://www.bccdc.ca/NR/rdonlyres/BC629780-7E03-4153-B67B-5CFD4F521DAC/0/Full2010AntibioticConsumptionReport_aug2012.pdf |archive-date=30 December 2013}}</ref> In 2010, over 20 million prescriptions were written, making it the 35th-most-commonly prescribed generic drug and the 5th-most-commonly prescribed antibacterial in the US.<ref>{{cite web |title = 2010 Top 200 generic drugs by total prescriptions |url=http://drugtopics.modernmedicine.com/drugtopics/data/articlestandard/drugtopics/252011/727243/article.pdf |access-date = 2 November 2012 |archive-date= 15 December 2012 |archive-url=https://web.archive.org/web/20121215070930/http://drugtopics.modernmedicine.com/drugtopics/data/articlestandard//drugtopics/252011/727243/article.pdf}}</ref>
The effects of 200–400&nbsp;mg of ciprofloxacin given intravenously are linear; drug accumulation does not occur when administered at 12 hour intervals. ] is approximately 70-80%, with no significant first pass effect. ] produces a similar ] levels as those achieved with administration of 500&nbsp;mg administered orally. IV administration over 60 minutes given every 8 hours produces similar serum levels of the drug as 750&nbsp;mg administered orally every 12 hours.<ref name="FDA 81532304, R.1" /> Biotransformation is hepatic. The ] is 4 hours.<ref name=ctcos/>


==History== ==History==
] ]
The first members of the quinolone antibacterial class were relatively low-potency drugs such as ], used mainly in the treatment of urinary tract infections owing to their renal excretion and propensity to be concentrated in urine.<ref>{{cite journal |vauthors = Mayrer AR, Andriole VT |title = Urinary tract antiseptics |journal = The Medical Clinics of North America |volume = 66 |issue = 1 |pages = 199–208 |date = January 1982 |pmid = 7038329 |doi = 10.1016/s0025-7125(16)31453-5 }}</ref> In 1979, the publication of a patent<ref>{{cite web |url=https://patents.google.com/patent/US4146719 |title=Patent US4146719 - Piperazinyl derivatives of quinoline carboxylic acids - Google Patents}}</ref> filed by the pharmaceutical arm of Kyorin Seiyaku Kabushiki Kaisha disclosed the discovery of ], and the demonstration that certain structural modifications including the attachment of a fluorine atom to the quinolone ring leads to dramatically enhanced antibacterial potency.<ref>{{cite journal |vauthors = Khan MY, Gruninger RP, Nelson SM, Klicker RE |title = Comparative in vitro activity of norfloxacin (MK-0366) and ten other oral antimicrobial agents against urinary bacterial isolates |journal = Antimicrobial Agents and Chemotherapy |volume = 21 |issue = 5 |pages = 848–51 |date = May 1982 |pmid = 6213200 |pmc = 182027 |doi = 10.1128/AAC.21.5.848 }}</ref> In the aftermath of this disclosure, several other pharmaceutical companies initiated research and development programs with the goal of discovering additional antibacterial agents of the fluoroquinolone class.
The patent history for ciprofloxacin makes reference to a 1982 European Patent (patent number 0049355), as well a German patent dated 21 January 1986. Bayer introduced ciprofloxacin in 1987 and it was later approved by the U.S. FDA on 22 October 1987 for use in the United States to treat specific bacterial infections. In 1991, the intravenous formulation was introduced. The current United States patent appears to be held by Bayer, being the assignee.<ref>{{cite web |author=Streuff, ''et al.'' |title=United States Patent 5,286,754 |url=http://patft.uspto.gov/netacgi/nph-Parser?u=%2Fnetahtml%2Fsrchnum.htm&Sect1=PTO1&Sect2=HITOFF&p=1&r=1&l=50&f=G&d=PALL&s1=5286754.PN.&OS=PN/5286754&RS=PN/5286754 |publisher=uspto.gov |location=USA |date=15 February 1994 |accessdate=30 August 2009}}</ref> The United States patent was applied for in January 1987, but was not approved until 1996 according to the patent history.


