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[[Antibiotic resistance|Resistance]] to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. Numerous [[pathogen]]s, including ''[[Staphylococcus aureus]]'', [[enterococci]], ''[[Streptococcus pyogenes]]'' and ''[[Klebsiella pneumoniae]] (quinolone-resistant)'' 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 = [[Center for Veterinary Medicine]] (CVM) |date=16 July 1996 |accessdate=12 August 2009}}</ref> In the meanwhile, some ''[[Burkholderia cepacia]]'', ''[[Clostridium innocuum]]'' and ''[[Enterococcus faecium]]'' have developed resistance to Ciprofloxacin to varying degrees.<ref>{{cite web|title=Ciprofloxacin spectrum of bacterial susceptibility and Resistance|url=http://www.toku-e.com/Upload/Products/PDS/20120618005735.pdf |accessdate=4 May 2012}}</ref>
[[Antibiotic resistance|Resistance]] to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. Numerous [[pathogen]]s, including ''[[Staphylococcus aureus]]'', [[enterococci]], ''[[Streptococcus pyogenes]]'' and ''[[Klebsiella pneumoniae]] (quinolone-resistant)'' 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 = [[Center for Veterinary Medicine]] (CVM) |date=16 July 1996 |accessdate=12 August 2009}}</ref> In the meanwhile, some ''[[Burkholderia cepacia]]'', ''[[Clostridium innocuum]]'' and ''[[Enterococcus faecium]]'' have developed resistance to Ciprofloxacin to varying degrees.<ref>{{cite web|title=Ciprofloxacin spectrum of bacterial susceptibility and Resistance|url=http://www.toku-e.com/Upload/Products/PDS/20120618005735.pdf |accessdate=4 May 2012}}</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.
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.For the population less than 15 to 20 percent clarithromycin resistance,clarithromycin amoxicillin is treated as first choice of resistant is proved by some of the researchers.Varieties of therapies such as rescue theraphy was proposed with different combinations for the patients who are failed in a treatment.Many of the methods are done to prove the efficacy ciprofloxacin based regimen in the eradication of helicobacterpylori infection.according to the theory proposed in the first 14 patients amoxicillin and clarithromycin were failed to treat H.''pylori'' infection.To know the presence of H.pylori in the body the biospsy specimens were taken one from the antrum and another one from the angulus and kept in 10 percent buffered formalin solution.After then the antrum biopsy is then transferred to portagem pylori follwed by steaking the ''antrum'' onto a columbus agar plates at a temperature of 37 degree celsius and incubated for 3 to 5 days by maintaining the 100% Humidity.By the researchers it was showed that the colony appearence.Further more Minimum inhibitory concentartion is proved by the intercept of the elliptical zone inhibition with the graded E-test strip.One of the study compared that 3-day ciprofloxacin and 7-day ciprofloxacin to treat the uncomplicated urinary tract infections in women. Moreover many methods are designed to know the efficacy of the ciprofloxacin. A 76 patients were taken,It was divided into two groups.To one of the groups ciprofloxacin was given 250mg twice a day for 3 days and to another group same 250 mg of ciprofloxacin was given twice a day for 7 days.Each groups should visit the clinician for three times that is for first visit is at the baseline, second visit is at the end of the treatment, third visit is for the 4 weeks of the following theraphy. Untill the results are obtained in the mean while thorough physical examination was done to the ciprofloxacin regimen received patients. During the First visit demographic and drug history of the patients were collected, during the second visit clinical information of the patient were observed and for the third visit resnponse of the theraphy was observed. It also proved that bacterial eradication of 3 day and 7 day ciprofloxacin regimen was upto 74.4% and 64.9%.Moreover microbial eradication rate of E.coli was up to 66.7% and 64.8% in the 3-day and 7-day regimen of ciprofloxacin.This study also proved that patients compliance with the 3 day ciprofloxacin has more effective in treatment of urinary tract infection when compared to 7 day ciprofloxacin regimen.One of the studies proved that antimicrobial resistance of ciprofloxacin against different pathogens.Many methods are determined to prove it.Several pathogens were isolated from the stools 10%, urine 46%,skin and ear 24%blood 20%.Infact ciprofloxacin 6mm disks were collected from the commercial market.ciprofloxacin also had a good acitivity against E.coli about 27.02% resistance was shown by this pathogen.K.pneumoniae showed 72.22% of resistance which have showed high resistance compared to other pathogens.


==Litigation==
==Litigation==

Revision as of 05:19, 12 October 2012

"Cipro" redirects here. For the Rome Metro station, see Cipro (Rome Metro).
Not to be confused with Cipralex, a brand name of the antidepressant escitalopram.
Ciprofloxacin
Clinical data
Trade namesCiloxan, Cipro, Neofloxin
AHFS/Drugs.comMonograph
MedlinePlusa688016
License data
Pregnancy
category
  • AU: B3
Routes of
administration		Oral, intravenous, topical (ear drops, eye drops)
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: WARNING[1]Rx-only
Pharmacokinetic data
Bioavailability69%[2]
MetabolismHepatic, including CYP1A2
Elimination half-life4 hours
ExcretionRenal
Identifiers
  • 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard100.123.026 Edit this at Wikidata
Chemical and physical data
FormulaC17H18FN3O3
Molar mass331.346 g·mol−1
3D model (JSmol)
  • c1c2c(cc(c1F)N3CCNCC3)n(cc(c2=O)C(=O)O)C4CC4
  • InChI=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) checkY
  • Key:MYSWGUAQZAJSOK-UHFFFAOYSA-N checkY
  (verify)

Ciprofloxacin (INN) is a synthetic antibiotic of the fluoroquinolone drug class.[3][4] It is a second-generation fluoroquinolone 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.

Ciprofloxacin was first patented in 1983 by Bayer A.G. and subsequently approved by the U.S. Food and Drug Administration (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, a characteristic it shares with other widely used antibacterial drugs such as amoxicillin, trimethoprim, azithromycin, cephalexin, and doxycycline.[5]

As of 2011 the FDA has added two black box warnings 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.[6]

Medical uses

Ciprofloxacin is used to treat a number of infections including: infections of bones and joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax, chancroid, among others.[7]

  • Urinary tract infections (recommended as a first-line antibiotic)[8]
  • Acute uncomplicated cystitis in females
  • Chronic bacterial prostatitis (not recommended as a first-line antibiotic choice)[9][10]
  • Lower respiratory tract infections (not recommended as a first-line antibiotic choice)[11][12][13]
  • Acute sinusitis (not recommended as a first-line antibiotic choice)[14]
  • Skin and skin structure infections
  • Bone and joint infections
  • Infectious diarrhea
  • Typhoid fever (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,[15] United States (including Hawaii), Canada,[16] and Scotland)[17] due to bacterial resistance. Fluoroquinolones are no longer recommended in the USA for this indication.[18]

Ciprofloxacin is not recommended for the treatment of tuberculosis.[19]

As well as in combination with other specific drugs:

  • Complicated intra-abdominal infections (in combination with metronidazole);
  • Empirical therapy for febrile neutropenic patients (in combination with piperacillin)

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 vs 6.0% and 9.5% for a panel of comparator antibiotics (mainly cephalosporins).[20] As such the pediatric use of ciprofloxacin is restricted to proven complicated urinary tract infections and pyelonephritis due to E. coli and inhalation anthrax.[21] Although FDA approved for this indication, ciprofloxacin is not to be considered a first line agent for inhalation anthrax in the pediatric population.[20][22][23][24] However, the fluoroquinolones are licensed to treat lower respiratory infections in children with cystic fibrosis in the UK.

