Ciprofloxacin

"Cipro" redirects here. For the Rome Metro station, see Cipro (Rome Metro).
Ciprofloxacin (INN)
Systematic (IUPAC) name
1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid
Clinical data
Trade names Ciloxan, Cipro, Neofloxin
AHFS/Drugs.com monograph
MedlinePlus a688016
Licence data US FDA:link
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Routes of
administration		 Oral, intravenous, topical (ear drops, eye drops)
Pharmacokinetic data
Bioavailability 69%[1]
Metabolism Hepatic, including CYP1A2
Biological half-life 4 hours
Excretion Kidneys
Identifiers
CAS Number 85721-33-1 YesY
ATC code J01MA02 S01AE03 S02AA15 S03AA07
PubChem CID 2764
DrugBank DB00537 YesY
ChemSpider 2662 YesY
UNII 5E8K9I0O4U YesY
KEGG D00186 YesY
ChEBI CHEBI:100241 YesY
ChEMBL CHEMBL8 YesY
NIAID ChemDB 001992
Chemical data
Formula C17H18FN3O3
Molar mass 331.346 g/mol
  (verify)

Ciprofloxacin is an antibiotic used to treat a number of bacterial infections.[2] This includes bone and joint infections, intra abdominal infections, certain type of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others.[2] For some infections it is used in addition to other antibiotics.[2] It can be taken by mouth or used intravenously.[2]

Common side effects include nausea, vomiting, diarrhea, and rash.[2] Ciprofloxacin increases the risk of tendon rupture and worsening muscle weakness in people with the neurological disorder myasthenia gravis.[2] Rates of side effects appear to be higher than some groups of antibiotics such as cephalosporins but lower than others such as clindamycin.[3] Studies in other animals raise concerns regarding use in pregnancy.[4] No problems were identified; however, in the children of a small number of women who took the medication.[4] It appears to be safe during breastfeeding.[2] It is a second-generation fluoroquinolone with a broad spectrum of activity.[5][6]

Ciprofloxacin was introduced in 1987.[7] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[8] It is available as a generic medication and not very expensive.[2][9] Wholesale it costs between 0.03 and 0.13 USD a dose.[10] In the United States it is sold for about 0.40 USD per dose.[2]

Medical uses

Ciprofloxacin is used to treat a wide variety of infections, including infections of bones and joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid.[11]

Ciprofloxacin only treats bacterial infections; it does not treat viral infections such as the common cold. For certain uses including acute sinusitis, lower respiratory tract infections and uncomplicated gonorrhea, ciprofloxacin is not considered a first-line agent.

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 Pseudomonas aeruginosa. For example, ciprofloxacin in combination with metronidazole is one of several first-line antibiotic regimens recommended by the Infectious Diseases Society of America for the treatment of community-acquired abdominal infections in adults.[12] It also features prominently in treatment guidelines for acute pyelonephritis, complicated or hospital-acquired urinary tract infection, acute or chronic prostatitis,[13] certain types of endocarditis,[14] certain skin infections,[15] and prosthetic joint infections.[16]

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 nitrofurantoin or trimethoprim/sulfamethoxazole.[17] The European Association of Urology 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”.[13]

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 Streptococcus pneumoniae.[18][19][20][21] "Respiratory quinolones" such as levofloxacin, 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 acute sinusitis.[22][23]

Ciprofloxacin is approved for the treatment of gonorrhea in many countries, but this recommendation is widely regarded as obsolete due to resistance development.[24][25][26][27]

Pregnancy

In the United States ciprofloxacin is pregnancy category C.[28] This category includes drugs for which no adequate and well-controlled studies in human pregnancy exist, and for which animal studies have suggested the potential for harm to the fetus, but potential benefits may warrant use of the drug in pregnant women despite potential risks. An expert review of published data on experiences with ciprofloxacin use during pregnancy by the Teratogen Information System 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.[29]

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.[30][31] The label notes, however, that these studies are insufficient to reliably evaluate the definitive safety or risk of less common defects by ciprofloxacin in pregnant women and their developing fetuses.