The fluoroquinolone program at ] focused on examining the effects of very minor changes to the norfloxacin structure.<ref>{{cite web |url=https://patents.google.com/patent/US4547503 |title=Patent US4547503 – 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-] pathogen '']'', making ciprofloxacin one of the most potent known drugs for the treatment of this intrinsically antibiotic-resistant pathogen.{{Medical citation needed|date=September 2015}}
In 2004, ciprofloxacin and ] together commanded 65% ($3.3 billion) of the global sales of the fluoroquinolone class.<ref>{{cite web |title=Commercial Perspectives: Fluoroquinolones - Established Products Drive Market Growth |url=https://www.leaddiscovery.co.uk/reports/843/Commercial_Perspectives_Fluoroquinolones_Established_Products_Drive_Market_Growth |date=28 January 2004 |accessdate=30 August 2009}}</ref> The first nine months of 2008 sales for ciprofloxacin were $242 million, as compared to $324 million for Bayer ].<ref>{{cite web |author= Katrin Schneider |title=Stockholders' Newsletter |url=http://www.stockholders-newsletter-q3-08.bayer.com/en/bayer_stockholders_newsletter_3Q_08.pdfx |publisher=Bayer AG |format=PDF |date=29 October 2008 |accessdate=30 August 2009}}</ref> Ciprofloxacin has been a highly successful drug for Bayer A. G., generating billions of dollars in revenue. "In 1999, Cipro was the eleventh most prescribed drug in the United States based on new prescriptions, and ranked twentieth in total United States sales. In 1999, Bayer's gross sales of Cipro in the United States were approximately $1.04 billion."<ref>{{cite web |title=Cipro |url=http://www.prescriptionaccess.org/lawsuitssettlements/past_lawsuits?id=0010 |publisher=Prescription Access |location=USA |accessdate=4 September 2009}}</ref> The sale of ciprofloxacin increased dramatically following the ] scare of 2001. On 24 October 2002, the Bush Administration (2001–2009) announced a deal between the government and Bayer Pharmaceuticals to purchase 100 million tablets of ciprofloxacin at a reduced price of $0.95 per pill. A full course of ciprofloxacin for postexposure prophylaxis (60 days) resulting from this arrangement costs the government $204 per person treated, compared with $12 per person treated with ], the drug normally used to treat anthrax, a difference of $192.<ref>{{cite web |author=Bayer Corporation |authorlink=Bayer |title=HHS, Bayer Agree to Cipro Purchase |url=http://www.hhs.gov/news/press/2001pres/20011024.html |publisher=U.S. Department of Health & Human Services |location=USA |date=24 October 2001 |accessdate=4 September 2009}} {{Dead link|date=September 2010|bot=H3llBot}}</ref>


The oral tablet form of ciprofloxacin was approved in October 1987,<ref>{{cite web |url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=019537&TABLE1=OB_Rx |title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations N019537 |publisher=U.S. ] (FDA) |access-date=5 January 2014 |url-status=live |archive-url=https://web.archive.org/web/20140106040918/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=019537&TABLE1=OB_Rx |archive-date=6 January 2014}}</ref> just one year after the approval of norfloxacin.<ref>{{cite web |url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=019384&TABLE1=OB_Rx |title=Orange Book Detail Record Search |publisher=U.S. ] (FDA) |url-status=live |archive-url=https://web.archive.org/web/20140106040606/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=019384&TABLE1=OB_Rx |archive-date=6 January 2014}}</ref> In 1991, the intravenous formulation was introduced. Ciprofloxacin sales reached a peak of about 2 ] euros in 2001, before Bayer's patent expired in 2004, after which annual sales have averaged around €200 million.<ref>{{cite web |url= https://www.sec.gov/Archives/edgar/data/1144145/000115697302000306/f00360e20vf.txt |title=www.sec.gov |url-status=live |archive-url= https://web.archive.org/web/20170709045332/https://www.sec.gov/Archives/edgar/data/1144145/000115697302000306/f00360e20vf.txt |archive-date=9 July 2017}}</ref><ref>Dan Prochilo for Law360 18 November 2013 {{webarchive |url=https://web.archive.org/web/20150318093001/http://www.law360.com/articles/489579/bayer-s-74m-cipro-pay-for-delay-deal-approved-in-calif |date=18 March 2015 }}</ref>
===Generic equivalents===