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.[25]

Indications include:

Ciprofloxacin is not recommended to treat community acquired pneumonia (CAP) as a stand-alone first-line agent due to its modest activity against Streptococcus pneumoniae, a common causative pathogen. "Respiratory quiniolones" such as levofloxacin, having greater activity against this pathogen, are recommended as first line agents for the treatment of CAP in patients with important co-morbidities and in patients requiring hospitalization (Infectious Diseases Society of America 2007). The guidelines include a warning that "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...."[28]

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...."[13][29] does not appear to have changed within these current guidelines.

Antibiotics may not improve the long-term clinical outcome for sinusitis.[30] When prescribed for chronic bronchitis and acute bacterial sinusitis, the use of the fluoroquinolone class offers no compelling advantages over established treatment.[31] Nor does antibiotic treatment help sore throats.[32] 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.[33] Additionally, antibiotics have no effect upon viral infections, such as the common head cold or viral respiratory infections.

Ciprofloxacin should not be used in infants as they have not developed sufficient enzymes to metabolize the drug.[citation needed] Severe adverse reaction may occur in this patient group.

Ciprofloxacin may be licensed for other uses, or restricted, by the various regulatory agencies worldwide.

Availability

Ciprofloxacin is available as tablets, intravenous solutions, eye and ear drops.

Contraindications

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.[34]

There are only four contraindications found within the 2009 package insert:[35]

  • "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."
  • "Concomitant administration with tizanidine is contraindicated."
  • "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."
  • "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."

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.[36]

Ciprofloxacin is also considered to be contraindicated within the pediatric population (except for the indications outlined under licensed use above), pregnancy, nursing mothers, and in patients with epilepsy or other seizure disorders.

  • Pregnancy

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.[37][38]

  • Pediatric population

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. 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.

Within the studies submitted in response to a Pediatric Written Request (ciprofloxacin, circa 2004), the rate of arthropathy was reported to be 9.3%.[39] Within the BPCA Pediatric Studies Summary for ciprofloxacin,[39] it was stated that the overall incidence of adverse events at six weeks was 41% compared to 31% in a control population treated with other antibiotics. 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,[40] supports the current expert opinion that the risk of permanent injury continues to outweigh the potential benefits of ciprofloxacin therapy in the pediatric population.

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.[21]

Adverse effects

See also: Adverse effects of fluoroquinolones

The safety of fluoroquinolones is similar to that of other antibiotics.[41] In most, adverse reactions are mild to moderate; however, occasionally serious adverse effects occur.[41][42] There have been a number of regulatory actions taken as a result of such adverse reactions, which included published warnings,[43][44] additional warnings and safety information added to the package inserts[45] together with the issuance of "Dear Doctor Letters"[46] 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 peripheral neuropathy (irreversible nerve damage), tendon damage, heart problems (prolonged QT Interval / torsades de pointes), pseudomembranous colitis, rhabdomyolysis (muscle breakdown), Stevens–Johnson syndrome, as well as concurrent usage of NSAIDs contributing to the severity of these reactions.[citation needed]

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."[47] It was not until 2008, (four years later) that the label revisions for ciprofloxacin included any warnings concerning heart problems (prolonged QT interval / torsade de pointes). Warnings concerning rhabdomyolysis and Stevens–Johnson syndrome were still absent from the package inserts as of September 2009.

The serious adverse effects that may occur as a result of ciprofloxacin therapy include irreversible peripheral neuropathy,[48][49] spontaneous tendon rupture and tendonitis,[50][51][52][53] acute liver failure or serious liver injury (hepatitis),[54][55] QTc prolongation/torsades de pointes,[21] toxic epidermal necrolysis (TEN),[56][57][57] and Stevens–Johnson syndrome, severe central nervous system disorders (CNS)[26] and Clostridium difficile associated disease (CDAD: pseudomembranous colitis),[58][59] as well as photosensitivity/phototoxicity reactions.

Psychotic reactions and confusional states, acute pancreatitis,[60] bone marrow depression, interstitial nephritis and hemolytic anemia may also occur during ciprofloxacin therapy.[61][62] Additional serious adverse reactions include temporary, as well as permanent, loss of vision,[63][64] irreversible double vision,[65] drug induced psychosis[66][67] and chorea (involuntary muscle movements),[68] impaired color vision, exanthema, abdominal pain, malaise, drug fever, dysaesthesia and eosinophilia.[69][70] Pseudotumor cerebri, 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.[71]

Children and the elderly are at a much greater risk of experiencing such adverse reactions.[72][73] Tendonitis and other forms of tendon damage may manifest during fluoroquinolone therapy, and long after it had been discontinued.[74]

Serious visual complications have also been reported to occur with ophthalmic fluoroquinolone therapy, which may also occur with ciprofloxacin eye drops, especially corneal perforation, but also evisceration and enucleation. This increased incidents of corneal perforation may be due to fluoroquinolones causing alterations in stromal collagen, leading to a reduction in tectonic strength.[75][76] As noted previously permanent double vision (diplopia) has also been reported.[65] An unusual case of seizures has also been reported with ciprofloxacin ear drops in an elderly patient.[77]

Some groups refer to these adverse events as "fluoroquinolone toxicity". 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 Public Citizen.[78] 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.[79]

Interactions

The toxicity of drugs that are metabolised by the cytochrome P450 system is enhanced by concomitant use of some quinolones. Coadministration may dangerously increase Coumadin (warfarin) activity; INR should be monitored closely. They may also interact with the GABA A receptor and cause neurological symptoms; this effect is augmented by certain nonsteroidal anti-inflammatory drugs.[80] Quercetin, a flavonol, occasionally used as a dietary supplement, may interact with fluoroquinolones, as quercetin competitively binds to bacterial DNA gyrase. Some foods, such as garlic and apples, contain high levels of quercetin; whether this inhibits or enhances the effect of fluoroquinolones is not entirely clear.[81] Ciprofloxacin can reduce phenytoin plasma levels, which may, in some cases, result in seizures.[82] Ciprofloxacin may interfere with the levels of thyroid medications resulting in hypothyroidism.[83]

On 9 November 2004, 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:

"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."[84]

Concurrent administration of ciprofloxacin with magnesium or aluminium 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.[85]

Significant drug interactions

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 musculoskeletal, central nervous, renal, and other systems.

Current or past treatment with oral corticosteroids is associated with an increased risk of achilles tendon rupture, especially in elderly patients who are also taking the fluoroquinolones.[86] This is the subject of Black box warnings in FDA and BNF labeling for quinolones.

The Committee on the Safety of Medicines and the FDA warn that central nervous system adverse effects, including seizure risk, may be increased when NSAIDs are combined with quinolones.[21][87] 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 synergistic increased antagonism of GABA neurotransmission.[42]

Ciprofloxacin's renal clearance may affect other drugs subject to renal clearance or otherwise affecting the kidney. The use of ciprofloxacin concomitantly with cyclosporine has also been associated with transient elevations in serum creatinine. Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin, potentially leading to increased plasma levels of methotrexate and risk of methotrexate toxicity. Probenecid interferes with renal tubular secretion of ciprofloxacin and produces an increase in the level of ciprofloxacin in serum.[21]

Some quinolones, including ciprofloxacin, exert an inhibitory effect on the cytochrome P-450 enzyme CYP1A2, thereby reducing clearance, and thus increasing blood levels of tizanidine and methylxanthines (for example, theophylline and caffeine).[88][89] The quinolones have also been reported to enhance the effects of warfarin or its derivatives.[21] 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 (levothyroxine), resulting in unexplained hypothyroidism.[90] Altered serum levels of phenytoin and carbamazepine (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.[21][91]