Breastfeeding

Fluoroquinolones have been reported as present in a mother's milk and thus passed on to the nursing child.[32][33] The U.S. FDA recommends that because of the risk of serious adverse reactions (including articular damage) in infants nursing from mothers taking ciprofloxacin, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Children

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:

1) Inhalational anthrax (postexposure)[34]

2) Complicated urinary tract infections and pyelonephritis due to Escherichia coli,[35] but never as first-line agents. 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.[36]

Spectrum of activity

Its spectrum of activity includes most strains of bacterial pathogens responsible for respiratory, urinary tract, gastrointestinal, and abdominal infections, including Gram-negative (Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, and Pseudomonas aeruginosa), and Gram-positive (methicillin-sensitive, but not methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Staphylococcus epidermidis, Enterococcus faecalis, and Streptococcus pyogenes) bacterial pathogens.

Bacterial 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 in recent years, leaving it significantly less effective than it would have been otherwise.[37][38]

Resistance to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. Numerous pathogens, including enterococci, Streptococcus pyogenes and Klebsiella pneumoniae (quinolone-resistant) now exhibit resistance.[39] Widespread veterinary usage of the fluoroquinolones, particularly in Europe, has been implicated.[40] Meanwhile, some Burkholderia cepacia, Clostridium innocuum and Enterococcus faecium strains have developed resistance to ciprofloxacin to varying degrees.[41]

Fluoroquinolones had become the class of antibiotics most commonly prescribed to adults in 2002.[42] Nearly half (42%) of those prescriptions in the U.S. were for conditions not approved by the FDA, such as acute bronchitis, otitis media, and acute upper respiratory tract infection, according to a study supported in part by the Agency for Healthcare Research and Quality.[42][43] 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.

Contraindications

Contraindications include:[44]

Ciprofloxacin is also considered to be contraindicated in children (except for the indications outlined above), in pregnancy, to nursing mothers, and in people with epilepsy or other seizure disorders.

Side effects

Rates of side effects appear to be higher than with some groups of antibiotics such as cephalosporins but lower than with others such as clindamycin.[3] Compared to other antibiotics some studies find a higher rate of side effects[45][46] while others find no difference.[47]

In pre-approval clinical trials of ciprofloxacin most of the adverse events reported were described as mild or moderate in severity, abated soon after the drug was discontinued, and required no treatment.[48] Ciprofloxacin was discontinued 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%.

Tendinitis

The black box warning on the U.S. FDA-approved ciprofloxacin label warns of an increased risk of tendinitis 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. Tendon rupture can occur during therapy or even months after discontinuation of the drug.[49] A case control study[50] performed using a UK medical care database found that fluoroquinolone use was associated with a 1.9-fold increase in tendon problems. The relative 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 (0.1%) cases of Achilles tendon rupture were identified. A study performed using an Italian healthcare database reached qualitatively similar conclusions.[51]

Nervous system

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 side 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 side effects such as tremors, psychosis, anxiety, hallucinations, paranoia, and suicide attempts, especially at higher doses.[3] Like other fluoroquinolones, it is also known to cause peripheral neuropathy that may be irreversible, such as weakness, burning pain, tingling, or numbness.[52]

Cancer

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.[53] 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 mg/kg to rats and mice, respectively (about 1.7 and 2.5 times the highest recommended therapeutic dose based upon mg/m2). 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.

Other

The other black box warning is that ciprofloxacin should not be used in patients with myasthenia gravis 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="www.accessdata.fda.gov"/[54]

Clostridium difficile-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.[55]

A wide range of rare but potentially fatal side effects spontaneously reported to the U.S. FDA or the subject of case reports published in medical journals includes, but is not limited to, toxic epidermal necrolysis, Stevens-Johnson syndrome, heart arrhythmias (torsades de pointes or QT prolongation), allergic pneumonitis, bone marrow suppression, hepatitis or liver failure,[56] and sensitivity to light. The drug should be discontinued if a rash, jaundice, or other sign of hypersentitivity occur.[57]