The name probably originates from the International Scientific Nomenclature: ci- (alteration of cycl-) + propyl + fluor- + ox- + az- + -mycin.<ref>{{cite dictionary |url=https://www.merriam-webster.com/dictionary/ciprofloxacin|access-date=10 April 2022 |entry=Ciprofloxacin |dictionary=Merriam-Webster.com Dictionary |publisher=Merriam-Webster|title=Definition of CIPROFLOXACIN }}</ref>
On 24 October 2001, The Prescription Access Litigation (PAL), filed suit to dissolve an agreement between Bayer and three of its competitors which produced ] (], ], and ]) that it claimed was blocking access to adequate supplies and cheaper, generic versions of ciprofloxacin. The plaintiffs charged that Bayer Corporation, a unit of Bayer AG, had unlawfully paid the three competing companies a total of $200 million to prevent cheaper, generic versions of ciprofloxacin from being brought to the market, as well as manipulating the price and supply of ciprofloxacin. Numerous other consumer advocacy groups joined the lawsuit. On 15 October 2008, five years after Bayer's patent had expired, the United States District Court for the Eastern District of New York granted Bayer's and the other defendants' motion for summary judgment, holding that any anticompetitive effects caused by the settlement agreements between Bayer and its codefendants were within the exclusionary zone of the patent and thus could not be redressed by federal antitrust law,<ref>{{cite web |author=United States Court of Appeals for the Federal Circuit |title=United States Court of Appeals for the Federal Circuit |url=http://www.cafc.uscourts.gov/opinions/08-1097.pdf |location=USA |format=PDF |year=2008 |accessdate=4 September 2009}} {{Dead link|date=September 2010|bot=H3llBot}}</ref> in effect upholding Bayer's agreement with its competitors.


===Black box warnings=== ==Society and culture==
{{See also|Quinolone#Black box warnings}}
Musculoskeletal disorders attributed to use of quinolone antibiotics were first reported in the medical literature in 1972, as an adverse reaction to ].<ref name="autogenerated604">{{cite journal |author=Bailey RR, Natale R, Linton AL |title=Nalidixic acid arthralgia |journal=Can Med Assoc J |volume=107 |issue=7 |pages=604 passim |year=1972 |month=October |pmid=4541768 |pmc=1940945 |first1=RR |first2=R |first3=AL |issn=0008-4409}}</ref> Rheumatic disease after use of a fluoroquinolone (]) was first reported 11 years later.<ref name="autogenerated590">{{cite journal |author=Bailey RR, Kirk JA, Peddie BA |title=Norfloxacin-induced rheumatic disease |journal=N Z Med J |volume=96 |issue=736 |page=590 |year=1983 |month=July |pmid=6223241 |first1=RR |first2=JA |first3=BA |issn=0028-8446 |url= |format=}}</ref> In response to a 1995 letter published in the '']'', representatives of the ] (FDA) stated that the agency would "update the labeling for all marketed fluoroquinolones to include a warning about the possibility of tendon rupture."<ref name="autogenerated193">{{cite journal |author=Szarfman A, Chen M, Blum MD |title=More on fluoroquinolone antibiotics and tendon rupture |journal=N Engl J Med |volume=332 |issue=3 |page=193 |year=1995 |month=January |pmid=7800023 |format=letter |doi=10.1056/NEJM199501193320319 |first1=A |first2=M |first3=MD |issn=0028-4793}}</ref>


===Economics===
By August 1996, the FDA had not taken action, and the consumer advocacy group ] filed a petition with the FDA prompting the agency to act.<ref>{{cite web |title=Petition to Require a Warning on All Fluoroquinolone Antibiotics (HRG Publication #1399) |date=August 1, 1996 |publisher=] |url=http://www.citizen.org/publications/release.cfm?ID=6595}} Retrieved on December 27, 2008.</ref> Two months later, the FDA published an alert in the ''FDA Medical Bulletin'' and requested that fluoroquinolone package inserts be amended to include information on this risk.<ref name=FDA1996>{{cite journal |title=Reports of adverse events with fluoroquinolones |journal=FDA Medical Bulletin |month=October | year=1996 |volume=26 |issue=3 |url=http://www.fqresearch.org/text_documents/FDA_Medical_Bulletin_1996.doc |format=Doc}}</ref>
It is available as a generic medication and not very expensive.<ref name=AHFS2015/><ref name=Ric2014/>