Overdose

Overdose of ciprofloxacin may result in reversible renal toxicity. Treatment of overdose includes emptying of the stomach via induced vomiting or by gastric lavage. Careful monitoring and supportive treatment, monitoring of renal function and maintaining adequate hydration is recommended by the manufacturer. Administration of magnesium, aluminium, or calcium containing antacids can reduce the absorption of ciprofloxacin. Hemodialysis or peritoneal dialysis removes only less than 10 percent of ciprofloxacin.[85] 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.[92]

Mechanism of action

Ciprofloxacin is a broad-spectrum antibiotic active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV,[93] 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)[94] 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.[95] 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.).[96]

Recent studies have demonstrated a correlation between mammalian cell cytotoxicity of the quinolones and the induction of micronuclei.[97][98][99][100] As such, some fluoroquinolones may cause injury to the chromosome of eukaryotic cells.[101][102][103][104][105][106]

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.[95][107][108]

Chemistry

Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C17H18FN3O3 and its molecular weight is 331.4 g/mol. It is a faintly yellowish to light yellow crystalline substance.[85]

Ciprofloxacin hydrochloride (USP) 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 C17H18FN3O3HCl•H2O.[85]

Pharmacokinetics

The effects of 200–400 mg of ciprofloxacin given intravenously are linear; drug accumulation does not occur when administered at 12 hour intervals. Bioavailability is approximately 70-80%, with no significant first pass effect. IV administration produces a similar serum levels as those achieved with administration of 500 mg administered orally. IV administration over 60 minutes given every 8 hours produces similar serum levels of the drug as 750 mg administered orally every 12 hours.[85] Biotransformation is hepatic. The elimination half life is 4 hours.[21]

History

Ciprofloxacin 250mg tablets from Ukraine

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.[109] The United States patent was applied for in January 1987, but was not approved until 1996 according to the patent history.

In 2004, ciprofloxacin and levofloxacin together commanded 65% ($3.3 billion) of the global sales of the fluoroquinolone class.[110] The first nine months of 2008 sales for ciprofloxacin were $242 million, as compared to $324 million for Bayer aspirin.[111] 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."[112] The sale of ciprofloxacin increased dramatically following the anthrax 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 doxycycline, an equally effective alternative. [113]

Generic equivalents

On 24 October 2001, The Prescription Access Litigation (PAL), filed suit to dissolve an agreement between Bayer and three of its competitors which produced generic versions of drugs (Barr Laboratories, Rugby Laboratories, and Hoechst-Marion-Roussel) 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,[114] in effect upholding Bayer's agreement with its competitors.

Black box warnings

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 nalidixic acid.[115] Rheumatic disease after use of a fluoroquinolone (norfloxacin) was first reported 11 years later.[116] In response to a 1995 letter published in the New England Journal of Medicine, representatives of the U.S. Food and Drug Administration (FDA) stated that the agency would "update the labeling [package insert] for all marketed fluoroquinolones to include a warning about the possibility of tendon rupture."[117]

By August 1996, the FDA had not taken action, and the consumer advocacy group Public Citizen filed a petition with the FDA prompting the agency to act.[118] 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.[50]

Nine years later, in 2005, the Illinois Attorney General filed a second petition with the FDA again seeking Black Box Warnings 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.[119] 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.[119][120] 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.[121][122] On 7 July 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.[123] The package inserts for Ciprofloxacin, Avelox (moxifloxacin), Proquin XR, Factive (gemifloxacin), Floxin (ofloxacin), Noroxin (norfloxacin) and Levaquin (levofloxacin) were amended on 8 September 2008 to include these new warnings.[124] Bayer, which manufactures Cipro, Avelox and Proquin XR, issued a Dear Healthcare Professional letter on 22 October concerning these changes.[125] Ortho-McNeil, the manufacturers of Levaquin, issued a similar letter in November.[126] through the Health Care Notification Network, a registration-only website that distributes drug alerts to licensed healthcare professionals.

On 25 February 2011[127] an 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.

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.

FDA warning letters

Additionally the manufacturers of ciprofloxacin (Bayer A.G.) received numerous warning letters from the United States Food and Drug Administration regarding false advertising and failure to provide adequate warnings within their promotional materials.[128][129]

Bacterial resistance

See also: Antibiotic abuse and 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,[130][131][132] 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.[133][134]

Resistance to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. Numerous pathogens, including Staphylococcus aureus, enterococci, Streptococcus pyogenes and Klebsiella pneumoniae (quinolone-resistant) now exhibit resistance worldwide.[135] Widespread veterinary usage of the fluoroquinolones, particularly in Europe, has been implicated.[136] In the meanwhile, some Burkholderia cepacia, Clostridium innocuum and Enterococcus faecium have developed resistance to Ciprofloxacin to varying degrees.[137]

Fluoroquinolones had become the most commonly prescribed class of antibiotics to adults in 2002.[138] 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.[138][139] 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.For the population less than 15 to 20 percent clarithromycin resistance,clarithromycin amoxicillin is treated as first choice of resistant is proved by some of the researchers.Varieties of therapies such as rescue theraphy was proposed with different combinations for the patients who are failed in a treatment.Many of the methods are done to prove the efficacy ciprofloxacin based regimen in the eradication of helicobacterpylori infection.according to the theory proposed in the first 14 patients amoxicillin and clarithromycin were failed to treat H.pylori infection.To know the presence of H.pylori in the body the biospsy specimens were taken one from the antrum and another one from the angulus and kept in 10 percent buffered formalin solution.After then the antrum biopsy is then transferred to portagem pylori follwed by steaking the antrum onto a columbus agar plates at a temperature of 37 degree celsius and incubated for 3 to 5 days by maintaining the 100% Humidity.By the researchers it was showed that the colony appearence.Further more Minimum inhibitory concentartion is proved by the intercept of the elliptical zone inhibition with the graded E-test strip.One of the study compared that 3-day ciprofloxacin and 7-day ciprofloxacin to treat the uncomplicated urinary tract infections in women. Moreover many methods are designed to know the efficacy of the ciprofloxacin. A 76 patients were taken,It was divided into two groups.To one of the groups ciprofloxacin was given 250mg twice a day for 3 days and to another group same 250 mg of ciprofloxacin was given twice a day for 7 days.Each groups should visit the clinician for three times that is for first visit is at the baseline, second visit is at the end of the treatment, third visit is for the 4 weeks of the following theraphy. Untill the results are obtained in the mean while thorough physical examination was done to the ciprofloxacin regimen received patients. During the First visit demographic and drug history of the patients were collected, during the second visit clinical information of the patient were observed and for the third visit resnponse of the theraphy was observed. It also proved that bacterial eradication of 3 day and 7 day ciprofloxacin regimen was upto 74.4% and 64.9%.Moreover microbial eradication rate of E.coli was up to 66.7% and 64.8% in the 3-day and 7-day regimen of ciprofloxacin.This study also proved that patients compliance with the 3 day ciprofloxacin has more effective in treatment of urinary tract infection when compared to 7 day ciprofloxacin regimen.One of the studies proved that antimicrobial resistance of ciprofloxacin against different pathogens.Many methods are determined to prove it.Several pathogens were isolated from the stools 10%, urine 46%,skin and ear 24%blood 20%.Infact ciprofloxacin 6mm disks were collected from the commercial market.ciprofloxacin also had a good acitivity against E.coli about 27.02% resistance was shown by this pathogen.K.pneumoniae showed 72.22% of resistance which have showed high resistance compared to other pathogens.

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.[140][141][142] 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.[143][144][145]

Brand names

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 Neofloxin in Bangladesh, in India it is marketed as Alcipro .In Russia Ciprex and "Cetraxal" in Spain. In Pakistan it is marketed as Axcin. In addition, ciprofloxacin is available as a generic drug under a variety of different brand names and is also available for limited use in veterinary medicine.