Children and the elderly are at a much greater risk of experiencing adverse reactions.[58][59]

Overdose

Overdose of ciprofloxacin may result in reversible renal toxicity. Treatment of overdose includes emptying of the stomach by induced vomiting or gastric lavage, as well as administration of antacids containing magnesium, aluminum, 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. Hemodialysis or peritoneal dialysis can only remove less than 10% of ciprofloxacin.[60] 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.[61]

Interactions

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 (sevelamer, lanthanum carbonate, sucralfate, didanosine), 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.[60][62][63]

Ciprofloxacin inhibits the drug-metabolizing enzyme CYP1A2 and thereby can reduce the clearance of drugs metabolized by that enzyme. CYP1A2 substrates that exhibit increased serum levels in ciprofloxacin-treated patients include tizanidine, theophylline, caffeine, methylxanthines, clozapine, olanzapine, and ropinirole. 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 cyclosporine is equivocal or conflicting.[63][64][65]

The Committee on 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.[64][66] The mechanism for this interaction may involve a synergistic increased antagonism of GABA neurotransmission.[67][68]

Altered serum levels of the antiepileptic drugs phenytoin and carbamazepine (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.[64][69][70]

Mechanism of action

Ciprofloxacin is a broad-spectrum antibiotic of the fluoroquinolone class. It is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV,[71] enzymes [72] necessary to separate bacterial DNA, thereby inhibiting cell division.

Pharmacokinetics

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,[73] 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.

Ciprofloxacin is weakly bound to serum proteins (20-40%), but is an inhibitor of the drug-metabolizing enzyme cytochrome P450 1A2, which leads to the potential for clinically important drug interactions with drugs metabolized by that enzyme.

Ciprofloxacin is about 70% orally available when administered orally, so a slightly higher dose is needed to achieve the same exposure when switching from IV to oral administration. A 750-mg immediate-release oral tablet given every 12 hours produces about the same area under the serum concentration curve (AUC) and peak serum concentration (Cmax) as a 400-mg dose given every 8 hours IV.[57] The extended release oral tablets[74] 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 Cmax, but the 24‑hour AUCs are equivalent.

Ciprofloxacin immediate-release tablets contain ciprofloxacin as the hydrochloride salt, and the XR tablets contain a mixture of the hydrochloride salt as the free base.

Chemical properties

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.[60]

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.[60]

Usage

Ciprofloxacin is the most widely used of the second-generation quinolone.[75][76] In 2010, over 20 million prescriptions were written, making it the 35th-most commonly prescribed drug, and the 5th-most commonly prescribed antibacterial, in the U.S.[77]

History

Ciprofloxacin 250-mg tablets from Ukraine

The first members of the quinolone antibacterial class were relatively low-potency drugs such as nalidixic acid, used mainly in the treatment of urinary tract infections owing to their renal excretion and propensity to be concentrated in urine.[78] In 1979, the publication of a patent[79] filed by the pharmaceutical arm of Kyorin Seiyaku Kabushiki Kaisha disclosed the discovery of norfloxacin, and the demonstration that certain structural modifications including the attachment of a fluorine atom to the quinolone ring leads to dramatically enhanced antibacterial potency.[80] 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 fluoroquinolone program at Bayer focused on examining the effects of very minor changes to the norfloxacin structure.[81][82] In 1983, the company published in vitro potency data for ciprofloxacin, a fluoroquinolone antibacterial having a chemical structure differing from that of norfloxacin by the presence of a single carbon atom.[83] This small change led to a two- to 10-fold increase in potency against most strains of Gram-negative bacteria. Importantly, this structural change led to a four-fold improvement in activity against the important Gram-negative pathogen Pseudomonas aeruginosa, making ciprofloxacin one of the most potent known drugs for the treatment of this intrinsically antibiotic-resistant pathogen.