===Generic equivalents===
Nine years later, in 2005, the ] filed a second petition with the FDA again seeking ]s and "Dear Doctor" letters emphasizing the risk of tendon rupture; the FDA responded that it had not yet been able to reach a decision on the matter.<ref name=Madigan>{{cite press release |title=Madigan, Public Citizen, petition FDA for "Black Box" warning regarding potential adverse effects of certain popular antibiotics |date=August 29, 2006 |publisher=Office of the Illinois Attorney General |url=http://www.illinoisattorneygeneral.gov/pressroom/2006_08/20060829.html | accessdate = 2008-12-27}} Full text of the and available from the Fluoroquinolone Toxicity Research Foundation, a U.S. consumer advocacy group.</ref> In 2006, Public Citizen, supported by the Illinois Attorney General, renewed its demand of ten years prior for Black Box Warnings by filing a third petition requesting such changes be made.<ref name=Madigan/><ref>{{cite web |title=Public Citizen Petitions the FDA to Include a Black Box Warning on Fluoroquinolone Antibiotics (HRG Publication #1781) |date=August 29, 2006 |publisher=Public Citizen |url=http://www.citizen.org/publications/release.cfm?ID=7453 | accessdate = 2008-12-27}}</ref> When the FDA failed to respond to these two petitions as required by law Public Citizen, in January 2008, filed suit to compel the FDA to respond to their 2006 petition.<ref>{{cite web |url=http://www.citizen.org/litigation/forms/cases/CaseDetails.cfm?cID=444 |title=Public Citizen v. Food and Drug Administration (FDA) (Fluoroquinolone) |date=January 3, 2008 |publisher=Public Citizen | accessdate = 2008-12-27}}</ref><ref>{{cite news |last=Ravn |first=Karen |title=Behind the FDA's 'black box' warnings |date=August 18, 2008 |publisher=] |url=http://articles.latimes.com/2008/aug/18/health/he-closer18 | accessdate = 2008-12-27}}</ref> On July 7, 2008 the FDA requested that the makers of systemic-use fluoroquinolones add a boxed warning regarding spontaneous tendon ruptures, and to develop a Medication Guide for patients.<ref name=FDA>{{cite press release |url=http://www.fda.gov/bbs/topics/NEWS/2008/NEW01858.html |title=FDA Requests Boxed Warnings on Fluoroquinolone Antimicrobial Drugs |publisher=] |date= 2008-07-08 | accessdate = 2008-10-11}}</ref> The package inserts for Ciprofloxacin, Avelox (]), Proquin XR, Factive (]), Floxin (]), Noroxin (]) and Levaquin (]) were amended on September 8, 2008 to include these new warnings.<ref>The complete labeling history of each drug is available from . Medication Guides are available from the FDA's system.</ref> ], which manufactures Cipro, Avelox and Proquin XR, issued a Dear Healthcare Professional letter on October 22 concerning these changes.<ref>{{cite web |last=MacCarthy |first=Paul |title=Important Change in the Avelox (moxifloxacin hydrochloride) and Cipro (ciprofloxacin) Complete Prescribing Information&nbsp;– Addition of Boxed Warning and Medication Guide Regarding Tendinitis and Tendon Rupture |date=October 22, 2008 |publisher=Bayer HealthCare Pharmaceuticals |url=http://www.cipro.com/html/pdf/dhpl.pdf |format=PDF| accessdate= 2008-12-27}}</ref> ], the manufacturers of Levaquin, issued a similar letter in November.<ref>{{cite web |last=Rosenthal |first=Norman |title=Important Change in the LEVAQUIN (Ievofloxacin) Complete Prescribing Information&nbsp;-Addition of Boxed Warning and Medication Guide Regarding Tendinitis and Tendon Rupture |month=November | year=2008 |publisher=Ortho-McNeil Janssen Scientific Affairs, LLC |url=http://www.fqresearch.org/pdf_files/Levaquin_11_2008_ortho_mcneil_dear_dr_letter.pdf |format=PDF| accessdate= 2008-12-27}}</ref> through the Health Care Notification Network, a registration-only website that distributes drug alerts to licensed healthcare professionals.
In October 2001, the Prescription Access Litigation (PAL) project filed suit to dissolve an agreement between Bayer and three of its competitors which produced ] (], ], and ]) that PAL claimed was blocking access to adequate supplies and cheaper, generic versions of ciprofloxacin. The plaintiffs charged that Bayer Corporation, a unit of Bayer AG, had unlawfully paid the three competing companies a total of $200 million to prevent cheaper, generic versions of ciprofloxacin from being brought to the market, as well as manipulating its price and supply. Numerous other consumer advocacy groups joined the lawsuit. On 15 October 2008, five years after Bayer's patent had expired, the United States District Court for the Eastern District of New York granted Bayer's and the other defendants' motion for summary judgment, holding that any anticompetitive effects caused by the settlement agreements between Bayer and its codefendants were within the exclusionary zone of the patent and thus could not be redressed by federal antitrust law,<ref>{{cite web |author=United States Court of Appeals for the Federal Circuit |title=United States Court of Appeals for the Federal Circuit |url=http://www.cafc.uscourts.gov/opinions/08-1097.pdf |location=USA |year=2008 |access-date=4 September 2009 |url-status=dead |archive-url=https://web.archive.org/web/20090827080527/http://www.cafc.uscourts.gov/opinions/08-1097.pdf |archive-date=27 August 2009 }}</ref> in effect upholding Bayer's agreement with its competitors.