See also

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  2. ^ Drusano GL, Standiford HC, Plaisance K, Forrest A, Leslie J, Caldwell J, GL (1986). "Absolute oral bioavailability of ciprofloxacin". Antimicrob Agents Chemother. 30 (3): 444–6. ISSN 0066-4804. PMC 180577. PMID 3777908. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); |first6= missing |last6= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Nelson, JM.; Chiller, TM.; Powers, JH.; Angulo, FJ. (2007). "Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story". Clin Infect Dis. 44 (7): 977–80. doi:10.1086/512369. PMID 17342653. {{cite journal}}: Unknown parameter |month= ignored (help)
  4. ^ Kawahara, S. (1998). "[Chemotherapeutic agents under study]". Nippon Rinsho. 56 (12): 3096–9. PMID 9883617. {{cite journal}}: Unknown parameter |month= ignored (help)
  5. ^ Cooper JG, Harboe K, Frost SK, Skadberg Ø, JG (2005). "Ciprofloxacin interacts with thyroid replacement therapy". BMJ. 330 (7498): 1002. doi:10.1136/bmj.330.7498.1002. ISSN 0959-8138. PMC 557149. PMID 15860826. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019537s075,020780s033lbl.pdf
  7. ^ "Ciprofloxacin-Hydrochloride". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
  8. ^ "Fluroquinolone Drug Class Review" (PDF). Oregon State University College of Pharmacy. 2002. Retrieved 9 September 2011.
  9. ^ Alexander, RB; Propert, KJ; Schaeffer, AJ; Landis, JR; Nickel, JC; O'Leary, MP; Pontari, MA; McNaughton-Collins, M; Shoskes, DA (19 October 2004). "Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial" (PDF). Annals of Internal Medicine. 141 (8): 581–9. PMID 15492337. Conclusion: Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms.
  10. ^ J. Dimitrakov. "A Prospective, Randomized, Double-Blind, Placebo-Controlled Study Of Antibiotics For The Treatment Of Category Iiib Chronic Pelvic Pain Syndrome In Men". Third International Chronic Prostatitis Network. Retrieved 4 September 2009. {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  11. ^ Zuger A (3 November 1998). "Ciprofloxacin for Acute Exacerbations of Chronic Bronchitis". Journal Watch (General). 1998 (1103): 4. Because of its unpredictable activity against the pneumococcus, ciprofloxacin is not usually considered a first-line treatment for respiratory infections...
  12. ^ Vardakas, KZ; Siempos, II; Grammatikos, A; Athanassa, Z; Korbila, IP; Falagas, ME (2008). "Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials". CMAJ. 179 (12): 1269–77. doi:10.1503/cmaj.080358. PMC 2585120. PMID 19047608. {{cite journal}}: Unknown parameter |month= ignored (help)
  13. ^ a b Donaldson, PM; Pallett, AP; Carroll, MP (1994). "Ciprofloxacin in general practice". BMJ (Clinical Research Ed.). 308 (6941): 1437. ISSN 0959-8138. PMC 2540361. PMID 8019264. {{cite journal}}: Unknown parameter |month= ignored (help)
  14. ^ Karageorgopoulos, DE.; Giannopoulou, KP.; Grammatikos, AP.; Dimopoulos, G.; Falagas, ME. (2008). "Fluoroquinolones compared with beta-lactam antibiotics for the treatment of acute bacterial sinusitis: a meta-analysis of randomized controlled trials". CMAJ. 178 (7): 845–54. doi:10.1503/cmaj.071157. PMC 2267830. PMID 18362380. {{cite journal}}: Unknown parameter |month= ignored (help)
  15. ^ (World Health Organization (WHO) Western Pacific Region Gonococcal Antimicrobial Susceptibility Programme (GASP) Report- 2000. Commun Dis Intell 2001; 25:274-277).
  16. ^ DEPARTMENT OF HEALTH AND HUMAN SERVICES (2004). "Gonococcal Isolate Surveillance Project (GISP) Annual Report - 2003" (PDF). USA: Center for Disease Controlo. Retrieved 31 August 2009. {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  17. ^ Hugh Young (22 July 2003). "Ciprofloxacin resistant gonorrhoea: the situation in Scotland and implications for therapy" (PDF). SCIEH Weekly Report - SCOTTISH CENTRE FOR INFECTION AND ENVIRONMENTAL HEALTH. 37. Scotland: National Health Service. ISSN 1357-4493.
  18. ^ Centers for Disease Control and Prevention (CDC) (13 April 2007). [Center for Disease Control "Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections"] (PDF). Morbidity and Mortality Weekly Report. 56 (14). USA: Center for Disease Control: 332–336. PMID 17431378. Retrieved 31 August 2009. {{cite journal}}: Check |url= value (help)
  19. ^ Ziganshina, LE; Vizel, AA; Squire, SB (2005). Ziganshina, Lilia (ed.). "Fluoroquinolones for treating tuberculosis". Cochrane database of systematic reviews (Online) (3): CD004795. doi:10.1002/14651858.CD004795.pub2. PMID 16034951. {{cite journal}}: Unknown parameter |month= ignored (help)
  20. ^ a b Meyer, Joette; Albrecht, Renata (16 March 2004). "Summary of Clinical Review of Studies Submitted in Response to a Pediatric Written Request" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 31 August 2009.
  21. ^ a b c d e f g h "Cipro Labeling Revision 10/03/2008 Supplement 068" (PDF). U.S. Food and Drug Administration (FDA). 3 October 2008. Retrieved 31 August 2009.
  22. ^ Chalumeau, M., M; Tonnelier, S; D'athis, P; Tréluyer, JM; Gendrel, D; Bréart, G; Pons, G; Pediatric Fluoroquinolone Safety Study Investigators, Investigators (2003). "Fluoroquinolone Safety in Pediatric Patients: A Prospective, Multicenter, Comparative Cohort Study in France" (PDF). Pediatrics. 111 (6 Pt 1): e714. doi:10.1542/peds.111.6.e714. ISSN 0031-4005. PMID 12777590. {{cite journal}}: Unknown parameter |month= ignored (help)
  23. ^ 62 Meeting of the Anti-Infective Drugs Advisory Committee
  24. ^ Farinas, Evelyn R (1 March 2005). "Consult: One-Year Post Pediatric Exclusivity Postmarketing Adverse Events Review" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 31 August 2009. {{cite web}}: More than one of |author= and |last= specified (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  25. ^ Lexi-Comp (2009). "Ciprofloxacin". Merk. Retrieved 4 September 2009. {{cite web}}: Unknown parameter |month= ignored (help)
  26. ^ a b Renata Albrecht (25 March 2004). "Cipro Labeling Revision Letter 03/25/2004 Supplement 049 Patient Population Altered" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 7 September 2009.
  27. ^ Dianne Murphy (30 August 2000). "Cipro Labeling Revision Letter 08/30/2000 Supplement 008 New or Modified Indication" (PDF). U.S. Food and Drug Administration (FDA).
  28. ^ Mandell, LA.; Wunderink, RG.; Anzueto, A.; Bartlett, JG.; Campbell, GD.; Dean, NC.; Dowell, SF.; File, TM.; Musher, DM. (2007). "Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults" (PDF). Clin Infect Dis. 44 (Suppl 2): S27–72. doi:10.1086/511159. PMID 17278083. {{cite journal}}: Unknown parameter |month= ignored (help)[dead link]
  29. ^ Körner, RJ.; Reeves, DS.; MacGowan, AP. (1994). "Dangers of oral fluoroquinolone treatment in community acquired upper respiratory tract infections". BMJ. 308 (6922): 191–2. PMC 2542530. PMID 8312775. {{cite journal}}: Unknown parameter |month= ignored (help)
  30. ^ van Buchem, F. L. (8 March 1997). "Primary-care-based randomised placebo-controlled trial of antibiotic treatment in acute maxillary sinusitis". The Lancet. 349 (9053): 683–687. doi:10.1016/S0140-6736(96)07585-X. PMID 9078199.