The oral tablet form of ciprofloxacin was approved in October 1987,[84] just one year after the approval of norfloxacin.[85] In 1991, the intravenous formulation was introduced. Ciprofloxacin sales reached a peak of about 2 billion euros in 2001, representing 34% of Bayer’s total pharmaceutical revenues, before Bayer's patent expired in 2004, after which annual sales have averaged around €200 million.[86][87]

Society and culture

Cost

It is available as a generic medication and not very expensive.[2][9] Wholesale it costs between 0.03 and 0.13 USD a dose.[10] In the United States it is sold for about 0.40 USD per dose.[2]

Generic equivalents

On 24 October 2001, the Prescription Access Litigation (PAL) project 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 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,[88] in effect upholding Bayer's agreement with its competitors.

Available forms

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 also available for local administration as eye drops and ear drops.

Litigation

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 suffered serious adverse effects from taking ciprofloxacin (Cipro) in the aftermath of the anthrax attacks in 2001. 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.[89] 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 cipro when they were given the option of taking the drug.[90][91]

References

  1. ↑ Drusano GL; Standiford HC; Plaisance K; Forrest A; Leslie J; Caldwell J (September 1986). "Absolute oral bioavailability of ciprofloxacin". Antimicrob Agents Chemother. 30 (3): 444–6. doi:10.1128/aac.30.3.444. ISSN 0066-4804. PMC 180577. PMID 3777908.
  2. 1 2 3 4 5 6 7 8 9 10 11 "Ciprofloxacin Hydrochloride". The American Society of Health-System Pharmacists. Retrieved Aug 23, 2015.
  3. 1 2 3 Heidelbaugh JJ, Holmstrom H; Holmstrom (April 2013). "The perils of prescribing fluoroquinolones". J Fam Pract 62 (4): 191–7. PMID 23570031.
  4. 1 2 "Prescribing medicines in pregnancy database". Australian Government. 23 Aug 2015.
  5. ↑ Ball P (July 2000). "Quinolone generations: natural history or natural selection?". J. Antimicrob. Chemother. 46 Suppl T1: 17–24. doi:10.1093/oxfordjournals.jac.a020889. PMID 10997595.
  6. ↑ Oliphant CM, Green GM; Green (February 2002). "Quinolones: a comprehensive review". Am Fam Physician 65 (3): 455–64. PMID 11858629.
  7. ↑ Oxford Handbook of Infectious Diseases and Microbiology. OUP Oxford. 2009. p. 56. ISBN 9780191039621.
  8. ↑ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
  9. 1 2 Hamilton, Richard J. (2014). Tarascon pharmacopoeia (15 ed.). Jones & Bartlett Publishers. p. 85. ISBN 9781284056716.
  10. 1 2 "Ciprofloxacin". International Drug Price Indicator Guide. Retrieved 24 August 2015.
  11. ↑ "Ciprofloxacin-Hydrochloride". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
  12. ↑ "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".
  13. 1 2 "www.uroweb.org" (PDF).
  14. ↑ "Infective Endocarditis".
  15. ↑ "Practice Guidelines for the Diagnosis and Management of Skin and Soft-Tissue Infections".
  16. ↑ "Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guidelines by the Infectious Diseases Society of America".
  17. ↑ "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".
  18. ↑ "pharmacy.oregonstate.edu" (PDF).
  19. ↑ 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...
  20. ↑ Vardakas, KZ; Siempos, II; Grammatikos, A; Athanassa, Z; Korbila, IP; Falagas, ME (December 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.
  21. ↑ Donaldson, PM; Pallett, AP; Carroll, MP (May 1994). "Ciprofloxacin in general practice". BMJ (Clinical Research Ed.) 308 (6941): 1437. doi:10.1136/bmj.308.6941.1437. ISSN 0959-8138. PMC 2540361. PMID 8019264.