===Available forms===
On February 25, 2011<ref>http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/019537s075,019847s047,019857s054,020780s033,021473s028ltr.pdf</ref> an
Ciprofloxacin for systemic administration is available as immediate-release tablets, as extended-release tablets, as an oral suspension, and as a solution for intravenous infusion. It is available for local administration as eye drops and ear drops. It is available in combination with ], with ], with ], and with ].<ref>{{cite web | title=Otovel (- ciprofloxacin and fluocinolone acetonide solution | website=DailyMed | date=12 September 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a7e4806-3138-4b7a-b798-a99e163ee846 | access-date=9 February 2024}}</ref>
additional Black Box warning was added to all the drugs within this class, including ciprofloxacin, stating that the fluoroquinolone class may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Such an adverse reaction is a potentially life-threatening event and may require ventilatory support.


===Litigation===
Review of the FDA website indicates that the majority of the generic versions of the fluoroquinolones have ''not'' been updated to include this Black Box Warning as of September 2009. Additionally there are numerous reports that this information has not been dessiminated to the pharmacist, the name brand products continue to contain the previous labels that are absent of this warning, and the Medication Guide has not been made available to the pharmicist or physician for distribution.
A class action was filed against Bayer AG on behalf of employees of the Brentwood Post Office in Washington, D.C., and workers at the U.S. Capitol, along with employees of American Media, Inc. in Florida and postal workers in general who alleged they developed serious adverse effects from taking ciprofloxacin in the aftermath of the ]. The action alleged Bayer failed to warn class members of the potential side effects of the drug, thereby violating the Pennsylvania Unfair Trade Practices and Consumer Protection Laws. The class action was defeated and the litigation abandoned by the plaintiffs.<ref>{{cite web |title=Legal Brief of Postal Employees Cases (EEOC, MSPB, District Courts) |url=http://www.lunewsviews.com/legal_briefs_archives.htm#cipro |archive-url=https://web.archive.org/web/20071021073109/http://www.lunewsviews.com/legal_briefs_archives.htm#cipro |archive-date=21 October 2007 |publisher=Postal Reporter |location=USA |access-date=9 September 2009}}</ref> A similar action was filed in 2003 in New Jersey by four New Jersey postal workers but was withdrawn for lack of grounds, as workers had been informed of the risks of ciprofloxacin when they were given the option of taking the drug.<ref>Los Angeles Times, from wire service reports. 19 October 2003 </ref><ref>Bill Lewis, President of Trenton Metro Area Local, American Postal Workers Union, AFL-CIO. 7 December 2003 {{webarchive |url=https://web.archive.org/web/20141023131440/http://trentonmetroarealocal.com/president_page.html |date=23 October 2014 }} Page accessed 23 October 2014</ref>


==Research==
===FDA warning letters===
As resistance to ciprofloxacin has grown since its introduction, research has been conducted to discover and develop analogs that can be effective against resistant bacteria; some have been looked at in antiviral models as well.<ref>{{cite journal |vauthors = Zhang GF, Liu X, Zhang S, Pan B, Liu ML |title = Ciprofloxacin derivatives and their antibacterial activities |journal = European Journal of Medicinal Chemistry |volume = 146 |pages = 599–612 |date = February 2018 |pmid = 29407984 |doi = 10.1016/j.ejmech.2018.01.078 }}</ref>
Additionally the manufacturers of ciprofloxacin (Bayer A.G.) received numerous warning letters from the United States ] regarding false advertising and failure to provide adequate warnings within their promotional materials.<ref>{{cite web |title=NDA #19-537 Cipro (ciprofloxacin) Tablets Macmis ID #7451 |accessdate=30 January 2009 |date=2 April 1999 |publisher=] (FDA)|url=http://www.fqresearch.org/pdf_files/040299_bayer.pdf}}</ref><ref>{{cite web |title=RE: Cipro HC Otic Suspension (Ciprofloxacin Hydrochloride and Hydrocortisone Otic Suspension) NDA 20-805 Ciloxan (ciprofloxacin ophthalmic) Solution NDA 19-992 MACMIS ID# 11015 |date=18 July 2003 |accessdate=30 January 2009 |publisher=] (FDA) |url=http://www.fqresearch.org/pdf_files/11015.pdf}}</ref>