  31. ^ "Moxifloxacin - a new fluoroquinolone antibacterial". Drug and Therapeutics Bulletin. 42 (8): 61. 2004. doi:10.1136/dtb.2004.42861. ISSN 0012-6543. PMID 15310155. {{cite journal}}: Unknown parameter |month= ignored (help)
  32. ^ Majeed, A, A; Harris, T, T (1997). "Acute otitis media in children". BMJ (Clinical research ed.). 315 (7104): 321–2. ISSN 0959-8138. PMC 2127258. PMID 9270442. {{cite journal}}: Unknown parameter |month= ignored (help)[dead link]
  33. ^ Hueston, Wj, WJ (1997). "Antibiotics: neither cost effective nor 'cough' effective" (Free full text). The Journal of family practice. 44 (3): 261–5. ISSN 0094-3509. PMID 9071245. {{cite journal}}: Unknown parameter |month= ignored (help)
  34. ^ Susan Blank (14 May 2004). "DOHMH ALERT #8:Fluoroquinolone-resistant gonorrhea, NYC". USA: New York County Medical Society. Retrieved 22 July 2009. {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  35. ^ "Cipro Labeling Revision 02/25/2011 Supplement 075" (PDF). U.S. Food and Drug Administration (FDA). 25 February 2011. Retrieved 1 April 2011.
  36. ^ Centers for Disease Control and Prevention (CDC) (1995). "Fluoroquinolone resistance in Neisseria gonorrhoeae—Colorado and Washington, 1995". MMWR Morb Mortal Wkly Rep. 44 (41): 761–4. ISSN 0149-2195. PMID 7565558. {{cite journal}}: Unknown parameter |month= ignored (help)
  37. ^ Shin HC, Kim JC, Chung MK, HC (2003). "Fetal and maternal tissue distribution of the new fluoroquinolone DW-116 in pregnant rats". Comp. Biochem. Physiol. C Toxicol. Pharmacol. 136 (1): 95–102. doi:10.1016/j.cca.2003.08.004. ISSN 1532-0456. PMID 14522602. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); |first6= missing |last6= (help); |first7= missing |last7= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  38. ^ Dan M, Weidekamm E, Sagiv R, Portmann R, Zakut H, M (1993). "Penetration of fleroxacin into breast milk and pharmacokinetics in lactating women". Antimicrob. Agents Chemother. 37 (2): 293–6. doi:10.1128/AAC.37.2.293. ISSN 0066-4804. PMC 187655. PMID 8452360. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  39. ^ a b Joette Meyer (16 March 2004). "Division of Special Pathogen and Immunologic Drug Products Summary of Clinical Review of Studies Submitted in Response to a Pediatric Written Request" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 22 July 2009. {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  40. ^ BAY 0 9867 Cipro Pediatric Use Study (QUIP) - Study Results - ClinicalTrials.gov
  41. ^ a b Owens Rc, Jr; Ambrose, PG (2005). "Antimicrobial safety: focus on fluoroquinolones". Clinical Infectious Diseases. 41 Suppl 2: S144–57. doi:10.1086/428055. ISSN 1058-4838. PMID 15942881. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  42. ^ a b De Sarro A, De Sarro G (2001). "Adverse reactions to fluoroquinolones. an overview on mechanistic aspects" (PDF). Curr. Med. Chem. 8 (4): 371–84. PMID 11172695. {{cite journal}}: Unknown parameter |month= ignored (help)
  43. ^ "FDA Requests Boxed Warnings on Fluoroquinolone Antimicrobial Drugs" (Press release). U.S. Food and Drug Administration (FDA). 8 July 2008. Retrieved 5 September 2009.
  44. ^ "Information for Healthcare Professionals: Fluoroquinolone Antimicrobial Drugs [ciprofloxacin (marketed as Cipro and generic ciprofloxacin), ciprofloxacin extended-release (marketed as Cipro XR and Proquin XR), gemifloxacin (marketed as Factive), levofloxacin (marketed as Levaquin), moxifloxacin (marketed as Avelox), norfloxacin (marketed as Noroxin), and ofloxacin (marketed as Floxin)]". U.S. Food and Drug Administration (FDA). 8 July 2008. Retrieved 5 September 2009.
  45. ^ "Drugs at FDA: FDA Approved Drug Products". U.S. Food and Drug Administration (FDA). Retrieved 5 September 2009.[verification needed]
  46. ^ Paul MacCarthy (22 October 2008). "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" (PDF). Bayer healthcare pharmaceuticals. Retrieved 5 September 2009.
  47. ^ Renata Albrecht (19 June 2006). "Cipro Labeling Revision Letter 06/19/2006 Supplement 062" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 5 September 2009.
  48. ^ Renata Albrecht (14 July 2004). "Cipro Labeling Revision Letter 07/14/2004 Supplement 053" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 5 September 2009.
  49. ^ Zehnder, D; Hoigné, R; Neftel, KA; Sieber, R (1995). "Painful dysaesthesia with ciprofloxacin". BMJ (Clinical research ed.). 311 (7014): 1204. ISSN 0959-8138. PMC 2551120. PMID 7488901. 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 {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); More than one of |author4= and |last4= specified (help); Unknown parameter |month= ignored (help)
  50. ^ a b "Reports of adverse events with fluoroquinolones" (Doc). FDA Medical Bulletin. 26 (3). 1996. {{cite journal}}: Unknown parameter |month= ignored (help)
  51. ^ Renata Albrecht (15 March 2004). "Cipro Labeling Revision Letter 03/15/2004 Supplement 048" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 5 September 2009.
  52. ^ FQresearch.org
  53. ^ Renata Albrecht (3 October 2008). "Cipro Labeling Revision letter 10/03/2008 Supplement 068" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 5 September 2009.
  54. ^ Sherman, O; Beizer, JL (1994). "Possible ciprofloxacin-induced acute cholestatic jaundice" (Free full text). The Annals of pharmacotherapy. 28 (10): 1162–4. ISSN 1060-0280. PMID 7841570. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  55. ^ Zimpfer, A; Propst, A; Mikuz, G; Vogel, W; Terracciano, L; Stadlmann, S (2004). "Ciprofloxacin-induced acute liver injury: case report and review of literature". Virchows Archiv : an international journal of pathology. 444 (1): 87–9. doi:10.1007/s00428-003-0917-9. ISSN 0945-6317. PMID 14994731. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); More than one of |author4= and |last4= specified (help); More than one of |author5= and |last5= specified (help); More than one of |author6= and |last6= specified (help); Unknown parameter |month= ignored (help)
  56. ^ Jongen-Lavrencic, M; Schneeberger; Van Der Hoeven (2003). "Ciprofloxacin-induced toxic epidermal necrolysis in a patient with systemic lupus erythematosus". Infection. 31 (6): 428–9. doi:10.1007/s15010-003-2128-3. ISSN 0300-8126. PMID 14735388. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); Unknown parameter |month= ignored (help)
  57. ^ a b Moshfeghi, M; Mandler (1993). "Ciprofloxacin-induced toxic epidermal necrolysis". The Annals of pharmacotherapy. 27 (12): 1467–9. ISSN 1060-0280. PMID 8305780. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  58. ^ Deshpande, A; Pant; Jain; Fraser; Rolston (2008). "Do fluoroquinolones predispose patients to Clostridium difficile associated disease? A review of the evidence". Current medical research and opinion. 24 (2): 329–33. doi:10.1185/030079908X253735. ISSN 0300-7995. PMID 18067688. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); More than one of |author4= and |last4= specified (help); More than one of |author5= and |last5= specified (help); Unknown parameter |month= ignored (help)