  22. ↑ Karageorgopoulos, DE.; Giannopoulou, KP.; Grammatikos, AP.; Dimopoulos, G.; Falagas, ME. (March 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.
  23. ↑ Chow AW, Benninger MS, Brook I; et al. (April 2012). "IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults". Clin. Infect. Dis. 54 (8): e72–e112. doi:10.1093/cid/cir1043. PMID 22438350.
  24. ↑ (World Health Organization (WHO) Western Pacific Region Gonococcal Antimicrobial Susceptibility Programme (GASP) Report- 2000. Commun Dis Intell 2001; 25:274-277)
  25. ↑ Department of Health and Human Services; Centers for Disease Control and Prevention (November 2004). "Gonococcal Isolate Surveillance Project (GISP) Annual Report - 2003" (PDF). USA: Center for Disease Controlo. Retrieved 31 August 2009.
  26. ↑ 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 (Scotland: National Health Service) 37. ISSN 1357-4493.
  27. ↑ Centers for Disease Control and Prevention (CDC) (13 April 2007). "Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections.". Morbidity and Mortality Weekly Report (PDF) (USA: Center for Disease Control) 56 (14): 332–336. PMID 17431378.
  28. ↑ FDA-approved drug label
  29. ↑ Friedman, J.; Polifka, J. (2000). Teratogenic effects of drugs: a resource for clinicians (TERIS). Baltimore, Maryland: Johns Hopkins University Press. pp. 149–195.
  30. ↑ Loebstein R, Addis A, Ho E, Andreou R, Sage S, Donnenfeld AE; et al. (1998). "Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study". Antimicrob Agents Chemother 42 (6): 1336–9. PMC 105599. PMID 9624471.
  31. ↑ Schaefer C, Amoura-Elefant E, Vial T, Ornoy A, Garbis H, Robert E; et al. (1996). "Pregnancy outcome after prenatal quinolone exposure. Evaluation of a case registry of the European Network of Teratology Information Services (ENTIS)". Eur J Obstet Gynecol Reprod Biol 69 (2): 83–9. doi:10.1016/0301-2115(95)02524-3. PMID 8902438.
  32. ↑ Shin HC, Kim JC, Chung MK, HC; Kim, JC; Chung, MK; Jung, YH; Kim, JS; Lee, MK; Amidon, GL (September 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.
  33. ↑ Dan M, Weidekamm E, Sagiv R, Portmann R, Zakut H, M; Weidekamm, E; Sagiv, R; Portmann, R; Zakut, H (February 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.
  34. ↑ 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.
  35. ↑ 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.
  36. ↑ Lexi-Comp (February 2009). "Ciprofloxacin". Merk. Retrieved 4 September 2009.
  37. ↑ A.C. Vatopoulos; V. Kalapothaki (1997). "Bacterial Resistance to Ciprofloxacin in Greece: Results from the National Electronic Surveillance System" (PDF).
  38. ↑ "Bacterial resistance prompts concern among health officials". 26 February 2009. Archived from the original on 5 March 2009.
  39. ↑ M Jacobs, Worldwide Overview of Antimicrobial Resistance. International Symposium on Antimicrobial Agents and Resistance 2005.
  40. ↑ "Update On Extra-Label Use Of Fluoroquinolones" (Press release). Center for Veterinary Medicine (CVM). 16 July 1996. Retrieved 12 August 2009.
  41. ↑ "Ciprofloxacin spectrum of bacterial susceptibility and Resistance" (PDF). Retrieved 4 May 2012.
  42. 1 2 Linder JA, Huang ES, Steinman MA, Gonzales R, Stafford RS; Huang; Steinman; Gonzales; Stafford (March 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.
  43. ↑ K08 HS14563 and HS11313
  44. ↑ "Cipro Labeling Revision 02/25/2011 Supplement 075" (PDF). US Food and Drug Administration (FDA). 25 February 2011. Retrieved 1 April 2011.