== References ==
==Overprescribing and bacterial resistance==
{{reflist}}
{{See also|Antibiotic abuse|Antibiotic resistance}}
Ciprofloxacin is commonly used for urinary tract and intestinal infections (traveler's diarrhea) and
was once considered a powerful antibiotic of last resort,<ref>Biosecurity requires drug reform. Jan 1, 2002 World Watch ISSN: 0896-0615</ref><ref>{{Cite journal | last1 = Nawaz | first1 = H. | last2 = Rauf | first2 = S. | last3 = Akhtar | first3 = K. | last4 = Khalid | first4 = AM. | title = Electrochemical DNA biosensor for the study of ciprofloxacin-DNA interaction. | journal = Anal Biochem | volume = 354 | issue = 1 | pages = 28–34 | month = July | year = 2006 | doi = 10.1016/j.ab.2006.04.004 | pmid = 16707087 | author2 = Rauf | author3 = Akhtar | author4 = Khalid }}</ref><ref>{{cite book |title=The Resistance Phenomenon in Microbes and Infectious Disease Vectors: Implications for Human Health and Strategies for Containment, Workshop Summary|url=http://books.google.com/?id=90F3Q6MnkcAC |publisher=National Academies Press |isbn=978-0309088541 |page=34 |chapter= |chapterurl= |author=Stacey L. Knobler ... |year=2003 }}</ref> used to treat especially tenacious infections. Not all physicians agreed with this assessment, as evidenced by its widespread use to treat minor infections as well as non-approved uses. As a result in recent years many bacteria have developed resistance to this drug, leaving it significantly less effective than it would have been otherwise.<ref>{{cite web |url=http://www.cdc.gov/ncidod/eid/vol5no3/pdf/vatopoulos.pdf |title=Bacterial Resistance to Ciprofloxacin in Greece: Results from the National Electronic Surveillance System |author=A.C. Vatopoulos |coauthors=V. Kalapothaki |format=PDF |year=1997 }}</ref><ref>{{cite web |url=http://www.health.state.mn.us/news/pressrel/2009/bacterial022609.html |title=Bacterial resistance prompts concern among health officials |first= |last= |author= |publisher= |location= |date=26 February 2009 }}{{dead link|date=April 2011}}</ref>


== External links ==
] to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. Numerous ]s, including '']'', ], and '']'' now exhibit resistance worldwide.<ref>M Jacobs, Worldwide Overview of Antimicrobial Resistance. International Symposium on Antimicrobial Agents and Resistance 2005.</ref> Widespread veterinary usage of the fluoroquinolones, particularly in Europe, has been implicated.<ref>{{cite press release |title=Update On Extra-Label Use Of Fluoroquinolones |url=http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm127657.htm |publisher = ] (CVM) |date=16 July 1996 |accessdate=12 August 2009}}</ref>

Fluoroquinolones had become the most commonly prescribed class of antibiotics to adults in 2002.<ref name="pmid15745724">{{cite journal |author=Linder JA, Huang ES, Steinman MA, Gonzales R, Stafford RS |title=Fluoroquinolone prescribing in the United States: 1995 to 2002 |journal=Am. J. Med. |volume=118 |issue=3 |pages=259–68 |year=2005 |month=March |pmid=15745724 |doi=10.1016/j.amjmed.2004.09.015 }}</ref> Nearly half (42%) of those prescriptions were for conditions not approved by the FDA, such as acute bronchitis, otitis media, and acute upper respiratory tract infection, according to a study that was supported in part by the Agency for Healthcare Research and Quality.<ref name="pmid15745724"/><ref>K08 HS14563 and HS11313</ref> Additionally, they were commonly prescribed for medical conditions that were not even bacterial to begin with, such as viral infections, or those to which no proven benefit existed.