  59. ^ Renata Albrecht (25 June 2007). "Cipro Labeling Revision letter 06/25/2007 Supplement 065" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 4 September 2009.
  60. ^ Mann, S; Thillainayagam (2000). "Is ciprofloxacin a new cause of acute pancreatitis?". Journal of Clinical Gastroenterology. 31 (4): 336. doi:10.1097/00004836-200012000-00014. ISSN 0192-0790. PMID 11129278. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  61. ^ Dutta, TK; Badhe (1999). "Ciprofloxacin-induced bone marrow depression". Postgraduate Medical Journal. 75 (887): 571–3. ISSN 0032-5473. PMC 1741342. PMID 10616701. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  62. ^ Lim, S; Alam (2003). "Ciprofloxacin-induced acute interstitial nephritis and autoimmune hemolytic anemia". Renal Failure. 25 (4): 647–51. doi:10.1081/JDI-120022557. ISSN 0886-022X. PMID 12911170. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  63. ^ Vrabec, TR; Sergott; Jaeger; Savino; Bosley (1990). "Reversible visual loss in a patient receiving high-dose ciprofloxacin hydrochloride (Cipro)". Ophthalmology. 97 (6): 707–10. ISSN 0161-6420. PMID 2374675. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); More than one of |author4= and |last4= specified (help); More than one of |author5= and |last5= specified (help); Unknown parameter |month= ignored (help)
  64. ^ Samarakoon, N; Harrisberg; Ell (2007). "Ciprofloxacin-induced toxic optic neuropathy". Clinical & experimental ophthalmology. 35 (1): 102–4. doi:10.1111/j.1442-9071.2007.01427.x. ISSN 1442-6404. PMID 17300586. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); Unknown parameter |month= ignored (help)
  65. ^ a b Fraunfelder, FW; Fraunfelder (2009). "Diplopia and fluoroquinolones". Ophthalmology. 116 (9): 1814–7. doi:10.1016/j.ophtha.2009.06.027. ISSN 0161-6420. PMID 19643481. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  66. ^ Mulhall, JP; Bergmann (1995). "Ciprofloxacin-induced acute psychosis". Urology. 46 (1): 102–3. doi:10.1016/S0090-4295(99)80171-X. ISSN 0090-4295. PMID 7604468. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  67. ^ Reeves, RR (1992). "Ciprofloxacin-induced psychosis". The Annals of pharmacotherapy. 26 (7–8): 930–1. ISSN 1060-0280. PMID 1504404. {{cite journal}}: Unknown parameter |month= ignored (help)
  68. ^ Azar, S; Ramjiani; Van Gerpen (2005). "Ciprofloxacin-induced chorea". Movement disorders : official journal of the Movement Disorder Society. 20 (4): 513–4, author reply 514. doi:10.1002/mds.20425. ISSN 0885-3185. PMID 15739219. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); Unknown parameter |month= ignored (help)
  69. ^ "Therapy of acute and chronic gram-negative osteomyelitis with ciprofloxacin. Report from a Swedish Study Group". The Journal of antimicrobial chemotherapy. 22 (2): 221–8. 1988. doi:10.1093/jac/22.2.221. ISSN 0305-7453. PMID 3053554. {{cite journal}}: Unknown parameter |month= ignored (help)
  70. ^ Zehnder, D; Hoigné; Neftel; Sieber (1995). "Painful dysaesthesia with ciprofloxacin". BMJ (Clinical research ed.). 311 (7014): 1204. ISSN 0959-8138. PMC 2551120. PMID 7488901. 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. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); More than one of |author4= and |last4= specified (help); Unknown parameter |month= ignored (help)
  71. ^ Winrow, AP; Supramaniam (1990). "Benign intracranial hypertension after ciprofloxacin administration". Archives of Disease in Childhood. 65 (10): 1165–6. doi:10.1136/adc.65.10.1165. ISSN 0003-9888. PMC 1792342. PMID 2248512. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  72. ^ Iannini, PB (2007). "The safety profile of moxifloxacin and other fluoroquinolones in special patient populations". Current medical research and opinion. 23 (6): 1403–13. doi:10.1185/030079907X188099. ISSN 0300-7995. PMID 17559736. {{cite journal}}: Unknown parameter |month= ignored (help)
  73. ^ Owens Rc, Jr; Ambrose (2005). "Antimicrobial safety: focus on fluoroquinolones". Clinical Infectious Diseases. 41 Suppl 2: S144–57. doi:10.1086/428055. ISSN 1058-4838. PMID 15942881. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  74. ^ Saint, F; Gueguen; Biserte; Fontaine; Mazeman (2000). "Rupture of the patellar ligament one month after treatment with fluoroquinolone". Revue de chirurgie orthopedique et reparatrice de l'appareil moteur. 86 (5): 495–7. ISSN 0035-1040. PMID 10970974. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); More than one of |author4= and |last4= specified (help); More than one of |author5= and |last5= specified (help); Unknown parameter |month= ignored (help)
  75. ^ Gangopadhyay, N; Daniell; Weih; Taylor (2000). "Fluoroquinolone and fortified antibiotics for treating bacterial corneal ulcers". The British journal of ophthalmology. 84 (4): 378–84. doi:10.1136/bjo.84.4.378. ISSN 0007-1161. PMC 1723447. PMID 10729294. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); More than one of |author4= and |last4= specified (help); Unknown parameter |month= ignored (help)
  76. ^ Walter, K; Tyler (2006). "Severe corneal toxicity after topical fluoroquinolone therapy: report of two cases". Cornea. 25 (7): 855–7. doi:10.1097/01.ico.0000224642.43601.14. ISSN 0277-3740. PMID 17068466. {{cite journal}}: More than one of |author2= and |last2= specified (help); Unknown parameter |month= ignored (help)
  77. ^ Orr, Cf; Rowe, Db (2003). "Eardrop attacks: seizures triggered by ciprofloxacin eardrops". The Medical journal of Australia. 178 (7): 343. ISSN 0025-729X. PMID 12670280. {{cite journal}}: Unknown parameter |month= ignored (help)
  78. ^ "Public Citizen Warns of Cipro Dangers". USA: Consumer affairs. 30 August 2006. Retrieved 7 September 2009.
  79. ^ "FDA orders 'black box' label on some antibiotics". CNN. 8 July 2008. Retrieved 8 July 2008.
  80. ^ Brouwers JR, JR (1992). "Drug interactions with quinolone antibacterials". Drug Saf. 7 (4): 268–81. doi:10.2165/00002018-199207040-00003. ISSN 0114-5916. PMID 1524699. {{cite journal}}: Unknown parameter |month= ignored (help)
  81. ^ Hilliard JJ, Krause HM, Bernstein JI, JJ (1995). "A comparison of active site binding of 4-quinolones and novel flavone gyrase inhibitors to DNA gyrase". Adv Exp Med Biol. 390: 59–69. ISSN 0065-2598. PMID 8718602. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); |first6= missing |last6= (help); |first7= missing |last7= (help)CS1 maint: multiple names: authors list (link)
  82. ^ Carol Langlois (1998). "Risk of seizures from concomitant use of ciprofloxacin and phenytoin in patients with epilepsy" (PDF). Canada: Canadian Adverse Drug Reaction Newsletter. Retrieved 30 January 2009. {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  83. ^ Cooper JG, Harboe K, Frost SK, Skadberg Ø, JG (2005). "Ciprofloxacin interacts with thyroid replacement therapy". BMJ. 330 (7498): 1002. doi:10.1136/bmj.330.7498.1002. ISSN 0959-8138. PMC 557149. PMID 15860826. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  84. ^ Renata Albrecht (9 November 2005). "Cipro Labeling Revision letter 11/09/2005 Supplement 060" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 8 September 2009.