  45. ↑ Brown KA, Khanafer N, Daneman N, Fisman DN; Khanafer; Daneman; Fisman (May 2013). "Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection". Antimicrob. Agents Chemother. 57 (5): 2326–32. doi:10.1128/AAC.02176-12. PMC 3632900. PMID 23478961.
  46. ↑ Falagas ME, Matthaiou DK, Vardakas KZ; Matthaiou; Vardakas (December 2006). "Fluoroquinolones vs beta-lactams for empirical treatment of immunocompetent patients with skin and soft tissue infections: a meta-analysis of randomized controlled trials". Mayo Clin. Proc. 81 (12): 1553–66. doi:10.4065/81.12.1553. PMID 17165634.
  47. ↑ Knottnerus BJ, Grigoryan L, Geerlings SE; et al. (December 2012). "Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: network meta-analysis of randomized trials". Fam Pract 29 (6): 659–70. doi:10.1093/fampra/cms029. PMID 22516128.
  48. ↑ FDA-approved package insert
  49. ↑ Saint, F; Gueguen; Biserte; Fontaine; Mazeman (September 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.
  50. ↑ van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HG, Stricker BH; Sturkenboom; Herings; Leufkens; Stricker (June 2002). "Fluoroquinolones and risk of Achilles tendon disorders: case-control study". BMJ 324 (7349): 1306–7. doi:10.1136/bmj.324.7349.1306. PMC 113766. PMID 12039823.
  51. ↑ Corrao G, Zambon A, Bertù L; et al. (2006). "Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control study". Drug Saf 29 (10): 889–96. doi:10.2165/00002018-200629100-00006. PMID 16970512.
  52. ↑ "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".
  53. ↑ "CIPRO® (ciprofloxacin hydrochloride) TABLETS
    CIPRO® (ciprofloxacin*) ORAL SUSPENSION"     (PDF).
  54. ↑ http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019537s075,020780s033lbl.pdf
  55. ↑ Deshpande A, Pant C, Jain A, Fraser TG, Rolston DD; Pant; Jain; Fraser; Rolston (2008). "Do fluoroquinolones predispose patients to Clostridium difficile associated disease? A review of the evidence". Curr Med Res Opin 24 (2): 329–33. doi:10.1185/030079908X253735. PMID 18067688.
  56. ↑ Alshammari TM, Larrat EP, Morrill HJ, Caffrey AR, Quilliam BJ, Laplante KL; Larrat; Morrill; Caffrey; Quilliam; Laplante (2014). "Risk of hepatotoxicity associated with fluoroquinolones: A national case-control safety study". Am J Health Syst Pharm 71 (1): 37–43. doi:10.2146/ajhp130165. PMID 24352180.
  57. 1 2 "Cipro Immediate Release Tablets Prescribing Information" (PDF).
  58. ↑ Iannini, PB (June 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.
  59. ↑ Owens Rc, Jr; Ambrose, P. G. (July 2005). "Antimicrobial safety: focus on fluoroquinolones". Clinical Infectious Diseases. 41 Suppl 2: S144–57. doi:10.1086/428055. ISSN 1058-4838. PMID 15942881.
  60. 1 2 3 4 "Cipro Labeling Revision 04/06/2009 Supplement 073" (PDF). US Food and Drug Administration. 6 April 2009. Retrieved 8 September 2009.
  61. ↑ 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.
  62. ↑ Rodvold KA, Piscitelli SC; Piscitelli (August 1993). "New oral macrolide and fluoroquinolone antibiotics: an overview of pharmacokinetics, interactions, and safety". Clin. Infect. Dis. 17 Suppl 1: S192–9. doi:10.1093/clinids/17.supplement_1.s192. PMID 8399914.
  63. 1 2 Bolhuis MS, Panday PN, Pranger AD, Kosterink JG, Alffenaar JW; Panday; Pranger; Kosterink; Alffenaar (2011). "Pharmacokinetic drug interactions of antimicrobial drugs: a systematic review on oxazolidinones, rifamycines, macrolides, fluoroquinolones, and Beta-lactams". Pharmaceutics 3 (4): 865–913. doi:10.3390/pharmaceutics3040865. PMC 3857062. PMID 24309312.
  64. 1 2 3 "Cipro Labeling Revision 10/03/2008 Supplement 068" (PDF). US Food and Drug Administration. 3 October 2008. Retrieved 31 August 2009.