==Litigation==
'''Bayer AG'''
A class action was filed against Bayer AG on behalf of employees of the Brentwood Post Office in Washington, D.C., and workers at the U.S. Capitol, along with employees of American Media, Inc. in Florida and postal workers in general who alleged that they suffered serious adverse effects from taking the antibiotic ciprofloxacin (Cipro) in the aftermath of the anthrax attacks in 2001. The adverse effects included; tendon rupture, seizures, intestinal problems, tendonitis, anxiety, insomnia, muscle aches, depression and meniscus tears. The action alleged that Bayer failed to warn class members of the potential side effects of the drug, thereby violating the Pennsylvania Unfair Trade Practices and Consumer Protection Laws. According to the allegations within the complaint, exposed individuals were not informed of the true safety profile of ciprofloxacin, the high rate of adverse events associated with its use, or the availability of safer and equally effective alternative drugs. The complaint further alleged that, as a result of taking Cipro, many individuals suffered severe and debilitating injuries. The action sought funding for a medical monitoring program and compensatory damages for those workers who have suffered side effects. In 2004, the law firm of Goodell, DeVries, Leech & Dann, LLP were retained as national counsel in this litigation. The class action was defeated and the litigation abandoned by the plaintiffs.<ref>{{cite web |title=Anthrax Scare Leaves Trail of Cipro Victims - Class Actions filed in Two States |url=http://www.sheller.com/NewsDetails.asp?NewsID=72 |publisher=Sheller Ludwig & Sheller |location=USA |date=17 October 2003 |accessdate=9 September 2009}} {{Dead link|date=September 2010|bot=H3llBot}}</ref><ref>{{cite web |title=Legal Brief of Postal Employees Cases (EEOC, MSPB, District Courts) |url=http://www.lunewsviews.com/legal_briefs_archives.htm#cipro |archiveurl=http://web.archive.org/web/20071021073109/http://www.lunewsviews.com/legal_briefs_archives.htm#cipro |archivedate=2007-10-21 |publisher=Postal Reporter |location=USA |accessdate=9 September 2009}}</ref><ref>{{cite web |author=Charles P. Goodell, Jr |title=Profile |url=http://www.gdldlaw.com/content/bio_goodell.htm |publisher=Goodell, DeVries, Leech &amp; Dann, LLP |location=USA |accessdate=9 September 2009}}</ref>
A similar action had been filed in New Jersey that covers New Jersey postal workers. Final disposition of that lawsuit is unknown. Following the addition of the Black Box Warning in 2008, regarding tendon damage, a significant number of product liability law firms began soliciting clients who have suffered a spontaneous tendon rupture following fluoroquinolone therapy.<ref>{{cite web |url=http://www.prlog.org/10088464-legalview-reveals-details-of-the-fda-mandated-black-box-warning-for-fluoroquinolone-antibiotics.html |title=LegalView Reveals Details of the FDA Mandated Black Box Warning For Fluoroquinolone Antibiotics |date=11 July 2008 |publisher=PRlog }}</ref><ref>{{cite web |url=http://www.zimbio.com/Shocking+Sports+Injuries/articles/W6tlqlrajER/Levaquin+Litigation+Moving+Ahead |title=Levaquin Litigation Moving Ahead |author=Cynthia Diaz |date=6 July 2009 |publisher=Zimbio |quote=In May we wrote that most litigation specialists expected thousands of people to file lawsuits against the makers of Levaquin and similar drugs...}}</ref><ref>{{cite web |url=http://www.reuters.com/article/pressRelease/idUS199242+03-Sep-2009+BW20090903 |title=Carey and Danis LLC Announces Four Lawsuits against the Makers of Levaquin |author=Carey and Danis LLC |publisher=Reuters |date=3 September 2009 }}</ref>

==See also==
*]
*]
*]

==References==
{{reflist|colwidth=30em}}

==External links==
{{Commons category}} {{Commons category}}
* {{cite web |title=Ciprofloxacin Ophthalmic |url=https://medlineplus.gov/druginfo/meds/a605005.html |website=MedlinePlus}}
*
*{{DMOZ|Society/Issues/Health/Drugs/Medical}}
*
*
*
*


{{-}}
{{QuinoloneAntiBiotics}} {{QuinoloneAntiBiotics}}
{{Piperazines}} {{Piperazines}}
{{Otologicals}} {{Otologicals}}
{{GABA receptor modulators}}
{{Portal bar | Medicine}}
{{Authority control}}


]
]
]
]
]
]
]
] ]
]
]
]
]
] ]
] ]
] ]
]

]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]