  85. ^ a b c d e "Cipro Labeling Revision 04/06/2009 Supplement 073" (PDF). U.S. Food and Drug Administration (FDA). 6 April 2009. Retrieved 8 September 2009.
  86. ^ van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HM, Rowlands S, Stricker BH, PD (2003). "Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids". Arch. Intern. Med. 163 (15): 1801–7. doi:10.1001/archinte.163.15.1801. ISSN 0003-9926. PMID 12912715. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); |first6= missing |last6= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  87. ^ Royal Pharmaceutical Society of Great Britain (2009). "5 Infections". British National Formulary (BNF 57). BMJ Group and RPS Publishing. ISBN 978-0-85369-845-6.
  88. ^ Harder S, Fuhr U, Staib AH, Wolff T, S (1989). "Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations". Am. J. Med. 87 (5A): 89S–91S. doi:10.1016/0002-9343(89)90031-4. ISSN 0002-9343. PMID 2589393. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |format= requires |url= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  89. ^ Janknegt R, R (1990). "Drug interactions with quinolones". J. Antimicrob. Chemother. 26 Suppl D: 7–29. ISSN 0305-7453. PMID 2286594. {{cite journal}}: Unknown parameter |month= ignored (help)
  90. ^ Cooper JG, Harboe K, Frost SK, Skadberg Ø, JG (2005-04). "Ciprofloxacin interacts with thyroid replacement therapy". BMJ. 330 (7498): 1002. doi:10.1136/bmj.330.7498.1002. ISSN 0959-8138. PMC 557149. PMID 15860826. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); Check date values in: |date= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  91. ^ Shahzadi A, Javed I, Aslam B; et al. (2011). "Therapeutic effects of ciprofloxacin on the pharmacokinetics of carbamazepine in healthy adult male volunteers" (PDF). Pak J Pharm Sci. 24 (1): 63–68. PMID 21190921. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help); line feed character in |title= at position 101 (help)CS1 maint: multiple names: authors list (link)
  92. ^ 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.
  93. ^ Drlica K, Zhao X, K (1 September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiol Mol Biol Rev. 61 (3): 377–92. ISSN 1092-2172. PMC 232616. PMID 9293187. {{cite journal}}: |first2= missing |last2= (help)
  94. ^ Robinson MJ, Martin BA, Gootz TD, McGuirk PR, Osheroff N, MJ (1992). "Effects of novel fluoroquinolones on the catalytic activities of eukaryotic topoisomerase II: Influence of the C-8 fluorine group" (PDF). Antimicrob. Agents Chemother. 36 (4): 751–6. ISSN 0066-4804. PMC 189387. PMID 1323952. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  95. ^ a b Sissi C, Palumbo M, C (2003). "The quinolone family: from antibacterial to anticancer agents". Curr Med Chem Anticancer Agents. 3 (6): 439–50. doi:10.2174/1568011033482279. ISSN 1568-0118. PMID 14529452. 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. {{cite journal}}: |first2= missing |last2= (help); Unknown parameter |month= ignored (help)
  96. ^ Hussy P, Maass G, Tümmler B, Grosse F, Schomburg U, P (1986). "Effect of 4-quinolones and novobiocin on calf thymus DNA polymerase alpha primase complex, topoisomerases I and II, and growth of mammalian lymphoblasts" (PDF). Antimicrob. Agents Chemother. 29 (6): 1073–8. doi:10.1128/AAC.29.6.1073. ISSN 0066-4804. PMC 180502. PMID 3015015. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  97. ^ Hosomi JA; Hosomi, J, .; Maeda, A, .; Oomori, Y, .; Yokota (1988). "Mutagenicity of norfloxacin and AM-833 in bacteria and mammalian cells". Rev. Infect. 1. 10. jstor.org: S148–S149. JSTOR 4454399. {{cite journal}}: |first2= has numeric name (help)
  98. ^ Forsgren A, Bredberg A, Pardee AB, Schlossman SF, Tedder TF, A (1987). "Effects of ciprofloxacin on eucaryotic pyrimidine nucleotide biosynthesis and cell growth" (PDF). Antimicrob. Agents Chemother. 31 (5): 774–9. doi:10.1128/AAC.31.5.774. ISSN 0066-4804. PMC 174831. PMID 3606077. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  99. ^ Gootz TD, Barrett JF, Sutcliffe JA, TD (1990). "Inhibitory effects of quinolone antibacterial agents on eucaryotic topoisomerases and related test systems". Antimicrob. Agents Chemother. 34 (1): 8–12. doi:10.1128/AAC.34.1.8. ISSN 0066-4804. PMC 171510. PMID 2158274. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  100. ^ Lawrence JW, Darkin-Rattray S, Xie F, Neims AH, Rowe TC, JW (1993). "4-Quinolones cause a selective loss of mitochondrial DNA from mouse L1210 leukemia cells". J. Cell. Biochem. 51 (2): 165–74. doi:10.1002/jcb.240510208. ISSN 0730-2312. PMID 8440750. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); |format= requires |url= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  101. ^ Elsea SH, Osheroff N, Nitiss JL, SH (1992). "Cytotoxicity of quinolones toward eukaryotic cells. Identification of topoisomerase II as the primary cellular target for the quinolone CP-115,953 in yeast". J. Biol. Chem. 267 (19): 13150–3. ISSN 0021-9258. PMID 1320012. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  102. ^ Suto MJ, Domagala JM, Roland GE, Mailloux GB, Cohen MA, MJ (1992). "Fluoroquinolones: relationships between structural variations, mammalian cell cytotoxicity, and antimicrobial activity". J. Med. Chem. 35 (25): 4745–50. doi:10.1021/jm00103a013. ISSN 0022-2623. PMID 1469702. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  103. ^ Enzmann H, Wiemann C, Ahr HJ, Schlüter G, H (1999). "Damage to mitochondrial DNA induced by the quinolone Bay y 3118 in embryonic turkey liver". Mutat. Res. 425 (2): 213–24. doi:10.1016/S0027-5107(99)00044-5. ISSN 0027-5107. PMID 10216214. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  104. ^ Kashida Y, Sasaki YF, Ohsawa K, Y (2002). "Mechanistic study on flumequine hepatocarcinogenicity focusing on DNA damage in mice". Toxicol. Sci. 69 (2): 317–21. doi:10.1093/toxsci/69.2.317. ISSN 1096-6080. PMID 12377980. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |first4= missing |last4= (help); |first5= missing |last5= (help); |first6= missing |last6= (help); |first7= missing |last7= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  105. ^ Thomas A, Tocher J, Edwards DI, A (1990). "Electrochemical characteristics of five quinolone drugs and their effect on DNA damage and repair in Escherichia coli". J. Antimicrob. Chemother. 25 (5): 733–44. doi:10.1093/jac/25.5.733. ISSN 0305-7453. PMID 2165050. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  106. ^ "Fluoroquinolones and Quinolones". The American Academy of Optometry (British Chapter). Retrieved 29 January 2009.
  107. ^ Al-Soud, Yaseen A.; Al-masoudi, Najim A (2003). "A new class of dihaloquinolones bearing N'-aldehydoglycosylhydrazides, mercapto-1,2,4-triazole, oxadiazoline and a-amino ester precursors: synthesis and antimicrobial activity". J. Braz. Chem. Soc. 14 (5). doi:10.1590/S0103-50532003000500014. 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... {{cite journal}}: Cite has empty unknown parameter: |month= (help); More than one of |author1= and |last1= specified (help)