  65. ↑ Janknegt R, R (November 1990). "Drug interactions with quinolones". J. Antimicrob. Chemother. 26 Suppl D: 7–29. doi:10.1093/jac/26.suppl_D.7. ISSN 0305-7453. PMID 2286594.
  66. ↑ 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.
  67. ↑ De Sarro A, De Sarro G; De Sarro (March 2001). "Adverse reactions to fluoroquinolones. an overview on mechanistic aspects". Curr. Med. Chem. 8 (4): 371–84. doi:10.2174/0929867013373435. PMID 11172695.
  68. ↑ Brouwers JR, JR (July 1992). "Drug interactions with quinolone antibacterials". Drug Saf 7 (4): 268–81. doi:10.2165/00002018-199207040-00003. ISSN 0114-5916. PMID 1524699.
  69. ↑ Shahzadi A, Javed I, Aslam B; et al. (January 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.
  70. ↑ Carol Langlois; Pascale Springuel (January 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.
  71. ↑ Drlica K, Zhao X, K; Zhao, X (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.
  72. ↑ Pommier Y., Leo E., Zhang H., Marchand C.; Leo; Zhang; Marchand (2010). "DNA topoisomerases and their poisoning by anticancer and antibacterial drugs". Chem. Biol 17 (5): 421–433. doi:10.1016/j.chembiol.2010.04.012. PMID 20534341.
  73. ↑ "Cipro IV Prescribing Information" (PDF).
  74. ↑ "Cipro XR Prescribing Information" (PDF).
  75. ↑ Goossens H, Ferech M, Coenen S, Stephens P; Ferech; Coenen; Stephens; European Surveillance of Antimicrobial Consumption Project Group (April 2007). "Comparison of outpatient systemic antibacterial use in 2004 in the United States and 27 European countries". Clin. Infect. Dis. 44 (8): 1091–5. doi:10.1086/512810. PMID 17366456.
  76. ↑ "British Columbia Annual Summary of Antibiotics Utilization 2010" (PDF).
  77. ↑ "http://drugtopics.modernmedicine.com/drugtopics/data/articlestandard/drugtopics/252011/727243/article.pdf" (PDF). Archived from the original (PDF) on 15 December 2012. Retrieved 2 November 2012. External link in |title= (help)
  78. ↑ Mayrer AR, Andriole VT; Andriole (January 1982). "Urinary tract antiseptics". Med. Clin. North Am. 66 (1): 199–208. PMID 7038329.
  79. ↑ "Patent US4146719 - Piperazinyl derivatives of quinoline carboxylic acids - Google Patents".
  80. ↑ "aac.asm.org" (PDF).
  81. ↑ "Patent US4547503 - 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[4-(oxo-alkyl)-1-piperazinyl ... - Google Patents".
  82. ↑ "Patent US4544658 - 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(alkyl-1-piperazinyl)quinoline-3 ... - Google Patents".
  83. ↑ Wise R, Andrews JM, Edwards LJ; Andrews; Edwards (April 1983). "In vitro activity of Bay 09867, a new quinoline derivative, compared with those of other antimicrobial agents". Antimicrob. Agents Chemother. 23 (4): 559–64. doi:10.1128/aac.23.4.559. PMC 184701. PMID 6222695.
  84. ↑ http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=019537&TABLE1=OB_Rx
  85. ↑ "Orange Book Detail Record Search".
  86. ↑ "www.sec.gov".
  87. ↑ Dan Prochilo for Law360 18 November 2013 Bayer’s $74M Cipro Pay-For-Delay Deal Approved In Calif.
  88. ↑ United States Court of Appeals for the Federal Circuit (2008). "United States Court of Appeals for the Federal Circuit" (PDF). USA. Archived from the original (PDF) on 27 August 2009. Retrieved 4 September 2009.
  89. ↑ "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.
  90. ↑ Los Angeles Times, from wire service reports. October 19, 2003 Postal Workers Sue Over Anthrax Scare Antibiotic
  91. ↑ Bill Lewis, President of Trenton Metro Area Local, American Postal Workers Union, AFL-CIO. December 7, 2003 Trenton Metro Area Local: Welcome to Bill's Corner Page accessed October 23, 2014

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