  108. ^ Yaseen A. Al-Soud a and Najim A. Al-Masoudi (2003). "A New Class of Dihaloquinolones Bearing N'-Aldehydoglycosylhydrazides, Mercapto-1,2,4-triazole, Oxadiazoline and α-Amino Ester Precursors: Synthesis and Antimicrobial Activity" (PDF). J. Braz. Chem. Soc. 14 (5): 790–796. doi:10.1590/S0103-50532003000500014. 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
  109. ^ Streuff; et al. (15 February 1994). "United States Patent 5,286,754". USA: uspto.gov. Retrieved 30 August 2009. {{cite web}}: Explicit use of et al. in: |author= (help)
  110. ^ "Commercial Perspectives: Fluoroquinolones - Established Products Drive Market Growth". 28 January 2004. Retrieved 30 August 2009.
  111. ^ Katrin Schneider (29 October 2008). "Stockholders' Newsletter" (PDF). Bayer AG. Retrieved 30 August 2009.
  112. ^ "Cipro". USA: Prescription Access. Retrieved 4 September 2009.
  113. ^ Bayer Corporation (24 October 2001). "HHS, Bayer Agree to Cipro Purchase". USA: U.S. Department of Health & Human Services. Retrieved 4 September 2009. [dead link]
  114. ^ United States Court of Appeals for the Federal Circuit (2008). "United States Court of Appeals for the Federal Circuit" (PDF). USA. Retrieved 4 September 2009. [dead link]
  115. ^ Bailey RR, Natale R, Linton AL, RR (1972). "Nalidixic acid arthralgia". Can Med Assoc J. 107 (7): 604 passim. ISSN 0008-4409. PMC 1940945. PMID 4541768. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  116. ^ Bailey RR, Kirk JA, Peddie BA, RR (1983). "Norfloxacin-induced rheumatic disease". N Z Med J. 96 (736): 590. ISSN 0028-8446. PMID 6223241. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  117. ^ Szarfman A, Chen M, Blum MD, A (1995). "More on fluoroquinolone antibiotics and tendon rupture". N Engl J Med. 332 (3): 193. doi:10.1056/NEJM199501193320319. ISSN 0028-4793. PMID 7800023. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); |format= requires |url= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  118. ^ "Petition to Require a Warning on All Fluoroquinolone Antibiotics (HRG Publication #1399)". Public Citizen. 1 August 1996. Retrieved on 27 December 2008.
  119. ^ a b "Madigan, Public Citizen, petition FDA for "Black Box" warning regarding potential adverse effects of certain popular antibiotics" (Press release). Office of the Illinois Attorney General. 29 August 2006. Retrieved 27 December 2008. Full text of the 2005 petition and FDA response available from the Fluoroquinolone Toxicity Research Foundation, a U.S. consumer advocacy group.
  120. ^ "Public Citizen Petitions the FDA to Include a Black Box Warning on Fluoroquinolone Antibiotics (HRG Publication #1781)". Public Citizen. 29 August 2006. Retrieved 27 December 2008.
  121. ^ "Public Citizen v. Food and Drug Administration (FDA) (Fluoroquinolone)". Public Citizen. 3 January 2008. Retrieved 27 December 2008.
  122. ^ Ravn, Karen (18 August 2008). "Behind the FDA's 'black box' warnings". Los Angeles Times. Retrieved 27 December 2008.
  123. ^ "FDA Requests Boxed Warnings on Fluoroquinolone Antimicrobial Drugs" (Press release). U.S. Food and Drug Administration. 8 July 2008. Retrieved 11 October 2008.
  124. ^ The complete labeling history of each drug is available from Drugs@FDA. Medication Guides are available from the FDA's MedWatch system.
  125. ^ MacCarthy, Paul (22 October 2008). "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" (PDF). Bayer HealthCare Pharmaceuticals. Retrieved 27 December 2008.
  126. ^ Rosenthal, Norman (2008). "Important Change in the LEVAQUIN (Ievofloxacin) Complete Prescribing Information -Addition of Boxed Warning and Medication Guide Regarding Tendinitis and Tendon Rupture" (PDF). Ortho-McNeil Janssen Scientific Affairs, LLC. Retrieved 27 December 2008. {{cite web}}: Unknown parameter |month= ignored (help)
  127. ^ http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/019537s075,019847s047,019857s054,020780s033,021473s028ltr.pdf
  128. ^ "NDA #19-537 Cipro (ciprofloxacin) Tablets Macmis ID #7451" (PDF). U.S. Food and Drug Administration (FDA). 2 April 1999. Retrieved 30 January 2009.
  129. ^ "RE: Cipro HC Otic Suspension (Ciprofloxacin Hydrochloride and Hydrocortisone Otic Suspension) NDA 20-805 Ciloxan (ciprofloxacin ophthalmic) Solution NDA 19-992 MACMIS ID# 11015" (PDF). U.S. Food and Drug Administration (FDA). 18 July 2003. Retrieved 30 January 2009.
  130. ^ Biosecurity requires drug reform. 1 January 2002 World Watch ISSN: 0896-0615
  131. ^ Nawaz, H.; Rauf, S.; Akhtar, K.; Khalid, AM. (2006). "Electrochemical DNA biosensor for the study of ciprofloxacin-DNA interaction". Anal Biochem. 354 (1): 28–34. doi:10.1016/j.ab.2006.04.004. PMID 16707087. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); More than one of |author4= and |last4= specified (help); Unknown parameter |month= ignored (help)
  132. ^ Stacey L. Knobler ... (2003). The Resistance Phenomenon in Microbes and Infectious Disease Vectors: Implications for Human Health and Strategies for Containment, Workshop Summary. National Academies Press. p. 34. ISBN 978-0-309-08854-1. {{cite book}}: Cite has empty unknown parameter: |chapterurl= (help)
  133. ^ A.C. Vatopoulos (1997). "Bacterial Resistance to Ciprofloxacin in Greece: Results from the National Electronic Surveillance System" (PDF). {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  134. ^ "Bacterial resistance prompts concern among health officials". 26 February 2009.[dead link]
  135. ^ M Jacobs, Worldwide Overview of Antimicrobial Resistance. International Symposium on Antimicrobial Agents and Resistance 2005.
  136. ^ "Update On Extra-Label Use Of Fluoroquinolones" (Press release). Center for Veterinary Medicine (CVM). 16 July 1996. Retrieved 12 August 2009.
  137. ^ "Ciprofloxacin spectrum of bacterial susceptibility and Resistance" (PDF). Retrieved 4 May 2012.
  138. ^ a b Linder JA, Huang ES, Steinman MA, Gonzales R, Stafford RS (2005). "Fluoroquinolone prescribing in the United States: 1995 to 2002". Am. J. Med. 118 (3): 259–68. doi:10.1016/j.amjmed.2004.09.015. PMID 15745724. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  139. ^ K08 HS14563 and HS11313
  140. ^ "Anthrax Scare Leaves Trail of Cipro Victims - Class Actions filed in Two States". USA: Sheller Ludwig & Sheller. 17 October 2003. Retrieved 9 September 2009. [dead link]
  141. ^ "Legal Brief of Postal Employees Cases (EEOC, MSPB, District Courts)". USA: Postal Reporter. Archived from the original on 21 October 2007. Retrieved 9 September 2009.
  142. ^ Charles P. Goodell, Jr. "Profile". USA: Goodell, DeVries, Leech & Dann, LLP. Retrieved 9 September 2009.
  143. ^ "LegalView Reveals Details of the FDA Mandated Black Box Warning For Fluoroquinolone Antibiotics". PRlog. 11 July 2008.
  144. ^ Cynthia Diaz (6 July 2009). "Levaquin Litigation Moving Ahead". Zimbio. In May we wrote that most litigation specialists expected thousands of people to file lawsuits against the makers of Levaquin and similar drugs...
  145. ^ Carey and Danis LLC (3 September 2009). "Carey and Danis LLC Announces Four Lawsuits against the Makers of Levaquin". Reuters.
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